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Sample records for adult diffuse astrocytoma

  1. Experience With Carbon Ion Radiotherapy for WHO Grade 2 Diffuse Astrocytomas

    SciTech Connect

    Hasegawa, Azusa; Mizoe, Jun-Etsu; Tsujii, Hirohiko; Kamada, Tadashi; Jingu, Keiichi; Iwadate, Yasuo; Nakazato, Youichi; Matsutani, Masao; Takakura, Kintomo

    2012-05-01

    Purpose: To assess outcomes of carbon ion radiotherapy for diffuse astrocytomas in adults. Methods and Materials: Between October 1994 and February 2002, 14 patients with diffuse astrocytoma, identified as eligible for carbon ion radiotherapy, were enrolled in a phase I/II clinical trial. Carbon ion radiotherapy was administered in 24 fractions over 6 weeks. The normal tissue morbidity was monitored carefully, and the carbon ion dose was escalated from 50.4 Gy equivalent (GyE) to 55.2 GyE. Patients were divided into two groups according to their carbon ion doses: a low-dose group in which 2 patients were irradiated with 46.2 GyE and 7 patients were irradiated with 50.4 GyE, and a high-dose group in which 5 patients were irradiated with 55.2 GyE. Results: Toxicities were within acceptable limits, and none of the patients developed Grade 3 or higher acute or late reactions. The median progression-free survival (PFS) time was 18 months for the low-dose group and 91 months for the high-dose group (p = 0.0030). The median overall survival (OS) time was 28 months for the low-dose group and not reached for the high-dose group (p = 0.0208). Conclusion: High-dose group patients showed significant improvement in PFS and OS rates compared to those in the low-dose group, and both dose groups showed acceptable toxicity.

  2. Prevention against diffuse spinal cord astrocytoma: can the Notch pathway be a novel treatment target?

    PubMed Central

    Sun, Jian-jun; Wang, Zhen-yu; Li, Ling-song; Yu, Hai-yan; Xu, Yong-sheng; Wu, Hai-bo; Luo, Yi; Liu, Bin; Zheng, Mei; Mao, Jin-long; Lou, Xiao-hui

    2015-01-01

    This study was designed to investigate whether the Notch pathway is involved in the development of diffuse spinal cord astrocytomas. BALB/c nude mice received injections of CD133+ and CD133− cell suspensions prepared using human recurrent diffuse spinal cord astrocytoma tissue through administration into the right parietal lobe. After 7–11 weeks, magnetic resonance imaging was performed weekly. Xenografts were observed on the surfaces of the brains of mice receiving the CD133+ cell suspension, and Notch-immunopositive expression was observed in the xenografts. By contrast, no xenografts appeared in the identical position on the surfaces of the brains of mice receiving the CD133− cell suspension, and Notch-immunopositive expression was hardly detected either. Hematoxylin-eosin staining and immunohistochemical staining revealed xenografts on the convex surfaces of the brains of mice that underwent CD133+ astrocytoma transplantation. Some sporadic astroglioma cells showed pseudopodium-like structures, which extended into the cerebral white matter. However, it should be emphasized that the subcortex xenograft with Notch-immunopositive expression was found in the fourth mouse received injection of CD133− astrocytoma cells. However, these findings suggest that the Notch pathway plays an important role in the formation of astrocytomas, and can be considered a novel treatment target for diffuse spinal cord astrocytoma. PMID:25883623

  3. Genetic Analysis of Diffuse High-Grade Astrocytomas in Infancy Defines a Novel Molecular Entity.

    PubMed

    Gielen, Gerrit H; Gessi, Marco; Buttarelli, Francesca R; Baldi, Caterina; Hammes, Jennifer; zur Muehlen, Anja; Doerner, Evelyn; Denkhaus, Dorota; Warmuth-Metz, Monika; Giangaspero, Felice; Lauriola, Libero; von Bueren, André O; Kramm, Christof M; Waha, Andreas; Pietsch, Torsten

    2015-07-01

    Pediatric high-grade gliomas are considered to be different when compared to adult high-grade gliomas in their pathogenesis and biological behavior. Recently, common genetic alterations, including mutations in the H3F3A/ATRX/DAXX pathway, have been described in approximately 30% of the pediatric cases. However, only few cases of infant high-grade gliomas have been analyzed so far. We investigated the molecular features of 35 infants with diffuse high-grade astrocytomas, including 8 anaplastic astrocytomas [World Health Organization (WHO) grade III] and 27 glioblastomas (WHO grade IV) by immunohistochemistry, multiplex ligation probe-dependent amplification (MLPA), pyrosequencing of glioma-associated genes and molecular inversion probe (MIP) assay. MIP and MLPA analyses showed that chromosomal alterations are significantly less frequent in infants compared with high-grade gliomas in older children and adults. We only identified H3F3A K27M in 2 of 34 cases (5.9%), with both tumors located in the posterior fossa. PDGFRA amplifications were absent, and CDKN2A loss could be observed only in two cases. Conversely, 1q gain (22.7%) and 6q loss (18.2%) were identified in a subgroup of tumors. Loss of SNORD located on chromosome 14q32 was observed in 27.3% of the infant tumors, a focal copy number change not previously described in gliomas. Our findings indicate that infant high-grade gliomas appear to represent a distinct genetic entity suggesting a different pathogenesis and biological behavior. PMID:25231549

  4. Microsomal membrane proteome of low grade diffuse astrocytomas: Differentially expressed proteins and candidate surveillance biomarkers

    PubMed Central

    Polisetty, Ravindra Varma; Gautam, Poonam; Gupta, Manoj Kumar; Sharma, Rakesh; Gowda, Harsha; Renu, Durairaj; Shivakumar, Bhadravathi Marigowda; Lakshmikantha, Akhila; Mariswamappa, Kiran; Ankathi, Praveen; Purohit, Aniruddh K.; Uppin, Megha S.; Sundaram, Challa; Sirdeshmukh, Ravi

    2016-01-01

    Diffuse astrocytoma (DA; WHO grade II) is a low-grade, primary brain neoplasm with high potential of recurrence as higher grade malignant form. We have analyzed differentially expressed membrane proteins from these tumors, using high-resolution mass spectrometry. A total of 2803 proteins were identified, 340 of them differentially expressed with minimum of 2 fold change and based on ≥2 unique peptides. Bioinformatics analysis of this dataset also revealed important molecular networks and pathways relevant to tumorigenesis, mTOR signaling pathway being a major pathway identified. Comparison of 340 differentially expressed proteins with the transcript data from Grade II diffuse astrocytomas reported earlier, revealed about 190 of the proteins correlate in their trends in expression. Considering progressive and recurrent nature of these tumors, we have mapped the differentially expressed proteins for their secretory potential, integrated the resulting list with similar list of proteins from anaplastic astrocytoma (WHO Grade III) tumors and provide a panel of proteins along with their proteotypic peptides, as a resource that would be useful for investigation as circulatory plasma markers for post-treatment surveillance of DA patients. PMID:27246909

  5. [Neoadjuvant chemotherapy for symptomatic non operable grade II fibrillary astrocytoma in adults].

    PubMed

    Lebrun, C; Fontaine, D; Vandenbos, F; Chanalet, S; Bourg, V; Frénay, M; Alchaar, H; Bleuse, A; Bondiau, P Y; Brunetto, J L; Chatel, M; Courdi, A; Darcourt, J; Fauchon, F; Guibert, F; Grellier, P; Lanteri-Minet, M; Lonjon, M; Michiels, J F; Paquis, P; Paquis, V; Ramaioli, A; Rasendrarijao, D

    2004-05-01

    We collected 6 case-reports of symptomatric non removable low grade fibrillary astrocytoma of adults treated with a procarbazine-CCNU-vincristine chemotherapy regimen. All patients had drug-resistant epilepsy but brain imaging was stable. Total gross resection was rejected because of Volume or tumor location. After 4 to 7 cycles of chemotherapy, 2 patients had partial response and one minor response on brain MRI. All of them were seizure-free. Progression free survival was not reached at 5 Years. Up-front chemotherapy for low-grade astrocytomas may be useful and has to be prospectively evaluated. PMID:15269670

  6. Efficacy of 68Ga-DOTATOC Positron Emission Tomography (PET) CT in Children and Young Adults With Brain Tumors

    ClinicalTrials.gov

    2016-09-07

    Acoustic Schwannoma; Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Meningioma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Choroid Plexus Tumor; Adult Craniopharyngioma; Adult Diffuse Astrocytoma; Adult Ependymoblastoma; Adult Ependymoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Grade I Meningioma; Adult Grade II Meningioma; Adult Medulloblastoma; Adult Meningeal Hemangiopericytoma; Adult Mixed Glioma; Adult Myxopapillary Ependymoma; Adult Oligodendroglioma; Adult Papillary Meningioma; Adult Pilocytic Astrocytoma; Adult Pineal Gland Astrocytoma; Adult Pineoblastoma; Adult Pineocytoma; Adult Subependymal Giant Cell Astrocytoma; Adult Subependymoma; Adult Supratentorial Primitive Neuroectodermal Tumor (PNET); Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Ependymoblastoma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood High-grade Cerebellar Astrocytoma; Childhood High-grade Cerebral Astrocytoma; Childhood Infratentorial Ependymoma; Childhood Low-grade Cerebellar Astrocytoma; Childhood Low-grade Cerebral Astrocytoma; Childhood Medulloepithelioma; Childhood Supratentorial Ependymoma; Meningeal Melanocytoma; Newly Diagnosed Childhood Ependymoma; Recurrent Adult Brain Tumor; Recurrent Childhood Anaplastic Astrocytoma; Recurrent Childhood Anaplastic Oligoastrocytoma; Recurrent Childhood Anaplastic Oligodendroglioma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Diffuse Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Fibrillary Astrocytoma; Recurrent Childhood Gemistocytic Astrocytoma; Recurrent Childhood Giant Cell Glioblastoma; Recurrent Childhood Glioblastoma; Recurrent Childhood Gliomatosis Cerebri; Recurrent Childhood Gliosarcoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood

  7. DNA repair gene XRCC4 codon 247 polymorphism modified diffusely infiltrating astrocytoma risk and prognosis.

    PubMed

    Lin, Zhong-Hui; Chen, Jin-Chun; Wang, Yun-Sun; Huang, Teng-Jiao; Wang, Jin; Long, Xi-Dai

    2013-12-27

    The DNA repair gene X-ray cross-complementary group 4 (XRCC4), an important caretaker of the overall genome stability, is thought to play a major role in human tumorigenesis. We investigated the association between an important polymorphic variant of this gene at codon 247 (rs373409) and diffusely infiltrating astrocytoma (DIA) risk and prognosis. This hospital-based case-control study investigated this association in the Guangxi population. In total, 242 cases with DIA and 358 age-, sex-, and race-matched healthy controls were genotyped using TaqMan-PCR technique. We found a significant difference in the frequency of XRCC4 genotypes between cases and controls. Compared with the homozygote of XRCC4 codon 247 Ala alleles (XRCC4-AA), the genotypes of XRCC4 codon 247 Ser alleles (namely XRCC4-AS or -SS) increased DIA risk (odds ratios [OR], 1.82 and 2.89, respectively). Furthermore, XRCC4 polymorphism was correlated with tumor dedifferentiation of DIA (r = 0.261, p < 0.01). Additionally, this polymorphism modified the overall survival of DIA patients (the median survival times were 26, 14, and 8 months for patients with XRCC4-AA, -AS, and -SS, respectively). Like tumor grade, XRCC4 codon 247 polymorphism was an independent prognostic factor influencing the survival of DIA. These results suggest that XRCC4 codon 247 polymorphism may be associated with DIA risk and prognosis among the Guangxi population.

  8. H3F3A K27M mutation in pediatric CNS tumors: a marker for diffuse high-grade astrocytomas.

    PubMed

    Gielen, Gerrit H; Gessi, Marco; Hammes, Jennifer; Kramm, Christof M; Waha, Andreas; Pietsch, Torsten

    2013-03-01

    Brain tumors are one of the most common childhood malignancies. Diffuse high-grade gliomas represent approximately 10% of pediatric brain tumors. Exon sequencing has identified a mutation in K27M of the histone H3.3 gene (H3F3A K27M and G34R/V) in about 20% of pediatric glioblastomas, but it remains to be seen whether these mutations can be considered specific for pediatric diffuse high-grade astrocytomas or also occur in other pediatric brain tumors. We performed a pyrosequencing-based analysis for the identification of H3F3A codon 27 and codon 34 mutations in 338 pediatric brain tumors. The K27M mutation occurred in 35 of 129 glioblastomas (27.1%) and in 5 of 28 (17.9%) anaplastic astrocytomas. None of the other tumor entities showed H3F3A K27M mutation. Because H3F3A K27M mutations occur exclusively in pediatric diffuse high-grade astrocytomas, analysis of codon 27 mutational status could be useful in the differential diagnosis of these neoplasms. PMID:23429371

  9. SU-E-J-212: MR Diffusion Tensor Imaging for Assessment of Tumor and Normal Brain Tissue Responses of Juvenile Pilocytic Astrocytoma Treated by Proton Therapy

    SciTech Connect

    Hou, P; Park, P; Li, H; Zhu, X; Mahajan, A; Grosshans, D

    2015-06-15

    Purpose: Diffusion tensor imaging (DTI) can measure molecular mobility at the cellular level, quantified by the apparent diffusion coefficient (ADC). DTI may also reveal axonal fiber directional information in the white matter, quantified by the fractional anisotropy (FA). Juvenile pilocytic astrocytoma (JPA) is a rare brain tumor that occurs in children and young adults. Proton therapy (PT) is increasingly used in the treatment of pediatric brain tumors including JPA. However, the response of both tumors and normal tissues to PT is currently under investigation. We report tumor and normal brain tissue responses for a pediatric case of JPA treated with PT assessed using DTI. Methods: A ten year old male with JPA of the left thalamus received passive scattered PT to a dose of 50.4 Gy (RBE) in 28 fractions. Post PT, the patient has been followed up in seven years. At each follow up, MRI imaging including DTI was performed to assess response. MR images were registered to the treatment planning CT and the GTV mapped onto each MRI. The GTV contour was then mirrored to the right side of brain through the patient’s middle line to represent normal brain tissue. ADC and FA were measured within the ROIs. Results: Proton therapy can completely spare contra lateral brain while the target volume received full prescribed dose. From a series of MRI ADC images before and after PT at different follow ups, the enhancement corresponding to GTV had nearly disappeared more than 2 years after PT. Both ADC and FA demonstrate that contralateral normal brain tissue were not affect by PT and the tumor volume reverted to normal ADC and FA values. Conclusion: DTI allowed quantitative evaluation of tumor and normal brain tissue responses to PT. Further study in a larger cohort is warranted.

  10. Identification of high versus lower risk clinical subgroups in a group of adult patients with supratentorial anaplastic astrocytomas.

    PubMed

    Decaestecker, C; Salmon, I; Camby, I; Dewitte, O; Pasteels, J L; Brotchi, J; Van Ham, P; Kiss, R

    1995-05-01

    The present work investigates whether computer-assisted techniques can contribute any significant information to the characterization of astrocytic tumor aggressiveness. Two complementary computer-assisted methods were used. The first method made use of the digital image analysis of Feulgen-stained nuclei, making it possible to compute 15 morphonuclear and 8 nuclear DNA content-related (ploidy level) parameters. The second method enabled the most discriminatory parameters to be determined. This second method is the Decision Tree technique, which forms part of the Supervised Learning Algorithms. These two techniques were applied to a series of 250 supratentorial astrocytic tumors of the adult. This series included 39 low-grade (astrocytomas, AST) and 211 high-grade (47 anaplastic astrocytomas, ANA, and 164 glioblastomas, GBM) astrocytic tumors. The results show that some AST, ANA and GBM did not fit within simple logical rules. These "complex" cases were labeled NC-AST, NC-ANA and NC-GBM because they were "non-classical" (NC) with respect to their cytological features. An analysis of survival data revealed that the patients with NC-GBM had the same survival period as patients with GBM. In sharp contrast, patients with ANA survived significantly longer than patients with NC-ANA. In fact, the patients with ANA had the same survival period as patients who died from AST, while the patients with NC-ANA had a survival period similar to those with GBM. All these data show that the computer-assisted techniques used in this study can actually provide the pathologist with significant information on the characterization of astrocytic tumor aggressiveness. PMID:7745436

  11. Magnetic resonance diffusion tensor imaging and fiber-tracking diffusion tensor tractography in the management of spinal astrocytomas

    PubMed Central

    Landi, Alessandro; Palmarini, Valeria; D’Elia, Alessandro; Marotta, Nicola; Salvati, Maurizio; Santoro, Antonio; Delfini, Roberto

    2016-01-01

    Some specially imaging of magnetic resonance imaging, the diffusion-weighted imaging (DWI), the diffusion tensor imaging and fractional anisotropy (FA), are useful to described, detect, and map the extent of spinal cord lesions. FA measurements may are used to predicting the outcome of patients who have spinal cord lesions. Fiber tracking enable to visualizing the integrity of white matter tracts surrounding some lesions, and this information could be used to formulating a differential diagnosis and planning biopsies or resection. In this article, we will describe the current uses for DWI and fiber tracking and speculate on others in which we believe these techniques will be useful in the future. PMID:26798625

  12. Magnetic resonance diffusion tensor imaging and fiber-tracking diffusion tensor tractography in the management of spinal astrocytomas.

    PubMed

    Landi, Alessandro; Palmarini, Valeria; D'Elia, Alessandro; Marotta, Nicola; Salvati, Maurizio; Santoro, Antonio; Delfini, Roberto

    2016-01-16

    Some specially imaging of magnetic resonance imaging, the diffusion-weighted imaging (DWI), the diffusion tensor imaging and fractional anisotropy (FA), are useful to described, detect, and map the extent of spinal cord lesions. FA measurements may are used to predicting the outcome of patients who have spinal cord lesions. Fiber tracking enable to visualizing the integrity of white matter tracts surrounding some lesions, and this information could be used to formulating a differential diagnosis and planning biopsies or resection. In this article, we will describe the current uses for DWI and fiber tracking and speculate on others in which we believe these techniques will be useful in the future.

  13. Insulin-like growth factor-1 content and pattern of expression correlates with histopathologic grade in diffusely infiltrating astrocytomas.

    PubMed

    Hirano, H; Lopes, M B; Laws, E R; Asakura, T; Goto, M; Carpenter, J E; Karns, L R; VandenBerg, S R

    1999-04-01

    Studies of experimental tumorigenesis have strongly implicated signaling of the insulin-like growth factor 1 (IGF-1) as a key component in astrocytic neoplasia; however, its role in the growth of low-grade and malignant human tumors is not well understood. Correlative analyses of IGF-1, p53, and Ki-67 (MIB-1) immunohistochemistry and IGF-1 receptor (IGF-1R) mRNA expression were performed to examine the cellular pattern of IGF-1 signaling in 39 cases of astrocytoma (World Health Organization grades II-IV). Tumor cells expressing IGF-1 and IGF-1R were present in all tumor grades. The proportion of tumor cells that expressed IGF-1 correlated with both histopathologic grade and Ki-67 labeling indices, while expression of IGF-1R mRNA correlated with Ki-67 indices. In cases where stereotactic tissue sampling could be identified with a specific tumor area by neuroimaging features, the numbers of IGF-1 immunoreactive cells correlated with the tumor zones of highest cellularity and Ki-67 labeling. In glioblastomas, the localization of IGF-1 immunoreactivity was notable for several features: frequent accentuation in the perivascular tumor cells surrounding microvascular hyperplasia; increased levels in reactive astrocytes at the margins of tumor infiltration; and selective expression in microvascular cells exhibiting endothelial/pericytic hyperplasia. IGF-1R expression was particularly prominent in tumor cells adjacent to both microvascular hyperplasia and palisading necrosis. These data suggest that IGF-1 signaling occurs early in astroglial tumorigenesis in the setting of cell proliferation. The distinctive correlative patterns of IGF-1 and IGF-1R expression in glioblastomas also suggest that IGF-1 signaling has an association with the development of malignant phenotypes related to aberrant angiogenesis and invasive tumor interactions with reactive brain.

  14. IDH1 mutation is prognostic for diffuse astrocytoma but not low-grade oligodendrogliomas in patients not treated with early radiotherapy.

    PubMed

    Iwadate, Yasuo; Matsutani, Tomoo; Hirono, Seiichiro; Ikegami, Shiro; Shinozaki, Natsuki; Saeki, Naokatsu

    2015-09-01

    Despite accumulating knowledge regarding molecular backgrounds, the optimal management strategy for low-grade gliomas remains controversial. One reason is the marked heterogeneity in the clinical course. To establish an accurate subclassification of low-grade gliomas, we retrospectively evaluated isocitrate dehydrogenase-1 (IDH1) mutation in clinical specimens of diffuse astrocytomas (DA) and oligodendroglial tumors separately. No patients were treated with early radiotherapy, and modified PCV chemotherapy was used for postoperative residual tumors or recurrence in oligodendroglial tumors. Immunohistochemical evaluation of IDH status, p53 status, O(6)-methylguanine methyltransferase expression, and the MIB-1 index were performed. The 1p and 19q status was analyzed with fluorescence in situ hybridization. Ninety-four patients were followed for a median period of 8.5 years. For DAs, p53 was prognostic for progression- free survival (PFS) and IDH1 was significant for overall survival (OS) with multivariate analysis. In contrast, for oligodendroglial tumors, none of the parameters was significant for PFS or OS. Thus, the significance of IDH1 mutation is not clear in oligodendroglial tumors that are homogeneously indolent and chemosensitive. In contrast, DAs are heterogeneous tumors including some potentially malignant tumors that can be predicted by examining the IDH1 mutation status.

  15. Pathology and Genetics of Diffuse Gliomas in Adults

    PubMed Central

    KOMORI, Takashi

    2015-01-01

    The current World Health Organization (WHO) classification of tumors of the central nervous system (CNS) is essentially a lineage-oriented classification based on a presumable developmental tree of CNS. A four-tiered WHO grading scheme has been successfully applied to a spectrum of diffusely infiltrative astrocytomas, but it is not fully applicable to other gliomas, including oligodendrogliomas and ependymomas. Recent genetic studies have revealed that the major categories of gliomas, such as circumscribe astrocytomas, infiltrating astrocytomas/oligodendrogliomas, and glioblastoma, roughly correspond to major genetic alterations, including isocitrate dehydrogenases (IDHs) 1/2 mutations, TP53 mutations, co-deletion of chromosome arms 1p/19q, and BRAF mutation/fusion. These genetic alterations are clinically significant in terms of the response to treatment(s) and/or the prognosis. It is, thus, rational that future classification of gliomas should be based on genotypes, rather than phenotypes, although the genetic features of each tumor are not sufficiently understood at present to draw a complete map of the gliomas, and genetic testing is not yet available worldwide, particularly in Asian and African countries. This review summarizes the current concepts of the WHO classification, as well as the current understanding of the major genetic alterations in glioma and the potential use of these alterations as diagnostic criteria. PMID:25744348

  16. [Supra-tentorial low-grade astrocytomas in adults. Prognostic factors and therapeutic indications. Apropos of a series of 141 patients].

    PubMed

    Loiseau, H; Bousquet, P; Rivel, J; Vital, C; Kantor, G; Rougier, A; Dartigues, J F; Cohadon, F

    1995-01-01

    An abundant literature provides informations upon the prognosis of supratentorial low grade (grade II) astrocytomas, but the series are quite heterogeneous in terms of clinical material, neuropathological evaluation and statistical methods of analysis. So, outcome, prognostic factors and therapeutical indications are poorly defined. A retrospective study of 141 adults patients suffering ordinary low grade astrocytoma diagnosed in our unit between 1978 and 1988 was conducted. A follow up of 5 years or more, since neuropathological diagnosis, was mandatory for inclusion. Endpoint of statistical analysis was duration of survival. Results were expressed after uni and multivariates analysis. Clinical and morphological features of our series were comparable to those previously reported in the literature. Median survival time was 52 months. Considering age at diagnosis, survival curve analysis showed highly significant differences (p < 0.0001) and established three prognostic classes of age (before 50, between 50 and 60, and after 60 years of age). Comparisons of survival curves showed significant statistical differences (p < 0.0001) according to pretreatment functional status. Analysis of a clinical condition using a functional scale is more powerful, from a statistical point of view, than an individual analysis of each constituting parameters. In this series a good correlation was found between functional status and age at diagnosis. Neurological deficit was more correlated to age than to tumor location. Multivariate analysis, using the Cox model, defined some parameters acting independently on duration of survival: fronto-parietal location (p < 0.0001), pretherapeutical functional status (p < 0.001), age at diagnosis (p = 0.001), deepseated or multicentric tumor, mass effect (p < 0.01), frontal location (p < 0.02), total surgical removal (p < 0.05). Non significant parameters were: radiotherapy, time before diagnosis, age of onset, sex, contrast enhancement on CT scan

  17. Poly-ADP-Ribose Polymerase as a Therapeutic Target in Pediatric Diffuse Intrinsic Pontine Glioma and Pediatric High-Grade Astrocytoma.

    PubMed

    Chornenkyy, Yevgen; Agnihotri, Sameer; Yu, Man; Buczkowicz, Pawel; Rakopoulos, Patricia; Golbourn, Brian; Garzia, Livia; Siddaway, Robert; Leung, Stephie; Rutka, James T; Taylor, Michael D; Dirks, Peter B; Hawkins, Cynthia

    2015-11-01

    Pediatric high-grade astrocytomas (pHGA) and diffuse intrinsic pontine gliomas (DIPG) are devastating malignancies for which no effective therapies exist. We investigated the therapeutic potential of PARP1 inhibition in preclinical models of pHGA and DIPG. PARP1 levels were characterized in pHGA and DIPG patient samples and tumor-derived cell lines. The effects of PARP inhibitors veliparib, olaparib, and niraparib as monotherapy or as radiosensitizers on cell viability, DNA damage, and PARP1 activity were evaluated in a panel of pHGA and DIPG cell lines. Survival benefit of niraparib was examined in an orthotopic xenograft model of pHGA. About 85% of pHGAs and 76% of DIPG tissue microarray samples expressed PARP1. Six of 8 primary cell lines highly expressed PARP1. Interestingly, across multiple cell lines, some PARP1 protein expression was required for response to PARP inhibition; however, there was no correlation between protein level or PARP1 activity and sensitivity to PARP inhibitors. Niraparib was the most effective at reducing cell viability and proliferation (MTT and Ki67). Niraparib induced DNA damage (γH2AX foci) and induced growth arrest. Pretreatment of pHGA cells with a sublethal dose of niraparib (1 μmol/L) before 2 Gy of ionizing radiation (IR) decreased the rate of DNA damage repair, colony growth, and relative cell number. Niraparib (50 mg/kg) inhibited PARP1 activity in vivo and extended survival of mice with orthotopic pHGA xenografts, when administered before IR (20 Gy, fractionated), relative to control mice (40 vs. 25 days). Our data provide in vitro and in vivo evidence that niraparib may be an effective radiosensitizer for pHGA and DIPG. PMID:26351319

  18. Erlotinib and Temsirolimus in Treating Patients With Recurrent Malignant Glioma

    ClinicalTrials.gov

    2015-05-29

    Adult Anaplastic Astrocytoma; Adult Anaplastic Oligodendroglioma; Adult Diffuse Astrocytoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Mixed Glioma; Adult Pilocytic Astrocytoma; Adult Pineal Gland Astrocytoma; Adult Subependymal Giant Cell Astrocytoma; Recurrent Adult Brain Tumor

  19. Patterns of practice and survival in a retrospective analysis of 1722 adult astrocytoma patients treated between 1985 and 2001 in 12 Italian radiation oncology centers

    SciTech Connect

    Magrini, Stefano Maria . E-mail: magrini@med.unibs.it; Ricardi, Umberto; Santoni, Riccardo; Krengli, Marco; Lupattelli, Marco; Cafaro, Ines; Scoccianti, Silvia; Menichelli, Claudia; Bertoni, Filippo; Enrici, Riccardo Maurizi; Tombolini, Vincenzo; Buglione, Michela; Pirtoli, Luigi

    2006-07-01

    Purpose: To analyze the patterns of practice and survival in a series of 1722 adult astrocytoma patients treated in 12 Italian radiotherapy centers. Methods and Materials: A total of 1722 patients were treated with postoperative radiotherapy (90% World Health Organization [WHO] Grade 3-4, 62% male, 44% aged >60 years, 25% with severe neurologic deficits, 44% after gross total resection, 52% with high-dose radiotherapy, and 16% with chemotherapy). Variations in the clinical-therapeutic features in three subsequent periods (1985 through 2001) were evaluated, along with overall survival for the different subgroups. Results: The proportion of women, of older patients, of those with worse neurologic performance status (NPS), with WHO Grade 4, and with smaller tumors increased with time, as did the proportion of those treated with radical surgery, hypofractionated radiotherapy, and more sophisticated radiotherapy techniques, after staging procedures progressively became more accurate. The main prognostic factors for overall survival were age, sex, neurologic performance status, WHO grade, extent of surgery, and radiation dose. Conclusions: Recently, broader selection criteria for radiotherapy were adopted, together with simpler techniques, smaller total doses, and larger fraction sizes for the worse prognostic categories. Younger, fit patients are treated more aggressively, more often in association with chemotherapy. Survival did not change over time. The accurate evaluation of neurologic status is therefore of utmost importance before the best treatment option for the individual patient is chosen.

  20. General Information about Childhood Astrocytomas

    MedlinePlus

    ... Research Childhood Astrocytomas Treatment (PDQ®)–Patient Version General Information About Childhood Astrocytomas Go to Health Professional Version ... the PDQ Pediatric Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

  1. Pilomyxoid Astrocytoma of the Brainstem

    PubMed Central

    Pereira, Francisco Otavio; Lombardi, Ismael Augusto; Mello, Adriana Yuki; Romero, Flavio Ramalho; Ducati, Luis Gustavo; Gabarra, Roberto Colichio; Zanini, Marco Antonio

    2013-01-01

    Abstract A pilomyxoid astrocytoma is a recently described tumor that occurs predominantly in the hypothalamic-chiasmatic region and is rarely found elsewhere. It has similar features as pilocytic astrocytomas, but has distinct histological characteristics and a poorer prognosis. A pilomyxoid astrocytoma is an aggressive tumor, and increased awareness is necessary with a suspect case. We present the first case of a pilomyxoid astrocytoma of the brainstem described after the newest World Health Organization classification of central nervous system tumors. PMID:23888217

  2. Pilomyxoid astrocytoma of the brainstem.

    PubMed

    Pereira, Francisco Otavio; Lombardi, Ismael Augusto; Mello, Adriana Yuki; Romero, Flavio Ramalho; Ducati, Luis Gustavo; Gabarra, Roberto Colichio; Zanini, Marco Antonio

    2013-04-15

    A pilomyxoid astrocytoma is a recently described tumor that occurs predominantly in the hypothalamic-chiasmatic region and is rarely found elsewhere. It has similar features as pilocytic astrocytomas, but has distinct histological characteristics and a poorer prognosis. A pilomyxoid astrocytoma is an aggressive tumor, and increased awareness is necessary with a suspect case. We present the first case of a pilomyxoid astrocytoma of the brainstem described after the newest World Health Organization classification of central nervous system tumors.

  3. Differential proteomics analysis of low- and high-grade of astrocytoma using iTRAQ quantification

    PubMed Central

    Ren, Tong; Lin, Shide; Wang, Zhongfeng; Shang, Aijia

    2016-01-01

    Astrocytoma is one of the most common types of brain tumor, which is histologically and clinically classified into four grades (I–IV): I (pilocytic astrocytoma), II (diffuse astrocytoma), III (anaplastic astrocytoma), and IV (glioblastoma multiforme). A higher grade astrocytoma represents a worse prognosis and is more aggressive. In this study, we compared the differential proteome profile of astrocytoma from grades I to IV. The protein samples from clinical specimens of grades I, II, III, and IV astrocytoma were analyzed by two-dimensional liquid chromatography–tandem mass spectrometry and isobaric tags for relative and absolute quantitation and quantification. A total of 2,190 proteins were identified. Compared to grade I astrocytoma, 173 (12.4%), 304 (14%), and 462 (21.2%) proteins were aberrantly expressed in grades II, III, and IV, respectively. By bioinformatics analysis, the cell proliferation, invasion, and angiogenesis-related pathways increase from low- to high-grade of astrocytoma. Five differentially expressed proteins were validated by Western blot. Within them, matrix metalloproteinase-9 and metalloproteinase inhibitor 1 were upregulated in glioblastoma multiforme group; whereas fibulin-2 and -5 were downregulated in grade II/III/IV astrocytoma, and the negative expression was significantly associated with advanced clinical stage. Functional analysis showed that both fibulin-2 and -5 may exert an antitumor effect by inhibiting cell proliferation, in vitro migration/invasion in glioma cells. New molecular biomarkers are likely to be used for accurate classification of astrocytoma and likely to be the target for drug development. PMID:27713642

  4. Sunitinib in Treating Patients With Recurrent Malignant Gliomas

    ClinicalTrials.gov

    2016-01-29

    Adult Anaplastic Astrocytoma; Adult Diffuse Astrocytoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Mixed Glioma; Adult Oligodendroglioma; Adult Pineal Gland Astrocytoma

  5. Use of EF5 to Measure the Oxygen Level in Tumor Cells of Patients Undergoing Surgery or Biopsy for Newly Diagnosed Supratentorial Malignant Glioma

    ClinicalTrials.gov

    2013-01-15

    Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Oligodendroglioma; Adult Diffuse Astrocytoma; Adult Ependymoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Mixed Glioma; Adult Myxopapillary Ependymoma; Adult Oligodendroglioma; Adult Pilocytic Astrocytoma; Adult Pineal Gland Astrocytoma; Adult Subependymoma

  6. Pilomyxoid astrocytoma with high proliferation index.

    PubMed

    Pruthi, Sonam Kumar; Chakraborti, Shrijeet; Naik, Ramadas; Ballal, C K

    2013-09-01

    Pilomyxoid astrocytomas is an uncommon aggressive piloid neoplasm, closely related to pilocytic astrocytomas and typically presents in the very young but can occur in older children and rarely in adults. A 12-years-old male presented with focal seizures, headache and vomiting of 10 days duration. Computed tomogram showed a hypo- to hyperdense and peripherally enhancing, solid-cystic lesion in the left temporal lobe. Histopathological examination revealed a characteristic tumor composed of bipolar cells arranged in dyscohesive sheets, angiocentric pattern in a loose myxoid background, with brisk mitotic activity and foci of necrosis. No Rosenthal fibers or eosinophilic granular bodies were seen. The tumor cells showed strong GFAP and scattered p53 positivity, but were negative for EMA. Ki-67 positivity ranged from 30 to 40%, highest reported till date. The patient was treated with radiotherapy and concurrent temozolamide and the tumor recurred after two years. PMID:24470824

  7. Copy Number Profiling of Brazilian Astrocytomas

    PubMed Central

    Bidinotto, Lucas Tadeu; Torrieri, Raul; Mackay, Alan; Almeida, Gisele Caravina; Viana-Pereira, Marta; Cruvinel-Carloni, Adriana; Spina, Maria Luisa; Campanella, Nathalia Cristina; Pereira de Menezes, Weder; Clara, Carlos Afonso; Becker, Aline Paixão; Jones, Chris; Reis, Rui Manuel

    2016-01-01

    Copy number alterations (CNA) are one of the driving mechanisms of glioma tumorigenesis, and are currently used as important biomarkers in the routine setting. Therefore, we performed CNA profiling of 65 astrocytomas of distinct malignant grades (WHO grade I–IV) of Brazilian origin, using array-CGH and microsatellite instability analysis (MSI), and investigated their correlation with TERT and IDH1 mutational status and clinico-pathological features. Furthermore, in silico analysis using the Oncomine database was performed to validate our findings and extend the findings to gene expression level. We found that the number of genomic alterations increases in accordance with glioma grade. In glioblastomas (GBM), the most common alterations were gene amplifications (PDGFRA, KIT, KDR, EGFR, and MET) and deletions (CDKN2A and PTEN). Log-rank analysis correlated EGFR amplification and/or chr7 gain with better survival of the patients. MSI was observed in 11% of GBMs. A total of 69% of GBMs presented TERT mutation, whereas IDH1 mutation was most frequent in diffuse (85.7%) and anaplastic (100%) astrocytomas. The combination of 1p19q deletion and TERT and IDH1 mutational status separated tumor groups that showed distinct age of diagnosis and outcome. In silico validation pointed to less explored genes that may be worthy of future investigation, such as CDK2, DMRTA1, and MTAP. Herein, using an extensive integrated analysis, we indicated potentially important genes, not extensively studied in gliomas, that could be further explored to assess their biological and clinical impact in astrocytomas. PMID:27172220

  8. Overexpression of vascular adhesion protein-1 is associated with poor prognosis of astrocytomas.

    PubMed

    Kostoro, Joanna; Chang, Shu-Jyuan; Clark Lai, Yen-Chang; Wu, Chun-Chieh; Chai, Chee-Yin; Kwan, Aij-Lie

    2016-06-01

    Vascular adhesion protein-1 (VAP-1) is one of the endothelial adhesion molecules that is believed to play a role in tumor progression and metastasis, supporting cancer cell extravasation. Very few studies have been performed on analyzing the contribution of VAP-1 in brain tumor. Astrocytomas are the most common type of brain tumors, which are classified by World Health Organization (WHO) into four grades according to the degree of malignancy. This study was designed to investigate VAP-1 expression level in different astrocytoma grades and its correlation with clinicopathological features as well as prognosis of astrocytoma patients. Eighty-seven patients with different grades of astrocytoma (WHO Grade I-Grade IV) were enrolled in this study. The expression of VAP-1 was assayed by immunohistochemistry. The correlation between VAP-1 expression and clinicopathological features was evaluated by Chi-square test, and overall survival was analyzed by Kaplan-Meier method. Cox regression analysis was applied to analyze the independent influence of each parameter on overall survival. The expression level of VAP-1 was significantly higher in diffuse astrocytoma than those of pilocytic astrocytoma (p < 0.0001). In the subgroup analysis, upregulated VAP-1 expression was frequently found in older age patients (≥50 years). The VAP-1 expression was found to be significantly correlated with the overall survival (p = 0.0002). There was a statistical correlation between VAP-1(high) tumors in diffuse astrocytoma and VAP-1(low) tumors in pilocytic astrocytoma (p < 0.0001). Multivariate Cox analysis indicated VAP-1 was an independent predictive marker for poorer prognosis (p = 0.0036). Therefore, VAP-1 could be a promising prognostic biomarker in astrocytoma.

  9. Temsirolimus and Perifosine in Treating Patients With Recurrent or Progressive Malignant Glioma

    ClinicalTrials.gov

    2016-07-06

    Adult Anaplastic Astrocytoma; Adult Anaplastic Oligodendroglioma; Adult Diffuse Astrocytoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Mixed Glioma; Adult Oligodendroglioma; Recurrent Adult Brain Neoplasm

  10. Erlotinib Hydrochloride and Isotretinoin in Treating Patients With Recurrent Malignant Glioma

    ClinicalTrials.gov

    2015-07-27

    Adult Anaplastic Astrocytoma; Adult Anaplastic Oligodendroglioma; Adult Diffuse Astrocytoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Mixed Glioma; Adult Oligodendroglioma; Recurrent Adult Brain Tumor

  11. Coexistent dysembryoplastic neuroepithelial tumour and pilocytic astrocytoma

    PubMed Central

    Nasit, Jitendra G.; Shah, Payal; Zalawadia, Himanshu

    2016-01-01

    Dysembryoplastic neuroepithelial tumour (DNET) is an uncommon mixed glioneuronal tumour. DNET is classified as Grade I neoplasm in revised World Health Organization classification of tumors of the nervous system. DNET is commonly seen in the temporal lobe of children and young adults with features of pharmacoresistant complex partial seizures. Tumors arising in association with DNETs are rare. Only two cases of pilocytic astrocytoma (PA) arising in DNETs are reported. Surgical excision is the only successful management with favourable prognosis. The development of recurrence and malignancy after subtotal or even after complete excision challenges the premise of stability and highlights the importance of close clinical follow up. Here, a case of DNET with area of PA is described which helps in understanding the pathogenesis and biological behavior of DNET.

  12. Coexistent dysembryoplastic neuroepithelial tumour and pilocytic astrocytoma

    PubMed Central

    Nasit, Jitendra G.; Shah, Payal; Zalawadia, Himanshu

    2016-01-01

    Dysembryoplastic neuroepithelial tumour (DNET) is an uncommon mixed glioneuronal tumour. DNET is classified as Grade I neoplasm in revised World Health Organization classification of tumors of the nervous system. DNET is commonly seen in the temporal lobe of children and young adults with features of pharmacoresistant complex partial seizures. Tumors arising in association with DNETs are rare. Only two cases of pilocytic astrocytoma (PA) arising in DNETs are reported. Surgical excision is the only successful management with favourable prognosis. The development of recurrence and malignancy after subtotal or even after complete excision challenges the premise of stability and highlights the importance of close clinical follow up. Here, a case of DNET with area of PA is described which helps in understanding the pathogenesis and biological behavior of DNET. PMID:27695565

  13. Fluorine F 18 Fluorodopa-Labeled PET Scan in Planning Surgery and Radiation Therapy in Treating Patients With Newly Diagnosed High- or Low-Grade Malignant Glioma

    ClinicalTrials.gov

    2016-10-10

    Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Diffuse Astrocytoma; Adult Ependymoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Mixed Glioma; Adult Myxopapillary Ependymoma; Adult Oligodendroglioma; Adult Pilocytic Astrocytoma; Adult Pineal Gland Astrocytoma; Adult Subependymal Giant Cell Astrocytoma; Adult Subependymoma

  14. Optic nerve astrocytoma in a dog.

    PubMed

    Rozov, Orr; Piñeyro, Pablo E; Zimmerman, Kurt L; Herring, Ian P; Matusow, Rachel; Rossmeisl, John H; Jortner, Bernard S; Dreyfus, Jennifer

    2016-09-01

    Intracranial astrocytomas are relatively uncommon in dogs and optic nerve astrocytomas even more so. This neoplasm should be considered as differential in canine patients with vision loss, retinal detachment, ocular mass, and histopathologic findings of infiltrative fusiform to polygonal glial cells possibly associated with glomeruloid vascular proliferation. PMID:27648262

  15. Alisertib and Fractionated Stereotactic Radiosurgery in Treating Patients With Recurrent High Grade Gliomas

    ClinicalTrials.gov

    2016-10-19

    Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Diffuse Astrocytoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Mixed Glioma; Adult Oligodendroglioma; Adult Pilocytic Astrocytoma; Adult Pineal Gland Astrocytoma; Adult Subependymal Giant Cell Astrocytoma; Recurrent Adult Brain Tumor

  16. Astrocytoma of the cerebral aqueduct.

    PubMed

    Solá, J; Arcas, I; Martínez-Lage, J F; Martínez Pérez, M; Esteban, J A; Poza, M

    1987-01-01

    The authors report the case of a 9-year-old girl with a low-grade astrocytoma of the mesencephalon that occluded the sylvian aqueduct. Symptoms, signs, and neuroradiological investigations led to the clinical impression of aqueductal stenosis. The presence of a tumor was diagnosed by cerebrospinal fluid cytology and confirmed at postmortem examination. This is the first reported instance of this tumor being diagnosed by cerebrospinal fluid cytology and the third report of a diagnosis in a living patient. The authors stress the value of CSF cytology in evaluating a typical case of hydrocephalus.

  17. Brain astrocytomas: biopsy, then irradiation.

    PubMed

    Lunsford, L D; Somaza, S; Kondziolka, D; Flickinger, J C

    1995-01-01

    We believe that every patient who has clinical symptoms and neurodiagnostic imaging signs suggesting a low-grade glial neoplasm should undergo early diagnosis and treatment. Observation is not warranted for a tumor that has a median survival of 5 years. The value of cytoreductive surgery for many patients has yet to be proven. It is incumbent on neurosurgeons who advocate this approach to show that this more aggressive treatment strategy is preferable to minimally invasive techniques, such as stereotactic biopsy followed by radiation therapy. Clearly, some patients who have a glial tumor require early cytoreductive surgery: those with mass effect and significant neurologic deficits. Otherwise, they will not be able to tolerate fractionated radiation therapy. Because the long-term survival rate is very poor, observation is not warranted in patients with suspected glial neoplasm. Early stereotactic biopsy immediately identifies those patients who, in fact, have more anaplastic tumors and a much worse prognosis. Such patients may benefit from early, aggressive treatments such as cytoreductive surgery, chemotherapy, and radiation. Applying this philosophy, we have achieved a median survival of more than 10 years in patients with astrocytoma. Most patients maintain a high KPS rating, and most do not require delayed cytoreductive surgery. Although we believe that the outcomes of future patients with astrocytomas will improve, we must establish whether such improvement is related to better therapeutic options, earlier recognition enabled by advanced neuroimaging, or the availability of corticosteroids (28, 30). We also believe that neurosurgeons and neuro-oncologists should stop arguing over whether cytoreductive surgery is warranted. For some patients it is, and for others it is not. This prolonged controversy indicates the basic impotence with which neurosurgeons approach glial tumors. Our energy and efforts should be devoted toward more concrete and positive goals in

  18. Molecular analysis of diffuse intrinsic brainstem gliomas in adults.

    PubMed

    Reyes-Botero, German; Giry, Marine; Mokhtari, Karima; Labussière, Marianne; Idbaih, Ahmed; Delattre, Jean-Yves; Laigle-Donadey, Florence; Sanson, Marc

    2014-01-01

    Diffuse intrinsic brainstem gliomas (DIBG) account for 1-2 % of adult gliomas. Their biological characteristics are scarcely understood and whether DIBG are biologically different from supratentorial gliomas remains to be established. We analyzed 17 DIBG samples for IDH1 R132H, alpha internexin, p53, and Ki67 expression, and, in a subset with sufficient DNA amount, for IDH1 and histone H3 mutational status, genomic profiling and MGMT promoter methylation status. A series of 738 adult supratentorial gliomas was used for comparison. Median age at diagnosis was 41 years (range 18.9-65.3 years). Median overall survival was 48.7 months (57 months for low-grade vs. 16 months for high-grade gliomas, p < 0.01). IDH1 sequencing revealed two mutations (IDH1 (R132G) , IDH1 (R132C) ) out of 7 DIBG whereas the R132H IDH1 enzyme was detected in 1/17 DIBG, suggesting that IDH1 mutations are mostly non R132H in DIBG (2/2), in contrast to supratentorial gliomas (31/313; p = 0.01). Mutations in histone genes H3F3A (encoding H3.3) and HIST1H3B (encoding H3.1) were found in 3/8 (37.5 %) of the DIBG (two H3F3A (K27M) and one HIST1H3B (K27M) ) versus 6/205 (2.9 %) of the supratentorial high-grade gliomas (four H3F3A (G34R) and two H3F3A (K27M) ) (p = 0.002). The CGH array showed a higher frequency of chromosome arm 1q gain, 9q gain and 11q loss in DIBG compared to the supratentorial high-grade gliomas, which had a less frequent chromosome 7 gain, and a less frequent chromosome 10 loss. No EGFR amplification was found. These data suggest that adult DIBG differ from adult supratentorial gliomas. In particular, histone genes (H3F3A (K27M) , HIST1H3B (K27M) ) mutations are frequent in adult DIBG whereas IDH1 (R132H) mutations are rare. PMID:24242757

  19. Diffusion tensor tractography findings in schizophrenia across the adult lifespan.

    PubMed

    Voineskos, Aristotle N; Lobaugh, Nancy J; Bouix, Sylvain; Rajji, Tarek K; Miranda, Dielle; Kennedy, James L; Mulsant, Benoit H; Pollock, Bruce G; Shenton, Martha E

    2010-05-01

    In healthy adult individuals, late life is a dynamic time of change with respect to the microstructural integrity of white matter tracts. Yet, elderly individuals are generally excluded from diffusion tensor imaging studies in schizophrenia. Therefore, we examined microstructural integrity of frontotemporal and interhemispheric white matter tracts in schizophrenia across the adult lifespan. Diffusion tensor imaging data from 25 younger schizophrenic patients (< or = 55 years), 25 younger controls, 25 older schizophrenic patients (> or = 56 years) and 25 older controls were analysed. Patients with schizophrenia in each group were individually matched to controls. Whole-brain tractography and clustering segmentation were employed to isolate white matter tracts. Groups were compared using repeated measures analysis of variance with 12 within-group measures of fractional anisotropy: (left and right) uncinate fasciculus, arcuate fasciculus, inferior longitudinal fasciculus, inferior occipito-frontal fasciculus, cingulum bundle, and genu and splenium of the corpus callosum. For each white matter tract, fractional anisotropy was then regressed against age in patients and controls, and correlation coefficients compared. The main effect of group (F(3,92) = 12.2, P < 0.001), and group by tract interactions (F(26,832) = 1.68, P = 0.018) were evident for fractional anisotropy values. Younger patients had significantly lower fractional anisotropy than younger controls (Bonferroni-corrected alpha = 0.0042) in the left uncinate fasciculus (t(48) = 3.7, P = 0.001) and right cingulum bundle (t(48) = 3.6, P = 0.001), with considerable effect size, but the older groups did not differ. Schizophrenic patients did not demonstrate accelerated age-related decline compared with healthy controls in any white matter tract. To our knowledge, this is the first study to examine the microstructural integrity of frontotemporal white matter tracts across the adult lifespan in schizophrenia. The

  20. Anticancer activity of glucomoringin isothiocyanate in human malignant astrocytoma cells.

    PubMed

    Rajan, Thangavelu Soundara; De Nicola, Gina Rosalinda; Iori, Renato; Rollin, Patrick; Bramanti, Placido; Mazzon, Emanuela

    2016-04-01

    Isothiocyanates (ITCs) released from their glucosinolate precursors have been shown to inhibit tumorigenesis and they have received significant attention as potential chemotherapeutic agents against cancer. Astrocytoma grade IV is the most frequent and most malignant primary brain tumor in adults without any curative treatment. New therapeutic drugs are therefore urgently required. In the present study, we investigated the in vitro antitumor activity of the glycosylated isothiocyanate moringin [4-(α-l-rhamnopyranosyloxy)benzyl isothiocyanate] produced from quantitative myrosinase-induced hydrolysis of glucomoringin (GMG) under neutral pH value. We have evaluated the potency of moringin on apoptosis induction and cell death in human astrocytoma grade IV CCF-STTG1 cells. Moringin showed to be effective in inducing apoptosis through p53 and Bax activation and Bcl-2 inhibition. In addition, oxidative stress related Nrf2 transcription factor and its upstream regulator CK2 alpha expressions were modulated at higher doses, which indicated the involvement of oxidative stress-mediated apoptosis induced by moringin. Moreover, significant reduction in 5S rRNA was noticed with moringin treatment. Our in vitro results demonstrated the antitumor efficacy of moringin derived from myrosinase-hydrolysis of GMG in human malignant astrocytoma cells. PMID:26882972

  1. Low-grade astrocytomas of childhood.

    PubMed

    Rekate, H L; Rakfal, S M

    1991-05-01

    Low-grade astrocytomas are the single most common form of pediatric brain tumor, representing 28% of the total. Prolonged survival and even cures can be expected in a substantial proportion of patients who present with these tumors. For a variety of reasons, the overall oncologic management of children with low-grade astrocytomas is extremely controversial. This article analyzes the available information related to the management of various forms of low-grade astrocytoma in childhood while awaiting the performance of a long-term national cooperative study on the natural history and management of this common pediatric brain tumor.

  2. Astrocytoma

    MedlinePlus

    ... Tumor PNET Schwannoma Risk Factors Brain Tumor Facts Brain Tumor Dictionary Webinars Anytime Learning About Us Our Founders Board of Directors Staff ... Tumor PNET Schwannoma Risk Factors Brain Tumor Facts Brain Tumor Dictionary Webinars Anytime Learning Subscribe for e-updates Please leave this field ...

  3. Mitotic recombination of chromosome 17 in astrocytomas

    SciTech Connect

    James, C.D.; Carlbom, E.; Nordenskjold, M.; Collins, V.P.; Cavenee, W.K. )

    1989-04-01

    Allelic combinations at seven loci on human chromosome 17 defined by restriction fragment length polymorphisms were determined in tumor and normal tissues from 35 patients with gliomas. Loss of constitutional heterozygosity at one or more of these loci was observed in 8 of the 24 tumors displaying astrocytic differentiation and in the single primitive neuroectodermal tumor examined. The astrocytomas showing these losses included examples of each adult malignancy grade of the disease, including glioblastoma (malignancy grade IV), and seven of them demonstrated concurrent maintenance of heterozygosity for at least one chromosome 17 locus. Determination of allele dosage together with the genotypic data indicated that the tumor chromosomes 17 were derived by mitotic recombination in 7 of the 9 cases with shared homozygosity of the region 17p11.2-ptr in all cases. In contrast, tumors of oligodendrocytic, ependymal, or mixed cellular differentiation did not exhibit loss of alleles at any of the loci examined. These data suggest that the somatic attainment of homozygosity for loci on chromosome 17p is frequently associated with the oncogenesis of central nervous system tumors, particularly those showing solely astrocytic differentiation, and that mitotic recombination mapping is a useful approach towards the subregional localization of a locus whose rearrangement is involved in this disease.

  4. Astrocytoma with involvement of medulla oblongata, spinal cord and spinal nerves in a raccoon (Procyon lotor)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Neoplasms affecting the central and peripheral nervous systems of wild animals are extremely rare. Described are clinical signs, pathologic and immunohistochemical findings in an adult female raccoon (Procyon lotor) with an astrocytoma which involved brainstem, cervical spinal cord and roots of the ...

  5. Frontal lobe astrocytoma following radiotherapy for medulloblastoma

    SciTech Connect

    Cohen, M.S.; Kushner, M.J.; Dell, S.

    1981-05-01

    A young woman had a frontal lobe astrocytoma 14 years after successful treatment of a posterior fossa medulloblastoma by surgery and whole-neuraxis irradiation. The association of these two tumors is rare, and it is unlikely that the second tumor was the result of metastasis and differentiation of residual or recurrent medulloblastoma. We review the evidence supporting this view and also the likelihood that the astrocytoma was induced by the prior radiation.

  6. [An unusual and misleading form of pilocytic astrocytoma].

    PubMed

    Burel-Vandenbos, Fanny; Jouvet, Anne; Chanalet, Stéphane; Lonjon, Michel; Cardot-Leccia, Nathalie; Michiels, Jean-François

    2006-04-01

    Pilocytic astrocytoma is histologically characterized by a biphasic pattern. We report a myxoid form of frontocallosal pilocytic astrocytoma in a 13-year-old girl. MRI showed a relatively well-defined tumor with necrosis and ring-like zone of contrast enhancement. Histological examination showed a monophasic tumor composed of piloid cells on a myxoid background corresponding to a pilomyxoid astrocytoma. This unusual form of pilocytic astrocytoma can be mistaken for a high grade infiltrating glioma. Pilomyxoid astrocytoma is more aggressive than classic pilocytic astrocytoma and has to be distinguished from it. PMID:16791125

  7. Expression patterns of Wnt signaling component, secreted frizzled‑related protein 3 in astrocytoma and glioblastoma.

    PubMed

    Pećina-Šlaus, Nives; Kafka, Anja; Varošanec, Ana Maria; Marković, Leon; Krsnik, Željka; Njirić, Niko; Mrak, Goran

    2016-05-01

    Secreted frizzled-related protein 3 (SFRP3) is a member of the family of soluble proteins, which modulate the Wnt signaling cascade. Novel research has identified aberrant expression of SFRPs in different types of cancer. In the present study the expression intensities and localizations of the SFRP3 protein across different histopathological grades of astrocytic brain tumors were investigated by immunohistochemistry, digital scanning and image analysis. The results demonstrated that the differences between expression levels and malignancy grades were statistically significant. Tumors were classified into four malignancy grades according to the World Health Organization guidelines. Moderate (P=0.014) and strong (P=0.028) nuclear expression levels were significantly different in pilocytic (grade I) and diffuse (grade II) astrocytomas demonstrating higher expression values, as compared with anaplastic astrocytoma (grade III) and glioblastoma (grade IV). When the sample was divided into two groups, the moderate and high cytoplasmic expression levels were observed to be significantly higher in glioblastomas than in the group comprising astrocytoma II and III. Furthermore, the results indicated that high grade tumors were associated with lower values of moderate (P=0.002) and strong (P=0.018) nuclear expression in comparison to low grade tumors. Analysis of cytoplasmic staining demonstrated that strong cytoplasmic expression was significantly higher in the astrocytoma III and IV group than in the astrocytoma I and II group (P=0.048). Furthermore, lower grade astrocytomas exhibited reduced membranous SFRP3 staining when compared with higher grade astrocytomas and this difference was statistically significant (P=0.036). The present results demonstrated that SFRP3 protein expression levels were decreased in the nucleus in higher grade astrocytoma (indicating the expected behavior of an antagonist of Wnt signaling), whereas when the SFRP3 was located in the

  8. Expression patterns of Wnt signaling component, secreted frizzled‑related protein 3 in astrocytoma and glioblastoma.

    PubMed

    Pećina-Šlaus, Nives; Kafka, Anja; Varošanec, Ana Maria; Marković, Leon; Krsnik, Željka; Njirić, Niko; Mrak, Goran

    2016-05-01

    Secreted frizzled-related protein 3 (SFRP3) is a member of the family of soluble proteins, which modulate the Wnt signaling cascade. Novel research has identified aberrant expression of SFRPs in different types of cancer. In the present study the expression intensities and localizations of the SFRP3 protein across different histopathological grades of astrocytic brain tumors were investigated by immunohistochemistry, digital scanning and image analysis. The results demonstrated that the differences between expression levels and malignancy grades were statistically significant. Tumors were classified into four malignancy grades according to the World Health Organization guidelines. Moderate (P=0.014) and strong (P=0.028) nuclear expression levels were significantly different in pilocytic (grade I) and diffuse (grade II) astrocytomas demonstrating higher expression values, as compared with anaplastic astrocytoma (grade III) and glioblastoma (grade IV). When the sample was divided into two groups, the moderate and high cytoplasmic expression levels were observed to be significantly higher in glioblastomas than in the group comprising astrocytoma II and III. Furthermore, the results indicated that high grade tumors were associated with lower values of moderate (P=0.002) and strong (P=0.018) nuclear expression in comparison to low grade tumors. Analysis of cytoplasmic staining demonstrated that strong cytoplasmic expression was significantly higher in the astrocytoma III and IV group than in the astrocytoma I and II group (P=0.048). Furthermore, lower grade astrocytomas exhibited reduced membranous SFRP3 staining when compared with higher grade astrocytomas and this difference was statistically significant (P=0.036). The present results demonstrated that SFRP3 protein expression levels were decreased in the nucleus in higher grade astrocytoma (indicating the expected behavior of an antagonist of Wnt signaling), whereas when the SFRP3 was located in the

  9. Expression patterns of Wnt signaling component, secreted frizzled-related protein 3 in astrocytoma and glioblastoma

    PubMed Central

    PEĆINA-ŠLAUS, NIVES; KAFKA, ANJA; VAROŠANEC, ANA MARIA; MARKOVIĆ, LEON; KRSNIK, ŽELJKA; NJIRIĆ, NIKO; MRAK, GORAN

    2016-01-01

    Secreted frizzled-related protein 3 (SFRP3) is a member of the family of soluble proteins, which modulate the Wnt signaling cascade. Novel research has identified aberrant expression of SFRPs in different types of cancer. In the present study the expression intensities and localizations of the SFRP3 protein across different histopathological grades of astrocytic brain tumors were investigated by immunohistochemistry, digital scanning and image analysis. The results demonstrated that the differences between expression levels and malignancy grades were statistically significant. Tumors were classified into four malignancy grades according to the World Health Organization guidelines. Moderate (P=0.014) and strong (P=0.028) nuclear expression levels were significantly different in pilocytic (grade I) and diffuse (grade II) astrocytomas demonstrating higher expression values, as compared with anaplastic astrocytoma (grade III) and glioblastoma (grade IV). When the sample was divided into two groups, the moderate and high cytoplasmic expression levels were observed to be significantly higher in glioblastomas than in the group comprising astrocytoma II and III. Furthermore, the results indicated that high grade tumors were associated with lower values of moderate (P=0.002) and strong (P=0.018) nuclear expression in comparison to low grade tumors. Analysis of cytoplasmic staining demonstrated that strong cytoplasmic expression was significantly higher in the astrocytoma III and IV group than in the astrocytoma I and II group (P=0.048). Furthermore, lower grade astrocytomas exhibited reduced membranous SFRP3 staining when compared with higher grade astrocytomas and this difference was statistically significant (P=0.036). The present results demonstrated that SFRP3 protein expression levels were decreased in the nucleus in higher grade astrocytoma (indicating the expected behavior of an antagonist of Wnt signaling), whereas when the SFRP3 was located in the cytoplasm an

  10. SOX10 Distinguishes Pilocytic and Pilomyxoid Astrocytomas From Ependymomas but Shows No Differences in Expression Level in Ependymomas From Infants Versus Older Children or Among Molecular Subgroups.

    PubMed

    Kleinschmidt-DeMasters, B K; Donson, Andrew M; Richmond, Abby M; Pekmezci, Melike; Tihan, Tarik; Foreman, Nicholas K

    2016-04-01

    SOX10 is important in nonneoplastic oligodendroglial development, but mRNA transcripts and protein expression are identified in a wider variety of CNS glial neoplasms than oligodendrogliomas. We previously demonstrated high levels of SOX10 mRNA and protein in pilocytic astrocytomas (PAs) but not ependymomas (EPNs). We now extend these studies to investigate subsets of these 2 tumors that affect infants, pilomyxoid astrocytomas (PMAs) and infant (<1 year) ependymomas (iEPNs). By gene expression microarray analysis, we found that iEPNs and all EPNs in older children showed very low SOX10 expression levels, on average 7.1-fold below normal control tissues. EPN groups showed no significant difference in SOX10 expression between iEPN and EPN. PAs/PMAs had 24.1/29.4-fold higher transcript levels, respectively, than those in normal tissues. Using immunohistochemical analysis of adult, pediatric, and infantile EPNs and of PAs/PMAs, we found that EPNs from multiple anatomical locations and both age groups (n = 228) never showed 3+ diffuse nuclear immunostaining for SOX10; the majority were scored at 0 or 1+. Conversely, almost all pediatric and adult PAs and PMAs (n = 47) were scored as 3+. These results suggest that in select settings, SOX10 immunohistochemistry can supplement the diagnosis of PMA and PA and aid in distinguishing them from EPNs. PMID:26945037

  11. 18F FDOPA PET/CT or PET/MRI in Measuring Tumors in Patients With Newly Diagnosed or Recurrent Gliomas

    ClinicalTrials.gov

    2016-06-22

    Adult Anaplastic Ependymoma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Diffuse Astrocytoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Mixed Glioma; Adult Oligodendroglioma; Adult Pilocytic Astrocytoma; Adult Pineal Gland Astrocytoma; Adult Subependymal Giant Cell Astrocytoma; Childhood High-grade Cerebellar Astrocytoma; Childhood High-grade Cerebral Astrocytoma; Childhood Low-grade Cerebellar Astrocytoma; Childhood Low-grade Cerebral Astrocytoma; Recurrent Adult Brain Tumor; Recurrent Childhood Anaplastic Astrocytoma; Recurrent Childhood Anaplastic Oligoastrocytoma; Recurrent Childhood Anaplastic Oligodendroglioma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Diffuse Astrocytoma; Recurrent Childhood Fibrillary Astrocytoma; Recurrent Childhood Gemistocytic Astrocytoma; Recurrent Childhood Giant Cell Glioblastoma; Recurrent Childhood Glioblastoma; Recurrent Childhood Gliomatosis Cerebri; Recurrent Childhood Gliosarcoma; Recurrent Childhood Oligoastrocytoma; Recurrent Childhood Oligodendroglioma; Recurrent Childhood Pilomyxoid Astrocytoma; Recurrent Childhood Protoplasmic Astrocytoma; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Recurrent Childhood Visual Pathway Glioma; Untreated Childhood Anaplastic Astrocytoma; Untreated Childhood Anaplastic Oligoastrocytoma; Untreated Childhood Anaplastic Oligodendroglioma; Untreated Childhood Brain Stem Glioma; Untreated Childhood Cerebellar Astrocytoma; Untreated Childhood Cerebral Astrocytoma; Untreated Childhood Diffuse Astrocytoma; Untreated Childhood Fibrillary Astrocytoma; Untreated Childhood Gemistocytic Astrocytoma; Untreated Childhood Giant Cell Glioblastoma; Untreated Childhood Glioblastoma; Untreated Childhood Gliomatosis Cerebri; Untreated Childhood Gliosarcoma; Untreated Childhood

  12. Coincidence of spinal tumor (astrocytoma) and non-specific encephalomyelitis.

    PubMed

    Burgetova, Andrea; Vaneckova, Manuela; Nytrova, Petra; Matej, Radoslav; Seidl, Zdenek

    2012-01-01

    The aim of this paper is to demonstrate that differential diagnostics of intra-medullary spinal lesions can sometimes be very difficult, even when the latest complement examinations are used, including magnetic resonance imaging. The particular case dealt with here was complicated by the presence of two different pathological processes. We present the case report, where the case history, clinical course and results of the paraclinical examinations, including the magnetic resonance imaging, suggested an intra-medullary inflammatory/demyelinating process. The post-mortem histological finding was a surprise, because besides signs of non-specific encephalomyelitis, it also displayed signs of a spinal tumor (histological character of diffuse astrocytoma grade II-III). We would like to emphasize some important facts in our discussion, especially from the perspective of the magnetic resonance imaging. Finally, we would like to ask if the presence of both pathologies (astrocytoma and nonspecific myelitis) was coincidental, or if the myelitis had an iatrogenic etiology (by therapy, by infection during the lumbar punctions). PMID:23391981

  13. Coincidence of spinal tumor (astrocytoma) and non-specific encephalomyelitis.

    PubMed

    Burgetova, Andrea; Vaneckova, Manuela; Nytrova, Petra; Matej, Radoslav; Seidl, Zdenek

    2012-12-01

    The aim of this paper is to demonstrate that differential diagnostics of intra-medullary spinal lesions can sometimes be very difficult, even when the latest complement examinations are used, including magnetic resonance imaging. The particular case dealt with here was complicated by the presence of two different pathological processes. We present the case report, where the case history, clinical course and results of the paraclinical examinations, including the magnetic resonance imaging, suggested an intra-medullary inflammatory/demyelinating process. The post-mortem histological finding was a surprise, because besides signs of non-specific encephalomyelitis, it also displayed signs of a spinal tumor (histological character of diffuse astrocytoma grade II-III). We would like to emphasize some important facts in our discussion, especially from the perspective of the magnetic resonance imaging. Finally, we would like to ask if the presence of both pathologies (astrocytoma and nonspecific myelitis) was coincidental, or if the myelitis had an iatrogenic etiology (by therapy, by infection during the lumbar punctions). PMID:23391883

  14. Prognostic value of platelet derived growth factor α receptor expression in grade 2 astrocytomas and oligoastrocytomas

    PubMed Central

    Ribom, D; Andrae, J; Frielingsdorf, M; Hartman, M; Nister, M; Smits, A

    2002-01-01

    Objective: To determine whether the expression of platelet derived growth factor α receptor (PDGFRα) in low grade astrocytomas and oligoastrocytomas is associated with survival. Methods: Formalin fixed and paraffin embedded tumour samples of 40 consecutive patients with supratentorial diffuse astrocytomas and oligoastrocytomas of WHO grade 2, resected between 1986 and 1993, were used for immunohistochemical staining. The fraction of tumour cells expressing PDGFRα protein was quantified and entered into univariate and multivariate survival analyses. Changes in PDGFα expression over time were analysed in seven patients in whom reoperations had been performed. Results: Patients with a relatively high fraction of PDGFRα expressing cells had a more favourable outcome in both univariate (p = 0.04) and multivariate analyses (p = 0.02). Expression of PDGFRα was greater in oligoastrocytomas than in astrocytomas (p = 0.05). In four reoperated patients with histologically confirmed malignant transformation, there was a marked decrease in the number of cells expressing the receptor. Conclusions: There is an association between high PDGFRα expression and long survival time in patients with grade 2 astrocytomas and oligoastrocytomas. The findings suggest that expression of the receptor may be a useful prognostic marker in such patients. PMID:12023424

  15. Proton Beam Radiation Therapy in Treating Patients With Low Grade Gliomas

    ClinicalTrials.gov

    2015-12-14

    Adult Brain Tumor; Adult Brain Stem Glioma; Adult Diffuse Astrocytoma; Adult Ependymoma; Adult Grade II Meningioma; Adult Melanocytic Lesion; Adult Meningeal Hemangiopericytoma; Adult Mixed Glioma; Adult Oligodendroglioma; Adult Pineal Gland Astrocytoma; Adult Pineocytoma; Recurrent Adult Brain Tumor

  16. Insight from uncertainty: bootstrap-derived diffusion metrics differentially predict memory function among older adults.

    PubMed

    Vorburger, Robert S; Habeck, Christian G; Narkhede, Atul; Guzman, Vanessa A; Manly, Jennifer J; Brickman, Adam M

    2016-01-01

    Diffusion tensor imaging suffers from an intrinsic low signal-to-noise ratio. Bootstrap algorithms have been introduced to provide a non-parametric method to estimate the uncertainty of the measured diffusion parameters. To quantify the variability of the principal diffusion direction, bootstrap-derived metrics such as the cone of uncertainty have been proposed. However, bootstrap-derived metrics are not independent of the underlying diffusion profile. A higher mean diffusivity causes a smaller signal-to-noise ratio and, thus, increases the measurement uncertainty. Moreover, the goodness of the tensor model, which relies strongly on the complexity of the underlying diffusion profile, influences bootstrap-derived metrics as well. The presented simulations clearly depict the cone of uncertainty as a function of the underlying diffusion profile. Since the relationship of the cone of uncertainty and common diffusion parameters, such as the mean diffusivity and the fractional anisotropy, is not linear, the cone of uncertainty has a different sensitivity. In vivo analysis of the fornix reveals the cone of uncertainty to be a predictor of memory function among older adults. No significant correlation occurs with the common diffusion parameters. The present work not only demonstrates the cone of uncertainty as a function of the actual diffusion profile, but also discloses the cone of uncertainty as a sensitive predictor of memory function. Future studies should incorporate bootstrap-derived metrics to provide more comprehensive analysis.

  17. [Pilocytic astrocytoma of the cerebrum presenting in an elderly patient: a case report].

    PubMed

    Yoshida, Yuya; Tsukada, Toshiyuki; Hashimoto, Masaaki; Hayashi, Yutaka

    2011-09-01

    We report a case of pilocytic astrocytoma of the cerebrum presenting in an elderly patient. A 76-year-old man was admitted to our department due to the development of dysarthria. MRI showed a cystic mass with an enhanced small mural nodule in the left frontal lobe. At surgery, the cyst contents were aspirated, and the mural nodule was excised. Histological examination showed a pattern that is usually seen in pilocytic astrocytoma of the cerebellum, including loose and compact areas composed of pilocytic and stellate cells, a few eosinophilic granular bodies, but not Rosenthal fibers. Pilocytic astrocytoma is a common type of pediatric brain tumor that can arise within either the cerebellum or the hypothalamic/chiasmatic region, but rarely seen in the cerebral hemisphere at an advanced age. To our knowledge, only 45 cases of pilocytic astrocytoma of the cerebrum developing in an adult are reported. In those cases, the symptoms of the disease developed during the third decade of life. The onset at a most advanced age as in the present case is thought to be extremely rare.

  18. Adult Education. Proven Exemplary Educational Programs and Practices: A Collection from the National Diffusion Network (NDN).

    ERIC Educational Resources Information Center

    Michigan State Board of Education, Lansing.

    This booklet provides descriptions of 16 adult education programs that have been validated as successful by the Joint Dissemination Review Panel (JDRP), U.S. Department of Education and that are being promoted by the National Diffusion Network (NDN). Although the programs were developed by individual school districts in response to local needs,…

  19. Identity Diffusion as a Function of Sex-Roles in Adult Women.

    ERIC Educational Resources Information Center

    Jabury, Donald Eugene

    This study sought to demonstrate that the relative degree of adult female identity diffusion, as well as certain personality correlates, would be a function of specific sex roles and their combinations. Three groups of 32 women each were selected as married and noncareer, married and career, or unmarried and career women. They were administered a…

  20. Children are not like older adults: A diffusion model analysis of developmental changes in speeded responses

    PubMed Central

    Ratcliff, Roger; Love, Jessica; Thompson, Clarissa A.; Opfer, John E.

    2011-01-01

    Children (N = 130; Mage = 8.51–15.68 years) and college-aged adults (N = 72; Mage = 20.50 years) completed numerosity discrimination and lexical decision tasks. Children produced longer response times (RTs) than adults. Ratcliff’s (1978) diffusion model, which divides processing into components (e.g., quality of evidence, decision criteria settings, nondecision time) was fit to the accuracy and RT distribution data. Differences in all components were responsible for slowing in children in these tasks. Children extract lower quality evidence than college-aged adults, unlike older adults who extract a similar quality of evidence as college-aged adults. Thus, processing components responsible for changes in RTs at the beginning of the lifespan are somewhat different from those responsible for changes occurring with healthy aging. PMID:22188547

  1. Prognostic significance of astrocyte elevated gene-1 in human astrocytomas

    PubMed Central

    He, Zhangxiu; He, Meihui; Wang, Chao; Xu, Baozhan; Tong, Liping; He, Junming; Sun, Bowen; Wei, Lanlan; Chu, Ming

    2014-01-01

    Astrocyte Elevated Gene-1 (AEG-1) has been proposed as a biomarker for a variety of cancers. This study aimed to investigate the expression of AEG-1 in human astrocytomas and the correlation between AEG-1 expression and clinicopathologic variables of astrocytomas. AEG-1 expression in four pairs of matched astrocytomas tissues and 5 cell lines was detected by immunohistochemical and Western blot analysis. In addition, AEG-1 protein expression was examined by immunohistochemical staining in 204 cases, including 32 normal brain tissues, 80 Low-malignant astrocytomas (LMAs) and 92 High-Malignant astrocytomas (HMAs). AEG-1 expression in 31 LMAs and 29 HMAs samples was detected by RT-PCR and Western blot analysis. We detected AEG-1 expression in normal neurons and glioma cell lines U87, U251 and M059K, but not in normal glial cells. Immunohistochemical analysis showed that 128 of 172 (74.4%) paraffin-embedded archival astrocytomas samples exhibited positive AEG-1 expression. Statistical analysis suggested that higher AEG-1 level was significantly correlated with histological grade of astrocytomas. In addition, AEG-1 mRNA and protein expression was higher in HMAs than in LMAs. AEG-1 expression had no correlation with the gender or age of astrocytoma patients. In summary, our data suggest that AEG-1 may represent a novel prognostic marker for astrocytomas. PMID:25197376

  2. Intracellular tortuosity underlies slow cAMP diffusion in adult ventricular myocytes

    PubMed Central

    Richards, Mark; Lomas, Oliver; Jalink, Kees; Ford, Kerrie L.; Vaughan-Jones, Richard D.; Lefkimmiatis, Konstantinos; Swietach, Pawel

    2016-01-01

    Aims 3′,5′-Cyclic adenosine monophosphate (cAMP) signals in the heart are often confined to concentration microdomains shaped by cAMP diffusion and enzymatic degradation. While the importance of phosphodiesterases (degradative enzymes) in sculpting cAMP microdomains is well established in cardiomyocytes, less is known about cAMP diffusivity (DcAMP) and factors affecting it. Many earlier studies have reported fast diffusivity, which argues against sharply defined microdomains. Methods and results [cAMP] dynamics in the cytoplasm of adult rat ventricular myocytes were imaged using a fourth generation genetically encoded FRET-based sensor. The [cAMP]-response to the addition and removal of isoproterenol (β-adrenoceptor agonist) quantified the rates of cAMP synthesis and degradation. To obtain a read out of DcAMP, a stable [cAMP] gradient was generated using a microfluidic device which delivered agonist to one half of the myocyte only. After accounting for phosphodiesterase activity, DcAMP was calculated to be 32 µm2/s; an order of magnitude lower than in water. Diffusivity was independent of the amount of cAMP produced. Saturating cAMP-binding sites with the analogue 6-Bnz-cAMP did not accelerate DcAMP, arguing against a role of buffering in restricting cAMP mobility. cAMP diffused at a comparable rate to chemically unrelated but similar sized molecules, arguing for a common physical cause of restricted diffusivity. Lower mitochondrial density and order in neonatal cardiac myocytes allowed for faster diffusion, demonstrating the importance of mitochondria as physical barriers to cAMP mobility. Conclusion In adult cardiac myocytes, tortuosity due to physical barriers, notably mitochondria, restricts cAMP diffusion to levels that are more compatible with microdomain signalling. PMID:27089919

  3. High-grade astrocytoma (Glioblastoma Multiforme) in an Atlantic spotted dolphin (Stenella frontalis).

    PubMed

    Díaz-Delgado, J; Sacchini, S; Suárez-Bonnet, A; Sierra, E; Arbelo, M; Espinosa, A; Rodríguez-Grau Bassas, E; Mompeo, B; Pérez, L; Fernández, A

    2015-01-01

    This report describes the gross, microscopical and immunohistochemical features of a high-grade astrocytoma (glioblastoma multiforme) in an adult male Atlantic spotted dolphin (Stenella frontalis). On necropsy examination, a 5 × 2.5 × 2 cm, poorly demarcated, red, friable and locally expansile mass effaced the thalamus and the left periventricular region and extended to the left lateral ventricle of the brain. Microscopically, the mass consisted of haphazardly arranged bundles and rows of interweaving polygonal to spindle-shaped cells. These often palisaded along serpentine foci of necrosis and were surrounded by prominent vessels. Immunohistochemically, the neoplastic cells expressed glial fibrillary acidic protein, but not vimentin, S100 protein, neuron-specific enolase or neurofilament protein. A diagnosis of high-grade astrocytoma was made and this represents the first description of a glioma in a cetacean species. PMID:25728810

  4. Extracellular space diffusion analysis in the infant and adult rat striatum using magnetic resonance imaging.

    PubMed

    Yang, Shuangfeng; Wang, Yan; Li, Kai; Tang, Xiaolu; Zhang, Kuo; Shi, Chunyan; Han, Hongbin; Peng, Yun

    2016-10-01

    The extracellular space (ECS) in the brain provides an extrasynaptic transfer channel among neurons, axons and glial cells. It is particularly important in the early stage after birth, when angiogenesis is not yet complete and the ECS may provide the main pathway for metabolite transport. However, the characteristics of extracellular transport remain unclear. In this study, a novel magnetic resonance imaging (MRI) method was used to perform real-time visualization and quantification of diffusion in the brain ECS of infant (postnatal day 10 (P10)) and adult rats. Using a modified diffusion equation and the linear relationship between the signal intensity and the gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) concentration, diffusion parameters were obtained; these parameters include the effective diffusion coefficient (D*), clearance rate (k'), tortuosity (λ) and the volume fraction of distribution (Vd%). There were significant differences in the diffusion parameters between P10 and adult rats. This finding provides a reference for future treatment of brain diseases using drugs administered via interstitial pathways.

  5. A Diffusion Model Analysis of Adult Age Differences in Episodic and Semantic Long-Term Memory Retrieval

    ERIC Educational Resources Information Center

    Spaniol, Julia; Madden, David J.; Voss, Andreas

    2006-01-01

    Two experiments investigated adult age differences in episodic and semantic long-term memory tasks, as a test of the hypothesis of specific age-related decline in context memory. Older adults were slower and exhibited lower episodic accuracy than younger adults. Fits of the diffusion model (R. Ratcliff, 1978) revealed age-related increases in…

  6. Classification of astrocytomas and malignant astrocytomas by principal components analysis and a neural net.

    PubMed

    McKeown, M J; Ramsay, D A

    1996-12-01

    The classification of astrocytomas, astrocytomas with anaplastic foci and glioblastoma multiformes is not always straightforward because the tumors form a histological continuum. The use of principal component analysis (PCA) and neural nets in the classification of these tumors is explored. PCA was performed on 14 histological features recorded from 52 gliomas classified by the Radiation Therapy Oncology Group method (17 astrocytomas, 18 astrocytomas with anaplastic foci, 17 glioblastoma multiformes). Four of the 14 possible 'scores' derived from this analysis were selected to summarize the histological variability seen in all the tumors. These scores were mostly significantly different between tumor types and were thus used to successfully train a neural net to correctly classify these tumors. The first principal component (score) supported the use of increasing cellularity, mitoses, endothelial proliferation, and necrosis in differentiating between the tumor categories, but accounted for only 39% of the variability seen. Other histological features that were significant components of the other scores included the presence of multinucleated or giant cells, gemistocytes, atypical mitoses and changes in nuclear chromatin. Computer programs derived from the methodology described provide a way of standardizing glioma diagnosis and may be extended to assist with management decisions.

  7. A multi-disciplinary consensus statement concerning surgical approaches to low-grade, high-grade astrocytomas and diffuse intrinsic pontine gliomas in childhood (CPN Paris 2011) using the Delphi method.

    PubMed

    Walker, David A; Liu, JoFen; Kieran, Mark; Jabado, Nada; Picton, Susan; Packer, Roger; St Rose, Christian

    2013-04-01

    Astrocytic tumors account for 42% of childhood brain tumors, arising in all anatomical regions and associated with neurofibromatosis type 1 (NF1) in 15%. Anatomical site determines the degree and risk of resectability; the more complete resection, the better the survival rates. New biological markers and modern radiotherapy techniques are altering the risk assessments of clinical decisions for tumor resection and biopsy. The increasingly distinct pediatric neuro-oncology multidisciplinary team (PNMDT) is developing a distinct evidence base. A multidisciplinary consensus conference on pediatric neurosurgery was held in February 2011, where 92 invited participants reviewed evidence for clinical management of hypothalamic chiasmatic glioma (HCLGG), diffuse intrinsic pontine glioma (DIPG), and high-grade glioma (HGG). Twenty-seven statements were drafted and subjected to online Delphi consensus voting by participants, seeking >70% agreement from >60% of respondents; where <70% consensus occurred, the statement was modified and resubmitted for voting. Twenty-seven statements meeting consensus criteria are reported. For HCLGG, statements describing overall therapeutic purpose and indications for biopsy, observation, or treatment aimed at limiting the risk of visual damage and the need for on-going clinical trials were made. Primary surgical resection was not recommended. For DIPG, biopsy was recommended to ascertain biological characteristics to enhance understanding and targeting of treatments, especially in clinical trials. For HGG, biopsy is essential, the World Health Organization classification was recommended; selection of surgical strategy to achieve gross total resection in a single or multistep process should be discussed with the PNMDT and integrated with trials based drug strategies for adjuvant therapies.

  8. Radiation Therapy for Pilocytic Astrocytomas of Childhood

    SciTech Connect

    Mansur, David B.; Rubin, Joshua B.; Kidd, Elizabeth A.; King, Allison A.; Hollander, Abby S.; Smyth, Matthew D.; Limbrick, David D.; Park, T.S.; Leonard, Jeffrey R.

    2011-03-01

    Purpose: Though radiation therapy is generally considered the most effective treatment for unresectable pilocytic astrocytomas in children, there are few data to support this claim. To examine the efficacy of radiation therapy for pediatric pilocytic astrocytomas, we retrospectively reviewed the experience at our institution. Methods and Materials: Thirty-five patients 18 years old or younger with unresectable tumors and without evidence of neurofibromatosis have been treated since 1982. Patients were treated with local radiation fields to a median dose of 54 Gy. Six patients were treated with radiosurgery to a median dose of 15.5 Gy. Five patients were treated with initial chemotherapy and irradiated after progression. Results: All patients were alive after a median follow-up of 5.0 years. However, progression-free survival was 68.7%. None of 11 infratentorial tumors progressed compared with 6 of 20 supratentorial tumors. A trend toward improved progression-free survival was seen with radiosurgery (80%) compared with external beam alone (66%), but this difference did not reach statistical significance. Eight of the 9 patients progressing after therapy did so within the irradiated volume. Conclusions: Although the survival of these children is excellent, almost one third of patients have progressive disease after definitive radiotherapy. Improvements in tumor control are needed in this patient population, and the optimal therapy has not been fully defined. Prospective trials comparing initial chemotherapy to radiation therapy are warranted.

  9. Corpus callosum size and diffusion tensor anisotropy in adolescents and adults with schizophrenia.

    PubMed

    Balevich, Emily C; Haznedar, M Mehmet; Wang, Eugene; Newmark, Randall E; Bloom, Rachel; Schneiderman, Jason S; Aronowitz, Jonathan; Tang, Cheuk Y; Chu, King-Wai; Byne, William; Buchsbaum, Monte S; Hazlett, Erin A

    2015-03-30

    The corpus callosum has been implicated as a region of dysfunctional connectivity in schizophrenia, but the association between age and callosal pathology is unclear. Magnetic resonance imaging (MRI) and diffusion-tensor imaging (DTI) were performed on adults (n=34) and adolescents (n=17) with schizophrenia and adult (n=33) and adolescent (n=15) age- and sex-matched healthy controls. The corpus callosum was manually traced on each participant׳s MRI, and the DTI scan was co-registered to the MRI. The corpus callosum was divided into five anteroposterior segments. Area and anisotropy were calculated for each segment. Both patient groups demonstrated reduced callosal anisotropy; however, the adolescents exhibited reductions mostly in anterior regions while the reductions were more prominent in posterior regions of the adults. The adolescent patients showed greater decreases in absolute area as compared with the adult patients, particularly in the anterior segments. However, the adults showed greater reductions when area was considered relative to whole brain white matter volume. Our results suggest that the initial stages of the illness are characterized by deficiencies in frontal connections, and the chronic phase is characterized by deficits in the posterior corpus callosum; or, alternatively, adolescent-onset schizophrenia may represent a different or more severe form of the illness.

  10. [A case of pontine astrocytoma with unusual neuroimaging features].

    PubMed

    Matsuoka, Hidenori; Maruyama, Daisuke; Takegami, Tetsuro; Hamasaki, Tomoyuki; Kakita, Kiyohito; Mineura, Katsuyoshi

    2009-10-01

    We would like to report a rare case of pontine glioma with unusual neuroimaging features. The patient was a 3-year-old girl who suffered from chronic nausea and gait disturbance for several months. Computed tomography (CT) demonstrated ventricular dilatation, and ventricular peritoneal (VP) shunt was performed for idiopathic hydrocephalus at another hospital. Fever of unknown origin continued for a month after the VP shunt. At our hospital, cerebrospinal fluid examination showed bacterial meningitis, and it was assumed that shunt infection lead to shunt failure. Magnetic resonance imaging (MRI) revealed hydrocephalus and pontine swelling, and serial MRI suggested brainstem tumor extending to the bilateral thalamus. The patient underwent stereotactic biopsy of the left thalamic tumor, under general anesthesia, and the histological diagnosis was anaplastic astrocytoma. Diffuse pontine glioma rarely increases without cranial nerve deficits. In the present case, pontine glioma extended to the bilateral thalamus symmetrically. It was difficult to diagnose the presented lesion as pontine glioma in the early period because of its unusual neuroimaging.

  11. Alterations of Hippocampal Projections in Adult Macaques with Neonatal Hippocampal Lesions: A Diffusion Tensor Imaging Study

    PubMed Central

    Meng, Yuguang; Payne, Christa; Li, Longchuan; Hu, Xiaoping; Zhang, Xiaodong; Bachevalier, Jocelyne

    2014-01-01

    Neuropsychological and brain imaging studies have demonstrated persistent deficits in memory functions and structural changes after neonatal neurotoxic hippocampal lesion in monkeys. However, the relevant microstructural changes in the white matter of affected brain regions following this early insult remain unknown. This study assessed white matter integrity in the main hippocampal projections of adult macaque monkeys with neonatal hippocampal lesions, by diffusion tensor imaging (DTI). Data analysis was performed using tract-based spatial statistics (TBSS) and compared with volume of interest statistics. Alterations of fractional anisotropy (FA) and diffusivity indices were observed in fornix, temporal stem, ventromedial prefrontal cortex and optical radiations. To further validate the lesion effects on the prefrontal cortex, probabilistic diffusion tractography was used to examine the integrity of the fiber connections between hippocampus and ventromedial prefrontal cortex, and alterations were found in these connections. In addition, increased radial diffusivity in the left ventromedial prefrontal cortex correlated negatively with the severity of deficits in working memory in the same monkeys. The findings revealed microstructural changes due to neonatal hippocampal lesion, and confirmed that neonatal neurotoxic hippocampal lesions resulted in significant and enduring functional alterations in the hippocampal projection system. PMID:25204865

  12. Ammonium-induced calcium mobilization in 1321N1 astrocytoma cells

    SciTech Connect

    Hillmann, Petra; Koese, Meryem; Soehl, Kristina; Mueller, Christa E.

    2008-02-15

    High blood levels of ammonium/ammonia (NH{sub 4}{sup +}/NH{sub 3}) are associated with severe neurotoxicity as observed in hepatic encephalopathy (HE). Astrocytes are the main targets of ammonium toxicity, while neuronal cells are less vulnerable. In the present study, an astrocytoma cell line 1321N1 and a neuroblastoma glioma hybrid cell line NG108-15 were used as model systems for astrocytes and neuronal cells, respectively. Ammonium salts evoked a transient increase in intracellular calcium concentrations ([Ca{sup 2+}]{sub i}) in astrocytoma (EC{sub 50} = 6.38 mM), but not in NG108-15 cells. The ammonium-induced increase in [Ca{sup 2+}]{sub i} was due to an intracellular effect of NH{sub 4}{sup +}/NH{sub 3} and was independent of extracellular calcium. Acetate completely inhibited the ammonium effect. Ammonium potently reduced calcium signaling by G{sub q} protein-coupled receptors (H{sub 1} and M3) expressed on the cells. Ammonium (5 mM) also significantly inhibited the proliferation of 1321N1 astrocytoma cells. While mRNA for the mammalian ammonium transporters RhBG and RhCG could not be detected in 1321N1 astrocytoma cells, both transporters were expressed in NG108-15 cells. RhBG and RhBC in brain may promote the excretion of NH{sub 3}/NH{sub 4}{sup +} from neuronal cells. Cellular uptake of NH{sub 4}{sup +}/NH{sub 3} was mainly by passive diffusion of NH{sub 3}. Human 1321N1 astrocytoma cells appear to be an excellent, easily accessible human model for studying HE, which can substitute animal studies, while NG108-15 cells may be useful for investigating the role of the recently discovered Rhesus family type ammonium transporters in neuronal cells. Our findings may contribute to the understanding of pathologic ammonium effects in different brain cells, and to the treatment of hyperammonemia.

  13. Prognostic Relevance of Histomolecular Classification of Diffuse Adult High-Grade Gliomas with Necrosis.

    PubMed

    Figarella-Branger, Dominique; Mokhtari, Karima; Colin, Carole; Uro-Coste, Emmanuelle; Jouvet, Anne; Dehais, Caroline; Carpentier, Catherine; Villa, Chiara; Maurage, Claude-Alain; Eimer, Sandrine; Polivka, Marc; Vignaud, Jean-Michel; Laquerriere, Annie; Sevestre, Henri; Lechapt-Zalcman, Emmanuelle; Quintin-Roué, Isabelle; Aubriot-Lorton, Marie-Hélène; Diebold, Marie-Danièle; Viennet, Gabriel; Adam, Clovis; Loussouarn, Delphine; Michalak, Sophie; Rigau, Valérie; Heitzmann, Anne; Vandenbos, Fanny; Forest, Fabien; Chiforeanu, Danchristian; Tortel, Marie-Claire; Labrousse, François; Chenard, Marie-Pierre; Nguyen, Anh Tuan; Varlet, Pascale; Kemeny, Jean Louis; Levillain, Pierre-Marie; Cazals-Hatem, Dominique; Richard, Pomone; Delattre, Jean-Yves

    2015-07-01

    Diffuse adult high-grade gliomas (HGGs) with necrosis encompass anaplastic oligodendrogliomas (AOs) with necrosis (grade III), glioblastomas (GBM, grade IV) and glioblastomas with an oligodendroglial component (GBMO, grade IV). Here, we aimed to search for prognostic relevance of histological classification and molecular alterations of these tumors. About 210 patients were included (63 AO, 56 GBM and 91 GBMO). GBMO group was split into "anaplastic oligoastrocytoma (AOA) with necrosis grade IV/GBMO," restricted to tumors showing intermingled astrocytic and oligodendroglial component, and "GBM/GBMO" based on tumors presenting oligodendroglial foci and features of GBM. Genomic arrays, IDH1 R132H expression analyses and IDH direct sequencing were performed. 1p/19q co-deletion characterized AO, whereas no IDH1 R132H expression and intact 1p/19q characterized both GBM and GBM/GBMO. AOA with necrosis/GBMO mainly demonstrated IDH1 R132H expression and intact 1p/19q. Other IDH1 or IDH2 mutations were extremely rare. Both histological and molecular classifications were predictive of progression free survival (PFS) and overall survival (OS) (P < 10(-4) ). Diffuse adult HGGs with necrosis can be split into three histomolecular groups of prognostic relevance: 1p/19q co-deleted AO, IDH1 R132H-GBM and 1p/19q intact IDH1 R132H+ gliomas that might be classified as IDH1 R132H+ GBM. Because of histomolecular heterogeneity, we suggest to remove the name GBMO.

  14. Applications of hybrid diffuse optics for clinical management of adults after brain injury

    NASA Astrophysics Data System (ADS)

    Kim, Meeri Nam

    Information about cerebral blood flow (CBF) is valuable for clinical management of patients after severe brain injury. Unfortunately, current modalities for monitoring brain are often limited by hurdles that include high cost, low throughput, exposure to ionizing radiation, probe invasiveness, and increased risk to critically ill patients when transportation out of their room or unit is required. A further limitation of current technologies is an inability to provide continuous bedside measurements that are often desirable for unstable patients. Here we explore the clinical utility of diffuse correlation spectroscopy (DCS) as an alternative approach for bedside CBF monitoring. DCS uses the rapid intensity fluctuations of near-infrared light to derive a continuous measure of changes in blood flow without ionizing radiation or invasive probing. Concurrently, we employ another optical technique, called diffuse optical spectroscopy (DOS), to derive changes in cerebral oxyhemoglobin ( HbO2) and deoxyhemoglobin (Hb) concentrations. Our clinical studies integrate DCS with DOS into a single hybrid instrument that simultaneously monitors CBF and HbO2/Hb in the injured adult brain. The first parts of this dissertation present the motivations for monitoring blood flow in injured brain, as well as the theory underlying diffuse optics technology. The next section elaborates on details of the hybrid instrumentation. The final chapters describe four human subject studies carried out with these methods. Each of these studies investigates an aspect of the potential of the hybrid monitor in clinical applications involving adult brain. The studies include: (1) validation of DCS-measured CBF against xenon-enhanced computed tomography in brain-injured adults; (2) a study of the effects of age and gender on posture-change-induced CBF variation in healthy subjects; (3) a study of the efficacy of DCS/DOS for monitoring neurocritical care patients during various medical interventions such

  15. Pathology, Molecular Genetics, and Epigenetics of Diffuse Intrinsic Pontine Glioma.

    PubMed

    Buczkowicz, Pawel; Hawkins, Cynthia

    2015-01-01

    Diffuse intrinsic pontine glioma (DIPG) is a devastating pediatric brain cancer with no effective therapy. Histological similarity of DIPG to supratentorial high-grade astrocytomas of adults has led to assumptions that these entities possess similar underlying molecular properties and therefore similar therapeutic responses to standard therapies. The failure of all clinical trials in the last 30 years to improve DIPG patient outcome has suggested otherwise. Recent studies employing next-generation sequencing and microarray technologies have provided a breadth of evidence highlighting the unique molecular genetics and epigenetics of this cancer, distinguishing it from both adult and pediatric cerebral high-grade astrocytomas. This review describes the most common molecular genetic and epigenetic signatures of DIPG in the context of molecular subgroups and histopathological diagnosis, including this tumor entity's unique mutational landscape, copy number alterations, and structural variants, as well as epigenetic changes on the global DNA and histone levels. The increased knowledge of DIPG biology and histopathology has opened doors to new diagnostic and therapeutic avenues. PMID:26175967

  16. Pathology, Molecular Genetics, and Epigenetics of Diffuse Intrinsic Pontine Glioma

    PubMed Central

    Buczkowicz, Pawel; Hawkins, Cynthia

    2015-01-01

    Diffuse intrinsic pontine glioma (DIPG) is a devastating pediatric brain cancer with no effective therapy. Histological similarity of DIPG to supratentorial high-grade astrocytomas of adults has led to assumptions that these entities possess similar underlying molecular properties and therefore similar therapeutic responses to standard therapies. The failure of all clinical trials in the last 30 years to improve DIPG patient outcome has suggested otherwise. Recent studies employing next-generation sequencing and microarray technologies have provided a breadth of evidence highlighting the unique molecular genetics and epigenetics of this cancer, distinguishing it from both adult and pediatric cerebral high-grade astrocytomas. This review describes the most common molecular genetic and epigenetic signatures of DIPG in the context of molecular subgroups and histopathological diagnosis, including this tumor entity’s unique mutational landscape, copy number alterations, and structural variants, as well as epigenetic changes on the global DNA and histone levels. The increased knowledge of DIPG biology and histopathology has opened doors to new diagnostic and therapeutic avenues. PMID:26175967

  17. RO4929097, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Malignant Glioma

    ClinicalTrials.gov

    2015-09-28

    Acoustic Schwannoma; Adult Anaplastic (Malignant) Meningioma; Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Brain Stem Glioma; Adult Choroid Plexus Neoplasm; Adult Craniopharyngioma; Adult Diffuse Astrocytoma; Adult Ependymoblastoma; Adult Ependymoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Grade I Meningioma; Adult Grade II Meningioma; Adult Medulloblastoma; Adult Mixed Glioma; Adult Myxopapillary Ependymoma; Adult Oligodendroglioma; Adult Papillary Meningioma; Adult Pilocytic Astrocytoma; Adult Pineal Gland Astrocytoma; Adult Pineoblastoma; Adult Pineocytoma; Adult Primary Melanocytic Lesion of Meninges; Adult Subependymal Giant Cell Astrocytoma; Adult Subependymoma; Adult Supratentorial Primitive Neuroectodermal Tumor; Malignant Adult Intracranial Hemangiopericytoma

  18. Positron Emission Tomography Using Fluorine F 18 EF5 to Find Oxygen in Tumor Cells of Patients Who Are Undergoing Surgery or Biopsy for Newly Diagnosed Brain Tumors

    ClinicalTrials.gov

    2013-01-15

    Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Central Nervous System Germ Cell Tumor; Adult Choroid Plexus Tumor; Adult Craniopharyngioma; Adult Diffuse Astrocytoma; Adult Ependymoblastoma; Adult Ependymoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Grade I Meningioma; Adult Grade II Meningioma; Adult Grade III Meningioma; Adult Medulloblastoma; Adult Meningeal Hemangiopericytoma; Adult Mixed Glioma; Adult Myxopapillary Ependymoma; Adult Oligodendroglioma; Adult Pilocytic Astrocytoma; Adult Pineoblastoma; Adult Pineocytoma; Adult Subependymoma; Adult Supratentorial Primitive Neuroectodermal Tumor (PNET); Meningeal Melanocytoma

  19. miRNA regulation of Sirtuin-1 expression in human astrocytoma

    PubMed Central

    Romeo, Sara Giovanna; Conti, Alfredo; Polito, Francesca; Tomasello, Chiara; Barresi, Valeria; La Torre, Domenico La; Cucinotta, Maria; Angileri, Flavio Filippo; Bartolotta, Marcello; Di Giorgio, Rosa Maria; Aguennouz, M'Hammed

    2016-01-01

    Sirtuins are a family of 7 histone deacetylases largely involved in the regulation of cell proliferation, survival and death. The role of sirtuins in tumorigenesis and cancer progression has been previously studied in certain cancer types. Few studies have investigated sirtuin expression in gliomas, with controversial results. The aim of the present study was to investigate the expression of sirtuin-1 (Sirt-1) in diffuse astrocytoma [low grade astrocytoma (LGA)], anaplastic astrocytoma (AA) and glioblastoma multiforme (GBM) and in primary glioma cell lines: PLGAC (primary LGA cells); PAAC (primary AA cells); and PGBMC (primary GBM cells). Tumor samples were obtained from patients who underwent craniotomy for microsurgical tumor resection at the Neurosurgery Unit of the University of Messina between 2011 and 2014. Sirt-1 expression was qualitatively analyzed in 30 human glial tumor samples and 5 non-neoplastic brain tissue (NBT) specimens using immunohistochemistry and western blotting techniques. Sirt-1 expression was quantitatively analyzed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). In addition, Sirt-1 expression in primary cell lines was investigated by immunoblotting and RT-qPCR. Sirt-1 expression was downregulated in gliomas compared to NBTs. Sirt-1 levels also varied among different tumor grades, with more evident downregulation in high-grade (P<0.001) than low-grade tumors (P<0.01). These data were confirmed in cell lines, with the exception of upregulation of protein level in the highest malignancy grade cell lines. The present results suggest a role for miRNA-34a, miRNA-132 and miRNA-217 in the epigenetic control of Sirt-1 during gliomagenesis and progression, and demonstrate the different implications of Sirt-1 in human tissues and cell lines. Furthermore, the present results reveal that Sirt-1 may be an intrinsic regulator of tumor progression and the regulation of Sirt-1 involves complex molecular pathways. However, the

  20. The molecular biology of WHO grade I astrocytomas

    PubMed Central

    Marko, Nicholas F.; Weil, Robert J.

    2012-01-01

    World Health Organization (WHO) grade I astrocytomas include pilocytic astrocytoma (PA) and subependymal giant cell astrocytoma (SEGA). As technologies in pharmacologic neo-adjuvant therapy continue to progress and as molecular characteristics are progressively recognized as potential markers of both clinically significant tumor subtypes and response to therapy, interest in the biology of these tumors has surged. An updated review of the current knowledge of the molecular biology of these tumors is needed. We conducted a Medline search to identify published literature discussing the molecular biology of grade I astrocytomas. We then summarized this literature and discuss it in a logical framework through which the complex biology of these tumors can be clearly understood. A comprehensive review of the molecular biology of WHO grade I astrocytomas is presented. The past several years have seen rapid progress in the level of understanding of PA in particular, but the molecular literature regarding both PA and SEGA remains nebulous, ambiguous, and occasionally contradictory. In this review we provide a comprehensive discussion of the current understanding of the chromosomal, genomic, and epigenomic features of both PA and SEGA and provide a logical framework in which these data can be more readily understood. PMID:23090984

  1. The molecular biology of WHO grade I astrocytomas.

    PubMed

    Marko, Nicholas F; Weil, Robert J

    2012-12-01

    World Health Organization (WHO) grade I astrocytomas include pilocytic astrocytoma (PA) and subependymal giant cell astrocytoma (SEGA). As technologies in pharmacologic neo-adjuvant therapy continue to progress and as molecular characteristics are progressively recognized as potential markers of both clinically significant tumor subtypes and response to therapy, interest in the biology of these tumors has surged. An updated review of the current knowledge of the molecular biology of these tumors is needed. We conducted a Medline search to identify published literature discussing the molecular biology of grade I astrocytomas. We then summarized this literature and discuss it in a logical framework through which the complex biology of these tumors can be clearly understood. A comprehensive review of the molecular biology of WHO grade I astrocytomas is presented. The past several years have seen rapid progress in the level of understanding of PA in particular, but the molecular literature regarding both PA and SEGA remains nebulous, ambiguous, and occasionally contradictory. In this review we provide a comprehensive discussion of the current understanding of the chromosomal, genomic, and epigenomic features of both PA and SEGA and provide a logical framework in which these data can be more readily understood.

  2. Prognostic Relevance of Histomolecular Classification of Diffuse Adult High-Grade Gliomas with Necrosis.

    PubMed

    Figarella-Branger, Dominique; Mokhtari, Karima; Colin, Carole; Uro-Coste, Emmanuelle; Jouvet, Anne; Dehais, Caroline; Carpentier, Catherine; Villa, Chiara; Maurage, Claude-Alain; Eimer, Sandrine; Polivka, Marc; Vignaud, Jean-Michel; Laquerriere, Annie; Sevestre, Henri; Lechapt-Zalcman, Emmanuelle; Quintin-Roué, Isabelle; Aubriot-Lorton, Marie-Hélène; Diebold, Marie-Danièle; Viennet, Gabriel; Adam, Clovis; Loussouarn, Delphine; Michalak, Sophie; Rigau, Valérie; Heitzmann, Anne; Vandenbos, Fanny; Forest, Fabien; Chiforeanu, Danchristian; Tortel, Marie-Claire; Labrousse, François; Chenard, Marie-Pierre; Nguyen, Anh Tuan; Varlet, Pascale; Kemeny, Jean Louis; Levillain, Pierre-Marie; Cazals-Hatem, Dominique; Richard, Pomone; Delattre, Jean-Yves

    2015-07-01

    Diffuse adult high-grade gliomas (HGGs) with necrosis encompass anaplastic oligodendrogliomas (AOs) with necrosis (grade III), glioblastomas (GBM, grade IV) and glioblastomas with an oligodendroglial component (GBMO, grade IV). Here, we aimed to search for prognostic relevance of histological classification and molecular alterations of these tumors. About 210 patients were included (63 AO, 56 GBM and 91 GBMO). GBMO group was split into "anaplastic oligoastrocytoma (AOA) with necrosis grade IV/GBMO," restricted to tumors showing intermingled astrocytic and oligodendroglial component, and "GBM/GBMO" based on tumors presenting oligodendroglial foci and features of GBM. Genomic arrays, IDH1 R132H expression analyses and IDH direct sequencing were performed. 1p/19q co-deletion characterized AO, whereas no IDH1 R132H expression and intact 1p/19q characterized both GBM and GBM/GBMO. AOA with necrosis/GBMO mainly demonstrated IDH1 R132H expression and intact 1p/19q. Other IDH1 or IDH2 mutations were extremely rare. Both histological and molecular classifications were predictive of progression free survival (PFS) and overall survival (OS) (P < 10(-4) ). Diffuse adult HGGs with necrosis can be split into three histomolecular groups of prognostic relevance: 1p/19q co-deleted AO, IDH1 R132H-GBM and 1p/19q intact IDH1 R132H+ gliomas that might be classified as IDH1 R132H+ GBM. Because of histomolecular heterogeneity, we suggest to remove the name GBMO. PMID:25407774

  3. Retinotopic mapping of adult human visual cortex with high-density diffuse optical tomography

    PubMed Central

    Zeff, Benjamin W.; White, Brian R.; Dehghani, Hamid; Schlaggar, Bradley L.; Culver, Joseph P.

    2007-01-01

    Functional neuroimaging is a vital element of neuroscience and cognitive research and, increasingly, is an important clinical tool. Diffuse optical imaging is an emerging, noninvasive technique with unique portability and hemodynamic contrast capabilities for mapping brain function in young subjects and subjects in enriched or clinical environments. We have developed a high-performance, high-density diffuse optical tomography (DOT) system that overcomes previous limitations and enables superior image quality. We show herein the utility of the DOT system by presenting functional hemodynamic maps of the adult human visual cortex. The functional brain images have a high contrast-to-noise ratio, allowing visualization of individual activations and highly repeatable mapping within and across subjects. With the improved spatial resolution and localization, we were able to image functional responses of 1.7 cm in extent and shifts of <1 cm. Cortical maps of angle and eccentricity in the visual field are consistent with retinotopic studies using functional MRI and positron-emission tomography. These results demonstrate that high-density DOT is a practical and powerful tool for mapping function in the human cortex. PMID:17616584

  4. The role of connexin43-Src interaction in astrocytomas: A molecular puzzle.

    PubMed

    Tabernero, A; Gangoso, E; Jaraíz-Rodríguez, M; Medina, J M

    2016-05-26

    Connexin43 (Cx43) as a building block of gap junction channels and hemichannels exerts important functions in astrocytes. When these cells acquire a malignant phenotype Cx43 protein but not mRNA levels are downregulated, being negligible in high-grade astrocytoma or glioblastoma multiforme, the most common and deadliest of malignant primary brain tumors in adults. Some microRNAs associated to glioma target Cx43 and could explain the lack of correlation between mRNA and protein levels of Cx43 found in some high-grade astrocytomas. More importantly, these microRNAs could be a promising therapeutic target. A great number of studies have confirmed the relationship between cancer and connexins that was proposed by Loewenstein more than 40years ago, but these studies have also revealed that this is a very complex relationship. Indeed, restoring Cx43 to glioma cells reduces their rate of proliferation and their tumorigenicity but this tumor suppressor effect could be counterbalanced by its effects on invasiveness, adhesion and migration. The mechanisms underlying these effects suggest the participation of a great variety of proteins that bind to different regions of Cx43. The present review focuses on an intrinsically disordered region of the C-terminal domain of Cx43 in which converges the interaction of several proteins, including the proto-oncogene Src. We summarize data that indicate that Cx43-Src interaction inhibits the oncogenic activity of Src and promotes a conformational change in the structure of Cx43 that allosterically modifies the binding to other important signaling proteins. As a consequence, crucial cell functions, such as proliferation or migration, could be strongly affected. We propose that the knowledge of the structural basis of the antitumorigenic effect of Cx43 on astrocytomas could help to design new therapies against this incurable disease. PMID:25711938

  5. The role of connexin43-Src interaction in astrocytomas: A molecular puzzle.

    PubMed

    Tabernero, A; Gangoso, E; Jaraíz-Rodríguez, M; Medina, J M

    2016-05-26

    Connexin43 (Cx43) as a building block of gap junction channels and hemichannels exerts important functions in astrocytes. When these cells acquire a malignant phenotype Cx43 protein but not mRNA levels are downregulated, being negligible in high-grade astrocytoma or glioblastoma multiforme, the most common and deadliest of malignant primary brain tumors in adults. Some microRNAs associated to glioma target Cx43 and could explain the lack of correlation between mRNA and protein levels of Cx43 found in some high-grade astrocytomas. More importantly, these microRNAs could be a promising therapeutic target. A great number of studies have confirmed the relationship between cancer and connexins that was proposed by Loewenstein more than 40years ago, but these studies have also revealed that this is a very complex relationship. Indeed, restoring Cx43 to glioma cells reduces their rate of proliferation and their tumorigenicity but this tumor suppressor effect could be counterbalanced by its effects on invasiveness, adhesion and migration. The mechanisms underlying these effects suggest the participation of a great variety of proteins that bind to different regions of Cx43. The present review focuses on an intrinsically disordered region of the C-terminal domain of Cx43 in which converges the interaction of several proteins, including the proto-oncogene Src. We summarize data that indicate that Cx43-Src interaction inhibits the oncogenic activity of Src and promotes a conformational change in the structure of Cx43 that allosterically modifies the binding to other important signaling proteins. As a consequence, crucial cell functions, such as proliferation or migration, could be strongly affected. We propose that the knowledge of the structural basis of the antitumorigenic effect of Cx43 on astrocytomas could help to design new therapies against this incurable disease.

  6. Yoga Therapy in Treating Patients With Malignant Brain Tumors

    ClinicalTrials.gov

    2015-07-27

    Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Meningioma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Choroid Plexus Tumor; Adult Diffuse Astrocytoma; Adult Ependymoblastoma; Adult Ependymoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Grade II Meningioma; Adult Medulloblastoma; Adult Meningeal Hemangiopericytoma; Adult Mixed Glioma; Adult Oligodendroglioma; Adult Papillary Meningioma; Adult Pineal Gland Astrocytoma; Adult Pineoblastoma; Adult Pineocytoma; Adult Supratentorial Primitive Neuroectodermal Tumor (PNET); Recurrent Adult Brain Tumor

  7. Glutamate involvement in calcium–dependent migration of astrocytoma cells

    PubMed Central

    2014-01-01

    Background Astrocytoma are known to have altered glutamate machinery that results in the release of large amounts of glutamate into the extracellular space but the precise role of glutamate in favoring cancer processes has not yet been fully established. Several studies suggested that glutamate might provoke active killing of neurons thereby producing space for cancer cells to proliferate and migrate. Previously, we observed that calcium promotes disassembly of integrin-containing focal adhesions in astrocytoma, thus providing a link between calcium signaling and cell migration. The aim of this study was to determine how calcium signaling and glutamate transmission cooperate to promote enhanced astrocytoma migration. Methods The wound-healing model was used to assay migration of human U87MG astrocytoma cells and allowed to monitor calcium signaling during the migration process. The effect of glutamate on calcium signaling was evaluated together with the amount of glutamate released by astrocytoma during cell migration. Results We observed that glutamate stimulates motility in serum-starved cells, whereas in the presence of serum, inhibitors of glutamate receptors reduce migration. Migration speed was also reduced in presence of an intracellular calcium chelator. During migration, cells displayed spontaneous Ca2+ transients. L-THA, an inhibitor of glutamate re-uptake increased the frequency of Ca2+ oscillations in oscillating cells and induced Ca2+ oscillations in quiescent cells. The frequency of migration-associated Ca2+ oscillations was reduced by prior incubation with glutamate receptor antagonists or with an anti-β1 integrin antibody. Application of glutamate induced increases in internal free Ca2+ concentration ([Ca2+]i). Finally we found that compounds known to increase [Ca2+]i in astrocytomas such as thapsigagin, ionomycin or the metabotropic glutamate receptor agonist t-ACPD, are able to induce glutamate release. Conclusion Our data demonstrate that

  8. Non-random aneuploidy specifies subgroups of pilocytic astrocytoma and correlates with older age

    PubMed Central

    Khuong-Quang, Dong-Anh; Bechet, Denise; Gayden, Tenzin; Kool, Marcel; De Jay, Nicolas; Jacob, Karine; Gerges, Noha; Hutter, Barbara; Şeker-Cin, Huriye; Witt, Hendrik; Montpetit, Alexandre; Brunet, Sébastien; Lepage, Pierre; Bourret, Geneviève; Klekner, Almos; Bognár, László; Hauser, Peter; Garami, Miklós; Farmer, Jean-Pierre; Montes, Jose-Luis; Atkinson, Jeffrey; Lambert, Sally; Kwan, Tony; Korshunov, Andrey; Tabori, Uri; Collins, V. Peter; Albrecht, Steffen; Faury, Damien; Pfister, Stefan M.; Paulus, Werner; Hasselblatt, Martin; Jones, David T.W.; Jabado, Nada

    2015-01-01

    Pilocytic astrocytoma (PA) is the most common brain tumor in children but is rare in adults, and hence poorly studied in this age group. We investigated 222 PA and report increased aneuploidy in older patients. Aneuploid genomes were identified in 45% of adult compared with 17% of pediatric PA. Gains were non-random, favoring chromosomes 5, 7, 6 and 11 in order of frequency, and preferentially affecting non-cerebellar PA and tumors with BRAF V600E mutations and not with KIAA1549-BRAF fusions or FGFR1 mutations. Aneuploid PA differentially expressed genes involved in CNS development, the unfolded protein response, and regulators of genomic stability and the cell cycle (MDM2, PLK2),whose correlated programs were overexpressed specifically in aneuploid PA compared to other glial tumors. Thus, convergence of pathways affecting the cell cycle and genomic stability may favor aneuploidy in PA, possibly representing an additional molecular driver in older patients with this brain tumor. PMID:26378811

  9. Progesterone Induces the Growth and Infiltration of Human Astrocytoma Cells Implanted in the Cerebral Cortex of the Rat

    PubMed Central

    Germán-Castelán, Liliana; Manjarrez-Marmolejo, Joaquín; González-Arenas, Aliesha; González-Morán, María Genoveva; Camacho-Arroyo, Ignacio

    2014-01-01

    Progesterone (P4) promotes cell proliferation in several types of cancer, including brain tumors such as astrocytomas, the most common and aggressive primary intracerebral neoplasm in humans. In this work, we studied the effects of P4 and its intracellular receptor antagonist, RU486, on growth and infiltration of U373 cells derived from a human astrocytoma grade III, implanted in the motor cortex of adult male rats, using two treatment schemes. In the first one, fifteen days after cells implantation, rats were daily subcutaneously treated with vehicle (propylene glycol, 160 μL), P4 (1 mg), RU486 (5 mg), or P4 + RU486 (1 mg and 5 mg, resp.) for 21 days. In the second one, treatments started 8 weeks after cells implantation and lasted for 14 days. In both schemes we found that P4 significantly increased the tumor area as compared with the rest of the treatments, whereas RU486 blocked P4 effects. All rats treated with P4 showed tumor infiltration, while 28.6% and 42.9% of the animals treated with RU486 and P4 + RU486, respectively, presented it. Our data suggest that P4 promotes growth and migration of human astrocytoma cells implanted in the motor cortex of the rat through the interaction with its intracellular receptor. PMID:24982875

  10. Notch signaling activation in pediatric low-grade astrocytoma.

    PubMed

    Brandt, William D; Schreck, Karisa C; Bar, Eli E; Taylor, Isabella; Marchionni, Luigi; Raabe, Eric; Eberhart, Charles G; Rodriguez, Fausto J

    2015-02-01

    Pilocytic astrocytoma (PA) is the most common primary brain tumor in children; various signaling pathways have been implicated in its biology. The Notch signaling pathway has been found to play a role in the development, stem cell biology, and pathogenesis of several cancers, but its role in PA has not been investigated. We studied alterations in Notch signaling components in tumor tissue from 18 patients with PA and 4 with other low-grade astrocytomas to identify much needed therapeutic targets. We found that Notch pathway members were overexpressed at the mRNA (NOTCH1, NOTCH2, HEY1, HEY2) and protein (HES1) levels in PAs at various anatomic sites compared with non-neoplastic brain samples. These changes were not associated with specific BRAF alterations. Inhibiting the Notch pathway in the pediatric low-grade astrocytoma cell lines Res186 and Res259 using either RNA interference or a γ-secretase inhibitor resulted in variable, but significant, reduction in cell growth and migration. This study suggests a potential role for Notch signaling in pediatric low-grade astrocytoma tumorigenesis and that Notch signaling may be a viable pathway therapeutic target. PMID:25575134

  11. PDGFRA gain in low-grade diffuse gliomas.

    PubMed

    Motomura, Kazuya; Mittelbronn, Michel; Paulus, Werner; Brokinkel, Benjamin; Keyvani, Kathy; Sure, Ulrich; Wrede, Karsten; Nakazato, Yoichi; Tanaka, Yuko; Nonoguchi, Naosuke; Pierscianek, Daniela; Kim, Young-Ho; Mariani, Luigi; Vital, Anne; Perry, Arie; Ohgaki, Hiroko

    2013-01-01

    Glioblastomas with a proneural expression signature are characterized by frequent IDH1 mutations (i.e. genetic hallmarks of secondary glioblastomas) and PDGFRA (platelet-derived growth factor receptor-α) amplification. Mutations in IDH1/2 are frequent and early genetic events in diffuse astrocytomas (World Health Organization grade II), precursor to secondary glioblastomas, but little is known about the role and timing of PDGFRA amplification in these tumors. We assessed PDGFRA gain in 342 low-grade diffuse gliomas by quantitative polymerase chain reaction. Gain in PDGFRA was detected in 27 (16.3%) of 166 diffuse astrocytomas, significantly more frequent than in oligodendrogliomas (3 [2.6%] of 115, p < 0.0001). Analyses using previously published data from our laboratory showed an inverse correlation between PDGFRA gain and IDH1/2 mutations (p = 0.018) or 1p/19q loss (p < 0.0001). The vast majority of diffuse astrocytomas showed IDH1/2 mutations and/or PDGFRA gain (154 [93%] of 166). Mean survival of diffuse astrocytoma patients with PDGFRA gain was 8.8 ± 1.6 years, similar to that with IDH1/2 mutations (7.8 ± 0.5 years) or TP53 mutations (7.6 ± 0.6 years) but significantly longer than those with MET gain (4.4 ± 0.7 years). Dual-color fluorescence in situ hybridization in 6 diffuse astrocytomas with PDGFRA/MET co-gain identified by quantitative polymerase chain reaction revealed that PDGFRA and MET were typically amplified in different tumor cell populations. Tumor cells with coamplification were also focally observed, suggesting intratumoral heterogeneity, even in diffuse astrocytomas.

  12. Magnetic resonance imaging features of intracranial astrocytomas and oligodendrogliomas in dogs.

    PubMed

    Young, Benjamin D; Levine, Jonathan M; Porter, Brian F; Chen-Allen, Annie V; Rossmeisl, John H; Platt, Simon R; Kent, Marc; Fosgate, Geoffrey T; Schatzberg, Scott J

    2011-01-01

    Astrocytomas and oligodendrogliomas represent one third of histologically confirmed canine brain tumors. Our purpose was to describe the magnetic resonance (MR) imaging features of histologically confirmed canine intracranial astrocytomas and oligodendrogliomas and to examine for MR features that differentiate these tumor types. Thirty animals with confirmed astrocytoma (14) or oligodendroglioma (16) were studied. All oligodendrogliomas and 12 astrocytomas were located in the cerebrum or thalamus, with the remainder of astrocytomas in the cerebellum or caudal brainstem. Most (27/30) tumors were associated with both gray and white matter. The signal characteristics of both tumor types were hypointense on T1-weighted images (12 each) and hyperintense on T2-weighted images (11/14 astrocytomas, 12/16 oligodendrogliomas). For astrocytomas and oligodendrogliomas, respectively, common findings were contrast enhancement (10/13, 11/15), ring-like contrast enhancement (6/10, 9/11), cystic regions within the mass (7/14, 12/16), and hemorrhage (4/14, 6/16). Oligodendrogliomas were significantly more likely to contact the brain surface (meninges) than astrocytomas (14/16, 7/14, respectively, P=0.046). Contact with the lateral ventricle was the most common finding, occurring in 13/14 astrocytomas and 14/16 oligodendrogliomas. No MR features were identified that reliably distinguished between these two tumor types. Contrast enhancement was more common in high-grade tumors (III or IV) than low-grade tumors (II, P=0.008). PMID:21388463

  13. Expression of aquaporin8 in human astrocytomas: Correlation with pathologic grade

    SciTech Connect

    Zhu, Shu-juan; Wang, Ke-jian; Gan, Sheng-wei; Xu, Jin; Xu, Shi-ye; Sun, Shan-quan

    2013-10-11

    Highlights: •AQP8 is mainly distributed in the cytoplasm of human astrocytoma cells. •AQP8 over-expressed in human astrocytomas, especially glioblastoma. •The up-regulation of AQP8 is related to the pathological grade of human astrocytomas. •AQP8 may contribute to the growth and proliferation of astrocytomas. -- Abstract: Aquaporin8 (AQP8), a member of the aquaporin (AQP) protein family, is weakly distributed in mammalian brains. Previous studies on AQP8 have focused mainly on the digestive and the reproductive systems. AQP8 has a pivotal role in keeping the fluid and electrolyte balance. In this study, we investigated the expression changes of AQP8 in 75 cases of human brain astrocytic tumors using immunohistochemistry, Western blotting, and reverse transcription polymerase chain reaction. The results demonstrated that AQP8 was mainly distributed in the cytoplasm of astrocytoma cells. The expression levels and immunoreactive score of AQP8 protein and mRNA increased in low-grade astrocytomas, and further increased in high-grade astrocytomas, especially in glioblastoma. Therefore, AQP8 may contribute to the proliferation of astrocytomas, and may be a biomarker and candidate therapy target for patients with astrocytomas.

  14. Neurosurgical management of adult diffuse low grade gliomas in Canada: a multi-center survey.

    PubMed

    Khan, Osaama H; Mason, Warren; Kongkham, Paul N; Bernstein, Mark; Zadeh, Gelareh

    2016-01-01

    Adult diffuse low-grade gliomas are slow growing, World Health Organization grade II lesions with insidious onset and ultimate anaplastic transformation. The timing of surgery remains controversial with polarized practices continuing to govern patient management. As a result, the management of these patients is variable. The goal of this questionnaire was to evaluate practice patterns in Canada. An online invitation for a questionnaire including diagnostic, preoperative, perioperative, and postoperative parameters and three cases with magnetic resonance imaging data with questions to various treatment options in these patients was sent to practicing neurosurgeons and trainees. Survey was sent to 356 email addresses with 87 (24.7%) responses collected. The range of years of practice was less than 10 years 36% (n = 23), 11-20 years 28% (n = 18), over 21 years 37% (n = 24). Twenty-two neurosurgery students of various years of training completed the survey. 94% (n = 47) of surgeons and trainees (n = 20) believe that we do not know the "right treatment". 90% of surgeons do not obtain formal preoperative neurocognitive assessments. 21% (n = 13) of surgeons and 23% of trainees (n = 5) perform a biopsy upon first presentation. A gross total resection was believed to increase progression free survival (surgeons: 75%, n = 46; trainees: 95%, n = 21) and to increase overall survival (surgeons: 64%, n = 39, trainees: 68%, n = 15). Intraoperative MRI was only used by 8% of surgeons. Awake craniotomy was the procedure of choice for eloquent tumors by 80% (n = 48) of surgeons and 100% of trainees. Of those surgeons who perform awake craniotomy 93% perform cortical stimulation and 38% performed subcortical stimulation. Using the aid of three hypothetical cases with progressive complexities in tumor eloquence there was a trend for younger surgeons to operate earlier, and use awake craniotomy to obtain greater extent of resection with the aid of cortical stimulation when compared to

  15. Age related differences in reaction time components and diffusion properties of normal-appearing white matter in healthy adults.

    PubMed

    Yang, Yiqin; Bender, Andrew R; Raz, Naftali

    2015-01-01

    Deterioration of the white matter (WM) is viewed as the neural substrate of age differences in speed of information processing (reaction time, RT). However, the relationship between WM and RT components is rarely examined in healthy aging. We assessed the relationship between RT components derived from the Ratcliff diffusion model and micro-structural properties of normal-appearing WM (NAWM) in 90 healthy adults (age 18-82 years). We replicated all major extant findings pertaining to age differences in RT components and WM: lower drift rate, greater response conservativeness, longer non-decision time, lower fractional anisotropy (FA), greater mean (MD), axial (AD) and radial (RD) diffusivity were associated with advanced age. Age differences in anterior regions of the cerebral WM exceeded those in posterior regions. However, the only relationship between RT components and WM was the positive association between DR in the body of the corpus callosum and non-decision time. Thus, in healthy adults, age differences in NAWM diffusion properties are not a major contributor to age differences in RT components. Longitudinal studies with more precise and specific estimates of regional myelin content and evaluation of the contribution of age-related vascular risk factors are necessary to understand cerebral substrates of age-related cognitive slowing.

  16. [Immediate and remote results of treatment of cerebellar astrocytoma].

    PubMed

    Kunicki, A; Czerwiński, L

    1980-01-01

    Cerebellar astrocytoma accounted for 10% of all brain tumours treated at the Department of Neurosurgery, Medical Academy in Cracow in the years 1946 to 1968. It accounted for 16.6% of all gliomas, and 57% of subtentorial gliomas. Table I shows the distribution of the tumour according to age groups. The male:female sex ratio was near 1.0. In 124 cases the tumour was situated in the cerebellar hemispheres and in 91 in the vermis. The present study is based on an analysis of 215 cases with 124 tumours in the hemispheres and 91 in the vermis. In the hemispheres 77.8% of astrocytomas had cavities, while 22.2% were solid. In the vermis 60.6% of the tumours had cavities and 39.4% had no cavities. Infiltration of the brain stem or adherence to the floor of the fourth ventricle are mentioned in the protocols of 19 operations. The most frequent tumour in childhood and adolescence was pilocytic astrocytoma, in adulthood fibrillary and protoplasmic astrocytomas prevailed. In 10 cases of the last mentioned variety evidence of anaplasia was found. In the first four years when all operations were performed under local analgesia or rectal general anaesthesia the operative mortality was 21.5%, and in the subgroup of 40 first cases it was even 25%. After introduction of endotracheal anaesthesia the operative mortality fell to 13%, and in the subgroup of 40 last cases it was 9%. Detailed data about follow-up observations are available in 93 cases. Thirteen of them were disabled because of complete or nearly complete loss of vision. Nine of them completed schools for the blind and work in gainful occupations ad two founded families. Three patients are completely disabled because of equilibrium disturbances and ataxia. Two children attended a special school. The remaining 85 patients regarded themselves as healthy. This group comprised 66 patients operated upon at the age from 2 to 14 years, 12 were treated at the age from 15 to 21 years and 7 above that age. Some of them had high

  17. Participation and diffusion effects of a peer-intervention for HIV prevention among adults in rural Malawi.

    PubMed

    Crittenden, Kathleen S; Kaponda, Chrissie P N; Jere, Diana L; McCreary, Linda L; Norr, Kathleen F

    2015-05-01

    This paper examines whether a peer group intervention that reduced self-reported risky behaviors for rural adults in Malawi also had impacts on non-participants in the same communities. We randomly assigned two districts to the intervention and control conditions, and conducted surveys at baseline and 18 months post-intervention using unmatched independent random samples of intervention and control communities in 2003-2006. The six-session peer group intervention was offered to same-gender groups by trained volunteers. In this analysis, we divided the post-intervention sample into three exposure groups: 243 participants and 170 non-participants from the intervention district (total n = 415) and 413 control individuals. Controlling for demographics and participation, there were significant favorable diffusion effects on five partially overlapping behavioral outcomes: partner communication, ever used condoms, unprotected sex, recent HIV test, and a community HIV prevention index. Non-participants in the intervention district had more favorable outcomes on these behaviors than survey respondents in the control district. One behavioral outcome, community HIV prevention, showed both participation and diffusion effects. Participating in the intervention had a significant effect on six psychosocial outcomes: HIV knowledge (two measures), hope, condom attitudes, and self-efficacy for community HIV prevention and for safer sex; there were no diffusion effects. This pattern of results suggests that the behavioral changes promoted in the intervention spread to others in the same community, most likely through direct contact between participants and non-participants. These findings support the idea that diffusion of HIV-related behavior changes can occur for peer group interventions in communities, adding to the body of research supporting diffusion of innovations theory as a robust approach to accelerating change. If diffusion occurs, peer group intervention may be more

  18. Participation and Diffusion Effects of a Peer-Intervention for HIV Prevention among Adults in Rural Malawi

    PubMed Central

    Crittenden, Kathleen S.; Kaponda, Chrissie P. N.; Jere, Diana L.; McCreary, Linda L.; Norr, Kathleen F.

    2015-01-01

    This paper examines whether a peer group intervention that reduced self-reported risky behaviors for rural adults in Malawi also had impacts on non-participants in the same communities. We randomly assigned two districts to the intervention and control conditions, and conducted surveys at baseline and 18 months post-intervention using unmatched independent random samples of intervention and control communities in 2003-2006. The six-session peer group intervention was offered to same-gender groups by trained volunteers. In this analysis, we divided the post-intervention sample into three exposure groups: 243 participants and 170 non-participants from the intervention district (total n=415) and 413 control individuals. Controlling for demographics and participation, there were significant favorable diffusion effects on five partially overlapping behavioral outcomes: partner communication, ever used condoms, unprotected sex, recent HIV test, and a community HIV prevention index. Non-participants in the intervention district had more favorable outcomes on these behaviors than survey respondents in the control district. One behavioral outcome, community HIV prevention, showed both participation and diffusion effects. Participating in the intervention had a significant effect on six psychosocial outcomes: HIV knowledge (two measures), hope, condom attitudes, and self-efficacy for community HIV prevention and for safer sex; there were no diffusion effects. This pattern of results suggests that the behavioral changes promoted in the intervention spread to others in the same community, most likely through direct contact between participants and non-participants. These findings support the idea that diffusion of HIV-related behavior changes can occur for peer group interventions in communities, adding to the body of research supporting diffusion of innovations theory as a robust approach to accelerating change. If diffusion occurs, peer group intervention may be more cost

  19. Nitroproteins in Human Astrocytomas Discovered by Gel Electrophoresis and Tandem Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Peng, Fang; Li, Jianglin; Guo, Tianyao; Yang, Haiyan; Li, Maoyu; Sang, Shushan; Li, Xuejun; Desiderio, Dominic M.; Zhan, Xianquan

    2015-12-01

    Protein tyrosine nitration is involved in the pathogenesis of highly fatal astrocytomas, a type of brain cancer. To understand the molecular mechanisms of astrocytomas and to discover new biomarkers/therapeutic targets, we sought to identify nitroproteins in human astrocytoma tissue. Anti-nitrotyrosine immunoreaction-positive proteins from a high-grade astrocytoma tissue were detected with two-dimensional gel electrophoresis (2DGE)-based nitrotyrosine immunoblots, and identified with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Fifty-seven nitrotyrosine immunopositive protein spots were detected. A total of 870 proteins (nitrated and non-nitrated) in nitrotyrosine-immunopositive 2D gel spots were identified, and 18 nitroproteins and their 20 nitrotyrosine sites were identified with MS/MS analysis. These nitroproteins participate in multiple processes, including drug-resistance, signal transduction, cytoskeleton, transcription and translation, cell proliferation and apoptosis, immune response, phenotypic dedifferentiation, cell migration, and metastasis. Among those nitroproteins that might play a role in astrocytomas was nitro-sorcin, which is involved in drug resistance and metastasis and might play a role in the spread and treatment of an astrocytoma. Semiquantitative immune-based measurements of different sorcin expressions were found among different grades of astrocytomas relative to controls, and a semiquantitative increased nitration level in high-grade astrocytoma relative to control. Nitro-β-tubulin functions in cytoskeleton and cell migration. Semiquantitative immunoreactivity of β-tubulin showed increased expression among different grades of astrocytomas relative to controls and semiquantitatively increased nitration level in high-grade astrocytoma relative to control. Each nitroprotein was rationalized and related to the corresponding functional system to provide new insights into tyrosine nitration and its potential role in the

  20. Diffusion of Technology: Frequency of Use for Younger and Older Adults

    PubMed Central

    Olson, Katherine E.; O’Brien, Marita A.; Rogers, Wendy A.; Charness, Neil

    2012-01-01

    Objectives When we think of technology-savvy consumers, older adults are typically not the first persons that come to mind. The common misconception is that older adults do not want to use or cannot use technology. But for an increasing number of older adults, this is not true (Pew Internet and American Life Project, 2003). Older adults do use technologies similar to their younger counterparts, but perhaps at different usage rates. Previous research has identified that there may be subgroups of older adults, “Silver Surfers”, whose adoption patterns mimic younger adults (Pew Internet and American Life Project, 2003). Much of the previous research on age-related differences in technology usage has only investigated usage broadly -- from a “used” or “not used” standpoint. The present study investigated age-related differences in overall usage of technologies, as well as frequency of technology usage (i.e., never, occasional, or frequent). Methods The data were gathered through a questionnaire from younger adults (N=430) and older adults (N=251) in three geographically separate and ethnically diverse areas of the United States. Results We found that younger adults use a greater breadth of technologies than older adults. However, age-related differences in usage and the frequency of use depend on the technology domain. Conclusion This paper presents technology usage and frequency data to highlight age-related differences and similarities. The results provide insights into older and younger adults’ technology-use patterns, which in turn provide a basis for expectations about knowledge differences. Designers and trainers can benefit from understanding experience and knowledge differences. PMID:22685360

  1. Carfilzomib, Rituximab, and Combination Chemotherapy in Treating Patients With Diffuse Large B-Cell Lymphoma

    ClinicalTrials.gov

    2016-09-29

    Contiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Stage I Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma

  2. Expression Profile of MiR-128 in the Astrocytoma Patients and Cell Lines.

    PubMed

    Xu, Jingjing; Liu, Yuqiong; Guo, Si; Ma, Shengli; Xiao, Lin; Wei, Na; Xue, Rui

    2016-09-01

    Malignant astrocytomas are the most common primary brain tumors. The critical characterizes of astrocyomas are their aggressive and infiltrative in the brain, which leads to uncontrollable by conventional forms of therapy. MicroRNAs are small RNAs that had been found to regulate their targets by specific binding to the 3'-untranslated region (3'UTR) of mRNA. Recent advances in understanding the molecular biology of these tumors have revealed that microRNA (miRNA) disruption may play important roles in the pathogenesis of astrocytomas. And some of the miRNA alterations were found in the serum of astrocytoma patients. In this study, we studied the expression profile of miR-128, in the different stages of astrocytoma tissues and two human astrocytoma cell lines, A172 and T98G cells. We found that the levels of miR-128 are decreased in the A172 and T98G cells when compared to normal human astrocyte (NHA). Furthermore, the levels of miR-128 decreased gradually to the pathological stages of astrocytomas. We also identified that TROVE2 is a novel target of miR-128 by the luciferase reporter system. Furthermore, the expression levels of TROVE2 are dramatically increased with the pathological stages increasing. Finally, the levels of TROVE2 are negatively correlated with miR-128 in astrocytoma tissues. Our data provided novel evidence for the miR-128 and TROVE2 in the development of human astrocytomas. PMID:26307612

  3. Outcome of Patients With Pilocytic Astrocytoma and Leptomeningeal Dissemination

    SciTech Connect

    Mazloom, Ali; Hodges, Joseph C.; Teh, Bin S.; Chintagumpala, Murali; Paulino, Arnold C.

    2012-10-01

    Purpose: To determine the patient, tumor, and treatment characteristics of patients with pilocytic astrocytoma (PA) and leptomeningeal dissemination (LMD). Methods and Materials: A PubMed search of English-language studies pertaining to PA with LMD was performed using a combination of keywords that included juvenile pilocytic astrocytoma, low-grade astrocytoma, low-grade glioma, leptomeningeal dissemination, neuraxis spread, and radiotherapy. We found 26 studies with 58 patients between 1976 and 2005 that met these criteria. Results: The median survival for PA patients with LMD was 65 months. The 1-, 2-, and 5-year overall survival (OS) rate after the diagnosis of LMD was 81.1%, 75.7%, and 55.5%. The 1-, 2-, and 5-year progression-free survival (PFS) rate after the diagnosis of LMD was 69.3%, 66.5%, and 34.6%, respectively. Age, gender, primary site location, timing of LMD presentation (synchronous vs. metachronous), and LMD location did not significantly influence OS or PFS. No statistically significant difference was found in OS or PFS between the chemotherapy and radiotherapy groups. Likewise, no difference was found in OS or PFS according to the use of craniospinal irradiation vs. less extensive RT fields. Conclusions: Approximately one-half of PA patients were alive 5 years after the diagnosis of LMD. Both chemotherapy and radiotherapy have efficacy against LMD. Although the use of craniospinal irradiation did not have an effect on PFS, the patient numbers were small and a larger number treated with craniospinal irradiation is needed to determine its efficacy.

  4. Radical proposal for the treatment of malignant astrocytoma

    SciTech Connect

    Karlsson, U.; Black, P.; Nair, S.; Yablon, J.S.; Brady, L.W. )

    1991-02-01

    The traditional treatment for anaplastic astrocytoma (AAF) and glioblastoma multiforme (GBM) leads to local relapse. The recurring element is assumed to be previously radioresistant, reorganizing hypoxic cells that require up to three times the traditional photon irradiation dose for inactivation. We are proposing to coagulate the original lesion with high-dose precision brachytherapy, immediately followed by resection to save the patient from secondary effects of the necrotic region. The treatment then continues with adjuvant external beam radiation therapy to the local surrounding brain and concomitant chemotherapy. The approach inverts the traditional regimen. It has the virtue of being precise, avoiding secondary effects of the necrotic tumor, and satisfying accepted radiobiological principles.

  5. Management of Pediatric Spinal Cord Astrocytomas: Outcomes With Adjuvant Radiation

    SciTech Connect

    Guss, Zachary D.; Moningi, Shalini; Jallo, George I.; Cohen, Kenneth J.; Wharam, Moody D.; Terezakis, Stephanie A.

    2013-04-01

    Purpose: Pediatric intramedullary spinal cord tumors are exceedingly rare; in the United States, 100 to 200 cases are recognized annually, of these, most are astrocytomas. The purpose of this study is to report the outcomes in pediatric patients with spinal cord astrocytomas treated at a tertiary care center. Methods and Materials: An institutional review board-approved retrospective single-institution study was performed for pediatric patients with spinal cord astrocytomas treated at our hospital from 1990 to 2010. The patients were evaluated on the extent of resection, progression-free survival (PFS), and development of radiation-related toxicities. Kaplan-Meier curves and multivariate regression model methods were used for analysis. Results: Twenty-nine patients were included in the study, 24 with grade 1 or 2 (low-grade) tumors and 5 with grade 3 or 4 (high-grade) tumors. The median follow-up time was 55 months (range, 1-215 months) for patients with low-grade tumors and 17 months (range, 10-52 months) for those with high-grade tumors. Thirteen patients in the cohort received chemotherapy. All patients underwent at least 1 surgical resection. Twelve patients received radiation therapy to a median radiation dose of 47.5 Gy (range, 28.6-54.0 Gy). Fifteen patients with low-grade tumors and 1 patient with a high-grade tumor exhibited stable disease at the last follow-up visit. Acute toxicities of radiation therapy were low grade, whereas long-term sequelae were infrequent and manageable when they arose. All patients with low-grade tumors were alive at the last follow-up visit, compared with 1 patient with a high-grade tumor. Conclusion: Primary pediatric spinal cord astrocytomas vary widely in presentation and clinical course. Histopathologic grade remains a major prognostic factor. Patients with low-grade tumors tend to have excellent disease control and long-term survival compared to those with high-grade tumors. This experience suggests that radiation therapy

  6. Multigenerational Effects of Rearing Atmospheric Oxygen Level on the Tracheal Dimensions and Diffusing Capacities of Pupal and Adult Drosophila melanogaster.

    PubMed

    Klok, C Jaco; Kaiser, Alexander; Socha, John J; Lee, Wah-Keat; Harrison, Jon F

    2016-01-01

    Insects are small relative to vertebrates, and were larger in the Paleozoic when atmospheric oxygen levels were higher. The safety margin for oxygen delivery does not increase in larger insects, due to an increased mass-specific investment in the tracheal system and a greater use of convection in larger insects. Prior studies have shown that the dimensions and number of tracheal system branches varies inversely with rearing oxygen in embryonic and larval insects. Here we tested whether rearing in 10, 21, or 40 kPa atmospheric oxygen atmospheres for 5-7 generations affected the tracheal dimensions and diffusing capacities of pupal and adult Drosophila. Abdominal tracheae and pupal snorkel tracheae showed weak responses to oxygen, while leg tracheae showed strong, but imperfect compensatory changes. The diffusing capacity of leg tracheae appears closely matched to predicted oxygen transport needs by diffusion, perhaps explaining the consistent and significant responses of these tracheae to rearing oxygen. The reduced investment in tracheal structure in insects reared in higher oxygen levels may be important for conserving tissue PO2 and may provide an important mechanism for insects to invest only the space and materials necessary into respiratory structure. PMID:27343104

  7. Multigenerational Effects of Rearing Atmospheric Oxygen Level on the Tracheal Dimensions and Diffusing Capacities of Pupal and Adult Drosophila melanogaster.

    PubMed

    Klok, C Jaco; Kaiser, Alexander; Socha, John J; Lee, Wah-Keat; Harrison, Jon F

    2016-01-01

    Insects are small relative to vertebrates, and were larger in the Paleozoic when atmospheric oxygen levels were higher. The safety margin for oxygen delivery does not increase in larger insects, due to an increased mass-specific investment in the tracheal system and a greater use of convection in larger insects. Prior studies have shown that the dimensions and number of tracheal system branches varies inversely with rearing oxygen in embryonic and larval insects. Here we tested whether rearing in 10, 21, or 40 kPa atmospheric oxygen atmospheres for 5-7 generations affected the tracheal dimensions and diffusing capacities of pupal and adult Drosophila. Abdominal tracheae and pupal snorkel tracheae showed weak responses to oxygen, while leg tracheae showed strong, but imperfect compensatory changes. The diffusing capacity of leg tracheae appears closely matched to predicted oxygen transport needs by diffusion, perhaps explaining the consistent and significant responses of these tracheae to rearing oxygen. The reduced investment in tracheal structure in insects reared in higher oxygen levels may be important for conserving tissue PO2 and may provide an important mechanism for insects to invest only the space and materials necessary into respiratory structure.

  8. Pre-Surgical Integration of fMRI and DTI of the Sensorimotor System in Transcortical Resection of a High-Grade Insular Astrocytoma

    PubMed Central

    Ekstrand, Chelsea L.; Mickleborough, Marla J. S.; Fourney, Daryl R.; Gould, Layla A.; Lorentz, Eric J.; Ellchuk, Tasha; Borowsky, Ron W.

    2016-01-01

    Herein we report on a patient with a WHO Grade III astrocytoma in the right insular region in close proximity to the internal capsule who underwent a right frontotemporal craniotomy. Total gross resection of insular gliomas remains surgically challenging based on the possibility of damage to the corticospinal tracts. However, maximizing the extent of resection has been shown to decrease future adverse outcomes. Thus, the goal of such surgeries should focus on maximizing extent of resection while minimizing possible adverse outcomes. In this case, pre-surgical planning included integration of functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI), to localize motor and sensory pathways. Novel fMRI tasks were individually developed for the patient to maximize both somatosensory and motor activation simultaneously in areas in close proximity to the tumor. Information obtained was used to optimize resection trajectory and extent, facilitating gross total resection of the astrocytoma. Across all three motor-sensory tasks administered, fMRI revealed an area of interest just superior and lateral to the astrocytoma. Further, DTI analyses showed displacement of the corona radiata around the superior dorsal surface of the astrocytoma, extending in the direction of the activation found using fMRI. Taking into account these results, a transcortical superior temporal gyrus surgical approach was chosen in order to avoid the area of interest identified by fMRI and DTI. Total gross resection was achieved and minor post-surgical motor and sensory deficits were temporary. This case highlights the utility of comprehensive pre-surgical planning, including fMRI and DTI, to maximize surgical outcomes on a case-by-case basis. PMID:27013996

  9. High expression of the stem cell marker nestin is an adverse prognostic factor in WHO grade II-III astrocytomas and oligoastrocytomas

    PubMed Central

    Hatanpaa, Kimmo J.; Foong, Chan; Raisanen, Jack M.; Oliver, Dwight; Hiemenz, Matthew C.; Burns, Dennis K.; White, Charles L.; Whitworth, L. Anthony; Mickey, Bruce; Stegner, Martha; Habib, Amyn A.; Fink, Karen; Maher, Elizabeth A.; Bachoo, Robert M.

    2015-01-01

    Infiltrating astrocytomas and oligoastrocytomas of low to anaplastic grade (WHO grades II and III), in spite of being associated with a wide range of clinical outcomes, can be difficult to subclassify and grade by the current histopathologic criteria. Unlike oligodendrogliomas and anaplastic oligodendrogliomas that can be identified by the 1p/19q codeletion and the more malignant glioblastomas (WHO grade IV astrocytomas) that can be diagnosed solely based on objective features on routine hematoxylin and eosin sections, no such objective criteria exist for the subclassification of grade II-III astrocytomas and oligoastrocytomas (A+OA II-III). In this study, we evaluated the prognostic and predictive value of the stem cell marker nestin in adult A+OA II-III (n=50) using immunohistochemistry and computer-assisted analysis on tissue microarrays. In addition, the correlation between nestin mRNA level and total survival was analyzed in the NCI Rembrandt database. The results showed that high nestin expression is a strong adverse prognostic factor for total survival (p=0.0004). The strength of the correlation was comparable to but independent of the isocitrate dehydrogenase 1/2 (IDH 1/2) mutation status. Histopathological grading and subclassification did not correlate significantly with outcome, although the interpretation of this finding is limited by the fact that grade III tumors were treated more aggressively than grade II tumors. These results suggest that nestin level and IDH 1/2 mutation status are strong prognostic features in A+OA II-III and possibly more helpful for treatment planning than routine histopathological variables such as oligodendroglial component (astrocytoma vs. oligoastrocytoma) and WHO grade (grade II vs. III). PMID:24519516

  10. Intraoperative Squash Cytologic Features of Subependymal Giant Cell Astrocytoma.

    PubMed

    Nasit, Jitendra; Vaghsiya, Viren; Hiryur, Srilaxmi; Patel, Smita

    2016-01-01

    Subependymal giant cell astrocytoma (SEGA) is a low grade (WHO Grade I) tumor, usually seen in patients with tuberous sclerosis complex and commonly occurs at a lateral ventricular location. Intraoperative squash cytologic features can help in differentiating SEGA from gemistocytic astrocytoma (GA), giant cell glioblastoma and ependymoma, in proper clinical context and radiological findings, which may alter the surgical management. Here, we present a case of SEGA with squash cytologic findings and a review of cytology findings of SEGA presently available in the literature. Loose cohesive clusters of large polygonal cells containing an eccentric nucleus, evenly distributed granular chromatin, distinct to prominent nucleoli, and moderate to the abundant eosinophilic cytoplasm in a hair-like fibrillar background are the key cytologic features of SEGA. Other important features are moderate anisonucleosis and frequent binucleation and multinucleation. The absence of mitoses, necrosis, and vascular endothelial proliferation are important negative features. Other consistent features are cellular smears, few dispersed cells, few spindly strap-like cells, rare intranuclear cytoplasmic inclusion, and perivascular pseudorosettes. PMID:27013816

  11. Intraoperative Squash Cytologic Features of Subependymal Giant Cell Astrocytoma

    PubMed Central

    Nasit, Jitendra; Vaghsiya, Viren; Hiryur, Srilaxmi; Patel, Smita

    2016-01-01

    Subependymal giant cell astrocytoma (SEGA) is a low grade (WHO Grade I) tumor, usually seen in patients with tuberous sclerosis complex and commonly occurs at a lateral ventricular location. Intraoperative squash cytologic features can help in differentiating SEGA from gemistocytic astrocytoma (GA), giant cell glioblastoma and ependymoma, in proper clinical context and radiological findings, which may alter the surgical management. Here, we present a case of SEGA with squash cytologic findings and a review of cytology findings of SEGA presently available in the literature. Loose cohesive clusters of large polygonal cells containing an eccentric nucleus, evenly distributed granular chromatin, distinct to prominent nucleoli, and moderate to the abundant eosinophilic cytoplasm in a hair-like fibrillar background are the key cytologic features of SEGA. Other important features are moderate anisonucleosis and frequent binucleation and multinucleation. The absence of mitoses, necrosis, and vascular endothelial proliferation are important negative features. Other consistent features are cellular smears, few dispersed cells, few spindly strap-like cells, rare intranuclear cytoplasmic inclusion, and perivascular pseudorosettes. PMID:27013816

  12. Neuritin expression and its relation with proliferation, apoptosis, and angiogenesis in human astrocytoma.

    PubMed

    Zhang, Lei; Zhao, Yonggeng; Wang, Cheng-guo; Fei, Zhou; Wang, Yuan; Li, Lexiang; Li, Liang; Zhen, Hai-ning

    2011-09-01

    Neuritin, a new member of the neurotrophic factor family, plays an important role in promoting neuronal survival, differentiation, function, and repair. However, whether neuritin is expressed in human astrocytoma and involved in their proliferation, apoptosis, and angiogenesis remains unclear. The expression of neuritin messenger RNA, protein and the relationship with proliferation, apoptosis, and angiogenesis were examined in human astrocytoma samples and three glioma cell lines by immunohistochemistry, Western blot, and quantitative real-time RT-PCR and so on. And neuritin immunoreactivity score (IRS), proliferative index (PI), apoptotic index (AI), overall daily growth (ODG), and microvessel density (MVD) in brain astrocytoma were measured. The results showed that neuritin was overexpressed in human astrocytoma samples, and the overexpression correlated positively with the malignancy of astrocytomas as reflected by changes in proliferation, apoptosis, and angiogenesis markers. In our study, we found neuritin is overexpressed in astrocytoma, which may be an important factor in tumorigenesis and progression of astrocytoma, and can be used as a target for biological therapy. PMID:20405246

  13. NPAS3 Demonstrates Features of a Tumor Suppressive Role in Driving the Progression of Astrocytomas

    PubMed Central

    Moreira, Frederico; Kiehl, Tim-Rasmus; So, Kelvin; Ajeawung, Norbert F.; Honculada, Carmelita; Gould, Peter; Pieper, Russell O.; Kamnasaran, Deepak

    2011-01-01

    Malignant astrocytomas, the most common primary brain tumors, are predominantly fatal. Improved treatments will require a better understanding of the biological features of high-grade astrocytomas. To better understand the role of neuronal PAS 3 (NPAS3) in diseases in human beings, it was investigated as a candidate for astrocytomagenesis based on the presence of aberrant protein expression in greater than 70% of a human astrocytoma panel (n = 433) and most notably in surgically resected malignant lesions. In subsequent functional studies, it was concluded that NPAS3 exhibits features of a tumor-suppressor, which drives the progression of astrocytomas by modulating the cell cycle, proliferation, apoptosis, and cell migration/invasion and has a further influence on the viability of endothelial cells. Of clinical importance, absence of NPAS3 expression in glioblastomas was a significantly negative prognostic marker of survival. In addition, malignant astrocytomas lacking NPAS3 expression demonstrated loss of function mutations, which were associated with loss of heterozygosity. While overexpressed NPAS3 in malignant glioma cell lines significantly suppressed transformation, the converse decreased expression considerably induced more aggressive growth. In addition, knockdown NPAS3 expression in a human astrocyte cell line in concert with the human papillomavirus E6 and E7 oncogenes induced growth of malignant astrocytomas. In conclusion, NPAS3 drives the progression of human malignant astrocytomas as a tumor suppressor and is a negative prognostication marker for survival. PMID:21703424

  14. Ki-67 immunostaining in astrocytomas: Association with histopathological grade – A South Indian study

    PubMed Central

    Shivaprasad, Nandish Vastrad; Satish, Suchitha; Ravishankar, Sunila; Vimalambike, Manjunath Gubbi

    2016-01-01

    Background: Astrocytomas are the most common primary tumor of the central nervous system. The distinction between different tumor grades can be tested despite criteria given by the World Health Organization (WHO). Ki-67 is a potent biological marker used in grading of astrocytomas, which estimates growth of the neoplasm quantitatively and will help in predicting prognosis accurately. Objectives: The aim of this was to study the proliferative activity using Ki-67 immunostaining and to assess the relationship of Ki-67 staining with the histopathological grading of astrocytomas. Patients and Methods: Thirty cases of histologically proven astrocytomas were studied. The histopathological grade was assessed using the 2007 WHO criteria. Immunohistochemistry for Ki-67 was done on paraffin-embedded wax sections. P < 0.05 was considered statistically significant. Results: Thirty cases of astrocytomas studied showed a male preponderance (M:F = 1.72:1) with a mean age of 48.1 years. Of these, Grade I, (n = 1, 3.33%), Grade II, (n = 7, 23.3%), Grade III (n = 6, 20%), and Grade IV (n = 16, 53.3%) astrocytomas were analyzed. The mean Ki-67 labeling index (LI) in Grades I, II, III, and IV was 0.02, 0.81, 9.14, and 17.81, respectively. Statistically significant difference was seen in the Ki-67 LI of low-grade (Grade II) and high-grade astrocytomas (Grades III and IV). There was concordance between histopathological grading and Ki-67 LI in 27 (90%) and discordance in 3 (10%) cases. Conclusion: Ki-67 LI varies considerably in different grades of astrocytomas and considerable overlaps can be observed between them. It can be of great help in situations where there is a lack of correlation between clinical parameters and histopathological diagnosis. Determination of Ki-67 LI should constitute a part of routine investigations in patients with astrocytomas.

  15. Ki-67 immunostaining in astrocytomas: Association with histopathological grade – A South Indian study

    PubMed Central

    Shivaprasad, Nandish Vastrad; Satish, Suchitha; Ravishankar, Sunila; Vimalambike, Manjunath Gubbi

    2016-01-01

    Background: Astrocytomas are the most common primary tumor of the central nervous system. The distinction between different tumor grades can be tested despite criteria given by the World Health Organization (WHO). Ki-67 is a potent biological marker used in grading of astrocytomas, which estimates growth of the neoplasm quantitatively and will help in predicting prognosis accurately. Objectives: The aim of this was to study the proliferative activity using Ki-67 immunostaining and to assess the relationship of Ki-67 staining with the histopathological grading of astrocytomas. Patients and Methods: Thirty cases of histologically proven astrocytomas were studied. The histopathological grade was assessed using the 2007 WHO criteria. Immunohistochemistry for Ki-67 was done on paraffin-embedded wax sections. P < 0.05 was considered statistically significant. Results: Thirty cases of astrocytomas studied showed a male preponderance (M:F = 1.72:1) with a mean age of 48.1 years. Of these, Grade I, (n = 1, 3.33%), Grade II, (n = 7, 23.3%), Grade III (n = 6, 20%), and Grade IV (n = 16, 53.3%) astrocytomas were analyzed. The mean Ki-67 labeling index (LI) in Grades I, II, III, and IV was 0.02, 0.81, 9.14, and 17.81, respectively. Statistically significant difference was seen in the Ki-67 LI of low-grade (Grade II) and high-grade astrocytomas (Grades III and IV). There was concordance between histopathological grading and Ki-67 LI in 27 (90%) and discordance in 3 (10%) cases. Conclusion: Ki-67 LI varies considerably in different grades of astrocytomas and considerable overlaps can be observed between them. It can be of great help in situations where there is a lack of correlation between clinical parameters and histopathological diagnosis. Determination of Ki-67 LI should constitute a part of routine investigations in patients with astrocytomas. PMID:27695229

  16. Heterogeneous vascular permeability and alternative diffusion barrier in sensory circumventricular organs of adult mouse brain.

    PubMed

    Morita, Shoko; Furube, Eriko; Mannari, Tetsuya; Okuda, Hiroaki; Tatsumi, Kouko; Wanaka, Akio; Miyata, Seiji

    2016-02-01

    Fenestrated capillaries of the sensory circumventricular organs (CVOs), including the organum vasculosum of the lamina terminalis, the subfornical organ and the area postrema, lack completeness of the blood-brain barrier (BBB) to sense a variety of blood-derived molecules and to convey the information into other brain regions. We examine the vascular permeability of blood-derived molecules and the expression of tight-junction proteins in sensory CVOs. The present tracer assays revealed that blood-derived dextran 10 k (Dex10k) having a molecular weight (MW) of 10,000 remained in the perivascular space between the inner and outer basement membranes, but fluorescein isothiocyanate (FITC; MW: 389) and Dex3k (MW: 3000) diffused into the parenchyma. The vascular permeability of FITC was higher at central subdivisions than at distal subdivisions. Neither FITC nor Dex3k diffused beyond the dense network of glial fibrillar acidic protein (GFAP)-positive astrocytes/tanycytes. The expression of tight-junction proteins such as occludin, claudin-5 and zonula occludens-1 (ZO-1) was undetectable at the central subdivisions of the sensory CVOs but some was expressed at the distal subdivisions. Electron microscopic observation showed that capillaries were surrounded with numerous layers of astrocyte processes and dendrites. The expression of occludin and ZO-1 was also observed as puncta on GFAP-positive astrocytes/tanycytes of the sensory CVOs. Our study thus demonstrates the heterogeneity of vascular permeability and expression of tight-junction proteins and indicates that the outer basement membrane and dense astrocyte/tanycyte connection are possible alternative mechanisms for a diffusion barrier of blood-derived molecules, instead of the BBB. PMID:26048259

  17. Pilomyxoid Astrocytoma (PMA) Shows Significant Differences in Gene Expression vs. Pilocytic Astrocytoma (PA) and Variable Tendency Toward Maturation to PA.

    PubMed

    Kleinschmidt-DeMasters, Bette K; Donson, Andrew M; Vogel, Hannes; Foreman, Nicholas K

    2015-07-01

    Pilomyxoid astrocytomas (PMAs) manifest a more aggressive clinical course than pilocytic astrocytomas (PAs). Development of effective therapies demands a better biological understanding of PMA. We first conducted gene expression microarray analysis of 9 PMA and 13 PA from infra- and supratentorial sites. Unsupervised hierarchical clustering analysis demonstrated that tumors are grouped according to anatomic site, not diagnosis. Gene expression profiles were then contrasted between eight PMAs and six PAs, all supratentorial/hypothalamic/chiasmal. Clinical outcome of PMAs varied, with four out of four patients with diencephalic syndrome succumbing to disease, one of whom showed bulky metastatic leptomeningeal spread at autopsy, with bimodal maturation to PA in some areas and de-differentiation to glioblastoma in others. A surviving child has undergone multiple surgical debulking, with progressive maturation to PA over time. Ontology-enrichment analysis identified overexpression in PMAs of extracellular matrix and mitosis-related genes. Genes overexpressed in PMA vs. PA, ranked according to fold-change, included developmental genes H19, DACT2, extracellular matrix collagens (COL2A1; COL1A1) and IGF2BP3 (IMP3), the latter previously identified as an adverse prognostic factor in PMA and PA.

  18. Pilomyxoid astrocytoma (PMA) shows significant differences in gene expression versus pilocytic astrocytoma (PA) and variable tendency toward maturation to PA

    PubMed Central

    Kleinschmidt-DeMasters, B.K.; Donson, Andrew M.; Vogel, Hannes; Foreman, Nicholas K.

    2015-01-01

    Pilomyxoid astrocytomas (PMAs) manifest a more aggressive clinical course than pilocytic astrocytomas (PAs). Development of effective therapies demands a better biological understanding of PMA. We first conducted gene expression microarray analysis of 9 PMA and 13 PA from infra- and supra-tentorial sites. Unsupervised hierarchical clustering analysis demonstrated that tumors grouped according to anatomic site, not diagnosis. Gene expression profiles were then contrasted between 8 PMAs and 6 PAs, all supratentorial/hypothalamic/chiasmal. Clinical outcome of PMAs varied, with 4/4 patients with diencephalic syndrome succumbing to disease, one of whom showed bulky metastatic leptomeningeal spread at autopsy, with bimodal maturation to PA in some areas and de-differentiation to glioblastoma in others. A surviving child has undergone multiple surgical debulkings, with progressive maturation to PA over time. Ontology-enrichment analysis identified overexpression in PMAs of extracellular matrix and mitosis-related genes. Genes overexpressed in PMA versus PA, ranked according to fold-change, included developmental genes H19, DACT2, extracellular matrix collagens (COL2A1;COL1A1) and IGF2BP3 (IMP3), the latter previously identified as an adverse prognostic factor in PMA and PA. PMID:25521223

  19. Expression of estrogen and progesterone receptors in astrocytomas: a literature review.

    PubMed

    Tavares, Cléciton Braga; Gomes-Braga, Francisca das Chagas Sheyla Almeida; Costa-Silva, Danylo Rafhael; Escórcio-Dourado, Carla Solange; Borges, Umbelina Soares; Conde-Junior, Airton Mendes; Barros-Oliveira, Maria da Conceição; Sousa, Emerson Brandão; Barros, Lorena da Rocha; Martins, Luana Mota; Facina, Gil; da-Silva, Benedito Borges

    2016-08-01

    Gliomas are the most common type of primary central nervous system neoplasm. Astrocytomas are the most prevalent type of glioma and these tumors may be influenced by sex steroid hormones. A literature review for the presence of estrogen and progesterone receptors in astrocytomas was conducted in the PubMed database using the following MeSH terms: "estrogen receptor beta" OR "estrogen receptor alpha" OR "estrogen receptor antagonists" OR "progesterone receptors" OR "astrocytoma" OR "glioma" OR "glioblastoma". Among the 111 articles identified, 13 studies met our inclusion criteria. The majority of reports showed the presence of estrogen and progesterone receptors in astrocytomas. Overall, higher tumor grades were associated with decreased estrogen receptor expression and increased progesterone receptor expression. PMID:27626480

  20. Alpha6 beta4 and alpha6 beta1 integrins in astrocytomas and other CNS tumors.

    PubMed

    Previtali, S; Quattrini, A; Nemni, R; Truci, G; Ducati, A; Wrabetz, L; Canal, N

    1996-04-01

    Laminin may alter the biological behavior of gliomas. Therefore, we investigated the expression of two laminin receptors, alpha6 beta1 and alpha6 beta4 integrins in normal brain, astrogliotic brain, and astrocytomas as compared to other central nervous system (CNS) tumors. In most CNS tumors, the expression of these integrins was unchanged in neoplastic as compared to normal counterpart cells. In contrast, increased numbers of reactive and neoplastic astrocytes expressed beta4 integrin as compared to normal astrocytes, whereas alpha6 and beta1 integrin expression did not change. Conversely, lower numbers of astrocytoma blood vessels expressed beta4, whereas all blood vessels in normal brain expressed beta4. These data suggest that the profile of laminin receptors changes in neoplastic astrocytes and in astrocytoma blood vessels; this change may play an important role in astrocytoma pathogenesis.

  1. Medium-grade astrocytoma in a cougar (Puma concolor).

    PubMed

    Kondo, Hirotaka; Leone, Angelique M; Erlacher-Reid, Claire; Gary, Joy; Kiupel, Matti; Farina, Lisa L; Abbott, Jeffrey R

    2012-12-01

    A 17-year-old, male castrated cougar (Puma concolor) was presented minimally responsive and severely depressed, with bilateral mydriasis and absent pupillary light response. On gross examination of the brain, there was a tan-to-gray, invasive mass with a central cavitation on the ventral aspect in the left cerebral hemisphere, rostral to the caudate nucleus. On histopathologic examination, the mass was composed of sheets of medium-sized, round-to-polygonal cells that were multifocally separated by islands of neuropil. Approximately 80% of the neoplastic cells showed strong cytoplasmic labeling for glial fibrillary acidic protein. These findings were consistent with a medium-grade astrocytoma. To the authors' knowledge, neoplastic disease of the central nervous system has not been previously reported in cougars.

  2. Pediatric high-grade astrocytomas: a distinct neuro-oncological paradigm.

    PubMed

    Gerges, Noha; Fontebasso, Adam M; Albrecht, Steffen; Faury, Damien; Jabado, Nada

    2013-01-01

    Brain tumors are the leading cause of cancer-related death in children. High-grade astrocytomas (HGAs), in particular, are lethal in children across all ages. Integrative genome-wide analyses of the tumor's genome, transcriptome and epigenome, using next-generation sequencing technologies and genome-wide DNA methylation arrays, have provided valuable breakthroughs in our understanding of the pathogenesis of HGAs across all ages. Recent profiling studies have provided insight into the epigenetic nature of gliomas in young adults and HGAs in children, particularly with the identification of recurrent gain-of-function driver mutations in the isocitrate dehydrogenase 1 and 2 genes (IDH1/2) and the epigenetic influence of their oncometabolite 2-hydroxyglutarate, as well as mutations in the histone 3 variant 3 gene (H3F3A) and loss-of-function mutations in the histone 3 lysine 36 trimethyltransferase gene (SETD2). Mutations in H3F3A result in amino acid substitutions at residues thought to directly (K27M) or indirectly (G34R/V) affect histone post-translational modifications, suggesting they have the capacity to affect the epigenome in a profound manner. Here, we review recent genomic studies, and discuss evidence supporting the molecular characterization of pediatric HGAs to complement traditional approaches, such as histology of resected tumors. We also describe newly identified molecular mechanisms and discuss putative therapeutic approaches for HGAs specific to pediatrics, highlighting the necessity for the evolution of HGA disease management approaches. PMID:23906214

  3. Children are not just little adults: recent advances in understanding of diffuse intrinsic pontine glioma biology.

    PubMed

    Schroeder, Kristin M; Hoeman, Christine M; Becher, Oren J

    2014-01-01

    Diffuse intrinsic pontine glioma (DIPG) is a high-grade glioma that originates in the pons and is seen exclusively in children. Despite numerous efforts to improve treatment, DIPG remains incurable with 90% of children dying within 2 y of diagnosis, making it one of the leading causes of death in children with brain tumors. With the advent of new genomic tools, the genetic landscape of DIPG is slowly being unraveled. The most common genetic alterations include a K27M mutation in H3.3 or H3.1, which are found in up to 78% of DIPGs, whereas p53 mutations are found in up to 77%. Other recently discovered alterations include amplification of components of the receptor tyrosine kinase/Ras/phosphatidylinositol 3-kinase signaling pathway, particularly platelet-derived growth factor receptor A. Recapitulating such alterations, genetically engineered DIPG preclinical models have been developed, and DIPG xenograft models have also been established. Both models have strengths and weaknesses but can help with the prioritization of novel agents for clinical trials for children with DIPG. As we move forward, it is important that we continue to study the complex and unique biology of DIPG and develop improved preclinical models to increase our understanding of DIPG pathogenesis, allowing translation into successful therapies in the not too distant future. PMID:24192697

  4. Astrocytoma grade IV (glioblastoma multiforme) displays 3 subtypes with unique expression profiles of intermediate filament proteins.

    PubMed

    Skalli, Omar; Wilhelmsson, Ulrika; Orndahl, Charlotte; Fekete, Boglarka; Malmgren, Kristina; Rydenhag, Bertil; Pekny, Milos

    2013-10-01

    Astrocytoma grade IV (glioblastoma multiforme) is the most common and most malignant tumor of the central nervous system and is currently noncurable. Here, we have examined a population-based cohort of 47 patients with grade IV astrocytoma, who underwent tumor surgery at Sahlgrenska University Hospital in Sweden and who survived after surgery for less than 200 days (short survivors, 28 patients) and more than 500 days (long survivors, 19 patients). For each tumor, we ascertained information on patient age, sex, tumor location, oncological treatment, and survival after surgery. The analysis of the tumor volume and the extent of tumor resection (incomplete versus complete resection of the macroscopic tumor) was made retrospectively from the preoperative radiological investigations and, when available, also from postoperative radiology. We performed semiquantitative immunohistochemical evaluation of the presence of intermediate filament (nanofilament) proteins glial fibrillary acidic protein, vimentin, nestin, and synemin in tumor cells. The intermediate filament system helps cells and tissues to cope with various types of stress, and thus, it might affect the malignant potential of grade IV astrocytoma. We propose a subclassification of astrocytomas grade IV with respect to the expression of the intermediate filament proteins glial fibrillary acidic protein, vimentin, nestin, and synemin, namely, type A, B, and C. Our results suggest that the expression of the intermediate filament proteins glial fibrillary acidic protein, vimentin, nestin, and synemin is coregulated in grade IV astrocytomas. The expression patterns of the intermediate filament proteins in astrocytoma type A, B, and C might have biological and clinical significance. PMID:23791210

  5. [Gross tumor volume (GTV) and clinical target volume (CTV) in adult gliomas].

    PubMed

    Kantor, G; Loiseau, H; Vital, A; Mazeron, J J

    2001-10-01

    Glioblastoma multiform and astrocytoma are the most frequent primary cancer of the central nervous system of adult. Definitions of gross tumor volume (GTV) and clinical target volume (CTV) are based on the confrontation of clinical presentation (age, performance status, neurologic symptoms...), histological type and imaging aspects. For glioblastoma multiform, the GTV can be defined by the area of contrast enhancement observed on the CT scan or MRI. Definition of the CTV can be more difficult and have to take into account the risk of presence of isolated malignant cells in the oedema surrounding the tumor or in the adjacent brain structures. The classical concept of GTV plus a safety margin of 2 cm around is discussed with a CTV containing at least all the oedematous area and eventually adjacent brain structures (nuclei, corpus callosum or other long associative fibers...). For low grade astrocytoma, the definition of GTV can be difficult if the tumoral infiltration is diffuse without nodular visible tumor. CTV corresponds to at least T2 MRI hypersignal area when visible. For postoperative tumor, technical considerations are important for the detection of residual tumor. A safety margin around the resected area is designed according to the risk of presence of isolated cells or involvement of adjacent brain structures. PMID:11715309

  6. Reference values of pulmonary diffusing capacity for nitric oxide in an adult population.

    PubMed

    Zavorsky, Gerald S; Cao, Jiguo; Murias, Juan M

    2008-02-01

    Our objective was to create reference values for single-breath DLNO based on a sample of non-smoking healthy males and females using a short breath-hold time. The sample included 130 individuals varied in age (18-85 yr), height (149-190 cm), and weight (49.4-102.6 kg). The subjects performed single-breath-hold maneuvers at rest inhaling 41 +/- 6 ppm NO and a standard diffusion mixture. The breath-hold time was 5.5 +/ -0.6 s. Multiple linear regression with backward elimination of the independent variables age, weight, gender, and either measured lung volume (called alveolar volume or VA) or height revealed specific prediction equations for DLNO. Inserting VA instead of height into the regression equation determined how much of an abnormality of DLNO was due to gas exchange versus low lung volume. The predicted DLNO adjusted for lung volume (ml/min/mmHg) = DLNO = 73.1 + 17.26 x (VA)+17.56 x (gender) - 1.0 x (age). The predicted DLNO unadjusted for lung volume (ml/min/mmHg) = -20.1 + 1.167 x (height)+31.81 x (gender) - 1.21 x (age). For gender, 1 = males, 0 = females; VA = liters; height = cm. Age, gender and VA (lung volume) were the best predictors of DLNO and DLCO. Weight was not a good independent predictor of DLNO or DLCO. When normalizing for height and age, women have 650 ml lower forced vital capacity, 660 ml lower VA, and a 6 and 32 ml/min/mmHg lower DLCO and DLNO, respectively, compared to men. Normalizing for lung volume and age, women have, on average, a 3.2 and 18 ml/min/mmHg lower DLCO and DLNO, respectively, compared to men.

  7. Delineation of Early and Later Adult Onset Depression by Diffusion Tensor Imaging

    PubMed Central

    Yu, Hongjun; Nie, Binbin; Li, Na; Luo, Chunrong; Li, Haijun; Liu, Fang; Bai, Yan; Shan, Baoci; Xu, Lin; Xu, Xiufeng

    2014-01-01

    Background Due to a lack of evidence, there is no consistent age of onset to define early onset (EO) versus later onset (LO) major depressive disorder (MDD). Fractional anisotropy (FA), derived from diffusion tensor imaging (DTI), has been widely used to study neuropsychiatric disorders by providing information about the brain circuitry, abnormalities of which might facilitate the delineation of EO versus LO MDD. Method In this study, 61 pairs of untreated, non-elderly, first-episode MDD patients and healthy controls (HCs) aged 18–45 years old received DTI scans. The voxel-based analysis method (VBM), classification analysis, using the Statistical Package for the Social Sciences (SPSS), and regression analyses were used to determine abnormal FA clusters and their correlations with age of onset and clinical symptoms. Results Classification analysis suggested in the best model that there were two subgroups of MDD patients, delineated by an age of onset of 30 years old, by which MDD patients could be divided into EO (18–29 years old) and LO (30–45 years old) groups. LO MDD was characterized by decreased FA, especially in the white matter (WM) of the fronto-occipital fasciculus and posterior limb of internal capsule, with a negative correlation with the severity of depressive symptoms; in marked contrast, EO MDD showed increased FA, especially in the WM of the corpus callosum, corticospinal midbrain and inferior fronto-occipital fasciculus, while FA of the WM near the midbrain had a positive correlation with the severity of depressive symptoms. Conclusion Specific abnormalities of the brain circuitry in EO vs. LO MDD were delineated by an age of onset of 30 years old, as demonstrated by distinct abnormal FA clusters with opposite correlations with clinical symptoms. This DTI study supported the evidence of an exact age for the delineation of MDD, which could have broad multidisciplinary importance. Trial Registration ClinicalTrials.gov NCT00703742 PMID:25393297

  8. Oblimersen Sodium and Combination Chemotherapy in Treating Patients With Newly Diagnosed Stage I, Stage II, Stage III, or Stage IV Diffuse Large B-Cell Lymphoma

    ClinicalTrials.gov

    2012-10-11

    Contiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Stage I Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma

  9. Rituximab and Combination Chemotherapy in Treating Patients With Previously Untreated High- or High-Intermediate-Risk Diffuse Large B-Cell Lymphoma

    ClinicalTrials.gov

    2016-03-01

    Contiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Stage I Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma

  10. Assessment of a multi-layered diffuse correlation spectroscopy method for monitoring cerebral blood flow in adults

    PubMed Central

    Verdecchia, Kyle; Diop, Mamadou; Lee, Albert; Morrison, Laura B.; Lee, Ting-Yim; St. Lawrence, Keith

    2016-01-01

    Diffuse correlation spectroscopy (DCS) is a promising technique for brain monitoring as it can provide a continuous signal that is directly related to cerebral blood flow (CBF); however, signal contamination from extracerebral tissue can cause flow underestimations. The goal of this study was to investigate whether a multi-layered (ML) model that accounts for light propagation through the different tissue layers could successfully separate scalp and brain flow when applied to DCS data acquired at multiple source-detector distances. The method was first validated with phantom experiments. Next, experiments were conducted in a pig model of the adult head with a mean extracerebral tissue thickness of 9.8 ± 0.4 mm. Reductions in CBF were measured by ML DCS and computed tomography perfusion for validation; excellent agreement was observed by a mean difference of 1.2 ± 4.6% (CI95%: −31.1 and 28.6) between the two modalities, which was not significantly different.

  11. Assessment of a multi-layered diffuse correlation spectroscopy method for monitoring cerebral blood flow in adults

    PubMed Central

    Verdecchia, Kyle; Diop, Mamadou; Lee, Albert; Morrison, Laura B.; Lee, Ting-Yim; St. Lawrence, Keith

    2016-01-01

    Diffuse correlation spectroscopy (DCS) is a promising technique for brain monitoring as it can provide a continuous signal that is directly related to cerebral blood flow (CBF); however, signal contamination from extracerebral tissue can cause flow underestimations. The goal of this study was to investigate whether a multi-layered (ML) model that accounts for light propagation through the different tissue layers could successfully separate scalp and brain flow when applied to DCS data acquired at multiple source-detector distances. The method was first validated with phantom experiments. Next, experiments were conducted in a pig model of the adult head with a mean extracerebral tissue thickness of 9.8 ± 0.4 mm. Reductions in CBF were measured by ML DCS and computed tomography perfusion for validation; excellent agreement was observed by a mean difference of 1.2 ± 4.6% (CI95%: −31.1 and 28.6) between the two modalities, which was not significantly different. PMID:27699127

  12. Clinical significance of B7-H6 protein expression in astrocytoma.

    PubMed

    Guo, Jian-Gui; Guo, Cheng-Cheng; He, Zhen-Qiang; Liu, Zhi-Gang; Wang, Yang; Mou, Yong-Gao

    2016-01-01

    Currently, immunotherapy by blocking the immune checkpoint inhibitors, such as anti-PD-1, has been carried out in many clinical studies on recurrent glioma, and the preliminary results are satisfactory, which provides a rationale for the exploration of immune checkpoint inhibitors in glioma. B7-H6 is a newly discovered member of the B7 family, which triggers antitumor of natural killer cell cytotoxicity and cytokine secretion by binding the NKp30 receptor. B7-H6 mRNA and protein expressions, which are not detected in normal tissues, are expressed mainly on the cell surface of various primary tumors and cell lines. However, up until now, there is no data about the clinical significance of B7-H6 expression in astrocytoma patients. The present study provides an investigation on the relationship between prognostic and clinical value of B7-H6 protein in astrocytoma tissues. All the astrocytic glioma tissues were stained for B7-H6. Immunohistochemistry stain of 122 astrocytoma samples showed that immunoreactivity of B7-H6 was seen predominantly in the cytoplasm. The B7-H6 expression did not show significant relevance with patient age, sex distribution, Karnofsky performance status score, extent of resection, and tumor location in astrocytoma patients, but B7-H6 positive expression is significantly associated with World Health Organization grade (P=0.046). However, the survival rate after operation presented no significant difference of B7-H6 expression in astrocytoma patients. Kaplan-Meier analysis and the log-rank test revealed that B7-H6 expression cannot predict the overall survival. In all, it seems that the B7-H6 expression might be a marker to differentiate the World Health Organization grade level of astrocytoma, but the prognosis value of B7-H6 in astrocytoma should be studied in detail. PMID:27330308

  13. Roles of the functional loss of p53 and other genes in astrocytoma tumorigenesis and progression.

    PubMed Central

    Nozaki, M.; Tada, M.; Kobayashi, H.; Zhang, C. L.; Sawamura, Y.; Abe, H.; Ishii, N.; Van Meir, E. G.

    1999-01-01

    Loss of function of the p53 tumor suppressor gene due to mutation occurs early in astrocytoma tumorigenesis in about 30-40% of cases. This is believed to confer a growth advantage to the cells, allowing them to clonally expand due to loss of the p53-controlled G1 checkpoint and apoptosis. Genetic instability due to the impaired ability of p53 to mediate DNA damage repair further facilitates the acquisition of new genetic abnormalities, leading to malignant progression of an astrocytoma into anaplastic astrocytoma. This is reflected by a high rate of p53 mutation (60-70%) in anaplastic astrocytomas. The cell cycle control gets further compromised in astrocytoma by alterations in one of the G1/S transition control genes, either loss of the p16/CDKN2 or RB genes or amplification of the cyclin D gene. The final progression process leading to glioblastoma multiforme seems to need additional genetic abnormalities in the long arm of chromosome 10; one of which is deletion and/or functional loss of the PTEN/MMAC1 gene. Glioblastomas also occur as primary (de novo) lesions in patients of older age, without p53 gene loss but with amplification of the epidermal growth factor receptor (EGFR) genes. In contrast to the secondary glioblastomas that evolve from astrocytoma cells with p53 mutations in younger patients, primary glioblastomas seem to be resistant to radiation therapy and thus show a poorer prognosis. The evaluation and design of therapeutic modalities aimed at preventing malignant progression of astrocytomas and glioblastomas should now be based on stratifying patients with astrocytic tumors according to their genetic diagnosis. PMID:11550308

  14. Model-Based Evaluation of Spontaneous Tumor Regression in Pilocytic Astrocytoma.

    PubMed

    Buder, Thomas; Deutsch, Andreas; Klink, Barbara; Voss-Böhme, Anja

    2015-12-01

    Pilocytic astrocytoma (PA) is the most common brain tumor in children. This tumor is usually benign and has a good prognosis. Total resection is the treatment of choice and will cure the majority of patients. However, often only partial resection is possible due to the location of the tumor. In that case, spontaneous regression, regrowth, or progression to a more aggressive form have been observed. The dependency between the residual tumor size and spontaneous regression is not understood yet. Therefore, the prognosis is largely unpredictable and there is controversy regarding the management of patients for whom complete resection cannot be achieved. Strategies span from pure observation (wait and see) to combinations of surgery, adjuvant chemotherapy, and radiotherapy. Here, we introduce a mathematical model to investigate the growth and progression behavior of PA. In particular, we propose a Markov chain model incorporating cell proliferation and death as well as mutations. Our model analysis shows that the tumor behavior after partial resection is essentially determined by a risk coefficient γ, which can be deduced from epidemiological data about PA. Our results quantitatively predict the regression probability of a partially resected benign PA given the residual tumor size and lead to the hypothesis that this dependency is linear, implying that removing any amount of tumor mass will improve prognosis. This finding stands in contrast to diffuse malignant glioma where an extent of resection threshold has been experimentally shown, below which no benefit for survival is expected. These results have important implications for future therapeutic studies in PA that should include residual tumor volume as a prognostic factor. PMID:26658166

  15. Pseudoprogression in children, adolescents and young adults with non-brainstem high grade glioma and diffuse intrinsic pontine glioma.

    PubMed

    Carceller, Fernando; Fowkes, Lucy A; Khabra, Komel; Moreno, Lucas; Saran, Frank; Burford, Anna; Mackay, Alan; Jones, David T W; Hovestadt, Volker; Marshall, Lynley V; Vaidya, Sucheta; Mandeville, Henry; Jerome, Neil; Bridges, Leslie R; Laxton, Ross; Al-Sarraj, Safa; Pfister, Stefan M; Leach, Martin O; Pearson, Andrew D J; Jones, Chris; Koh, Dow-Mu; Zacharoulis, Stergios

    2016-08-01

    Pseudoprogression (PsP) is a treatment-related phenomenon which hinders response interpretation. Its prevalence and clinical impact have not been evaluated in children/adolescents. We assessed the characteristics, risk factors and prognosis of PsP in children/adolescents and young-adults diagnosed with non-brainstem high grade gliomas (HGG) and diffuse intrinsic pontine gliomas (DIPG). Patients aged 1-21 years diagnosed with HGG or DIPG between 1995 and 2012 who had completed radiotherapy were eligible. PsP was assessed according to study-specific criteria and correlated with first-line treatment, molecular biomarkers and survival. Ninety-one patients (47 HGG, 44 DIPG) were evaluable. Median age: 10 years (range, 2-20). Eleven episodes of PsP were observed in 10 patients (4 HGG, 6 DIPG). Rates of PsP: 8.5 % (HGG); 13.6 % (DIPG). Two episodes of PsP were based on clinical findings alone; nine episodes had concurrent radiological changes: increased size of lesions (n = 5), new focal enhancement (n = 4). Temozolomide, MGMT methylation or H3F3A mutations were not found to be associated with increased occurrence of PsP. For HGG, 1-year progression-free survival (PFS) was 41.9 % no-PsP versus 100 % PsP (p = 0.041); differences in 1-year overall survival (OS) were not significant. For DIPG, differences in 1-year PFS and OS were not statistically significant. Hazard ratio (95 %CI) of PsP for OS was 0.551 (0.168-1.803; p = 0.325) in HGG; and 0.308 (0.107-0.882; p = 0.028) in DIPG. PsP occurred in both pediatric HGG and DIPG patients at a comparable rate to adult HGG. PsP was associated with improved 1-yr PFS in HGG patients. PsP had a protective effect upon OS in DIPG patients. PMID:27180091

  16. IDH-1R132H mutation status in diffuse glioma patients: implications for classification

    PubMed Central

    Wang, Peng-fei; Liu, Ning; Song, Hong-wang; Yao, Kun; Jiang, Tao; Li, Shou-wei; Yan, Chang-Xiang

    2016-01-01

    WHO2007 grading of diffuse gliomas in adults is well-established. However, IDH mutations make classification of gliomas according to the WHO2007 edition controversial. Here, we characterized IDH-1R132H mut status in a cohort of 670 adult patients with different WHO2007 grades of diffuse glioma. Patient characteristics, clinical data and prognoses were obtained from medical records. Patients with IDH-1R132H mut were younger and had better clinical outcomes than those without mutations. Differences in age among patients with astrocytomas of different WHO2007 grades were eliminated after patients were grouped based on IDH-1R132H status. IDH-1R132H mut was present more often in patients with lower Ki-67 and MGMT protein levels and higher mutant p53 levels. Ki-67 was also strongly associated with WHO2007 grade independently of IDH-1R132H mut status. Moreover, patients with Ki-67<30 survived longer than those with Ki-67≥30, regardless of IDH-1R132H mut status. Patients in the IDH-1R132H mut group with lower MGMT protein levels also had better clinical outcomes than those in other groups. Our results indicate that to better treat gliomas, IDH mutation status should be included when determining WHO2007 grade in glioma patients. PMID:27120786

  17. Specific detection of methionine 27 mutation in histone 3 variants (H3K27M) in fixed tissue from high-grade astrocytomas.

    PubMed

    Bechet, Denise; Gielen, Gerrit G H; Korshunov, Andrey; Pfister, Stefan M; Rousso, Caterina; Faury, Damien; Fiset, Pierre-Olivier; Benlimane, Naciba; Lewis, Peter W; Lu, Chao; David Allis, C; Kieran, Mark W; Ligon, Keith L; Pietsch, Torsten; Ellezam, Benjamin; Albrecht, Steffen; Jabado, Nada

    2014-11-01

    Studies in pediatric high-grade astrocytomas (HGA) by our group and others have uncovered recurrent somatic mutations affecting highly conserved residues in histone 3 (H3) variants. One of these mutations leads to analogous p.Lys27Met (K27M) mutations in both H3.3 and H3.1 variants, is associated with rapid fatal outcome, and occurs specifically in HGA of the midline in children and young adults. This includes diffuse intrinsic pontine gliomas (80 %) and thalamic or spinal HGA (>90 %), which are surgically challenging locations with often limited tumor material available and critical need for specific histopathological markers. Here, we analyzed formalin-fixed paraffin-embedded tissues from 143 pediatric HGA and 297 other primary brain tumors or normal brain. Immunohistochemical staining for H3K27M was compared to tumor genotype, and also compared to H3 tri-methylated lysine 27 (H3K27me3) staining, previously shown to be drastically decreased in samples carrying this mutation. There was a 100 % concordance between genotype and immunohistochemical analysis of H3K27M in tumor samples. Mutant H3K27M was expressed in the majority of tumor cells, indicating limited intra-tumor heterogeneity for this specific mutation within the limits of our dataset. Both H3.1 and H3.3K27M mutants were recognized by this antibody while non-neoplastic elements, such as endothelial and vascular smooth muscle cells or lymphocytes, did not stain. H3K27me3 immunoreactivity was largely mutually exclusive with H3K27M positivity. These results demonstrate that mutant H3K27M can be specifically identified with high specificity and sensitivity using an H3K27M antibody and immunohistochemistry. Use of this antibody in the clinical setting will prove very useful for diagnosis, especially in the context of small biopsies in challenging midline tumors and will help orient care in the context of the extremely poor prognosis associated with this mutation. PMID:25200321

  18. Molecular Profiling Reveals Biologically Discrete Subsets and Pathways of Progression in Diffuse Glioma.

    PubMed

    Ceccarelli, Michele; Barthel, Floris P; Malta, Tathiane M; Sabedot, Thais S; Salama, Sofie R; Murray, Bradley A; Morozova, Olena; Newton, Yulia; Radenbaugh, Amie; Pagnotta, Stefano M; Anjum, Samreen; Wang, Jiguang; Manyam, Ganiraju; Zoppoli, Pietro; Ling, Shiyun; Rao, Arjun A; Grifford, Mia; Cherniack, Andrew D; Zhang, Hailei; Poisson, Laila; Carlotti, Carlos Gilberto; Tirapelli, Daniela Pretti da Cunha; Rao, Arvind; Mikkelsen, Tom; Lau, Ching C; Yung, W K Alfred; Rabadan, Raul; Huse, Jason; Brat, Daniel J; Lehman, Norman L; Barnholtz-Sloan, Jill S; Zheng, Siyuan; Hess, Kenneth; Rao, Ganesh; Meyerson, Matthew; Beroukhim, Rameen; Cooper, Lee; Akbani, Rehan; Wrensch, Margaret; Haussler, David; Aldape, Kenneth D; Laird, Peter W; Gutmann, David H; Noushmehr, Houtan; Iavarone, Antonio; Verhaak, Roel G W

    2016-01-28

    Therapy development for adult diffuse glioma is hindered by incomplete knowledge of somatic glioma driving alterations and suboptimal disease classification. We defined the complete set of genes associated with 1,122 diffuse grade II-III-IV gliomas from The Cancer Genome Atlas and used molecular profiles to improve disease classification, identify molecular correlations, and provide insights into the progression from low- to high-grade disease. Whole-genome sequencing data analysis determined that ATRX but not TERT promoter mutations are associated with increased telomere length. Recent advances in glioma classification based on IDH mutation and 1p/19q co-deletion status were recapitulated through analysis of DNA methylation profiles, which identified clinically relevant molecular subsets. A subtype of IDH mutant glioma was associated with DNA demethylation and poor outcome; a group of IDH-wild-type diffuse glioma showed molecular similarity to pilocytic astrocytoma and relatively favorable survival. Understanding of cohesive disease groups may aid improved clinical outcomes. PMID:26824661

  19. Expression of estrogen and progesterone receptors in astrocytomas: a literature review

    PubMed Central

    Tavares, Cléciton Braga; Gomes-Braga, Francisca das Chagas Sheyla Almeida; Costa-Silva, Danylo Rafhael; Escórcio-Dourado, Carla Solange; Borges, Umbelina Soares; Conde, Airton Mendes; da Conceição Barros-Oliveira, Maria; Sousa, Emerson Brandão; da Rocha Barros, Lorena; Martins, Luana Mota; Facina, Gil; da-Silva, Benedito Borges

    2016-01-01

    Gliomas are the most common type of primary central nervous system neoplasm. Astrocytomas are the most prevalent type of glioma and these tumors may be influenced by sex steroid hormones. A literature review for the presence of estrogen and progesterone receptors in astrocytomas was conducted in the PubMed database using the following MeSH terms: “estrogen receptor beta” OR “estrogen receptor alpha” OR “estrogen receptor antagonists” OR “progesterone receptors” OR “astrocytoma” OR “glioma” OR “glioblastoma”. Among the 111 articles identified, 13 studies met our inclusion criteria. The majority of reports showed the presence of estrogen and progesterone receptors in astrocytomas. Overall, higher tumor grades were associated with decreased estrogen receptor expression and increased progesterone receptor expression. PMID:27626480

  20. Expression of estrogen and progesterone receptors in astrocytomas: a literature review

    PubMed Central

    Tavares, Cléciton Braga; Gomes-Braga, Francisca das Chagas Sheyla Almeida; Costa-Silva, Danylo Rafhael; Escórcio-Dourado, Carla Solange; Borges, Umbelina Soares; Conde, Airton Mendes; da Conceição Barros-Oliveira, Maria; Sousa, Emerson Brandão; da Rocha Barros, Lorena; Martins, Luana Mota; Facina, Gil; da-Silva, Benedito Borges

    2016-01-01

    Gliomas are the most common type of primary central nervous system neoplasm. Astrocytomas are the most prevalent type of glioma and these tumors may be influenced by sex steroid hormones. A literature review for the presence of estrogen and progesterone receptors in astrocytomas was conducted in the PubMed database using the following MeSH terms: “estrogen receptor beta” OR “estrogen receptor alpha” OR “estrogen receptor antagonists” OR “progesterone receptors” OR “astrocytoma” OR “glioma” OR “glioblastoma”. Among the 111 articles identified, 13 studies met our inclusion criteria. The majority of reports showed the presence of estrogen and progesterone receptors in astrocytomas. Overall, higher tumor grades were associated with decreased estrogen receptor expression and increased progesterone receptor expression.

  1. p53 mutations are associated with 17p allelic loss in grade II and grade III astrocytoma.

    PubMed

    von Deimling, A; Eibl, R H; Ohgaki, H; Louis, D N; von Ammon, K; Petersen, I; Kleihues, P; Chung, R Y; Wiestler, O D; Seizinger, B R

    1992-05-15

    Loss of genetic material on the short arm of chromosome 17 is observed in approximately 40% of human astrocytomas (WHO grades II and III) and in approximately 30% of cases of glioblastoma multiforme (WHO grade IV). Previous studies of glioblastoma multiforme have shown that the p53 gene, located on the short arm of chromosome 17, is frequently mutated in these glioblastomas. To explore whether lower-grade astrocytomas are also associated with corresponding mutations of the p53 gene, we have investigated a series of 22 human astrocytomas of WHO grades II and III both for loss of heterozygosity on chromosome 17p and for p53 mutations. Mutations in the conserved regions of the p53 gene were identified by single strand conformation polymorphism analysis of exons 5, 6, 7, and 8 and were verified by direct DNA sequencing of the polymerase chain reaction products. p53 mutations were observed in 3 of 8 grade II astrocytomas and 4 of 14 grade II astrocytomas. In all 22 tumors, allelic loss of the short arm of chromosome 17 was investigated by restriction fragment length polymorphism analysis. One-half of the grade II astrocytomas (4 of 8) and grade III astrocytomas (7 of 14) exhibited allelic loss on chromosome 17p. Mutations in the p53 gene were exclusively observed in tumors with allelic loss on 17p. Our results show that p53 mutations are not restricted to glioblastoma multiforme and may be important in the tumorigenesis of lower-grade astrocytomas and that p53 mutations in lower-grade astrocytomas are associated with loss of chromosome 17p. These findings are consistent with a recessive mechanism of action of p53 in WHO grade II and III astrocytoma tumorigenesis.

  2. Stereotactic Radiosurgery for Recurrent or Unresectable Pilocytic Astrocytoma

    SciTech Connect

    Hallemeier, Christopher L.; Pollock, Bruce E.; Schomberg, Paula J.; Link, Michael J.; Brown, Paul D.; Stafford, Scott L.

    2012-05-01

    Purpose: To report the outcomes in patients with recurrent or unresectable pilocytic astrocytoma (PA) treated with Gamma Knife stereotactic radiosurgery (SRS). Methods and Materials: Retrospective review of 18 patients (20 lesions) with biopsy-confirmed PA having SRS at our institution from 1992 through 2005. Results: The median patient age at SRS was 23 years (range, 4-56). Thirteen patients (72%) had undergone one or more previous surgical resections, and 10 (56%) had previously received external-beam radiation therapy (EBRT). The median SRS treatment volume was 9.1 cm{sup 3} (range, 0.7-26.7). The median tumor margin dose was 15 Gy (range, 12-20). The median follow-up was 8.0 years (range, 0.5-15). Overall survival at 1, 5, and 10 years after SRS was 94%, 71%, and 71%, respectively. Tumor progression (local solid progression, n = 4; local solid progression + distant, n = 1; distant, n = 2; cyst development/progression, n = 4) was noted in 11 patients (61%). Progression-free survival at 1, 5, and 10 years was 65%, 41%, and 17%, respectively. Prior EBRT was associated with inferior overall survival (5-year risk, 100% vs. 50%, p = 0.03) and progression-free survival (5-year risk, 71% vs. 20%, p = 0.008). Nine of 11 patients with tumor-related symptoms improved after SRS. Symptomatic edema after SRS occurred in 8 patients (44%), which resolved with short-term corticosteroid therapy in the majority of those without early disease progression. Conclusions: SRS has low permanent radiation-related morbidity and durable local tumor control, making it a meaningful treatment option for patients with recurrent or unresectable PA in whom surgery and/or EBRT has failed.

  3. Bevacizumab and Cediranib Maleate in Treating Patients With Metastatic or Unresectable Solid Tumor, Lymphoma, Intracranial Glioblastoma, Gliosarcoma or Anaplastic Astrocytoma

    ClinicalTrials.gov

    2014-02-14

    Adult Grade III Lymphomatoid Granulomatosis; Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Childhood Burkitt Lymphoma; Childhood Diffuse Large Cell Lymphoma; Childhood Grade III Lymphomatoid Granulomatosis; Childhood Immunoblastic Large Cell Lymphoma; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Progressive Hairy Cell Leukemia, Initial Treatment; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent/Refractory Childhood Hodgkin Lymphoma; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Hodgkin Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Adult T-cell Leukemia/Lymphoma; Stage IV Childhood Anaplastic Large Cell Lymphoma; Stage IV Childhood Hodgkin Lymphoma; Stage IV

  4. Impaired tooth root development after treatment of a cerebellar astrocytoma: A case report

    SciTech Connect

    Eckles, T.A.; Kalkwarf, K.L.

    1989-10-01

    A young man, previously treated by surgical resection of a grade III cerebellar astrocytoma in combination with irradiation and chemotherapy, was found to display severe generalized root agenesis. This patient also exhibited secondary hypothyroidism and decreased levels of growth hormone. These factors are discussed in relation to their possible role in impaired root development.

  5. Expression of vascular endothelial growth factor-b in human astrocytoma.

    PubMed Central

    Gollmer, J. C.; Ladoux, A.; Gioanni, J.; Paquis, P.; Dubreuil, A.; Chatel, M.; Frelin, C.

    2000-01-01

    Growth of human malignant gliomas is stringently dependent on an angiogenic process that probably involves vascular endothelial growth factor (VEGF). Expressions of mRNA coding for the different forms of VEGF were analyzed in surgical specimens from human astrocytomas. Low levels of placental growth factor (PGF) and VEGFC mRNA were observed in polymerase chain reaction, but not in Northern blot experiments. VEGF mRNA was found in some but not all grade and grade IV astrocytomas. VEGFB mRNA was observed in all tissue samples analyzed irrespective of the tumor grade. A new splice variant of VEGFB (VEGFB155) that lacks exons 5 and 6 is described. Expressions of VEGF mRNA in cultured glioblastomas cells were upregulated by hypoxia, but the sensitivity of the cells to hypoxia was reduced as compared with normal rat astrocytes. VEGF expression was depressed by dexamethasone. Expressions of VEGFB mRNA were affected neither by hypoxia nor by dexamethasone. The results indicate a coexpression of VEGF mRNA and VEGFB mRNA in human astrocytomas. Expression of VEGFB is markedly different from that of VEGF. Possible roles of VEGFB as a cofactor for hypoxia-induced angiogenesis in human astrocytomas are discussed. PMID:11303624

  6. PTEN protein expression correlates with PTEN gene molecular changes but not with VEGF expression in astrocytomas.

    PubMed

    Idoate, M A; Soria, E; Lozano, M D; Sola, J J; Panizo, A; de Alava, E; Manrique, M; Pardo-Mindán, F J

    2003-09-01

    PTEN gene (10q23) is a relevant tumor suppressor gene whose protein is a phosphatase involved in the control of angiogenesis of some tumors including astrocytomas. There are no studies correlating molecular changes of PTEN and the immunohistochemical expression of its protein (pPTEN) with the expression of vascular endothelial growth factor (VEGF) in astrocytomas. Fifty-six surgically resected brain gliomas, 10 grade 2, 16 grade 3, and 30 grade 4, were studied by a combined approach, consisting of (1) PCR analysis using four microsatellite markers against the PTEN gene region (10q23), (2) the FISH technique to test chromosome 10 using a pericentromeric probe, and (3) immunohistochemical evaluation of pPTEN and VEGF. Loss of heterozygosity (LOH) of PTEN was observed in 10% of fibrillary grade 2 astrocytomas and all gemistocytic ones. In high-grade tumors, LOH was more frequent in grade 4 than in grade 3 (> or =2 loci deleted, 83% and 56%, respectively). Monosomy for chromosome 10 was observed especially in high-grade tumors (6% of grade 3 and 50% of grade 4) and in 20% of grade 2 tumors, corresponding to gemistocytic astrocytomas. Results with both antibodies against PTEN were concordant: loss of cytoplasmic immunoreactivity was frequently observed according to homogeneous or heterogeneous patterns in 70% and 50% of grades 4 and 3, respectively, but not in grade 2. Immunonegativity of pPTEN was associated with PTEN gene deletion (> or =2 loci deleted) (P = 0.04) but not with monosomy. Cytoplasmic immunoreactivity against VEGF was observed in high-grade and in gemistocytic astrocytomas, but not in conventional grade 2 tumors. Tumor expression of pPTEN was not associated with immunoreactivity against VEGF when the same areas were considered. In conclusion, loss of PTEN expression is frequent in high-grade astrocytomas, but not in grade 2 tumors, and correlates with PTEN deletion and loss of chromosome 10. PTEN immunoreactivity does not correlate with VEGF expression

  7. Expression and hormonal regulation of membrane progesterone receptors in human astrocytoma cells.

    PubMed

    Valadez-Cosmes, Paulina; Germán-Castelán, Liliana; González-Arenas, Aliesha; Velasco-Velázquez, Marco A; Hansberg-Pastor, Valeria; Camacho-Arroyo, Ignacio

    2015-11-01

    Progesterone (P) participates in the regulation of the growth of several tumors, including astrocytomas, the most common and malignant human brain tumors. It has been reported that P induces astrocytomas growth in part by its interaction with its intracellular receptors (PR). Recently, it has been reported that membrane progesterone receptors (mPRs) are expressed in ovarian and breast cancer cells, and that P could exert some actions through these receptors, however, it is unknown whether mPRs are expressed in astrocytomas. In this work, U251 and U87 cell lines derived from human astrocytomas grade IV were used to study the expression, localization and hormonal regulation of three mPRs subtypes. Using RT-qPCR and Western blot techniques, we found that mPRα and mPRβ are clearly expressed at mRNA and protein levels in astrocytoma cells whereas mPRγ was barely expressed in these cells. Immunofluorescence staining showed that mPRα and mPRβ were mainly located in the cell surface. Flow cytometry assays demonstrated that in U251 and U87 cells, mPRβ is expressed by a higher percentage of both permeabilized and non-permeabilized cells as compared with mPRα. The percentage of cells expressing mPRγ was very low. P and estradiol (E) (10, 100 nM and 1 μM) decreased mPRα protein content at 12 h. In contrast, both P (100 nM and 1 μM) and E (10 and 100 nM) increased mPRβ content. Finally, by in silico analysis, we identified that mPRα, mPRβ and mPRγ promoters contain several progesterone and estrogen response elements. Our results indicate that mPRs are expressed in human astrocytoma cells, exhibiting a differential regulation by E and P. These data suggest that some P actions in astrocytoma cells may be mediated by mPRs. PMID:26275946

  8. Diffusion tensor imaging reveals adolescent binge ethanol-induced brain structural integrity alterations in adult rats that correlate with behavioral dysfunction.

    PubMed

    Vetreno, Ryan P; Yaxley, Richard; Paniagua, Beatriz; Crews, Fulton T

    2016-07-01

    Adolescence is characterized by considerable brain maturation that coincides with the development of adult behavior. Binge drinking is common during adolescence and can have deleterious effects on brain maturation because of the heightened neuroplasticity of the adolescent brain. Using an animal model of adolescent intermittent ethanol [AIE; 5.0 g/kg, intragastric, 20 percent EtOH w/v; 2 days on/2 days off from postnatal day (P)25 to P55], we assessed the adult brain structural volumes and integrity on P80 and P220 using diffusion tensor imaging (DTI). While we did not observe a long-term effect of AIE on structural volumes, AIE did reduce axial diffusivity (AD) in the cerebellum, hippocampus and neocortex. Radial diffusivity (RD) was reduced in the hippocampus and neocortex of AIE-treated animals. Prior AIE treatment did not affect fractional anisotropy (FA), but did lead to long-term reductions of mean diffusivity (MD) in both the cerebellum and corpus callosum. AIE resulted in increased anxiety-like behavior and diminished object recognition memory, the latter of which was positively correlated with DTI measures. Across aging, whole brain volumes increased, as did volumes of the corpus callosum and neocortex. This was accompanied by age-associated AD reductions in the cerebellum and neocortex as well as RD and MD reductions in the cerebellum. Further, we found that FA increased in both the cerebellum and corpus callosum as rats aged from P80 to P220. Thus, both age and AIE treatment caused long-term changes to brain structural integrity that could contribute to cognitive dysfunction.

  9. Progesterone promotes cell migration, invasion and cofilin activation in human astrocytoma cells.

    PubMed

    Piña-Medina, Ana Gabriela; Hansberg-Pastor, Valeria; González-Arenas, Aliesha; Cerbón, Marco; Camacho-Arroyo, Ignacio

    2016-01-01

    Astrocytomas are the most common and aggressive primary brain tumors in humans. Invasiveness of these tumors has been attributed in part to deregulation of cell motility-dependent cytoskeletal dynamics that involves actin-binding proteins such as cofilin. Progesterone (P4) has been found to induce migration and invasion of cells derived from breast cancer and endothelium. However, the role of P4 in migration and invasion of astrocytoma cells as well as its effects on astrocytomas cytoskeleton remodeling is not known. In this work we evaluated these aspects in D54 and U251 cells derived from human astrocytomas from the highest degree of malignancy (grade IV, glioblastoma). Our results showed that in scratch-wound assays P4 increased the number of D54 and U251 cells migrating from 3 to 48 h. Both RU486, a P4 receptor (PR) antagonist, and an oligonucleotide antisense against PR significantly blocked P4 effects. Transwell assays showed that P4 significantly increased the number of invasive cells at 24h. As in the case of migration, this effect was blocked by RU486. Finally, by Western blotting, an increase in the cofilin/p-cofilin ratio at 15 and 30 min and a decrease at 30 and 60 min in U251 and D54 cells, respectively, was observed after P4, P4+RU486 and RU486 treatments. These data suggest that P4 increases human astrocytoma cells migration and invasion through its intracellular receptor, and that cofilin activation by P4 is independent of PR action. PMID:26639431

  10. Carfilzomib, Rituximab, Ifosfamide, Carboplatin, and Etoposide in Treating Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma

    ClinicalTrials.gov

    2016-08-01

    Contiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Stage I Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma

  11. Intraarterial Infusion Of Erbitux and Bevacizumab For Relapsed/Refractory Intracranial Glioma In Patients Under 22

    ClinicalTrials.gov

    2016-03-16

    Glioblastoma Multiforme; Fibrillary Astrocytoma of Brain; Glioma of Brainstem; Anaplastic Astrocytoma; Pilomyxoid Astrocytoma; Mixed Oligodendroglioma-Astrocytoma; Brain Stem Glioma; Diffuse Intrinsic Pontine Glioma

  12. The expression of Wnt-1 inducible signaling pathway protein-2 in astrocytoma: Correlation between pathological grade and clinical outcome.

    PubMed

    Xiao, Gelei; Tang, Zhi; Yuan, Xianrui; Yuan, Jian; Zhao, Jie; Zhang, Zhiping; He, Zhengwen; Liu, Jingping

    2015-01-01

    Wnt-1 inducible signaling pathway protein-2 (WISP-2) is a member of the CCN family, which is critical for the control of cell morphology, motion, adhesion and other processes involved in tumorigenesis. The expression pattern and clinical significance of WISP-2 in astrocytomas remains unclear. In this study, reverse transcription-polymerase chain reaction was performed to systematically investigate the expression of WISP-2 in 47 astrocytoma tissues of different pathological grades and 10 normal brain tissues. The mRNA expression levels of WISP-2 in the astrocytoma tissues were observed to be significantly higher than those in the normal brain tissues. Furthermore, the upregulation of WISP-2 was found to be associated with astrocytomas of higher pathological grades. Subsequently, 154 astrocytoma and 15 normal brain tissues were analyzed using immunohistochemistry and similar results were obtained. Univariate and multivariate survival analyses were used to determine the correlations between WISP-2 expression and overall survival (OS) and progression-free survival (PFS). The results indicated that the expression of WISP-2 was found to negatively correlate with patient PFS and OS. These results demonstrated that the WISP-2 protein is involved in the pathogenesis and progression of human astrocytomas and may serve as a malignant biomarker of this disease.

  13. Is Upregulation of Aquaporin 4-M1 Isoform Responsible for the Loss of Typical Orthogonal Arrays of Particles in Astrocytomas?

    PubMed Central

    Fallier-Becker, Petra; Nieser, Maike; Wenzel, Ulrike; Ritz, Rainer; Noell, Susan

    2016-01-01

    The astrocytic endfoot membranes of the healthy blood-brain barrier—contacting the capillary—are covered with a large number of the water channel aquaporin 4 (AQP4). They form orthogonal arrays of particles (OAPs), which consist of AQP4 isoform M1 and M23. Under pathologic conditions, AQP4 is distributed over the whole cell and no or only small OAPs are found. From cell culture experiments, it is known that cells transfected only with AQP4-M1 do not form OAPs or only small ones. We hypothesized that in astrocytomas the situation may be comparable to the in vitro experiments expecting an upregulation of AQP4-M1. Quantitative Real-time PCR (qRT-PCR) of different graded astrocytomas revealed an upregulation of both isoforms AQP4 M1 and M23 in all astrocytomas investigated. In freeze fracture replicas of low-grade malignancy astrocytomas, more OAPs than in high-grade malignancy astrocytomas were found. In vitro, cultured glioma cells did not express AQP4, whereas healthy astrocytes revealed a slight upregulation of both isoforms and only a few OAPs in freeze fracture analysis. Taken together, we found a correlation between the decrease of OAPs and increasing grade of malignancy of astrocytomas but this was not consistent with an upregulation of AQP4-M1 in relation to AQP4 M23. PMID:27483250

  14. Histopathological spectrum of paediatric diffuse intrinsic pontine glioma: diagnostic and therapeutic implications.

    PubMed

    Buczkowicz, Pawel; Bartels, Ute; Bouffet, Eric; Becher, Oren; Hawkins, Cynthia

    2014-10-01

    Diffuse intrinsic pontine glioma (DIPG) is the main cause of brain tumour-related death in children. In the majority of cases diagnosis is based on clinical and MRI findings, resulting in the scarcity of pre-treatment specimens available to study. Our group has developed an autopsy-based protocol to investigate the histologic and biologic spectrum of DIPG. This has also allowed us to investigate the terminal pattern of disease and gain a better understanding of what challenges we are facing in treating DIPG. Here, we review 72 DIPG cases with well documented clinical history and molecular data and describe the pathological features of this disease in relation to clinical and genetic features. Fifty-three of the samples were autopsy material (7 pre-treatment) and 19 were pre-treatment biopsy/surgical specimens. Upon histological review, 62 patients had high-grade astrocytomas (18 WHO grade III and 44 WHO grade IV patients), 8 had WHO grade II astrocytomas, and 2 had features of primitive neuroectodermal tumour (PNET). K27M-H3 mutations were exclusively found in tumours with WHO grade II-IV astrocytoma histology. K27M-H3.1 and ACVR1 mutations as well as ALT phenotype were only found in WHO grade III-IV astrocytomas, while PIK3CA mutations and PDGFRA gains/amplifications were found in WHO grade II-IV astrocytomas. Approximately 1/3 of DIPG patients had leptomeningeal spread of their tumour. Further, diffuse invasion of the brainstem, spinal cord and thalamus was common with some cases showing spread as distant as the frontal lobes. These findings suggest that focal radiation may be inadequate for some of these patients. Importantly, we show that clinically classic DIPGs represent a diverse histologic spectrum, including multiple cases which would fit WHO criteria of grade II astrocytoma which nevertheless behave clinically as high-grade astrocytomas and harbour the histone K27M-H3.3 mutation. This suggests that the current WHO astrocytoma grading scheme may not

  15. Spinal Intradural, Extramedullary Ependymoma with Astrocytoma Component: A Case Report and Review of the Literature

    PubMed Central

    Weinstein, Gene M.; Arkun, Knarik; Kryzanski, James; Lanfranchi, Michael; Gupta, Gaurav K.; Bedi, Harprit

    2016-01-01

    Ependymomas are common spinal lesions, with the vast majority arising in an intramedullary location. Several cases have been described in the literature of ependymomas in an intradural, extramedullary location. The authors present a case of a 56-year-old female who presented with several weeks of lower back pain and weakness. MRI revealed an intradural, extramedullary enhancing mass at L1-L2. The mass was successfully resected surgically. Pathologic evaluation revealed a low grade glioma with components of both ependymoma and pilocytic astrocytoma with MUTYH G382D mutation. Extramedullary ependymomas are very rare tumors. To the authors' knowledge, this is the first case of ependymoma/astrocytoma collision tumors described in an extramedullary location. PMID:27313931

  16. Spinal Intradural, Extramedullary Ependymoma with Astrocytoma Component: A Case Report and Review of the Literature.

    PubMed

    Weinstein, Gene M; Arkun, Knarik; Kryzanski, James; Lanfranchi, Michael; Gupta, Gaurav K; Bedi, Harprit

    2016-01-01

    Ependymomas are common spinal lesions, with the vast majority arising in an intramedullary location. Several cases have been described in the literature of ependymomas in an intradural, extramedullary location. The authors present a case of a 56-year-old female who presented with several weeks of lower back pain and weakness. MRI revealed an intradural, extramedullary enhancing mass at L1-L2. The mass was successfully resected surgically. Pathologic evaluation revealed a low grade glioma with components of both ependymoma and pilocytic astrocytoma with MUTYH G382D mutation. Extramedullary ependymomas are very rare tumors. To the authors' knowledge, this is the first case of ependymoma/astrocytoma collision tumors described in an extramedullary location. PMID:27313931

  17. Specific localization of thallium 201 in human high-grade astrocytoma by microautoradiography.

    PubMed

    Mountz, J M; Raymond, P A; McKeever, P E; Modell, J G; Hood, T W; Barthel, L K; Stafford-Schuck, K A

    1989-07-15

    The ability to accurately distinguish remaining or recurrent high-grade astrocytoma from necrosis or edema following treatment is essential to optimal patient management. Thallium 201 planar gamma-camera imaging has been shown to be helpful in detecting recurrent high-grade astrocytoma; however, due to tissue heterogeneity adjacent to and within tumor, the cellular specificity and quantification of 201Tl uptake are largely unknown. In order to determine which tissues are responsible for the radioisotope uptake, microautoradiographic techniques were used to examine multiple tissue sections from five patients with high-grade astrocytoma. Each patient received 5 mCi of 201Tl i.v. 1 h prior to tumor removal. Additionally, all patients received computerized tomographic and 201Tl planar gamma-camera scans prior to surgery. Following surgery, the excised tissue specimens were tentatively classified by gross pathological examination and then immediately processed for dry mount autoradiography; grain density was determined over regions containing tumor, adjacent and uninvolved brain tissue, necrotic tissue, and background. Highly significant differences were found in grain densities (201Tl uptake) between tumor and uninvolved brain tissue, as well as between uninvolved brain tissue and necrotic tissue; there was no significant difference between background grain density and that in necrotic tissue. Mean grain densities (grains/cm2 +/- 1 SD) across patients were: tumor, 102 +/- 23; adjacent, uninvolved brain tissue, 29 +/- 11; necrotic tissue, 6.2 +/- 1.1; and background, 7.0 +/- 4.1. We conclude that the ability of 201Tl to selectively image high-grade astrocytoma is due to its preferential uptake into tumor cells.

  18. Vorinostat, Rituximab, and Combination Chemotherapy in Treating Patients With Newly Diagnosed Stage II, Stage III, or Stage IV Diffuse Large B-Cell Lymphoma

    ClinicalTrials.gov

    2016-09-08

    Stage II Contiguous Adult Diffuse Large Cell Lymphoma; Stage II Non-Contiguous Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma

  19. S0349 Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone With or Without Oblimersen in Treating Patients With Advanced Diffuse Large B-Cell Non-Hodgkin's Lymphoma

    ClinicalTrials.gov

    2013-01-04

    Contiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma

  20. Low-grade glioma: supratentorial astrocytoma, oligodendroglioma, and oligoastrocytoma in adults.

    PubMed

    Ashby, Lynn S; Shapiro, William R

    2004-05-01

    Low-grade glioma is not a single diagnosis but a category of biologically diverse neoplasms. They are indolent, progressive, and, following anaplastic transformation, invariably fatal. Neuro-oncologists have not established a treatment standard for these tumors. However, it is clear that "low-grade" is not synonymous with "benign," and treatment is required sometime in the course of the disease. Previously, achieving a consensus had been limited by a lack of class I evidence. Physicians treated patients based on retrospective series and personal experience. Currently, results from prospective clinical trials are becoming available. These studies have provided data that may serve as treatment guidelines. Additional results regarding the identification of prognostic variables have raised more questions to be answered. Attention is now directed to the importance of translational research to better define these neoplasms. In the future, it will be necessary to distinguish among low-grade gliomas and identify therapies that may differ between them.

  1. A study of loss of heterozygosity at 70 loci in anaplastic astrocytoma and glioblastoma multiforme with implications for tumor evolution.

    PubMed Central

    Wooten, E. C.; Fults, D.; Duggirala, R.; Williams, K.; Kyritsis, A. P.; Bondy, M. L.; Levin, V. A.; O'Connell, P.

    1999-01-01

    Cancers that arise from astrocytes in the adult CNS present as either anaplastic astrocytomas (AAs) or as more aggressive glioblastomas multiforme (GBMs). GBMs either form de novo or progress from AAs. We proposed to examine the molecular genetic relationship between these CNS tumors by conducting a genome-wide allelic imbalance analysis that included 70 loci on examples of AA and GBM. We found significant loss of heterozygosity (LOH) at 13 discrete chromosomal loci in both AAs and GBMs. Loss was significant in both AAs and GBMs at 9 of these loci. AAs show the highest rates of LOH at chromosomes 1p, 4q, 6p, 9p, 11p, 11q, 13q, 14q, 15p, 17p, 17q, and 19q. GBMs showed the greatest losses at 1p, 6q, 8p, 9p, 10p, 10q, 11p, 13q, 17p, 17q, 18p, 18q, and 19q. GBMs also demonstrated significant amplification at the epidermal growth factor receptor locus (7p12). These data suggest that there are three classes of loci involved in glioma evolution. First are loci that are likely involved in early events in the evolution of both AAs and GBMs. The second class consists of AA-specific loci, typified by higher LOH frequency than observed in GBMs (4q, 6p, 17p, 17q, 19q). The third class consists of GBM-specific loci (6q, 8p, 10, 18q). Damage at these loci may either lead to de novo GBMs or permit existing AAs to progress to GBMs. Glioma-related LOH profiles may have prognostic implications that could lead to better diagnosis and treatment of brain cancer patients. PMID:11550311

  2. MicroRNA profiling in pediatric pilocytic astrocytoma reveals biologically relevant targets, including PBX3, NFIB, and METAP2

    PubMed Central

    Ho, Cheng-Ying; Bar, Eli; Giannini, Caterina; Marchionni, Luigi; Karajannis, Matthias A.; Zagzag, David; Gutmann, David H.; Eberhart, Charles G.; Rodriguez, Fausto J.

    2013-01-01

    Pilocytic astrocytoma (PA) is a World Health Organization grade I glioma that occurs most commonly in children and young adults. Specific genetic alterations have been described in PA, but the pathogenesis remains poorly understood. We studied microRNA (miRNA) alterations in a large cohort of patients with PA. A total of 43 PA, including 35 sporadic grade I PA, 4 neurofibromatosis-1 (NF1)–associated PA, and 4 PA with pilomyxoid features, as well as 5 nonneoplastic brain controls were examined. BRAF fusion status was assessed in most cases. RNA was examined using the Agilent Human miRNA Microarray V3 platform. Expression of miRNA subsets was validated using quantitative real-time PCR (qRT-PCR) with Taqman probes. Validation of predicted protein targets was performed on tissue microarrays with the use of immunohistochemistry. We identified a subset of miRNAs that were differentially expressed in pediatric PAs versus normal brain tissue: 13 miRNAs were underexpressed, and 20 miRNAs were overexpressed in tumors. Differences were validated by qRT-PCR in a subset, with mean fold change in tumor versus brain of -17 (miR-124), -15 (miR-129), and 19.8 (miR-21). Searching for predicted protein targets in Targetscan, we identified a number of known and putative oncogenes that were predicted targets of miRNA sets relatively underexpressed in PA. Predicted targets with increased expression at the mRNA and/or protein level in PA included PBX3, METAP2, and NFIB. A unique miRNA profile exists in PA, compared with brain tissue. These miRNAs and their targets may play a role in the pathogenesis of PA. PMID:23161775

  3. B7-H3, a potential therapeutic target, is expressed in diffuse intrinsic pontine glioma.

    PubMed

    Zhou, Zhiping; Luther, Neal; Ibrahim, George M; Hawkins, Cynthia; Vibhakar, Rajeev; Handler, Michael H; Souweidane, Mark M

    2013-02-01

    Diffuse intrinsic pontine glioma (DIPG) is a brain cancer with a median survival of only 1 year. Lack of molecular characterization of this tumor impedes the development of novel therapies. Membrane protein B7-H3, aka CD276, involved in interactions with host defenses in certain cancers, has been shown to be over-expressed in the majority of malignant neuroectodermal tumors including adult high-grade glioma. Targeting B7-H3 with a monoclonal antibody has demonstrated safety and efficacy in the salvage treatment of stage IV childhood neuroblastoma, another neuroectodermal tumor. It thus stands to reason that B7-H3 might serve as a therapeutic target in DIPG. B7-H3 immunoreactivity was determined in DIPG and non-diffuse brainstem glioma specimens with immunohistochemistry. In addition, B7-H3 mRNA expression was evaluated with microarrays in another set of specimens. All of the nine (100 %) DIPG specimens were shown to be B7-H3 immunoreactive. In the non-diffuse brainstem glioma group, none of the eight WHO grade I specimens showed B7-H3 immunoreactivity and nine of the 24 WHO grade II specimens (37.5 %) showed B7-H3 immunoreactivity. The association between histological grade and B7-H3 immunoreactivity was statistically highly significant. B7-H3 mRNA expression was also significantly higher in DIPG samples than in normal brain and juvenile pilocytic astrocytoma (WHO grade I) specimens. In summary, B7-H3 is over-expressed in DIPG. Given the need for novel treatment in this disease, antibody-based immunotherapy against B7-H3 in DIPG warrants further investigation.

  4. Phenotypic variations in NF1-associated low grade astrocytomas: possible role for increased mTOR activation in a subset

    PubMed Central

    Jentoft, Mark; Giannini, Caterina; Cen, Ling; Scheithauer, Bernd W; Hoesley, Bridget; Sarkaria, Jann N; Abell-Aleff, Patrice C; Rodriguez, Erika F; Li, Ying; Rodriguez, Fausto J

    2011-01-01

    Low grade astrocytomas are the most common CNS tumors in neurofibromatosis type 1(NF1) patients. While most are classic pilocytic astrocytomas (PA), some are difficult to classify, and have been termed “low grade astrocytoma subtype indeterminate” (LGSI). Some of these tumors exhibit peculiar morphologies, including plump cytoplasmic processes and macronucleoli. In the current study we performed electron microscopy, followed by gene expression, immunohistochemicai and western blot analyses in an effort to identify biological differences underlying phenotypic variation in NF1-associated low grade astrocytoma. Electron microscopy demonstrated intermediate filaments and frequent Rosenthal fiber material in both PA and LGSI. Dense core granules and/or aligned microtubules were present in the LGSI group (2 of 3 cases) and in the PA group (1 of 10 cases). Analysis of global gene expression data obtained using Affymetrix HG-U133 Plus2.0 chips (5 PA, 1 LGSI), and western blot analysis for phospho-S6 (1 LGSI, 2 PA) demonstrated a gene expression profile reflecting “neuronal differentiation” and increased phospho-S6 immunoreactivity consistent with mTOR activation in the LGSI compared with PA. These findings were confirmed by immunohistochemistry for neuronal markers, as well as combined phospho-S6/ phospho-p70S6K immunoreactivity in 4 (of 4) LGSI vs. 5 (of 13) NF1-associated PA (p=0.02), and 13 (of 39) sporadic PA. Phospho-ERK immunoreactivity was uniformly present in PA and LGSI groups, while BRAF duplication was absent by FISH in 8 NF1-associated low grade astrocytomas. In summary, differential expression of neuronal-related genes and increased mTOR activation may underlie phenotypic variations in NF1-associated low grade astrocytomas. PMID:21228927

  5. Leksell Gamma Knife treatment for pilocytic astrocytomas: long-term results.

    PubMed

    Simonova, Gabriela; Kozubikova, Petra; Liscak, Roman; Novotny, Josef

    2016-07-01

    OBJECTIVE The purpose of this study was to evaluate long-term treatment results, radiation-related toxicity, and prognostic factors for the progression-free survival (PFS) of patients with pilocytic astrocytomas treated by means of stereotactic radiosurgery with a Leksell Gamma Knife. METHODS A total of 25 patients with pilocytic astrocytomas underwent Gamma Knife surgery during the period 1992-2002. The median target volume was 2700 mm(3) (range 205-25,000 mm(3)). The 18 patients treated with 5 daily fractions received a median minimum target dose of 25 Gy. Doses for the 2 patients treated with 10 fractions over 5 days (2 fractions delivered on the same day at least 6 hours apart) were 23 and 28 Gy. For the 5 patients treated with a single fraction, the minimum target dose ranged from 13 to 20 Gy (median 16 Gy). RESULTS Complete regression occurred in 10 patients (40%) and partial regression in 10 patients (40%). The 10-year overall survival rate was 96% and the 10-year PFS rate was 80%. Target volume appeared to be a significant prognostic factor for PFS (p = 0.037). Temporary Grade 3 toxicity appeared in 2 patients (8%), and these patients were treated with corticosteroids for 2 months. Permanent Grade 4 toxicity appeared in 2 patients (8%) and was associated with neurocognitive dysfunction. In these 2 individuals, the neurocognitive dysfunction was also felt to be in part the result of the additional therapeutic interventions (4 in one case and 6 in the other) required to achieve durable control of their tumors. CONCLUSIONS Radiosurgery represents an alternative treatment modality for small residual or recurrent volumes of pilocytic astrocytomas and provides long-term local control. Target volume appears to be the most important factor affecting PFS. PMID:26991883

  6. Clinical review of pediatric pilocytic astrocytomas treated at a tertiary care hospital in Pakistan

    PubMed Central

    Khan, Muhib A.; Godil, Saniya S.; Tabani, Halima; Panju, Sukaina A.; Enam, Syed A.

    2012-01-01

    Background: Pilocytic Astrocytoma (PA) is a common type of brain tumor in the pediatric population. They have a fairly good prognosis. This study describes PAs in detail, with a focus on the demographic factors, presenting features, management and prognosis, and aims, to identify the negative outcome predictors in our population, which can affect the course of the disease. This article will add to the understanding of PAs from a third world perspective. Methods: The Aga Khan University medical records (1995 – 2007) were reviewed, to study the clinical features, management, and outcome of patients (0 – 15 years) with Pilocytic Astrocytomas (PAs) in our population. After a thorough review of the medical records, all the PAs diagnosed on the basis of histopathology at our Pathology Laboratory, during this period, were included in the study. Results: Twenty-two patients were included with a mean age of 9.25 years. Male-to-female ratio was 1 : 1. The most common presenting feature was a sign of increased intracranial pressure. The most common location was the cerebellum followed by the cerebrum. Fifteen patients underwent maximum surgical resection. Three had recurrence, despite no residual tumor. There were 10 Intensive Care Unit (ICU) admissions and one inpatient mortality. Fifteen patients followed up in the clinic: Eight had recurrence and four underwent repeat surgery (three showed clinical improvement). Hydrocephalus was a predictor of ICU admission. Solid consistency was found to be a marker of recurrence. Conclusion: Pilocytic Astrocytomas are the most common pediatric brain tumors in our population, commonly located in the cerebellum. Complete resection is the best treatment option, but some tumors are aggressive and recurrence is not uncommon. The possible negative outcome predictors are age, source of admission, extent of resection, hydrocephalus, and solid consistency. PMID:23050204

  7. Neuroinflammation, hyperphosphorylated tau, diffuse amyloid plaques, and down-regulation of the cellular prion protein in air pollution exposed children and young adults.

    PubMed

    Calderón-Garcidueñas, Lilian; Kavanaugh, Michael; Block, Michelle; D'Angiulli, Amedeo; Delgado-Chávez, Ricardo; Torres-Jardón, Ricardo; González-Maciel, Angelica; Reynoso-Robles, Rafael; Osnaya, Norma; Villarreal-Calderon, Rodolfo; Guo, Ruixin; Hua, Zhaowei; Zhu, Hongtu; Perry, George; Diaz, Philippe

    2012-01-01

    Air pollution exposures have been linked to neuroinflammation and neuropathology. Autopsy samples of the frontal cortex from control (n = 8) and pollution-exposed (n = 35) children and young adults were analyzed by RT-PCR (n = 43) and microarray analysis (n = 12) for gene expression changes in oxidative stress, DNA damage signaling, NFκB signaling, inflammation, and neurodegeneration pathways. The effect of apolipoprotein E (APOE) genotype on the presence of protein aggregates associated with Alzheimer's disease (AD) pathology was also explored. Exposed urbanites displayed differential (>2-fold) regulation of 134 genes. Forty percent exhibited tau hyperphosphorylation with pre-tangle material and 51% had amyloid-β (Aβ) diffuse plaques compared with 0% in controls. APOE4 carriers had greater hyperphosphorylated tau and diffuse Aβ plaques versus E3 carriers (Q = 7.82, p = 0.005). Upregulated gene network clusters included IL1, NFκB, TNF, IFN, and TLRs. A 15-fold frontal down-regulation of the prion-related protein (PrP(C)) was seen in highly exposed subjects. The down-regulation of the PrP(C) is critical given its important roles for neuroprotection, neurodegeneration, and mood disorder states. Elevation of indices of neuroinflammation and oxidative stress, down-regulation of the PrP(C) and AD-associated pathology are present in young megacity residents. The inducible regulation of gene expression suggests they are evolving different mechanisms in an attempt to cope with the constant state of inflammation and oxidative stress related to their environmental exposures. Together, these data support a role for air pollution in CNS damage and its impact upon the developing brain and the potential etiology of AD and mood disorders. PMID:21955814

  8. Development of Brain Structural Connectivity between Ages 12 and 30: A 4-Tesla Diffusion Imaging Study in 439 Adolescents and Adults

    PubMed Central

    Dennis, Emily L.; Jahanshad, Neda; McMahon, Katie L.; de Zubicaray, Greig I.; Martin, Nicholas G.; Hickie, Ian B.; Toga, Arthur W.; Wright, Margaret J.; Thompson, Paul M.

    2013-01-01

    Understanding how the brain matures in healthy individuals is critical for evaluating deviations from normal development in psychiatric and neurodevelopmental disorders. The brain’s anatomical networks are profoundly re-modeled between childhood and adulthood, and diffusion tractography offers unprecedented power to reconstruct these networks and neural pathways in vivo. Here we tracked changes in structural connectivity and network efficiency in 439 right-handed individuals aged 12 to 30 (211 female/126 male adults, mean age=23.6, SD=2.19; 31 female/24 male 12 year olds, mean age=12.3, SD=0.18; and 25 female/22 male 16 year olds, mean age=16.2, SD=0.37). All participants were scanned with high angular resolution diffusion imaging (HARDI) at 4 Tesla. After we performed whole brain tractography, 70 cortical gyral-based regions of interest were extracted from each participant’s co-registered anatomical scans. The degree of fiber connections between all pairs of cortical regions, or nodes, were found to create symmetric fiber density matrices, reflecting the structural brain network. From those 70×70 matrices we computed graph theory metrics characterizing structural connectivity. Several key global and nodal metrics changed across development, showing increased network integration, with some connections pruned and others strengthened. The increases and decreases in fiber density, however, were not distributed proportionally across the brain. The frontal cortex had a disproportionate number of decreases in fiber density while the temporal cortex had a disproportionate number of increases in fiber density. This large-scale analysis of the developing structural connectome offers a foundation to develop statistical criteria for aberrant brain connectivity as the human brain matures. PMID:22982357

  9. Updated therapeutic strategy for adult low-grade glioma stratified by resection and tumor subtype.

    PubMed

    Nitta, Masayuki; Muragaki, Yoshihiro; Maruyama, Takashi; Iseki, Hiroshi; Ikuta, Soko; Konishi, Yoshiyuki; Saito, Taichi; Tamura, Manabu; Chernov, Michael; Watanabe, Atsushi; Okamoto, Saori; Maebayashi, Katsuya; Mitsuhashi, Norio; Okada, Yoshikazu

    2013-01-01

    The importance of surgical resection for patients with supratentorial low-grade glioma (LGG) remains controversial. This retrospective study of patients (n = 153) treated between 2000 to 2010 at a single institution assessed whether increasing the extent of resection (EOR) was associated with improved progression-free survival (PFS) and overall survival (OS). Histological subtypes of World Health Organization grade II tumors were as follows: diffuse astrocytoma in 49 patients (32.0%), oligoastrocytoma in 45 patients (29.4%), and oligodendroglioma in 59 patients (38.6%). Median pre- and postoperative tumor volumes and median EOR were 29.0 cm(3) (range 0.7-162 cm(3)) and 1.7 cm(3) (range 0-135.7 cm(3)) and 95%, respectively. Five- and 10-year OS for all LGG patients were 95.1% and 85.4%, respectively. Eight-year OS for diffuse astrocytoma, oligoastrocytoma, and oligodendroglioma were 70.7%, 91.2%, and 98.3%, respectively. Five-year PFS for diffuse astrocytoma, oligoastrocytoma, and oligodendroglioma were 42.6%, 71.3%, and 62.7%, respectively. Patients were divided into two groups by EOR ≥90% and <90%, and OS and PFS were analyzed. Both OS and PFS were significantly longer in patients with ≥90% EOR. Increased EOR resulted in better PFS for diffuse astrocytoma but not for oligodendroglioma. Multivariate analysis identified age and EOR as parameters significantly associated with OS. The only parameter associated with PFS was EOR. Based on these findings, we established updated therapeutic strategies for LGG. If surgery resulted in EOR <90%, patients with astrocytoma will require second-look surgery, whereas patients with oligodendroglioma or oligoastrocytoma, which are sensitive to chemotherapy, will be treated with chemotherapy.

  10. Psychologic and neurologic function following treatment for childhood temporal lobe astrocytoma.

    PubMed

    Mulhern, R K; Kovnar, E H; Kun, L E; Crisco, J J; Williams, J M

    1988-01-01

    Seven school-aged children treated for temporal lobe astrocytomas with surgical resection and irradiation were prospectively tested to evaluate their intellectual, academic, personality, and neurologic status after therapy. At their most recent follow-up examination, neuropsychologic functioning was adequate in only two patients. The other five children manifested either intellectual deterioration, learning disability, mental retardation, or psychopathology. These deficits were associated with poor postoperative performance status, inadequate seizure control, tumor recurrence, and younger age at diagnosis. No pattern of intellectual, academic, or personality dysfunction emerged in association with left- versus right-hemisphere tumors.

  11. Ollier disease with anaplastic astrocytoma: A review of the literature and a unique case

    PubMed Central

    Gajavelli, Srikanth; Nakhla, Jonathan; Nasser, Rani; Yassari, Reza; Weidenheim, Karen M.; Graber, Jerome

    2016-01-01

    Background: Ollier disease is a rare, nonfamilial disorder that primary affects the long bones and cartilage of joints with multiple enchondromas. It is associated with a higher risk of central nervous system (CNS) malignancies; although the incidence is unknown. Case Description: Here, we present the case of a 55-year-old woman who developed an anaplastic astrocytoma with a known diagnosis of Ollier disease with a survival time of over 3 years. Conclusion: This report draws attention to the rarity of this disease and the paucity of information regarding CNS involvement in Ollier disease, as well as reviews the current literature.

  12. Differential prefrontal-like deficit in children after cerebellar astrocytoma and medulloblastoma tumor

    PubMed Central

    Vaquero, Encarna; Gómez, Carlos M; Quintero, Eliana A; González-Rosa, Javier J; Márquez, Javier

    2008-01-01

    Background This study was realized thanks to the collaboration of children and adolescents who had been resected from cerebellar tumors. The medulloblastoma group (CE+, n = 7) in addition to surgery received radiation and chemotherapy. The astrocytoma group (CE, n = 13) did not receive additional treatments. Each clinical group was compared in their executive functioning with a paired control group (n = 12). The performances of the clinical groups with respect to controls were compared considering the tumor's localization (vermis or hemisphere) and the affectation (or not) of the dentate nucleus. Executive variables were correlated with the age at surgery, the time between surgery-evaluation and the resected volume. Methods The executive functioning was assessed by means of WCST, Complex Rey Figure, Controlled Oral Word Association Test (letter and animal categories), Digits span (WISC-R verbal scale) and Stroop test. These tests are very sensitive to dorsolateral PFC and/or to medial frontal cortex functions. The scores for the non-verbal Raven IQ were also obtained. Direct scores were corrected by age and transformed in standard scores using normative data. The neuropsychological evaluation was made at 3.25 (SD = 2.74) years from surgery in CE group and at 6.47 (SD = 2.77) in CE+ group. Results The Medulloblastoma group showed severe executive deficit (≤ 1.5 SD below normal mean) in all assessed tests, the most severe occurring in vermal patients. The Astrocytoma group also showed executive deficits in digits span, semantic fluency (animal category) and moderate to slight deficit in Stroop (word and colour) tests. In the astrocytoma group, the tumor's localization and dentate affectation showed different profile and level of impairment: moderate to slight for vermal and hemispheric patients respectively. The resected volume, age at surgery and the time between surgery-evaluation correlated with some neuropsychological executive variables. Conclusion Results

  13. Infratentorial benign cystic meningioma mimicking a hemangioblastoma radiologically and a pilocytic astrocytoma intraoperatively: a case report

    PubMed Central

    2013-01-01

    Introduction Cystic meningiomas are rare variants of meningiomas; they can pose a radiological diagnostic dilemma. Case presentation We present a rare case of a 30-year-old Chinese woman with a histopathological diagnosis of infratentorial cystic meningioma (World Health Organization Grade 1) in which the features in imaging modalities were suggestive of a hemangioblastoma. Intraoperatively, however, the gross macroscopic features were more in keeping with a pilocytic astrocytoma. Conclusion In benign cystic meningiomas, particularly the infratentorial variety, radiological findings utilizing the various imaging modalities and intraoperative impressions may not be reflective of or in keeping with the final histopathological diagnosis. PMID:23537099

  14. Massive Calcified Cerebellar Pilocytic Astrocytoma with Rapid Recurrence : A Rare Case.

    PubMed

    Aydemir, Fatih; Kardes, Ozgur; Kayaselçuk, Fazilet; Tufan, Kadir

    2016-09-01

    Pilocytic astrocytomas (PAs) are World Heath Organization Grade I tumors and are most common in children. PA calcification is not a common finding and has been reported more frequently in the optic nerve, hypothalamic/thalamus and superficially located cerebral tumors. We present a cerebellar PA in a 3-year-old male patient with cystic components and massive calcification areas. The residual tumor grew rapidly after the first operation, and the patient was operated on again. A histopathological examination revealed polar spongioblastoma-like cells. Massive calcification is not a common feature in PAs and can lead to difficulties in radiological and pathological differential diagnoses. PMID:27651876

  15. Ollier disease with anaplastic astrocytoma: A review of the literature and a unique case

    PubMed Central

    Gajavelli, Srikanth; Nakhla, Jonathan; Nasser, Rani; Yassari, Reza; Weidenheim, Karen M.; Graber, Jerome

    2016-01-01

    Background: Ollier disease is a rare, nonfamilial disorder that primary affects the long bones and cartilage of joints with multiple enchondromas. It is associated with a higher risk of central nervous system (CNS) malignancies; although the incidence is unknown. Case Description: Here, we present the case of a 55-year-old woman who developed an anaplastic astrocytoma with a known diagnosis of Ollier disease with a survival time of over 3 years. Conclusion: This report draws attention to the rarity of this disease and the paucity of information regarding CNS involvement in Ollier disease, as well as reviews the current literature. PMID:27656320

  16. Massive Calcified Cerebellar Pilocytic Astrocytoma with Rapid Recurrence : A Rare Case

    PubMed Central

    Kardes, Ozgur; Kayaselçuk, Fazilet; Tufan, Kadir

    2016-01-01

    Pilocytic astrocytomas (PAs) are World Heath Organization Grade I tumors and are most common in children. PA calcification is not a common finding and has been reported more frequently in the optic nerve, hypothalamic/thalamus and superficially located cerebral tumors. We present a cerebellar PA in a 3-year-old male patient with cystic components and massive calcification areas. The residual tumor grew rapidly after the first operation, and the patient was operated on again. A histopathological examination revealed polar spongioblastoma-like cells. Massive calcification is not a common feature in PAs and can lead to difficulties in radiological and pathological differential diagnoses. PMID:27651876

  17. Massive Calcified Cerebellar Pilocytic Astrocytoma with Rapid Recurrence : A Rare Case

    PubMed Central

    Kardes, Ozgur; Kayaselçuk, Fazilet; Tufan, Kadir

    2016-01-01

    Pilocytic astrocytomas (PAs) are World Heath Organization Grade I tumors and are most common in children. PA calcification is not a common finding and has been reported more frequently in the optic nerve, hypothalamic/thalamus and superficially located cerebral tumors. We present a cerebellar PA in a 3-year-old male patient with cystic components and massive calcification areas. The residual tumor grew rapidly after the first operation, and the patient was operated on again. A histopathological examination revealed polar spongioblastoma-like cells. Massive calcification is not a common feature in PAs and can lead to difficulties in radiological and pathological differential diagnoses.

  18. Multiparametric Characterization of Grade 2 Glioma Subtypes Using Magnetic Resonance Spectroscopic, Perfusion, and Diffusion Imaging1

    PubMed Central

    Bian, Wei; Khayal, Inas S; Lupo, Janine M; McGue, Colleen; Vandenberg, Scott; Lamborn, Kathleen R; Chang, Susan M; Cha, Soonmee; Nelson, Sarah J

    2009-01-01

    BACKGROUND AND PURPOSE: The purpose of this study was to derive quantitative parameters from magnetic resonance (MR) spectroscopic, perfusion, and diffusion imaging of grade 2 gliomas according to the World Health Organization and to investigate how these multiple imaging modalities can contribute to evaluating their histologic subtypes and spatial characteristics. MATERIALS AND METHODS: MR spectroscopic, perfusion, and diffusion images from 56 patients with newly diagnosed grade 2 glioma (24 oligodendrogliomas, 18 astrocytomas, and 14 oligoastrocytomas) were retrospectively studied. Metabolite intensities, relative cerebral blood volume (rCBV), and apparent diffusion coefficient (ADC) were statistically evaluated. RESULTS: The 75th percentile rCBV and median ADC were significantly different between oligodendrogliomas and astrocytomas (P < .0001) and between oligodendrogliomas and oligoastrocytomas (P < .001). Logistic regression analysis identified both 75th percentile rCBV and median ADC as significant variables in the differentiation of oligodendrogliomas from astrocytomas and oligoastrocytomas. Group differences in metabolite intensities were not significant, but there was a much larger variation in the volumes and maximum values of metabolic abnormalities for patients with oligodendroglioma compared with the other tumor subtypes. CONCLUSIONS: Perfusion and diffusion imaging provide quantitative MR parameters that can help to differentiate grade 2 oligodendrogliomas from grade 2 astrocytomas and oligoastrocytomas. The large variations in the magnitude and spatial extent of the metabolic lesions between patients and the fact that their values are not correlated with the other imaging parameters indicate that MR spectroscopic imaging may provide complementary information that is helpful in targeting therapy, evaluating residual disease, and assessing response to therapy. PMID:19956389

  19. Low-, medium- and high-dose steroids with or without aminocaproic acid in adult hematopoietic SCT patients with diffuse alveolar hemorrhage.

    PubMed

    Rathi, N K; Tanner, A R; Dinh, A; Dong, W; Feng, L; Ensor, J; Wallace, S K; Haque, S A; Rondon, G; Price, K J; Popat, U; Nates, J L

    2015-03-01

    Diffuse alveolar hemorrhage (DAH) is a poorly understood complication of transplantation carrying a high mortality. Patients commonly deteriorate and require intensive care unit (ICU) admission. Treatment with high-dose steroids and aminocaproic acid (ACA) has been suggested. The current study examined 119 critically ill adult hematopoietic transplant patients treated for DAH. Patients were subdivided into low-, medium- and high-dose steroid groups with or without ACA. All groups had similar baseline characteristics and severity of illness scores. Primary objectives were 30, 60, 100 day, ICU and hospital mortality. Overall mortality (n=119) on day 100 was high at 85%. In the steroids and ACA cohort (n=82), there were no significant differences in 30, 60, 100, day, ICU and hospital mortality between the dosing groups. In the steroids only cohort (n=37), the low-dose steroid group had a lower ICU and hospital mortality (P=0.02). Adjunctive treatment with ACA did not produce differences in outcomes. In the multivariate analysis, medium- and high-dose steroids were associated with a higher ICU mortality (P=0.01) as compared with the low-dose group. Our data suggest that treatment strategies may need to be reanalyzed to avoid potentially unnecessary and potentially harmful therapies.

  20. Mean diffusivity of globus pallidus associated with verbal creativity measured by divergent thinking and creativity‐related temperaments in young healthy adults

    PubMed Central

    Taki, Yasuyuki; Sekiguchi, Atsushi; Hashizume, Hiroshi; Nouchi, Rui; Sassa, Yuko; Kotozaki, Yuka; Miyauchi, Carlos Makoto; Yokoyama, Ryoichi; Iizuka, Kunio; Nakagawa, Seishu; Nagase, Tomomi; Kunitoki, Keiko; Kawashima, Ryuta

    2015-01-01

    Abstract Recent investigations revealed mean diffusivity (MD) in gray matter and white matter areas is correlated with individual cognitive differences in healthy subjects and show unique properties and sensitivity that other neuroimaging tools donot have. In this study, we tested the hypothesis that the MD in the dopaminergic system is associated with individual differences in verbal creativity measured by divergent thinking (VCDT) and novelty seeking based on prior studies suggesting associations between these and dopaminergic functions. We examined this issue in a large sample of right‐handed healthy young adults. We used analyses of MD and a psychological measure of VCDT, as well as personality measures of the Temperament and Character Inventory (TCI). Our results revealed associations between higher VCDT and lower MD in the bilateral globus pallidus. Furthermore, not only higher novelty seeking, but also lower harm avoidance, higher self‐directedness, and higher self‐transcendence were robustly associated with lower MD in the right globus pallidus, whereas higher persistence was associated with lower MD in the left globus pallidus. These personality variables were also associated with VCDT. The globus pallidus receives the dopaminergic input from the substantia nigra and plays a key role in motivation which is critically linked to dopamine. These results suggested the MD in the globus pallidus, underlie the association between VCDT and multiple personalities in TCI including novelty seeking. Hum Brain Mapp 36:1808–1827, 2015. © 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. PMID:25627674

  1. Mean diffusivity of globus pallidus associated with verbal creativity measured by divergent thinking and creativity-related temperaments in young healthy adults.

    PubMed

    Takeuchi, Hikaru; Taki, Yasuyuki; Sekiguchi, Atsushi; Hashizume, Hiroshi; Nouchi, Rui; Sassa, Yuko; Kotozaki, Yuka; Miyauchi, Carlos Makoto; Yokoyama, Ryoichi; Iizuka, Kunio; Nakagawa, Seishu; Nagase, Tomomi; Kunitoki, Keiko; Kawashima, Ryuta

    2015-05-01

    Recent investigations revealed mean diffusivity (MD) in gray matter and white matter areas is correlated with individual cognitive differences in healthy subjects and show unique properties and sensitivity that other neuroimaging tools donot have. In this study, we tested the hypothesis that the MD in the dopaminergic system is associated with individual differences in verbal creativity measured by divergent thinking (VCDT) and novelty seeking based on prior studies suggesting associations between these and dopaminergic functions. We examined this issue in a large sample of right-handed healthy young adults. We used analyses of MD and a psychological measure of VCDT, as well as personality measures of the Temperament and Character Inventory (TCI). Our results revealed associations between higher VCDT and lower MD in the bilateral globus pallidus. Furthermore, not only higher novelty seeking, but also lower harm avoidance, higher self-directedness, and higher self-transcendence were robustly associated with lower MD in the right globus pallidus, whereas higher persistence was associated with lower MD in the left globus pallidus. These personality variables were also associated with VCDT. The globus pallidus receives the dopaminergic input from the substantia nigra and plays a key role in motivation which is critically linked to dopamine. These results suggested the MD in the globus pallidus, underlie the association between VCDT and multiple personalities in TCI including novelty seeking.

  2. Dexamethasone acts as a radiosensitizer in three astrocytoma cell lines via oxidative stress.

    PubMed

    Ortega-Martínez, Sylvia

    2015-08-01

    Glucocorticoids (GCs), which act on stress pathways, are well-established in the co-treatment of different kinds of tumors; however, the underlying mechanisms by which GCs act are not yet well elucidated. As such, this work investigates the role of glucocorticoids, specifically dexamethasone (DEXA), in the processes referred to as DNA damage and DNA damage response (DDR), establishing a new approach in three astrocytomas cell lines (CT2A, APP.PS1 L.1 and APP.PS1 L.3). The results show that DEXA administration increased the basal levels of gamma-H2AX foci, keeping them higher 4h after irradiation (IR) of the cells, compared to untreated cells. This means that DEXA might cause increased radiosensitivity in these cell lines. On the other hand, DEXA did not have an apparent effect on the formation and disappearance of the 53BP1 foci. Furthermore, it was found that DEXA administered 2h before IR led to a radical change in DNA repair kinetics, even DEXA does not affect cell cycle. It is important to highlight that DEXA produced cell death in these cell lines compared to untreated cells. Finally and most important, the high levels of gamma-H2AX could be reversed by administration of ascorbic acid, a potent blocker of reactive oxygen species, suggesting that DEXA acts by causing DNA damage via oxidative stress. These exiting findings suggest that DEXA might promote radiosensitivity in brain tumors, specifically in astrocytoma-like tumors.

  3. Pleiotrophin promotes vascular abnormalization in gliomas and correlates with poor survival in patients with astrocytomas.

    PubMed

    Zhang, Lei; Kundu, Soumi; Feenstra, Tjerk; Li, Xiujuan; Jin, Chuan; Laaniste, Liisi; El Hassan, Tamador Elsir Abu; Ohlin, K Elisabet; Yu, Di; Olofsson, Tommie; Olsson, Anna-Karin; Pontén, Fredrik; Magnusson, Peetra U; Nilsson, Karin Forsberg; Essand, Magnus; Smits, Anja; Dieterich, Lothar C; Dimberg, Anna

    2015-12-01

    Glioblastomas are aggressive astrocytomas characterized by endothelial cell proliferation and abnormal vasculature, which can cause brain edema and increase patient morbidity. We identified the heparin-binding cytokine pleiotrophin as a driver of vascular abnormalization in glioma. Pleiotrophin abundance was greater in high-grade human astrocytomas and correlated with poor survival. Anaplastic lymphoma kinase (ALK), which is a receptor that is activated by pleiotrophin, was present in mural cells associated with abnormal vessels. Orthotopically implanted gliomas formed from GL261 cells that were engineered to produce pleiotrophin showed increased microvessel density and enhanced tumor growth compared with gliomas formed from control GL261 cells. The survival of mice with pleiotrophin-producing gliomas was shorter than that of mice with gliomas that did not produce pleiotrophin. Vessels in pleiotrophin-producing gliomas were poorly perfused and abnormal, a phenotype that was associated with increased deposition of vascular endothelial growth factor (VEGF) in direct proximity to the vasculature. The growth of pleiotrophin-producing GL261 gliomas was inhibited by treatment with the ALK inhibitor crizotinib, the ALK inhibitor ceritinib, or the VEGF receptor inhibitor cediranib, whereas control GL261 tumors did not respond to either inhibitor. Our findings link pleiotrophin abundance in gliomas with survival in humans and mice, and show that pleiotrophin promotes glioma progression through increased VEGF deposition and vascular abnormalization. PMID:26645582

  4. Effect of radiotherapy on brain glucose metabolism in patients operated on for low grade astrocytoma

    PubMed Central

    Bruehlmeier, M; Roelcke, U; Amsler, B; Schubert, K; Hausmann, O; von Ammon, K; Radu, E; Gratzl, O; Landmann, C; Leenders, K

    1999-01-01

    OBJECTIVE—To assess the effect of postoperative radiotherapy on brain glucose metabolism (CMRGlu) of operated patients with low grade astrocytomas.
METHODS—PET and 18F-fluorodeoxyglucose was used to measure absolute CMRGlu in patients with fibrillary astrocytoma (WHO II) of the frontal lobe, who did (n=7) or did not (n=12) receive radiotherapy subsequent to first debulking tumour resection. In addition, statistical parametric mapping (SPM95) was applied to assess the pattern of relative CMRGlu associated with the frontal tumour. Data were compared with 12 healthy controls.
RESULTS—A global reduction of absolute CMRGlu was found when either patients with or without radiotherapy were compared with controls (ROI analysis). Brain areas of relative CMRGlu reduction were found in the brain ipsilateral and contralateral to the tumour, comparing both patient groups with controls by SPM ("tumour diaschisis effect"). Superimposed, absolute CMRGlu in the contralateral frontal, parietal, occipital cortex as well as in the white matter was on average 17% lower in patients receiving radiotherapy than in patients who did not.
CONCLUSIONS—The data discriminate a tumour effect from a radiotherapy effect, and support the view of adverse effects of radiotherapy on brain not directly involved by tumour.

 PMID:10209180

  5. Acetylcholine as a mitogen: muscarinic receptor-mediated proliferation of rat astrocytes and human astrocytoma cells.

    PubMed

    Guizzetti, M; Costa, P; Peters, J; Costa, L G

    1996-02-22

    The mitogenic effect of muscarinic receptor agonists in glial cells has been characterized in rat cortical astrocytes and human 132 1N1 astrocytoma cells. The muscarinic receptor agonist carbachol caused a dose- and time-dependent increase in proliferation, as measured by [3H]thymidine incorporation. The mitogenic effect was mimicked by several muscarinic, but not nicotinic receptor agonists, and was blocked by muscarinic receptor antagonists. Reverse transcription-polymerase chain reaction (RT-PCR) experiments indicated the presence of m2, m3 and to a lesser degree, m5 muscarinic receptor mRNA in both astrocytes and astrocytoma cells. Proliferation experiments with subtype-specific muscarinic receptor antagonists suggest that carbachol-induced proliferation is due to activation of muscarinic M3 receptors. The phorbol ester 12-O-tetradecanoyl-phorbol 13-acetate (TPA) also stimulated glial cell proliferation. Down-regulation of protein kinase C, or the protein kinase C antagonist 1,5-(isoquinolynsulfanyl)-2-methylpiperazine dihydrochloride (H7) blocked proliferation induced by either TPA or carbachol. Of other neurotransmitters tested, histamine caused glial cell proliferation, norepinephrine and gamma-aminobutyric acid were ineffective, while serotonin and glutamate inhibited basal or serum-stimulated proliferation. PMID:8666059

  6. Proteome alteration of U251 human astrocytoma cell after inhibiting retinoic acid synthesis.

    PubMed

    Zhang, Ming; Wan, Chunling; Ji, Baohu; Zhang, Zhao; Zhu, Hui; Tian, Nan; La, Yujuan; Huang, Ke; Jiang, Lei; He, Guang; Gao, Linhan; Zhao, Xinzhi; Shi, Yongyong; Huang, Gang; Feng, Guoyin; He, Lin

    2009-03-01

    Retinoic acid (Ra) is crucial for the patterning and neuronal differentiation in the central nervous system (CNS). Ra deficiency in animals disrupts the motor activities and memory abilities. The molecular mechanisms underlying these behavior abnormalities remain largely unknown. In the current study, we treated the astrocytoma cells with citral, an inhibitor of Ra synthesis. We analyzed the differences in the protein concentrations between the treated and untreated astrocytoma cells by two-dimensional gel electrophoresis (2-DE), Imagemaster software, and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). In total, 39 of 46 altered protein spots with significant mascot scores were identified representing 36 proteins, that were involved in significantly altered glutamate metabolism, lipid metabolism, mitochondrial function, and oxidative stress response by Ingenuity Pathway Analysis (IPA). Altered 3-phosphoglycerate dehydrogenase (PHGDH) was also observed in western blot. These data provide some clues for explaining the behavioral changes caused by Ra deficiency, and support the hypothesis that Ra signaling is associated with some symptoms of neurodegenerative disorders and schizophrenia. PMID:19089318

  7. The Regulation of RhoA at Focal Adhesions by StarD13 is Important for Astrocytoma Cell Motility

    PubMed Central

    Khalil, Bassem D.; Hanna, Samer; Saykali, Bechara A.; El-Sitt, Sally; Nasrallah, Anita; Marston, Daniel; El-Sabban, Marwan; Hahn, Klaus M.; Symons, Marc; El-Sibai, Mirvat

    2015-01-01

    Malignant astrocytomas are highly invasive into adjacent and distant regions of the normal brain. Rho GTPases are small monomeric G proteins that play important roles in cytoskeleton rearrangement, cell motility, and tumor invasion. In the present study, we show that the knock down of StarD13, a GTPase activating protein (GAP) for RhoA and Cdc42, inhibits astrocytoma cell migration through modulating focal adhesion dynamics and cell adhesion. This effect is mediated by the resulting constitutive activation of RhoA and the subsequent indirect inhibition of Rac. Using Total Internal Reflection Fluorescence (TIRF)-based Förster Resonance Energy Transfer (FRET), we show that RhoA activity localizes with focal adhesions at the basal surface of astrocytoma cells. Moreover, the knock down of StarD13 inhibits the cycling of RhoA activation at the rear edge of cells, which makes them defective in retracting their tail. This study highlights the importance of the regulation of RhoA activity in focal adhesions of astrocytoma cells and establishes StarD13 as a GAP playing a major role in this process. PMID:24333506

  8. Pilocytic Astrocytoma of the Optic Pathway: A Tumour Deriving from Radial Glia Cells with a Specific Gene Signature

    ERIC Educational Resources Information Center

    Tchoghandjian, Aurelie; Fernandez, Carla; Colin, Carole; El Ayachi, Ikbale; Voutsinos-Porche, Brigitte; Fina, Frederic; Scavarda, Didier; Piercecchi-Marti, Marie-Dominique; Intagliata, Dominique; Ouafik, L'Houcine; Fraslon-Vanhulle, Caroline; Figarella-Branger, Dominique

    2009-01-01

    Pilocytic astrocytomas are WHO grade I gliomas that occur predominantly in childhood. They share features of both astroglial and oligodendroglial lineages. These tumours affect preferentially the cerebellum (benign clinical course) and the optic pathway, especially the hypothalamo-chiasmatic region (poor prognosis). Understanding the molecular…

  9. Sleeping beauty-mediated somatic mutagenesis implicates CSF1 in the formation of high-grade astrocytomas.

    PubMed

    Bender, Aaron M; Collier, Lara S; Rodriguez, Fausto J; Tieu, Christina; Larson, Jon D; Halder, Chandralekha; Mahlum, Eric; Kollmeyer, Thomas M; Akagi, Keiko; Sarkar, Gobinda; Largaespada, David A; Jenkins, Robert B

    2010-05-01

    The Sleeping Beauty (SB) transposon system has been used as an insertional mutagenesis tool to identify novel cancer genes. To identify glioma-associated genes, we evaluated tumor formation in the brain tissue from 117 transgenic mice that had undergone constitutive SB-mediated transposition. Upon analysis, 21 samples (18%) contained neoplastic tissue with features of high-grade astrocytomas. These tumors expressed glial markers and were histologically similar to human glioma. Genomic DNA from SB-induced astrocytoma tissue was extracted and transposon insertion sites were identified. Insertions in the growth factor gene Csf1 were found in 13 of the 21 tumors (62%), clustered in introns 5 and 8. Using reverse transcription-PCR, we documented increased Csf1 RNAs in tumor versus adjacent normal tissue, with the identification of transposon-terminated Csf1 mRNAs in astrocytomas with SB insertions in intron 8. Analysis of human glioblastomas revealed increased levels of Csf1 RNA and protein. Together, these results indicate that SB-insertional mutagenesis can identify high-grade astrocytoma-associated genes and they imply an important role for CSF1 in the development of these tumors. PMID:20388773

  10. Screening feature genes of astrocytoma using a combined method of microarray gene expression profiling and bioinformatics analysis

    PubMed Central

    Cai, Yong; Zhong, Xingming; Wang, Yiqi; Yang, Jianguo

    2015-01-01

    The aim of our study was to find feature genes associated with astrocytoma and correlative gene functions which can distinguish cancer tissue from adjacent non-tumor astrocyte tissues. Gene expression profile GSE15824 was downloaded from Gene Expression Omnibus database which included 8 astrocytoma tissues and 3 adjacent non-tumor astrocyte samples. The raw data were first transformed into probe-level data and the differentially expressed genes (DEGs) between tissues of patients with astrocytoma and normal specimen were identified using T-test in samr package of R. The Database for Annotation, Visualization and Integrated Discovery (DAVID) was applied to analyze the gene ontology (GO) enrichment on gene functions and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Finally, corresponding protein-protein interaction (PPI) networks of DEGs was constructed using the Cytoscape based on the data collected from STRING online datasets. A total of 3072 genes, including 1799 up-regulated genes and 1273 down-regulated genes, were filtered as DEGs, and we learnt that the DEGs including AQP4, PMP2, SRARCL1 and SLC1A2CAMs etc and that AQP4 was most significantly related to cell osmotic pressure. Three feature genes in KEGG pathway are highly enriched in cancer specimen while two genes are in the normal tissues. The discovery of featured genes significantly related to the regulation of cell osmotic pressure, has the potential to use in clinic for diagnosis of astrocytoma in future. In addition, it has a great significance on studying mechanism, distinguishing normal and cancer tissues, and exploring new treatments for astrocytoma. However, further experiments were needed to confirm our result. PMID:26770395

  11. Screening feature genes of astrocytoma using a combined method of microarray gene expression profiling and bioinformatics analysis.

    PubMed

    Cai, Yong; Zhong, Xingming; Wang, Yiqi; Yang, Jianguo

    2015-01-01

    The aim of our study was to find feature genes associated with astrocytoma and correlative gene functions which can distinguish cancer tissue from adjacent non-tumor astrocyte tissues. Gene expression profile GSE15824 was downloaded from Gene Expression Omnibus database which included 8 astrocytoma tissues and 3 adjacent non-tumor astrocyte samples. The raw data were first transformed into probe-level data and the differentially expressed genes (DEGs) between tissues of patients with astrocytoma and normal specimen were identified using T-test in samr package of R. The Database for Annotation, Visualization and Integrated Discovery (DAVID) was applied to analyze the gene ontology (GO) enrichment on gene functions and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Finally, corresponding protein-protein interaction (PPI) networks of DEGs was constructed using the Cytoscape based on the data collected from STRING online datasets. A total of 3072 genes, including 1799 up-regulated genes and 1273 down-regulated genes, were filtered as DEGs, and we learnt that the DEGs including AQP4, PMP2, SRARCL1 and SLC1A2CAMs etc and that AQP4 was most significantly related to cell osmotic pressure. Three feature genes in KEGG pathway are highly enriched in cancer specimen while two genes are in the normal tissues. The discovery of featured genes significantly related to the regulation of cell osmotic pressure, has the potential to use in clinic for diagnosis of astrocytoma in future. In addition, it has a great significance on studying mechanism, distinguishing normal and cancer tissues, and exploring new treatments for astrocytoma. However, further experiments were needed to confirm our result. PMID:26770395

  12. Low grade astrocytoma in children under the age of three years: a report from the Canadian pediatric brain tumour consortium.

    PubMed

    Johnston, Donna L; Keene, Daniel; Bartels, Ute; Carret, Anne-Sophie; Crooks, Bruce; Eisenstat, David D; Fryer, Chris; Lafay-Cousin, Lucie; Larouche, Valerie; Moghrabi, Albert; Wilson, Beverly; Zelcer, Shayna; Silva, Mariana; Bouffet, Eric

    2015-08-01

    In children under the age of 3 years, the most common solid tumors are brain tumors. Low grade astrocytomas represent 30-40 % of brain tumours in this age group. This study reviewed the incidence, characteristics, therapy, and outcome of children less than 36 months of age diagnosed with a low grade astrocytoma from 1990 to 2005 in Canada. A data bank was established using data collected from Canadian pediatric oncology centers on children less than age 3 diagnosed with brain tumors between 1990 and 2005. Cases of low grade astrocytoma were extracted from this data bank and their characteristics summarized. From the 579 cases in the data bank, 153 cases of low grade astrocytoma (26 %) were identified. The mean duration of symptoms prior to presentation was 13 weeks, and 53 % of patients underwent a greater than 90 % resection of their tumor, while 30 % underwent 10-90 % resection. Seventy-one percent of patients received no further therapy after surgery and of the 45 who received therapy following surgery, 43 received chemotherapy, and 5 received radiation therapy. Sixty-eight patients had recurrence or progression of their tumor. Eighty-seven percent of patients were alive at the time of the survey with a 2 year survival rate of 95.3 ± 1.8 %, 5 year survival rate of 93.1 ± 2.1 % and 10 year survival rate of 89.1 ± 2.8 %. The 5 year survival rate for Canadian children less than 36 months of age with a low grade astrocytoma was 93.0 ± 2.8 % which is similar to that for older children with this tumor.

  13. Granular cell astrocytoma: report of a case and review of the literature.

    PubMed

    Caporalini, Chiara; Buccoliero, Anna Maria; Scoccianti, Silvia; Moscardi, Selene; Simoni, Antonella; Pansini, Luigi; Bordi, Lorenzo; Ammannati, Franco; Taddei, Gian Luigi

    2016-01-01

    A 54-year-old man with no remarkable past medical history was referred to our hospital for the appearance of generalized tonic clonic seizures with loss of consciousness, preceded by phosphenes at the right eye. On magnetic resonance imaging, a contrast-enhanced tumor in the left occipital lobe with peripheral edema was noted. He underwent craniotomy, and the entire mass was removed. Microscopic examination revealed infiltrative atypical astrocytes (glial fibrillary acidic protein, GFAP, positive) with discrete borders and granular cytoplasm. Ki-67 labeling index was 40%. The tumor was diagnosed as a high-grade granular cell astrocytoma (GCA). Postoperative radiotherapy combined with temozolomide was administered. GCAs are aggressive lesions and should not to be confused with localized, benign granular cell tumors or with other non neoplastic granular cell changes in the central nervous system (CNS). GCAs are rare tumors. At this time, only 63 supratentorial/ hemispheric cases, including our case, have been reported in literature. PMID:27125869

  14. Expression of corticosteroid-binding globulin in human astrocytoma cell line.

    PubMed

    Pusch, Larissa; Wegmann, Sonja; Caldwell, Jack D; Jirikowski, Gustav F

    2009-06-01

    Glial tumor cells are known to be sensitive to glucocorticoids (GC) in vivo and in vitro. Here we studied the expression of corticosteroid-binding globulin (CBG) in the low-grade malignant human astrocytoma cell line 1321N1. CBG was observed in cytoplasm of most of these cells with immunocytochemistry. RT-PCR revealed the presence of the respective mRNA. Only scattered cells contained nuclear immunoreactivity for glucocorticoid receptor as visualized by double immunostaining. Immunoreactive CBG could be recovered from the supernatant of cultures that had been exposed to 10(-5) M cortisol. Our observations indicate the endogenous expression of CBG in 1321N1 cells which may occur independently from classical glucocorticoid receptor pathways. Cortisol seems to facilitate liberation of CBG in a paracrine manner, perhaps through membrane action of the steroid. Effects of adrenal steroids on proliferation and apoptosis of certain glial tumors may in part depend on these mechanisms.

  15. Induction of high grade astrocytoma (HGA) by protons: Molecular mechanisms and RBE considerations

    NASA Astrophysics Data System (ADS)

    Dalrymple, G. V.; Leichner, P. K.; Harrison, K. A.; Cox, A. B.; Hardy, K. A.; Salmon, Y. L.; Mitchell, J. C.

    1994-10-01

    Protons of a specific energy, 55 MeV, have been found to induce primary high grade astrocytomas (HGA) in the Rhesus monkey (Macaca mulatta). Brain tumors of this type were not induced by protons of other energies (32-2,300 MeV). Induction of HGA has been identified in human patients who have had radiation therapy to the head. We believe that the induction of HGA in the monkey is a consequence of dose distribution, not some unique ``toxic'' property of protons. Comparison of the human experience with the monkey data indicates the RBE for induction of brain tumors to be about one. It is unlikely that protons cause an unusual change in oncogenic expression, as compared to conventional electromagnetic radiation.

  16. Expression of immediate early genes after treatment of human astrocytoma cells with radiation and taxol

    SciTech Connect

    Gubits, R.M.; Geard, C.R.; Schiff, P.B.

    1993-10-20

    The promising chemotherapeutic agent, taxol, has been shown to sensitize the G18 line of human astrocytoma cells to ionizing radiation. The present studies were performed to identify specific changes in gene expression associated with this altered sensitivity. The products of immediate early genes, which are induced transiently in cells in response to a variety of treatments, including growth factors, neurotransmitters, and irradiation with UV light or X rays, are thought to initiate a cascade of genetic responses to alterations in cellular environment. The present results demonstrate a dramatic attenuation in one immediate early gene response in association with a treatment that enhances radiosensitivity in a refractory human brain tumor line. 22 refs., 5 figs., 1 tab.

  17. Imaging findings of anaplastic astrocytoma in a child with maple syrup urine disease: a case report.

    PubMed

    Aw-Zoretic, Jessie; Wadhwani, Nitin R; Lulla, Rishi R; Rishi, Lulla R; Ryan, Maura E

    2015-09-01

    Maple syrup urine disease (MSUD) is an inborn error of branched-chain amino acid metabolism, which usually presents in childhood with encephalopathy due to cerebral edema and dysmyelination. Even with treatment, metabolic stressors may precipitate later episodes of acute decompensation. Changes related to cerebral and white matter edema have been described by magnetic resonance imaging (MRI), and imaging can aid in both initial diagnosis and evaluation of decompensation. To date, there are no published known reports of cancer in patients with MSUD. Here, we present the first case report of an anaplastic astrocytoma in a teenager with MSUD, with a discussion of imaging findings and the use of magnetic resonance spectroscopy (MRS) to help distinguish between tumor and metabolic changes. PMID:26084772

  18. [Problems with flute playing: an otological problem? Case report of a peculiar cerebellar astrocytoma].

    PubMed

    Forton, G; Verlooy, J; Cras, P; Parizel, P; Van de Heyning, P

    1992-01-01

    A rare case of cerebellar astrocytoma presenting as a cerebellopontine angle tumour is discussed. A 35-year old woman noticed a bizarre twitching and fatigability of the left upper lip while playing the flute. There was also a mild hearing loss on the left side and she sometimes felt unsure of herself when walking. A thorough examination by means of speech audiometry, electronystagmography, ABR, CT-scan and MRI revealed a large, partly calcified mass occupying the cerebellopontine angle. Only the histological examination of the surgical specimen revealed the true nature of the tumour. The special characteristics of this tumour and the unusual clinical course are discussed. The importance of a good histological diagnosis is stressed.

  19. Cystic pilomyxoid astrocytoma on suprasellar region in 7-year-old girl: Treatment and strategy

    PubMed Central

    Tjahjadi, Mardjono; Arifin, M. Zafrullah; Sobana, Mirna; Avianti, Astri; Caropeboka, M. Sinatrya; Eka, Priandana Adya; Agustina, Hasrayati

    2015-01-01

    Pilomyxoid astrocytoma (PMA) is a recently described entity with similar features to pilocytic astrocytoma but with a rare occurrence. As a new diagnosis, no treatment guideline of PMA has been established; but generally, as for any low-grade gliomas, radical resection is performed if the location is favorable. In this report, we wished to share our experience treating the PMA. The authors presented a case of a 7-year-old girl with bitemporal hemianopia. From the history, the patient had a 4-month history of headache, following with nausea and projectile vomiting 1 week before hospital admission. Past history of seizure, weakness of left extremities, and decreased consciousness were reported. Computed tomography (CT) scanning showed acute obstructive hydrocephalus and an isohypodense mass at suprasellar region with the cystic component. We performed ventriculo-peritoneal-shunt to reduce the acute hydrocephalus, followed by craniotomy tumor removal 2 weeks later. The patient underwent radiotherapy and medical rehabilitation. Diagnosis of PMA was made on the basis of pathologic anatomy result, which showed a myxoid background with pseudorosette. Postoperative CT showed a residual tumor at right parasellar area without hydrocephalus. After the surgery, the treatment was followed with radiotherapy for 20 times within 2 months. Postradiation CT performed 1-year later showed a significant reduction of the tumor mass. There were no new postoperative deficits. The patient had improvement of the visual field and motor strength. The authors reported a case of a 7-year-old girl with PMA. Surgical resection combined with radiotherapy was performed to control the growth of PMA. More observation and further studies are required to refine the treatment methods. PMID:25972955

  20. Mitochondrial lactate metabolism is involved in antioxidative defense in human astrocytoma cells.

    PubMed

    Lemire, Joseph; Auger, Christopher; Mailloux, Ryan; Appanna, Vasu D

    2014-04-01

    Although lactate has traditionally been known to be an end product of anaerobic metabolism, recent studies have revealed its disparate biological functions. Oxidative energy production and cell signaling are two important roles assigned to this monocarboxylic acid. Here we demonstrate that mitochondrial lactate metabolism to pyruvate mediated by lactate dehydrogenase (LDH) in a human astrocytic cell line is involved in antioxidative defense. The pooling of this α-ketoacid helps to detoxify reactive oxygen species, with the concomitant formation of acetate. In-gel activity assays following blue native PAGE electrophoresis were utilized to demonstrate the increase in mitochondrial LDH activity coupled to the decrease in pyruvate dehydrogenase activity in the cells challenged by oxidative stress. The enhanced production of pyruvate with the concomitant formation of acetate in astrocytoma cells was monitored by high-performance liquid chromatography. The ability of pyruvate to fend off oxidative stress was visualized by fluorescence microscopy with the aid of the dye 2',7'-dichlorodihydrofluorescein diacetate. Immunoblotting helped confirm the presence of elevated levels of LDH in cells exposed to oxidative stress, and recovery experiments were performed with pyruvate to diminish the oxidative burden on the astrocytoma. The acetate, generated as a consequence of the antioxidative attribute of pyruvate, was subsequently channeled toward the production of lipids, a process facilitated by the upregulation in activity of acetyl-CoA synthetase and acetyl-CoA carboxylase, as demonstrated by in-gel activity assays. The mitochondrial lactate metabolism mediated by LDH appears to play an important role in antioxidative defence in this astrocytic system.

  1. Use of a portable CT scanner during resection of subcortical supratentorial astrocytomas of childhood.

    PubMed

    Gwinn, R; Cleary, K; Medlock, M

    2000-01-01

    The development of intraoperative imaging has made it possible to visualize shifting brain structures during surgery, and may allow greater intraoperative discrimination of normal and abnormal tissue. This may provide greater confidence to the neurosurgeon to proceed with a more extensive resection while decreasing postoperative morbidity. We investigated the intraoperative use of a portable CT scanner in the resection of 4 cases of supratentorial, subcortical astrocytomas of childhood to assess its usefulness in determining the endpoint of the dissection. We operated on 4 patients, ages 3-17, with astrocytomas. Three were thalamic, and 1 was based primarily in the caudate nucleus. The approach to the basal ganglia was transcallosal in 3 and transtemporal in 1. Specific observations on the intraoperative use of the portable CT scanner included its overall facility, any additional operative time required, the overall quality of the images, intraoperative decisions made based on the images and problems associated with its use. These observations are presented with a review of intraoperative imaging as it pertains to deep pediatric brain tumors. The CT scanner was helpful in limiting the dissection of the hypothalamic and midbrain regions and in localizing remaining abnormal tissue. The scans allowed informed decisions about leaving margins of the tumor which were adjacent to vital structures, but dit not prove to be a decisive factor in providing a complete resection. The following observations are worth noting: (1) average imaging time was 20 min per scan; (2) the extent and location of residual enhancing tumor was easily identified despite other materials in the surgical bed; (3) air/tissue interfaces limit resolution; (4) tumors retain contrast long enough to obtain multiple scans without additional dye, and (5) the cost profile of a mobile CT scanner is superior to that of a fixed intraoperative CT scanner.

  2. Dexamethasone acts as a radiosensitizer in three astrocytoma cell lines via oxidative stress

    PubMed Central

    Ortega-Martínez, Sylvia

    2015-01-01

    Glucocorticoids (GCs), which act on stress pathways, are well-established in the co-treatment of different kinds of tumors; however, the underlying mechanisms by which GCs act are not yet well elucidated. As such, this work investigates the role of glucocorticoids, specifically dexamethasone (DEXA), in the processes referred to as DNA damage and DNA damage response (DDR), establishing a new approach in three astrocytomas cell lines (CT2A, APP.PS1 L.1 and APP.PS1 L.3). The results show that DEXA administration increased the basal levels of gamma-H2AX foci, keeping them higher 4 h after irradiation (IR) of the cells, compared to untreated cells. This means that DEXA might cause increased radiosensitivity in these cell lines. On the other hand, DEXA did not have an apparent effect on the formation and disappearance of the 53BP1 foci. Furthermore, it was found that DEXA administered 2 h before IR led to a radical change in DNA repair kinetics, even DEXA does not affect cell cycle. It is important to highlight that DEXA produced cell death in these cell lines compared to untreated cells. Finally and most important, the high levels of gamma-H2AX could be reversed by administration of ascorbic acid, a potent blocker of reactive oxygen species, suggesting that DEXA acts by causing DNA damage via oxidative stress. These exiting findings suggest that DEXA might promote radiosensitivity in brain tumors, specifically in astrocytoma-like tumors. PMID:26160768

  3. Veliparib, Radiation Therapy, and Temozolomide in Treating Younger Patients With Newly Diagnosed Diffuse Pontine Gliomas

    ClinicalTrials.gov

    2016-10-05

    Childhood Mixed Glioma; Untreated Childhood Anaplastic Astrocytoma; Untreated Childhood Brain Stem Glioma; Untreated Childhood Fibrillary Astrocytoma; Untreated Childhood Giant Cell Glioblastoma; Untreated Childhood Glioblastoma; Untreated Childhood Gliosarcoma

  4. The use of dual growing rods to correct spinal deformity secondary to a low-grade spinal cord astrocytoma

    PubMed Central

    Kuhn, Elizabeth N.; Muthigi, Akhil; Frino, John; Powers, Alexander K.

    2015-01-01

    Pediatric intramedullary spinal cord astrocytomas are rare, and the majority are low grade, typically carrying a low risk of mortality, but a high risk of morbidity. Quality of life is, therefore, an important consideration in treating concomitant progressive kyphoscoliosis. Compared with fusion-based spinal stabilization, fusionless techniques may limit some complications related to early instrumentation of the developing spine. Another consideration is the timing of radiation therapy relative to both spinal maturity and spinal instrumentation. To date, there have been no reports of the use of a fusionless technique to treat spinal deformity secondary to an intramedullary spinal cord tumor. Herein, we report the use of fusionless spinal stabilization with dual growing rods in a boy with low-grade spinal cord astrocytoma after radiation therapy. PMID:26468485

  5. Evaluation of O6-methylguanine-DNA methyltransferase enzyme expression effect on survival of patients with Grade 4 brain astrocytoma

    PubMed Central

    Hemati, Simin; Sayadi, Ali; Mahzooni, Parvin; Sirous, Mehry

    2014-01-01

    Background: High-grade astrocytoma (Grade 4) or glioblastoma multiforme (GBM) are deadly brain tumors. New therapies attempt to increase lifetime and quality of life in patients with malignant astrocytoma. O6-methylguanine-DNA methyltransferase (MGMT) enzyme expression may be effective in prognosis and response to treatment of these patients. The aim of this study was assessment of MGMT enzyme expression in patients with astrocytoma Grade 4. Materials and Methods: In this study, 48 patients with GBM that were treated with surgery, chemotherapy and radiotherapy were investigated and followed-up for 47 months for the survival rate. Pathology blocks of patients were examined for MGMT enzyme expression using immunohistochemistry method. Results: The patients were 34 males and 14 females. The ages ranged from 24 to 77 years, with a mean age of 53.52 ± 13.39 years. There was no significant difference between two groups (positive and negative MGMT enzyme expression) in overall survival (median [range] 11.5 [4-30] vs. 13 [5-22], P = 0.9). The results of our study showed that patients although who were undergone near total surgery had higher overall survival than the group of patients who had biopsy only however, it was not significant. Patients who were treated with temozolomide (TMZ) (Temodal, Merck Canada) had significant overall median survival (14.5) more than the patients who were treated with Procarbazine (Roche, Swiss)-Lomustine (Lilly, USA)-Vincristine (Lilly, USA) regimen (8.75) (P < 0.05). Conclusion: O6-methylguanine-DNA methyltransferase enzyme expression had no effect on survival of patients with Grade 4 brain astrocytoma TMZ may increase survival rate. PMID:25097625

  6. First-line nitrosourea-based chemotherapy in symptomatic non-resectable supratentorial pure low-grade astrocytomas.

    PubMed

    Frenay, M P; Fontaine, D; Vandenbos, F; Lebrun, C

    2005-09-01

    At the present time, there are no proven beneficial effects of chemotherapy (CT) for the treatment of pure low-grade astrocytomas. Brain radiotherapy (RT) still remains the standard treatment in order to reduce or delay tumor progression or symptoms, despite possible long-term neurologic complications. We report 10 patients, with histologically proven pure low-grade fibrillary astrocytomas, to which we administered a first-line nitrosourea-based CT. All patients were symptomatic with pharmaco-resistant epilepsy or neurologic symptoms, and had been rejected for neurosurgical resection. All patients with epilepsy had a clinical improvement with reduction in seizure frequency and 60% became seizure-free. CT was well tolerated; all patients developed myelosuppression with 40% of grade III/IV hematotoxicity. Seven were alive at the time of writing with a mean follow-up of 6.5 years (3.5-12) from first recorded symptoms. The three deceased patients died 7.5, 7.5, and 8.5 years from first symptoms. These results demonstrate that some patients with symptomatic non-resectable fibrillary low-grade astrocytomas can be treated with up-front CT to improve their neurologic status. This report suggests that benefits of CT on symptoms, survival, and quality of life should be prospectively compared with RT. PMID:16128869

  7. Promoter Methylation of RASSF1A Associates to Adult Secondary Glioblastomas and Pediatric Glioblastomas

    PubMed Central

    Muñoz, Jorge; Inda, María del Mar; Lázcoz, Paula; Zazpe, Idoya; Fan, Xing; Alfaro, Jorge; Tuñón, Teresa; Rey, Juan A.; Castresana, Javier S.

    2012-01-01

    While allelic losses and mutations of tumor suppressor genes implicated in the etiology of astrocytoma have been widely assessed, the role of epigenetics is still a matter of study. We analyzed the frequency of promoter hypermethylation by methylation-specific PCR (MSP) in five tumor suppressor genes (PTEN, MGMT, RASSF1A, p14ARF, and p16INK4A), in astrocytoma samples and cell lines. RASSF1A was the most frequently hypermethylated gene in all grades of astrocytoma samples, in cell lines, and in adult secondary GBM. It was followed by MGMT. PTEN showed a slight methylation signal in only one GBM and one pilocytic astrocytoma, and in two cell lines; while p14ARF and p16INK4A did not show any evidence of methylation in primary tumors or cell lines. In pediatric GBM, RASSF1A was again the most frequently altered gene, followed by MGMT; PTEN, p14 and p16 showed no alterations. Lack or reduced expression of RASSF1A in cell lines was correlated with the presence of methylation. RASSF1A promoter hypermethylation might be used as a diagnostic marker for secondary GBM and pediatric GBM. Promoter hypermethylation might not be an important inactivation mechanism in other genes like PTEN, p14ARF and p16INK4A, in which other alterations (mutations, homozygous deletions) are prevalent. PMID:22389839

  8. Type and frequency of IDH1 and IDH2 mutations are related to astrocytic and oligodendroglial differentiation and age: a study of 1,010 diffuse gliomas.

    PubMed

    Hartmann, Christian; Meyer, Jochen; Balss, Jörg; Capper, David; Mueller, Wolf; Christians, Arne; Felsberg, Jörg; Wolter, Marietta; Mawrin, Christian; Wick, Wolfgang; Weller, Michael; Herold-Mende, Christel; Unterberg, Andreas; Jeuken, Judith W M; Wesseling, Peter; Reifenberger, Guido; von Deimling, Andreas

    2009-10-01

    Somatic mutations in the IDH1 gene encoding cytosolic NADP+-dependent isocitrate dehydrogenase have been shown in the majority of astrocytomas, oligodendrogliomas and oligoastrocytomas of WHO grades II and III. IDH2 encoding mitochondrial NADP+-dependent isocitrate dehydrogenase is also mutated in these tumors, albeit at much lower frequencies. Preliminary data suggest an importance of IDH1 mutation for prognosis showing that patients with anaplastic astrocytomas, oligodendrogliomas and oligoastrocytomas harboring IDH1 mutations seem to fare much better than patients without this mutation in their tumors. To determine mutation types and their frequencies, we examined 1,010 diffuse gliomas. We detected 716 IDH1 mutations and 31 IDH2 mutations. We found 165 IDH1 (72.7%) and 2 IDH2 mutations (0.9%) in 227 diffuse astrocytomas WHO grade II, 146 IDH1 (64.0%) and 2 IDH2 mutations (0.9%) in 228 anaplastic astrocytomas WHO grade III, 105 IDH1 (82.0%) and 6 IDH2 mutations (4.7%) in 128 oligodendrogliomas WHO grade II, 121 IDH1 (69.5%) and 9 IDH2 mutations (5.2%) in 174 anaplastic oligodendrogliomas WHO grade III, 62 IDH1 (81.6%) and 1 IDH2 mutations (1.3%) in 76 oligoastrocytomas WHO grade II and 117 IDH1 (66.1%) and 11 IDH2 mutations (6.2%) in 177 anaplastic oligoastrocytomas WHO grade III. We report on an inverse association of IDH1 and IDH2 mutations in these gliomas and a non-random distribution of the mutation types within the tumor entities. IDH1 mutations of the R132C type are strongly associated with astrocytoma, while IDH2 mutations predominantly occur in oligodendroglial tumors. In addition, patients with anaplastic glioma harboring IDH1 mutations were on average 6 years younger than those without these alterations.

  9. A Phase I Study of Mebendazole for the Treatment of Pediatric Gliomas

    ClinicalTrials.gov

    2016-07-08

    Pilomyxoid Astrocytoma; Pilocytic Astrocytoma; Glioma, Astrocytic; Optic Nerve Glioma; Pleomorphic Xanthoastrocytoma; Glioblastoma Multiforme; Anaplastic Astrocytoma; Gliosarcoma; Diffuse Intrinsic Pontine Glioma; DIPG; Low-grade Glioma; Brainstem Glioma

  10. Cytotoxicity Effects of Different Surfactant Molecules Conjugated to Carbon Nanotubes on Human Astrocytoma Cells

    NASA Astrophysics Data System (ADS)

    Dong, Lifeng; Witkowski, Colette M.; Craig, Michael M.; Greenwade, Molly M.; Joseph, Katherine L.

    2009-12-01

    Phase contrast and epifluorescence microscopy were utilized to monitor morphological changes in human astrocytoma cells during a time-course exposure to single-walled carbon nanotube (SWCNT) conjugates with different surfactants and to investigate sub-cellular distribution of the nanotube conjugates, respectively. Experimental results demonstrate that cytotoxicity of the nanotube/surfactant conjugates is related to the toxicity of surfactant molecules attached on the nanotube surfaces. Both sodium dodecyl sulfate (SDS) and sodium dodecylbenzene sulfonate (SDBS) are toxic to cells. Exposure to CNT/SDS conjugates (0.5 mg/mL) for less than 5 min caused changes in cell morphology resulting in a distinctly spherical shape compared to untreated cells. In contrast, sodium cholate (SC) and CNT/SC did not affect cell morphology, proliferation, or growth. These data indicate that SC is an environmentally friendly surfactant for the purification and dispersion of SWCNTs. Epifluorescence microscopy analysis of CNT/DNA conjugates revealed distribution in the cytoplasm of cells and did not show adverse effects on cell morphology, proliferation, or viability during a 72-h incubation. These observations suggest that the SWCNTs could be used as non-viral vectors for diagnostic and therapeutic molecules across the blood-brain barrier to the brain and the central nervous system.

  11. KIAA1549: BRAF Gene Fusion and FGFR1 Hotspot Mutations Are Prognostic Factors in Pilocytic Astrocytomas.

    PubMed

    Becker, Aline Paixão; Scapulatempo-Neto, Cristovam; Carloni, Adriana C; Paulino, Alessandra; Sheren, Jamie; Aisner, Dara L; Musselwhite, Evelyn; Clara, Carlos; Machado, Hélio R; Oliveira, Ricardo S; Neder, Luciano; Varella-Garcia, Marileila; Reis, Rui M

    2015-07-01

    Up to 20% of patients with pilocytic astrocytoma (PA) experience a poor outcome. BRAF alterations and Fibroblast growth factor receptor 1 (FGFR1) point mutations are key molecular alterations in Pas, but their clinical implications are not established. We aimed to determine the frequency and prognostic role of these alterations in a cohort of 69 patients with PAs. We assessed KIAA1549:BRAF fusion by fluorescence in situ hybridization and BRAF (exon 15) mutations by capillary sequencing. In addition, FGFR1 expression was analyzed using immunohistochemistry, and this was compared with gene amplification and hotspot mutations (exons 12 and 14) assessed by fluorescence in situ hybridization and capillary sequencing. KIAA1549:BRAF fusion was identified in almost 60% of cases. Two tumors harbored mutated BRAF. Despite high FGFR1 expression overall, no cases had FGFR1 amplifications. Three cases harbored a FGFR1 p.K656E point mutation. No correlation was observed between BRAF and FGFR1 alterations. The cases were predominantly pediatric (87%), and no statistical differences were observed in molecular alterations-related patient ages. In summary, we confirmed the high frequency of KIAA1549:BRAF fusion in PAs and its association with a better outcome. Oncogenic mutations of FGFR1, although rare, occurred in a subset of patients with worse outcome. These molecular alterations may constitute alternative targets for novel clinical approaches, when radical surgical resection is unachievable. PMID:26083571

  12. Rapid increase in cystic volume of an anaplastic astrocytoma misdiagnosed as neurocysticercosis: A case report

    PubMed Central

    Li, Hong-Jiang; Han, Hong-Xiu; Feng, Dong-Fu

    2016-01-01

    Reports describing a rapid increase in the cystic volume of anaplastic astrocytoma (AA) in a short time frame are rare. The present study reports the case of a 68-year-old male who was admitted to the No. 9 People's Hospital, Shanghai Jiaotong University School of Medicine (Shanghai, China), with a small cystic brain lesion and positive immunological testing for cysticercosis. Head magnetic resonance imaging (MRI) showed a cystic lesion, 6 mm in diameter, in the left frontal lobe. Neurocysticercosis was suspected and the patient was treated with a clinical trial of albendazole and steroids. A period of 25 days later, the patient's condition had deteriorated, and MRI revealed a cystic lesion in the left frontal lobe; thereafter, the cystic lesion was removed and a diagnosis of AA was established. The tumor was soft, ivory white and gelatinous due to myxoid degeneration. In this case, tumor-related angiogenesis and microvascular extravasation (blood-brain barrier disruption) may have been the main cause of the rapid increase in the cystic volume in such a short time frame. The similarity of the glioma and cysticercus antigens may have been the cause of the positive reactions in the cystic fluid. The present study reports the rare occurrence of a rapid increase of cystic volume and potential diagnostic difficulties.

  13. Recurrent somatic mutations in ACVR1 in pediatric midline high-grade astrocytoma

    PubMed Central

    Fontebasso, Adam M.; Papillon-Cavanagh, Simon; Schwartzentruber, Jeremy; Nikbakht, Hamid; Gerges, Noha; Fiset, Pierre-Olivier; Bechet, Denise; Faury, Damien; De Jay, Nicolas; Ramkissoon, Lori; Corcoran, Aoife; Jones, David T W; Sturm, Dominik; Johann, Pascal; Tomita, Tadanori; Goldman, Stewart; Nagib, Mahmoud; Bendel, Anne; Goumnerova, Liliana; Bowers, Daniel C.; Leonard, Jeffrey R.; Rubin, Joshua B.; Alden, Tord; Browd, Samuel; Geyer, J. Russell; Leary, Sarah; Jallo, George; Cohen, Kenneth; Gupta, Nalin; Prados, Michael D.; Carret, Anne-Sophie; Ellezam, Benjamin; Crevier, Louis; Klekner, Almos; Bognar, Laszlo; Hauser, Peter; Garami, Miklos; Myseros, John; Dong, Zhifeng; Siegel, Peter M.; Malkin, Hayley; Ligon, Azra; Albrecht, Steffen; Pfister, Stefan M.; Ligon, Keith L.; Majewski, Jacek; Jabado, Nada; Kieran, Mark W

    2014-01-01

    Midline pediatric high-grade astrocytomas (pHGAs) are incurable with few treatment targets identified. Most tumors harbor K27M mutations on histone 3 variants. In 40 treatment-naïve midline pHGAs, 39 analyzed by whole-exome sequencing, we find additional somatic mutations specific to tumor location. Gain-of-function mutations in ACVR1 occur in tumors of the pons in conjunction with H3.1 K27M, while FGFR1 mutations/fusions occur in thalamic tumors associated with H3.3 K27M. Hyper-activation of the bone morphogenetic protein (BMP)/ACVR1 developmental pathway in pHGAs harbouring ACVR1 mutations led to increased phospho-SMAD1/5/8 expression and up-regulation of BMP downstream early response genes in tumour cells. Global DNA methylation profiles were significantly associated with the K27M mutation regardless of the mutant H3 variant and irrespective of tumor location, supporting its role in driving the epigenetic phenotype. This significantly expands the potential treatment targets and further justifies pre-treatment biopsy in pHGA as a means to orient therapeutic efforts in this disease. PMID:24705250

  14. Rapid increase in cystic volume of an anaplastic astrocytoma misdiagnosed as neurocysticercosis: A case report

    PubMed Central

    Li, Hong-Jiang; Han, Hong-Xiu; Feng, Dong-Fu

    2016-01-01

    Reports describing a rapid increase in the cystic volume of anaplastic astrocytoma (AA) in a short time frame are rare. The present study reports the case of a 68-year-old male who was admitted to the No. 9 People's Hospital, Shanghai Jiaotong University School of Medicine (Shanghai, China), with a small cystic brain lesion and positive immunological testing for cysticercosis. Head magnetic resonance imaging (MRI) showed a cystic lesion, 6 mm in diameter, in the left frontal lobe. Neurocysticercosis was suspected and the patient was treated with a clinical trial of albendazole and steroids. A period of 25 days later, the patient's condition had deteriorated, and MRI revealed a cystic lesion in the left frontal lobe; thereafter, the cystic lesion was removed and a diagnosis of AA was established. The tumor was soft, ivory white and gelatinous due to myxoid degeneration. In this case, tumor-related angiogenesis and microvascular extravasation (blood-brain barrier disruption) may have been the main cause of the rapid increase in the cystic volume in such a short time frame. The similarity of the glioma and cysticercus antigens may have been the cause of the positive reactions in the cystic fluid. The present study reports the rare occurrence of a rapid increase of cystic volume and potential diagnostic difficulties. PMID:27698865

  15. Stereotactic interstitial brachytherapy of malignant astrocytomas with remarks on postimplantation computed tomographic appearance

    SciTech Connect

    Willis, B.K.; Heilbrun, M.P.; Sapozink, M.D.; McDonald, P.R.

    1988-09-01

    Seventeen patients were treated with stereotactically implanted high activity iodine-125 seeds, 12 patients for recurrent malignant astrocytomas (Protocol I) and 5 patients for newly diagnosed glioblastomas (Protocol II). Total radiation dosage to the recurrent tumors in Protocol I, including prior external beam irradiation, averaged 13,500 cGy. In the follow-up period of 6 to 50 months, the survival rate was 93% at 6 months, 60% at 12 months, 50% at 18 months, and 38% at 24 months after implantation. In Protocol II, brachytherapy was used as an interstitial radiation boost to the conventional treatment of newly diagnosed glioblastomas. External beam therapy and interstitial brachytherapy provided 11,000 cGy to these tumors. In the follow-up period of 15 to 27 months, there was a 100% survival at 12 months, 75% at 18 months, and 25% at 24 months after implantation. Eight of our 17 patients required reoperation for persistent or recurrent mass lesions at 6 to 15 months postimplantation; 7 were found to harbor masses of radionecrosis containing nests of anaplastic astrocytes; 1 had frank tumor recurrence. Median survival in this group of patients requiring reoperation was 18.7 months postimplantation. In a review of postimplantation computed tomographic scans, significant mass effect and crossover of hypodensity or enhancement into the corpus callosum or opposite hemisphere were found to have prognostic significance; persistent areas of contrast enhancement and excessive peritumoral hypodensity did not.

  16. Effect of brefelamide on HGF-induced survival of 1321N1 human astrocytoma cells.

    PubMed

    Honma, Shigeyoshi; Takasaka, Sachina; Ishikawa, Takahiro; Shibuya, Takahiro; Mitazaki, Satoru; Abe, Sumiko; Yoshida, Makoto

    2016-06-01

    Malignant gliomas are characterized by their high level of resistance to chemo- and radiotherapy and new treatment options are urgently required. We previously demonstrated that brefelamide, an aromatic amide isolated from methanol extracts of cellular slime molds Dictyostelium brefeldianum and D. giganteum, had antiproliferative effects on 1321N1 human astrocytoma cells, a model of glioma. In this study, we investigated the mechanisms by which brefelamide inhibited 1321N1 and PC12 rat pheochromocytoma cell proliferation. When cells were cultured in serum-free medium, hepatocyte growth factor (HGF) increased survival of 1321N1 cells but not PC12 cells. HGF receptor, c-MET, was strongly expressed in 1321N1 cells, but not in PC12 cells. Pretreatment of 1321N1 cells with brefelamide inhibited both HGF-induced cell survival and expression of c-MET. Phosphorylation of extracellular signal-regulated kinase (ERK) and AKT was increased by HGF, but these changes were inhibited by brefelamide pretreatment. Moreover, HGF mRNA levels and secretion were reduced by brefelamide. These results suggest that brefelamide reduces survival of 1321N1 cells via multiple effects including suppression of HGF receptor expression and HGF secretion and inhibition of ERK and AKT phosphorylation. PMID:27130674

  17. Cytotoxicity effects of different surfactant molecules conjugated to carbon nanotubes on human astrocytoma cells.

    PubMed

    Dong, Lifeng; Witkowski, Colette M; Craig, Michael M; Greenwade, Molly M; Joseph, Katherine L

    2009-01-01

    Phase contrast and epifluorescence microscopy were utilized to monitor morphological changes in human astrocytoma cells during a time-course exposure to single-walled carbon nanotube (SWCNT) conjugates with different surfactants and to investigate sub-cellular distribution of the nanotube conjugates, respectively. Experimental results demonstrate that cytotoxicity of the nanotube/surfactant conjugates is related to the toxicity of surfactant molecules attached on the nanotube surfaces. Both sodium dodecyl sulfate (SDS) and sodium dodecylbenzene sulfonate (SDBS) are toxic to cells. Exposure to CNT/SDS conjugates (0.5 mg/mL) for less than 5 min caused changes in cell morphology resulting in a distinctly spherical shape compared to untreated cells. In contrast, sodium cholate (SC) and CNT/SC did not affect cell morphology, proliferation, or growth. These data indicate that SC is an environmentally friendly surfactant for the purification and dispersion of SWCNTs. Epifluorescence microscopy analysis of CNT/DNA conjugates revealed distribution in the cytoplasm of cells and did not show adverse effects on cell morphology, proliferation, or viability during a 72-h incubation. These observations suggest that the SWCNTs could be used as non-viral vectors for diagnostic and therapeutic molecules across the blood-brain barrier to the brain and the central nervous system. PMID:20652100

  18. Cytotoxicity Effects of Different Surfactant Molecules Conjugated to Carbon Nanotubes on Human Astrocytoma Cells

    PubMed Central

    2009-01-01

    Phase contrast and epifluorescence microscopy were utilized to monitor morphological changes in human astrocytoma cells during a time-course exposure to single-walled carbon nanotube (SWCNT) conjugates with different surfactants and to investigate sub-cellular distribution of the nanotube conjugates, respectively. Experimental results demonstrate that cytotoxicity of the nanotube/surfactant conjugates is related to the toxicity of surfactant molecules attached on the nanotube surfaces. Both sodium dodecyl sulfate (SDS) and sodium dodecylbenzene sulfonate (SDBS) are toxic to cells. Exposure to CNT/SDS conjugates (0.5 mg/mL) for less than 5 min caused changes in cell morphology resulting in a distinctly spherical shape compared to untreated cells. In contrast, sodium cholate (SC) and CNT/SC did not affect cell morphology, proliferation, or growth. These data indicate that SC is an environmentally friendly surfactant for the purification and dispersion of SWCNTs. Epifluorescence microscopy analysis of CNT/DNA conjugates revealed distribution in the cytoplasm of cells and did not show adverse effects on cell morphology, proliferation, or viability during a 72-h incubation. These observations suggest that the SWCNTs could be used as non-viral vectors for diagnostic and therapeutic molecules across the blood–brain barrier to the brain and the central nervous system. PMID:20652100

  19. Diffusion MRI

    NASA Astrophysics Data System (ADS)

    Fukuyama, Hidenao

    Recent advances of magnetic resonance imaging have been described, especially stressed on the diffusion sequences. We have recently applied the diffusion sequence to functional brain imaging, and found the appropriate results. In addition to the neurosciences fields, diffusion weighted images have improved the accuracies of clinical diagnosis depending upon magnetic resonance images in stroke as well as inflammations.

  20. Integrated proteomic platforms for the comparative characterization of medulloblastoma and pilocytic astrocytoma pediatric brain tumors: a preliminary study.

    PubMed

    Martelli, Claudia; Iavarone, Federica; D'Angelo, Luca; Arba, Morena; Vincenzoni, Federica; Inserra, Ilaria; Delfino, Daniela; Rossetti, Diana Valeria; Caretto, Marta; Massimi, Luca; Tamburrini, Gianpiero; Di Rocco, Concezio; Caldarelli, Massimo; Messana, Irene; Castagnola, Massimo; Sanna, Maria Teresa; Desiderio, Claudia

    2015-06-01

    A top-down/bottom-up integrated proteomic approach based on LC-MS and 2-DE analysis was applied for comparative characterization of medulloblastoma and pilocytic astrocytoma posterior cranial fossa pediatric brain tumor tissues. Although rare, primary brain tumors are the most frequent solid tumors in the pediatric age. Among them the medulloblastoma is the prevalent malignant tumor in childhood while pilocytic astrocytoma is the most common, rarely showing a malignant progression. Due to the limited availability of this kind of sample, the study was applied to pooled tumor tissues for a preliminary investigation. The results showed different proteomic profiles of the two tumors and evidenced interesting differential expression of several proteins and peptides. Top-down proteomics of acid-soluble fractions of brain tumor homogenates ascribed a potential biomarker role of malignancy to β- and α-thymosins and their truncated proteoforms and to C-terminal truncated (des-GG) ubiquitin, resulting exclusively detected or over-expressed in the highly malignant medulloblastoma. The bottom-up proteomics of the acid-soluble fraction identified several proteins, some of them in common with 2-DE analysis of acid-insoluble pellets. Peroxiredoxin-1, peptidyl-prolyl cis-trans isomerase A, triosephosphate isomerase, pyruvate kinase PKM, tubulin beta and alpha chains, heat shock protein HSP-90-beta and different histones characterized the medulloblastoma while the Ig kappa chain C region, serotransferrin, tubulin beta 2A chain and vimentin the pilocytic astrocytoma. The two proteomic strategies, with their pros and cons, well complemented each other in characterizing the proteome of brain tumor tissues and in disclosing potential disease biomarkers to be validated in a future study on individual samples of both tumor histotypes. PMID:25909245

  1. Modern Media and Instructional Technology in Vocational Education: Some Experiences of the Diffusion of New Technology in the Adult Education Institutions.

    ERIC Educational Resources Information Center

    Maki-Komsi, Saija; Ropo, Eero

    A study investigated teachers' experiences of educational and cultural change in adult education institutions. The initial assumption of the study was that the institutional shift from traditional teacher-dominated, face-to-face teaching to networked teamwork that emphasizes students' independence is not only a methodological or technological…

  2. [10-year follow-up of C3-C7 cervical laminectomy for intramedullary grade I astrocytoma].

    PubMed

    Staudte, H W; Busch, G

    In an eight years old boy we operated an intramedullary astrocytoma grade I and reimplanted the laminae C4-7 en bloc. A good stability was achieved. Ten years later only one segment remained intact, the others showing spontaneous fusion as a major draw back. This is possibly due to subperiostal dissection and bracing. No spinal stenosis occurred. An overuse of the remaining disc C4/5 might lead to a secondary degenerative stenosis. The operation is simple and might avoid swan neck deformity in children after large decompression of dorsal structures. PMID:8342307

  3. Long survival in a child with a mutated K27M-H3.3 pilocytic astrocytoma.

    PubMed

    Hochart, Audrey; Escande, Fabienne; Rocourt, Nathalie; Grill, Jacques; Koubi-Pick, Valérie; Beaujot, Juliette; Meignan, Samuel; Vinchon, Matthieu; Maurage, Claude Alain; Leblond, Pierre

    2015-04-01

    We report the first case of a child with a H3F3A K27M mutated pilocytic astrocytoma, who presented with a 10 years survival, and underwent spontaneous malignant transformation. The complex tumoral chromosomal rearrangements were consistent for genomic instability and for the histopathological features of malignant transformation into glioblastoma. H3F3A K27M mutations are rarely observed in benign neoplasms and may be associated with an adverse outcome. This mutation might not be the major driver that led to the onset of tumorigenesis, and we could consider that the associated TP53 mutation, would be required for malignant transformation. PMID:25909089

  4. Long survival in a child with a mutated K27M-H3.3 pilocytic astrocytoma

    PubMed Central

    Hochart, Audrey; Escande, Fabienne; Rocourt, Nathalie; Grill, Jacques; Koubi-Pick, Valérie; Beaujot, Juliette; Meignan, Samuel; Vinchon, Matthieu; Maurage, Claude Alain; Leblond, Pierre

    2015-01-01

    We report the first case of a child with a H3F3A K27M mutated pilocytic astrocytoma, who presented with a 10 years survival, and underwent spontaneous malignant transformation. The complex tumoral chromosomal rearrangements were consistent for genomic instability and for the histopathological features of malignant transformation into glioblastoma. H3F3A K27M mutations are rarely observed in benign neoplasms and may be associated with an adverse outcome. This mutation might not be the major driver that led to the onset of tumorigenesis, and we could consider that the associated TP53 mutation, would be required for malignant transformation. PMID:25909089

  5. Energy-dependent cell volume maintenance in UC-11MG human astrocytomas.

    PubMed

    Lomneth, R; Gruenstein, E I

    1989-10-01

    Swelling of astrocytes in the brain is a major cause of the morbidity and mortality associated with stroke and head trauma. Using a human astrocytoma cell line (UC-11MG) as a model system, we studied cell volume changes caused by ATP depletion under conditions mimicking hypoxia. ATP levels were reduced to less than 10% of control using the metabolic inhibitors KCN or antimycin in combination with glucose deprivation. This was sufficient to eliminate ouabain-sensitive 86Rb+ uptake, indicating the Na+-K+-adenosinetriphosphatase was not operating. Furosemide-sensitive 86Rb+ uptake was reduced by approximately 60%, indicating Na+-K+-2Cl- cotransport was also sensitive to ATP loss. ATP depletion resulted in a 30-40% reduction of cell volume within 60 min. ATP depletion also resulted in a net loss of intracellular K+. This loss of K+ could be blocked by Ba2+, indicating the K+ loss was through a conductive channel. When the net K+ loss was blocked by Ba2+, the volume decrease was also prevented. The cells remained viable throughout the time period as judged by exclusion of ethidium bromide by 99% of the cells and recovery of ATP levels to 75% of control within 60 min. We conclude that ATP depletion, following inhibition of glycolysis and oxidative phosphorylation, causes astrocytes to shrink because of a more rapid loss of K+ than uptake of Na+. Thus it appears that ATP depletion alone is not sufficient to account for the rapid phase of astrocytic swelling observed during cerebral ischemia. PMID:2801931

  6. Apoptosis and telomeres shortening related to HIV-1 induced oxidative stress in an astrocytoma cell line

    PubMed Central

    Pollicita, Michela; Muscoli, Carolina; Sgura, Antonella; Biasin, Alberto; Granato, Teresa; Masuelli, Laura; Mollace, Vincenzo; Tanzarella, Caterina; Del Duca, Claudio; Rodinò, Paola; Perno, Carlo Federico; Aquaro, Stefano

    2009-01-01

    Background Oxidative stress plays a key role in the neuropathogenesis of Human Immunodeficiency Virus-1 (HIV-1) infection causing apoptosis of astroglia cells and neurons. Recent data have shown that oxidative stress is also responsible for the acceleration of human fibroblast telomere shortening in vitro. In the present study we analyzed the potential relations occurring between free radicals formation and telomere length during HIV-1 mediated astroglial death. Results To this end, U373 human astrocytoma cells have been directly exposed to X4-using HIV-1IIIB strain, for 1, 3 or 5 days and treated (where requested) with N-acetylcysteine (NAC), a cysteine donor involved in the synthesis of glutathione (GSH, a cellular antioxidant) and apoptosis has been evaluated by FACS analysis. Quantitative-FISH (Q-FISH) has been employed for studying the telomere length while intracellular reduced/oxidized glutathione (GSH/GSSG) ratio has been determined by High-Performance Liquid Chromatography (HPLC). Incubation of U373 with HIV-1IIIB led to significant induction of cellular apoptosis that was reduced in the presence of 1 mM NAC. Moreover, NAC improved the GSH/GSSG, a sensitive indicator of oxidative stress, that significantly decreased after HIV-1IIIB exposure in U373. Analysis of telomere length in HIV-1 exposed U373 showed a statistically significant telomere shortening, that was completely reverted in NAC-treated U373. Conclusion Our results support the role of HIV-1-mediated oxidative stress in astrocytic death and the importance of antioxidant compounds in preventing these cellular damages. Moreover, these data indicate that the telomere structure, target for oxidative damage, could be the key sensor of cell apoptosis induced by oxidative stress after HIV infection. PMID:19463156

  7. Everolimus for subependymal giant cell astrocytoma: 5‐year final analysis

    PubMed Central

    Agricola, Karen; Mays, Maxwell; Tudor, Cindy; Care, Marguerite M.; Holland‐Bouley, Katherine; Berkowitz, Noah; Miao, Sara; Peyrard, Séverine; Krueger, Darcy A.

    2015-01-01

    Objective To analyze the cumulative efficacy and safety of everolimus in treating subependymal giant cell astrocytomas (SEGA) associated with tuberous sclerosis complex (TSC) from an open‐label phase II study (NCT00411619). Updated data became available from the conclusion of the extension phase and are presented in this ≥5‐year analysis. Methods Patients aged ≥ 3 years with a definite diagnosis of TSC and increasing SEGA lesion size (≥2 magnetic resonance imaging scans) received everolimus starting at 3mg/m2/day (titrated to target blood trough levels of 5–15ng/ml). The primary efficacy endpoint was reduction from baseline in primary SEGA volume. Results As of the study completion date (January 28, 2014), 22 of 28 (78.6%) initially enrolled patients finished the study per protocol. Median (range) duration of exposure to everolimus was 67.8 (4.7–83.2) months; 12 (52.2%) and 14 (60.9%) of 23 patients experienced SEGA volume reductions of ≥50% and ≥30% relative to baseline, respectively, after 60 months of treatment. The proportion of patients experiencing daily seizures was reduced from 7 of 26 (26.9%) patients at baseline to 2 of 18 (11.1%) patients at month 60. Most commonly reported adverse events (AEs) were upper respiratory tract infection and stomatitis of mostly grade 1 or 2 severity. No patient discontinued treatment due to AEs. The frequency of emergence of most AEs decreased over the course of the study. Interpretation Everolimus continues to demonstrate a sustained effect on SEGA tumor reduction over ≥5 years of treatment. Everolimus remained well‐tolerated, and no new safety concerns were noted. Ann Neurol 2015;78:929–938 PMID:26381530

  8. Genomic deletions correlate with underexpression of novel candidate genes at six loci in pediatric pilocytic astrocytoma.

    PubMed

    Potter, Nicola; Karakoula, Aikaterini; Phipps, Kim P; Harkness, William; Hayward, Richard; Thompson, Dominic N P; Jacques, Thomas S; Harding, Brian; Thomas, David G T; Palmer, Rodger W; Rees, Jeremy; Darling, John; Warr, Tracy J

    2008-08-01

    The molecular pathogenesis of pediatric pilocytic astrocytoma (PA) is not well defined. Previous cytogenetic and molecular studies have not identified nonrandom genetic aberrations. To correlate differential gene expression and genomic copy number aberrations (CNAs) in PA, we have used Affymetrix GeneChip HG_U133A to generate gene expression profiles of 19 pediatric patients and the SpectralChip 2600 to investigate CNAs in 11 of these tumors. Hierarchical clustering according to expression profile similarity grouped tumors and controls separately. We identified 1844 genes that showed significant differential expression between tumor and normal controls, with a large number clearly influencing phosphatidylinositol and mitogen-activated protein kinase signaling in PA. Most CNAs identified in this study were single-clone alterations. However, a small region of loss involving up to seven adjacent clones at 7q11.23 was observed in seven tumors and correlated with the underexpression of BCL7B. Loss of four individual clones was also associated with reduced gene expression including SH3GL2 at 9p21.2-p23, BCL7A (which shares 90% sequence homology with BCL7B) at 12q24.33, DRD1IP at 10q26.3, and TUBG2 and CNTNAP1 at 17q21.31. Moreover, the down-regulation of FOXG1B at 14q12 correlated with loss within the gene promoter region in most tumors. This is the first study to correlate differential gene expression with CNAs in PA. PMID:18670637

  9. Prognostic impact of the 2016 WHO classification of diffuse gliomas in the French POLA cohort.

    PubMed

    Tabouret, Emeline; Nguyen, Anh Tuan; Dehais, Caroline; Carpentier, Catherine; Ducray, François; Idbaih, Ahmed; Mokhtari, Karima; Jouvet, Anne; Uro-Coste, Emmanuelle; Colin, Carole; Chinot, Olivier; Loiseau, Hugues; Moyal, Elisabeth; Maurage, Claude-Alain; Polivka, Marc; Lechapt-Zalcman, Emmanuèle; Desenclos, Christine; Meyronet, David; Delattre, Jean-Yves; Figarella-Branger, Dominique

    2016-10-01

    The new WHO classification of diffuse gliomas has been refined and now includes the 1p/19q codeletion, IDH1/2 mutation, and histone H3-K27M mutation. Our objective was to assess the prognostic value of the updated 2016 WHO classification in the French POLA cohort. All cases of high-grade oligodendroglial tumors sent for central pathological review and included into the French nationwide POLA cohort were reclassified according to the updated 4th WHO classification. In total, 1041 patients were included, with a median age at diagnosis of 50.4 years (range 17.1-84.4). Based on the new histomolecular classification, diagnoses included anaplastic oligodendroglioma IDH mutant and 1p/19q-codeleted (32.5 %), anaplastic astrocytoma IDH mutant (IDH (mut)) (11.0 %), anaplastic astrocytoma IDH wild type (IDH (wt)) (5.3 %), glioblastoma IDH (mut) (17.1 %), and glioblastoma IDH (wt) (33.2 %). Ten patients presented with a diffuse midline tumor, H3 K27M mutant. The new WHO classification was prognostic for progression-free survival (PFS) and overall survival (OS) (p < 0.001). We did not find prognosis differences between grades III and IV for IDH (mut) 1p/19q intact and IDH (wt) gliomas in univariate and multivariate analyses. Among anaplastic astrocytoma IDH (wt), cases with chromosome arm 7p gain and 10q loss (55 %) had shorter PFS than the others (p = 0.027). In conclusion, the new WHO histomolecular classification of diffuse gliomas presented with high prognostic value. Grading was not discriminant between grade III and IV high-grade gliomas.

  10. Prognostic impact of the 2016 WHO classification of diffuse gliomas in the French POLA cohort.

    PubMed

    Tabouret, Emeline; Nguyen, Anh Tuan; Dehais, Caroline; Carpentier, Catherine; Ducray, François; Idbaih, Ahmed; Mokhtari, Karima; Jouvet, Anne; Uro-Coste, Emmanuelle; Colin, Carole; Chinot, Olivier; Loiseau, Hugues; Moyal, Elisabeth; Maurage, Claude-Alain; Polivka, Marc; Lechapt-Zalcman, Emmanuèle; Desenclos, Christine; Meyronet, David; Delattre, Jean-Yves; Figarella-Branger, Dominique

    2016-10-01

    The new WHO classification of diffuse gliomas has been refined and now includes the 1p/19q codeletion, IDH1/2 mutation, and histone H3-K27M mutation. Our objective was to assess the prognostic value of the updated 2016 WHO classification in the French POLA cohort. All cases of high-grade oligodendroglial tumors sent for central pathological review and included into the French nationwide POLA cohort were reclassified according to the updated 4th WHO classification. In total, 1041 patients were included, with a median age at diagnosis of 50.4 years (range 17.1-84.4). Based on the new histomolecular classification, diagnoses included anaplastic oligodendroglioma IDH mutant and 1p/19q-codeleted (32.5 %), anaplastic astrocytoma IDH mutant (IDH (mut)) (11.0 %), anaplastic astrocytoma IDH wild type (IDH (wt)) (5.3 %), glioblastoma IDH (mut) (17.1 %), and glioblastoma IDH (wt) (33.2 %). Ten patients presented with a diffuse midline tumor, H3 K27M mutant. The new WHO classification was prognostic for progression-free survival (PFS) and overall survival (OS) (p < 0.001). We did not find prognosis differences between grades III and IV for IDH (mut) 1p/19q intact and IDH (wt) gliomas in univariate and multivariate analyses. Among anaplastic astrocytoma IDH (wt), cases with chromosome arm 7p gain and 10q loss (55 %) had shorter PFS than the others (p = 0.027). In conclusion, the new WHO histomolecular classification of diffuse gliomas presented with high prognostic value. Grading was not discriminant between grade III and IV high-grade gliomas. PMID:27573687

  11. Phytometabolite Dehydroleucodine Induces Cell Cycle Arrest, Apoptosis, and DNA Damage in Human Astrocytoma Cells through p73/p53 Regulation

    PubMed Central

    Bailon-Moscoso, Natalia; González-Arévalo, Gabriela; Velásquez-Rojas, Gabriela; Malagon, Omar; Vidari, Giovanni; Zentella-Dehesa, Alejandro; Ratovitski, Edward A.; Ostrosky-Wegman, Patricia

    2015-01-01

    Accumulating evidence supports the idea that secondary metabolites obtained from medicinal plants (phytometabolites) may be important contributors in the development of new chemotherapeutic agents to reduce the occurrence or recurrence of cancer. Our study focused on Dehydroleucodine (DhL), a sesquiterpene found in the provinces of Loja and Zamora-Chinchipe. In this study, we showed that DhL displayed cytostatic and cytotoxic activities on the human cerebral astrocytoma D384 cell line. With lactone isolated from Gynoxys verrucosa Wedd, a medicinal plant from Ecuador, we found that DhL induced cell death in D384 cells by triggering cell cycle arrest and inducing apoptosis and DNA damage. We further found that the cell death resulted in the increased expression of CDKN1A and BAX proteins. A marked induction of the levels of total TP73 and phosphorylated TP53, TP73, and γ-H2AX proteins was observed in D384 cells exposed to DhL, but no increase in total TP53 levels was detected. Overall these studies demonstrated the marked effect of DhL on the diminished survival of human astrocytoma cells through the induced expression of TP73 and phosphorylation of TP73 and TP53, suggesting their key roles in the tumor cell response to DhL treatment. PMID:26309132

  12. Phytometabolite Dehydroleucodine Induces Cell Cycle Arrest, Apoptosis, and DNA Damage in Human Astrocytoma Cells through p73/p53 Regulation.

    PubMed

    Bailon-Moscoso, Natalia; González-Arévalo, Gabriela; Velásquez-Rojas, Gabriela; Malagon, Omar; Vidari, Giovanni; Zentella-Dehesa, Alejandro; Ratovitski, Edward A; Ostrosky-Wegman, Patricia

    2015-01-01

    Accumulating evidence supports the idea that secondary metabolites obtained from medicinal plants (phytometabolites) may be important contributors in the development of new chemotherapeutic agents to reduce the occurrence or recurrence of cancer. Our study focused on Dehydroleucodine (DhL), a sesquiterpene found in the provinces of Loja and Zamora-Chinchipe. In this study, we showed that DhL displayed cytostatic and cytotoxic activities on the human cerebral astrocytoma D384 cell line. With lactone isolated from Gynoxys verrucosa Wedd, a medicinal plant from Ecuador, we found that DhL induced cell death in D384 cells by triggering cell cycle arrest and inducing apoptosis and DNA damage. We further found that the cell death resulted in the increased expression of CDKN1A and BAX proteins. A marked induction of the levels of total TP73 and phosphorylated TP53, TP73, and γ-H2AX proteins was observed in D384 cells exposed to DhL, but no increase in total TP53 levels was detected. Overall these studies demonstrated the marked effect of DhL on the diminished survival of human astrocytoma cells through the induced expression of TP73 and phosphorylation of TP73 and TP53, suggesting their key roles in the tumor cell response to DhL treatment. PMID:26309132

  13. Prognostic significance of an apoptotic index and apoptosis/proliferation ratio for patients with high-grade astrocytomas.

    PubMed Central

    Kuriyama, Hiroko; Lamborn, Kathleen R.; O'Fallon, Judith R.; Iturria, N.; Sebo, Thomas; Schaefer, Paul L.; Scheithauer, Bernd W.; Buckner, Jan C.; Kuriyama, Nagato; Jenkins, Robert B.; Israel, Mark A.

    2002-01-01

    We evaluated the association of spontaneous apoptosis and an apoptosis/proliferation index with survival to determine the potential of such measures to serve as predictive markers for patients with glioblastoma multiforme (GBM). We examined the extent of spontaneous apoptosis in tumors from newly diagnosed patients, 75 with GBM and 21 with anaplastic astrocytoma, who were entered on treatment protocols of the North Central Cancer Treatment Group. In the group of GBM patients, those with a higher apoptotic index tended to live longer ( P = 0.04; Cox proportional hazards model including performance score, age, and extent of resection in a multivariate model). We found that the apoptotic index values for anaplastic astrocytoma patients tended to be lower than those in the GBM patients, although with small sample sizes, the result was not statistically significant ( P = 0.1). We also examined expression of the Ki-67 cell proliferation antigen immunohistochemically using the MIB-1 monoclonal antibody. Ki-67 expression did not provide additional information regarding the survival of patients with GBM. In this group of GBM patients, those patients with higher apoptotic index/proliferation ratios had a better prognosis than did those with a low ratio ( P < 0.021, same model as above). These findings suggest that both apoptosis and a cell death/cell proliferation ratio are associated with patient survival, and they may be useful for either the clinical evaluation of patients with GBM or the stratification of patients for treatment evaluation. PMID:12084348

  14. Clinical Factors for Prognosis and Treatment Guidance of Spinal Cord Astrocytoma

    PubMed Central

    Hida, Kazutoshi; Yano, Shunsuke; Aoyama, Takeshi; Koyanagi, Izumi; Sasamori, Toru; Hamauch, Shuji; Houkin, Kiyohiro

    2016-01-01

    Study Design Retrospective study. Purpose To obtain information useful in establishing treatment guidelines by evaluating baseline clinical features and treatment outcomes of patients with spinal cord astrocytoma (SCA). Overview of Literature The optimal management of SCA remains controversial, and there are no standard guidelines. Methods The study included 20 patients with low-grade and 13 with high-grade SCA surgically treated between 1989 and 2014. Patients were classified according to the extent of surgical resection. Survival was assessed using Kaplan–Meier plots and compared between groups by log-rank tests. Neurological status was defined by the modified McCormick scale and compared between groups by Mann–Whitney U tests. Results Surgical resection was performed for 19 of 20 low-grade (95%) and 10 of 13 high-grade (76.9%) SCA patients. Only nine patients (27.3%) underwent gross total resection, all of whom had low-grade SCA. Of all patients, 51.5% showed deteriorated neurological status compared to preoperative baseline. Median overall survival was significantly longer for low-grade SCA than that (91 months, 78% at 5 years vs. 15 months, 31% at 5 years; p=0.007). Low-grade SCA patients benefited from more aggressive resection, whereas high-grade SCA patients did not. Multivariate analysis revealed histology status (hazard ratio [HR], 0.30; 95% confidence interval [CI], 0.09–0.98; p<0.05) and postoperative neurological status (HR, 0.12; CI, 0.02–0.95; p<0.05) as independent predictors of longer overall survival. Adjuvant radiotherapy had no significant impact on survival rate. However, a trend for increased survival was observed with radiation cordotomy (RCT) in high-grade SCA patients. Conclusions Aggressive resection for low-grade and RCT may prolong survival. Preservation of neurological status is an important treatment goal. Given the low incidence of SCA, establishing strong collaborative, interdisciplinary, and multi-institutional study groups

  15. Conserved POU-binding site linked to SP1-binding site within FZD5 promoter: Transcriptional mechanisms of FZD5 in undifferentiated human ES cells, fetal liver/spleen, adult colon, pancreatic islet, and diffuse-type gastric cancer.

    PubMed

    Katoh, Yuriko; Katoh, Masaru

    2007-03-01

    Canonical WNT signals are transduced through Frizzled (FZD) family receptor and LRP5/LRP6 co-receptor to upregulate FGF20, JAG1, DKK1, WISP1, CCND1 and MYC genes for cell-fate determination, while non-canonical WNT signals are transduced through FZD family receptor and ROR2/PTK7/RYK co-receptor to activate RHOA/RHOU/RAC/CDC42, JNK, PKC, NLK and NFAT signaling cascades for the regulation of tissue polarity, cell movement, and adhesion. We previously reported molecular cloning and characterization of human FZD5, which showed six amino-acid substitutions with human Hfz5. FZD5, functioning as WNT5A receptor, is the key molecule in the fields of oncology, regenerative medicine, cardiology, rheumatology, diabetology, and gastroenterology. Here, comparative integromics analyses on FZD5 orthologs were performed by using bioinformatics (Techint) and human intelligence (Humint). Chimpanzee FZD5 and cow Fzd5 genes were identified within NW_104292.1 and AC166656.2 genome sequences, respectively. FZD5 orthologs were seven-transmembrane proteins with extracellular Frizzled domain, leucine zipper motif around the 5th transmembrane domain, and cytoplasmic DVL- and PDZ-binding motifs. Ser523 and Ser529 around the DVL-binding motif of FZD5 orthologs were putative aPKC phosphorylation sites. POU5F1 (OCT4)-binding site linked to SP1-binding site within the 5'-promoter region of human FZD5 gene was evolutionarily conserved among mammalian FZD5 orthologs. POU5F1 was more related to POU2F and POU3F subfamily members. POU5F1 was preferentially expressed in undifferentiated human embryonic stem (ES) cells, pancreatic islet, and diffuse-type gastric cancer. POU2F1 (OCT1) was expressed in ES cells, fetal liver/spleen, adult colon, POU2F2 in ES cells, fetal liver/spleen, and POU2F3 in diffuse-type gastric cancer. Multiple SP1/KLF family members, other than KLF2 or KLF4, were expressed in undifferentiated human ES cells. Together, these facts indicate that POU5F1 and POU2F subfamily members

  16. Quantitative chromatin pattern description in Feulgen-stained nuclei as a diagnostic tool to characterize the oligodendroglial and astroglial components in mixed oligo-astrocytomas.

    PubMed

    Decaestecker, C; Lopes, B S; Gordower, L; Camby, I; Cras, P; Martin, J J; Kiss, R; VandenBerg, S R; Salmon, I

    1997-04-01

    The oligoastrocytoma, as a mixed glioma, represents a nosologic dilemma with respect to precisely defining the oligodendroglial and astroglial phenotypes that constitute the neoplastic cell lineages of these tumors. In this study, cell image analysis with Feulgen-stained nuclei was used to distinguish between oligodendroglial and astrocytic phenotypes in oligodendrogliomas and astrocytomas and then applied to mixed oligoastrocytomas. Quantitative features with respect to chromatin pattern (30 variables) and DNA ploidy (8 variables) were evaluated on Feulgen-stained nuclei in a series of 71 gliomas using computer-assisted microscopy. These included 32 oligodendrogliomas (OLG group: 24 grade II and 8 grade III tumors according to the WHO classification), 32 astrocytomas (AST group: 13 grade II and 19 grade III tumors), and 7 oligoastrocytomas (OLGAST group). Initially, image analysis with multivariate statistical analyses (Discriminant Analysis) could identify each glial tumor group. Highly significant statistical differences were obtained distinguishing the morphonuclear features of oligodendrogliomas from those of astrocytomas, regardless of their histological grade. When compared with the 7 mixed oligoastrocytomas under study, 5 exhibited DNA ploidy and chromatin pattern characteristics similar to grade II oligodendrogliomas, I to grade III oligodendrogliomas, and I to grade II astrocytomas. Using multifactorial statistical analyses (Discriminant Analysis combined with Principal Component Analysis). It was possible to quantify the proportion of "typical" glial cell phenotypes that compose grade II and III oligodendrogliomas and grade II and III astrocytomas in each mixed glioma. Cytometric image analysis may be an important adjunct to routine histopathology for the reproducible identification of neoplasms containing a mixture of oligodendroglial and astrocytic phenotypes. PMID:9100670

  17. Vaneless diffusers

    NASA Astrophysics Data System (ADS)

    Senoo, Y.

    The influence of vaneless diffusers on flow in centrifugal compressors, particularly on surge, is discussed. A vaneless diffuser can demonstrate stable operation in a wide flow range only if it is installed with a backward leaning blade impeller. The circumferential distortion of flow in the impeller disappears quickly in the vaneless diffuser. The axial distortion of flow at the diffuser inlet does not decay easily. In large specific speed compressors, flow out of the impeller is distorted axially. Pressure recovery of diffusers at distorted inlet flow is considerably improved by half guide vanes. The best height of the vanes is a little 1/2 diffuser width. In small specific speed compressors, flow out of the impeller is not much distorted and pressure recovery can be predicted with one-dimensional flow analysis. Wall friction loss is significant in narrow diffusers. The large pressure drop at a small flow rate can cause the positive gradient of the pressure-flow rate characteristic curve, which may cause surging.

  18. Diffuse radiation

    NASA Technical Reports Server (NTRS)

    1981-01-01

    A diffuse celestial radiation which is isotropic at least on a course scale were measured from the soft X-ray region to about 150 MeV, at which energy the intensity falls below that of the galactic emission for most galactic latitudes. The spectral shape, the intensity, and the established degree of isotropy of this diffuse radiation already place severe constraints on the possible explanations for this radiation. Among the extragalactic theories, the more promising explanations of the isotropic diffuse emission appear to be radiation from exceptional galaxies from matter antimatter annihilation at the boundaries of superclusters of galaxies of matter and antimatter in baryon symmetric big bang models. Other possible sources for extragalactic diffuse gamma radiation are discussed and include normal galaxies, clusters of galaxies, primordial cosmic rays interacting with intergalactic matter, primordial black holes, and cosmic ray leakage from galaxies.

  19. Diffusion barriers

    NASA Technical Reports Server (NTRS)

    Nicolet, M. A.

    1983-01-01

    The choice of the metallic film for the contact to a semiconductor device is discussed. One way to try to stabilize a contact is by interposing a thin film of a material that has low diffusivity for the atoms in question. This thin film application is known as a diffusion barrier. Three types of barriers can be distinguished. The stuffed barrier derives its low atomic diffusivity to impurities that concentrate along the extended defects of a polycrystalline layer. Sacrificial barriers exploit the fact that some (elemental) thin films react in a laterally uniform and reproducible fashion. Sacrificial barriers have the advantage that the point of their failure is predictable. Passive barriers are those most closely approximating an ideal barrier. The most-studied case is that of sputtered TiN films. Stuffed barriers may be viewed as passive barriers whose low diffusivity material extends along the defects of the polycrystalline host.

  20. Microwave-assisted antigen retrieval and incubation with cox-2 antibody of archival paraffin-embedded human oligodendroglioma and astrocytomas.

    PubMed

    Temel, Sehime G; Minbay, F Zehra; Kahveci, Zeynep; Jennes, Lothar

    2006-09-30

    Immunohistochemistry is an important tool that is often used for the diagnosis of pathologies; however, the length of time required to process the tissue is relatively long. Furthermore, the quality and sensitivity of immunohistochemical staining is affected by formalin fixation which results in variable loss of antigenicity, known as masking effect. Here we assess the effect of microwave irradiation on the incubation time required to obtain high quality immunohistochemical staining for cox-2 using archival formalin-fixed, paraffin-embedded human oligodendrogliomas and astrocytomas. The results show that intermittent microwave irradiation during the incubation with the primary antibody reduced the time requirement to 5 min while the staining quality was indistinguishable from 1 or 24 h long incubations. Thus, the use of this procedure results in a significant saving of time which is important for a timely diagnosis of pathological conditions that await treatment.

  1. p53 protein in low-grade astrocytomas: a study with long-term follow-up.

    PubMed Central

    Iuzzolino, P.; Ghimenton, C.; Nicolato, A.; Giorgiutti, F.; Fina, P.; Doglioni, C.; Barbareschi, M.

    1994-01-01

    The immunohistochemical expression of p53 protein (p53) was examined in 52 patients out of a series of 66 patients with low-grade astrocytomas with long-term follow-up. All patients were also evaluated for several clinical and histological features, among which only preoperative Karnofsky score and the extent of surgery were statistically significant parameters to predict outcome on multivariate analysis. p53 accumulation was seen in 46.1% of patients, with a wide range of percentage of positive cells. Median survival for p53-positive and p53-negative patients was 41 and 37 months respectively. The survival curves of p53-positive and -negative patients were not statistically different. However, the curves showed a trend towards a more aggressive course in p53-positive patients beginning 3-4 years after surgery. Five years after diagnosis the survival estimate with the Kaplan-Meier method was 21.2% for patients with p53-positive tumours and 45.9% for patients with p53-negative tumours. This trend is not due to different distribution of major clinical prognostic factors (age, incomplete resection or Karnofsky status). The trend could be related to the time needed by the p53-positive clone to outgrow the rest of the p53-negative neoplastic cell population. This hypothesis is further supported by the fact that the five recurrences which were surgically removed (one anaplastic astrocytoma and four glioblastomas) derived from p53-positive tumours and were themselves intensely p53 positive. Images Figure 1 PMID:8123492

  2. Subnanomolar concentrations of thrombin enhance the volume-sensitive efflux of taurine from human 1321N1 astrocytoma cells.

    PubMed

    Cheema, Tooba A; Ward, Caroline E; Fisher, Stephen K

    2005-11-01

    The ability of subnanomolar concentrations of thrombin to protect both neurons and glia from ischemia and other metabolic insults has recently been reported. In this study, we demonstrate an additional neuroprotective property of thrombin; its ability to promote the release of the organic osmolyte, taurine, in response to hypoosmotic stress. Incubation of human 1321N1 astrocytoma cells with hypo-osmolar buffers (320-227 mOsM) resulted in a time-dependent release of taurine. Inclusion of thrombin (EC(50) = 60 pM) resulted in a marked increase in taurine efflux that, although evident under isotonic conditions (340 mOsM), was maximal at an osmolarity of 270 mOsM (3-4-fold stimulation). Thrombin-stimulated taurine efflux was dependent upon its protease activity and could be mimicked by addition of the peptide SFLLRN, a proteinase activated receptor-1 (PAR-1) subtype-specific ligand. Inclusion of anion channel blockers known to inhibit the volume-sensitive organic osmolyte anion channel attenuated thrombin-stimulated taurine release. Depletion of intracellular Ca(2+) with either 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) or thapsigargin, or alternatively, inhibition of protein kinase C (PKC) with bisindolylmaleimide or chelerythrine resulted in a 30 to 50% inhibition of thrombin-stimulated taurine efflux. Under conditions in which intracellular Ca(2+) was depleted and PKC activity inhibited, thrombin-stimulated taurine efflux was reduced by >85%. The results indicate that activation of PAR-1 receptors by thrombin facilitates the ability of 1321N1 astrocytoma cells to release osmolytes in response to a reduction in osmolarity via a mechanism that is dependent on intracellular Ca(2+) and PKC activity. PMID:16051696

  3. Paradoxical role of 3-methyladenine in pyocyanin-induced toxicity in 1321N1 astrocytoma and SH-SY5Y neuroblastoma cells.

    PubMed

    McFarland, Amelia J; Grant, Gary D; Perkins, Anthony V; Flegg, Cameron; Davey, Andrew K; Allsopp, Tristan J; Renshaw, Gillian; Kavanagh, Justin; McDermott, Catherine M; Anoopkumar-Dukie, Shailendra

    2013-01-01

    The role of autophagy in pyocyanin (PCN)-induced toxicity in the central nervous system (CNS) remains unclear, with only evidence from our group identifying it as a mechanism underlying toxicity in 1321N1 astrocytoma cells. Therefore, the aim of this study was to further examine the role of autophagy in PCN-induced toxicity in the CNS. To achieve this, we exposed 1321N1 astrocytoma and SH-SY5Y neuroblastoma cells to PCN (0-100 μmol/L) and tested the contribution of autophagy by measuring the impact of the autophagy inhibitor 3-methyladenine (3-MA) using a series of biochemical and molecular markers. Pretreatment of 1321N1 astrocytoma cells with 3-MA (5 mmol/L) decreased the PCN-induced acidic vesicular organelle and autophagosome formation as measured using acridine orange and green fluorescent protein-LC3 -LC3 fluorescence, respectively. Furthermore, 3-MA (5 mmol/L) significantly protected 1321N1 astrocytoma cells against PCN-induced toxicity. In contrast pretreatment with 3-MA (5 mmol/L) increased PCN-induced toxicity in SH-SY5Y neuroblastoma cells. Given the influence of autophagy in inflammatory responses, we investigated whether the observed effects in this study involved inflammatory mediators. The PCN (100 μmol/L) significantly increased the production of interleukin-8 (IL-8), prostaglandin E2 (PGE₂), and leukotriene B4 (LTB₄) in both cell lines. Consistent with its paradoxical role in modulating PCN-induced toxicity, 3-MA (5 mmol/L) significantly reduced the PCN-induced production of IL-8, PGE₂, and LTB₄ in 1321N1 astrocytoma cells but augmented their production in SH-SY5Y neuroblastoma cells. In conclusion, we show here for the first time the paradoxical role of autophagy in mediating PCN-induced toxicity in 1321N1 astrocytoma and SH-SY5Y neuroblastoma cells and provide novel evidence that these actions may be mediated by effects on IL-8, PGE₂, and LTB₄ production.

  4. MiR-181b-5p Downregulates NOVA1 to Suppress Proliferation, Migration and Invasion and Promote Apoptosis in Astrocytoma

    PubMed Central

    Shao, Naiyuan; Wang, Rong; Xue, Lian; Wang, Suinuan; Xia, Xiwei; Yang, Yilin

    2014-01-01

    MicroRNAs (miRNAs) are small, short noncoding RNAs that modulate the expression of numerous genes by targeting their mRNA. Numerous abnormal miRNA expression patterns are observed in various human malignancies, and certain miRNAs can act as oncogenes or tumor suppressors. Astrocytoma, the most common neuroepithelial cancer, represents the majority of malignant brain tumors in humans. In our previous studies, we found that the downregulation of miR-181b-5p in astrocytomas is associated with a poor prognosis. The aim of the present study was to investigate the functional role of miR-181b-5p and its possible target genes. miR-181b-5p was significantly downregulated in astrocytoma specimens, and the reduced expression of miR-181b-5p was inversely correlated with the clinical stage. The ectopic expression of miR-181b-5p inhibited proliferation, migration and invasion and induced apoptosis in astrocytoma cancer cells in vitro. The NOVA1 (neuro-oncological ventral antigen 1) gene was further identified as a novel direct target of miR-181b-5p. Specifically, miR-181b-5p bound directly to the 3'-untranslated region (UTR) of NOVA1 and suppressed its expression. In clinical specimens, NOVA1 was overexpressed, and its protein levels were inversely correlated with miR-181b-5p expression. Furthermore, the changing level of NOVA1 was significantly associated with a poor survival outcome. Similar to restoring miR-181b-5p expression, downregulating NOVA1 inhibited cell growth, migration and invasion. Overexpression of NOVA1 reversed the inhibitory effects of miR-181b-5p. Our results indicate that miR-181b-5p is a tumor suppressor in astrocytoma that inhibits tumor progression by targeting NOVA1. These findings suggest that miR-181b-5p may serve as a novel therapeutic target for astrocytoma. PMID:25299073

  5. Worldwide dietary therapies for adults with epilepsy and other disorders.

    PubMed

    Cervenka, Mackenzie C; Henry, Bobbie; Nathan, Janak; Wood, Susan; Volek, Jeff S

    2013-08-01

    During the 3rd International Symposium on Dietary Therapies held in Chicago, Illinois, there was a first-ever, half-day session devoted to the management of adults with epilepsy and other disorders with dietary treatments. Speakers from 3 different continents shared their successes, challenges, and future directions in their management of these patients. Diets used to treat adults included the classic ketogenic diet, the modified Atkins diet, and a low glycemic index treatment. The utility of dietary therapies was demonstrated not only in patients with epilepsy but also patients with propriospinal myoclonus, astrocytoma, type 2 diabetes, obesity, hyperlipidemia, and metabolic disorder. The session provided evidence that dietary therapies are safe and effective in adults.

  6. Diagnostic, treatment, and demographic factors influencing survival in a population-based study of adult glioma patients in the San Francisco Bay Area.

    PubMed

    Wrensch, Margaret; Rice, Terri; Miike, Rei; McMillan, Alex; Lamborn, Kathleen R; Aldape, Kenneth; Prados, Michael D

    2006-01-01

    We compare survival estimates for population-based glioma cases by using two diagnostic coding schemes, (1) the International Classification of Diseases, Oncology, second edition (ICD-O-2) as reported by the Surveillance, Epidemiology, and End Results (SEER) program and (2) central neuropathology review diagnosis based on the World Health Organization II classification. In addition, among review categories, we estimate survival in relation to several patient demographic and treatment factors. Eligible cases included adults residing in the San Francisco Bay SEER Area with newly diagnosed, histologically confirmed glioma during the years 1991-1994 and 1997-1999. The study group included participating subjects for whom subsequent central neuropathology review confirmed glioma. We determined treatments, vital status, and other factors by using registry, interview, medical record, and active follow-up data. Survival differences between anaplastic astrocytoma (AA) and astrocytoma were apparent from review diagnoses (median months of survival for AA, 13.0 [95% CI, 9.9-19.5], and astrocytoma, 101.3 [95% CI lower limit, 42.1; upper limit not yet reached]), but not with ICD-O-2 diagnoses reported by SEER (median months of survival for AA, 16.6 [95% CI, 12.0-20.7], and astrocytoma, not otherwise specified, 17.2 [95% CI, 10.6-71.6]). This finding emphasizes the need for improvements in coding for nonglioblastoma astrocytomas to provide better population survival estimates. When review diagnosis was used, younger age and resection (vs. biopsy) were statistically significant for all histology groups analyzed by multivariable Cox proportional hazard models. Additional statistically significant variables were as follows: among 517 glioblastoma patients, radiation treatment and being married; among 105 AA patients, inclusion of chemotherapy in the initial treatment; and among 106 patients with nonanaplastic oligodendroglial tumors, college education. Further consideration of impact

  7. Diagnostic, treatment, and demographic factors influencing survival in a population-based study of adult glioma patients in the San Francisco Bay Area1

    PubMed Central

    Wrensch, Margaret; Rice, Terri; Miike, Rei; McMillan, Alex; Lamborn, Kathleen R.; Aldape, Kenneth; Prados, Michael D.

    2006-01-01

    We compare survival estimates for population-based glioma cases by using two diagnostic coding schemes, (1) the International Classification of Diseases, Oncology, second edition (ICD-O-2) as reported by the Surveillance, Epidemiology, and End Results (SEER) program and (2) central neuropathology review diagnosis based on the World Health Organization II classification. In addition, among review categories, we estimate survival in relation to several patient demographic and treatment factors. Eligible cases included adults residing in the San Francisco Bay SEER Area with newly diagnosed, histologically confirmed glioma during the years 1991–1994 and 1997–1999. The study group included participating subjects for whom subsequent central neuropathology review confirmed glioma. We determined treatments, vital status, and other factors by using registry, interview, medical record, and active follow-up data. Survival differences between anaplastic astrocytoma (AA) and astrocytoma were apparent from review diagnoses (median months of survival for AA, 13.0 [95% CI, 9.9–19.5], and astrocytoma, 101.3 [95% CI lower limit, 42.1; upper limit not yet reached]), but not with ICD-O-2 diagnoses reported by SEER (median months of survival for AA, 16.6 [95% CI, 12.0–20.7], and astrocytoma, not otherwise specified, 17.2 [95% CI, 10.6–71.6]). This finding emphasizes the need for improvements in coding for nonglioblastoma astrocytomas to provide better population survival estimates. When review diagnosis was used, younger age and resection (vs. biopsy) were statistically significant for all histology groups analyzed by multivariable Cox proportional hazard models. Additional statistically significant variables were as follows: among 517 glioblastoma patients, radiation treatment and being married; among 105 AA patients, inclusion of chemotherapy in the initial treatment; and among 106 patients with nonanaplastic oligodendroglial tumors, college education. Further consideration

  8. Demonstrating Diffusion

    ERIC Educational Resources Information Center

    Foy, Barry G.

    1977-01-01

    Two demonstrations are described. Materials and instructions for demonstrating movement of molecules into cytoplasm using agar blocks, phenolphthalein, and sodium hydroxide are given. A simple method for demonstrating that the rate of diffusion of a gas is inversely proportional to its molecular weight is also presented. (AJ)

  9. Relativistic diffusion

    NASA Astrophysics Data System (ADS)

    Haba, Z.

    2009-02-01

    We discuss relativistic diffusion in proper time in the approach of Schay (Ph.D. thesis, Princeton University, Princeton, NJ, 1961) and Dudley [Ark. Mat. 6, 241 (1965)]. We derive (Langevin) stochastic differential equations in various coordinates. We show that in some coordinates the stochastic differential equations become linear. We obtain momentum probability distribution in an explicit form. We discuss a relativistic particle diffusing in an external electromagnetic field. We solve the Langevin equations in the case of parallel electric and magnetic fields. We derive a kinetic equation for the evolution of the probability distribution. We discuss drag terms leading to an equilibrium distribution. The relativistic analog of the Ornstein-Uhlenbeck process is not unique. We show that if the drag comes from a diffusion approximation to the master equation then its form is strongly restricted. The drag leading to the Tsallis equilibrium distribution satisfies this restriction whereas the one of the Jüttner distribution does not. We show that any function of the relativistic energy can be the equilibrium distribution for a particle in a static electric field. A preliminary study of the time evolution with friction is presented. It is shown that the problem is equivalent to quantum mechanics of a particle moving on a hyperboloid with a potential determined by the drag. A relation to diffusions appearing in heavy ion collisions is briefly discussed.

  10. Defusing Diffusion

    ERIC Educational Resources Information Center

    Dou, Remy; Hogan, DaNel; Kossover, Mark; Spuck, Timothy; Young, Sarah

    2013-01-01

    Diffusion has often been taught in science courses as one of the primary ways by which molecules travel, particularly within organisms. For years, classroom teachers have used the same common demonstrations to illustrate this concept (e.g., placing drops of food coloring in a beaker of water). Most of the time, the main contributor to the motion…

  11. Relativistic diffusion.

    PubMed

    Haba, Z

    2009-02-01

    We discuss relativistic diffusion in proper time in the approach of Schay (Ph.D. thesis, Princeton University, Princeton, NJ, 1961) and Dudley [Ark. Mat. 6, 241 (1965)]. We derive (Langevin) stochastic differential equations in various coordinates. We show that in some coordinates the stochastic differential equations become linear. We obtain momentum probability distribution in an explicit form. We discuss a relativistic particle diffusing in an external electromagnetic field. We solve the Langevin equations in the case of parallel electric and magnetic fields. We derive a kinetic equation for the evolution of the probability distribution. We discuss drag terms leading to an equilibrium distribution. The relativistic analog of the Ornstein-Uhlenbeck process is not unique. We show that if the drag comes from a diffusion approximation to the master equation then its form is strongly restricted. The drag leading to the Tsallis equilibrium distribution satisfies this restriction whereas the one of the Jüttner distribution does not. We show that any function of the relativistic energy can be the equilibrium distribution for a particle in a static electric field. A preliminary study of the time evolution with friction is presented. It is shown that the problem is equivalent to quantum mechanics of a particle moving on a hyperboloid with a potential determined by the drag. A relation to diffusions appearing in heavy ion collisions is briefly discussed.

  12. An image-analysis system based on support vector machines for automatic grade diagnosis of brain-tumour astrocytomas in clinical routine.

    PubMed

    Glotsos, D; Spyridonos, P; Cavouras, D; Ravazoula, P; Dadioti, P Arapantoni; Nikiforidis, G

    2005-09-01

    An image-analysis system based on the concept of Support Vector Machines (SVM) was developed to assist in grade diagnosis of brain tumour astrocytomas in clinical routine. One hundred and forty biopsies of astrocytomas were characterized according to the WHO system as grade II, III and IV. Images from biopsies were digitized, and cell nuclei regions were automatically detected by encoding texture variations in a set of wavelet, autocorrelation and parzen estimated descriptors and using an unsupervised SVM clustering methodology. Based on morphological and textural nuclear features, a decision-tree classification scheme distinguished between different grades of tumours employing an SVM classifier. The system was validated for clinical material collected from two different hospitals. On average, the SVM clustering algorithm correctly identified and accurately delineated 95% of all nuclei. Low-grade tumours were distinguished from high-grade tumours with an accuracy of 90.2% and grade III from grade IV with an accuracy of 88.3% The system was tested in a new clinical data set, and the classification rates were 87.5 and 83.8%, respectively. Segmentation and classification results are very encouraging, considering that the method was developed based on every-day clinical standards. The proposed methodology might be used in parallel with conventional grading to support the regular diagnostic procedure and reduce subjectivity in astrocytomas grading. PMID:16403707

  13. Targeting the MAP kinase pathway in astrocytoma cells using a recombinant anthrax lethal toxin as a way to inhibit cell motility and invasion.

    PubMed

    Al-Dimassi, Saleh; Salloum, Gilbert; Saykali, Bechara; Khoury, Oula; Liu, Shihui; Leppla, Stephen H; Abi-Habib, Ralph; El-Sibai, Mirvat

    2016-05-01

    Malignant astrocytomas are highly invasive into adjacent and distant regions of the normal brain. Understanding and targeting cancer cell invasion is an important therapeutic approach. Cell invasion is a complex process that replies on many signaling pathways including the mitogen-activated protein (MAP) kinase (MAPK). In many cell lines, the use of MAPK-targeted drugs proved to be a potential method to inhibit cancer cell motility. In the present study, we use a recombinant anthrax lethal toxin (LeTx), which selectively inhibits the MAPK pathway, in order to target invasion. LeTx proved ineffective on cell survival in astrocytoma (as well as normal cells). However, astrocytoma cells that were treated with LeTx showed a significant decrease in cell motility as seen by wound healing as well as random 2D motility in serum. The cells also showed a decrease in invasion across a collagen matrix. The effect of LeTx on cell migration was mediated though the deregulation of Rho GTPases, which play a role in cell motility. Finally, the effect of LeTx on cell migration and Rho GTPases was mimicked by the inhibition of the MAPK pathway. In this study, we describe for the first time the effect of the LeTx on cancer cell motility and invasion not cell survival making it a potentially selective brain tumor invasion inhibitor. PMID:26984023

  14. Deguelins, Natural Product Modulators of NF1-Defective Astrocytoma Cell Growth Identified by High-Throughput Screening of Partially Purified Natural Product Extracts.

    PubMed

    Henrich, Curtis J; Cartner, Laura K; Wilson, Jennifer A; Fuller, Richard W; Rizzo, Anthony E; Reilly, Karlyne M; McMahon, James B; Gustafson, Kirk R

    2015-11-25

    A high-throughput screening assay for modulators of Trp53/NF1 mutant astrocytoma cell growth was adapted for use with natural product extracts and applied to a novel collection of prefractionated/partially purified extracts. Screening 68 427 samples identified active fractions from 95 unique extracts, including the terrestrial plant Millettia ichthyotona. Only three of these extracts showed activity in the crude extract form, thus demonstrating the utility of a partial purification approach for natural product screening. The NF1 screening assay was used to guide purification of active compounds from the M. ichthyotona extract, which yielded the two rotenones deguelin (1) and dehydrodeguelin (2). The deguelins have been reported to affect growth of a number of cancer cell lines. They potently inhibited growth of only one of a panel of NF1/Trp53 mutant murine astrocytoma cell lines, possibly related to epigenetic factors, but had no effect on the growth of normal astrocytes. These results suggest the potential utility of deguelins as tools for further investigating NF1 astrocytoma cell growth. These bioprobes were identified only as a result of screening partially purified natural product extracts. PMID:26467198

  15. Diffusion bonding

    DOEpatents

    Anderson, Robert C.

    1976-06-22

    1. A method for joining beryllium to beryllium by diffusion bonding, comprising the steps of coating at least one surface portion of at least two beryllium pieces with nickel, positioning a coated surface portion in a contiguous relationship with an other surface portion, subjecting the contiguously disposed surface portions to an environment having an atmosphere at a pressure lower than ambient pressure, applying a force upon the beryllium pieces for causing the contiguous surface portions to abut against each other, heating the contiguous surface portions to a maximum temperature less than the melting temperature of the beryllium, substantially uniformly decreasing the applied force while increasing the temperature after attaining a temperature substantially above room temperature, and maintaining a portion of the applied force at a temperature corresponding to about maximum temperature for a duration sufficient to effect the diffusion bond between the contiguous surface portions.

  16. Detection of TNF inhibitors (soluble receptors) in the sera and tumor cyst fluid of patients with malignant astrocytomas of the brain.

    PubMed

    Ammirati, M; Rao, S; Granger, G

    2001-10-01

    Patients with malignant astrocytomas of the brain exhibit varying degrees of immunosuppression with only a few factors responsible for this immunosuppression having been characterized. The soluble forms of the 55 kDa and 75 kDa membrane receptors for tumor necrosis factor (sTNF-R's) have been shown to bind to and inhibit the activity of TNF. The present studies analyze levels of sTNF-R's in the sera and tumor cyst fluids of patients with malignant astrocytomas. Using sensitive ELISA techniques, serum levels of the 55 and 75 kDa sTNF-R's in 17 patients tested were found to be elevated (55 kDa of 2.29 ( 2.85 ng/ml and 75 kDa of 4.98 ( 4.03 ng/ml( as compared to 20 normal controls (55 kDa of of 1.21 ( 0.91 ng/ml and 75 kDa of 1.85 ( 0.40 ng/ml( although this was only statistically significant for the 75 kDa sTNF-R (P=0.006). Brain tymor cyst fluid samples obtained from eight patients were shown to have very high levels of both sTNF-R's ranging from 4.16 to 17.17 ng/ml for the 55 kDa receptor and 4.83 to 19.96 ng/ml for the 75 kDa receptor. Six of these cyst fluid samples were also tested for their ability to inhibit TNF cytolytic activity using an in vitro assay. All samples tested had TNF inhibitory activity. Immunohistochemical studies on patient tumor samples showed high levels of expression of these receptors both in the cytoplasm and the cell surface of astrocytoma cells. We propose that sTNF-R's may be shed by astrocytoma cells and may have a role in both local and systemic immunosuppression observed in astrocytoma patients. Finally, the potential role of serum level of sTNF-R's as tumor markers to follow the treatment and the progression of disease in these patients are discussed. PMID:11578951

  17. Genetic characterization of adult infratentorial gliomas.

    PubMed

    Miwa, Tomoru; Hirose, Yuichi; Sasaki, Hikaru; Ikeda, Eiji; Yoshida, Kazunari; Kawase, Takeshi

    2009-02-01

    Adult infratentorial gliomas are rare and have not been well studied. We therefore conducted genetic analysis of those tumors to see if there was any characteristic that could be relevant in clinical management and understanding of tumorigenesis. Nineteen adult infratentorial gliomas were analyzed for chromosomal aberration by comparative genomic hybridization, and for expression of p53 and epidermal growth factor receptor (EGFR) by immunohistochemistry. The most frequent chromosomal aberration was the gain of 7p, and five of the seven cerebellar or fourth ventricle malignant gliomas had that aberration. However, the gain of 7q, the characteristic abnormality of supratentorial astrocytomas commonly associated with the gaining of 7p, was observed only in 1 of 11 adult infratentorial astrocytic tumors. Combined losses of 1p and 19q, the genetic hallmark of oligodendroglioma, were not observed. Results of immunohistochemistry of p53 and EGFR were comparable to those reported in supratentorial gliomas. Our findings might suggest the presence of distinct tumorigenic pathway in adult infratentorial gliomas.

  18. Integrated analysis of DNA methylation profiles and gene expression profiles to identify genes associated with pilocytic astrocytomas.

    PubMed

    Zhou, Ruigang; Man, Yigang

    2016-04-01

    The present study performed an integral analysis of the gene expression and DNA methylation profile of pilocytic astrocytomas (PAs). Weighted gene co-expression network analysis (WGCNA) was also performed to examine and identify the genes correlated to PAs, to identify candidate therapeutic targets for the treatment of PAs. The DNA methylation profile and gene expression profile were downloaded from the Gene Expression Omnibus database. Following screening of the differentially expressed genes (DEGs) and differentially methylated regions (DMRs), respectively, integrated analysis of the DEGs and DMRs was performed to detect their correlation. Subsequently, the WGCNA algorithm was applied to identify the significant modules and construct the co‑expression network associated with PAs. Furthermore, Gene Ontology enrichment analysis of the associated genes was performed using the Database for Annotation, Visualization and Integrated Discovery. A total number of 2,259 DEGs and 235 DMRs were screened out. Integrated analysis revealed that 30 DEGs were DMRs with prominent negative correlation (cor=‑0.82; P=0.02). Based on the DEGs, the gene co‑expression network was constructed, and nine network modules associated with PAs were identified. The functional analysis results showed that genes relevant to PAs were closely associated with cell differentiation modulation. The screened PA-associated genes were significantly different at the expression and methylation levels. These genes may be used as reliable candidate target genes for the treatment of PAs.

  19. Dysphasia and Phantosmia as First Presentation of Multifocal Cerebral Anaplastic Astrocytomas: Case Report and Review of the Literatures

    PubMed Central

    Kong, Xiangyi; Wang, Yu; Liu, Shuai; Lu, Zhaohui; Wu, Huanwen; Mao, Xinxin; Cheng, Xin; Gao, Jun; Guan, Jian; Yang, Yi; Li, Yongning; Xing, Bing; Ma, Wenbin; Wang, Renzhi

    2015-01-01

    Abstract Multifocal cerebral gliomas (MCGs) represent approximately 10% of gliomas and are frequently mistaken as metastases of an unknown primary cancer site. Most MCGs are glioblastomas with <4 lesions supratentorially, and are lack of typical symptoms and special detections. Through a rare MCG case, we aim to present this rarity and emphasize the need to correctly diagnose multiple intracranial lesions using a variety of diagnostic modalities to ensure that the patient receives proper treatment. We present a case of multifocal cerebral anaplastic astrocytomas with a total of 8 lesions located in the left frontal lobe and invading the lateral ventricle, presenting with dysphasia and phantosmia. The disease course, including diagnosis and treatment, is presented and analyzed in detail. The pertinent literature is reviewed regarding this uncommon entity. After an initial impression of brain metastasis from lung cancer because of the magnetic resonance imaging (MRI) resemblance and history of chronic bronchitis, we were able to use positron emission tomography (PET) and excisional biopsy to get the final diagnosis. After 10 months, the patient's overall condition deteriorated and succumbed to his disease. MCGs are easy to be misdiagnosed as metastatic diseases. In addition to MRI, PET adds more biochemical and molecular information and is helpful in the differentiation. Although uncommon, if multiple lesions are present in various locations in the hemispheres, MCG should be kept in mind. PMID:25997068

  20. Hypofractionated high-dose irradiation for the treatment of malignant astrocytomas using simultaneous integrated boost technique by IMRT

    SciTech Connect

    Iuchi, Toshihiko; Hatano, Kazuo; Narita, Yuichiro; Kodama, Takashi; Yamaki, Tomohiro; Osato, Katsunobu

    2006-04-01

    Purpose: We evaluated the clinical significance of hypofractionated high-dose irradiation using simultaneous integrated boost technique with intensity-modulated radiation therapy (IMRT) for the treatment of malignant astrocytomas (MAs). Methods and Materials: Twenty-five patients with MAs were treated by IMRT. Three layered planning target volumes (PTVs) were contoured. PTV-1 was the area of enhanced lesion with 5-mm margin; PTV-2 was the area with 15-mm margin surrounding the PTV-1; PTV-3 was the area of perifocal edema. Irradiation was performed in 8 fractions, and only the dose for PTV-1 was escalated from 48 Gy to 68 Gy while maintaining the dose for PTV-2 (40 Gy) and PTV-3 (32 Gy). The clinical outcome of IMRT was compared with 60 MA patients treated by conventional external beam irradiation (EBI). Results: The progression-free survival of patients in the IMRT group was significantly longer than that in the EBI group (p < 0.0001). No distant failure was observed in both groups. In the IMRT group, dissemination was the most frequent cause of death (70%). The overall survival of patients in the IMRT group was better than that in the EBI group (p = 0.043). Conclusions: Our regimen of IMRT contributed to the control of both the regional and infiltrating tumors, resulting in better survival of patients.

  1. Dysphasia and phantosmia as first presentation of multifocal cerebral anaplastic astrocytomas: case report and review of the literatures.

    PubMed

    Kong, Xiangyi; Wang, Yu; Liu, Shuai; Lu, Zhaohui; Wu, Huanwen; Mao, Xinxin; Cheng, Xin; Gao, Jun; Guan, Jian; Yang, Yi; Li, Yongning; Xing, Bing; Ma, Wenbin; Wang, Renzhi

    2015-05-01

    Multifocal cerebral gliomas (MCGs) represent approximately 10% of gliomas and are frequently mistaken as metastases of an unknown primary cancer site. Most MCGs are glioblastomas with <4 lesions supratentorially, and are lack of typical symptoms and special detections.Through a rare MCG case, we aim to present this rarity and emphasize the need to correctly diagnose multiple intracranial lesions using a variety of diagnostic modalities to ensure that the patient receives proper treatment.We present a case of multifocal cerebral anaplastic astrocytomas with a total of 8 lesions located in the left frontal lobe and invading the lateral ventricle, presenting with dysphasia and phantosmia. The disease course, including diagnosis and treatment, is presented and analyzed in detail. The pertinent literature is reviewed regarding this uncommon entity.After an initial impression of brain metastasis from lung cancer because of the magnetic resonance imaging (MRI) resemblance and history of chronic bronchitis, we were able to use positron emission tomography (PET) and excisional biopsy to get the final diagnosis. After 10 months, the patient's overall condition deteriorated and succumbed to his disease.MCGs are easy to be misdiagnosed as metastatic diseases. In addition to MRI, PET adds more biochemical and molecular information and is helpful in the differentiation. Although uncommon, if multiple lesions are present in various locations in the hemispheres, MCG should be kept in mind. PMID:25997068

  2. A fraction of neurofibromin interacts with PML bodies in the nucleus of the CCF astrocytoma cell line

    SciTech Connect

    Godin, Fabienne; Villette, Sandrine; Vallee, Beatrice; Doudeau, Michel; Morisset-Lopez, Severine; Ardourel, Maryvonne; Hevor, Tobias; Pichon, Chantal; Benedetti, Helene

    2012-02-24

    Highlights: Black-Right-Pointing-Pointer We validate the use of specific anti-Nf1 antibodies for immunofluorescence studies. Black-Right-Pointing-Pointer We detect Nf1 in the cytoplasm and nucleus of CCF cells. Black-Right-Pointing-Pointer We demonstrate that Nf1 partially colocalizes with PML nuclear bodies. Black-Right-Pointing-Pointer We demonstrate that there is a direct interaction between a fraction of Nf1 and the PML bodies. -- Abstract: Neurofibromatosis type 1 is a common genetic disease that causes nervous system tumors, and cognitive deficits. It is due to mutations within the NF1 gene, which encodes the Nf1 protein. Nf1 has been shown to be involved in the regulation of Ras, cAMP and actin cytoskeleton dynamics. In this study, using immunofluorescence experiments, we have shown a partial nuclear localization of Nf1 in the astrocytoma cell line: CCF and we have demonstrated that Nf1 partially colocalizes with PML (promyelocytic leukemia) nuclear bodies. A direct interaction between Nf1 and the multiprotein complex has further been demonstrated using 'in situ' proximity ligation assay (PLA).

  3. Immediate disappearance of hemifacial spasm after partial removal of ponto-medullary junction anaplastic astrocytoma: case report.

    PubMed

    Castiglione, Melina; Broggi, Morgan; Cordella, Roberto; Acerbi, Francesco; Ferroli, Paolo

    2015-04-01

    Hemifacial spasm (HFS) is generally caused by a neurovascular conflict (NC) at the root exit zone (REZ) of the facial nerve at the brainstem. Although a direct compression to the seventh cranial nerve (CN) by the anterior inferior cerebellar artery (AICA) is generally the most frequent cause, secondary HFS may be related to other pathological conditions. HFS due to an intracranial mass lesion is exceptionally rare and it has been reported in very few cases. The online database was searched for English-language articles reporting cases of HFS due to brainstem mass lesions and the possible pathophysiological mechanisms involved in its genesis. A 47-year-old man affected by an anaplastic astrocytoma of the brainstem at the level of the ponto-medullary junction developed right HFS. He underwent a subtotal surgical removal of the tumor with complete resolution of the HFS. This is the ninth reported case of HFS caused by an intrinsic brainstem tumor. The exceptional rarity of the relationship between intra-axial tumors and peripheral HFS was analyzed. PMID:25382264

  4. Expression and function of the receptor protein tyrosine phosphatase zeta and its ligand pleiotrophin in human astrocytomas.

    PubMed

    Ulbricht, Ulrike; Brockmann, Marc A; Aigner, Achim; Eckerich, Carmen; Müller, Sabine; Fillbrandt, Regina; Westphal, Manfred; Lamszus, Katrin

    2003-12-01

    Using subtractive cloning combined with cDNA array analysis, we previously identified the genes encoding for the protein tyrosine phosphatase zeta/receptor-type protein tyrosine phosphatase beta (PTPzeta/RPTPbeta) and its ligand pleiotrophin (PTN) as overexpressed in human glioblastomas compared to normal brain. Both molecules have been implicated in neuronal migration during central nervous system development, and PTN is known to be involved in tumor growth and angiogenesis. We confirm overexpression of both molecules at the protein level in astrocytic gliomas of different malignancy grades. PTPzeta/RPTPbeta immunoreactivity was associated with increasing malignancy grade and localized predominantly to the tumor cells. PTN immunoreactivity as determined by ELISA and immunohistochemistry analysis was increased in low-grade astrocytomas compared to normal brain. Further increase in malignant gliomas was marginal, and thus no correlation with malignancy grade or microvessel density was present. However, PTN levels were significantly associated with those of fibroblast growth factor-2, suggesting co-regulation of both factors. Functionally, PTN induced weak chemotactic and strong haptotactic migration of glioblastoma and cerebral microvascular endothelial cells. Haptotaxis of glioblastoma cells towards PTN was specifically inhibited by an anti-PTPzeta/RPTPbeta antibody. Our findings suggest that upregulated expression of PTN and PTPzeta/RPTPbeta in human astrocytic tumor cells can create an autocrine loop that is important for glioma cell migration. Although PTN is a secreted growth factor, it appears to exert its mitogenic effects mostly in a matrix-immobilized form, serving as a substrate for migrating tumor cells.

  5. The sarin-like organophosphorus agent bis(isopropyl methyl)phosphonate induces ER stress in human astrocytoma cells.

    PubMed

    Arima, Yosuke; Shiraishi, Hiroaki; Saito, Atsushi; Yoshimoto, Kanji; Namera, Akira; Makita, Ryosuke; Murata, Kazuhiro; Imaizumi, Kazunori; Nagao, Masataka

    2016-01-01

    Organophosphorus (OP) compounds such as sarin are toxic agents that irreversibly inhibit the enzyme acetylcholinesterase. A recent study showed that OP compounds also have multiple toxicity mechanisms, and another suggested that endoplasmic reticulum (ER) dysfunction contributes to OP toxicity. However, the signaling pathway and mechanisms involved are poorly understood. We examined whether the sarin-like OP agent bis(isopropyl methyl)phosphonate (BIMP), which exhibits toxicity similar to that of sarin, induced ER stress in human astrocytoma CCF-STTG1 cells. Our results demonstrate that BIMP exposure reduced cell viability. Moreover, it induced changes in mitochondrial membrane potential and increased cleavage of caspase 3. Treatment with BIMP increased the mRNA levels of the ER stress marker genes binding immunoglobulin protein (BiP) and the transcription factor C/EBP homologous protein (CHOP). Furthermore, BIMP increased the protein expressions and phosphorylation of BiP, CHOP, and protein kinase RNA-like ER kinase and the phosphorylation of eukaryotic translation initiation factor 2. Compared to BIMP treatment alone, pretreatment with the CHOP siRNA, siCHOP, decreased BIMP-dependent CHOP expression and improved CCF-STTG1 cell viability. Our findings suggest that BIMP induced mitochondrial dysfunction and apoptotic cell death event mediated by ER stress in CCF-STTG1 cells and that treatment targeted at managing ER stress has the potential to attenuate the toxicity of OP nerve agents. PMID:27665771

  6. DIFFUSION PUMP

    DOEpatents

    Levenson, L.

    1963-09-01

    A high-vacuum diffusion pump is described, featuring a novel housing geometry for enhancing pumping speed. An upright, cylindrical lower housing portion is surmounted by a concentric, upright, cylindrical upper housing portion of substantially larger diameter; an uppermost nozzle, disposed concentrically within the upper portion, is adapted to eject downwardly a conical sheet of liquid outwardly to impinge upon the uppermost extremity of the interior wall of the lower portion. Preferably this nozzle is mounted upon a pedestal rising coaxially from within the lower portion and projecting up into said upper portion. (AEC)

  7. Adult Books for Young Adults.

    ERIC Educational Resources Information Center

    Carter, Betty

    1997-01-01

    Considers the differences between young adult and adult books and maintains that teachers must be familiar with young adults' tastes for both. Suggests that traffic between these publishing divisions is a two-way street, with young adults reading adult books and adults reading young adult books. (TB)

  8. Extracellular matrix glycoproteins and diffusion barriers in human astrocytic tumours.

    PubMed

    Zámecník, J; Vargová, L; Homola, A; Kodet, R; Syková, E

    2004-08-01

    The extracellular matrix (ECM) and changes in the size and geometry of the extracellular space (ECS) in tumour tissue are thought to be of critical importance in influencing the migratory abilities of tumour cells as well as the delivery of therapeutic agents into the tumour. In 21 astrocytic neoplasms, the ECM composition was investigated in situ by the immunohistochemical detection of ECM glycoproteins (tenascin, laminin, vitronectin, fibronectin, collagen types I-VI). To explain the changes in ECS size and to detect barriers to diffusion in the tumour tissue, the ECM composition, the cellularity, the density of glial fibrillary acidic protein (GFAP)-positive tumour cell processes and the proliferative activity of the tumours were compared with the size and geometry of the ECS. The ECS volume fraction and the complex of hindrances to diffusion in the ECS (i.e. the tortuosity) were revealed by the real-time iontophoretic tetramethylammonium method. Increased proliferative activity of the tumours correlated with increased ECS volume fraction and tortuosity. The tortuosity of the tumour tissue was not significantly influenced by tumour cell density. Higher tortuosity was found in low-grade astrocytomas associated with the presence of a dense net of GFAP-positive fibrillary processes of the tumour cells. The increase in tortuosity in high-grade tumours correlated with an increased accumulation of ECM molecules, particularly of tenascin. We conclude that the increased malignancy of astrocytic tumours correlates with increases in both ECS volume and ECM deposition.

  9. Subependymal giant cell astrocytoma: a lesion with activated mTOR pathway and constant expression of glutamine synthetase.

    PubMed

    Buccoliero, Anna Maria; Caporalini, Chiara; Giordano, Flavio; Mussa, Federico; Scagnet, Mirko; Moscardi, Selene; Baroni, Gianna; Genitori, Lorenzo; Taddei, Gian Luigi

    2016-01-01

    Subependymal giant-cell astrocytoma (SEGA) is a rare tumor associated with tuberous sclerosis complex (TSC). TSC mainly involves the central nervous system (CNS) where SEGA, subependymal nodules, and cortical tubers may be present. First studies suggested the astrocytic nature of SEGA while successive studies demonstrated the mixed glio-neuronal nature. There are similarities between TSC-associated CNS lesions and type IIb focal cortical dysplasia (FCD). In all these pathologies, mammalian target of rapamycin (mTOR) pathway activation has been demonstrated. Recent data evidenced that balloon cells in FCD IIb express glutamine synthetase (GS). GS is involved in the clearance of glutamate. Cells expressing GS might exert an antiepileptic role. We evaluated by immunohistochemistry the glial fibrillary acidic protein (GFAP), neurofilaments (NF), and GS expression and the mTOR status (mTOR and phosphorylated ribosomal protein S6) in 16 SEGAs and 2 cortical tubers. Our purpose was to emphasize the mixed nature of SEGA and to further investigate the similarities between TSC-related CNS lesions (in particular SEGA) and FCD IIb. We confirm the glio-neuronal nature and the common activation of the mTOR pathway in SEGAs. In addition, we report for the first time that these tumors, analogously to FCD IIb, commonly express GS. Notably, the expression of mTOR, phosphorylated ribosomal protein S6, and GS was restricted to gemistocytic-like GFAP-negative cells. GS expression and mTOR pathway activation were also documented in cortical tubers. Further studies are necessary to understand the significance of GS expression in SEGAs as well as in cortical tubers. PMID:27390104

  10. Subependymal giant cell astrocytoma: a lesion with activated mTOR pathway and constant expression of glutamine synthetase.

    PubMed

    Buccoliero, Anna Maria; Caporalini, Chiara; Giordano, Flavio; Mussa, Federico; Scagnet, Mirko; Moscardi, Selene; Baroni, Gianna; Genitori, Lorenzo; Taddei, Gian Luigi

    2016-01-01

    Subependymal giant-cell astrocytoma (SEGA) is a rare tumor associated with tuberous sclerosis complex (TSC). TSC mainly involves the central nervous system (CNS) where SEGA, subependymal nodules, and cortical tubers may be present. First studies suggested the astrocytic nature of SEGA while successive studies demonstrated the mixed glio-neuronal nature. There are similarities between TSC-associated CNS lesions and type IIb focal cortical dysplasia (FCD). In all these pathologies, mammalian target of rapamycin (mTOR) pathway activation has been demonstrated. Recent data evidenced that balloon cells in FCD IIb express glutamine synthetase (GS). GS is involved in the clearance of glutamate. Cells expressing GS might exert an antiepileptic role. We evaluated by immunohistochemistry the glial fibrillary acidic protein (GFAP), neurofilaments (NF), and GS expression and the mTOR status (mTOR and phosphorylated ribosomal protein S6) in 16 SEGAs and 2 cortical tubers. Our purpose was to emphasize the mixed nature of SEGA and to further investigate the similarities between TSC-related CNS lesions (in particular SEGA) and FCD IIb. We confirm the glio-neuronal nature and the common activation of the mTOR pathway in SEGAs. In addition, we report for the first time that these tumors, analogously to FCD IIb, commonly express GS. Notably, the expression of mTOR, phosphorylated ribosomal protein S6, and GS was restricted to gemistocytic-like GFAP-negative cells. GS expression and mTOR pathway activation were also documented in cortical tubers. Further studies are necessary to understand the significance of GS expression in SEGAs as well as in cortical tubers.

  11. Emotional Functioning and School Contentment in Adolescent Survivors of Acute Myeloid Leukemia, Infratentorial Astrocytoma, and Wilms Tumor.

    PubMed

    Jóhannsdóttir, Inga M; Moum, Torbjørn; Hjermstad, Marianne J; Wesenberg, Finn; Hjorth, Lars; Schrøder, Henrik; Lähteenmäki, Päivi M; Jónmundsson, Gudmundur; Loge, Jon H

    2011-09-01

    Purpose: Cancer in childhood may disrupt normal developmental processes and cause psychosocial problems in adolescent survivors of childhood cancers (ACCSs). Previous studies report inconsistent findings. Study aims were to assess subjective well-being (SWB), psychological distress, and school contentment in survivors of three dissimilar childhood cancers. Patients and methods: Nordic patients treated for acute myeloid leukemia (AML), infratentorial astrocytoma (IA), and Wilms tumor (WT) in childhood from 1985 to 2001, aged ≥1 year at diagnosis, and aged 13-18 years at the time of study were eligible for this questionnaire-based survey that included items on SWB, psychological distress, school contentment, self-esteem, and personality traits; 65% (151/231) responded. An age-equivalent group from a Norwegian health survey (n=7910) served as controls. Results: The median age of ACCSs was 16 years; 52% were males. ACCSs reported better SWB (p=0.004) and self-esteem (p<0.001). They had fewer social problems in school (p=0.004) and their school contentment tended to be higher than controls. SWB and school contentment were positively influenced by self-esteem. However, ACCSs reported higher levels of psychological distress (p=0.002), mostly attributable to general worrying. No significant differences in outcomes were found across diagnoses, and time since diagnosis did not significantly affect the results. Conclusion: The overall emotional functioning of ACCSs was good, possibly due to changes in their perception of well-being after having survived a life-threatening disease. However, they seemed more worried than their peers. This may cause an additional strain at a vulnerable period in life.

  12. Screening genes crucial for pediatric pilocytic astrocytoma using weighted gene coexpression network analysis combined with methylation data analysis.

    PubMed

    Zhao, H; Cai, W; Su, S; Zhi, D; Lu, J; Liu, S

    2014-10-01

    To identify novel genes associated with pediatric pilocytic astrocytoma (PA) for better understanding the molecular mechanism underlying the pediatric PA pathogenesis. Gene expression profile data of GSE50161 and GSE44971 and the methylation data of GSE44684 were downloaded from Gene Expression Omnibus. The differentially expressed genes (DEGs) between PA and normal control samples were screened using the limma package in R, and then used to construct weighted gene coexpression network (WGCN) using the WGCN analysis (WGCNA) package in R. Significant modules of DEGs were selected using the clustering analysis. Function enrichment analysis of the DEGs in significant modules were performed using the WGCNA package and clusterprofiler package in R. Correlation between methylation sites of DEGs and PA was analyzed using the CpGassoc package in R. Totally, 3479 DEGs were screened in PA samples. Thereinto, 3424 DEGs were used to construct the WGCN. Several significant modules of DEGs were selected based on the WGCN, in which the turquoise module was positively related to PA, whereas blue module was negatively related to PA. DEGs (for example, DOCK2 (dedicator of cytokinesis 2), DOCK8 and FCGR2A (Fc fragment of IgG, low affinity IIa)) in blue module were mainly involved in Fc gamma R-mediated phagocytosis pathway and natural killer cell-mediated cytotoxicity pathway. Methylations of 14 DEGs among the top 30 genes in blue module were related to PA. Our data suggest that DOCK2, DOCK8 and FCGR2A may represent potential therapeutic targets in PA that merits further investigation. PMID:25257306

  13. Screening genes crucial for pediatric pilocytic astrocytoma using weighted gene coexpression network analysis combined with methylation data analysis.

    PubMed

    Zhao, H; Cai, W; Su, S; Zhi, D; Lu, J; Liu, S

    2014-10-01

    To identify novel genes associated with pediatric pilocytic astrocytoma (PA) for better understanding the molecular mechanism underlying the pediatric PA pathogenesis. Gene expression profile data of GSE50161 and GSE44971 and the methylation data of GSE44684 were downloaded from Gene Expression Omnibus. The differentially expressed genes (DEGs) between PA and normal control samples were screened using the limma package in R, and then used to construct weighted gene coexpression network (WGCN) using the WGCN analysis (WGCNA) package in R. Significant modules of DEGs were selected using the clustering analysis. Function enrichment analysis of the DEGs in significant modules were performed using the WGCNA package and clusterprofiler package in R. Correlation between methylation sites of DEGs and PA was analyzed using the CpGassoc package in R. Totally, 3479 DEGs were screened in PA samples. Thereinto, 3424 DEGs were used to construct the WGCN. Several significant modules of DEGs were selected based on the WGCN, in which the turquoise module was positively related to PA, whereas blue module was negatively related to PA. DEGs (for example, DOCK2 (dedicator of cytokinesis 2), DOCK8 and FCGR2A (Fc fragment of IgG, low affinity IIa)) in blue module were mainly involved in Fc gamma R-mediated phagocytosis pathway and natural killer cell-mediated cytotoxicity pathway. Methylations of 14 DEGs among the top 30 genes in blue module were related to PA. Our data suggest that DOCK2, DOCK8 and FCGR2A may represent potential therapeutic targets in PA that merits further investigation.

  14. Diffuse anaplastic leptomeningeal oligodendrogliomatosis mimicking neurosarcoidosis.

    PubMed

    Leep Hunderfund, Andrea N; Zabad, Rana K; Aksamit, Allen J; Morris, Jonathan M; Meyer, Fredric B; Thorell, William E; Parisi, Joseph E; Giannini, Caterina

    2013-06-01

    Diffuse leptomeningeal oligodendrogliomatosis is a rare, frequently fatal CNS malignancy that most often affects children.(1) Although potentially treatable with chemotherapy and radiation, the radiologic findings are nonspecific and pathologic confirmation of the diagnosis is difficult. We describe an adult patient whose initial presentation mimicked neurosarcoidosis. Despite extensive imaging abnormalities, 3 biopsies were required before the diagnosis of diffuse leptomeningeal oligodendrogliomatosis was confirmed. PMID:23914328

  15. NIST Diffusion Data Center

    National Institute of Standards and Technology Data Gateway

    NIST Diffusion Data Center (Web, free access)   The NIST Diffusion Data Center is a collection of over 14,100 international papers, theses, and government reports on diffusion published before 1980.

  16. Parallel flow diffusion battery

    DOEpatents

    Yeh, H.C.; Cheng, Y.S.

    1984-01-01

    A parallel flow diffusion battery for determining the mass distribution of an aerosol has a plurality of diffusion cells mounted in parallel to an aerosol stream, each diffusion cell including a stack of mesh wire screens of different density.

  17. Parallel flow diffusion battery

    DOEpatents

    Yeh, Hsu-Chi; Cheng, Yung-Sung

    1984-08-07

    A parallel flow diffusion battery for determining the mass distribution of an aerosol has a plurality of diffusion cells mounted in parallel to an aerosol stream, each diffusion cell including a stack of mesh wire screens of different density.

  18. Decreased survival of glioma patients with astrocytoma grade IV (glioblastoma multiforme) associated with long-term use of mobile and cordless phones.

    PubMed

    Carlberg, Michael; Hardell, Lennart

    2014-10-16

    On 31 May 2011 the WHO International Agency for Research on Cancer (IARC) categorised radiofrequency electromagnetic fields (RF-EMFs) from mobile phones, and from other devices that emit similar non-ionising electromagnetic fields, as a Group 2B, i.e., a "possible", human carcinogen. A causal association would be strengthened if it could be shown that the use of wireless phones has an impact on the survival of glioma patients. We analysed survival of 1678 glioma patients in our 1997-2003 and 2007-2009 case-control studies. Use of wireless phones in the >20 years latency group (time since first use) yielded an increased hazard ratio (HR) = 1.7, 95% confidence interval (CI) = 1.2-2.3 for glioma. For astrocytoma grade IV (glioblastoma multiforme; n = 926) mobile phone use yielded HR = 2.0, 95% CI = 1.4-2.9 and cordless phone use HR = 3.4, 95% CI = 1.04-11 in the same latency category. The hazard ratio for astrocytoma grade IV increased statistically significant per year of latency for wireless phones, HR = 1.020, 95% CI = 1.007-1.033, but not per 100 h cumulative use, HR = 1.002, 95% CI = 0.999-1.005. HR was not statistically significant increased for other types of glioma. Due to the relationship with survival the classification of IARC is strengthened and RF-EMF should be regarded as human carcinogen requiring urgent revision of current exposure guidelines.

  19. LPS induces mediators of neuroinflammation, cell proliferation, and GFAP expression in human astrocytoma cells U373MG: the anti-inflammatory and anti-proliferative effect of guggulipid.

    PubMed

    Niranjan, Rituraj; Nagarajan, Rajasekar; Hanif, Kashif; Nath, Chandishwar; Shukla, Rakesh

    2014-03-01

    Neuroinflammation has been considered to be an integrated part of human neurodegenerative diseases. In this study, we examined the effect of guggulipid on cell proliferation, nitrite release, interleukin IL-6 and IL-1 beta release, and expression of COX-2 and glial fibrillary acidic protein (GFAP) in LPS-stimulated U373MG cells. LPS significantly stimulated human astrocytoma cells U373MG by up-regulating these neuroinflammatory mediators. Guggulipid alone had no effect on the cell proliferation of U373MG cells. The up regulation in nitrite release, cell proliferation, and release of IL-6 and IL-1 beta in LPS stimulated human astrocytoma cells were dose-dependently inhibited by co-treatment with guggulipid. The expression level of COX-2 and GFAP proteins was up regulated by LPS but the increased level of COX-2 and GFAP was significantly down regulated by treatment with guggulipid. These data indicate that guggulipid has a modulatory effect on all these parameters, which might explain its beneficial effect in the treatment of neuroinflammation-associated disorders directly relating to human aspects.

  20. Predominant role of plasma membrane monoamine transporters in monoamine transport in 1321N1, a human astrocytoma-derived cell line.

    PubMed

    Naganuma, Fumito; Yoshikawa, Takeo; Nakamura, Tadaho; Iida, Tomomitsu; Harada, Ryuichi; Mohsen, Attayeb S; Miura, Yamato; Yanai, Kazuhiko

    2014-05-01

    Monoamine neurotransmitters should be immediately removed from the synaptic cleft to avoid excessive neuronal activity. Recent studies have shown that astrocytes and neurons are involved in monoamine removal. However, the mechanism of monoamine transport by astrocytes is not entirely clear. We aimed to elucidate the transporters responsible for monoamine transport in 1321N1, a human astrocytoma-derived cell line. First, we confirmed that 1321N1 cells transported dopamine, serotonin, norepinephrine, and histamine in a time- and dose-dependent manner. Kinetics analysis suggested the involvement of low-affinity monoamine transporters, such as organic cation transporter (OCT) 2 and 3 and plasma membrane monoamine transporter (PMAT). Monoamine transport in 1321N1 cells was not Na(+) /Cl(-) dependent but was inhibited by decynium-22, an inhibitor of low-affinity monoamine transporters, which supported the importance of low-affinity transporters. RT-PCR assays revealed that 1321N1 cells expressed OCT3 and PMAT but no other neurotransmitter transporters. Another human astrocytoma-derived cell line, U251MG, and primary human astrocytes also exhibited the same gene expression pattern. Gene-knockdown assays revealed that 1321N1 and primary human astrocytes could transport monoamines predominantly through PMAT and partly through OCT3. These results might indicate that PMAT and OCT3 in human astrocytes are involved in monoamine clearance.

  1. Homozygous loss of ADAM3A revealed by genome-wide analysis of pediatric high-grade glioma and diffuse intrinsic pontine gliomas

    PubMed Central

    Barrow, Jennifer; Adamowicz-Brice, Martyna; Cartmill, Maria; MacArthur, Donald; Lowe, James; Robson, Keith; Brundler, Marie-Anne; Walker, David A.; Coyle, Beth; Grundy, Richard

    2011-01-01

    Overall, pediatric high-grade glioma (pHGG) has a poor prognosis, in part due to the lack of understanding of the underlying biology. High-resolution 244 K oligo array comparative genomic hybridization (CGH) was used to analyze DNA from 38 formalin-fixed paraffin-embedded predominantly pretreatment pHGG samples, including 13 diffuse intrinsic pontine gliomas (DIPGs). The patterns of gains and losses were distinct from those seen in HGG arising in adults. In particular, we found 1q gain in up to 27% of our cohort compared with 9% reported in adults. A total of 13% had a balanced genetic profile with no large-scale copy number alterations. Homozygous loss at 8p12 was seen in 6 of 38 (16%) cases of pHGG. This novel deletion, which includes the ADAM3A gene, was confirmed by quantitative real-time PCR (qPCR). Loss of CDKN2A/CDKN2B in 4 of 38 (10%) samples by oligo array CGH was confirmed by fluorescent in situ hybridization on tissue microarrays and was restricted to supratentorial tumors. Only ∼50% of supratentorial tumors were positive for CDKN2B expression by immunohistochemistry (IHC), while ∼75% of infratentorial tumors were positive for CDKN2B expression (P = 0.03). Amplification of the 4q11–13 region was detected in 8% of cases and included PDGFRA and KIT, and subsequent qPCR analysis was consistent with the amplification of PDGFRA. MYCN amplification was seen in 5% of samples being significantly associated with anaplastic astrocytomas (P= 0.03). Overall, DIPG shared similar spectrum of changes to supratentorial HGG with some notable differences, including high-frequency loss of 17p and 14q and lack of CDKN2A/CDKN2B deletion. Informative genetic data providing insight into the underlying biology and potential therapeutic possibilities can be generated from archival tissue and typically small biopsies from DIPG. Our findings highlight the importance of obtaining pretreatment samples. PMID:21138945

  2. Diffusing Diffusivity: A Model for Anomalous, yet Brownian, Diffusion

    NASA Astrophysics Data System (ADS)

    Chubynsky, Mykyta V.; Slater, Gary W.

    2014-08-01

    Wang et al. [Proc. Natl. Acad. Sci. U.S.A. 106, 15160 (2009)] have found that in several systems the linear time dependence of the mean-square displacement (MSD) of diffusing colloidal particles, typical of normal diffusion, is accompanied by a non-Gaussian displacement distribution G(x ,t), with roughly exponential tails at short times, a situation they termed "anomalous yet Brownian" diffusion. The diversity of systems in which this is observed calls for a generic model. We present such a model where there is diffusivity memory but no direction memory in the particle trajectory, and we show that it leads to both a linear MSD and a non-Gaussian G(x ,t) at short times. In our model, the diffusivity is undergoing a (perhaps biased) random walk, hence the expression "diffusing diffusivity". G(x ,t) is predicted to be exactly exponential at short times if the distribution of diffusivities is itself exponential, but an exponential remains a good fit for a variety of diffusivity distributions. Moreover, our generic model can be modified to produce subdiffusion.

  3. Superoxide anion radical (O2(-)) degrades methylmercury to inorganic mercury in human astrocytoma cell line (CCF-STTG1).

    PubMed

    Mailloux, Ryan J; Yumvihoze, Emmanuel; Chan, Hing Man

    2015-09-01

    Methylmercury (MeHg) is a global pollutant that is affecting the health of millions of people worldwide. However, the mechanism of MeHg toxicity still remains somewhat elusive and there is no treatment. It has been known for some time that MeHg can be progressively converted to inorganic mercury (iHg) in various tissues including the brain. Recent work has suggested that cleavage of the carbon-metal bond in MeHg in a biological environment is facilitated by reactive oxygen species (ROS). However, the oxyradical species that actually mediates this process has not been identified. Here, we provide evidence that superoxide anion radical (O2(-)) can convert MeHg to iHg. The calculated second-order rate constant for the degradation of 1μM MeHg by O2(-) generated by xanthine/xanthine oxidase was calculated to be 2×10(5)M(-1)s(-1). We were also able to show that this bioconversion can proceed in intact CCF-STTG1 human astrocytoma cells exposed to paraquat (PQ), a O2(-) generating viologen. Notably, exposure of cells to increasing amounts of PQ led to a dose dependent increase in both MeHg and iHg. Indeed, a 24h exposure to 500μM PQ induced a ∼13-fold and ∼18-fold increase in intracellular MeHg and iHg respectively. These effects were inhibited by superoxide dismutase mimetic MnTBAP. In addition, we also observed that a 24h exposure to a biologically relevant concentration of MeHg (1μM) did not induce cell death, oxidative stress, or even changes in cellular O2(-) and H2O2. However, co-exposure to PQ enhanced MeHg toxicity which was associated with a robust increase in cell death and oxidative stress. Collectively our results show that O2(-) can bioconvert MeHg to iHg in vitro and in intact cells exposed to conditions that simulate high intracellular O2(-) production. In addition, we show for the first time that O2(-) mediated degradation of MeHg to iHg enhances the toxicity of MeHg by facilitating an accumulation of both MeHg and iHg in the intracellular

  4. Prognostic value of the extent of resection in supratentorial WHO grade II astrocytomas stratified for IDH1 mutation status: a single-center volumetric analysis.

    PubMed

    Jungk, Christine; Scherer, Moritz; Mock, Andreas; Capper, David; Radbruch, Alexander; von Deimling, Andreas; Bendszus, Martin; Herold-Mende, Christel; Unterberg, Andreas

    2016-09-01

    Current evidence supports a maximized extent of resection (EOR) in low-grade gliomas (LGG), regardless of different histological subtypes and molecular markers. We therefore evaluated the prognostic impact of extensive, mainly intraoperative (i)MRI-guided surgery in low-grade astrocytomas stratified for IDH1 mutation status. Retrospective assessment of 46 consecutive cases of newly diagnosed supratentorial WHO grade II astrocytomas treated during the last decade was performed. IDH1 mutation status was obtained for all patients. Volumetric analysis of tumor volumes was performed pre-, intra-, early postoperatively and at first follow-up. Survival analysis was conducted with uni-and multivariate regression models implementing clinical parameters and continuous volumetric variables. Median EOR was 90.4 % (range 17.5-100 %) and was increased to 94.9 % (range 34.8-100 %) in iMRI-guided resections (n = 33). A greater EOR was prognostic for increased progression-free survival (HR 0.23, p = 0.031) and time to re-intervention (TTR) (HR 0.23, p = 0.03). In IDH1 mutant patients, smaller residual tumor volumes were associated with increased TTR (HR 1.01, p = 0.03). IDH1 mutation (38/46 cases) was an independent positive prognosticator for overall survival (OS) in multivariate analysis (HR 0.09, p = 0.002), while extensive surgery had limited impact upon OS. In a subgroup of patients with ≥40 % EOR (n = 39), however, initial and residual tumor volumes were prognostic for OS (HR 1.03, p = 0.005 and HR 1.08, p = 0.007, respectively), persistent to adjustment for IDH1. No association between EOR and neurologic morbidity was found. In this analysis of low-grade astrocytomas stratified for IDH1, extensive tumor resections were prognostic for progression and TTR and, in patients with ≥40 % EOR, for OS. PMID:27344556

  5. Effect of retinoic acid and ethanol on retinoic acid receptor beta and glial fibrillary acidic protein mRNA expression in human astrocytoma cells.

    PubMed

    Grummer, M A; Salih, Z N; Zachman, R D

    2000-11-17

    This work explores the hypothesis that perturbations caused by ethanol on the regulatory role of retinoids in brain development may be a mechanism involved in the neuropathology of fetal alcohol syndrome. The interaction of ethanol and retinoic acid (RA) on RA receptor (RAR) beta and glial fibrillary acidic protein (GFAP) mRNA expression is evaluated. In the U-373 MG astrocytoma, mRNA expression of RAR beta was increased and GFAP was decreased by RA. Ethanol decreased the expression of RAR beta mRNA, but increased that of GFAP. The RA-stimulated increase in RAR beta was not affected by the presence of ethanol. RA prevented the ethanol-induced increase in GFAP mRNA. Cycloheximide abolished only the GFAP response to ethanol. This work shows that an interrelationship between ethanol and RA exists in the astrocyte. PMID:11058790

  6. Effects of La0.2Ce0.6Eu0.2F3 nanoparticles capped with polyethylene glycol on human astrocytoma cells in vitro

    NASA Astrophysics Data System (ADS)

    Withers, Nathan J.; Brandt, Yekaterina; Rivera, Antonio C.; Armijo, Leisha M.; Cook, Nathaniel C.; Osiński, Marek

    2012-03-01

    Lanthanide fluoride colloidal nanocrystals offer a way to improve the diagnosis and treatment of cancer through the enhanced absorption of ionizing radiation, as well as providing visible luminescence. In order to explore this possibility, cytotoxicity assays need to be performed on mammalian cells in vitro, to show minimum levels of biocompatibility for future experiments. 20% lanthanum 60% cerium and 20% europium lanthanide fluoride nanocrystals were capped with polyethylene glycol (PEG) of molecular weight 4000 and suspended in deionized water. These nanocrystals were characterized by transmission electron microscopy, muffle furnace ashing, absorbance spectroscopy, dynamic light scattering, and photoluminescence spectroscopy. Visible light microscopy and trypan blue staining was performed on the cells to assay the cytotoxicity of the nanocrystal on the human astrocytoma line U-87 MG, purchased from ATCC.

  7. Stages of Childhood Astrocytomas

    MedlinePlus

    ... before the cancer is diagnosed and continue for months or years. Signs or symptoms caused by the ... after treatment. Some cancer treatments cause side effects months or years after treatment has ended. Side effects ...

  8. Microfabricated diffusion source

    DOEpatents

    Oborny, Michael C.; Frye-Mason, Gregory C.; Manginell, Ronald P.

    2008-07-15

    A microfabricated diffusion source to provide for a controlled diffusion rate of a vapor comprises a porous reservoir formed in a substrate that can be filled with a liquid, a headspace cavity for evaporation of the vapor therein, a diffusion channel to provide a controlled diffusion of the vapor, and an outlet to release the vapor into a gas stream. The microfabricated diffusion source can provide a calibration standard for a microanalytical system. The microanalytical system with an integral diffusion source can be fabricated with microelectromechanical systems technologies.

  9. Cytosolic phospholipase A2 is coupled to muscarinic receptors in the human astrocytoma cell line 1321N1: characterization of the transducing mechanism.

    PubMed Central

    Bayon, Y; Hernandez, M; Alonso, A; Nuñez, L; Garcia-Sancho, J; Leslie, C; Sanchez Crespo, M; Nieto, M L

    1997-01-01

    The cholinergic agonist carbachol induced the release of arachidonic acid in the 1321N1 astrocytoma cell line, and this was blocked by atropine, suggesting the involvement of muscarinic receptors. To assess the mechanisms of signalling involved in the response to carbachol, a set of compounds characterized by eliciting responses through different mechanisms was tested. A combination of 4beta-phorbol 12beta-myristate 13alpha-acetate and thapsigargin, an inhibitor of endomembrane Ca2+-ATPase that induces a prolonged elevation of cytosolic Ca2+ concentration, induced an optimal response, suggesting at first glance that both protein kinase C (PKC) and Ca2+ mobilization were involved in the response. This was consistent with the observation that carbachol elicited Ca2+ mobilization and PKC-dependent phosphorylation of cytosolic phospholipase A2 (cPLA2; phosphatide sn-2-acylhydrolase, EC 3.1.1.4) as measured by a decrease in electrophoretic mobility. Nevertheless, the release of arachidonate induced by carbachol was unaltered in media containing decreased concentrations of Ca2+ or in the presence of neomycin, a potent inhibitor of phospholipase C which blocks phosphoinositide turnover and Ca2+ mobilization. Guanosine 5'-[gamma-thio]triphosphate added to the cell-free homogenate induced both [3H]arachidonate release and cPLA2 translocation to the cell membrane fraction in the absence of Ca2+, thus suggesting the existence of an alternative mechanism of cPLA2 translocation dependent on G-proteins and independent of Ca2+ mobilization. From the combination of experiments utilizing biochemical and immunological tools the involvement of cPLA2 was ascertained. In summary, these data indicate the existence in the astrocytoma cell line 1321N1 of a pathway involving the cPLA2 which couples the release of arachidonate to the occupancy of receptors for a neurotransmitter, requires PKC activity and G-proteins and might operate in the absence of Ca2+ mobilization. PMID:9173894

  10. Thrombin produces phosphorylation of cytosolic phospholipase A2 by a mitogen-activated protein kinase kinase-independent mechanism in the human astrocytoma cell line 1321N1.

    PubMed Central

    Hernández, M; Bayón, Y; Sánchez Crespo, M; Nieto, M L

    1997-01-01

    The release of [3H]arachidonic acid was studied in the 1321N1 astrocytoma cell line upon stimulation with thrombin. The effect of thrombin was antagonized by hirudin only when both compounds were added simultaneously, which suggests activation of thrombin receptor. Evidence that the cytosolic phospholipase A2 (cPLA2) takes part in thrombin-induced arachidonate release was provided by the finding that thrombin induced retardation of the mobility of cPLA2 in SDS/polyacrylamide gels, which is a feature of the activation of cPLA2 by mitogen-activated protein (MAP) kinases. Thrombin induced activation of two members of the MAP kinase family whose consensus primary sequence appears in cPLA2, namely p42-MAP kinase and c-Jun kinase. However, the activation of c-Jun kinase preceded the phosphorylation of cPLA2 more clearly than the activation of p42-MAK kinase did. Both cPLA2 and c-Jun kinase activation were not affected by PD-98059, a specific inhibitor of MAP kinase kinases, which indeed completely blocked p42-MAP kinase shift. Heat shock, a well-known activator of c-Jun kinase, also phosphorylated cPLA2 but not p42-MAP kinase. These data indicate the existence in astrocytoma cells of a signalling pathway triggered by thrombin receptor stimulation that activates a kinase cascade acting on the Pro-Leu-Ser-Pro consensus primary sequence, activates cPLA2, and associates the release of arachidonate with nuclear signalling pathways. PMID:9359863

  11. Hybrid Diffusion Imaging

    PubMed Central

    Wu, Yu-Chien; Alexander, Andrew L.

    2007-01-01

    Diffusion measurements in the human central nervous system are complex to characterize and a broad spectrum of methods have been proposed. In this study, a comprehensive diffusion encoding and analysis approach, Hybrid Diffusion Imaging (HYDI), is described. The HYDI encoding scheme is composed of multiple concentric “shells” of constant diffusion-weighting, which may be used to characterize the signal behavior with low, moderate and high diffusion-weighting. HYDI facilitates the application of multiple data-analyses strategies including diffusion tensor imaging (DTI), multi-exponential diffusion measurements, diffusion spectrum imaging (DSI) and q-ball imaging (QBI). These different analysis strategies may provide complementary information. DTI measures (mean diffusivity and fractional anisotropy) may be estimated from either data in the inner shells or the entire HYDI data. Fast and slow diffusivities were estimated using a nonlinear least-squares bi-exponential fit on geometric means of the HYDI shells. DSI measurements from the entire HYDI data yield empirical model-independent diffusion information and are well-suited for characterizing tissue regions with complex diffusion behavior. DSI measurements were characterized using the zero displacement probability and the mean squared displacement. The outermost HYDI shell was analyzed using QBI analysis to estimate the orientation distribution function (ODF), which is useful for characterizing the directions of multiple fiber groups within a voxel. In this study, a HYDI encoding scheme with 102 diffusion-weighted measurements was obtained over most of the human cerebrum in under 30 minutes. PMID:17481920

  12. Diffusion bonding aeroengine components

    NASA Astrophysics Data System (ADS)

    Fitzpatrick, G. A.; Broughton, T.

    1988-10-01

    The use of diffusion bonding processes at Rolls-Royce for the manufacture of titanium-alloy aircraft engine components and structures is described. A liquid-phase diffusion bonding process called activated diffusion bonding has been developed for the manufacture of the hollow titanium wide chord fan blade. In addition, solid-state diffusion bonding is being used in the manufacture of hollow vane/blade airfoil constructions mainly in conjunction with superplastic forming and hot forming techniques.

  13. Updating applied diffusion models

    SciTech Connect

    Weil, J.C.

    1985-11-01

    Most diffusion models currently used in air quality applications are substantially out of date with understanding of turbulence and diffusion in the planetary boundary layer. Under a Cooperative Agreement with the Environmental Protection Agency, the American Meteorological Society organized a workshop to help improve the basis of such models, their physics and hopefuly their performance. Reviews and recommendations were made on models in three areas: diffusion in the convective boundary layer (CBL), diffusion in the stabe boundary layer (SBL), and model uncertainty.

  14. Diffusion Strategy Guide.

    ERIC Educational Resources Information Center

    McCutcheon, James R.; Sanders, John R.

    A methodology is presented for planning and managing the spread of educational innovations. The first portion of the guide develops a theoretical framework for diffusion which summarizes and capitalizes on the latest marketing and on the latest marketing and diffusion research findings. Major stages in the diffusion paradigm discussed include…

  15. Reduce Confusion about Diffusion.

    ERIC Educational Resources Information Center

    Hebrank, Mary R.

    1997-01-01

    Presents activities that allow students to explore the fundamental but poorly understood concept of diffusion by appealing to their kinesthetic senses first, then challenging their analytical skills as they try to deduce the mathematical principle involved. Presents a computer simulation of diffusion and discusses diffusion's limitations and…

  16. Handbook on atmospheric diffusion

    SciTech Connect

    Hanna, S.R.; Briggs, G.A.; Hosker, R.P. Jr.

    1982-01-01

    Basic meteorological concepts are covered as well as plume rise, source effects, and diffusion models. Chapters are included on cooling tower plumes and urban diffusion. Suggestions are given for calculating diffusion in special situations, such as for instantaneous releases over complex terrain, over long distances, and during times when chemical reactions or dry or wet deposition are important. (PSB)

  17. Li diffusion in zircon

    NASA Astrophysics Data System (ADS)

    Cherniak, D. J.; Watson, E. B.

    2010-09-01

    Diffusion of Li under anhydrous conditions at 1 atm and under fluid-present elevated pressure (1.0-1.2 GPa) conditions has been measured in natural zircon. The source of diffusant for 1-atm experiments was ground natural spodumene, which was sealed under vacuum in silica glass capsules with polished slabs of zircon. An experiment using a Dy-bearing source was also conducted to evaluate possible rate-limiting effects on Li diffusion of slow-diffusing REE+3 that might provide charge balance. Diffusion experiments performed in the presence of H2O-CO2 fluid were run in a piston-cylinder apparatus, using a source consisting of a powdered mixture of spodumene, quartz and zircon with oxalic acid added to produce H2O-CO2 fluid. Nuclear reaction analysis (NRA) with the resonant nuclear reaction 7Li(p,γ)8Be was used to measure diffusion profiles for the experiments. The following Arrhenius parameters were obtained for Li diffusion normal to the c-axis over the temperature range 703-1.151°C at 1 atm for experiments run with the spodumene source: D_{text{Li}} = 7.17 × 10^{ - 7} { exp }( - 275 ± 11 {text{kJmol}}^{ - 1} /{text{RT}}){text{m}}2 {text{s}}^{ - 1}. Diffusivities are similar for transport parallel to the c-axis, indicating little anisotropy for Li diffusion in zircon. Similar Li diffusivities were also found for experiments run under fluid-present conditions and for the experiment run with the Dy-bearing source. Li diffusion is considerably faster than diffusion of other cations in zircon, with a smaller activation energy for diffusion. Although Li diffusion in zircon is comparatively rapid, zircons will be moderately retentive of Li signatures at mid-crustal metamorphic temperatures, but they are unlikely to retain this information for geologically significant times under high-grade metamorphism.

  18. Adult immunization

    PubMed Central

    Mehta, Bharti; Chawla, Sumit; Kumar Dharma, Vijay; Jindal, Harashish; Bhatt, Bhumika

    2014-01-01

    Vaccination is recommended throughout life to prevent vaccine-preventable diseases and their sequel. The primary focus of vaccination programs has historically been directed to childhood immunizations. For adults, chronic diseases have been the primary focus of preventive and medical health care, though there has been increased emphasis on preventing infectious diseases. Adult vaccination coverage, however, remains low for most of the routinely recommended vaccines. Though adults are less susceptible to fall prey to traditional infectious agents, the probability of exposure to infectious agents has increased manifold owing to globalization and increasing travel opportunities both within and across the countries. Thus, there is an urgent need to address the problem of adult immunization. The adult immunization enterprise is more complex, encompassing a wide variety of vaccines and a very diverse target population. There is no coordinated public health infrastructure to support an adult immunization program as there is for children. Moreover, there is little coordination among adult healthcare providers in terms of vaccine provision. Substantial improvement in adult vaccination is needed to reduce the health consequences of vaccine-preventable diseases among adults. Routine assessment of adult patient vaccination needs, recommendation, and offer of needed vaccines for adults should be incorporated into routine clinical care of adults. PMID:24128707

  19. Effect of new hybrids based on 5,16-pregnadiene scaffold linked to an anti-inflammatory drug on the growth of a human astrocytoma cell line (U373).

    PubMed

    Garrido, Mariana; González-Arenas, Aliesha; Camacho-Arroyo, Ignacio; Cabeza, Marisa; Alcaraz, Belén; Bratoeff, Eugene

    2015-03-26

    In spite of the fact that anaplastic astrocytoma is an uncommon disease, very often the pathology of this disease is associated with lethal effects due to the late diagnosis and unspecific treatments. This paper reports the synthesis and the biological effect on the growth of U373 cell line (human anaplastic astrocytoma) of new hybrid compounds based on 5,16-pregnadiene scaffold linked to an anti-inflammatory drug (6a-e). Moreover, we also determined the cell growth effect of five non-steroidal anti-inflammatory drugs (naproxen, ibuprofen, ketoprofen, indomethacin and sulindac) as well as the free steroidal alcohol 5. The results from this study indicated that sulindac as well as compound 5 decreased the number of U373 cells at different concentrations. However, when an anti-inflammatory drug was bound to the steroidal structure (5), the resulting compounds (6a-e) showed an enhanced biological effect with exception of hybrid 6c. Furthermore, derivative 6e (sulindac hybrid) did not allow cell growth during six days of experiment at a concentration of 10 μM. The overall data indicated that these molecules showed an anti-proliferative activity on anaplastic astrocytoma cell line. PMID:25666913

  20. Updating applied diffusion models

    SciTech Connect

    Weil, J.C.

    1985-01-01

    Most diffusion models currently used in air-quality applications are substantially out of date with understanding of turbulence and diffusion in the planetary boundary layer. Under a Cooperative Agreement with the Environmental Protection Agency, the American Meteorological Society organized a workshop to help improve the basis of such models, their physics and hopefully their performance. Reviews and recommendations were made on models in three areas: diffusion in the convective boundary layer (CBL), diffusion in the stable boundary layer (SBL), and model uncertainty. Progress has been made in all areas, but it is most significant and ready for application to practical models in the case of the CBL. This has resulted from a clear understanding of the vertical structure and diffusion in the CBL, as demonstrated by laboratory experiments, numerical simulations, and field observations. Understanding of turbulence structure and diffusion in the SBL is less complete and not yet ready for general use in applications.

  1. Radio-chemotherapy improves survival in IDH-mutant, 1p/19q non-codeleted secondary high-grade astrocytoma patients.

    PubMed

    Juratli, Tareq A; Lautenschläger, Tim; Geiger, Kathrin D; Pinzer, Thomas; Krause, Mechthild; Schackert, Gabriele; Krex, Dietmar

    2015-09-01

    Isocitrate dehydrogenase (IDH) mutations are beginning to drive decisions on therapy for glioma patients. Here we sought to determine the impact of adjuvant treatment in patients with IDH-mutant, 1p/19q non-codeleted secondary high-grade astrocytoma (sHGA) WHO grades III/IV. Clinical data of 109 sHGA patients grades III/IV, in addition to IDH mutation-, 1p/19q-codeletion- and MGMT-promoter methylation status-were retrospectively analyzed. Survival analysis in relation to adjuvant treatment modalities and molecular profiling were performed. Out of 109 patients, 88 patients (80.7 %) harbored IDH mutations, 30 patients had a 1p/19q-codeletion (27.5 %) and 69 patients (63.3 %) exhibited a methylated MGMT-promoter status. At a median follow-up of 9.8 years, 62 patients (57 %) died. The postsurgical treatment included: radio-chemotherapy (RT-CT; 54.5 %), RT alone (19.3 %), and CT alone (22.7 %). The median overall survival (OS) in the entire group was 3.4 years (1.9-6.7 years). Patients who received RT-CT had a significantly longer OS compared with those who underwent RT alone (6.5 vs. 1.2 years, HR 0.35, CI 0.32-0.51, p = 0.011). In the IDH-mutant 1p/19q non-codeleted sHGA subgroup the RT-CT cohort had a significantly longer OS in comparison to the RT cohort (6.4 vs. 1.2 years, HR 2.7, CI 1.1-6.5, p = 0.022). In the stepwise multivariable Cox model for OS of all 88 IDH-mutant sHGA patients, survival was strongly associated with only one factor, namely, adjuvant RT-CT at diagnosis of a sHGA. This retrospective long-term study demonstrates that RT and CT (mostly PCV) significantly improves progression-free and overall survival in IDH-mutant secondary high-grade astrocytoma patients, regardless of 1p/19q-codeletion status. PMID:26033545

  2. Gaseous diffusion system

    DOEpatents

    Garrett, George A.; Shacter, John

    1978-01-01

    1. A gaseous diffusion system comprising a plurality of diffusers connected in cascade to form a series of stages, each of said diffusers having a porous partition dividing it into a high pressure chamber and a low pressure chamber, and means for combining a portion of the enriched gas from a succeeding stage with a portion of the enriched gas from the low pressure chamber of each stage and feeding it into one extremity of the high pressure chamber thereof.

  3. Inpainting using airy diffusion

    NASA Astrophysics Data System (ADS)

    Lorduy Hernandez, Sara

    2015-09-01

    One inpainting procedure based on Airy diffusion is proposed, implemented via Maple and applied to some digital images. Airy diffusion is a partial differential equation with spatial derivatives of third order in contrast with the usual diffusion with spatial derivatives of second order. Airy diffusion generates the Airy semigroup in terms of the Airy functions which can be rewritten in terms of Bessel functions. The Airy diffusion can be used to smooth an image with the corresponding noise elimination via convolution. Also the Airy diffusion can be used to erase objects from an image. We build an algorithm using the Maple package ImageTools and such algorithm is tested using some images. Our results using Airy diffusion are compared with the similar results using standard diffusion. We observe that Airy diffusion generates powerful filters for image processing which could be incorporated in the usual packages for image processing such as ImageJ and Photoshop. Also is interesting to consider the possibility to incorporate the Airy filters as applications for smartphones and smart-glasses.

  4. Multicomponent diffusion revisited

    NASA Astrophysics Data System (ADS)

    Lam, S. H.

    2006-07-01

    The derivation of the multicomponent diffusion law is revisited. Following Furry [Am. J. Phys. 16, 63 (1948)], Williams [Am. J. Phys. 26, 467 (1958); Combustion Theory, 2nd ed. (Benjamin/Cummings , Menlo Park, CA,1985)] heuristically rederived the classical kinetic theory results using macroscopic equations, and pointed out that the dynamics of the mixture fluid had been assumed inviscid. This paper generalizes the derivation, shows that the inviscid assumption can easily be relaxed to add a new term to the classical diffusion law, and the thermal diffusion term can also be easily recovered. The nonuniqueness of the multicomponent diffusion coefficient matrix is emphasized and discussed.

  5. Experimental study of vortex diffusers

    SciTech Connect

    Shakerin, S.; Miller, P.L.

    1995-11-01

    This report documents experimental research performed on vortex diffusers used in ventilation and air-conditioning systems. The main objectives of the research were (1) to study the flow characteristics of isothermal jets issuing from vortex diffusers, (2) to compare the vortex diffuser`s performance with that of a conventional diffuser, and (3) to prepare a report that disseminates the results to the designers of ventilation and air-conditioning systems. The researchers considered three diffusers: a conventional round ceiling diffuser and two different styles of vortex diffusers. Overall, the vortex diffusers create slightly more induction of ambient air in comparison to the conventional diffuser.

  6. Phase II open label study of the oral vascular endothelial growth factor-receptor inhibitor PTK787/ZK222584 (vatalanib) in adult patients with refractory or relapsed diffuse large B-cell lymphoma.

    PubMed

    Brander, Danielle; Rizzieri, David; Gockerman, Jon; Diehl, Louis; Shea, Thomas Charles; Decastro, Carlos; Moore, Joseph O; Beaven, Anne

    2013-12-01

    PTK787/ZK222584 (vatalanib), an orally active inhibitor of vascular endothelial growth factor receptors (VEGFRs), was evaluated in this phase II study of 20 patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL). Patients received once-daily PTK787/ZK222584 at a target dose of 1250 mg. Eighteen patients were evaluable for response: one patient had a complete response (CR), six patients had stable disease but subsequently progressed, 10 patients had progressive disease by three cycles and one subject withdrew before response evaluation. The patient who attained a CR underwent autologous stem cell transplant and remains disease-free 76 months after study completion. There were no grade 4 toxicities. Grade 3 thrombocytopenia occurred in 20% and grade 3 hypertension occurred in 10%. There were no episodes of grade 3 proteinuria. In conclusion, PTK787/ZK222584 was well tolerated in a heavily pretreated population of patients with DLBCL, although its therapeutic potential as a single agent in DLBCL appears limited. PMID:23488610

  7. Cosmology with matter diffusion

    SciTech Connect

    Calogero, Simone; Velten, Hermano E-mail: velten@cce.ufes.br

    2013-11-01

    We construct a viable cosmological model based on velocity diffusion of matter particles. In order to ensure the conservation of the total energy-momentum tensor in the presence of diffusion, we include a cosmological scalar field φ which we identify with the dark energy component of the universe. The model is characterized by only one new degree of freedom, the diffusion parameter σ. The standard ΛCDM model can be recovered by setting σ = 0. If diffusion takes place (σ > 0) the dynamics of the matter and of the dark energy fields are coupled. We argue that the existence of a diffusion mechanism in the universe may serve as a theoretical motivation for interacting models. We constrain the background dynamics of the diffusion model with Supernovae, H(z) and BAO data. We also perform a perturbative analysis of this model in order to understand structure formation in the universe. We calculate the impact of diffusion both on the CMB spectrum, with particular attention to the integrated Sachs-Wolfe signal, and on the matter power spectrum P(k). The latter analysis places strong constraints on the magnitude of the diffusion mechanism but does not rule out the model.

  8. Speckle reducing anisotropic diffusion.

    PubMed

    Yu, Yongjian; Acton, Scott T

    2002-01-01

    This paper provides the derivation of speckle reducing anisotropic diffusion (SRAD), a diffusion method tailored to ultrasonic and radar imaging applications. SRAD is the edge-sensitive diffusion for speckled images, in the same way that conventional anisotropic diffusion is the edge-sensitive diffusion for images corrupted with additive noise. We first show that the Lee and Frost filters can be cast as partial differential equations, and then we derive SRAD by allowing edge-sensitive anisotropic diffusion within this context. Just as the Lee and Frost filters utilize the coefficient of variation in adaptive filtering, SRAD exploits the instantaneous coefficient of variation, which is shown to be a function of the local gradient magnitude and Laplacian operators. We validate the new algorithm using both synthetic and real linear scan ultrasonic imagery of the carotid artery. We also demonstrate the algorithm performance with real SAR data. The performance measures obtained by means of computer simulation of carotid artery images are compared with three existing speckle reduction schemes. In the presence of speckle noise, speckle reducing anisotropic diffusion excels over the traditional speckle removal filters and over the conventional anisotropic diffusion method in terms of mean preservation, variance reduction, and edge localization.

  9. Galactic Diffuse Emissions

    SciTech Connect

    Digel, Seth W.; /SLAC

    2007-10-25

    Interactions of cosmic rays with interstellar nucleons and photons make the Milky Way a bright, diffuse source of high-energy {gamma}-rays. Observationally, the results from EGRET, COMPTEL, and OSSE have now been extended to higher energies by ground-based experiments, with detections of diffuse emission in the Galactic center reported by H.E.S.S. in the range above 100 GeV and of diffuse emission in Cygnus by MILAGRO in the TeV range. In the range above 100 keV, INTEGRAL SPI has found that diffuse emission remains after point sources are accounted for. I will summarize current knowledge of diffuse {gamma}-ray emission from the Milky Way and review some open issues related to the diffuse emission -- some old, like the distribution of cosmic-ray sources and the origin of the 'excess' of GeV emission observed by EGRET, and some recently recognized, like the amount and distribution of molecular hydrogen not traced by CO emission -- and anticipate some of the advances that will be possible with the Large Area Telescope on GLAST. We plan to develop an accurate physical model for the diffuse emission, which will be useful for detecting and accurately characterizing emission from Galactic point sources as well as any Galactic diffuse emission from exotic processes, and for studying the unresolved extragalactic emission.

  10. Investigating Diffusion with Technology

    ERIC Educational Resources Information Center

    Miller, Jon S.; Windelborn, Augden F.

    2013-01-01

    The activities described here allow students to explore the concept of diffusion with the use of common equipment such as computers, webcams and analysis software. The procedure includes taking a series of digital pictures of a container of water with a webcam as a dye slowly diffuses. At known time points, measurements of the pixel densities…

  11. Anatomy of Particle Diffusion

    ERIC Educational Resources Information Center

    Bringuier, E.

    2009-01-01

    The paper analyses particle diffusion from a thermodynamic standpoint. The main goal of the paper is to highlight the conceptual connection between particle diffusion, which belongs to non-equilibrium statistical physics, and mechanics, which deals with particle motion, at the level of third-year university courses. We start out from the fact…

  12. BRAF Fusion Analysis in Pilocytic Astrocytomas: KIAA1549-BRAF 15-9 Fusions Are More Frequent in the Midline Than Within the Cerebellum

    PubMed Central

    Faulkner, Claire; Ellis, Hayley Patricia; Shaw, Abigail; Penman, Catherine; Palmer, Abigail; Wragg, Christopher; Greenslade, Mark; Haynes, Harry Russell; Williams, Hannah; Lowis, Stephen; White, Paul; Williams, Maggie; Capper, David; Kurian, Kathreena Mary

    2015-01-01

    Abstract Pilocytic astrocytomas (PAs) are increasingly tested for KIAA1549-BRAF fusions. We used reverse transcription polymerase chain reaction for the 3 most common KIAA1549-BRAF fusions, together with BRAF V600E and histone H3.3 K27M analyses to identify relationships of these molecular characteristics with clinical features in a cohort of 32 PA patients. In this group, the overall BRAF fusion detection rate was 24 (75%). Ten (42%) of the 24 had the 16-9 fusion, 8 (33%) had only the 15-9 fusion, and 1 (4%) of the patients had only the 16-11 fusion. In the PAs with only the 15-9 fusion, 1 PA was in the cerebellum and 7 were centered in the midline outside of the cerebellum, that is, in the hypothalamus (n = 4), optic pathways (n = 2), and brainstem (n = 1). Tumors within the cerebellum were negatively associated with fusion 15-9. Seven (22%) of the 32 patients had tumor-related deaths and 25 of the patients (78%) were alive between 2 and 14 years after initial biopsy. Age, sex, tumor location, 16-9 fusion, and 15-9 fusion were not associated with overall survival. Thus, in this small cohort, 15-9 KIAA1549-BRAF fusion was associated with midline PAs located outside of the cerebellum; these tumors, which are generally difficult to resect, are prone to recurrence. PMID:26222501

  13. BRAF Fusion Analysis in Pilocytic Astrocytomas: KIAA1549-BRAF 15-9 Fusions Are More Frequent in the Midline Than Within the Cerebellum.

    PubMed

    Faulkner, Claire; Ellis, Hayley Patricia; Shaw, Abigail; Penman, Catherine; Palmer, Abigail; Wragg, Christopher; Greenslade, Mark; Haynes, Harry Russell; Williams, Hannah; Lowis, Stephen; White, Paul; Williams, Maggie; Capper, David; Kurian, Kathreena Mary

    2015-09-01

    Pilocytic astrocytomas (PAs) are increasingly tested for KIAA1549-BRAF fusions. We used reverse transcription polymerase chain reaction for the 3 most common KIAA1549-BRAF fusions, together with BRAF V600E and histone H3.3 K27M analyses to identify relationships of these molecular characteristics with clinical features in a cohort of 32 PA patients. In this group, the overall BRAF fusion detection rate was 24 (75%). Ten (42%) of the 24 had the 16-9 fusion, 8 (33%) had only the 15-9 fusion, and 1 (4%) of the patients had only the 16-11 fusion. In the PAs with only the 15-9 fusion, 1 PA was in the cerebellum and 7 were centered in the midline outside of the cerebellum, that is, in the hypothalamus (n = 4), optic pathways (n = 2), and brainstem (n = 1). Tumors within the cerebellum were negatively associated with fusion 15-9. Seven (22%) of the 32 patients had tumor-related deaths and 25 of the patients (78%) were alive between 2 and 14 years after initial biopsy. Age, sex, tumor location, 16-9 fusion, and 15-9 fusion were not associated with overall survival. Thus, in this small cohort, 15-9 KIAA1549-BRAF fusion was associated with midline PAs located outside of the cerebellum; these tumors, which are generally difficult to resect, are prone to recurrence. PMID:26222501

  14. A novel mutation in NF1 is associated with diverse intra-familial phenotypic variation and astrocytoma in a Chinese family.

    PubMed

    Banerjee, Santasree; Dai, Yi; Liang, Shengran; Chen, Huishuang; Wang, Yanyan; Tang, Lihui; Wu, Jing; Huang, Hui

    2016-09-01

    Neurofibromatosis type 1 (NF1) is a dysregulated neurocutaneous disorder, characterized by neurofibromas and café-au-lait spots. NF1 is caused by mutations in the NF1 gene, encoding neurofibromin. Here, we present a clinical molecular study of a three-generation Chinese family with NF1. The proband was a male patient who showed café-au-lait spots and multiple subcutaneous neurofibromas over the whole body, but his siblings only had regional lesions. The man's daughter presented with severe headache and vomiting. Neurological examination revealed an intracranial space occupying lesion. Surgery was undertaken and the histopathological examination showed a grade I-II astrocytoma. Next-Generation sequencing (Illumina HiSeq2500 Analyzers; Illumina, San Diego, CA, USA) and Sanger sequencing (ABI PRISM 3730 automated sequencer; Applied Biosystems, Foster City, CA, USA) identified the c.227delA mutation in the NF1 gene in the man. The mutation is co-segregated with the disease phenotypes among the affected members of this family and was absent in 100 healthy controls. This novel mutation results in a frameshift (p.Asn78IlefsX7) as well as truncation of neurofibromin by formation of a premature stop codon. Our results not only extended the mutational and phenotypic spectra of the gene and the disease, but also highlight the importance of the other genetic or environmental factors in the development and severity of the disease. PMID:27234610

  15. miR-15a and miR-24-1 as putative prognostic microRNA signatures for pediatric pilocytic astrocytomas and ependymomas.

    PubMed

    Braoudaki, M; Lambrou, G I; Giannikou, K; Papadodima, S A; Lykoudi, A; Stefanaki, K; Sfakianos, G; Kolialexi, A; Tzortzatou-Stathopoulou, F; Tzetis, M; Kitsiou-Tzeli, S; Kanavakis, E

    2016-07-01

    In the current setting, we attempted to verify and validate miRNA candidates relevant to pediatric primary brain tumor progression and outcome, in order to provide data regarding the identification of novel prognostic biomarkers. Overall, 26 resected brain tumors were studied from children diagnosed with pilocytic astrocytomas (PAs) (n = 19) and ependymomas (EPs) (n = 7). As controls, deceased children who underwent autopsy and were not present with any brain malignancy were used. The experimental approach included microarrays covering 1211 miRNAs. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to validate the expression profiles of miR-15a and miR-24-1. The multiparameter analyses were performed with MATLAB. Matching differentially expressed miRNAs were detected in both PAs and EPs, following distinct comparisons with the control cohort; however, in several cases, they exhibited tissue-specific expression profiles. On correlations between miRNA expression and EP progression or outcome, miR-15a and miR-24-1 were found upregulated in EP relapsed and EP deceased cases when compared to EP clinical remission cases and EP survivors, respectively. Taken together, following several distinct associations between miRNA expression and diverse clinical parameters, the current study repeatedly highlighted miR-15a and miR-24-1 as candidate oncogenic molecules associated with inferior prognosis in children diagnosed with ependymoma. PMID:26813564

  16. Allele loss on chromosomes 10 and 17p and epidermal growth factor receptor gene amplification in human malignant astrocytoma related to prognosis.

    PubMed Central

    Leenstra, S.; Bijlsma, E. K.; Troost, D.; Oosting, J.; Westerveld, A.; Bosch, D. A.; Hulsebos, T. J.

    1994-01-01

    Patients with high-grade astrocytomas have a poor prognosis. However, considerable variation exists within this group of patients with respect to post-operative survival. In order to determine whether genetic alterations might be of help in subdividing this group, we used allele loss on chromosomes 10 and 17p and epidermal growth factor receptor (EGFR) gene amplification in the tumours as genetic parameters and determined their prognostic value. A series of 47 malignant (grade III and grade IV) tumours were genetically characterised, and four types of tumours were found. Type 1 tumours had loss of heterozygosity on chromosome arm 17p (LOH 17p) as the sole genetic alteration. Patients with this type of tumour were relatively young (mean age 39 years) and had a median survival period of 17 months. Type 2 tumours displayed only allele loss on chromosome 10 (LOH 10), type 3 tumours had LOH 10 + LOH 17p and type 4 tumours contained LOH 10 + EGFR gene amplification. Patients with types 2, 3 and 4 tumours were older (mean ages 59, 65 and 54 years respectively) and had a shorter survival (median duration 6, 3 and 2 months respectively) than type 1 patients. Multivariate analysis indicated that the genetic subdivision was a significant prognostic variable. In this study, age proved to be of minor importance with regard to survival. Our study revealed a predominance of frontally located tumours in patients with type 1 tumours, i.e. with LOH 17p only. Images Figure 2 PMID:7917918

  17. Desferrioxamine, an iron chelator, inhibits CXCL10 expression induced by polyinosinic-polycytidylic acid in U373MG human astrocytoma cells.

    PubMed

    Imaizumi, Tadaatsu; Sakashita, Nina; Mushiga, Yasuaki; Yoshida, Hidemi; Hayakari, Ryo; Xing, Fei; Wang, Liang; Matsumiya, Tomoh; Tanji, Kunikazu; Chiba, Yuki; Furudate, Ken; Kawaguchi, Shogo; Murakami, Manabu; Tanaka, Hiroshi

    2015-05-01

    Although iron is essential in physiological processes, accumulation of iron in central nervous system is associated with various neurological diseases including Alzheimer's disease and Parkinson's disease. Innate immune reactions are involved in the pathogenesis of those diseases, but roles of iron in innate immunity are not known well. In the present study, pretreatment of U373MG human astrocytoma cells with an iron chelator desferrioxamine (DFX) inhibited the expression of CXCL10 induced by a Toll-like receptor 3 (TLR3) agonist polyinosinic-polycytidylic acid (poly IC). Induction of interferon-β (IFN-β) was not affected, but phosphorylation of signal transducer and transcription 1 (STAT1) was decreased by DFX. We have previously reported that various IFN-stimulated genes (ISGs) are involved in CXCL10 induction by poly IC. Pretreatment with DFX also decreased the expression of these ISGs. Pretreatment of cells with FeSO4 counteracted inhibitory effects of DFX on ISG56, retinoic acid-inducible gene-I (RIG-I), CXCL10 and phosphorylation of STAT1. These results suggest that iron may positively regulate STAT1 phosphorylation and following signaling to express ISG56, RIG-I and CXCL10 in U373MG cells treated with poly IC. Iron may contribute to innate immune and inflammatory reactions elicited by the TLR3 signaling in astrocytes, and may play an important role in neuroinflammatory diseases.

  18. AUTOCOUNTER, an ImageJ JavaScript to analyze LC3B-GFP expression dynamics in autophagy-induced astrocytoma cells.

    PubMed

    Fassina, L; Magenes, G; Inzaghi, A; Palumbo, S; Allavena, G; Miracco, C; Pirtoli, L; Biggiogera, M; Comincini, S

    2012-10-11

    An ImageJ JavaScript, AUTOCOUNTER, was specifically developed to monitor and measure LC3B-GFP expression in living human astrocytoma cells, namely T98G and U373-MG. Discrete intracellular GFP fluorescent spots derived from transduction of a Baculovirus replication-defective vector (BacMam LC3B-GFP), followed by microscope examinations at different times. After viral transgene expression, autophagy was induced by Rapamycin administration and assayed in ph-p70S6K/p70S6K and LC3B immunoblotting expression as well as by electron microscopy examinations. A mutated transgene, defective in LC3B lipidation, was employed as a negative control to further exclude fluorescent dots derived from protein intracellular aggregation. The ImageJ JavaScript was then employed to evaluate and score the dynamics changes of the number and area of LC3B-GFP puncta per cell in time course assays and in complex microscope examinations. In conclusion, AUTOCOUNTER enabled to quantify LC3B-GFP expression and to monitor dynamics changes in number and shapes of autophagosomal-like vesicles: it might therefore represent a suitable algorithmic tool for in vitro autophagy modulation studies.

  19. The Tachykinin Peptide Neurokinin B Binds Copper Forming an Unusual [CuII(NKB)2] Complex and Inhibits Copper Uptake into 1321N1 Astrocytoma Cells

    PubMed Central

    2013-01-01

    Neurokinin B (NKB) is a member of the tachykinin family of neuropeptides that have neuroinflammatory, neuroimmunological, and neuroprotective functions. In a neuroprotective role, tachykinins can help protect cells against the neurotoxic processes observed in Alzheimer’s disease. A change in copper homeostasis is a clear feature of Alzheimer’s disease, and the dysregulation may be a contributory factor in toxicity. Copper has recently been shown to interact with neurokinin A and neuropeptide γ and can lead to generation of reactive oxygen species and peptide degradation, which suggests that copper may have a place in tachykinin function and potentially misfunction. To explore this, we have utilized a range of spectroscopic techniques to show that NKB, but not substance P, can bind CuII in an unusual [CuII(NKB)2] neutral complex that utilizes two N-terminal amine and two imidazole nitrogen ligands (from each molecule of NKB) and the binding substantially alters the structure of the peptide. Using 1321N1 astrocytoma cells, we show that copper can enter the cells and subsequently open plasma membrane calcium channels but when bound to neurokinin B copper ion uptake is inhibited. This data suggests a novel role for neurokinin B in protecting cells against copper-induced calcium changes and implicates the peptide in synaptic copper homeostasis. PMID:23875773

  20. Combustor diffuser interaction program

    NASA Technical Reports Server (NTRS)

    Srinivasan, Ram; Thorp, Daniel

    1986-01-01

    Advances in gas turbine engine performance are achieved by using compressor systems with high stage loading and low part count, which result in high exit Mach numbers. The diffuser and combustor systems in such engines should be optimized to reduce system pressure loss and to maximize the engine thrust-to-weight ratio and minimize length. The state-of-the-art combustor-diffuser systems do not meet these requirements. Detailed understanding of the combustor-diffuser flow field interaction is required for designing advanced gas turbine engines. An experimental study of the combustor-diffuser interaction (CDI) is being conducted to obtain data for the evaluation and improvement of analytical models applicable to a wide variety of diffuser designs. The CDI program consists of four technical phases: Literature Search; Baseline Configuration; Parametric Configurations; and Performance Configurations. Phase 2 of the program is in progress.

  1. Diffusion in Coulomb crystals.

    PubMed

    Hughto, J; Schneider, A S; Horowitz, C J; Berry, D K

    2011-07-01

    Diffusion in Coulomb crystals can be important for the structure of neutron star crusts. We determine diffusion constants D from molecular dynamics simulations. We find that D for Coulomb crystals with relatively soft-core 1/r interactions may be larger than D for Lennard-Jones or other solids with harder-core interactions. Diffusion, for simulations of nearly perfect body-centered-cubic lattices, involves the exchange of ions in ringlike configurations. Here ions "hop" in unison without the formation of long lived vacancies. Diffusion, for imperfect crystals, involves the motion of defects. Finally, we find that diffusion, for an amorphous system rapidly quenched from Coulomb parameter Γ=175 to Coulomb parameters up to Γ=1750, is fast enough that the system starts to crystalize during long simulation runs. These results strongly suggest that Coulomb solids in cold white dwarf stars, and the crust of neutron stars, will be crystalline and not amorphous. PMID:21867316

  2. Diffusion in Coulomb crystals.

    PubMed

    Hughto, J; Schneider, A S; Horowitz, C J; Berry, D K

    2011-07-01

    Diffusion in Coulomb crystals can be important for the structure of neutron star crusts. We determine diffusion constants D from molecular dynamics simulations. We find that D for Coulomb crystals with relatively soft-core 1/r interactions may be larger than D for Lennard-Jones or other solids with harder-core interactions. Diffusion, for simulations of nearly perfect body-centered-cubic lattices, involves the exchange of ions in ringlike configurations. Here ions "hop" in unison without the formation of long lived vacancies. Diffusion, for imperfect crystals, involves the motion of defects. Finally, we find that diffusion, for an amorphous system rapidly quenched from Coulomb parameter Γ=175 to Coulomb parameters up to Γ=1750, is fast enough that the system starts to crystalize during long simulation runs. These results strongly suggest that Coulomb solids in cold white dwarf stars, and the crust of neutron stars, will be crystalline and not amorphous.

  3. WEE1 Inhibitor MK-1775 and Local Radiation Therapy in Treating Younger Patients With Newly Diagnosed Diffuse Intrinsic Pontine Gliomas

    ClinicalTrials.gov

    2016-10-07

    Untreated Childhood Anaplastic Astrocytoma; Untreated Childhood Anaplastic Oligodendroglioma; Untreated Childhood Brain Stem Glioma; Untreated Childhood Giant Cell Glioblastoma; Untreated Childhood Glioblastoma; Untreated Childhood Gliosarcoma

  4. Helium Diffusion in Olivine

    NASA Astrophysics Data System (ADS)

    Cherniak, D. J.; Watson, E. B.

    2011-12-01

    Diffusion of helium has been characterized in natural Fe-bearing olivine (~Fo90) and synthetic forsterite. Polished, oriented slabs of olivine were implanted with 3He, at 100 keV at a dose of 5x1015/cm2 or at 3.0 MeV at a dose of 1x1016/cm2. A set of experiments on the implanted olivine were run in 1-atm furnaces. In addition to the one-atm experiments, experiments on implanted samples were also run at higher pressures (2.6 and 2.7 GPa) to assess the potential effects of pressure on He diffusion and the applicability of the measured diffusivities in describing He transport in the mantle. The high-pressure experiments were conducted in a piston-cylinder apparatus using an "ultra-soft" pressure cell, with the diffusion sample directly surrounded by AgCl. 3He distributions following experiments were measured with Nuclear Reaction Analysis using the reaction 3He(d,p)4He. This direct profiling method permits us to evaluate anisotropy of diffusion, which cannot be easily assessed using bulk-release methods. For diffusion in forsterite parallel to c we obtain the following Arrhenius relation over the temperatures 250-950°C: D = 3.91x10-6exp(-159 ± 4 kJ mol-1/RT) m2/sec. The data define a single Arrhenius line spanning more than 7 orders of magnitude in D and 700°C in temperature. Diffusion parallel to a appears slightly slower, yielding an activation energy for diffusion of 135 kJ/mol and a pre-exponential factor of 3.73x10-8 m2/sec. Diffusion parallel to b is slower than diffusion parallel to a (by about two-thirds of a log unit); for this orientation an activation energy of 138 kJ/mol and a pre-exponential factor of 1.34x10-8 m2/sec are obtained. This anisotropy is broadly consistent with observations for diffusion of Ni and Fe-Mg in olivine. Diffusion in Fe-bearing olivine (transport parallel to b) agrees within uncertainty with findings for He diffusion in forsterite. The higher-pressure experiments yield diffusivities in agreement with those from the 1-atm

  5. Urinary tract infection - adults

    MedlinePlus

    Bladder infection - adults; UTI - adults; Cystitis - bacterial - adults; Pyelonephritis - adults; Kidney infection - adults ... to the hospital if you: Are an older adult Have kidney stones or changes in the anatomy ...

  6. Tungsten diffusion in silicon

    SciTech Connect

    De Luca, A.; Texier, M.; Burle, N.; Oison, V.; Pichaud, B.; Portavoce, A.; Grosjean, C.

    2014-01-07

    Two doses (10{sup 13} and 10{sup 15} cm{sup −2}) of tungsten (W) atoms were implanted in different Si(001) wafers in order to study W diffusion in Si. The samples were annealed or oxidized at temperatures between 776 and 960 °C. The diffusion profiles were measured by secondary ion mass spectrometry, and defect formation was studied by transmission electron microscopy and atom probe tomography. W is shown to reduce Si recrystallization after implantation and to exhibit, in the temperature range investigated, a solubility limit close to 0.15%–0.2%, which is higher than the solubility limit of usual metallic impurities in Si. W diffusion exhibits unusual linear diffusion profiles with a maximum concentration always located at the Si surface, slower kinetics than other metals in Si, and promotes vacancy accumulation close to the Si surface, with the formation of hollow cavities in the case of the higher W dose. In addition, Si self-interstitial injection during oxidation is shown to promote W-Si clustering. Taking into account these observations, a diffusion model based on the simultaneous diffusion of interstitial W atoms and W-Si atomic pairs is proposed since usual models used to model diffusion of metallic impurities and dopants in Si cannot reproduce experimental observations.

  7. Tungsten diffusion in olivine

    NASA Astrophysics Data System (ADS)

    Cherniak, D. J.; Van Orman, J. A.

    2014-03-01

    Diffusion of tungsten has been characterized in synthetic forsterite and natural olivine (Fo90) under dry conditions. The source of diffusant was a mixture of magnesium tungstate and olivine powders. Experiments were prepared by sealing the source material and polished olivine under vacuum in silica glass ampoules with solid buffers to buffer at NNO or IW. Prepared capsules were annealed in 1 atm furnaces for times ranging from 45 min to several weeks, at temperatures from 1050 to 1450 °C. Tungsten distributions in the olivine were profiled by Rutherford Backscattering Spectrometry (RBS). The following Arrhenius relation is obtained for W diffusion in forsterite: D=1.0×10-8exp(-365±28 kJ mol/RT) m s Diffusivities for the synthetic forsterite and natural Fe-bearing olivine are similar, and tungsten diffusion in olivine shows little dependence on crystallographic orientation or oxygen fugacity. The slow diffusivities measured for W in olivine indicate that Hf-W ages in olivine-metal systems will close to diffusive exchange at higher temperatures than other chronometers commonly used in cosmochronology, and that tungsten isotopic signatures will be less likely to be reset by subsequent thermal events.

  8. Diffusion Flame Stabilization

    NASA Technical Reports Server (NTRS)

    Takahashi, Fumiaki; Katta, V. R.

    2006-01-01

    Diffusion flames are commonly used for industrial burners in furnaces and flares. Oxygen/fuel burners are usually diffusion burners, primarily for safety reasons, to prevent flashback and explosion in a potentially dangerous system. Furthermore, in most fires, condensed materials pyrolyze, vaporize, and burn in air as diffusion flames. As a result of the interaction of a diffusion flame with burner or condensed-fuel surfaces, a quenched space is formed, thus leaving a diffusion flame edge, which plays an important role in flame holding in combustion systems and fire spread through condensed fuels. Despite a long history of jet diffusion flame studies, lifting/blowoff mechanisms have not yet been fully understood, compared to those of premixed flames. In this study, the structure and stability of diffusion flames of gaseous hydrocarbon fuels in coflowing air at normal earth gravity have been investigated experimentally and computationally. Measurements of the critical mean jet velocity (U(sub jc)) of methane, ethane, or propane at lifting or blowoff were made as a function of the coflowing air velocity (U(sub a)) using a tube burner (i.d.: 2.87 mm). By using a computational fluid dynamics code with 33 species and 112 elementary reaction steps, the internal chemical-kinetic structures of the stabilizing region of methane and propane flames were investigated. A peak reactivity spot, i.e., reaction kernel, is formed in the flame stabilizing region due to back-diffusion of heat and radical species against an oxygen-rich incoming flow, thus holding the trailing diffusion flame. The simulated flame base moved downstream under flow conditions close to the measured stability limit.

  9. Diffusion Flame Stabilization

    NASA Technical Reports Server (NTRS)

    Takahashi, Fumiaki; Katta, Viswanath R.

    2007-01-01

    Diffusion flames are commonly used for industrial burners in furnaces and flares. Oxygen/fuel burners are usually diffusion burners, primarily for safety reasons, to prevent flashback and explosion in a potentially dangerous system. Furthermore, in most fires, condensed materials pyrolyze, vaporize, and burn in air as diffusion flames. As a result of the interaction of a diffusion flame with burner or condensed-fuel surfaces, a quenched space is formed, thus leaving a diffusion flame edge, which plays an important role in flame holding in combustion systems and fire spread through condensed fuels. Despite a long history of jet diffusion flame studies, lifting/blowoff mechanisms have not yet been fully understood, compared to those of premixed flames. In this study, the structure and stability of diffusion flames of gaseous hydrocarbon fuels in coflowing air at normal earth gravity have been investigated experimentally and computationally. Measurements of the critical mean jet velocity (U(sub jc)) of methane, ethane, or propane at lifting or blowoff were made as a function of the coflowing air velocity (U(sub a)) using a tube burner (i.d.: 2.87 mm) (Fig. 1, left). By using a computational fluid dynamics code with 33 species and 112 elementary reaction steps, the internal chemical-kinetic structures of the stabilizing region of methane and propane flames were investigated (Fig. 1, right). A peak reactivity spot, i.e., reaction kernel, is formed in the flame stabilizing region due to back-diffusion of heat and radical species against an oxygen-rich incoming flow, thus holding the trailing diffusion flame. The simulated flame base moved downstream under flow conditions close to the measured stability limit.

  10. Hereditary Diffuse Gastric Cancer

    MedlinePlus

    ... with the syndrome is recommended. What are the estimated cancer risks associated with HDGC? Not everyone who ... the lifetime risk for diffuse gastric cancer is estimated to be 70% to 80% for men and ...

  11. Multinomial Diffusion Equation

    SciTech Connect

    Balter, Ariel I.; Tartakovsky, Alexandre M.

    2011-06-01

    We have developed a novel stochastic, space/time discrete representation of particle diffusion (e.g. Brownian motion) based on discrete probability distributions. We show that in the limit of both very small time step and large concentration, our description is equivalent to the space/time continuous stochastic diffusion equation. Being discrete in both time and space, our model can be used as an extremely accurate, efficient, and stable stochastic finite-difference diffusion algorithm when concentrations are so small that computationally expensive particle-based methods are usually needed. Through numerical simulations, we show that our method can generate realizations that capture the statistical properties of particle simulations. While our method converges converges to both the correct ensemble mean and ensemble variance very quickly with decreasing time step, but for small concentration, the stochastic diffusion PDE does not, even for very small time steps.

  12. Lung diffusion testing

    MedlinePlus

    Lung diffusion testing measures how well the lungs exchange gases. This is an important part of lung testing , because ... gases do not move normally across the lung tissues into the blood vessels of the lung. This ...

  13. Investigating diffusion with technology

    NASA Astrophysics Data System (ADS)

    Miller, Jon S.; Windelborn, Augden F.

    2013-07-01

    The activities described here allow students to explore the concept of diffusion with the use of common equipment such as computers, webcams and analysis software. The procedure includes taking a series of digital pictures of a container of water with a webcam as a dye slowly diffuses. At known time points, measurements of the pixel densities (darkness) of the digital pictures are recorded and then plotted on a graph. The resulting graph of darkness versus time allows students to see the results of diffusion of the dye over time. Through modification of the basic lesson plan, students are able to investigate the influence of a variety of variables on diffusion. Furthermore, students are able to expand the boundaries of their thinking by formulating hypotheses and testing their hypotheses through experimentation. As a result, students acquire a relevant science experience through taking measurements, organizing data into tables, analysing data and drawing conclusions.

  14. Hydrogen Diffusion in Forsterite

    NASA Astrophysics Data System (ADS)

    Demouchy, S.; Mackwell, S.

    2002-12-01

    Physical and chemical properties of Earth's mantle are readily modified by interaction with volatiles, such as water. Thus, characterization of solubility and kinetics of incorporation for water in nominally anhydrous minerals is important in order to understand the behavior of Earth's interior under hydrous conditions. Experimental studies on the olivine-water system indicate that significant amounts of OH can dissolve within olivine as point defects (Bell and Rossman, 1992; Kohlstedt et al. 1996). Extending Kohlstedt and Mackwell's (1998) work, our study concerns the kinetics of hydrogen transport in the iron-free olivine-water system. This study is based on hydrogenation of forsterite samples during piston-cylinder and TZM cold-seal vessel experiments. We use infrared analyses in order to constrain the speciation of the mobile water-derived defects in forsterite single-crystal sample, and the rates of diffusion of such species under uppermost mantle conditions (0.2 to 1.5 GPa, 900 to 1100° C). Hydrogen defect transport in single crystals of forsterite is investigated for diffusion parallel to each crystallographic axis. Defect diffusivities are obtained by fitting a diffusion law to the OH content as a function of position in the sample. Our current results indicate that incorporation of hydroxyl species into iron-free olivine is a one-stage process with hydrogen diffusion linked to magnesium vacancy self-diffusion DV, such that DV = D~/3 = 10-12 m2/s at 1000° C parallel to [001], where D~ represents the chemical diffusivity. Those diffusion rates are slightly lower than in iron-bearing olivine for the same incorporation mechanism. The different concentration profiles show a clear anisotropy of diffusion, with fastest diffusion parallel to [001] as in iron-bearing olivine. Thus, while hydrogen solubilities are dependent on iron content, the rate of incorporation of water-derived species in olivine is not strongly coupled to the concentration of iron. This

  15. Nodal Diffusion & Transport Theory

    1992-02-19

    DIF3D solves multigroup diffusion theory eigenvalue, adjoint, fixed source, and criticality (concentration, buckling, and dimension search) problems in 1, 2, and 3-space dimensions for orthogonal (rectangular or cylindrical), triangular, and hexagonal geometries. Anisotropic diffusion theory coefficients are permitted. Flux and power density maps by mesh cell and regionwise balance integrals are provided. Although primarily designed for fast reactor problems, upscattering and internal black boundary conditions are also treated.

  16. Subchronic dermal application of N,N-diethyl m-toluamide (DEET) and permethrin to adult rats, alone or in combination, causes diffuse neuronal cell death and cytoskeletal abnormalities in the cerebral cortex and the hippocampus, and Purkinje neuron loss in the cerebellum.

    PubMed

    Abdel-Rahman, A; Shetty, A K; Abou-Donia, M B

    2001-11-01

    . Analysis of glial fibrillary acidic protein immunoreactivity revealed significant hypertrophy of astrocytes in the hippocampus and the cerebellum of all treated groups (24-106% increase). Thus, subchronic dermal application of DEET and permethrin to adult rats, alone or in combination, leads to a diffuse neuronal cell death in the cerebral cortex, the hippocampal formation, and the cerebellum. Collectively, the above alterations can lead to many physiological, pharmacological, and behavioral abnormalities, particularly motor deficits and learning and memory dysfunction. PMID:11681848

  17. Advanced manufacturing: Technology diffusion

    SciTech Connect

    Tesar, A.

    1995-12-01

    In this paper we examine how manufacturing technology diffuses rom the developers of technology across national borders to those who do not have the capability or resources to develop advanced technology on their own. None of the wide variety of technology diffusion mechanisms discussed in this paper are new, yet the opportunities to apply these mechanisms are growing. A dramatic increase in technology diffusion occurred over the last decade. The two major trends which probably drive this increase are a worldwide inclination towards ``freer`` markets and diminishing isolation. Technology is most rapidly diffusing from the US In fact, the US is supplying technology for the rest of the world. The value of the technology supplied by the US more than doubled from 1985 to 1992 (see the Introduction for details). History shows us that technology diffusion is inevitable. It is the rates at which technologies diffuse to other countries which can vary considerably. Manufacturers in these countries are increasingly able to absorb technology. Their manufacturing efficiency is expected to progress as technology becomes increasingly available and utilized.

  18. Multispecies diffusion models: A study of uranyl species diffusion

    SciTech Connect

    Liu, Chongxuan; Shang, Jianying; Zachara, John M.

    2011-12-14

    Rigorous numerical description of multi-species diffusion requires coupling of species, charge, and aqueous and surface complexation reactions that collectively affect diffusive fluxes. The applicability of a fully coupled diffusion model is, however, often constrained by the availability of species self-diffusion coefficients, as well as by computational complication for imposing charge conservation. In this study, several diffusion models with variable complexity in charge and species coupling were formulated and compared to describe reactive multi-species diffusion in groundwater. Diffusion of uranyl [U(VI)] species was used as an example in demonstrating the effectiveness of the models in describing multi-species diffusion. Numerical simulations found that a diffusion model with a single, common diffusion coefficient for all species was sufficient to describe multi-species U(VI) diffusion under steady-state condition of major chemical composition, but not under transient chemical conditions. Simulations revealed that a fully coupled diffusion model can be well approximated by a component-based diffusion model, which considers difference in diffusion coefficients between chemical components, but not between the species within each chemical component. This treatment significantly enhanced computational efficiency at the expense of minor charge conservation. The charge balance in the component-based diffusion model can be rigorously enforced, if necessary, by adding an artificial kinetic reaction term induced by the charge separation. The diffusion models were applied to describe U(VI) diffusive mass transfer in intragranular domains in two sediments collected from US Department of Energy's Hanford 300A where intragrain diffusion is a rate-limiting process controlling U(VI) adsorption and desorption. The grain-scale reactive diffusion model was able to describe U(VI) adsorption/desorption kinetics that has been described using a semi-empirical, multi-rate model

  19. Treatment of human astrocytoma U87 cells with silicon dioxide nanoparticles lowers their survival and alters their expression of mitochondrial and cell signaling proteins.

    PubMed

    Lai, James C K; Ananthakrishnan, Gayathri; Jandhyam, Sirisha; Dukhande, Vikas V; Bhushan, Alok; Gokhale, Mugdha; Daniels, Christopher K; Leung, Solomon W

    2010-10-05

    Recent evidence suggests silicon dioxide micro- and nanoparticles induce cytotoxic effects on lung cells. Thus, there is an increasing concern regarding their potential health hazard. Nevertheless, the putative toxicity of nanoparticles in mammalian cells has not yet been systematically investigated. We previously noted that several metallic oxide nanoparticles exert differential cytotoxic effects on human neural and nonneural cells. Therefore, we hypothesized that silicon dioxide nanoparticles induce cytotoxicity in U87 cells by lowering their survival by decreasing cell survival signaling and disturbing mitochondrial function. To investigate this hypothesis, we determined the activities of the key mitochondrial enzymes, citrate synthase and malate dehydrogenase, in astrocytoma U87 cells treated with silicon dioxide nanoparticles. In addition, we studied the expression of the mitochondrial DNA-encoded proteins, cytochrome C oxidase II and nicotinamide adenine dinucleotide (NADPH) dehydrogenase subunit 6, and cell signaling pathway protein extracellular signal-regulated kinase (ERK) and phosphorylated ERK in treated U87 cells. The activated form of ERK controls cell growth, differentiation, and proliferation. In parallel, we determined survival of U87 cells after treating them with various concentrations of silicon dioxide nanoparticles. Our results indicated that treatment with silicon dioxide nanoparticles induced decreases in U87 cell survival in a dose-related manner. The activities of citrate synthase and malate dehydrogenase in treated U87 cells were increased, possibly due to an energetic compensation in surviving cells. However, the expression of mitochondrial DNA-encoded cytochrome C oxidase subunit II and NADH dehydrogenase subunit 6 and the cell signaling protein ERK and phosphorylated ERK were altered in the treated U87 cells, suggesting that silicon dioxide nanoparticles induced disruption of mitochondrial DNA-encoded protein expression, leading to

  20. Coupling of the thrombin receptor to G12 may account for selective effects of thrombin on gene expression and DNA synthesis in 1321N1 astrocytoma cells.

    PubMed Central

    Post, G R; Collins, L R; Kennedy, E D; Moskowitz, S A; Aragay, A M; Goldstein, D; Brown, J H

    1996-01-01

    In 1321N1 astrocytoma cells, thrombin, but not carbachol, induces AP-1-mediated gene expression and DNA synthesis. To understand the divergent effects of these G protein-coupled receptor agonists on cellular responses, we examined Gq-dependent signaling events induced by thrombin receptor and muscarinic acetylcholine receptor stimulation. Thrombin and carbachol induce comparable changes in phosphoinositide and phosphatidylcholine hydrolysis, mobilization of intracellular Ca2+, diglyceride generation, and redistribution of protein kinase C; thus, activation of these Gq-signaling pathways appears to be insufficient for gene expression and mitogenesis. Thrombin increases Ras and mitogen-activated protein kinase activation to a greater extent than carbachol in 1321N1 cells. The effects of thrombin are not mediated through Gi, since ribosylation of Gi/Go proteins by pertussis toxin does not prevent thrombin-induced gene expression or thrombin-stimulated DNA synthesis. We recently reported that the pertussis toxin-insensitive G12 protein is required for thrombin-induced DNA synthesis. We demonstrate here, using transfection of receptors and G proteins in COS-7 cells, that G alpha 12 selectively couples the thrombin receptor to AP-1-mediated gene expression. This does not appear to result from increased mitogen-activated protein kinase activity but may reflect activation of a tyrosine kinase pathway. We suggest that preferential coupling of the thrombin receptor to G12 accounts for the selective ability of thrombin to stimulate Ras, mitogen-activated protein kinase, gene expression, and mitogenesis in 1321N1 cells. Images PMID:8930892

  1. Vorinostat and Combination Chemotherapy With Rituximab in Treating Patients With HIV-Related Diffuse Large B-Cell Non-Hodgkin Lymphoma or Other Aggressive B-Cell Lymphomas

    ClinicalTrials.gov

    2016-10-25

    AIDS-Related Diffuse Large Cell Lymphoma; AIDS-Related Plasmablastic Lymphoma; AIDS-Related Primary Effusion Lymphoma; Grade 3b Follicular Lymphoma; HIV Infection; Plasmablastic Lymphoma; Primary Effusion Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Stage I Adult Diffuse Large Cell Lymphoma; Stage I Grade 3 Follicular Lymphoma; Stage II Contiguous Adult Diffuse Large Cell Lymphoma; Stage II Grade 3 Contiguous Follicular Lymphoma; Stage II Grade 3 Non-Contiguous Follicular Lymphoma; Stage II Non-Contiguous Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Grade 3 Follicular Lymphoma

  2. Adult intussusception.

    PubMed Central

    Azar, T; Berger, D L

    1997-01-01

    OBJECTIVE: The objectives were to review adult intussusception, its diagnosis, and its treatment. SUMMARY BACKGROUND DATA: Adult intussusception represents 1% of all bowel obstructions, 5% of all intussusceptions, and 0.003%-0.02% of all hospital admissions. Intussusception is a different entity in adults than it is in children. METHODS: The records of all patients 18 years and older with the postoperative diagnosis of intussusception at the Massachusetts General Hospital during the years 1964 through 1993 were reviewed retrospectively. The 58 patients were divided into those with benign enteric, malignant enteric, benign colonic, and malignant colonic lesions associated with their intussusception. The diagnosis and treatment of each were reviewed. RESULTS: In 30 years at the Massachusetts General Hospital, there are 58 cases of surgically proven adult intussusception. The patients' mean age was 54.4 years. Most patients presented with symptoms consistent with bowel obstruction. There were 44 enteric and 14 colonic intussusceptions. Ninety-three percent of the intussusceptions were associated with a pathologic lesion. Forty-eight percent of the enteric lesions were malignant and 52% were benign. Forty-three percent of the colonic lesions were malignant and 57% were benign. CONCLUSIONS: Intussusception occurs rarely in adults. It presents with a variety of acute, intermittent, and chronic symptoms, thus making its preoperative diagnosis difficult. Computed tomography scanning proved to be the most useful diagnostic radiologic method. The diagnosis and treatment of adult intussusception are surgical. Surgical resection of the intussusception without reduction is the preferred treatment in adults, as almost half of both colonic and enteric intussusceptions are associated with malignancy. PMID:9296505

  3. Anomalous Diffusion Near Resonances

    SciTech Connect

    Sen, Tanaji; /Fermilab

    2010-05-01

    Synchro-betatron resonances can lead to emittance growth and the loss of luminosity. We consider the detailed dynamics of a bunch near such a low order resonance driven by crossing angles at the collision points. We characterize the nature of diffusion and find that it is anomalous and sub-diffusive. This affects both the shape of the beam distribution and the time scales for growth. Predictions of a simplified anomalous diffusion model are compared with direct simulations. Transport of particles near resonances is still not a well understood phenomenon. Often, without justification, phase space motion is assumed to be a normal diffusion process although at least one case of anomalous diffusion in beam dynamics has been reported [1]. Here we will focus on the motion near synchro-betatron resonances which can be excited by several means, including beams crossing at an angle at the collision points as in the LHC. We will consider low order resonances which couple the horizontal and longitudinal planes, both for simplicity and to observe large effects over short time scales. While the tunes we consider are not practical for a collider, nonetheless the transport mechanisms we uncover are also likely to operate at higher order resonances.

  4. Methodology and apparatus for diffuse photon mimaging

    DOEpatents

    Feng, Shechao C.; Zeng, Fanan; Zhao, Hui-Lin

    1997-12-09

    Non-invasive near infrared optical medical imaging devices for both hematoma detection in the brain and early tumor detection in the breast is achieved using image reconstruction which allows a mapping of the position dependent contrast diffusive propagation constants, which are related to the optical absorption coefficient and scattering coefficient in the tissue, at near infrared wavelengths. Spatial resolutions in the range of 5 mm for adult brain sizes and breast sizes can be achieved. The image reconstruction utilizes WKB approximation on most probable diffusion paths which has as lowest order approximation the straight line-of-sight between the plurality of sources and the plurality of detectors. The WKB approximation yields a set of linear equations in which the contrast optical absorption coefficients are the unknowns and for which signals can be generated to produce a pixel map of the contrast optical resolution of the scanned tissue.

  5. Methodology and apparatus for diffuse photon imaging

    DOEpatents

    Feng, S.C.; Zeng, F.; Zhao, H.L.

    1997-12-09

    Non-invasive near infrared optical medical imaging devices for both hematoma detection in the brain and early tumor detection in the breast is achieved using image reconstruction which allows a mapping of the position dependent contrast diffusive propagation constants, which are related to the optical absorption coefficient and scattering coefficient in the tissue, at near infrared wavelengths. Spatial resolutions in the range of 5 mm for adult brain sizes and breast sizes can be achieved. The image reconstruction utilizes WKB approximation on most probable diffusion paths which has as lowest order approximation the straight line-of-sight between the plurality of sources and the plurality of detectors. The WKB approximation yields a set of linear equations in which the contrast optical absorption coefficients are the unknowns and for which signals can be generated to produce a pixel map of the contrast optical resolution of the scanned tissue. 58 figs.

  6. Apparatus for diffusion separation

    DOEpatents

    Nierenberg, William A.; Pontius, Rex B.

    1976-08-10

    1. The method of testing the separation efficiency of porous permeable membranes which comprises causing a stream of a gaseous mixture to flow into contact with one face of a finely porous permeable membrane under such conditions that a major fraction of the mixture diffuses through the membrane, maintaining a rectangular cross section of the gaseous stream so flowing past said membrane, continuously recirculating the gas that diffuses through said membrane and continuously withdrawing the gas that does not diffuse through said membrane and maintaining the volume of said recirculating gas constant by continuously introducing into said continuously recirculating gas stream a mass of gas equivalent to that which is continuously withdrawn from said gas stream and comparing the concentrations of the light component in the entering gas, the withdrawn gas and the recirculated gas in order to determine the efficiency of said membrane.

  7. Cesium diffusion in graphite

    SciTech Connect

    Evans, R.B. III; Davis, W. Jr.; Sutton, A.L. Jr.

    1980-05-01

    Experiments on diffusion of /sup 137/Cs in five types of graphite were performed. The document provides a completion of the report that was started and includes a presentation of all of the diffusion data, previously unpublished. Except for data on mass transfer of /sup 137/Cs in the Hawker-Siddeley graphite, analyses of experimental results were initiated but not completed. The mass transfer process of cesium in HS-1-1 graphite at 600 to 1000/sup 0/C in a helium atmosphere is essentially pure diffusion wherein values of (E/epsilon) and ..delta..E of the equation D/epsilon = (D/epsilon)/sub 0/ exp (-..delta..E/RT) are about 4 x 10/sup -2/ cm/sup 2//s and 30 kcal/mole, respectively.

  8. Hydrogen diffusion in Zircon

    NASA Astrophysics Data System (ADS)

    Ingrin, Jannick; Zhang, Peipei

    2016-04-01

    Hydrogen mobility in gem quality zircon single crystals from Madagascar was investigated through H-D exchange experiments. Thin slices were annealed in a horizontal furnace flushed with a gas mixture of Ar/D2(10%) under ambient pressure between 900 ° C to 1150 ° C. FTIR analyses were performed on oriented slices before and after each annealing run. H diffusion along [100] and [010] follow the same diffusion law D = D0exp[-E /RT], with log D0 = 2.24 ± 1.57 (in m2/s) and E = 374 ± 39 kJ/mol. H diffusion along [001] follows a slightly more rapid diffusion law, with log D0 = 1.11 ± 0.22 (in m2/s) and E = 334 ± 49 kJ/mol. H diffusion in zircon has much higher activation energy and slower diffusivity than other NAMs below 1150 ° C even iron-poor garnets which are known to be among the slowest (Blanchard and Ingrin, 2004; Kurka et al. 2005). During H-D exchange zircon incorporates also deuterium. This hydration reaction involves uranium reduction as it is shown from the exchange of U5+ and U4+ characteristic bands in the near infrared region during annealing. It is the first time that a hydration reaction U5+ + OH‑ = U4+ + O2‑ + 1/2H2, is experimentally reported. The kinetics of deuterium incorporation is slightly slower than hydrogen diffusion, suggesting that the reaction is limited by hydrogen mobility. Hydrogen isotopic memory of zircon is higher than other NAMs. Zircons will be moderately retentive of H signatures at mid-crustal metamorphic temperatures. At 500 ° C, a zircon with a radius of 300 μm would retain its H isotopic signature over more than a million years. However, a zircon is unable to retain this information for geologically significant times under high-grade metamorphism unless the grain size is large enough. Refrences Blanchard, M. and Ingrin, J. (2004) Hydrogen diffusion in Dora Maira pyrope. Physics and Chemistry of Minerals, 31, 593-605. Kurka, A., Blanchard, M. and Ingrin, J. (2005) Kinetics of hydrogen extraction and deuteration in

  9. Hydrogen diffusion in Zircon

    NASA Astrophysics Data System (ADS)

    Ingrin, Jannick; Zhang, Peipei

    2016-04-01

    Hydrogen mobility in gem quality zircon single crystals from Madagascar was investigated through H-D exchange experiments. Thin slices were annealed in a horizontal furnace flushed with a gas mixture of Ar/D2(10%) under ambient pressure between 900 ° C to 1150 ° C. FTIR analyses were performed on oriented slices before and after each annealing run. H diffusion along [100] and [010] follow the same diffusion law D = D0exp[-E /RT], with log D0 = 2.24 ± 1.57 (in m2/s) and E = 374 ± 39 kJ/mol. H diffusion along [001] follows a slightly more rapid diffusion law, with log D0 = 1.11 ± 0.22 (in m2/s) and E = 334 ± 49 kJ/mol. H diffusion in zircon has much higher activation energy and slower diffusivity than other NAMs below 1150 ° C even iron-poor garnets which are known to be among the slowest (Blanchard and Ingrin, 2004; Kurka et al. 2005). During H-D exchange zircon incorporates also deuterium. This hydration reaction involves uranium reduction as it is shown from the exchange of U5+ and U4+ characteristic bands in the near infrared region during annealing. It is the first time that a hydration reaction U5+ + OH- = U4+ + O2- + 1/2H2, is experimentally reported. The kinetics of deuterium incorporation is slightly slower than hydrogen diffusion, suggesting that the reaction is limited by hydrogen mobility. Hydrogen isotopic memory of zircon is higher than other NAMs. Zircons will be moderately retentive of H signatures at mid-crustal metamorphic temperatures. At 500 ° C, a zircon with a radius of 300 μm would retain its H isotopic signature over more than a million years. However, a zircon is unable to retain this information for geologically significant times under high-grade metamorphism unless the grain size is large enough. Refrences Blanchard, M. and Ingrin, J. (2004) Hydrogen diffusion in Dora Maira pyrope. Physics and Chemistry of Minerals, 31, 593-605. Kurka, A., Blanchard, M. and Ingrin, J. (2005) Kinetics of hydrogen extraction and deuteration in

  10. Multispecies diffusion models: A study of uranyl species diffusion

    NASA Astrophysics Data System (ADS)

    Liu, Chongxuan; Shang, Jianying; Zachara, John M.

    2011-12-01

    Rigorous numerical description of multispecies diffusion requires coupling of species, charge, and aqueous and surface complexation reactions that collectively affect diffusive fluxes. The applicability of a fully coupled diffusion model is, however, often constrained by the availability of species self-diffusion coefficients, as well as by computational complication in imposing charge conservation. In this study, several diffusion models with variable complexity in charge and species coupling were formulated and compared to describe reactive multispecies diffusion in groundwater. Diffusion of uranyl [U(VI)] species was used as an example in demonstrating the effectiveness of the models in describing multispecies diffusion. Numerical simulations found that a diffusion model with a single, common diffusion coefficient for all species was sufficient to describe multispecies U(VI) diffusion under a steady state condition of major chemical composition, but not under transient chemical conditions. Simulations revealed that for multispecies U(VI) diffusion under transient chemical conditions, a fully coupled diffusion model could be well approximated by a component-based diffusion model when the diffusion coefficient for each chemical component was properly selected. The component-based diffusion model considers the difference in diffusion coefficients between chemical components, but not between the species within each chemical component. This treatment significantly enhanced computational efficiency at the expense of minor charge conservation. The charge balance in the component-based diffusion model can be enforced, if necessary, by adding a secondary migration term resulting from model simplification. The effect of ion activity coefficient gradients on multispecies diffusion is also discussed. The diffusion models were applied to describe U(VI) diffusive mass transfer in intragranular domains in two sediments collected from U.S. Department of Energy's Hanford 300A

  11. Thermal diffusivity of human serum and plasma

    NASA Astrophysics Data System (ADS)

    Mayén-Mondragón, R.; Yánez-Limón, J. M.; Palomares, P.; Sosa, M.; Bernal-Alvarado, J.

    2005-06-01

    Using a thermal lens experimental set up, the thermal diffusivity of human serum and plasma were measured. Several samples were studied and the results are reported as the average, including the standard deviation. The samples of serum and plasma were obtained in healthy adult donors from the Guanajuato State Blood Transfusion Center, Mexico; the donors were clinically tested and they were free of hepatitis, AIDS and other infectious diseases. The parameters reported were obtained using the thermal lens aberrant model with the lasers arranged in the mismatched mode.

  12. Osmosis and Diffusion

    ERIC Educational Resources Information Center

    Sack, Jeff

    2005-01-01

    OsmoBeaker is a CD-ROM designed to enhance the learning of diffusion and osmosis by presenting interactive experimentation to the student. The software provides several computer simulations that take the student through different scenarios with cells, having different concentrations of solutes in them.

  13. Thermodynamics of diffusion

    NASA Astrophysics Data System (ADS)

    Matuszak, Daniel

    Diffusion is the migration of molecules in the reference frame of a system's center of mass and it is a physical process that occurs in all chemical and biological systems. Diffusion generally involves intermolecular interactions that lead to clustering, adsorption, and phase transitions; as such, it is difficult to describe theoretically on a molecular level in systems containing both intermolecular repulsions and attractions. This work describes a simple thermodynamic approach that accounts for intermolecular attractions and repulsions (much like how the van der Waals equation does) to model and help provide an understanding of diffusion. The approach is an extension of the equilibrium Lattice Density Functional Theory of Aranovich and Donohue; it was developed with Mason and Lonsdale's guidelines on how to construct and test a transport theory. In the framework of lattice fluids, this new approach gives (a) correct equilibrium limits, (b) Fickian behavior for non-interacting systems, (c) correct departures from Fickian behavior in non-ideal systems, (d) the correct Maxwell-Stefan formulation, (e) symmetry behavior upon re-labeling species, (f) reasonable non-equilibrium phase behavior, (g) agreement with Molecular Dynamics simulations, (h) agreement with the theory of non-equilibrium thermodynamics, (i) a vanishing diffusive flux at the critical point, and (j) other qualitatively-correct behaviors when applied to problems in porous membranes and in packed beds.

  14. Water vapor diffusion membranes

    NASA Technical Reports Server (NTRS)

    Holland, F. F., Jr.; Smith, J. K.

    1974-01-01

    The program is reported, which was designed to define the membrane technology of the vapor diffusion water recovery process and to test this technology using commercially available or experimental membranes. One membrane was selected, on the basis of the defined technology, and was subjected to a 30-day demonstration trial.

  15. Ti Diffusion in Zircon

    NASA Astrophysics Data System (ADS)

    Cherniak, D. J.; Watson, E. B.

    2006-12-01

    Diffusion of Ti under anhydrous conditions at 1 atmosphere and under fluid-present conditions at 1.1-1.2 GPa has been measured in natural zircon. The source of diffusant for 1-atm experiments was a ZrO2- TiO2-ZrSiO4 mixture, with experiments run in Pt capsules. Diffusion experiments conducted in the presence of H2O-CO2 fluid were run in a piston-cylinder apparatus, using a source of ground TiO2, ZrSiO4 and SiO2, with oxalic acid added to produce H2O-CO2 vapor and partially melt the solid source material, yielding an assemblage of rutile + zircon + melt + vapor. Resonant nuclear reaction analysis (NRA) with the nuclear reaction ^{48}Ti(p,Γ)^{49}V was used to measure diffusion profiles for both sets of experiments. The following Arrhenius relation was obtained for Ti diffusion normal to c over the temperature range 1350-1550C at one atmosphere: DTi = 3.3x102 exp(-754 ± 56 kJ mol-1 /RT) m2sec-1 Ti diffusivities were found to be similar for experiments run under fluid-present conditions. A fit to all of the data yields the Arrhenius relation D = 1.3x103 exp(-741 ± 46 kJ mol-1 /RT) m2sec-1. These data suggest that zircon should be extremely retentive of Ti chemical signatures, indicating that the recently developed Ti-in-zircon crystallization geothermometer (Watson and Harrison, 2005; Watson et al., 2006) will be quite robust in preserving temperatures of zircon crystallization. Titanium diffuses somewhat faster in zircon than larger tetravalent cations U, Th, and Hf, but considerably more slowly than Pb, the REE, and oxygen; hence Ti crystallization temperatures may be retained under circumstances when radiometric ages or other types of geochemical information are lost. Watson EB, Harrison TM (2005) Science 308, 841-844. Watson EB, Wark DA, Thomas JB (2006) CMP(in press).

  16. Adult Children.

    ERIC Educational Resources Information Center

    Frazier, Billie H.

    This document contains a brief bibliography of peer-reviewed literature, with abstracts, on adult children. It is one of 12 bibliographies on aging prepared by the National Agricultural Library for its "Pathfinders" series of publications. Topics covered by the other 11 bibliographies include aging parents, dementia and Alzheimer's disease in the…

  17. Adult Psychology.

    ERIC Educational Resources Information Center

    Bischof, Ledford J.

    This volume comprehensively reviews the research on the psychology of the middle aged (ages 40-65). Topics include the concept of maturity and maturation models, the measurement and influences of adult self image; marriage and sexual patterns; intergenerational relationships between and children; vocations and avocations (work, retirement, play,…

  18. Heterogeneity of chemosensitivity in six clonal cell lines derived from a spontaneous murine astrocytoma and its relationship to genotypic and phenotypic characteristics.

    PubMed

    Bradford, R; Koppel, H; Pilkington, G J; Thomas, D G; Darling, J L

    1997-09-01

    Heterogeneity in drug sensitivity must, in part, account for the relative lack of success with single agent chemotherapy for glioblastoma multiforme (GBM). In order to develop in vitro model systems to investigate this, clones derived from the VM spontaneous murine astrocytoma have been characterised with regard to drug sensitivity. Six clonal cell lines have been tested for sensitivity to a panel of cytotoxic drugs using an intermediate duration 35S-methionine uptake assay. These lines have previously been extensively characterised with regard to morphological, antigenic, kinetic, tumourigenic potential in syngeneic animals and chromosomal properties and display considerable heterogeneity. The present study indicates that heterogeneity extends to sensitivity to all classes of cytotoxic drugs. The greatest difference in sensitivity between the clones was seen in response to cell cycle-specific drugs like the Vinca alkaloids (14-fold and 20-fold for vincristine (VCR) and vindesine (VIND) respectively), while the nitrosoureas, CCNU and BCNU displayed a smaller fold difference in sensitivity (4.3 and 3.6-fold difference respectively). All the clones were considerably more resistant to the adriamycin (ADM), cis-platinum (C-PLAT) and the Vinca alkaloids than the parental cell line although the difference in sensitivity between the clones and parental cell line were less marked for the nitrosoureas and procarbazine (PCB). It has also been possible to examine the relationship between drug sensitivity and the phenotypic and genotypic properties of these clonal cell lines. There is a relationship between chromosome number and sensitivity of a wide variety of cytotoxic drugs including the nitrosoureas, Vinca alkaloids, PCB, C-PLAT, BLEO but not ADR or 5-FU. Clones with small numbers of chromosomes were more resistant than clones with gross polyploidy. Similarly, sensitivity to Vinca alkaloids and ADM, but not other classes of drugs, was greatest in cells with numerous

  19. Erbium diffusion in silicon dioxide

    SciTech Connect

    Lu Yingwei; Julsgaard, B.; Petersen, M. Christian; Jensen, R. V. Skougaard; Pedersen, T. Garm; Pedersen, K.; Larsen, A. Nylandsted

    2010-10-04

    Erbium diffusion in silicon dioxide layers prepared by magnetron sputtering, chemical vapor deposition, and thermal growth has been investigated by secondary ion mass spectrometry, and diffusion coefficients have been extracted from simulations based on Fick's second law of diffusion. Erbium diffusion in magnetron sputtered silicon dioxide from buried erbium distributions has in particular been studied, and in this case a simple Arrhenius law can describe the diffusivity with an activation energy of 5.3{+-}0.1 eV. Within a factor of two, the erbium diffusion coefficients at a given temperature are identical for all investigated matrices.

  20. Instrumentation in Diffuse Optical Imaging

    PubMed Central

    Zhang, Xiaofeng

    2014-01-01

    Diffuse optical imaging is highly versatile and has a very broad range of applications in biology and medicine. It covers diffuse optical tomography, fluorescence diffuse optical tomography, bioluminescence, and a number of other new imaging methods. These methods of diffuse optical imaging have diversified instrument configurations but share the same core physical principle – light propagation in highly diffusive media, i.e., the biological tissue. In this review, the author summarizes the latest development in instrumentation and methodology available to diffuse optical imaging in terms of system architecture, light source, photo-detection, spectral separation, signal modulation, and lastly imaging contrast. PMID:24860804

  1. Vorinostat and Radiation Therapy Followed by Maintenance Therapy With Vorinostat in Treating Younger Patients With Newly Diagnosed Diffuse Intrinsic Pontine Glioma

    ClinicalTrials.gov

    2016-11-02

    Childhood Glioblastoma; Untreated Childhood Anaplastic Astrocytoma; Untreated Childhood Anaplastic Oligoastrocytoma; Untreated Childhood Brain Stem Glioma; Untreated Childhood Giant Cell Glioblastoma; Untreated Childhood Gliosarcoma

  2. ADULT EDUCATION OF MIGRANT ADULTS.

    ERIC Educational Resources Information Center

    BEAL, CATHERINE; AND OTHERS

    UNITS ON MIGRANT ADULT EDUCATION, AND A UNIT ON ORGANIZING INFORMAL GROUPS OF MIGRANT WOMEN TO DISCUSS MAINTAINING AND IMPROVING THEIR TEMPORARY HOMES, ARE PRESENTED. THE GOALS OF THE UNIT ON EDUCATION FOR MIGRANT MEN ARE ECONOMIC INDEPENDENCE, BETTER HEALTH AND WELL-BEING, AND BETTER HANDLING OF RESPONSIBILITIES. THE MAIN DIVISIONS OF THE…

  3. Stereotactic Radiosurgery in Treating Patients With Brain Tumors

    ClinicalTrials.gov

    2012-03-21

    Adult Central Nervous System Germ Cell Tumor; Adult Malignant Meningioma; Adult Medulloblastoma; Adult Noninfiltrating Astrocytoma; Adult Oligodendroglioma; Adult Craniopharyngioma; Adult Meningioma; Brain Metastases; Adult Ependymoma; Adult Pineal Parenchymal Tumor; Adult Brain Stem Glioma; Adult Infiltrating Astrocytoma; Mixed Gliomas; Stage IV Peripheral Primitive Neuroectodermal Tumor

  4. [Adult twins].

    PubMed

    Charlemaine, Christiane

    2006-12-31

    This paper explores the deep roots of closeness that twins share in their youngest age and their effect on their destiny at the adult age. Psychologists believe the bond between twins begins in utero and develops throughout the twins' lives. The four patterns of twinship described show that the twin bond is determined by the quality of parenting that twins receive in their infancy and early childhood. Common problems of adult twins bring about difficulties to adapt in a non-twin world. The nature versus nurture controversy has taken on new life focusing on inter-twin differences and the importance of parent-child interaction as fundamental to the growth and development of personality. PMID:17352324

  5. Fractal model of anomalous diffusion.

    PubMed

    Gmachowski, Lech

    2015-12-01

    An equation of motion is derived from fractal analysis of the Brownian particle trajectory in which the asymptotic fractal dimension of the trajectory has a required value. The formula makes it possible to calculate the time dependence of the mean square displacement for both short and long periods when the molecule diffuses anomalously. The anomalous diffusion which occurs after long periods is characterized by two variables, the transport coefficient and the anomalous diffusion exponent. An explicit formula is derived for the transport coefficient, which is related to the diffusion constant, as dependent on the Brownian step time, and the anomalous diffusion exponent. The model makes it possible to deduce anomalous diffusion properties from experimental data obtained even for short time periods and to estimate the transport coefficient in systems for which the diffusion behavior has been investigated. The results were confirmed for both sub and super-diffusion.

  6. Turbo fluid machinery and diffusers

    NASA Technical Reports Server (NTRS)

    Sakurai, T.

    1984-01-01

    The general theory behind turbo devices and diffusers is explained. Problems and the state of research on basic equations of flow and experimental and measuring methods are discussed. Conventional centrifugation-type compressor and fan diffusers are considered in detail.

  7. Diffuse UV Background Radiation

    NASA Astrophysics Data System (ADS)

    Conn Henry, Richard; Murthy, J.

    2012-01-01

    The diffuse UV sky is expected to glow with significant amounts of starlight that is scattered from the interstellar dust. The albedo and scattering pattern of the dust in the ultraviolet are both well established, and are both fairly independent of wavelength from 912 Å to 3000 Å. We present 1943 Voyager spectra of the diffuse cosmic background radiation from 500 Å to 1200 Å, and we compare their brightnesses, and their distribution on the sky, to those observed (Murthy et al., ApJ 724, 1389, 2010) from the GALEX mission at longer wavelengths (1530 Å). Significant differences appear, suggesting that background radiation components in addition to dust-scattered starlight may be present in both spectral regions.

  8. Nonlocal electrical diffusion equation

    NASA Astrophysics Data System (ADS)

    Gómez-Aguilar, J. F.; Escobar-Jiménez, R. F.; Olivares-Peregrino, V. H.; Benavides-Cruz, M.; Calderón-Ramón, C.

    2016-07-01

    In this paper, we present an analysis and modeling of the electrical diffusion equation using the fractional calculus approach. This alternative representation for the current density is expressed in terms of the Caputo derivatives, the order for the space domain is 0<β≤1 and for the time domain is 0<γ≤2. We present solutions for the full fractional equation involving space and time fractional derivatives using numerical methods based on Fourier variable separation. The case with spatial fractional derivatives leads to Levy flight type phenomena, while the time fractional equation is related to sub- or super diffusion. We show that the mathematical concept of fractional derivatives can be useful to understand the behavior of semiconductors, the design of solar panels, electrochemical phenomena and the description of anomalous complex processes.

  9. Diffusion dans les liquides

    NASA Astrophysics Data System (ADS)

    Dianoux, A. J.

    2003-09-01

    Après une brève introduction qui rappelle les concepts détaillés dans le cours de M. Bée, nous présentons un aperçu de trois de nos travaux sur l'étude de la diffusion. Tout d'abord la dynamique de l'eau, dans son état normal ou surfondu, révèle la complexité apportée par le réseau de liaisons hydrogène. Ensuite l'effet du confinement sur la dynamique de l'eau sera étudié dans le cas de la membrane Nafion. Enfin la diffusion dans les phases nématique et smectique A d'un cristal liquide permet d'obtenir la valeur du potentiel qui maintient les couches dans la phase smectique.

  10. Orientability and Diffusion Maps

    PubMed Central

    Singer, Amit; Wu, Hau-tieng

    2010-01-01

    One of the main objectives in the analysis of a high dimensional large data set is to learn its geometric and topological structure. Even though the data itself is parameterized as a point cloud in a high dimensional ambient space ℝp, the correlation between parameters often suggests the “manifold assumption” that the data points are distributed on (or near) a low dimensional Riemannian manifold ℳd embedded in ℝp, with d ≪ p. We introduce an algorithm that determines the orientability of the intrinsic manifold given a sufficiently large number of sampled data points. If the manifold is orientable, then our algorithm also provides an alternative procedure for computing the eigenfunctions of the Laplacian that are important in the diffusion map framework for reducing the dimensionality of the data. If the manifold is non-orientable, then we provide a modified diffusion mapping of its orientable double covering. PMID:21765628

  11. Galactic Diffuse Polarized Emission

    NASA Astrophysics Data System (ADS)

    Carretti, Ettore

    2011-12-01

    Diffuse polarized emission by synchrotron is a key tool to investigate magnetic fields in the Milky Way, particularly the ordered component of the large scale structure. Key observables are the synchrotron emission itself and the RM is by Faraday rotation. In this paper the main properties of the radio polarized diffuse emission and its use to investigate magnetic fields will be reviewed along with our current understanding of the galactic magnetic field and the data sets available. We will then focus on the future perspective discussing RM-synthesis - the new powerful instrument devised to unlock the information encoded in such an emission - and the surveys currently in progress like S-PASS and GMIMS.

  12. Thermal diffusivity imaging

    NASA Astrophysics Data System (ADS)

    Gfroerer, Tim; Phillips, Ryan; Rossi, Peter

    2015-11-01

    The tip of a rod is heated with a torch and brought into contact with the center of a metal sheet. A thermal camera is then used to image the temperature profile of the surface as a function of time. The infrared camera is capable of recording radiometric data with 1 mK resolution in nearly 105 pixels, so thermal diffusion can be monitored with unprecedented precision. With a frame rate of approximately 10 Hz, the pace of the data acquisition minimizes the loss of accuracy due to inevitable cooling mechanisms. We report diffusivity constants equal to 1.23 ± 0.06 cm2/s in copper and 0.70 ± 0.05 cm2/s in aluminum. The behavior is modeled with a straightforward but oddly under-utilized one-dimensional finite difference method.

  13. Mass transport by diffusion

    NASA Technical Reports Server (NTRS)

    Baird, James K.

    1987-01-01

    For the purpose of determining diffusion coefficients as required for electrodeposition studies and other applications, a diaphragm cell and an isothermal water bath were constructed. the calibration of the system is discussed. On the basis of three calibration runs on the diaphram cell, researchers concluded that the cell constant beta equals 0.12 cm -2 . Other calibration runs in progress should permit the cell constant to be determined with an accuracy of one percent.

  14. Peridynamic thermal diffusion

    SciTech Connect

    Oterkus, Selda; Madenci, Erdogan; Agwai, Abigail

    2014-05-15

    This study presents the derivation of ordinary state-based peridynamic heat conduction equation based on the Lagrangian formalism. The peridynamic heat conduction parameters are related to those of the classical theory. An explicit time stepping scheme is adopted for numerical solution of various benchmark problems with known solutions. It paves the way for applying the peridynamic theory to other physical fields such as neutronic diffusion and electrical potential distribution.

  15. Random diffusion model.

    PubMed

    Mazenko, Gene F

    2008-09-01

    We study the random diffusion model. This is a continuum model for a conserved scalar density field varphi driven by diffusive dynamics. The interesting feature of the dynamics is that the bare diffusion coefficient D is density dependent. In the simplest case, D=D[over ]+D_{1}deltavarphi , where D[over ] is the constant average diffusion constant. In the case where the driving effective Hamiltonian is quadratic, the model can be treated using perturbation theory in terms of the single nonlinear coupling D1 . We develop perturbation theory to fourth order in D1 . The are two ways of analyzing this perturbation theory. In one approach, developed by Kawasaki, at one-loop order one finds mode-coupling theory with an ergodic-nonergodic transition. An alternative more direct interpretation at one-loop order leads to a slowing down as the nonlinear coupling increases. Eventually one hits a critical coupling where the time decay becomes algebraic. Near this critical coupling a weak peak develops at a wave number well above the peak at q=0 associated with the conservation law. The width of this peak in Fourier space decreases with time and can be identified with a characteristic kinetic length which grows with a power law in time. For stronger coupling the system becomes metastable and then unstable. At two-loop order it is shown that the ergodic-nonergodic transition is not supported. It is demonstrated that the critical properties of the direct approach survive, going to higher order in perturbation theory.

  16. Diffusive Shock Acceleration

    NASA Astrophysics Data System (ADS)

    Baring, Matthew

    2003-04-01

    The process of diffusive acceleration of charged particles in shocked plasmas is widely invoked in astrophysics to account for the ubiquitous presence of signatures of non-thermal relativistic electrons and ions in the universe. This statistical energization mechanism, manifested in turbulent media, was first posited by Enrico Fermi in 1949 to explain the observed cosmic ray population, which exhibits an almost power-law distribution in rigidity. The absence of a momentum scale is a key characteristic of diffusive shock acceleration, and astrophysical systems generally only impose scales at the injection (low energy) and loss (high energy) ends of the particle spectrum. The existence of structure in the cosmic ray spectrum (the "knee") at around 3000 TeV has promoted contentions that there are at least two origins for cosmic rays, a galactic one supplying those up to the knee, and perhaps an extragalactic one that can explain even the ultra-high energy cosmic rays (UHECRs) seen at 1-300 EeV. Accounting for the UHECRs with familiar astrophysical sites of acceleration has historically proven difficult due to the need to assume high magnetic fields in order to reduce the shortest diffusive acceleration timescale, the ion gyroperiod, to meaningful values. Yet active galaxies and gamma-ray bursts remain strong and interesting candidate sources for UHECRs, turning the theoretical focus to relativistic shocks. This review summarizes properties of diffusive shock acceleration that are salient to the issue of UHECR generation. These include spectral indices, anisotropies, acceleration efficencies and timescales, as functions of the shock speed and mean field orientation, and also the degree of field turbulence. Astrophysical sites for UHECR production are also critiqued.

  17. Solute diffusion in liquid metals

    NASA Technical Reports Server (NTRS)

    Bhat, B. N.

    1973-01-01

    A gas model of diffusion in liquid metals is presented. In this model, ions of liquid metals are assumed to behave like the molecules in a dense gas. Diffusion coefficient of solute is discussed with reference to its mass, ionic size, and pair potential. The model is applied to the case of solute diffusion in liquid silver. An attempt was made to predict diffusion coefficients of solutes with reasonable accuracy.

  18. Obstructive sleep apnea - adults

    MedlinePlus

    Sleep apnea - obstructive - adults; Apnea - obstructive sleep apnea syndrome - adults; Sleep-disordered breathing - adults; OSA - adults ... When you sleep, all of the muscles in your body become more relaxed. This includes the muscles that help keep your ...

  19. Percolation of interaction diffusing particles

    NASA Technical Reports Server (NTRS)

    Selinger, Robin Blumberg; Stanley, H. Eugene

    1990-01-01

    The connectivity properties of systems of diffusing interacting particles with the blind and myopic diffusion rules are studied. It is found that the blind rule case is equivalent to the lattice gas with J = 0 in all dimensions. The connectivity properties of blind rule diffusion are described by random site percolation due to the fact that the density on neighboring sites is uncorrelated.

  20. The inhibitory effect of CIL-102 on the growth of human astrocytoma cells is mediated by the generation of reactive oxygen species and induction of ERK1/2 MAPK

    SciTech Connect

    Teng, Chih-Chuan; Kuo, Hsing-Chun; Cheng, Ho-Chen; Wang, Ting-Chung; Sze, Chun-I

    2012-08-15

    CIL-102 (1-[4-(furo[2,3-b]quinolin-4-ylamino)phenyl]ethanone) is the major active agent of the alkaloid derivative of Camptotheca acuminata, with multiple pharmacological activities, including anticancer effects and promotion of apoptosis. The mechanism by which CIL-102 inhibits growth remains poorly understood in human astrocytoma cells. Herein, we investigated the molecular mechanisms by which CIL-102 affects the generation of reactive oxygen species (ROS) and cell cycle G2/M arrest in glioma cells. Treatment of U87 cells with 1.0 μM CIL-102 resulted in phosphorylation of extracellular signal-related kinase (ERK1/2), downregulation of cell cycle-related proteins (cyclin A, cyclin B, cyclin D1, and cdk1), and phosphorylation of cdk1Tyr{sup 15} and Cdc25cSer{sup 216}. Furthermore, treatment with the ERK1/2 inhibitor PD98059 abolished CIL-102-induced Cdc25cSer{sup 216} expression and reversed CIL-102-inhibited cdk1 activation. In addition, N-acetyl cysteine (NAC), an ROS scavenger, blocked cell cycle G2/M arrest and phosphorylation of ERK1/2 and Cdc25cSer{sup 216} in U87 cells. CIL-102-mediated ERK1/2 and ROS production, and cell cycle arrest were blocked by treatment with specific inhibitors. In conclusion, we have identified a novel CIL-102-inhibited proliferation in U87 cells by activating the ERK1/2 and Cdc25cSer{sup 216} cell cycle-related proteins and inducing ROS production; this might be a new mechanism in human astrocytoma cells. -- Highlights: ► We show the effects of CIL-102 on the G2/M arrest of human astrocytoma cells. ► ROS and the Ras/ERK1/2 triggering pathways are involved in the CIL-102 treatment. ► CIL-102 induces sustained activation of ERK1/2 and Cdc25c and ROS are required.

  1. Teaching Adults. Third Edition.

    ERIC Educational Resources Information Center

    Rogers, Alan

    The question of how adult educators can make their teaching of adults more effective is explored in the context of recent work on adult lifelong learning. The following are among the topics discussed: (1) modes of adult education and the shift in focus from adult education to lifelong learning; (2) the contract between adult student and adult…

  2. Apparent diffusion coefficient and fractional anisotropy of newly diagnosed grade II gliomas†

    PubMed Central

    Khayal, Inas S.; McKnight, Tracy R.; McGue, Colleen; Vandenberg, Scott; Lamborn, Kathleen R.; Chang, Susan M.; Cha, Soonmee; Nelson, Sarah J.

    2013-01-01

    Distinguishing between low-grade oligodendrogliomas (ODs) and astrocytomas (AC) is of interest for defining prognosis and stratifying patients to specific treatment regimens. The purpose of this study was to determine if the apparent diffusion coefficient (ADC) and fractional anisotropy (FA) from diffusion imaging can help to differentiate between newly diagnosed grade II OD and AC subtypes and to evaluate the ADC and FA values for the mixed population of oligoastrocytomas (OA). Fifty-three patients with newly diagnosed grade II gliomas were studied using a 1.5T whole body scanner (23 ODs, 16 ACs, and 14 OAs). The imaging protocol included post-gadolinium T1-weighted images, T2-weighted images, and either three and/or six directional diffusion imaging sequence with b = 1000 s/mm2. Diffusion-weighted images were analyzed using in-house software to calculate maps of ADC and for six directional acquisitions, FA. The intensity values were normalized by values from normal appearing white matter (NAWM) to generate maps of normalized apparent diffusion coefficient (nADC) and normalized fractional anisotropy (nFA). The hyperintense region in the T2 weighted image was defined as the T2All region. A Mann–Whitney rank-sum test was performed on the 25th, median, and 75th nADC and nFA among the three subtypes. Logistic regression was performed to determine how well the nADC and nFA predict subtype. Lesions diagnosed as being OD had significantly lower nADC and significantly higher nFA, compared to AC. The nADC and nFA values individually classified the data with an accuracy of 87%. Combining the two did not enhance the classification. The patients with OA had nADC and nFA values between those of OD and AC. This suggests that ADC and FA may be helpful in directing tissue sampling to the most appropriate regions for taking biopsies in order to make a definitive diagnosis. PMID:19125391

  3. Particle diffusion in a spheromak

    SciTech Connect

    Meyerhofer, D.D.; Levinton, F.M.; Yamada, M.

    1988-01-01

    The local carbon particle diffusion coefficient was measured in the Proto S-1/C spheromak using a test particle injection scheme. When the plasma was not in a force-free Taylor state, and when there were pressure gradients in the plasma, the particle diffusion was five times that predicted by Bohm and was consistent with collisional drift wave diffusion. The diffusion appears to be driven by correlations of the fluctuating electric field and density. During the decay phase of the discharge when the plasma was in the Taylor state, the diffusion coefficient of the carbon was classical. 23 refs., 4 figs.

  4. Diffuse, Warm Ionized Gas

    NASA Astrophysics Data System (ADS)

    Haffner, L. M.

    2002-05-01

    Over the past decade, new high-sensitivity observations have significantly advanced our knowledge of the diffuse, ionized gas in spiral galaxies. This component of the interstellar medium, often referred to as Warm Ionized Medium (WIM) or Diffuse Ionized Gas (DIG), plays an important role in the complex stellar-interstellar matter and energy cycle. In examining the distribution and physical properties of this gas, we learn not only about the conditions of the medium but also about processes providing heating and ionization in the halos of spiral galaxies. For the Milky Way, three new Hα surveys are available providing large sky coverage, arc-minute spatial resolution, and the ability to kinematically resolve this prominent optical emission line. These new, global views show that the Warm Ionized Medium of the Galaxy is ubiquitous as previously suspected, is rich with filamentary structure down to current resolution limits, and can be traced into the halo at large distances from the Galactic plane. Observations of additional optical emission lines are beginning to probe the physical conditions of the WIM. Early results suggest variations in the temperature and ionization state of the gas which are not adequately explained by Lyman continuum stellar photoionization alone. In parallel with this intensive work in the Milky Way have been numerous studies about the diffuse, ionized gas in other spiral galaxies. Here, deep, face-on spiral investigations provide some of the best maps of the global DIG distribution in a galaxy and begin to allow a probe of the local link between star formation and the powering of ionized gas. In addition, ionized gas has been traced out to impressive distances (z > 3 kpc) in edge-on spirals, revealing out large-scale changes in the physical conditions and kinematics of galactic halos.

  5. Diffusion in silicon isotope heterostructures

    SciTech Connect

    Silvestri, Hughes Howland

    2004-05-14

    The simultaneous diffusion of Si and the dopants B, P, and As has been studied by the use of a multilayer structure of isotopically enriched Si. This structure, consisting of 5 pairs of 120 nm thick natural Si and {sup 28}Si enriched layers, enables the observation of {sup 30}Si self-diffusion from the natural layers into the {sup 28}Si enriched layers, as well as dopant diffusion from an implanted source in an amorphous Si cap layer, via Secondary Ion Mass Spectrometry (SIMS). The dopant diffusion created regions of the multilayer structure that were extrinsic at the diffusion temperatures. In these regions, the Fermi level shift due to the extrinsic condition altered the concentration and charge state of the native defects involved in the diffusion process, which affected the dopant and self-diffusion. The simultaneously recorded diffusion profiles enabled the modeling of the coupled dopant and self-diffusion. From the modeling of the simultaneous diffusion, the dopant diffusion mechanisms, the native defect charge states, and the self- and dopant diffusion coefficients can be determined. This information is necessary to enhance the physical modeling of dopant diffusion in Si. It is of particular interest to the modeling of future electronic Si devices, where the nanometer-scale features have created the need for precise physical models of atomic diffusion in Si. The modeling of the experimental profiles of simultaneous diffusion of B and Si under p-type extrinsic conditions revealed that both species are mediated by neutral and singly, positively charged Si self-interstitials. The diffusion of As and Si under extrinsic n-type conditions yielded a model consisting of the interstitialcy and vacancy mechanisms of diffusion via singly negatively charged self-interstitials and neutral vacancies. The simultaneous diffusion of P and Si has been modeled on the basis of neutral and singly negatively charged self-interstitials and neutral and singly positively charged P

  6. Accelerated stochastic diffusion processes

    NASA Astrophysics Data System (ADS)

    Garbaczewski, Piotr

    1990-07-01

    We give a purely probabilistic demonstration that all effects of non-random (external, conservative) forces on the diffusion process can be encoded in the Nelson ansatz for the second Newton law. Each random path of the process together with a probabilistic weight carries a phase accumulation (complex valued) weight. Random path summation (integration) of these weights leads to the transition probability density and transition amplitude respectively between two spatial points in a given time interval. The Bohm-Vigier, Fenyes-Nelson-Guerra and Feynman descriptions of the quantum particle behaviours are in fact equivalent.

  7. Turbulent forced diffusion flames

    SciTech Connect

    Arpaci, V.S.; Li, C.Y.

    1995-07-01

    It is the purpose of this study to introduce a turbulent microscale appropriate for forced diffusion flames and to propose models for fuel consumption and skin friction in terms of this scale. The study consists of four sections. Following the introduction, Section 2 recapitulates the laminar theories of reacting boundary layers in terms of dimensional arguments and proposes models for fuel consumption and skin friction. Section 3 extends these arguments by introducing a microscale appropriate for turbulent flames and, in terms of this scale, develops models for fuel consumption and skin friction, correlates the experimental data on skin friction, and Section 4 concludes the study.

  8. Diffusion from solid cylinders

    SciTech Connect

    Nestor, C.W. Jr.

    1980-01-01

    The problem considered is the diffusion of material from a solid cylinder initially containng a uniform concentration and immersed in a well-stirred bath which maintains the external concentration at zero. The Fourier-Bessel series form of the fraction of the original material removed from the cylinder as a function of time converges very slowly for small time. An alternate form was obtained, which converges reasonably rapidly for small time. The convergence acceleration method of P. Wynn was also used to provide an efficient method for computation. Numerical examples and program listings are included.

  9. Vapor Diffusion Apparatus

    NASA Technical Reports Server (NTRS)

    2001-01-01

    Vapor Diffusion Apparatus (VDA and VDA-2) was developed by the University of Alabama in Birmingham for NASA's Marshall Space Flight Center. In the original VDA, a protein solution and a precipitant are extruded by two plungers onto the tip of a small syringe and allowed to evaporate, raising the concentration and prompting protein molecules to crystallize. In the VDA-2 version, a third plunger was added to mix the two solutions before returning the mix to the syringe tip. The principal investigator is Dr. Larry Delucas of the University of Alabama in Birmingham

  10. Vapor Diffusion Apparatus

    NASA Technical Reports Server (NTRS)

    2001-01-01

    Vapor Diffusion Apparatus (VDA-2) was developed by the University of Alabama in Birmingham for NASA's Marshall Space Flight Center. In the original VDA, a protein solution and a precipitant are extruded by two plungers onto the tip of a small syringe and allowed to evaporate, raising the concentration and prompting protein molecules to crystallize. In the VDA-2 version, a third plunger was added to mix the two solutions before returning the mix to the syringe tip. The principal investigator is Dr. Larry Delucas of the University of Alabama in Birmingham.

  11. Diffusion characteristics of pediatric pineal tumors

    PubMed Central

    Whitehead, Matthew T; Siddiqui, Adeel; Klimo, Paul; Boop, Frederick A

    2015-01-01

    Background Diffusion weighted imaging (DWI) has been shown to be helpful in characterizing tumor cellularity, and predicting histology. Several works have evaluated this technique for pineal tumors; however studies to date have not focused on pediatric pineal tumors. Objective We evaluated the diffusion characteristics of pediatric pineal tumors to confirm if patterns seen in studies using mixed pediatric and adult populations remain valid. Materials and methods This retrospective study was performed after Institutional Review Board approval. We retrospectively evaluated all patients 18 years of age and younger with pineal tumors from a single institution where preoperative diffusion weighted imaging as well as histologic characterization was available. Results Twenty patients (13 male, 7 female) with pineal tumors were identified: seven with pineoblastoma, four with Primitive Neuroectodermal Tumor (PNET), two with other pineal tumors, and seven with germ cell tumors including two germinomas, three teratomas, and one mixed germinoma-teratoma. The mean apparent diffusion coefficient (ADC) values in pineoblastoma (544 ± 65 × 10–6 mm2/s) and pineoblastoma/PNET (595 ± 144 × 10–6 mm2/s) was lower than that of the germ cell tumors (1284 ± 334 × 10–6 mm2/s; p < 0.0001 vs pineoblastoma). One highly cellular germinoma had an ADC value of 694 × 10–6 mm2/s. Conclusion ADC values can aid in differentiation of pineoblastoma/PNET from germ cell tumors in a population of children with pineal masses. PMID:25963154

  12. Treatment Options for Childhood Astrocytomas

    MedlinePlus

    ... before the cancer is diagnosed and continue for months or years. Signs or symptoms caused by the ... after treatment. Some cancer treatments cause side effects months or years after treatment has ended. Side effects ...

  13. Apparatus for diffusion separation

    DOEpatents

    Nierenberg, William A.

    1976-08-10

    1. A diffuser separator apparatus which comprises a plurality of flow channels in a single stage, each of said channels having an inlet port and an outlet port and a constant cross sectional area between said ports, at least a portion of the defining surface of each of said channels being a diffusion separation membrane, and each of said channels having a different cross sectional area, means for connecting said channels in series so that each successive channel of said series has a smaller cross sectional area than the previous channel of said series, a source of gaseous mixture, individual means for flowing said gaseous mixture to the inlet port of each of said channels, gas receiving and analyzing means, individual means for flowing gas passing from each of said outlet ports and means for flowing gas passing through said membranes to said receiving and analyzing means, and individual means for connecting the outlet port of each channel with the inlet port of the channel having the next smaller cross sectional area.

  14. Diffusing obesity myths.

    PubMed

    Ramos Salas, X; Forhan, M; Sharma, A M

    2014-06-01

    Misinformation or myths about obesity can lead to weight bias and obesity stigma. Counteracting myths with facts and evidence has been shown to be effective educational tools to increase an individuals' knowledge about a certain condition and to reduce stigma.The purpose of this study was to identify common obesity myths within the healthcare and public domains and to develop evidence-based counterarguments to diffuse them. An online search of grey literature, media and public health information sources was conducted to identify common obesity myths. A list of 10 obesity myths was developed and reviewed by obesity experts and key opinion leaders. Counterarguments were developed using current research evidence and validated by obesity experts. A survey of obesity experts and health professionals was conducted to determine the usability and potential effectiveness of the myth-fact messages to reduce weight bias. A total of 754 individuals responded to the request to complete the survey. Of those who responded, 464 (61.5%) completed the survey. All 10 obesity myths were identified to be deeply pervasive within Canadian healthcare and public domains. Although the myth-fact messages were endorsed, respondents also indicated that they would likely not be sufficient to reduce weight bias. Diffusing deeply pervasive obesity myths will require multilevel approaches. PMID:25826775

  15. Sampling diffusive transition paths

    SciTech Connect

    F. Miller III, Thomas; Predescu, Cristian

    2006-10-12

    We address the problem of sampling double-ended diffusive paths. The ensemble of paths is expressed using a symmetric version of the Onsager-Machlup formula, which only requires evaluation of the force field and which, upon direct time discretization, gives rise to a symmetric integrator that is accurate to second order. Efficiently sampling this ensemble requires avoiding the well-known stiffness problem associated with sampling infinitesimal Brownian increments of the path, as well as a different type of stiffness associated with sampling the coarse features of long paths. The fine-features sampling stiffness is eliminated with the use of the fast sampling algorithm (FSA), and the coarse-feature sampling stiffness is avoided by introducing the sliding and sampling (S&S) algorithm. A key feature of the S&S algorithm is that it enables massively parallel computers to sample diffusive trajectories that are long in time. We use the algorithm to sample the transition path ensemble for the structural interconversion of the 38-atom Lennard-Jones cluster at low temperature.

  16. Anisotropic Thermal Diffusion

    NASA Astrophysics Data System (ADS)

    Gardiner, Thomas

    2013-10-01

    Anisotropic thermal diffusion in magnetized plasmas is an important physical phenomena for a diverse set of physical conditions ranging from astrophysical plasmas to MFE and ICF. Yet numerically simulating this phenomenon accurately poses significant challenges when the computational mesh is misaligned with respect to the magnetic field. Particularly when the temperature gradients are unresolved, one frequently finds entropy violating solutions with heat flowing from cold to hot zones for χ∥ /χ⊥ >=102 which is substantially smaller than the range of interest which can reach 1010 or higher. In this talk we present a new implicit algorithm for solving the anisotropic thermal diffusion equations and demonstrate its characteristics on what has become a fairly standard set of test problems in the literature. Sandia National Laboratories is a multi-program laboratory managed and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. Department of Energy's National Nuclear Security Administration under contract DE-AC04-94AL85000. SAND2013-5687A.

  17. Diffuse Alveolar Hemorrhage

    PubMed Central

    2013-01-01

    Diffuse alveolar hemorrhage (DAH) is a life-threatening and medical emergency that can be caused by numerous disorders and presents with hemoptysis, anemia, and diffuse alveolar infiltrates. Early bronchoscopy with bronchoalveolar lavage is usually required to confirm the diagnosis and rule out infection. Most cases of DAH are caused by capillaritis associated with systemic autoimmune diseases such as anti-neutrophil cytoplasmic antibody-associated vasculitis, anti-glomerular basement membrane disease, and systemic lupus erythematosus, but DAH may also result from coagulation disorders, drugs, inhaled toxins, or transplantation. The diagnosis of DAH relies on clinical suspicion combined with laboratory, radiologic, and pathologic findings. Early recognition is crucial, because prompt diagnosis and treatment is necessary for survival. Corticosteroids and immunosuppressive agents remain the gold standard. In patients with DAH, biopsy of involved sites can help to identify the cause and to direct therapy. This article aims to provide a general review of the causes and clinical presentation of DAH and to recommend a diagnostic approach and a management plan for the most common causes. PMID:23678356

  18. Diffuse alveolar hemorrhage.

    PubMed

    Park, Moo Suk

    2013-04-01

    Diffuse alveolar hemorrhage (DAH) is a life-threatening and medical emergency that can be caused by numerous disorders and presents with hemoptysis, anemia, and diffuse alveolar infiltrates. Early bronchoscopy with bronchoalveolar lavage is usually required to confirm the diagnosis and rule out infection. Most cases of DAH are caused by capillaritis associated with systemic autoimmune diseases such as anti-neutrophil cytoplasmic antibody-associated vasculitis, anti-glomerular basement membrane disease, and systemic lupus erythematosus, but DAH may also result from coagulation disorders, drugs, inhaled toxins, or transplantation. The diagnosis of DAH relies on clinical suspicion combined with laboratory, radiologic, and pathologic findings. Early recognition is crucial, because prompt diagnosis and treatment is necessary for survival. Corticosteroids and immunosuppressive agents remain the gold standard. In patients with DAH, biopsy of involved sites can help to identify the cause and to direct therapy. This article aims to provide a general review of the causes and clinical presentation of DAH and to recommend a diagnostic approach and a management plan for the most common causes.

  19. Configurational diffusion of coal macromolecules

    SciTech Connect

    Guin, J.A.; Curtis, C.W.; Tarrer, A.R.

    1991-01-01

    It has been reported that the most predominant constituents of coal extract are the polycyclic aromatic hydrocarbons. Yet the experimental values of diffusivity in ethyl acetate for the most of these materials were not available in the literature. Thus, the diffusion coefficients of some of these materials were measured to increase an understanding of the diffusional behavior of coal macromolecules. In an earlier quarterly report, the authors reported the diffusion coefficients of some model coal molecules determined using their diffusion cell with polycarbonate membranes. Subsequently, they have found that these polycarbonate membranes are semi-permeable to some of the model compounds, so that the measured diffusion flux was greater than that through the pores alone. This extra solute flux could result in over estimation of the diffusion coefficients, therefore, they have now re-measured these diffusivities using polyester, rather than polycarbonate, membranes. The polyester material is not permeable to the solute molecules, except through the open pore area. Thus the only diffusion flux is that through the pores, resulting in correct diffusion coefficients as reported herein. The detailed results are presented in the body of this report. Finally in the last section the authors discuss a slight departure in methodology of some of their earlier planned work. This change will have a positive beneficial impact on the results and speed-up the collection of configurational diffusion data in actual tortuous porous media. 12 refs., 3 figs., 4 tabs.

  20. Sucrose diffusion in aqueous solution.

    PubMed

    Price, Hannah C; Mattsson, Johan; Murray, Benjamin J

    2016-07-28

    The diffusion of sugar in aqueous solution is important both in nature and in technological applications, yet measurements of diffusion coefficients at low water content are scarce. We report directly measured sucrose diffusion coefficients in aqueous solution. Our technique utilises a Raman isotope tracer method to monitor the diffusion of non-deuterated and deuterated sucrose across a boundary between the two aqueous solutions. At a water activity of 0.4 (equivalent to 90 wt% sucrose) at room temperature, the diffusion coefficient of sucrose was determined to be approximately four orders of magnitude smaller than that of water in the same material. Using literature viscosity data, we show that, although inappropriate for the prediction of water diffusion, the Stokes-Einstein equation works well for predicting sucrose diffusion under the conditions studied. As well as providing information of importance to the fundamental understanding of diffusion in binary solutions, these data have technological, pharmaceutical and medical implications, for example in cryopreservation. Moreover, in the atmosphere, slow organic diffusion may have important implications for aerosol growth, chemistry and evaporation, where processes may be limited by the inability of a molecule to diffuse between the bulk and the surface of a particle. PMID:27364512

  1. Sucrose diffusion in aqueous solution

    PubMed Central

    Murray, Benjamin J.

    2016-01-01

    The diffusion of sugar in aqueous solution is important both in nature and in technological applications, yet measurements of diffusion coefficients at low water content are scarce. We report directly measured sucrose diffusion coefficients in aqueous solution. Our technique utilises a Raman isotope tracer method to monitor the diffusion of non-deuterated and deuterated sucrose across a boundary between the two aqueous solutions. At a water activity of 0.4 (equivalent to 90 wt% sucrose) at room temperature, the diffusion coefficient of sucrose was determined to be approximately four orders of magnitude smaller than that of water in the same material. Using literature viscosity data, we show that, although inappropriate for the prediction of water diffusion, the Stokes–Einstein equation works well for predicting sucrose diffusion under the conditions studied. As well as providing information of importance to the fundamental understanding of diffusion in binary solutions, these data have technological, pharmaceutical and medical implications, for example in cryopreservation. Moreover, in the atmosphere, slow organic diffusion may have important implications for aerosol growth, chemistry and evaporation, where processes may be limited by the inability of a molecule to diffuse between the bulk and the surface of a particle. PMID:27364512

  2. A Pilot Feasibility Study of Oral 5-Fluorocytosine and Genetically-Modified Neural Stem Cells Expressing E.Coli Cytosine Deaminase for Treatment of Recurrent High Grade Gliomas

    ClinicalTrials.gov

    2015-03-02

    Adult Anaplastic Astrocytoma; Recurrent Grade III Glioma; Recurrent Grade IV Glioma; Adult Anaplastic Oligodendroglioma; Adult Brain Tumor; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Mixed Glioma; Recurrent Adult Brain Tumor; Adult Anaplastic Oligoastrocytoma; Recurrent High Grade Glioma

  3. Bafetinib in Treating Patients With Recurrent High-Grade Glioma or Brain Metastases

    ClinicalTrials.gov

    2013-03-18

    Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Oligodendroglioma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Mixed Glioma; Recurrent Adult Brain Tumor; Tumors Metastatic to Brain; Adult Anaplastic Oligoastrocytoma

  4. The Harrison Diffusion Kinetics Regimes in Solute Grain Boundary Diffusion

    SciTech Connect

    Belova, Irina; Fiedler, T; Kulkarni, Nagraj S; Murch, Prof. Graeme

    2012-01-01

    Knowledge of the limits of the principal Harrison kinetics regimes (Type-A, B and C) for grain boundary diffusion is very important for the correct analysis of the depth profiles in a tracer diffusion experiment. These regimes for self-diffusion have been extensively studied in the past by making use of the phenomenological Lattice Monte Carlo (LMC) method with the result that the limits are now well established. The relationship of those self-diffusion limits to the corresponding ones for solute diffusion in the presence of solute segregation to the grain boundaries remains unclear. In the present study, the influence of solute segregation on the limits is investigated with the LMC method for the well-known parallel grain boundary slab model by showing the equivalence of two diffusion models. It is shown which diffusion parameters are useful for identifying the limits of the Harrison kinetics regimes for solute grain boundary diffusion. It is also shown how the measured segregation factor from the diffusion experiment in the Harrison Type-B kinetics regime may differ from the global segregation factor.

  5. Diffusing Diffusivity: Survival in a Crowded Rearranging and Bounded Domain.

    PubMed

    Jain, Rohit; Sebastian, Kizhakeyil L

    2016-09-01

    We consider a particle diffusing in a bounded, crowded, rearranging medium. The rearrangement happens on a time scale longer than the typical time scale of diffusion of the particle; as a result, effectively, the diffusion coefficient of the particle varies as a stochastic function of time. What is the probability that the particle will survive within the bounded region, given that it is absorbed the first time it hits the boundary of the region in which it diffuses? This question is of great interest in a variety of chemical and biological problems. If the diffusion coefficient is a constant, then analytical solutions for a variety of cases are available in the literature. However, there is no solution available for the case in which the diffusion coefficient is a random function of time. We discuss a class of models for which it is possible to find analytical solutions to the problem. We illustrate the method for a circular, two-dimensional region, but our methods are easy to apply to diffusion in arbitrary dimensions and spherical/rectangular regions. Our solution shows that if the dimension of the region is large, then only the average value of the diffusion coefficient determines the survival probability. However, for smaller-sized regions, one would be able to see the effects of the stochasticity of the diffusion coefficient. We also give generalizations of the results to N dimensions. PMID:27478982

  6. Chronic obstructive pulmonary disease - adults - discharge

    MedlinePlus

    ... adults - discharge; Chronic obstructive airways disease - adults - discharge; Chronic obstructive lung disease - adults - discharge; Chronic bronchitis - adults - discharge; Emphysema - adults - ...

  7. Adult flatfoot.

    PubMed

    Toullec, E

    2015-02-01

    Adult flatfoot is defined as a flattening of the medial arch of the foot in weight-bearing and lack of a propulsive gait. The 3 lesion levels are the talonavicular, tibiotarsal and midfoot joints. The subtalar joint is damaged by the consequent rotational defects. Clinical examination determines deformity and reducibility, and assesses any posterior tibialis muscle deficit, the posterior tibialis tendon and spring ligament being frequently subject to degenerative lesions. Radiographic examination in 3 incidences in weight-bearing is essential, to determine the principal level of deformity. Tendon (posterior tibialis tendon) and ligamentous lesions (spring ligament and interosseous ligament) are analyzed on MRI or ultrasound. In fixed deformities, CT explores for arthritic evolution or specific etiologies. 3D CT reconstruction can analyze bone and joint morphology and contribute to the planning of any osteotomy. Medical management associates insoles and physiotherapy. Acute painful flatfoot requires strict cast immobilization. Surgical treatment associates numerous combinations of procedures, currently under assessment for supple flatfoot: for the hindfoot: medial slide calcaneal osteotomy, calcaneal lengthening osteotomy, or arthroereisis; for the midfoot: arthrodesis on one or several rays, or first cuneiform or first metatarsal osteotomy; for the ankle: medial collateral ligament repair with tendon transfer. Fixed deformities require arthrodesis of one or several joint-lines in the hindfoot; for the ankle, total replacement after realignment of the foot, or tibiotalocalcaneal fusion or ankle and hindfoot fusion; and, for the midfoot, cuneonavicular or cuneometatarsal fusion. Tendinous procedures are often associated. Specific etiologies may need individualized procedures. In conclusion, adult flatfoot tends to be diagnosed and managed too late, with consequent impact on the ankle, the management of which is complex and poorly codified.

  8. Adult flatfoot.

    PubMed

    Toullec, E

    2015-02-01

    Adult flatfoot is defined as a flattening of the medial arch of the foot in weight-bearing and lack of a propulsive gait. The 3 lesion levels are the talonavicular, tibiotarsal and midfoot joints. The subtalar joint is damaged by the consequent rotational defects. Clinical examination determines deformity and reducibility, and assesses any posterior tibialis muscle deficit, the posterior tibialis tendon and spring ligament being frequently subject to degenerative lesions. Radiographic examination in 3 incidences in weight-bearing is essential, to determine the principal level of deformity. Tendon (posterior tibialis tendon) and ligamentous lesions (spring ligament and interosseous ligament) are analyzed on MRI or ultrasound. In fixed deformities, CT explores for arthritic evolution or specific etiologies. 3D CT reconstruction can analyze bone and joint morphology and contribute to the planning of any osteotomy. Medical management associates insoles and physiotherapy. Acute painful flatfoot requires strict cast immobilization. Surgical treatment associates numerous combinations of procedures, currently under assessment for supple flatfoot: for the hindfoot: medial slide calcaneal osteotomy, calcaneal lengthening osteotomy, or arthroereisis; for the midfoot: arthrodesis on one or several rays, or first cuneiform or first metatarsal osteotomy; for the ankle: medial collateral ligament repair with tendon transfer. Fixed deformities require arthrodesis of one or several joint-lines in the hindfoot; for the ankle, total replacement after realignment of the foot, or tibiotalocalcaneal fusion or ankle and hindfoot fusion; and, for the midfoot, cuneonavicular or cuneometatarsal fusion. Tendinous procedures are often associated. Specific etiologies may need individualized procedures. In conclusion, adult flatfoot tends to be diagnosed and managed too late, with consequent impact on the ankle, the management of which is complex and poorly codified. PMID:25595429

  9. Is anomalous transport diffusive

    SciTech Connect

    Rewoldt, G.

    1989-09-01

    It has often been assumed that the anomalous transport from saturated plasma instabilities is diffusive'' in the sense that the particle flux, {Gamma}, the electron energy flux, q{sub e}, and the ion energy flux, q{sub i}, can be written in forms that are linear in the density gradient, dn/dr, the electron temperature gradient, dT{sub e}/dr, and the ion temperature gradient dT{sub i}/dr. In the simplest form, {Gamma} = {minus} D{sub n}{sup n}(dn/dr), q{sub e} = {minus} D{sub e}{sup e}n(dT{sub e}/dr), and q{sub i} = {minus}D{sub i}{sup i}n(dT{sub i}/dr). A possible generalization of this is to include so-called off-diagonal'' terms, with {Gamma} = nV{sub n} {minus} D{sub n}{sup n}(dn/dr) {minus} D{sub n}{sup e}(n/T{sub e})(dT{sub e}/dr) {minus} D{sub n}{sup i}(n/T{sub i})(dT{sub i}/dr), with corresponding forms for the energy fluxes. Here, general results for the quasilinear particle and energy fluxes, resulting from tokamak linear microinstabilities, are evaluated to assess the relative importance of the diagonal and the off-diagonal terms. A further possible generatlization is to include also contributions to the fluxes from higher powers of the gradients, specifically quadratic'' contributions proportional to (dn/dr){sup 2}, (dn/dr)(dT{sub e}/dr), and so on. A procedure is described for evaluating the corresponding coefficients, and results are presented for illustrative realistic tokamak cases. Qualitatively, it is found that the off-diagonal diffusion coefficients can be as big as the diagonal ones, and that the quadratic terms can be larger than the linear ones. The results thus strongly suggest that the commonly used diffusive'' approximation with only diagonal terms, {Gamma} = {minus}D{sub n}{sup n}(dn/dr), and correspondingly for the energy fluxes, is not adequate in practice. 9 refs., 1 tabs.

  10. Apoplastic diffusion barriers in Arabidopsis.

    PubMed

    Nawrath, Christiane; Schreiber, Lukas; Franke, Rochus Benni; Geldner, Niko; Reina-Pinto, José J; Kunst, Ljerka

    2013-12-27

    During the development of Arabidopsis and other land plants, diffusion barriers are formed in the apoplast of specialized tissues within a variety of plant organs. While the cuticle of the epidermis is the primary diffusion barrier in the shoot, the Casparian strips and suberin lamellae of the endodermis and the periderm represent the diffusion barriers in the root. Different classes of molecules contribute to the formation of extracellular diffusion barriers in an organ- and tissue-specific manner. Cutin and wax are the major components of the cuticle, lignin forms the early Casparian strip, and suberin is deposited in the stage II endodermis and the periderm. The current status of our understanding of the relationships between the chemical structure, ultrastructure and physiological functions of plant diffusion barriers is discussed. Specific aspects of the synthesis of diffusion barrier components and protocols that can be used for the assessment of barrier function and important barrier properties are also presented.

  11. Apoplastic Diffusion Barriers in Arabidopsis

    PubMed Central

    Schreiber, Lukas; Franke, Rochus Benni; Geldner, Niko; Reina-Pinto, José J.; Kunst, Ljerka

    2013-01-01

    During the development of Arabidopsis and other land plants, diffusion barriers are formed in the apoplast of specialized tissues within a variety of plant organs. While the cuticle of the epidermis is the primary diffusion barrier in the shoot, the Casparian strips and suberin lamellae of the endodermis and the periderm represent the diffusion barriers in the root. Different classes of molecules contribute to the formation of extracellular diffusion barriers in an organ- and tissue-specific manner. Cutin and wax are the major components of the cuticle, lignin forms the early Casparian strip, and suberin is deposited in the stage II endodermis and the periderm. The current status of our understanding of the relationships between the chemical structure, ultrastructure and physiological functions of plant diffusion barriers is discussed. Specific aspects of the synthesis of diffusion barrier components and protocols that can be used for the assessment of barrier function and important barrier properties are also presented. PMID:24465172

  12. Osmosis and diffusion conceptual assessment.

    PubMed

    Fisher, Kathleen M; Williams, Kathy S; Lineback, Jennifer Evarts

    2011-01-01

    Biology student mastery regarding the mechanisms of diffusion and osmosis is difficult to achieve. To monitor comprehension of these processes among students at a large public university, we developed and validated an 18-item Osmosis and Diffusion Conceptual Assessment (ODCA). This assessment includes two-tiered items, some adopted or modified from the previously published Diffusion and Osmosis Diagnostic Test (DODT) and some newly developed items. The ODCA, a validated instrument containing fewer items than the DODT and emphasizing different content areas within the realm of osmosis and diffusion, better aligns with our curriculum. Creation of the ODCA involved removal of six DODT item pairs, modification of another six DODT item pairs, and development of three new item pairs addressing basic osmosis and diffusion concepts. Responses to ODCA items testing the same concepts as the DODT were remarkably similar to responses to the DODT collected from students 15 yr earlier, suggesting that student mastery regarding the mechanisms of diffusion and osmosis remains elusive.

  13. Light diffusing fiber optic chamber

    DOEpatents

    Maitland, Duncan J.

    2002-01-01

    A light diffusion system for transmitting light to a target area. The light is transmitted in a direction from a proximal end to a distal end by an optical fiber. A diffusing chamber is operatively connected to the optical fiber for transmitting the light from the proximal end to the distal end and transmitting said light to said target area. A plug is operatively connected to the diffusing chamber for increasing the light that is transmitted to the target area.

  14. Diffusion Coefficients in White Dwarfs

    NASA Astrophysics Data System (ADS)

    Saumon, D.; Starrett, C. E.; Daligault, J.

    2015-06-01

    Models of diffusion in white dwarfs universally rely on the coefficients calculated by Paquette et al. (1986). We present new calculations of diffusion coefficients based on an advanced microscopic theory of dense plasmas and a numerical simulation approach that intrinsically accounts for multiple collisions. Our method is validated against a state-of-the-art method and we present results for the diffusion of carbon ions in a helium plasma.

  15. Diffusion in Jammed Particle Packs.

    PubMed

    Bolintineanu, Dan S; Grest, Gary S; Lechman, Jeremy B; Silbert, Leonardo E

    2015-08-21

    Using random walk simulations we explore diffusive transport through monodisperse sphere packings over a range of packing fractions ϕ in the vicinity of the jamming transition at ϕ(c). Various diffusion properties are computed over several orders of magnitude in both time and packing pressure. Two well-separated regimes of normal "Fickian" diffusion, where the mean squared displacement is linear in time, are observed. The first corresponds to diffusion inside individual spheres, while the latter is the long-time bulk diffusion. The intermediate anomalous diffusion regime and the long-time value of the diffusion coefficient are both shown to be controlled by particle contacts, which in turn depend on proximity to ϕ(c). The time required to recover normal diffusion t* scales as (ϕ-ϕ(c))(-0.5) and the long-time diffusivity D(∞)∼(ϕ-ϕ(c))0.5, or D(∞)∼1/t*. It is shown that the distribution of mean first passage times associated with the escape of random walkers between neighboring particles controls both t* and D(∞) in the limit ϕ→ϕ(c).

  16. Enthalpy Diffusion in Multicomponent Flows

    SciTech Connect

    Cook, A W

    2009-01-20

    The conclusions of this paper are: (1) Enthalpy diffusion preserves the second law. (2) Euler solvers will not produce correct temperatures in mixing regions. (3) Navier-Stokes solvers will only produce correct temperatures if q{sub d} is included. (4) Errors from neglecting enthalpy diffusion are most severe when differences in molecular weights are large. (5) In addition to temperature, enthalpy diffusion affects density, dilatation and other fields in subtle ways. (6) Reacting flow simulations that neglect the term are a dubious proposition. (7) Turbulence models for RANS and LES closures should preserve consistency between energy and species diffusion.

  17. Diffusion rates for elevated releases

    SciTech Connect

    Ramsdell, J.V.

    1983-11-01

    A search of the literature related to diffusion from elevated sources has determined that an adequate data base exists for use in developing parameterizations for estimating diffusion rates for material released from free standing stacks at nuclear power plants. A review of published data analyses indicates that a new parameterization of horizontal diffusion rates specifically for elevated releases is not likely to significantly change the magnitudes of horizontal diffusion coefficients on the average. However, the uncertainties associated with horizontal diffusion coefficient estimates under any given set of atmospheric conditions could be reduced by a new parameterization. Similarly, a new parameterization of vertical diffusion rates would be unlikely to significantly alter the magnitudes of diffusion coefficients for unstable atmospheric conditons. However, for neutral and stable atmospheric conditions, a new parameterization of vertical diffusion rates might increase vertical diffusion coefficients significantly. The increase would move ground-level time-integrated concentration maxima closer to the plant and would increase the maxima. 55 references, 2 figures, 4 tables.

  18. Diffusion in Jammed Particle Packs.

    PubMed

    Bolintineanu, Dan S; Grest, Gary S; Lechman, Jeremy B; Silbert, Leonardo E

    2015-08-21

    Using random walk simulations we explore diffusive transport through monodisperse sphere packings over a range of packing fractions ϕ in the vicinity of the jamming transition at ϕ(c). Various diffusion properties are computed over several orders of magnitude in both time and packing pressure. Two well-separated regimes of normal "Fickian" diffusion, where the mean squared displacement is linear in time, are observed. The first corresponds to diffusion inside individual spheres, while the latter is the long-time bulk diffusion. The intermediate anomalous diffusion regime and the long-time value of the diffusion coefficient are both shown to be controlled by particle contacts, which in turn depend on proximity to ϕ(c). The time required to recover normal diffusion t* scales as (ϕ-ϕ(c))(-0.5) and the long-time diffusivity D(∞)∼(ϕ-ϕ(c))0.5, or D(∞)∼1/t*. It is shown that the distribution of mean first passage times associated with the escape of random walkers between neighboring particles controls both t* and D(∞) in the limit ϕ→ϕ(c). PMID:26340211

  19. Turing instability in reaction-diffusion systems with nonlinear diffusion

    NASA Astrophysics Data System (ADS)

    Zemskov, E. P.

    2013-10-01

    The Turing instability is studied in two-component reaction-diffusion systems with nonlinear diffusion terms, and the regions in parametric space where Turing patterns can form are determined. The boundaries between super- and subcritical bifurcations are found. Calculations are performed for one-dimensional brusselator and oregonator models.

  20. Turing instability in reaction-diffusion systems with nonlinear diffusion

    SciTech Connect

    Zemskov, E. P.

    2013-10-15

    The Turing instability is studied in two-component reaction-diffusion systems with nonlinear diffusion terms, and the regions in parametric space where Turing patterns can form are determined. The boundaries between super- and subcritical bifurcations are found. Calculations are performed for one-dimensional brusselator and oregonator models.

  1. Adult Still's disease

    MedlinePlus

    Still's disease - adult; AOSD ... than 1 out of 100,000 people develop adult-onset Still's disease each year. It affects women more often than men. The cause of adult Still's disease is unknown. No risk factors for ...

  2. Speckle in a thick diffuser

    NASA Astrophysics Data System (ADS)

    Chang, Nien-An

    Theory and experiments on speckle generated from a thick diffuser are presented in this thesis. An overview of speckle from a diffuser in a 4F optical processor gives a basic understanding of the speckle formation and properties. The speckle size depends on the F number of the system, while the interior properties of a diffuser are evident in the wavelength dependence of speckle. We then move on to analyzing speckle from a thick diffuser, which is composed of particles embedded in a host medium. Emphasis on the theory is placed on solving for the wavelength decorrelation of speckle in a thick diffuser. A brief overview of the scattering theory for a particle using the Lorenz-Mie theory is included. Then we present a careful analysis of the speckle created by propagation through a thick diffuser. In the analysis we use an angular spectrum approach that is valid in the non-paraxial case together with a decomposition of the thick diffuser into a cascade of many screens. This calculation is well-suited to numerical analysis and an original computer software program has been provided as an Appendix in this thesis. By adding the scattered field from the randomly-located particles on any screen and propagating through a free space between each screen, one can generate a speckled field after going through the whole cascade. The theoretical predictions are summarized and later compared with experimental results on a series of opal milk glass diffusers. In many practical applications it is particularly advantageous to have mild thick diffusers of controllable diffusivity. We have extensively studied a new diffuser series fabricated using polystyrene spheres of various diameters embedded in gelatin. Theory and experiments are in good agreement.

  3. Panic Disorder among Adults

    MedlinePlus

    ... Hyperactivity Disorder Among Children Autism Spectrum Disorder (ASD) Eating Disorders Among Adults - Anorexia Nervosa Eating Disorders Among Adults - Binge Eating Disorder Eating Disorders Among ...

  4. Bipolar Disorder Among Adults

    MedlinePlus

    ... Hyperactivity Disorder Among Children Autism Spectrum Disorder (ASD) Eating Disorders Among Adults - Anorexia Nervosa Eating Disorders Among Adults - Binge Eating Disorder Eating Disorders Among ...

  5. Major Depression Among Adults

    MedlinePlus

    ... Hyperactivity Disorder Among Children Autism Spectrum Disorder (ASD) Eating Disorders Among Adults - Anorexia Nervosa Eating Disorders Among Adults - Binge Eating Disorder Eating Disorders Among ...

  6. Chromatin remodeling defects in pediatric and young adult glioblastoma: a tale of a variant histone 3 tail.

    PubMed

    Fontebasso, Adam M; Liu, Xiao-Yang; Sturm, Dominik; Jabado, Nada

    2013-03-01

    Primary brain tumors occur in 8 out of 100 000 people and are the leading cause of cancer-related death in children. Among brain tumors, high-grade astrocytomas (HGAs) including glioblastoma multiforme (GBM) are aggressive and are lethal human cancers. Despite decades of concerted therapeutic efforts, HGAs remain essentially incurable in adults and children. Recent discoveries have revolutionized our understanding of these tumors in children and young adults. Recurrent somatic driver mutations in the tail of histone 3 variant 3 (H3.3), leading to amino acid substitutions at key residues, namely lysine (K) 27 (K27M) and glycine 34 (G34R/G34V), were identified as a new molecular mechanism in pediatric GBM. These mutations represent the pediatric counterpart of the recurrent mutations in isocitrate dehydrogenases (IDH) identified in young adult gliomas and provide a much-needed new pathway that can be targeted for therapeutic development. This review will provide an overview of the potential role of these mutations in altering chromatin structure and affecting specific molecular pathways ultimately leading to gliomagenesis. The distinct changes in chromatin structure and the specific downstream events induced by each mutation need characterizing independently if progress is to be made in tackling this devastating cancer. PMID:23432647

  7. Diffusion in jammed particle packs

    NASA Astrophysics Data System (ADS)

    Bolintineanu, Dan S.; Silbert, Leonardo E.; Grest, Gary S.; Lechman, Jeremy B.

    2015-03-01

    Diffusive transport in jammed particle packs is of interest for a number of applications, as well as being a potential indicator of structural properties near the jamming point. To this end, we report stochastic simulations of equilibrium diffusion through monodisperse sphere packs near the jamming point in the limit of a perfectly insulating surrounding medium. The time dependence of various diffusion properties is resolved over several orders of magnitude. Two time regimes of expected Fickian diffusion are observed, separated by an intermediate regime of anomalous diffusion. This intermediate regime grows as the particle volume fraction approaches the critical jamming transition. The diffusion behavior is fully controlled by the extent of the contacts between neighboring particles, which in turn depend on proximity to the jamming point. In particular, the mean first passage time associated with the escape of random walkers between neighboring particles is shown to control both the time to recover Fickian diffusion and the long time diffusivity. Scaling laws are established that relate these quantities to the difference between the actual and critical jamming volume fractions. Sandia National Laboratories is a multiprogram laboratory managed and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. Department of Energy's NNSA under Contract DE- AC04-94AL85000.

  8. Fractional diffusion on bounded domains

    SciTech Connect

    Defterli, Ozlem; D'Elia, Marta; Du, Qiang; Gunzburger, Max Donald; Lehoucq, Richard B.; Meerschaert, Mark M.

    2015-03-13

    We found that the mathematically correct specification of a fractional differential equation on a bounded domain requires specification of appropriate boundary conditions, or their fractional analogue. In this paper we discuss the application of nonlocal diffusion theory to specify well-posed fractional diffusion equations on bounded domains.

  9. Osmosis and Diffusion Conceptual Assessment

    ERIC Educational Resources Information Center

    Fisher, Kathleen M.; Williams, Kathy S.; Lineback, Jennifer Evarts

    2011-01-01

    Biology student mastery regarding the mechanisms of diffusion and osmosis is difficult to achieve. To monitor comprehension of these processes among students at a large public university, we developed and validated an 18-item Osmosis and Diffusion Conceptual Assessment (ODCA). This assessment includes two-tiered items, some adopted or modified…

  10. Teaching Diffusion with a Coin

    ERIC Educational Resources Information Center

    Haddad, Hamilton; Baldo, Marcus Vinicius Chrysostomo

    2010-01-01

    In this article, the authors describe an inexpensive and simple way to make students intuitively experience the probabilistic nature and nonorientated motion of diffusing particles. This understanding allows students to realize why diffusion works so well over short distances and becomes increasingly and rapidly less effective as the distances…

  11. Demonstrating Diffusion: Why the Confusion?

    ERIC Educational Resources Information Center

    Panizzon, Debra Lee

    1998-01-01

    Examines the principles of diffusion and how it may be confused with convection. Suggests that educators may be misleading students and clouding their understanding of the process. Provides two contemporary examples to explain the process of diffusion and how it differs from convection. (Author/CCM)

  12. The Diffusion of New Math.

    ERIC Educational Resources Information Center

    Ready, Patricia M.

    The life cycle of "new math" is fertile ground for the study of the diffusion of an innovation. New math arrived in 1958 to save the day for America after the Soviet Union launched Sputnik, the first successful space flight in 1957. In a period of 16 years an entire diffusion cycle was completed throughout the entire educational system of the…

  13. Thermal diffusivity of diamond films

    NASA Technical Reports Server (NTRS)

    Albin, Sacharia; Winfree, William P.; Crews, B. Scott

    1990-01-01

    A laser pulse technique to measure the thermal diffusivity of diamond films deposited on a silicon substrate is developed. The effective thermal diffusivity of diamond film on silicon was measured by observing the phase and amplitude of the cyclic thermal waves generated by the laser pulses. An analytical model is developed to calculate the effective in-plane (face-parallel) diffusivity of a two layer system. The model is used to reduce the effective thermal diffusivity of the diamond/silicon sample to a value for the thermal diffusivity and conductivity of the diamond film. Phase and amplitude measurements give similar results. The thermal conductivity of the films is found to be better than that of type 1a natural diamond.

  14. Enthalpy Diffusion in Multicomponent Flows

    SciTech Connect

    Cook, A W

    2008-11-12

    The enthalpy diffusion flux in the multicomponent energy equation is a well known yet frequently neglected term. It accounts for energy changes, associated with compositional changes, resulting from species diffusion. Enthalpy diffusion is important in flows where significant mixing occurs between species of dissimilar molecular weight. The term plays a critical role in preventing local violations of the entropy condition. In simulations of nonpremixed combustion, omission of the enthalpy flux can lead to anomalous temperature gradients, which may cause mixing regions to exceed ignition conditions. The term can also play a role in generating acoustic noise in turbulent mixing layers. Euler solvers that rely on numerical diffusion to mix fluids cannot accurately predict the temperature in mixed regions. On the other hand, Navier-Stokes solvers that incorporate enthalpy diffusion can provide much more accurate results.

  15. Heat transfer, diffusion, and evaporation

    NASA Technical Reports Server (NTRS)

    Nusselt, Wilhelm

    1954-01-01

    Although it has long been known that the differential equations of the heat-transfer and diffusion processes are identical, application to technical problems has only recently been made. In 1916 it was shown that the speed of oxidation of the carbon in iron ore depends upon the speed with which the oxygen of the combustion air diffuses through the core of gas surrounding the carbon surface. The identity previously referred to was then used to calculate the amount of oxygen diffusing to the carbon surface on the basis of the heat transfer between the gas stream and the carbon surface. Then in 1921, H. Thoma reversed that procedure; he used diffusion experiments to determine heat-transfer coefficients. Recently Lohrisch has extended this work by experiment. A technically very important application of the identity of heat transfer and diffusion is that of the cooling tower, since in this case both processes occur simultaneously.

  16. Portable vapor diffusion coefficient meter

    DOEpatents

    Ho, Clifford K.

    2007-06-12

    An apparatus for measuring the effective vapor diffusion coefficient of a test vapor diffusing through a sample of porous media contained within a test chamber. A chemical sensor measures the time-varying concentration of vapor that has diffused a known distance through the porous media. A data processor contained within the apparatus compares the measured sensor data with analytical predictions of the response curve based on the transient diffusion equation using Fick's Law, iterating on the choice of an effective vapor diffusion coefficient until the difference between the predicted and measured curves is minimized. Optionally, a purge fluid can forced through the porous media, permitting the apparatus to also measure a gas-phase permeability. The apparatus can be made lightweight, self-powered, and portable for use in the field.

  17. Ammonia diffusion through Nalophan™ bags.

    PubMed

    Sironi, Selena; Eusebio, Lidia; Dentoni, Licinia; Capelli, Laura; Del Rosso, Renato

    2014-01-01

    The aim of the work is to verify the diffusion rate of ammonia through the Nalophan™ film that constitutes the sampling bag, considering storage times ranging from 1 to 26 h. The ammonia decay over time was evaluated using gas-chromatography for the quantification of ammonia concentration inside the bag. The research assesses the roles of both of ammonia and water concentration gradients at the polymeric film interface on the diffusion process. The results show that both the ammonia concentration gradient and, in a less pronounced way, the water concentration gradient are the main 'engines' of ammonia diffusion. Double bags seem to represent a simple solution for preventing ammonia losses during storage. Another interesting result concerns the role of the bag surface on the ammonia diffusion rate: the higher the surface/volume (S/V) ratio, the higher the ammonia diffusion rate through the polymeric film.

  18. Diffusion of childbearing within cohabitation.

    PubMed

    Vitali, Agnese; Aassve, Arnstein; Lappegård, Trude

    2015-04-01

    The article analyzes the diffusion of childbearing within cohabitation in Norway, using municipality data over a 24-year period (1988-2011). Research has found substantial spatial heterogeneity in this phenomenon but also substantial spatial correlation, and the prevalence of childbearing within cohabitation has increased significantly over time. We consider several theoretical perspectives and implement a spatial panel model that allows accounting for autocorrelation not only on the dependent variable but also on key explanatory variables, and hence identifies the key determinants of diffusion of childbearing within cohabitation across space and over time. We find only partial support for the second demographic transition as a theory able to explain the diffusion of childbearing within cohabitation. Our results show that at least in the first phase of the diffusion (1988-1997), economic difficulties as measured by increased unemployment among men contributed to the diffusion of childbearing within cohabitation. However, the most important driver for childbearing within cohabitation is expansion in education for women.

  19. Diffusion in membranes: Toward a two-dimensional diffusion map

    NASA Astrophysics Data System (ADS)

    Toppozini, Laura; Garcia-Sakai, Victoria; Bewley, Robert; Dalgliesh, Robert; Perring, Toby; Rheinstädter, Maikel C.

    2015-01-01

    For decades, quasi-elastic neutron scattering has been the prime tool for studying molecular diffusion in membranes over relevant nanometer distances. These experiments are essential to our current understanding of molecular dynamics of lipids, proteins and membrane-active molecules. Recently, we presented experimental evidence from X-ray diffraction and quasi-elastic neutron scattering demonstrating that ethanol enhances the permeability of membranes. At the QENS 2014/WINS 2014 conference we presented a novel technique to measure diffusion across membranes employing 2-dimensional quasi-elastic neutron scattering. We present results from our preliminary analysis of an experiment on the cold neutron multi-chopper spectrometer LET at ISIS, where we studied the self-diffusion of water molecules along lipid membranes and have the possibility of studying the diffusion in membranes. By preparing highly oriented membrane stacks and aligning them horizontally in the spectrometer, our aim is to distinguish between lateral and transmembrane diffusion. Diffusion may also be measured at different locations in the membranes, such as the water layer and the hydrocarbon membrane core. With a complete analysis of the data, 2-dimensional mapping will enable us to determine diffusion channels of water and ethanol molecules to quantitatively determine nanoscale membrane permeability.

  20. Diffusion with optimal resetting

    NASA Astrophysics Data System (ADS)

    Evans, Martin R.; Majumdar, Satya N.

    2011-10-01

    We consider the mean time to absorption by an absorbing target of a diffusive particle with the addition of a process whereby the particle is reset to its initial position with rate r. We consider several generalizations of the model of Evans and Majumdar (2011 Phys. Rev. Lett.106 160601): (i) a space-dependent resetting rate r(x); (ii) resetting to a random position z drawn from a resetting distribution { P}(z); and (iii) a spatial distribution for the absorbing target PT(x). As an example of (i) we show that the introduction of a non-resetting window around the initial position can reduce the mean time to absorption provided that the initial position is sufficiently far from the target. We address the problem of optimal resetting, that is, minimizing the mean time to absorption for a given target distribution. For an exponentially decaying target distribution centred at the origin we show that a transition in the optimal resetting distribution occurs as the target distribution narrows.

  1. Photoacoustic thermal diffusion flowmetry

    PubMed Central

    Sheinfeld, Adi; Eyal, Avishay

    2012-01-01

    Thermal Diffusion Flowmetry (TDF) (also called Heat Clearance Method or Thermal Clearance Method) is a longstanding technique for measuring blood flow or blood perfusion in living tissues. Typically, temperature transients and/or gradients are induced in a volume of interest and the temporal and/or spatial temperature variations which follow are measured and used for calculation of the flow. In this work a new method for implementing TDF is studied theoretically and experimentally. The heat deposition which is required for TDF is implemented photothermally (PT) and the measurement of the induced temperature variations is done by photoacoustic (PA) thermometry. Both excitation light beams (the PT and the PA) are produced by directly modulated 830 nm laser diodes and are conveniently delivered to the volume under test by the same optical fiber. The method was tested experimentally using a blood-filled phantom vessel and the results were compared with a theoretical prediction based on the heat and the photoacoustic equations. The fitting of a simplified lumped thermal model to the experimental data yielded estimated values of the blood velocity at different flow rates. By combining additional optical sources at different wavelengths it will be possible to utilize the method for non-invasive simultaneous measurement of blood flow and oxygen saturation using a single fiber probe. PMID:22574267

  2. Diffuse gamma radiation

    NASA Technical Reports Server (NTRS)

    Fichtel, C. E.; Simpson, G. A.; Thompson, D. J.

    1977-01-01

    An examination of the intensity, energy spectrum, and spatial distribution of the diffuse gamma-radiation observed by SAS-2 satellite away from the galactic plane in the energy range above 35 MeV has shown that it consists of two components. One component is generally correlated with galactic latitudes, the atomic hydrogen column density was deduced from 21 cm measurements, and the continuum radio emission, believed to be synchrotron emission. It has an energy spectrum similar to that in the plane and joins smoothly to the intense radiation from the plane. It is therefore presumed to be of galactic origin. The other component is apparently isotropic, at least on a coarse scale, and has a steep energy spectrum. No evidence is found for a cosmic ray halo surrounding the galaxy in the shape of a sphere or oblate spheroid with galactic dimensions. Constraints for a halo model with significantly larger dimensions are set on the basis of an upper limit to the gamma-ray anisotropy.

  3. Diffuse Microwave Emission Survey

    NASA Astrophysics Data System (ADS)

    Shafer, R. A.; Mather, J.; Kogut, A.; Fixsen, D. J.; Seiffert, M.; Lubin, P. M.; Levin, S. M.

    1996-12-01

    The Diffuse Microwave Emission Survey (DIMES) is a mission concept selected by NASA in 1995 to answer fundamental questions about the content and history of the universe. DIMES will use a set of absolutely calibrated cryogenic radiometers from a space platform to measure the frequency spectrum of the cosmic microwave background (CMB) at wavelengths 15--0.3 cm (frequency 2--100 GHz) to precision 0.1 mK or better. Measurements at centimeter wavelengths probe different physical processes than the COBE-FIRAS spectra at shorter wavelengths, and complement the anisotropy measurements from DMR, balloon and ground-based instruments, and the planned MAP and COBRAS/SAMBA satellites. DIMES will observe the free-free signal from early photoionization to establish the precise epoch of structure formation, and will measure or limit energy release at redshift 10(4) < z < 10(7) by measuring the chemical potential distortion of the CMB spectrum. Both are likely under current cosmological theory and allowed by current measurement limits; even an upper limit at the expected sensitivity 10(-5) MJy/sr will place important constraints on the matter content, structure, and evolution of the universe. Detecting these distortions or showing that they do not exist constitutes the last frontier of CMB observations.

  4. Handheld Diffusion Test Cells

    NASA Technical Reports Server (NTRS)

    2001-01-01

    This photo shows the Handheld Diffusion Test Cell (HH-DTC) apparatus flown on the Space Shuttle. Similar cells (inside the plastic box) will be used in the Observable Protein Crystal Growth Apparatus (OPCGA) to be operated aboard the International Space Station (ISS). The principal investigator is Dr. Alex McPherson of the University of California, Irvine. Each individual cell comprises two sample chambers with a rotating center section that isolates the two from each other until the start of the experiment and after it is completed. The cells are made from optical-quality quartz glass to allow photography and interferometric observations. Each cell has a small light-emitting diode and lens to back-light the solution. In protein crystal growth experiments, a precipitating agent such as a salt solution is used to absorb and hold water but repel the protein molecules. This increases the concentration of protein until the molecules nucleate to form crystals. This cell is one of 96 that make up the experiment module portion of the OPCGA.

  5. Handheld Diffusion Test Cells

    NASA Technical Reports Server (NTRS)

    2001-01-01

    This photo shows an individual cell from the Handheld Diffusion Test Cell (HH-DTC) apparatus flown on the Space Shuttle. Similar cells will be used in the Observable Protein Crystal Growth Apparatus (OPCGA) to be operated aboard the International Space Station (ISS). The principal investigator is Dr. Alex McPherson of the University of California, Irvine. Each individual cell comprises two sample chambers with a rotating center section that isolates the two from each other until the start of the experiment and after it is completed. The cells are made from optical-quality quartz glass to allow photography and interferometric observations. Each cell has a small light-emitting diode and lens to back-light the solution. In protein crystal growth experiments, a precipitating agent such as a salt solution is used to absorb and hold water but repel the protein molecules. This increases the concentration of protein until the molecules nucleate to form crystals. This cell is one of 96 that make up the experiment module portion of the OPCGA.

  6. Transdermal diffusion of xenon in vitro using diffusion cells

    NASA Astrophysics Data System (ADS)

    Verkhovsky, A.; Petrov, E.

    2015-11-01

    The aim of this research was to study the diffusion rate of xenon through guinea pig skin and how viscosity of cosmetic component capryl/capric triglyceride (CCT) facilitates to deliver xenon to surface of skin patches. They were placed in Franz cell for 24 hours and diffusion rate and permeability of xenon were calculated. Thus diffusion rate was 0.031 mg/hour*cm2 and permeability was 0.003 cm/hour. Using Brookfield viscometer it was shown that viscosity of CCT decreased upon increasing xenon concentration. Obtained results can be utilized in developing of new xenon containing drugs for topical administration.

  7. Single file diffusion in microtubules

    NASA Astrophysics Data System (ADS)

    Rutenberg, Andrew; Farrell, Spencer; Brown, Aidan

    2015-03-01

    We investigate the single file diffusion (SFD) of large particles entering a confined tubular geometry, such as luminal diffusion of proteins inside microtubules or flagella. While single-file effects have no effect on particle density, we report significant single-file effects for individually-tracked tracer particle motion. Both exact and approximate ordering statistics of particles entering semi-infinite tubes agree well with our stochastic simulations. Considering initially empty semi-infinite tubes, with particles entering at one end starting from an initial time t = 0 , tracked particles display super-diffusive effective exponents just after they enter the system and trends towards diffusive exponents at later times. Equivalently, if diffusive exponents are assumed the effective diffusivity is reduced at early times and enhanced at later times through a logarithmic factor logN , where N is the number of particles in the tube. When we number each particle from the first (n = 1) to the most recent (n = N), we find good scaling collapse of the effective diffusivity for all n. Techniques that track individual particles, or local groups of particles, such as photo-activation or photobleaching, will exhibit single-file effects.

  8. Cytoplasmic hydrogen ion diffusion coefficient.

    PubMed Central

    al-Baldawi, N F; Abercrombie, R F

    1992-01-01

    The apparent cytoplasmic proton diffusion coefficient was measured using pH electrodes and samples of cytoplasm extracted from the giant neuron of a marine invertebrate. By suddenly changing the pH at one surface of the sample and recording the relaxation of pH within the sample, an apparent diffusion coefficient of 1.4 +/- 0.5 x 10(-6) cm2/s (N = 7) was measured in the acidic or neutral range of pH (6.0-7.2). This value is approximately 5x lower than the diffusion coefficient of the mobile pH buffers (approximately 8 x 10(-6) cm2/s) and approximately 68x lower than the diffusion coefficient of the hydronium ion (93 x 10(-6) cm2/s). A mobile pH buffer (approximately 15% of the buffering power) and an immobile buffer (approximately 85% of the buffering power) could quantitatively account for the results at acidic or neutral pH. At alkaline pH (8.2-8.6), the apparent proton diffusion coefficient increased to 4.1 +/- 0.8 x 10(-6) cm2/s (N = 7). This larger diffusion coefficient at alkaline pH could be explained quantitatively by the enhanced buffering power of the mobile amino acids. Under the conditions of these experiments, it is unlikely that hydroxide movement influences the apparent hydrogen ion diffusion coefficient. PMID:1617134

  9. Amplitude equations for reaction-diffusion systems with cross diffusion

    NASA Astrophysics Data System (ADS)

    Zemskov, Evgeny P.; Vanag, Vladimir K.; Epstein, Irving R.

    2011-09-01

    Using Taylor series expansion, multiscaling, and further expansion in powers of a small parameter, we develop general amplitude equations for two-variable reaction-diffusion systems with cross-diffusion terms in the cases of Hopf and Turing instabilities. We apply this analysis to the Oregonator and Brusselator models and find that inhibitor cross diffusion induced by the activator and activator cross diffusion induced by the inhibitor have opposite effects in the two models as a result of the different structure of their community matrices. Our analysis facilitates finding regions of supercritical and subcritical bifurcations, as well as wave and antiwave domains and domains of turbulent waves in the case of Hopf instability.

  10. Amplitude equations for reaction-diffusion systems with cross diffusion.

    PubMed

    Zemskov, Evgeny P; Vanag, Vladimir K; Epstein, Irving R

    2011-09-01

    Using Taylor series expansion, multiscaling, and further expansion in powers of a small parameter, we develop general amplitude equations for two-variable reaction-diffusion systems with cross-diffusion terms in the cases of Hopf and Turing instabilities. We apply this analysis to the Oregonator and Brusselator models and find that inhibitor cross diffusion induced by the activator and activator cross diffusion induced by the inhibitor have opposite effects in the two models as a result of the different structure of their community matrices. Our analysis facilitates finding regions of supercritical and subcritical bifurcations, as well as wave and antiwave domains and domains of turbulent waves in the case of Hopf instability. PMID:22060484

  11. Turing instabilities in reaction-diffusion systems with cross diffusion

    NASA Astrophysics Data System (ADS)

    Fanelli, Duccio; Cianci, Claudia; Di Patti, Francesca

    2013-04-01

    The Turing instability paradigm is revisited in the context of a multispecies diffusion scheme derived from a self-consistent microscopic formulation. The analysis is developed with reference to the case of two species. These latter share the same spatial reservoir and experience a degree of mutual interference due to the competition for the available resources. Turing instability can set in for all ratios of the main diffusivities, also when the (isolated) activator diffuses faster then the (isolated) inhibitor. This conclusion, at odd with the conventional vision, is here exemplified for the Brusselator model and ultimately stems from having assumed a generalized model of multispecies diffusion, fully anchored to first principles, which also holds under crowded conditions.

  12. Fick's Insights on Liquid Diffusion

    SciTech Connect

    Narasimhan, T.N.

    2004-10-07

    In 1855, Adolph Fick published ''On Liquid Diffusion'', mathematically treating salt movements in liquids as a diffusion process, analogous to heat diffusion. Less recognized is the fact that Fick also provided a detailed account of the implications of salt diffusion to transport through membranes. A careful look at Fick (1855) shows that his conceptualization of molecular diffusion was more comprehensive than could be captured with the mathematical methods available to him, and therefore his expression, referred to as Fick's Law, dealt only with salt flux. He viewed salt diffusion in liquids as a binary process, with salt moving in one way and water moving in the other. Fick's analysis of the consequences of such a binary process operating in a hydrophilic pore in a membrane offers insights that are relevant to earth systems. This paper draws attention to Fick's rationale, and its implications to hydrogeological systems. Fick (1829-1901; Figure 1), a gifted scientist, published the first book on medical physics (Fick, 1858), discussing the application of optics, solid mechanics, gas diffusion, and heat budget to biological systems. Fick's paper is divisible into two parts. The first describes his experimental verification of the applicability of Fourier's equation to liquid diffusion. The second is a detailed discussion of diffusion through a membrane. Although Fick's Law specifically quantifies solute flux, Fick visualized a simultaneous movement of water and stated, ''It is evident that a volume of water equal to that of the salt passes simultaneously out of the upper stratum into the lower.'' (Fick, 1855, p.30). Fick drew upon Fourier's model purely by analogy. He assumed that concentration gradient impelled salt movement, without inquiring why concentration gradient should constitute a driving force. As for water movement, he stated intuitively, ''a force of suction comes into play on each side of the membrane, proportional to the difference of concentration

  13. Adult Recruitment Practices.

    ERIC Educational Resources Information Center

    Kaufman, Juliet, Ed.; And Others

    Findings of an American College Testing Program 1981 survey on college recruitment of adult students are summarized, and 12 articles on adult recruitment are presented. Titles and authors are as follows: "Adult Recruitment Practices: A Report of a National Survey" (Patricia Spratt, Juliet Kaufmann, Lee Noel); "Three Programs for Adults in Shopping…

  14. ALUMINUM IMPURITY DIFFUSION IN MAGNESIUM

    SciTech Connect

    Brennan, Sarah; Warren, Andrew; Coffey, Kevin; Kulkarni, Nagraj S; Todd, Peter J; Sohn, Yong Ho; Klimov, Mikhail

    2012-01-01

    The Al impurity diffusion in polycrystalline Mg (99.9%) via depth profiling with secondary ion mass spectrometry was studied in the temperature range of 673-573K, utilizing the thin film method and thin film solution to the diffusion equation. Multiple samples were utilized and multiple profiles were obtained to determine statistically confident coefficient with maximum standard deviation of 16%. Activation energy and pre-exponential factor of Al impurity diffusion in Mg was determined as 155 kJ/mole and 3.9 x 10-3 m2/sec.

  15. BEAM DIFFUSION MEASUREMENTS AT RHIC.

    SciTech Connect

    FLILLER,R.P.,IIIDREES,A.GASSNER,D.MCINTYRE,G.PEGGS,S.TRBOJEVIC,D.

    2003-05-12

    During a store, particles from the beam core continually diffuse outwards into the halo through a variety of mechanisms. Understanding the diffusion rate as a function of particle amplitude can help discover which processes are important to halo growth. A collimator can be used to measure the amplitude growth rate as a function of the particle amplitude. In this paper we present results of diffusion measurements performed at the Relativistic Heavy Ion Collider (RHIC) with fully stripped gold ions, deuterons, and protons. We compare these results with measurements from previous years, and simulations, and discuss any factors that relate to beam growth in RHIC.

  16. Interference of diffusive light waves.

    PubMed

    Schmitt, J M; Knüttel, A; Knutson, J R

    1992-10-01

    We examine interference effects resulting from the superposition of photon-density waves produced by coherently modulated light incident upon a turbid medium. Photon-diffusion theory is used to derive expressions for the ac magnitude and phase of the aggregate diffusive wave produced in full- and half-space volumes by two sources. Using a frequency-domain spectrometer operating at 410 MHz, we verify interference patterns predicted by the model in scattering samples having optical properties similar to those of skin tissue. Potential imaging applications of interfering diffusive waves are discussed in the context of the theoretical and experimental results.

  17. Diffuser for augmenting a wind turbine

    DOEpatents

    Foreman, Kenneth M.; Gilbert, Barry L.

    1984-01-01

    A diffuser for augmenting a wind turbine having means for energizing the boundary layer at several locations along the diffuser walls is improved by the addition of a short collar extending radially outward from the outlet of the diffuser.

  18. Improved diffuser for augmenting a wind turbine

    DOEpatents

    Foreman, K.M.; Gilbert, B.L.

    A diffuser for augmenting a wind turbine having means for energizing the boundary layer at several locations along the diffuser walls is improved by the addition of a short collar extending radially outward from the outlet of the diffuser.

  19. Floating-diffusion electrometer with adjustable sensitivity

    NASA Technical Reports Server (NTRS)

    Tower, John R. (Inventor)

    1989-01-01

    The effective capacitance of the floating diffusion in a floating-diffusion electrometer is modified to adjust electrometer sensitivity. This is done by changing the direct potential applied to a gate electrode proximate to the floating diffusion.

  20. Adult medulloblastoma: multiagent chemotherapy.

    PubMed Central

    Greenberg, H. S.; Chamberlain, M. C.; Glantz, M. J.; Wang, S.

    2001-01-01

    and 6 relapsed after completing all therapy at 18, 18, 26, 30, 40, and 48 months. The estimated median survival of all patients was 56 months (95% confidence interval, 27 to infinity) with 11 patients alive; for the Packer protocol, median survival was 36 months, and for the POG protocol, it was 57 months (P = 0.058). The hazard ratio was 0 (95% confidence interval, 0 to infinity). Toxicity during the Packer protocol was moderately severe, with only 1 of 10 patients able to complete all therapy. Two patients had severe abdominal pain during CSRT + vincristine, and 5 had peripheral neuropathy during vincristine therapy. Hearing loss (>20 dB) occurred in 7, neutropenia (<500 microl) in 6, thrombocytopenia (<50,000 microl) in 6, nephrotoxicity (>25% decrease by creatinine clearance) in 2, and decreased pulmonary function (diffusing capacity for carbon monoxide decrease >40%) in 1. On the POG protocol, only 1 patient had persistent nausea and vomiting, 2 had peripheral neuropathy, and 3 had hearing deficit (>20 dB) or tinnitus. The POG and Packer protocols did not have a statistically significant difference in relapse-free or overall survival because of the small sample size. The POG protocol seemed to have less nonhematologic toxicity. Adults on the Packer protocol appeared to have shorter median survival and greater toxicity than did children. To know whether adding adjuvant chemotherapy to craniospinal radiation in adult therapy increases relapse-free and overall survival, we must await the results of a larger randomized controlled clinical trial. PMID:11305414

  1. Flow development through interturbine diffusers

    SciTech Connect

    Dominy, R.G.; Kirkham, D.A.; Smith, A.D.

    1998-04-01

    Interturbine diffusers offer the potential advantage of reducing the flow coefficient in the following stages, leading to increased efficiency. The flows associated with these ducts differ from those in simple annular diffusers both as a consequence of their high-curvature S-shaped geometry and of the presence of wakes created by the upstream turbine. Experimental data and numerical simulations clearly reveal the generation of significant secondary flows as the flow develops through the diffuser in the presence of cross-passage pressure gradients. The further influence of inlet swirl is also demonstrated. Data from experimental measurements with and without an upstream turbine are discussed and computational simulations are shown not only to give a good prediction of the flow development within the diffuser but also to demonstrate the importance of modeling the fully three-dimensional nature of the flow.

  2. Diffusion technique stabilizes resistor values

    NASA Technical Reports Server (NTRS)

    Gallagher, R. C.; Giuliano, M. N.

    1966-01-01

    Reduction of the contact resistance stabilizes the values, over a broad temperature range, of resistors used in linear integrated circuits. This reduction is accomplished by p-plus diffusion under the alloyed aluminum contacts.

  3. Geometric diffusion of quantum trajectories.

    PubMed

    Yang, Fan; Liu, Ren-Bao

    2015-07-16

    A quantum object can acquire a geometric phase (such as Berry phases and Aharonov-Bohm phases) when evolving along a path in a parameter space with non-trivial gauge structures. Inherent to quantum evolutions of wavepackets, quantum diffusion occurs along quantum trajectories. Here we show that quantum diffusion can also be geometric as characterized by the imaginary part of a geometric phase. The geometric quantum diffusion results from interference between different instantaneous eigenstate pathways which have different geometric phases during the adiabatic evolution. As a specific example, we study the quantum trajectories of optically excited electron-hole pairs in time-reversal symmetric insulators, driven by an elliptically polarized terahertz field. The imaginary geometric phase manifests itself as elliptical polarization in the terahertz sideband generation. The geometric quantum diffusion adds a new dimension to geometric phases and may have applications in many fields of physics, e.g., transport in topological insulators and novel electro-optical effects.

  4. Fractional-calculus diffusion equation

    PubMed Central

    2010-01-01

    Background Sequel to the work on the quantization of nonconservative systems using fractional calculus and quantization of a system with Brownian motion, which aims to consider the dissipation effects in quantum-mechanical description of microscale systems. Results The canonical quantization of a system represented classically by one-dimensional Fick's law, and the diffusion equation is carried out according to the Dirac method. A suitable Lagrangian, and Hamiltonian, describing the diffusive system, are constructed and the Hamiltonian is transformed to Schrodinger's equation which is solved. An application regarding implementation of the developed mathematical method to the analysis of diffusion, osmosis, which is a biological application of the diffusion process, is carried out. Schrödinger's equation is solved. Conclusions The plot of the probability function represents clearly the dissipative and drift forces and hence the osmosis, which agrees totally with the macro-scale view, or the classical-version osmosis. PMID:20492677

  5. Adult Cancers in Adolescents and Young Adults.

    PubMed

    Laurence, Valérie; Marples, Maria; Stark, Daniel P

    2016-01-01

    The pattern of cancer seen in young people changes with increasing age, transitioning from childhood- to adult-type cancer in adolescence and the third decade. The risk factors, presentation and biology of cancer in young adults differ from those in the older adult population. Factors of particular significance in adolescents and young adults (AYAs) include genetic predisposition to adult-type cancer, diagnostic uncertainty, long-term morbidity and considerations of fertility. New systemic therapies are being introduced that can prolong life and even increase the chance of cure, but the impact on AYAs is uncertain, as these patients are often under-represented in clinical trials. Here, we discuss the management of AYAs with 3 of the most common cancers affecting adults, when they emerge in the AYA populations, and therefore are currently met by medical oncologists - breast cancer, colorectal cancer and melanoma. PMID:27595357

  6. Validation of practical diffusion approximation for virtual near infrared spectroscopy using a digital head phantom

    NASA Astrophysics Data System (ADS)

    Oki, Yosuke; Kawaguchi, Hiroshi; Okada, Eiji

    2009-03-01

    Light propagation in the digital head phantom for virtual near infrared spectroscopy and imaging is calculated by diffusion theory. In theory, diffusion approximation is not valid in a low-scattering cerebrospinal fluid (CSF) layer around the brain. The optical path length and spatial sensitivity profile predicted by the finite element method based upon the diffusion theory are compared with those predicted by the Monte Carlo method to validate a practical implementation of diffusion approximation to light propagation in an adult head. The transport scattering coefficient of the CSF layer is varied from 0.01 to 1.0 mm-1 to evaluate the influence of that layer on the error caused by diffusion approximation. The error is practically ignored and the geometry of the brain surface such as the sulcus structure in the digital head phantom scarcely affects the error when the transport scattering coefficient of the CSF layer is greater than 0.3 mm-1.

  7. Uphill diffusion in multicomponent mixtures.

    PubMed

    Krishna, Rajamani

    2015-05-21

    Molecular diffusion is an omnipresent phenomena that is important in a wide variety of contexts in chemical, physical, and biological processes. In the majority of cases, the diffusion process can be adequately described by Fick's law that postulates a linear relationship between the flux of any species and its own concentration gradient. Most commonly, a component diffuses down the concentration gradient. The major objective of this review is to highlight a very wide variety of situations that cause the uphill transport of one constituent in the mixture. Uphill diffusion may occur in multicomponent mixtures in which the diffusion flux of any species is strongly coupled to that of its partner species. Such coupling effects often arise from strong thermodynamic non-idealities. For a quantitative description we need to use chemical potential gradients as driving forces. The transport of ionic species in aqueous solutions is coupled with its partner ions because of the electro-neutrality constraints; such constraints may accelerate or decelerate a specific ion. When uphill diffusion occurs, we observe transient overshoots during equilibration; the equilibration process follows serpentine trajectories in composition space. For mixtures of liquids, alloys, ceramics and glasses the serpentine trajectories could cause entry into meta-stable composition zones; such entry could result in phenomena such as spinodal decomposition, spontaneous emulsification, and the Ouzo effect. For distillation of multicomponent mixtures that form azeotropes, uphill diffusion may allow crossing of distillation boundaries that are normally forbidden. For mixture separations with microporous adsorbents, uphill diffusion can cause supra-equilibrium loadings to be achieved during transient uptake within crystals; this allows the possibility of over-riding adsorption equilibrium for achieving difficult separations.

  8. Boron diffusion in silicon devices

    DOEpatents

    Rohatgi, Ajeet; Kim, Dong Seop; Nakayashiki, Kenta; Rounsaville, Brian

    2010-09-07

    Disclosed are various embodiments that include a process, an arrangement, and an apparatus for boron diffusion in a wafer. In one representative embodiment, a process is provided in which a boric oxide solution is applied to a surface of the wafer. Thereafter, the wafer is subjected to a fast heat ramp-up associated with a first heating cycle that results in a release of an amount of boron for diffusion into the wafer.

  9. Visualization of Diffusion within Nanoarrays.

    PubMed

    Liu, Yang; Holzinger, Angelika; Knittel, Peter; Poltorak, Lukasz; Gamero-Quijano, Alonso; Rickard, William D A; Walcarius, Alain; Herzog, Grégoire; Kranz, Christine; Arrigan, Damien W M

    2016-07-01

    The direct experimental characterization of diffusion processes at nanoscale remains a challenge that could help elucidate processes in biology, medicine and technology. In this report, two experimental approaches were employed to visualize ion diffusion profiles at the orifices of nanopores (radius (ra) of 86 ± 6 nm) in array format: (1) electrochemically assisted formation of silica deposits based on surfactant ion transfer across nanointerfaces between two immiscible electrolyte solutions (nanoITIES); (2) combined atomic force - scanning electrochemical microscopy (AFM-SECM) imaging of topography and redox species diffusion through the nanopores. The nature of the diffusion zones formed around the pores is directly related to the interpore distance within the array. Nanopore arrays with different ratios of pore center-to-center separation (rc) to pore radius (ra) were fabricated by focused ion beam (FIB) milling of silicon nitride (SiN) membranes, with 100 pores in a hexagonal arrangement. The ion diffusion profiles determined by the two visualization methods indicated the formation of overlapped or independent diffusion profiles at nanopore arrays with rc/ra ratios of 21 ± 2 and 91 ± 7, respectively. In particular, the silica deposition method resulted in formation of a single deposit encompassing the complete array with closer nanopore arrangement, whereas individual silica deposits were formed around each nanopore within the more widely spaced array. The methods reveal direct experimental evidence of diffusion zones at nanopore arrays and provide practical illustration that the pore-pore separation within such arrays has a significant impact on diffusional transport as the pore size is reduced to the nanoscale. These approaches to nanoscale diffusion zone visualization open up possibilities for better understanding of molecular transport processes within miniaturized systems. PMID:27264360

  10. Uphill diffusion in multicomponent mixtures.

    PubMed

    Krishna, Rajamani

    2015-05-21

    Molecular diffusion is an omnipresent phenomena that is important in a wide variety of contexts in chemical, physical, and biological processes. In the majority of cases, the diffusion process can be adequately described by Fick's law that postulates a linear relationship between the flux of any species and its own concentration gradient. Most commonly, a component diffuses down the concentration gradient. The major objective of this review is to highlight a very wide variety of situations that cause the uphill transport of one constituent in the mixture. Uphill diffusion may occur in multicomponent mixtures in which the diffusion flux of any species is strongly coupled to that of its partner species. Such coupling effects often arise from strong thermodynamic non-idealities. For a quantitative description we need to use chemical potential gradients as driving forces. The transport of ionic species in aqueous solutions is coupled with its partner ions because of the electro-neutrality constraints; such constraints may accelerate or decelerate a specific ion. When uphill diffusion occurs, we observe transient overshoots during equilibration; the equilibration process follows serpentine trajectories in composition space. For mixtures of liquids, alloys, ceramics and glasses the serpentine trajectories could cause entry into meta-stable composition zones; such entry could result in phenomena such as spinodal decomposition, spontaneous emulsification, and the Ouzo effect. For distillation of multicomponent mixtures that form azeotropes, uphill diffusion may allow crossing of distillation boundaries that are normally forbidden. For mixture separations with microporous adsorbents, uphill diffusion can cause supra-equilibrium loadings to be achieved during transient uptake within crystals; this allows the possibility of over-riding adsorption equilibrium for achieving difficult separations. PMID:25761383

  11. Diffusion in silicate melts: III. Empirical models for multicomponent diffusion

    NASA Astrophysics Data System (ADS)

    Yan, Liang; Richter, Frank M.; Chamberlin, Laurinda

    1997-12-01

    Empirical models for multicomponent diffusion in an isotropic fluid were derived by splitting the component's dispersion velocity into two parts: (a) an intrinsic velocity which is proportional to each component's electrochemical potential gradient and independent of reference frame and (b) a net interaction velocity which is both model and reference frame dependent. Simple molecules (e.g., M pO q) were chosen as endmember components. The interaction velocity is assumed to be either the same for each component (leading to a common relaxation velocity U) or proportional to a common interaction force ( F). U or F is constrained by requiring no local buildup in either volume or charge. The most general form of the model-derived diffusion matrix [ D] can be written as a product of a model-dependent kinetic matrix [ L] and a model independent thermodynamic matrix [ G], [ D] = [ L] · [ G]. The elements of [ G] are functions of derivatives of chemical potential with respect to concentration. The elements of [ L] are functions of concentration and partial molar volume of the endmember components, Cio and Vio, and self diffusivity Di, and charge number zi of individual diffusing species. When component n is taken as the dependent variable they can be written in a common form L ij = D jδ ij + C io[V noD n - V joD j)A i + (p nz nD n - p jz jD j)B i] where the functional forms of the scaling factors Ai and Bi depend on the model considered. The off-diagonal element Lij ( i ≠ j) is directly proportional to the concentration of component i, and thus negligible when i is a dilute component. The salient feature of kinetic interaction or relaxation is to slow down larger (volume or charge) and faster diffusing components and to speed up smaller (volume or charge) and slower moving species, in order to prevent local volume or charge buildup. Empirical models for multicomponent diffusion were tested in the ternary system CaOAl 2O 3SiO 2 at 1500°C and 1 GPa over a large

  12. Diffusion MRI: Pitfalls, literature review and future directions of research in mild traumatic brain injury.

    PubMed

    Delouche, Aurélie; Attyé, Arnaud; Heck, Olivier; Grand, Sylvie; Kastler, Adrian; Lamalle, Laurent; Renard, Felix; Krainik, Alexandre

    2016-01-01

    Mild traumatic brain injury (mTBI) is a leading cause of disability in adults, many of whom report a distressing combination of physical, emotional and cognitive symptoms, collectively known as post-concussion syndrome, that persist after the injury. Significant developments in magnetic resonance diffusion imaging, involving voxel-based quantitative analysis through the measurement of fractional anisotropy or mean diffusivity, have enhanced our knowledge on the different stages of mTBI pathophysiology. Other diffusion imaging-derived techniques, including diffusion kurtosis imaging with multi-shell diffusion and high-order tractography models, have recently demonstrated their usefulness in mTBI. Our review starts by briefly outlining the physical basis of diffusion tensor imaging including the pitfalls for use in brain trauma, before discussing findings from diagnostic trials testing its usefulness in assessing brain structural changes in patients with mTBI. Use of different post-processing techniques for the diffusion imaging data, identified the corpus callosum as the most frequently injured structure in mTBI, particularly at sub-acute and chronic stages, and a crucial location for evaluating functional outcome. However, structural changes appear too subtle for identification using traditional diffusion biomarkers, thus disallowing expansion of these techniques into clinical practice. In this regard, more advanced diffusion techniques are promising in the assessment of this complex disease.

  13. Lipid diffusion in alcoholic environment.

    PubMed

    Rifici, Simona; Corsaro, Carmelo; Crupi, Cristina; Nibali, Valeria Conti; Branca, Caterina; D'Angelo, Giovanna; Wanderlingh, Ulderico

    2014-08-01

    We have studied the effects of a high concentration of butanol and octanol on the phase behavior and on the lateral mobility of 1,2-palmitoyl-sn-glycero-3-phosphocholine (DPPC) by means of differential scanning calorimetry and pulsed-gradient stimulated-echo (PGSTE) NMR spectroscopy. A lowering of the lipid transition from the gel to the liquid-crystalline state for the membrane-alcohol systems has been observed. NMR measurements reveal three distinct diffusions in the DPPC-alcohol systems, characterized by a high, intermediate, and slow diffusivity, ascribed to the water, the alcohol, and the lipid, respectively. The lipid diffusion process is promoted in the liquid phase while it is hindered in the interdigitated phase due to the presence of alcohols. Furthermore, in the interdigitated phase, lipid lateral diffusion coefficients show a slight temperature dependence. To the best of our knowledge, this is the first time that lateral diffusion coefficients on alcohol with so a long chain, and at low temperatures, are reported. By the Arrhenius plots of the temperature dependence of the diffusion coefficients, we have evaluated the apparent activation energy in both the liquid and in the interdigitated phase. The presence of alcohol increases this value in both phases. An explanation in terms of a free volume model that takes into account also for energy factors is proposed.

  14. Gibbs Ringing in Diffusion MRI

    PubMed Central

    Veraart, Jelle; Fieremans, Els; Jelescu, Ileana O.; Knoll, Florian; Novikov, Dmitry S.

    2016-01-01

    Purpose To study and reduce the effect of Gibbs ringing artifact on computed diffusion parameters. Methods We reduce the ringing by extrapolating the k-space of each diffusion weighted image beyond the measured part by selecting an adequate regularization term. We evaluate several regularization terms and tune the regularization parameter to find the best compromise between anatomical accuracy of the reconstructed image and suppression of the Gibbs artifact. Results We demonstrate empirically and analytically that the Gibbs artifact, which is typically observed near sharp edges in magnetic resonance images, has a significant impact on the quantification of diffusion model parameters, even for infinitesimal diffusion weighting. We find the second order total generalized variation to be a good choice for the penalty term to regularize the extrapolation of the k-space, as it provides a parsimonious representation of images, a practically full suppression of Gibbs ringing, and the absence of staircasing artifacts typical for total variation methods. Conclusions Regularized extrapolation of the k-space data significantly reduces truncation artifacts without compromising spatial resolution in comparison to the default option of window filtering. In particular, accuracy of estimating diffusion tensor imaging and diffusion kurtosis imaging parameters improves so much that unconstrained fits become possible. PMID:26257388

  15. Osmosis and Diffusion Conceptual Assessment

    PubMed Central

    Fisher, Kathleen M.; Williams, Kathy S.; Lineback, Jennifer Evarts

    2011-01-01

    Biology student mastery regarding the mechanisms of diffusion and osmosis is difficult to achieve. To monitor comprehension of these processes among students at a large public university, we developed and validated an 18-item Osmosis and Diffusion Conceptual Assessment (ODCA). This assessment includes two-tiered items, some adopted or modified from the previously published Diffusion and Osmosis Diagnostic Test (DODT) and some newly developed items. The ODCA, a validated instrument containing fewer items than the DODT and emphasizing different content areas within the realm of osmosis and diffusion, better aligns with our curriculum. Creation of the ODCA involved removal of six DODT item pairs, modification of another six DODT item pairs, and development of three new item pairs addressing basic osmosis and diffusion concepts. Responses to ODCA items testing the same concepts as the DODT were remarkably similar to responses to the DODT collected from students 15 yr earlier, suggesting that student mastery regarding the mechanisms of diffusion and osmosis remains elusive. PMID:22135375

  16. Diffusion path representation for two-phase ternary diffusion couples

    SciTech Connect

    Dayananda, M A; Venkatasubramanian, R

    1986-01-01

    Several two-phase, solid-solid diffusion couples from diffusion studies in the ternary Cu-Ni-Zn, Fe-Ni-Al and Cu-Ag-Au systems were investigated for their analytical representation on the basis of characteristic path parameters. The concentration profiles were examined in terms of relative concentration variables for cross-over compositions and internal consistency. The diffusion paths delineated single or double S-shaped curves crossing the straight line joining the terminal alloy compositions once or thrice. Cross-over compositions were identified in the individual phase regions or at an interface. Based on the symmetry between the path segments on either side of cross-over compositions, the paths were analytically represented with the aid of cross-over compositions and path slopes at these compositions, considered as path parameters. Exprestion for the ratios of diffusion depth on the two sides of the Matano plane were derived in terms of cross-over compositions and the estimated ratios of diffusion depths were found to be consistent with those observed from the concentration profiles.

  17. Interferon-stimulated gene (ISG) 60, as well as ISG56 and ISG54, positively regulates TLR3/IFN-β/STAT1 axis in U373MG human astrocytoma cells.

    PubMed

    Imaizumi, Tadaatsu; Yoshida, Hidemi; Hayakari, Ryo; Xing, Fei; Wang, Lian; Matsumiya, Tomoh; Tanji, Kunikazu; Kawaguchi, Shogo; Murakami, Manabu; Tanaka, Hiroshi

    2016-04-01

    Treatment of cells with interferons (IFNs) induces the phosphorylation of signal transducer and activator of transcription 1 (STAT1), leading to the expression of hundreds of IFN-stimulated genes (ISGs). ISGs exert various antiviral and pro-inflammatory reactions. We have previously reported that ISG56 and ISG54 are induced by polyinosinic-polycytidylic acid (poly IC), an authentic agonist for Toll-like receptor 3 (TLR3), in U373MG human astrocytoma cells. ISG56 and ISG54 are also named as IFN-induced proteins with tetratricopeptide repeats (IFIT) 1 and IFIT2, respectively. In the present study, we demonstrated that poly IC induces the expression of ISG60, also named as IFIT3, in U373MG cells. RNA interference experiments showed that the induction of ISG60 by poly IC was mediated by TLR3, IFN-β, ISG56 and ISG54, whereas ISG60 is involved in poly IC-induced expression of ISG56, ISG54 and a chemokine CXCL10. The level of phosphorylated STAT1 was enhanced by poly IC, and it was inhibited by knockdown of ISG56, ISG54 or ISG60. These results suggest that there is a positive feedback loop between phosphorylated STAT1 and these ISGs. PMID:26423178

  18. Bilateral Brain Regions Associated with Naming in Older Adults

    ERIC Educational Resources Information Center

    Obler, Loraine K.; Rykhlevskaia, Elena; Schnyer, David; Clark-Cotton, Manuella R.; Spiro, Avron, III; Hyun, JungMoon; Kim, Dae-Shik; Goral, Mira; Albert, Martin L.

    2010-01-01

    To determine structural brain correlates of naming abilities in older adults, we tested 24 individuals aged 56-79 on two confrontation-naming tests (the Boston Naming Test (BNT) and the Action Naming Test (ANT)), then collected from these individuals structural Magnetic-Resonance Imaging (MRI) and Diffusion Tensor Imaging (DTI) data. Overall,…

  19. Accelerated changes in white matter microstructure during aging: a longitudinal diffusion tensor imaging study.

    PubMed

    Sexton, Claire E; Walhovd, Kristine B; Storsve, Andreas B; Tamnes, Christian K; Westlye, Lars T; Johansen-Berg, Heidi; Fjell, Anders M

    2014-11-12

    It is well established that human brain white matter structure changes with aging, but the timescale and spatial distribution of this change remain uncertain. Cross-sectional diffusion tensor imaging (DTI) studies indicate that, after a period of relative stability during adulthood, there is an accelerated decline in anisotropy and increase in diffusivity values during senescence; and, spatially, results have been discussed within the context of several anatomical frameworks. However, inferring trajectories of change from cross-sectional data can be challenging; and, as yet, there have been no longitudinal reports of the timescale and spatial distribution of age-related white matter change in healthy adults across the adult lifespan. In a longitudinal DTI study of 203 adults between 20 and 84 years of age, we used tract-based spatial statistics to characterize the pattern of annual change in fractional anisotropy, axial diffusivity, radial diffusivity, and mean diffusivity and examined whether there was an acceleration of change with age. We found extensive and overlapping significant annual decreases in fractional anisotropy, and increases in axial diffusivity, radial diffusivity, and mean diffusivity. Spatially, results were consistent with inferior-to-superior gradients of lesser-to-greater vulnerability. Annual change increased with age, particularly within superior regions, with age-related decline estimated to begin in the fifth decade. Charting white matter microstructural changes in healthy aging provides essential context to clinical studies, and future studies should compare age trajectories between healthy participants and at-risk populations and also explore the relationship between DTI rates of change and cognitive decline.

  20. Predicting diffusive alveolar oxygen transfer from carbon monoxide-diffusing capacity in exercising foxhounds

    PubMed Central

    Hsia, Connie C. W.; Wagner, Peter D.; Dane, D. Merrill; Wagner, Harrieth E.; Johnson, Robert L.

    2008-01-01

    Although lung diffusing capacity for carbon monoxide (DlCO) is a widely used test of diffusive O2 transfer, few studies have directly related DlCO to O2-diffusing capacity (DlO2); none has used the components of DlCO, i.e., conductance of alveolar membrane and capillary blood, to predict DlO2 from rest to exercise. To understand the relationship between DlCO and DlO2 at matched levels of cardiac output, we analyzed cumulative data from rest to heavy exercise in 43 adult dogs, with normal lungs or reduced lung capacity following lung resection, that were studied by two techniques. 1) A rebreathing (RB) technique was used to measure DlCO and pulmonary blood flow at two O2 tensions, independent of O2 exchange. DlCO was partitioned into CO-diffusing capacity of alveolar membrane and pulmonary capillary blood volume using the Roughton-Forster equation and converted into an equivalent DlO2, [DlO2(RB)]. 2) A multiple inert-gas elimination technique (MIGET) was used to measure ventilation-perfusion distributions, O2 and CO2 exchange under hypoxia, to derive DlO2 [DlO2(MIGET)] by the Lilienthal-Riley technique and Bohr integration. For direct comparisons, DlO2(RB) was interpolated to the cardiac output measured by the Fick principle corresponding to DlO2(MIGET). The DlO2-to-DlCO ratio averaged 1.61. Correlation between DlO2(RB) and DlO2(MIGET) was similar in normal and post-resection groups. Overall, DlO2(MIGET) = 0.975 DlO2(RB); mean difference between the two techniques was under 5% for both animal groups. We conclude that, despite various uncertainties inherent in these two disparate methods, the Roughton-Forster equation adequately predicts diffusive O2 transfer from rest to heavy exercise in canines with normal, as well as reduced, lung capacities. PMID:18719238

  1. Diffuse Gamma Rays Galactic and Extragalactic Diffuse Emission

    NASA Technical Reports Server (NTRS)

    Moskalenko, Igor V.; Strong, Andrew W.; Reimer, Olaf

    2004-01-01

    Diffuse gamma rays consist of several components: truly diffuse emission from the interstellar medium, the extragalactic background, whose origin is not firmly established yet, and the contribution from unresolved and faint Galactic point sources. One approach to unravel these components is to study the diffuse emission from the interstellar medium, which traces the interactions of high energy particles with interstellar gas and radiation fields. Because of its origin such emission is potentially able to reveal much about the sources and propagation of cosmic rays. The extragalactic background, if reliably determined, can be used in cosmological and blazar studies. Studying the derived average spectrum of faint Galactic sources may be able to give a clue to the nature of the emitting objects.

  2. One stage removal of periaqueductal glioma in adult via infratentorial supracerebellar and transaqueductal approaches.

    PubMed

    Koziarski, A; Zieliński, G; Podgórski, J K; Warczyńska, A

    2004-02-01

    Most cases of periaqueductal tumours were found in children and adolescents, so treatment modalities in adults are not evaluated yet. A case of 40 years old woman with tectal and periaqueductal protoplasmatic astrocytoma grade II with history of headache and episodes of syncope is described. MRI showed triventricular hydrocephalus. After a shunt procedure she was doing well for about 15 months. Then she became somnolent, disoriented, and Parinaud syndrome appeared. The solid tumour was resected microsurgically in one stage. A part of it was removed via the supracerebellar infratentorial approach and tectal plate incision. The remainder of the tumour was removed through the fourth ventricle and the aqueduct which was filled by tumour mass. Postoperatively bilateral ptosis, vertical gaze palsy, slight horizontal gaze limitation and pupilloplegia were the main neurological sequelae. They all almost completely resolved within a year. The patient is doing well two and half years after the surgery. MRI showed patency of the aqueduct and no residual tumour. The authors suggest, that direct surgical attempt at total tumour removal should be considered in cases of periaqueductal and tectal gliomas. They also believe it is the first described case, in whom this type of tumour was totally removed by a combined transtectal and transaqueductal route.

  3. Kramers turnover: From energy diffusion to spatial diffusion using metadynamics

    NASA Astrophysics Data System (ADS)

    Tiwary, Pratyush; Berne, B. J.

    2016-04-01

    We consider the rate of transition for a particle between two metastable states coupled to a thermal environment for various magnitudes of the coupling strength using the recently proposed infrequent metadynamics approach [P. Tiwary and M. Parrinello, Phys. Rev. Lett. 111, 230602 (2013)]. We are interested in understanding how this approach for obtaining rate constants performs as the dynamics regime changes from energy diffusion to spatial diffusion. Reassuringly, we find that the approach works remarkably well for various coupling strengths in the strong coupling regime, and to some extent even in the weak coupling regime.

  4. A Diffusion Approach to Study Leadership Reform

    ERIC Educational Resources Information Center

    Adams, Curt M.; Jean-Marie, Gaetane

    2011-01-01

    Purpose: This study aims to draw on elements of diffusion theory to understand leadership reform. Many diffusion studies examine the spread of an innovation across social units but the objective is to examine diffusion of a collective leadership model within school units. Specifically, the strength of reform diffusion is tested to account for…

  5. Predicting vulnerability to sleep deprivation using diffusion model parameters.

    PubMed

    Patanaik, Amiya; Zagorodnov, Vitali; Kwoh, Chee Keong; Chee, Michael W L

    2014-10-01

    We used diffusion modelling to predict vulnerability to decline in psychomotor vigilance task (PVT) performance following a night of total sleep deprivation (SD). A total of 135 healthy young adults (69 women, age = 21.9 ± 1.7 years) participated in several within-subject cross-over design studies that incorporated the PVT. Participants were classified as vulnerable (lower tertile) or non-vulnerable (upper tertile) according to their change in lapse rate [lapse = reaction time (RT) ≥ 500 ms] between the evening before (ESD) and the morning after SD. RT data were fitted using Ratcliff's diffusion model. Although both groups showed significant change in RT during SD, there was no significant group difference in RT during the ESD session. In contrast, during ESD, the mean diffusion drift of vulnerable subjects was significantly lower than for non-vulnerable subjects. Mean drift and non-decision times were both adversely affected by sleep deprivation. Both mean drift and non-decision time showed significant state × vulnerability interaction. Diffusion modelling appears to have promise in predicting vulnerability to vigilance decline induced by a night of total sleep deprivation.

  6. Adult Congenital Heart Association

    MedlinePlus

    ... survivable, manageable, yet in the routine years between infancy and adulthood, sometimes forgettable. The Adult Congenital Heart ... understand the continuum of the disease from its infancy. The Adult Congential Heart Association brings together valuable ...

  7. Immunization Schedules for Adults

    MedlinePlus

    ... ACIP Vaccination Recommendations Why Immunize? Vaccines: The Basics Immunization Schedules for Adults in Easy-to-read Formats ... previous immunizations. View or Print a Schedule Recommended Immunizations for Adults (19 Years and Older) by Age ...

  8. Diffusion Tensor Imaging Correlates of Reading Ability in Dysfluent and Non-Impaired Readers

    ERIC Educational Resources Information Center

    Lebel, Catherine; Shaywitz, Bennett; Holahan, John; Shaywitz, Sally; Marchione, Karen; Beaulieu, Christian

    2013-01-01

    Many children and adults have specific reading disabilities; insight into the brain structure underlying these difficulties is evolving from imaging. Previous research highlights the left temporal-parietal white matter as important in reading, yet the degree of involvement of other areas remains unclear. Diffusion tensor imaging (DTI) and…

  9. Devitrite-based optical diffusers.

    PubMed

    Butt, Haider; Knowles, Kevin M; Montelongo, Yunuen; Amaratunga, Gehan A J; Wilkinson, Timothy D

    2014-03-25

    Devitrite is a novel material produced by heat treatment of commercial soda-lime-silica glass. It consists of fans of needle-like crystals which can extend up to several millimeters and have interspacings of up to a few hundred nanometers. To date, only the material properties of devitrite have been reported, and there has been a distinct lack of research on using it for optical applications. In this study, we demonstrate that randomly oriented fans of devitrite crystals can act as highly efficient diffusers for visible light. Devitrite crystals produce phase modulation of light because of their relatively high anisotropy. The nanoscale spacings between these needles enable light to be diffused to large scattering angles. Experimentally measured results suggest that light diffusion patterns with beam widths of up to 120° are produced. Since devitrite is an inexpensive material to produce, it has the potential to be used in a variety of commercial applications.

  10. Anomalous diffusion in silo drainage.

    PubMed

    Arévalo, R; Garcimartín, A; Maza, D

    2007-06-01

    The silo discharge process is studied by molecular dynamics simulations. The development of the velocity profile and the probability density function for the displacements in the horizontal and vertical axis are obtained. The PDFs obtained at the beginning of the discharge reveal non-Gaussian statistics and superdiffusive behaviors. When the stationary flow is developed, the PDFs at shorter temporal scales are non-Gaussian too. For big orifices a well-defined transition between ballistic and diffusive regime is observed. In the case of a small outlet orifice, no well-defined transition is observed. We use a nonlinear diffusion equation introduced in the framework of non-extensive thermodynamics in order to describe the movements of the grains. The solution of this equation gives a well-defined relationship (gamma = 2/(3 - q)) between the anomalous diffusion exponent gamma and the entropic parameter q introduced by the non-extensive formalism to fit the PDF of the fluctuations.

  11. Load Diffusion in Composite Structures

    NASA Technical Reports Server (NTRS)

    Horgan, Cornelius O.; Simmonds, J. G.

    2000-01-01

    This research has been concerned with load diffusion in composite structures. Fundamental solid mechanics studies were carried out to provide a basis for assessing the complicated modeling necessary for large scale structures used by NASA. An understanding of the fundamental mechanisms of load diffusion in composite subcomponents is essential in developing primary composite structures. Analytical models of load diffusion behavior are extremely valuable in building an intuitive base for developing refined modeling strategies and assessing results from finite element analyses. The decay behavior of stresses and other field quantities provides a significant aid towards this process. The results are also amendable to parameter study with a large parameter space and should be useful in structural tailoring studies.

  12. Nonlinear Diffusion and Transient Osmosis

    NASA Astrophysics Data System (ADS)

    Akira, Igarashi; Lamberto, Rondoni; Antonio, Botrugno; Marco, Pizzi

    2011-08-01

    We investigate both analytically and numerically the concentration dynamics of a solution in two containers connected by a narrow and short channel, in which diffusion obeys a porous medium equation. We also consider the variation of the pressure in the containers due to the flow of matter in the channel. In particular, we identify a phenomenon, which depends on the transport of matter across nano-porous membranes, which we call “transient osmosis". We find that nonlinear diffusion of the porous medium equation type allows numerous different osmotic-like phenomena, which are not present in the case of ordinary Fickian diffusion. Experimental results suggest one possible candidate for transiently osmotic processes.

  13. Water vapor diffusion membranes, 2

    NASA Technical Reports Server (NTRS)

    Holland, F. F.; Klein, E.; Smith, J. K.; Eyer, C.

    1976-01-01

    Transport mechanisms were investigated for the three different types of water vapor diffusion membranes. Membranes representing porous wetting and porous nonwetting structures as well as dense diffusive membrane structures were investigated for water permeation rate as a function of: (1) temperature, (2) solids composition in solution, and (3) such hydrodynamic parameters as sweep gas flow rate, solution flow rate and cell geometry. These properties were measured using nitrogen sweep gas to collect the effluent. In addition, the chemical stability to chromic acid-stabilized urine was measured for several of each type of membrane. A technology based on the mechanism of vapor transport was developed, whereby the vapor diffusion rates and relative susceptibility of membranes to fouling and failure could be projected for long-term vapor recovery trials using natural chromic acid-stabilized urine.

  14. Liberal Adult Education.

    ERIC Educational Resources Information Center

    Toiviainen, Timo

    1988-01-01

    Discusses providers of and the concept of liberal adult education in Finland. Providers include (1) folk high schools, (2) adult education centers, (3) voluntary popular organizations, (4) public libraries, (5) evening schools, (6) cooperative groups formed of universities and other adult education providers, (7) summer universities, and (8)…

  15. Comparing Adult Education Worldwide.

    ERIC Educational Resources Information Center

    Charters, Alexander N.; And Others

    Comparative international adult education, defined as that field in which adult educators from various countries compare their own institutions and practices with those of their counterparts in other nations, is examined. Provided is an account of adult education in nine European socialist countries (including the Soviet Union), as well as…

  16. Adult Numeracy Core Curriculum.

    ERIC Educational Resources Information Center

    Steeds, Andrew, Ed.

    Designed primarily for adult literacy teachers and tutors, this curriculum describes the content of what should be taught in numeracy programs in order to meet the individual needs of adults through the selection and teaching of skills appropriate to those adults' needs. An introduction describes national standards and qualifications, learners,…

  17. Adult Educators' Core Competences

    ERIC Educational Resources Information Center

    Wahlgren, Bjarne

    2016-01-01

    Which competences do professional adult educators need? This research note discusses the topic from a comparative perspective, finding that adult educators' required competences are wide-ranging, heterogeneous and complex. They are subject to context in terms of national and cultural environment as well as the kind of adult education concerned…

  18. Adults Learning. Fourth Edition.

    ERIC Educational Resources Information Center

    Rogers, Jenny

    Aimed at anyone who wants to know how to teach adults, this guide aims to build confidence, offer practical advice, and give the real-life flavor of helping fellow adults develop. Chapter 1 addresses adult learners: mindsets, motivation, and learning (learning cycle, learning styles, relevance, reinforcement and practice, experience, learning to…

  19. Adult Education in Hungary.

    ERIC Educational Resources Information Center

    Csoma, Gyula; And Others

    Beginning with a brief survey of the national system, this work covers provisions since 1945 for adult education in Hungary. Educational objectives and other theoretical aspects of adult education in Hungarian society are described, together with the eight year elementary program, technical and vocational adult schools, general and professional…

  20. An Adult ESL Curriculum.

    ERIC Educational Resources Information Center

    South Carolina Literacy Resource Center, Columbia.

    This curriculum framework for adult literacy was written by 21 South Carolina adult English-as-a-Second-Language (ESL) instructors, as submitted to the South Carolina Literacy Resource Center. It is based on current theories in the fields of adult education and second language acquisition and is designed to be flexible so that it may be adapted to…