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Sample records for glial tumor specimens

  1. Glial tumors with neuronal differentiation.

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    Park, Chul-Kee; Phi, Ji Hoon; Park, Sung-Hye

    2015-01-01

    Immunohistochemical studies for neuronal differentiation in glial tumors revealed subsets of tumors having both characteristics of glial and neuronal lineages. Glial tumors with neuronal differentiation can be observed with diverse phenotypes and histologic grades. The rosette-forming glioneuronal tumor of the fourth ventricle and papillary glioneuronal tumor have been newly classified as distinct disease entities. There are other candidates for classification, such as the glioneuronal tumor without pseudopapillary architecture, glioneuronal tumor with neuropil-like islands, and the malignant glioneuronal tumor. The clinical significance of these previously unclassified tumors should be confirmed. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Molecular genetic studies of glial tumors in children

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    P. S. Soltan

    2016-01-01

    Full Text Available Glioblastomas are the most frequent malignant neoplasm among primary brain tumors of childhood. Despite the advances in a multimodality treatment approach including neurosurgery, radiotherapy and chemotherapy, the overall survival of such patients remains poor and doesn’t exceed 14 months. The using of targeted agents such as gefitinib in unselected patient populations showed insufficient efficacy. Nowadays, the most perspective approach is a selection of patient populations potentially sensitive to targeted therapy based on predictive markers of response. We performed a comprehensive analysis of the mutational patterns in 30 glioblastomas of children. Data Analysis was based on the new method of mass spectrometry (OncoCarta v1.0, Sequenom that enabled us to estimate 298 mutations in 19 genes and to identify 10 mutations in 9 tumors (30 %. Mutations were found in BRAF, CDK, HRAS, EGFR, FGFR, MET and PI3K. The most mutated pathway was EGFR – in 20 % of the samples (6/30. The obtained results seem to be very promising in terms of possibilities of using new targeted agents including BRAF inhibitors for treatment of children with glial brain tumors.

  3. Early-postoperative magnetic resonance imaging in glial tumors: prediction of tumor regrowth and recurrence

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    Ekinci, Gazanfer; Akpinar, Ihsan N. E-mail: i.akpinar@mailcity.com; Baltacioglu, Feyyaz; Erzen, Canan; Kilic, Tuerker; Elmaci, Ilhan; Pamir, Necmettin

    2003-02-01

    Objective: This study investigated the value of early-postoperative magnetic resonance (EPMR) imaging in the detection of residual glial tumor and investigated the role of EPMR for the prediction of tumor regrowth and recurrence. Methods and materials: We retrospectively analyzed pre- and post-operative magnetic resonance imaging results from 50 adult patients who underwent surgical treatment for supratentorial glial tumor. There were glioblastoma multiforme in 25 patients, astrocytoma (grades II and III) in 11 patients, oligodendroglioma (grades II and III) in 9 patients, and oligoastrocytoma (grades II and III) in 5 patients. EPMR imaging was performed within 24 h after surgery. EPMR findings were compared with the neurosurgeon's intraoperative estimation of gross tumor removal. Patterns of contrast enhancement at the resection site, in residual and developing tumor tissue and blood at the resection site were evaluated on EPMR and in follow-up studies. 'Residual tumor' was defined as contrast enhancing mass at the operative site on EPMR. 'Regrowth' was defined as contrast enhancing mass detected on follow-up in the same location as the primary tumor. 'Recurrence' was defined as appearance of a mass lesion in the brain parenchyma distant from the resection bed during follow-up. Results: Nineteen patients showed no evidence of residual tumor, regrowth, or recurrence on EPMR or any of the later follow-up radiological examinations. EPMR identified 20 cases of residual tumor. Follow-up showed tumor regrowth in 10 patients, and tumor recurrence in 1 case. EPMR showed contrast enhancement of the resection bed in 45 of the 50 patients. Four of the 20 residual tumors showed a thick linear enhancement pattern, and the other 16 cases exhibited thick linear-nodular enhancement. No thin linear enhancement was observed in the residual tumor group. Nine of the 10-regrowth tumors showed a thick linear-nodular enhancement pattern, and one

  4. Magnetic resonance spectroscopy in patients with cerebral glial tumors

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    Ugarte Moreno, Dayana; Ugarte Suarez, Jose Carlos; Pinnera Moliner, Jesus; Gonzalez, Jose Jordan

    2013-01-01

    The incidence of the intracranial primitive tumors is about 1 to 12 cases for 100 000 inhabitants per year. The most frequent tumors are gliomas that include tumors like astrocytomas benign and malignant. We studied twenty nine patients who were sent to Medical Surgical Research Center to make a magnetic resonance with spectroscopy, in a period of 18 months. The histological result was obtained by biopsy or autopsy

  5. Advanced MR diagnostic imaging in pediatric glial cell tumors: from morphological to pathophysiological evaluation

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    Balev, B.; Georgiev, R.; Novakova, M.

    2013-01-01

    Full text: Introduction: The conventional MR imaging is important, and in most cases necessary imaging tool for studying the macroscopic structure, for localization and distribution of a glial brain tumor. It is an integral part of the optimal MR protocol, which further comprises a diffusion, perfusion techniques, techniques for the permeability and oxygenation assessment, as well as MR spectroscopy to the metabolism assessment. What you will learn: Glial brain tumors in children - incidence, histology, classification, diagnosis; Nature and principles of MR diffusion, perfusion, techniques for permeability and oxygenation assessment, MR spectroscopy; Contemporary techniques allowing to obtain not only MR morphological information but also to evaluate the tumor the pathophysiology: the cellular atypia, cellularity, tumor neovascularization, oxygen consumption, metabolism, status of the blood-brain barrier. This assessment determines the biological potential of the tumor, treatment options and prognosis. Discussion: The findings from conventional MR examinations, incl. administration of gadolinium contrast agents are associated with the degree of glioma and can be useful for their classification. Taking into account that from 20% to 45 % of the unenhanced supratentorial gliomas are malignant, some low-grade gliomas enhance (ganglioglioma, pilocytic astrocytoma, oligodendroglioma), 9% of malignant gliomas have no contrast enhancement, and in general, the contrast enhancement is not seen as a reliable indicator for the infiltration extent. The contemporary MR techniques improve the assessment of the pathophysiology of the tumor which is relevant to its histology and biological potential. Conclusion: Modern MR techniques besides purely diagnostic advantages (determine the extent and distribution of glioma), enable: differentiation of tumor recurrence from radiation necrosis; identification of optimal locations for biopsy or operative resection; prognosis, planning and

  6. Cerenkov and radioluminescence imaging of brain tumor specimens during neurosurgery

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    Spinelli, Antonello Enrico; Schiariti, Marco P.; Grana, Chiara M.; Ferrari, Mahila; Cremonesi, Marta; Boschi, Federico

    2016-05-01

    We presented the first example of Cerenkov luminescence imaging (CLI) and radioluminescence imaging (RLI) of human tumor specimens. A patient with a brain meningioma localized in the left parietal region was injected with 166 MBq of Y90-DOTATOC the day before neurosurgery. The specimens of the tumor removed during surgery were imaged using both CLI and RLI using an optical imager prototype developed in our laboratory. The system is based on a cooled electron multiplied charge coupled device coupled with an f/0.95 17-mm C-mount lens. We showed for the first time the possibility of obtaining CLI and RLI images of fresh human brain tumor specimens removed during neurosurgery.

  7. Promotion of seminomatous tumors by targeted overexpression of glial cell line-derived neurotrophic factor in mouse testis

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    Meng, X.; de rooij, D. G.; Westerdahl, K.; Saarma, M.; Sariola, H.

    2001-01-01

    We show with transgenic mice that targeted overexpression of glial cell line-derived neurotrophic factor (GDNF) in undifferentiated spermatogonia promotes malignant testicular tumors, which express germ-cell markers. The tumors are invasive and contain aneuploid cells, but no distant metastases have

  8. MicroRNA-145 is downregulated in glial tumors and regulates glioma cell migration by targeting connective tissue growth factor.

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    Lee, Hae Kyung; Bier, Ariel; Cazacu, Simona; Finniss, Susan; Xiang, Cunli; Twito, Hodaya; Poisson, Laila M; Mikkelsen, Tom; Slavin, Shimon; Jacoby, Elad; Yalon, Michal; Toren, Amos; Rempel, Sandra A; Brodie, Chaya

    2013-01-01

    Glioblastomas (GBM), the most common and aggressive type of malignant glioma, are characterized by increased invasion into the surrounding brain tissues. Despite intensive therapeutic strategies, the median survival of GBM patients has remained dismal over the last decades. In this study we examined the expression of miR-145 in glial tumors and its function in glioma cells. Using TCGA analysis and real-time PCR we found that the expression of miR-145/143 cluster was downregulated in astrocytic tumors compared to normal brain specimens and in glioma cells and glioma stem cells (GSCs) compared to normal astrocytes and neural stem cells. Moreover, the low expression of both miR-145 and miR-143 in GBM was correlated with poor patient prognosis. Transfection of glioma cells with miR-145 mimic or transduction with a lentivirus vector expressing pre-miR 145 significantly decreased the migration and invasion of glioma cells. We identified connective tissue growth factor (CTGF) as a novel target of miR-145 in glioma cells; transfection of the cells with this miRNA decreased the expression of CTGF as determined by Western blot analysis and the expression of its 3'-UTR fused to luciferase. Overexpression of a CTGF plasmid lacking the 3'-UTR and administration of recombinant CTGF protein abrogated the inhibitory effect of miR-145 on glioma cell migration. Similarly, we found that silencing of CTGF decreased the migration of glioma cells. CTGF silencing also decreased the expression of SPARC, phospho-FAK and FAK and overexpression of SPARC abrogated the inhibitory effect of CTGF silencing on cell migration. These results demonstrate that miR-145 is downregulated in glial tumors and its low expression in GBM predicts poor patient prognosis. In addition miR-145 regulates glioma cell migration by targeting CTGF which downregulates SPARC expression. Therefore, miR-145 is an attractive therapeutic target for anti-invasive treatment of astrocytic tumors.

  9. MicroRNA-145 is downregulated in glial tumors and regulates glioma cell migration by targeting connective tissue growth factor.

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    Hae Kyung Lee

    Full Text Available Glioblastomas (GBM, the most common and aggressive type of malignant glioma, are characterized by increased invasion into the surrounding brain tissues. Despite intensive therapeutic strategies, the median survival of GBM patients has remained dismal over the last decades. In this study we examined the expression of miR-145 in glial tumors and its function in glioma cells. Using TCGA analysis and real-time PCR we found that the expression of miR-145/143 cluster was downregulated in astrocytic tumors compared to normal brain specimens and in glioma cells and glioma stem cells (GSCs compared to normal astrocytes and neural stem cells. Moreover, the low expression of both miR-145 and miR-143 in GBM was correlated with poor patient prognosis. Transfection of glioma cells with miR-145 mimic or transduction with a lentivirus vector expressing pre-miR 145 significantly decreased the migration and invasion of glioma cells. We identified connective tissue growth factor (CTGF as a novel target of miR-145 in glioma cells; transfection of the cells with this miRNA decreased the expression of CTGF as determined by Western blot analysis and the expression of its 3'-UTR fused to luciferase. Overexpression of a CTGF plasmid lacking the 3'-UTR and administration of recombinant CTGF protein abrogated the inhibitory effect of miR-145 on glioma cell migration. Similarly, we found that silencing of CTGF decreased the migration of glioma cells. CTGF silencing also decreased the expression of SPARC, phospho-FAK and FAK and overexpression of SPARC abrogated the inhibitory effect of CTGF silencing on cell migration. These results demonstrate that miR-145 is downregulated in glial tumors and its low expression in GBM predicts poor patient prognosis. In addition miR-145 regulates glioma cell migration by targeting CTGF which downregulates SPARC expression. Therefore, miR-145 is an attractive therapeutic target for anti-invasive treatment of astrocytic tumors.

  10. DIAGNOSTIC VALUE OF THE DEJA VU PHENOMENON IN THE CLINICAL PICTURE OF GLIAL BRAIN TUMORS

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    Pavel Nikolaevich Vlasov

    2009-01-01

    This investigation was undertaken to study the implication of the DV phenomenon in the clinical picture of glial brain tumors (GBT. One hundred and sixty-one subjects (mean age 29,2±6,4 years; males 47%, including 129 healthy individuals and 32 patients with GBT, were examined. In the clinical picture of GBT with seizures, DV is a common symptom that is encountered in the involvement of predominantly the right temporal lobe and accompanied by generalized convulsive attacks and olfactory hallucinations. DV in GBT occurs more than once daily; its duration is a few (as many as 5 minutes; DV is characterized by a negative emotional tinge and attended by fear

  11. Cytogenetic evaluation of human glial tumors: correlation of overexpression of epidermal growth factor receptor (EGFB) with abnormalities of chromosome 7

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    Bell, C.W.

    1987-01-01

    Chromosome banding analysis of human glial tumors were performed using G- and Q-banding techniques in an attempt to establish recurring sites of chromosome change. Results revealed a nonrandom karyotypic profile including aneuploidy and considerable variation in chromosome number (range 40 → 200). All tumors examined displayed numerical abnormalities, with the most common numeric change being a gain of chromosome 7. An attempt was then made to correlate the observed chromosome 7 changes with activation of the cellular proto-oncogene c-erb-B, whose produce is the epidermal growth factor receptor (EGFR). Six human glial tumors were analyzed for 125 I-EGF binding, EGFR gene copy number, EGFR gene rearrangement, mRNA expression, and karyotypic profile. Saturation analysis at 4 0 C revealed significant numbers of EGFR's in all 6 tumors. Southern blotting analysis utilizing cDNA probes for the EGFR failed to demonstrate significant amplification or structural rearrangement of the EFGR gene. The results suggest that overexpression of the EGFR may be related to an alternative mechanism, other than gene amplification and elevated mRNA levels, such as the regulation of receptor biosynthesis and degradation. In summary, findings indicate that alterations of chromosome 7 are the most prevalent chromosomal change in human glial tumors, and that these alterations may lead to overexpression of the protooncogene c-erb-B

  12. Susceptibility Imaging in Glial Tumor Grading; Using 3 Tesla Magnetic Resonance (MR) System and 32 Channel Head Coil.

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    Aydin, Omer; Buyukkaya, Ramazan; Hakyemez, Bahattin

    2017-01-01

    Susceptibility weighted imaging (SWI) is a velocity compensated, high-resolution three-dimensional (3D) spoiled gradient-echo sequence that uses magnitude and filtered-phase data. SWI seems to be a valuable tool for non-invasive evaluation of central nervous system gliomas. Relative cerebral blood volume (rCBV) ratio is one of the best noninvasive methods for glioma grading. Degree of intratumoral susceptibility signal (ITSS) on SWI correlates with rCBV ratio and histopathological grade. This study investigated the effectiveness of ITSS grading and rCBV ratio in preoperative assessment. Thirty-one patients (17 males and 14 females) with histopathogical diagnosis of glial tumor undergoing routine cranial MRI, SWI, and perfusion MRI examinations between October 2011 and July 2013 were retrospectively enrolled. All examinations were performed using 3T apparatus with 32-channel head coil. We used ITSS number for SWI grading. Correlations between SWI grade, rCBV ratio, and pathological grading were evaluated. ROC analysis was performed to determine the optimal rCBV ratio to distinguish between high-grade and low-grade glial tumors. There was a strong positive correlation between both pathological and SWI grading. We determined the optimal rCBV ratio to discriminate between high-grade and low-grade tumors to be 2.21. In conclusion, perfusion MRI and SWI using 3T MR and 32-channel head coil may provide useful information for preoperative glial tumor grading. SWI can be used as an accessory to perfusion MR technique in preoperative tumor grading.

  13. Métodos diagnósticos en los tumores gliales de tipo astrocíticos

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    Letyer Pérez Ortiz

    2004-03-01

    Full Text Available Los tumores cerebrales constituyen un problema realmente complejo para la mayoría de los profesionales dedicados a su diagnóstico y tratamiento. El paciente con un tumor cerebral constituye un desafío científico, ético y hasta emocional para el radiólogo y el neurocirujano. Desde el descubrimiento de los rayos X en 1895 la radiología, y posteriormente la neurorradiología como disciplina, han sido de indudable utilidad en la detección de estas lesiones. En las últimas décadas el desarrollo alcanzado por las técnicas de neuroimagen ha permitido realizar un diagnóstico certero, lo que ha permitido definir la localización precisa del tumor, los detalles estructurales perilesionales, la evidencia de daño de la barrera hematoencefálica, el edema cerebral y el grado de malignidad tumoral a través de los estudios imagenológicos funcionales. Con este trabajo se pretende realizar un bosquejo general sobre los métodos diagnósticos más utilizados en la detección de los tumores gliales, paso previo e imprescindible para proceder a su tratamiento y predecir pronósticoThe brain tumors are a real complex problem for most of the professionals devoted to their diagnosis and treatment. The patient with a brain tumor is a scientific, ethical and emotional challenge for the radiologist and the neurosurgeon. Since the discovery of the X-rays in 1895, radiology and later neuroradiology, as a discipline, have been unquestionably useful in the detection of injuries. During the last decades, the development attained by the neuroimaging techniques has allowed to make an accurate diagnosis and to determine the exact location of the tumor, the structural perilesional details, the evidence of damage of the hematoencephalic barrier, the brain edema, and the degree of tumoral malignity through the functional imaging studies. In this paper, we pretend to make a general review on the most used diagnostic methods in the detection of glial tumors, an

  14. [Impact of driving restrictions disclosure on quality of life of patients with a glial tumor: A prospective study].

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    Bergot, Lydie; Cuchard, Solenn; Mazeaud, Sylvie; Magro, Elsa; Seizeur, Romuald

    2016-03-01

    Disclosure of driving restrictions on patients with glial tumors is a complex and difficult task. The difficulty of such task lies in the moral and ethical conflicts it generates for the patient on one hand and caregivers on the other. These aforementioned conflicts impinge upon the patient's quality of life which is one of the important aspects of neuro-oncologic care. In a prospective survey of 31 patients diagnosed with glial tumors, we studied how the patient perceived the disclosure of driving restrictions specifically the amount of retained information, and the level of distress. It seems that patients fail to assess the juridical implications of driving restrictions. The impact on quality of life as well as psychological and social aspects of these restrictions must not be taken lightly especially in young patients with low-grade glioma who has a long life expectancy. Therefore, we believe that planning a specific psychological and social accompaniment of the patient in relation to driving restrictions is an undeniable necessity. Copyright © 2016 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

  15. Comparative expression analysis reveals lineage relationships between human and murine gliomas and a dominance of glial signatures during tumor propagation in vitro.

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    Henriquez, Nico V; Forshew, Tim; Tatevossian, Ruth; Ellis, Matthew; Richard-Loendt, Angela; Rogers, Hazel; Jacques, Thomas S; Reitboeck, Pablo Garcia; Pearce, Kerra; Sheer, Denise; Grundy, Richard G; Brandner, Sebastian

    2013-09-15

    Brain tumors are thought to originate from stem/progenitor cell populations that acquire specific genetic mutations. Although current preclinical models have relevance to human pathogenesis, most do not recapitulate the histogenesis of the human disease. Recently, a large series of human gliomas and medulloblastomas were analyzed for genetic signatures of prognosis and therapeutic response. Using a mouse model system that generates three distinct types of intrinsic brain tumors, we correlated RNA and protein expression levels with human brain tumors. A combination of genetic mutations and cellular environment during tumor propagation defined the incidence and phenotype of intrinsic murine tumors. Importantly, in vitro passage of cancer stem cells uniformly promoted a glial expression profile in culture and in brain tumors. Gene expression profiling revealed that experimental gliomas corresponded to distinct subclasses of human glioblastoma, whereas experimental supratentorial primitive neuroectodermal tumors (sPNET) correspond to atypical teratoid/rhabdoid tumor (AT/RT), a rare childhood tumor. ©2013 AACR.

  16. Clonal mutations in primary human glial tumors: evidence in support of the mutator hypothesis

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    Sarkar Chitra

    2007-10-01

    Full Text Available Abstract Background A verifiable consequence of the mutator hypothesis is that even low grade neoplasms would accumulate a large number of mutations that do not influence the tumor phenotype (clonal mutations. In this study, we have attempted to quantify the number of clonal mutations in primary human gliomas of astrocytic cell origin. These alterations were identified in tumor tissue, microscopically confirmed to have over 70% neoplastic cells. Methods Random Amplified Polymorphic DNA (RAPD analysis was performed using a set of fifteen 10-mer primers of arbitrary but definite sequences in 17 WHO grade II astrocytomas (low grade diffuse astrocytoma or DA and 16 WHO grade IV astrocytomas (Glioblastoma Multiforme or GBM. The RAPD profile of the tumor tissue was compared with that of the leucocyte DNA of the same patient and alteration(s scored. A quantitative estimate of the overall genomic changes in these tumors was obtained by 2 different modes of calculation. Results The overall change in the tumors was estimated to be 4.24% in DA and 2.29% in GBM by one method and 11.96% and 6.03% in DA and GBM respectively by the other. The difference between high and lower grade tumors was statistically significant by both methods. Conclusion This study demonstrates the presence of extensive clonal mutations in gliomas, more in lower grade. This is consistent with our earlier work demonstrating that technique like RAPD analysis, unbiased for locus, is able to demonstrate more intra-tumor genetic heterogeneity in lower grade gliomas compared to higher grade. The results support the mutator hypothesis proposed by Loeb.

  17. Clonal mutations in primary human glial tumors: evidence in support of the mutator hypothesis

    International Nuclear Information System (INIS)

    Misra, Anjan; Chattopadhyay, Parthaprasad; Chosdol, Kunzang; Sarkar, Chitra; Mahapatra, Ashok K; Sinha, Subrata

    2007-01-01

    A verifiable consequence of the mutator hypothesis is that even low grade neoplasms would accumulate a large number of mutations that do not influence the tumor phenotype (clonal mutations). In this study, we have attempted to quantify the number of clonal mutations in primary human gliomas of astrocytic cell origin. These alterations were identified in tumor tissue, microscopically confirmed to have over 70% neoplastic cells. Random Amplified Polymorphic DNA (RAPD) analysis was performed using a set of fifteen 10-mer primers of arbitrary but definite sequences in 17 WHO grade II astrocytomas (low grade diffuse astrocytoma or DA) and 16 WHO grade IV astrocytomas (Glioblastoma Multiforme or GBM). The RAPD profile of the tumor tissue was compared with that of the leucocyte DNA of the same patient and alteration(s) scored. A quantitative estimate of the overall genomic changes in these tumors was obtained by 2 different modes of calculation. The overall change in the tumors was estimated to be 4.24% in DA and 2.29% in GBM by one method and 11.96% and 6.03% in DA and GBM respectively by the other. The difference between high and lower grade tumors was statistically significant by both methods. This study demonstrates the presence of extensive clonal mutations in gliomas, more in lower grade. This is consistent with our earlier work demonstrating that technique like RAPD analysis, unbiased for locus, is able to demonstrate more intra-tumor genetic heterogeneity in lower grade gliomas compared to higher grade. The results support the mutator hypothesis proposed by Loeb

  18. Characterization of glial tumors in PET/CT 18F-dopa and in perfusion MRI

    International Nuclear Information System (INIS)

    Nioche, Christophe

    2011-01-01

    MRI provides morphological information about a tumour, as well as information regarding its micro-vascularisation of the tumour. In PET/CT, accumulation of 18 F-Dopa in tumour cells results from the metabolic activity greater than that of healthy tissues.We studied 28 gliomas for which we analysed data from MRI and PET/CT. A registration method has been developed to combine information from both PET and MRI and to extract volumes of interest consistent with the information included in the two modalities. In these volumes, the tumour compartment and normal tissue compartment were identified using a Gaussian mixture model. Parameters from PET or MRI data were then calculated in these compartments. ROC analyses combined with linear discriminant analyses were used to assess whether joint observation of standardized uptake value (SUVmax) and relative Cerebral Blood Volume (rCBV) or of relative rk1 and rCBV could distinguish between low grade and high grade tumours. We found that using this joint analysis, 82% of high-grade tumors and 70% of low grade tumors were correctly classified (AUC of 0.88 for [SUVmax, rCBV] and of 0.92 for [rk1, rCBV]). Considering the combined information from [SUVmax, rCBV], the sensitivity for detecting high-grade tumors was 95% with a specificity of 60%. The negative predictive value was 52% for a positive predictive value of 95%. Similarly, considering the combined information from [rk1, rCBV], we also obtain a specificity of 60% associated with a 95% sensitivity for detecting high-grade tumors, with a negative predictive value of 60% and positive predictive value of 95%. Our work shows that joint analysis of information from microvascular and metabolic is possible by combining PET and MR imaging data. However, we found that, in our patient population, the microvascular information obtained through MR did not achieve better discrimination than the metabolic information derived from PET only. (author)

  19. Negative predictive value of ultrasound in predicting tumor-free margins in specimen sonography

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    Naz, S.; Hafeez, S.; Hussain, Z.; Hilal, K.

    2017-01-01

    Objective: To evaluate the success of ultrasound in post-excision specimen visualization, and negative predictive value of ultrasound for estimation of tumor-free margins using histopathology as the gold standard. Study Design: Cross-sectional analytical study. Place and Duration of Study: The Aga Khan University Hospital, Karachi, Pakistan, from May 2010 till January 2013. Methodology: Sonography of all breast nodules was done before and after exicision by two female radiologists with at least five years clinical experience. All surgeries were performed by the same referring breast surgeons. All nodules were non-palpable and had histopathology as well as specimen sonography performed at AKUH. Subjects were excluded, if histopathology was not available, post-procedure sonogram not done or done in another hospital and nodules that were not seen on ultrasound. After needle localization in 47 patients using ultrasound and in 7 patients using mammogram was done, sonogram was conducted in all 54 lesions. These were then assessed by ultrasound for detection of lesion and tumor-free margins in malignant lesion. Post-excision ultrasound was performed for the evaluation of lesion whether visualized or absent with localizing needle in situ, lesion dimensions, depth measurement between the superior margin of the lesion and its edge. Results: All 54 lesions were present on post-exicison scan, out of which 28 were documented as malignant and 26 as benign. Ultrasound declared all specimens as tumor-free. On histopathology, two lesions were documented as having tumor-positive margins and were proven to be invasive lobular carcinoma. Therefore, the negative predictive value of the specimen sonography for margin detection was 26/28 (92.8%). Conclusion: Ultrasound of the excised breast tumor specimen is a simple and reliable technique for confirmation of the tumor-free margins in non-palpable breast lesions. (author)

  20. Loss of NOTCH2 Positively Predicts Survival in Subgroups of Human Glial Brain Tumors

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    Boulay, Jean-Louis; Miserez, André R.; Zweifel, Christian; Sivasankaran, Balasubramanian; Kana, Veronika; Ghaffari, Anthony; Luyken, Cordelia; Sabel, Michael; Zerrouqi, Abdessamad; Wasner, Morten; Meir, Erwin Van; Tolnay, Markus; Reifenberger, Guido; Merlo, Adrian

    2007-01-01

    The structural complexity of chromosome 1p centromeric region has been an obstacle for fine mapping of tumor suppressor genes in this area. Loss of heterozygosity (LOH) on chromosome 1p is associated with the longer survival of oligodendroglioma (OD) patients. To test the clinical relevance of 1p loss in glioblastomas (GBM) patients and identifiy the underlying tumor suppressor locus, we constructed a somatic deletion map on chromosome 1p in 26 OG and 118 GBM. Deletion hotspots at 4 microsatellite markers located at 1p36.3, 1p36.1, 1p22 and 1p11 defined 10 distinct haplotypes that were related to patient survival. We found that loss of 1p centromeric marker D1S2696 within NOTCH2 intron 12 was associated with favorable prognosis in OD (P = 0.0007) as well as in GBM (P = 0.0175), while 19q loss, concomitant with 1p LOH in OD, had no influence on GBM survival (P = 0.918). Assessment of the intra-chromosomal ratio between NOTCH2 and its 1q21 pericentric duplication N2N (N2/N2N-test) allowed delineation of a consistent centromeric breakpoint in OD that also contained a minimally lost area in GBM. OD and GBM showed distinct deletion patterns that converged to the NOTCH2 gene in both glioma subtypes. Moreover, the N2/N2N-test disclosed homozygous deletions of NOTCH2 in primary OD. The N2/N2N test distinguished OD from GBM with a specificity of 100% and a sensitivity of 97%. Combined assessment of NOTCH2 genetic markers D1S2696 and N2/N2N predicted 24-month survival with an accuracy (0.925) that is equivalent to histological classification combined with the D1S2696 status (0.954) and higher than current genetic evaluation by 1p/19q LOH (0.762). Our data propose NOTCH2 as a powerful new molecular test to detect prognostically favorable gliomas. PMID:17593975

  1. Loss of NOTCH2 positively predicts survival in subgroups of human glial brain tumors.

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    Jean-Louis Boulay

    Full Text Available The structural complexity of chromosome 1p centromeric region has been an obstacle for fine mapping of tumor suppressor genes in this area. Loss of heterozygosity (LOH on chromosome 1p is associated with the longer survival of oligodendroglioma (OD patients. To test the clinical relevance of 1p loss in glioblastomas (GBM patients and identifiy the underlying tumor suppressor locus, we constructed a somatic deletion map on chromosome 1p in 26 OG and 118 GBM. Deletion hotspots at 4 microsatellite markers located at 1p36.3, 1p36.1, 1p22 and 1p11 defined 10 distinct haplotypes that were related to patient survival. We found that loss of 1p centromeric marker D1S2696 within NOTCH2 intron 12 was associated with favorable prognosis in OD (P = 0.0007 as well as in GBM (P = 0.0175, while 19q loss, concomitant with 1p LOH in OD, had no influence on GBM survival (P = 0.918. Assessment of the intra-chromosomal ratio between NOTCH2 and its 1q21 pericentric duplication N2N (N2/N2N-test allowed delineation of a consistent centromeric breakpoint in OD that also contained a minimally lost area in GBM. OD and GBM showed distinct deletion patterns that converged to the NOTCH2 gene in both glioma subtypes. Moreover, the N2/N2N-test disclosed homozygous deletions of NOTCH2 in primary OD. The N2/N2N test distinguished OD from GBM with a specificity of 100% and a sensitivity of 97%. Combined assessment of NOTCH2 genetic markers D1S2696 and N2/N2N predicted 24-month survival with an accuracy (0.925 that is equivalent to histological classification combined with the D1S2696 status (0.954 and higher than current genetic evaluation by 1p/19q LOH (0.762. Our data propose NOTCH2 as a powerful new molecular test to detect prognostically favorable gliomas.

  2. Significant histologic features differentiating cellular fibroadenoma from phyllodes tumor on core needle biopsy specimens.

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    Yasir, Saba; Gamez, Roberto; Jenkins, Sarah; Visscher, Daniel W; Nassar, Aziza

    2014-09-01

    Cellular fibroepithelial lesions (CFELs) are a heterogeneous group of tumors encompassing cellular fibroadenoma (CFA) and phyllodes tumor (PT). Distinction between the two is challenging on core needle biopsy (CNB) specimens. The objective of this study was to evaluate histologic features that can help distinguish PT from CFA on CNB specimens. Records of all patients diagnosed with CFELs on CNB specimens with follow-up excision between January 2002 and December 2012 were retrieved. Histopathologic stromal features were evaluated on CNB specimens, including mitoses per 10 high-power fields (hpf), overgrowth, increased cellularity, fragmentation, adipose tissue infiltration, heterogeneity, subepithelial condensation, and nuclear pleomorphism. Twenty-seven (42.2%) of 64 were diagnosed as PT (24 benign PTs and three borderline PTs) and 37 (57.8%) as CFA on excision. All features except for increased stromal cellularity were statistically significant. The average number of histologic features seen in PT and CFA was 3.9 and 1.4, respectively (odds ratio [OR], 7.27; 95% confidence interval [CI], 2.44-21.69; P = .0004). The average number of mitoses per 10 hpf was 3.0 for PT compared with 0.8 for CFA (OR, 2.14; 95% CI, 1.18-3.86; P = .01). The presence of mitoses (three or more) and/or total histologic features of three or more on CNB specimens were the most helpful features in predicting PT on excision. Copyright© by the American Society for Clinical Pathology.

  3. TumorTracer: a method to identify the tissue of origin from the somatic mutations of a tumor specimen

    DEFF Research Database (Denmark)

    Marquard, Andrea Marion; Birkbak, Nicolai Juul; Thomas, Cecilia Engel

    2015-01-01

    A substantial proportion of cancer cases present with a metastatic tumor and require further testing to determine the primary site; many of these are never fully diagnosed and remain cancer of unknown primary origin (CUP). It has been previously demonstrated that the somatic point mutations......-copy-number classifier on three independent data sets: 1669 newly available public tumors of various types, a cohort of 91 breast metastases, and a set of 24 specimens from 9 lung cancer patients subjected to multiregion sequencing. The cross-validation accuracy was highest when all three types of information were used...... detected in a tumor can be used to identify its site of origin with limited accuracy. We hypothesized that higher accuracy could be achieved by a classification algorithm based on the following feature sets: 1) the number of nonsynonymous point mutations in a set of 232 specific cancer-associated genes, 2...

  4. Mouse mammary tumor virus-like gene sequences are present in lung patient specimens

    Directory of Open Access Journals (Sweden)

    Rodríguez-Padilla Cristina

    2011-09-01

    Full Text Available Abstract Background Previous studies have reported on the presence of Murine Mammary Tumor Virus (MMTV-like gene sequences in human cancer tissue specimens. Here, we search for MMTV-like gene sequences in lung diseases including carcinomas specimens from a Mexican population. This study was based on our previous study reporting that the INER51 lung cancer cell line, from a pleural effusion of a Mexican patient, contains MMTV-like env gene sequences. Results The MMTV-like env gene sequences have been detected in three out of 18 specimens studied, by PCR using a specific set of MMTV-like primers. The three identified MMTV-like gene sequences, which were assigned as INER6, HZ101, and HZ14, were 99%, 98%, and 97% homologous, respectively, as compared to GenBank sequence accession number AY161347. The INER6 and HZ-101 samples were isolated from lung cancer specimens, and the HZ-14 was isolated from an acute inflammatory lung infiltrate sample. Two of the env sequences exhibited disruption of the reading frame due to mutations. Conclusion In summary, we identified the presence of MMTV-like gene sequences in 2 out of 11 (18% of the lung carcinomas and 1 out of 7 (14% of acute inflamatory lung infiltrate specimens studied of a Mexican Population.

  5. Tumor containing fragment number influences immunohistochemistry positive rate of HER2 in biopsy specimens of gastric cancer.

    Science.gov (United States)

    Xu, Chen; Liu, Yalan; Ge, Xiaowen; Jiang, Dongxian; Zhang, Ying; Ji, Yuan; Hou, Jun; Huang, Jie; Su, Jieakesu; Zeng, Haiying; Qin, Jing; Hou, Yingyong

    2017-05-26

    HER2 assessment in biopsy specimens of gastric cancer (GC) is challenging because of the intratumoral heterogeneity. False negative results may be get because of limited biopsy material. The aim of this study is to explore how tumor-containing fragment number and biopsy specimen number affect HER2 immunohistochemistry (IHC) positive rate. Eight hundred and ninety biopsy specimens and 459 paired resected specimens were collected. IHC staining of HER2 was performed. HER2 IHC positive (scored 3+) rate was compared based on tumor-containing fragment number, biopsy specimen number, average size and tumor tissue proportion of tumor-containing fragments. The positive predictability of biopsy specimens to resected specimens was analyzed based on tumor fragment number. HER2 IHC positive rates were 2.0, 3.5, 7.0, 13.2, 17.1, and 15.9% when tumor fragment numbers were 1, 2, 3, 4, 5 and 6 respectively. The rate rose with the increase of tumor fragment number (P = 0.004). ROC curve analysis showed that biopsy specimens exhibited positive predictability when tumor fragment number reached 3, but showed better performance when the number was ≥4 (P fragment number reached 4, no statistic differences were reached in either HER2 IHC positive rate or positive predictability with further increase of the number (P > 0.05). HER2 IHC positive rate was not associated with biopsy number (P = 0.127), average size of tumor fragments (P = 0.397), and tumor tissue proportion of tumor fragments (P = 0.825) directly. The number of tumor-containing fragments influences HER2 IHC positive (scored 3+) rate. Greater than or equal to 4 (≥4) tumor fragments give better results in the positive rate as well as positive predictability. We recommend the number of tumor containing fragments be described in the HER2 IHC pathology reports for clinical reference in endoscopic biopsy specimens of GC.

  6. A Unique Model System for Tumor Progression in GBM Comprising Two Developed Human Neuro-Epithelial Cell Lines with Differential Transforming Potential and Coexpressing Neuronal and Glial Markers

    Directory of Open Access Journals (Sweden)

    Anjali Shiras

    2003-11-01

    Full Text Available The molecular mechanisms involved in tumor progression from a low-grade astrocytoma to the most malignant glioblastoma multiforme (GBM have been hampered due to lack of suitable experimental models. We have established a model of tumor progression comprising of two cell lines derived from the same astrocytoma tumor with a set of features corresponding to low-grade glioma (as in HNGC-1 and high-grade GBM (as in HNGC-2. The HNGC-1 cell line is slowgrowing, contact-inhibited, nontumorigenic, and noninvasive, whereas HNGC-2 is a rapidly proliferating, anchorage-independent, highly tumorigenic, and invasive cell line. The proliferation of cell lines is independent of the addition of exogenous growth factors. Interestingly, the HNGC-2 cell line displays a near-haploid karyotype except for a disomy of chromosome 2. The two cell lines express the neuronal precursor and progenitor markers vimentin, nestin, MAP-2, and NFP160, as well as glial differentiation protein S100μ. The HNGC-1 cell line also expresses markers of mature neurons like Tuj1 and GFAP, an astrocytic differentiation marker, hence contributing toward a more morphologically differentiated phenotype with a propensity for neural differentiation in vitro. Additionally, overexpression of epidermal growth factor receptor and c-erbB2, and loss of fibronectin were observed only in the HNGC-2 cell line, implicating the significance of these pathways in tumor progression. This in vitro model system assumes importance in unraveling the cellular and molecular mechanisms in differentiation, transformation, and gliomagenesis.

  7. Diagnosis of gastrointestinal stromal tumors from minute specimens: cytomorphology, immunohistochemistry, and molecular diagnostic findings.

    Science.gov (United States)

    Layfield, Lester J; Wallander, Michelle L

    2012-06-01

    Gastrointestinal stromal tumors (GIST) are the most common mesenchymal neoplasm arising from the gastrointestinal tract. Workup of these lesions includes morphologic study and immunohistochemical and often molecular diagnostic analysis. Historically, these neoplasms had been included under a number of diagnostic categories including leiomyoma, leiomyosarcoma, schwannoma, and leiomyoblastoma. The lesions that were clearly sarcomatous were difficult to treat and therapeutically refractory to chemotherapeutic agents. Significant progress in our understanding of these neoplasms and our ability to successfully treat them occurred following the discovery that they were immunoreactive for KIT protein and harbored activating mutations in the KIT gene. Many are initially diagnosed by fine-needle aspiration (FNA) but workup may include mutational analysis to help direct therapy. This review outlines a practical approach to the cytologic diagnosis of GISTs and their molecular workup on small specimens obtained by FNA or core biopsy. Copyright © 2012 Wiley Periodicals, Inc.

  8. Performance of next-generation sequencing on small tumor specimens and/or low tumor content samples using a commercially available platform.

    Directory of Open Access Journals (Sweden)

    Scott Morris

    Full Text Available Next generation sequencing tests (NGS are usually performed on relatively small core biopsy or fine needle aspiration (FNA samples. Data is limited on what amount of tumor by volume or minimum number of FNA passes are needed to yield sufficient material for running NGS. We sought to identify the amount of tumor for running the PCDx NGS platform.2,723 consecutive tumor tissues of all cancer types were queried and reviewed for inclusion. Information on tumor volume, success of performing NGS, and results of NGS were compiled. Assessment of sequence analysis, mutation calling and sensitivity, quality control, drug associations, and data aggregation and analysis were performed.6.4% of samples were rejected from all testing due to insufficient tumor quantity. The number of genes with insufficient sensitivity make definitive mutation calls increased as the percentage of tumor decreased, reaching statistical significance below 5% tumor content. The number of drug associations also decreased with a lower percentage of tumor, but this difference only became significant between 1-3%. The number of drug associations did decrease with smaller tissue size as expected. Neither specimen size or percentage of tumor affected the ability to pass mRNA quality control. A tumor area of 10 mm2 provides a good margin of error for specimens to yield adequate drug association results.Specimen suitability remains a major obstacle to clinical NGS testing. We determined that PCR-based library creation methods allow the use of smaller specimens, and those with a lower percentage of tumor cells to be run on the PCDx NGS platform.

  9. Tumor Size on Abdominal MRI Versus Pathologic Specimen in Resected Pancreatic Adenocarcinoma: Implications for Radiation Treatment Planning

    Energy Technology Data Exchange (ETDEWEB)

    Hall, William A., E-mail: whall4@emory.edu [Department of Radiation Oncology, Emory University, Atlanta, Georgia (United States); Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Mikell, John L. [Department of Radiation Oncology, Emory University, Atlanta, Georgia (United States); Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Mittal, Pardeep [Department of Radiology, Emory University, Atlanta, Georgia (United States); Colbert, Lauren [Department of Radiation Oncology, Emory University, Atlanta, Georgia (United States); Prabhu, Roshan S. [Department of Radiation Oncology, Emory University, Atlanta, Georgia (United States); Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Kooby, David A. [Department of Surgery, Emory University, Atlanta, Georgia (United States); Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Nickleach, Dana [Biostatistics and Bioinformatics Shared Resource, Emory University, Atlanta, Georgia (United States); Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Hanley, Krisztina [Department of Pathology, Emory University, Atlanta, Georgia (United States); Sarmiento, Juan M. [Department of Surgery, Emory University, Atlanta, Georgia (United States); Ali, Arif N.; Landry, Jerome C. [Department of Radiation Oncology, Emory University, Atlanta, Georgia (United States); Winship Cancer Institute, Emory University, Atlanta, Georgia (United States)

    2013-05-01

    Purpose: We assessed the accuracy of abdominal magnetic resonance imaging (MRI) for determining tumor size by comparing the preoperative contrast-enhanced T1-weighted gradient echo (3-dimensional [3D] volumetric interpolated breath-hold [VIBE]) MRI tumor size with pathologic specimen size. Methods and Materials: The records of 92 patients who had both preoperative contrast-enhanced 3D VIBE MRI images and detailed pathologic specimen measurements were available for review. Primary tumor size from the MRI was independently measured by a single diagnostic radiologist (P.M.) who was blinded to the pathology reports. Pathologic tumor measurements from gross specimens were obtained from the pathology reports. The maximum dimensions of tumor measured in any plane on the MRI and the gross specimen were compared. The median difference between the pathology sample and the MRI measurements was calculated. A paired t test was conducted to test for differences between the MRI and pathology measurements. The Pearson correlation coefficient was used to measure the association of disparity between the MRI and pathology sizes with the pathology size. Disparities relative to pathology size were also examined and tested for significance using a 1-sample t test. Results: The median patient age was 64.5 years. The primary site was pancreatic head in 81 patients, body in 4, and tail in 7. Three patients were American Joint Commission on Cancer stage IA, 7 stage IB, 21 stage IIA, 58 stage IIB, and 3 stage III. The 3D VIBE MRI underestimated tumor size by a median difference of 4 mm (range, −34-22 mm). The median largest tumor dimensions on MRI and pathology specimen were 2.65 cm (range, 1.5-9.5 cm) and 3.2 cm (range, 1.3-10 cm), respectively. Conclusions: Contrast-enhanced 3D VIBE MRI underestimates tumor size by 4 mm when compared with pathologic specimen. Advanced abdominal MRI sequences warrant further investigation for radiation therapy planning in pancreatic adenocarcinoma before

  10. Tumor Size on Abdominal MRI Versus Pathologic Specimen in Resected Pancreatic Adenocarcinoma: Implications for Radiation Treatment Planning

    International Nuclear Information System (INIS)

    Hall, William A.; Mikell, John L.; Mittal, Pardeep; Colbert, Lauren; Prabhu, Roshan S.; Kooby, David A.; Nickleach, Dana; Hanley, Krisztina; Sarmiento, Juan M.; Ali, Arif N.; Landry, Jerome C.

    2013-01-01

    Purpose: We assessed the accuracy of abdominal magnetic resonance imaging (MRI) for determining tumor size by comparing the preoperative contrast-enhanced T1-weighted gradient echo (3-dimensional [3D] volumetric interpolated breath-hold [VIBE]) MRI tumor size with pathologic specimen size. Methods and Materials: The records of 92 patients who had both preoperative contrast-enhanced 3D VIBE MRI images and detailed pathologic specimen measurements were available for review. Primary tumor size from the MRI was independently measured by a single diagnostic radiologist (P.M.) who was blinded to the pathology reports. Pathologic tumor measurements from gross specimens were obtained from the pathology reports. The maximum dimensions of tumor measured in any plane on the MRI and the gross specimen were compared. The median difference between the pathology sample and the MRI measurements was calculated. A paired t test was conducted to test for differences between the MRI and pathology measurements. The Pearson correlation coefficient was used to measure the association of disparity between the MRI and pathology sizes with the pathology size. Disparities relative to pathology size were also examined and tested for significance using a 1-sample t test. Results: The median patient age was 64.5 years. The primary site was pancreatic head in 81 patients, body in 4, and tail in 7. Three patients were American Joint Commission on Cancer stage IA, 7 stage IB, 21 stage IIA, 58 stage IIB, and 3 stage III. The 3D VIBE MRI underestimated tumor size by a median difference of 4 mm (range, −34-22 mm). The median largest tumor dimensions on MRI and pathology specimen were 2.65 cm (range, 1.5-9.5 cm) and 3.2 cm (range, 1.3-10 cm), respectively. Conclusions: Contrast-enhanced 3D VIBE MRI underestimates tumor size by 4 mm when compared with pathologic specimen. Advanced abdominal MRI sequences warrant further investigation for radiation therapy planning in pancreatic adenocarcinoma before

  11. Correlation Between Ki-67 Index, World Health Organization Grade and Patient Survival in Glial Tumors With Astrocytic Differentiation

    Science.gov (United States)

    Dzhenkov, Deyan L; Kitanova, Martina; Donev, Ivan S; Ghenev, Peter

    2017-01-01

    Background Glioblastoma multiforme (GBM) is a class IV astrocytic tumor, the most malignant of the four groups of World Health Organization (WHO) tumors with astrocytic differentiation. Aim The aim of this study was to estab­lish whether a correlation exists between the Ki-67 index of tumors with astrocytic differentiation, WHO grade, and patient survival. Materials and methods A retrospective non-clinical approach to patient selection was chosen for the aim of the study. A total of 47 patients diagnosed and treated for CNS tumors with astrocytic differentiation in the St. Marina University Hospital, Varna, Bulgaria, from September 2012 to July 2016 were retrospectively included into the study cohort. The cases were tested for their immunohistochemistry (IHC) reaction with Ki-67 after their original Hematoxylin and Eosin and IHC slides were reviewed by a single author and blind coded. The Ki-67 positivity index of the nuclei was estimated after digitalization of the slides and calculated by the ImmunoRatio automated count­ing tool. The individual Ki-67 index and patient survival of each case were statistically compared. Results The histopathological groups, after the blind Ki-67 index automated calculation was carried out, revealed no WHO grade I, two WHO grade II samples, four WHO grade III samples and 41 WHO grade IV cases, and these were included in the analysis. The two samples of WHO grade II astrocytic tumors had a mean Ki-67 index of 25%; however, they comprised tumors with an individual index of 43% and 7%, both individual values with a highly unlikely index for this group. The four samples of WHO grade III had a mean Ki-67 index of 4%, standard deviation ±2.16 (p>0.05), with the lowest index being 1% and the highest one being 6%. Both WHO grade II and III did not include enough samples to allow for a proper statistical analysis of patient survival. The 41 GBM cases had a mean Ki-67 index of 17.34%, standard deviation ±10.79 (p>0

  12. Label-free reflectance hyperspectral imaging for tumor margin assessment: a pilot study on surgical specimens of cancer patients

    Science.gov (United States)

    Fei, Baowei; Lu, Guolan; Wang, Xu; Zhang, Hongzheng; Little, James V.; Patel, Mihir R.; Griffith, Christopher C.; El-Diery, Mark W.; Chen, Amy Y.

    2017-08-01

    A label-free, hyperspectral imaging (HSI) approach has been proposed for tumor margin assessment. HSI data, i.e., hypercube (x,y,λ), consist of a series of high-resolution images of the same field of view that are acquired at different wavelengths. Every pixel on an HSI image has an optical spectrum. In this pilot clinical study, a pipeline of a machine-learning-based quantification method for HSI data was implemented and evaluated in patient specimens. Spectral features from HSI data were used for the classification of cancer and normal tissue. Surgical tissue specimens were collected from 16 human patients who underwent head and neck (H&N) cancer surgery. HSI, autofluorescence images, and fluorescence images with 2-deoxy-2-[(7-nitro-2,1,3-benzoxadiazol-4-yl)amino]-D-glucose (2-NBDG) and proflavine were acquired from each specimen. Digitized histologic slides were examined by an H&N pathologist. The HSI and classification method were able to distinguish between cancer and normal tissue from the oral cavity with an average accuracy of 90%±8%, sensitivity of 89%±9%, and specificity of 91%±6%. For tissue specimens from the thyroid, the method achieved an average accuracy of 94%±6%, sensitivity of 94%±6%, and specificity of 95%±6%. HSI outperformed autofluorescence imaging or fluorescence imaging with vital dye (2-NBDG or proflavine). This study demonstrated the feasibility of label-free, HSI for tumor margin assessment in surgical tissue specimens of H&N cancer patients. Further development of the HSI technology is warranted for its application in image-guided surgery.

  13. A semiautomatic CT-based ensemble segmentation of lung tumors: comparison with oncologists' delineations and with the surgical specimen.

    Science.gov (United States)

    Rios Velazquez, Emmanuel; Aerts, Hugo J W L; Gu, Yuhua; Goldgof, Dmitry B; De Ruysscher, Dirk; Dekker, Andre; Korn, René; Gillies, Robert J; Lambin, Philippe

    2012-11-01

    To assess the clinical relevance of a semiautomatic CT-based ensemble segmentation method, by comparing it to pathology and to CT/PET manual delineations by five independent radiation oncologists in non-small cell lung cancer (NSCLC). For 20 NSCLC patients (stages Ib-IIIb) the primary tumor was delineated manually on CT/PET scans by five independent radiation oncologists and segmented using a CT based semi-automatic tool. Tumor volume and overlap fractions between manual and semiautomatic-segmented volumes were compared. All measurements were correlated with the maximal diameter on macroscopic examination of the surgical specimen. Imaging data are available on www.cancerdata.org. High overlap fractions were observed between the semi-automatically segmented volumes and the intersection (92.5±9.0, mean±SD) and union (94.2±6.8) of the manual delineations. No statistically significant differences in tumor volume were observed between the semiautomatic segmentation (71.4±83.2 cm(3), mean±SD) and manual delineations (81.9±94.1 cm(3); p=0.57). The maximal tumor diameter of the semiautomatic-segmented tumor correlated strongly with the macroscopic diameter of the primary tumor (r=0.96). Semiautomatic segmentation of the primary tumor on CT demonstrated high agreement with CT/PET manual delineations and strongly correlated with the macroscopic diameter considered as the "gold standard". This method may be used routinely in clinical practice and could be employed as a starting point for treatment planning, target definition in multi-center clinical trials or for high throughput data mining research. This method is particularly suitable for peripherally located tumors. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  14. Direct identification of an HPV-16 tumor antigen from cervical cancer biopsy specimens

    Directory of Open Access Journals (Sweden)

    Derin B Keskin

    2011-12-01

    Full Text Available Persistent infection with high-risk human papilloma viruses (HPV is the worldwide cause of many cancers, including cervical, anal, vulval, vaginal, penile and oropharyngeal. Since T cells naturally eliminate the majority of chronic HPV infections by recognizing epitopes displayed on virally altered epithelium, we exploited Poisson detection mass spectrometry (MS3 to identify those epitopes and inform future T cell-based vaccine design. Nine cervical cancer biopsies from HPV-16 positive HLA-A*02 patients were obtained, histopathology determined, and E7 oncogene PCR-amplified from tumor DNA and sequenced. Conservation of E7 oncogene coding segments was found in all tumors. MS3 analysis of HLA-A*02 immunoprecipitates detected E711-19 peptide (YMLDLQPET in seven of the nine tumor biopsies. The remaining two samples were E711-19 negative and lacked the HLA-A*02 binding GILT thioreductase peptide despite possessing binding-competent HLA-A*02 alleles. Thus, the conserved E711-19 peptide is a dominant HLA-A*02 binding tumor antigen in HPV-16 transformed cervical squamous and adenocarcinomas. Findings that a minority of HLA-A*02:01 tumors lack expression of both E711-19 and a peptide from a thioreductase important in processing of cysteine-rich proteins like E7 underscore the value of physical detection, define a potential additional tumor escape mechanism and have implications for therapeutic cancer vaccine development.

  15. Identification of tumor specimens by DNA analysis in a case of histocytological paraffin tissue block swapping

    Science.gov (United States)

    Raina, Anupuma; Yadav, Bhuvnesh; Ali, Sher; Das Dogra, Tirath

    2011-01-01

    We report on a patient who was diagnosed with high-grade breast carcinoma by all the pre-surgery clinical evidence of malignancy, but histopathological reports did not reveal any such tumor residue in the post-surgical tissue block. This raised a suspicion that either exchange of block, labeling error, or a technical error took place during gross examination of the tissue. The mastectomy residue was unprocurable to sort out the problem. So, two doubtful paraffin blocks were sent for DNA fingerprinting analysis. The partial DNA profiles (8-9/15 loci) were obtained from histocytological blocks. The random matching probability for both the paraffin blocks and the patient’s blood were found to be 1 in 4.43E4, 1.89E6, and 8.83E13, respectively for Asian population. Multiplex short tandem repeat analysis applied in this case determined that the cause of tumor absence was an error in gross examination of the post-surgical tissue. Moreover, the analysis helped in justifying the therapy given to the patient. Thus, with DNA fingerprinting technique, it was concluded that there was no exchange of the blocks between the two patients operated on the same day and the treatment given to the concerned patient was in the right direction. PMID:21674839

  16. Digestive tumor bank protocol: from surgical specimens to genomic studies of digestive cancers.

    Science.gov (United States)

    Popescu, I; Stroescu, C; Dumitrascu, T; Herlea, V; Paslaru, Liliana; Lazar, V; Boissin, H; Taieb, J; Horeanga, Ionela

    2006-01-01

    Cancer is a complex polygenic and multifactorial disease, resulting from successive dynamic changes in the genome of somatic cells and from the accumulation of molecular alterations in both tumour cells and host cells. For the majority of cancers, including many malignancies of the gastrointestinal tract, our current means of diagnosis and treatment of the tumors are grossly insufficient. In recent years the development of several gene expression profiling methods such as comparative genomic hybridization (CGH), differential display, serial analysis of gene expression (SAGE) and DNA arrays, together with the sequencing of the human genome, has provided an opportunity to monitor and investigate the complete cascade of molecular events leading to tumor development and progression. Given the central role played by surgeons in the current management of patients with solid cancers, it is of paramount importance for them to know the principles characterizing this laboratory tools to critically assess the results originating from this biotechnology. We describe in this article the scientific partnership between Fundeni Clinical Institute Bucharest, Romania and RNtech Company, Paris, France for the development of a center of biological resources (Biobank) as well as the standardized protocol of working with the biological samples, the ongoing projects and the future perspectives.

  17. Ga-68 DOTATOC PET/CT-Guided Biopsy and Cryoablation with Autoradiography of Biopsy Specimen for Treatment of Tumor-Induced Osteomalacia

    Energy Technology Data Exchange (ETDEWEB)

    Maybody, Majid, E-mail: maybodym@mskcc.org [Memorial Sloan Kettering Cancer Center, Interventional Radiology Service (United States); Grewal, Ravinder K. [Memorial Sloan Kettering Cancer Center, Molecular Imaging and Therapy Service, Department of Radiology (United States); Healey, John H. [Memorial Sloan Kettering Cancer Center, Orthopedic Surgical Oncology Service, Department of Surgery (United States); Antonescu, Cristina R. [Memorial Sloan Kettering Cancer Center, Department of Pathology (United States); Fanchon, Louise [Memorial Sloan Kettering Cancer Center, Department of Physics (United States); Hwang, Sinchun [Memorial Sloan Kettering Cancer Center, Department of Radiology (United States); Carrasquillo, Jorge A. [Memorial Sloan Kettering Cancer Center, Molecular Imaging and Therapy Service, Department of Radiology (United States); Kirov, Assen [Memorial Sloan Kettering Cancer Center, Department of Physics (United States); Farooki, Azeez [Memorial Sloan Kettering Cancer Center, Department of Medicine (United States)

    2016-09-15

    Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused by small benign tumors of mesenchymal origin also known as phosphaturic mesenchymal tumors mixed connective tissue variant. Excellent prognosis is expected with eradication of the culprit tumor. These small tumors are notoriously difficult to localize with conventional imaging studies; this often leads to an extensive work up and prolonged morbidity. We report a patient with clinical diagnosis of TIO whose culprit tumor was localized with Ga-68 DOTATOC PET/CT and MRI. Biopsy and cryoablation were performed under Ga-68 DOTATOC PET/CT guidance. Autoradiography of the biopsy specimen was performed and showed in situ correlation between Ga-68 DOTATOC uptake and histopathology with millimeter resolution.

  18. Photodynamic damage of glial cells in crayfish ventral nerve cord

    Science.gov (United States)

    Kolosov, M. S.; Duz, E.; Uzdensky, A. B.

    2011-03-01

    Photodynamic therapy (PDT) is a promising method for treatment of brain tumors, the most of which are of glial origin. In the present work we studied PDT-mediated injury of glial cells in nerve tissue, specifically, in abdominal connectives in the crayfish ventral nerve cord. The preparation was photosensitized with alumophthalocyanine Photosens and irradiated 30 min with the diode laser (670 nm, 0.1 or 0.15 W/cm2). After following incubation in the darkness during 1- 10 hours it was fluorochromed with Hoechst 33342 and propidium iodide to reveal nuclei of living, necrotic and apoptotic cells. The chain-like location of the glial nuclei allowed visualization of those enveloping giant axons and blood vessels. The level of glial necrosis in control preparations was about 2-5 %. Apoptosis was not observed in control preparations. PDT significantly increased necrosis of glial cells to 52 or 67 % just after irradiation with 0.1 or 0.15 W/cm2, respectively. Apoptosis of glial cells was observed only at 10 hours after light exposure. Upper layers of the glial envelope of the connectives were injured stronger comparing to deep ones: the level of glial necrosis decreased from 100 to 30 % upon moving from the connective surface to the plane of the giant axon inside the connective. Survival of glial cells was also high in the vicinity of blood vessels. One can suggest that giant axons and blood vessels protect neighboring glial cells from photodynamic damage. The mechanism of such protective action remains to be elucidated.

  19. Exploiting fruit byproducts for eco-friendly nanosynthesis: Citrus × clementina peel extract mediated fabrication of silver nanoparticles with high efficacy against microbial pathogens and rat glial tumor C6 cells.

    Science.gov (United States)

    Saratale, Rijuta Ganesh; Shin, Han-Seung; Kumar, Gopalakrishnan; Benelli, Giovanni; Ghodake, Gajanan S; Jiang, Yuan Yuan; Kim, Dong Su; Saratale, Ganesh Dattatraya

    2018-04-01

    Process byproducts from the fruit industry may represent a cheap and reliable source of green reducing agents to be used in current bio-nanosynthesis. This study reports the use of orange (Citrus × clementina) peel aqueous extract (OPE) for one-pot green synthesis of silver nanoparticles (AgNPs) with high effectiveness against various microbial pathogens as well as rat glial tumor C6 cells. The effects of various operational parameters on the synthesis of AgNPs were systematically investigated. The morphology, particle size, and properties of synthesized AgNPs were characterized using UV-visible spectroscopy, x-ray diffraction, x-ray photoelectron spectroscopy, field emission scanning electron microscopy, energy-dispersive x-ray spectroscopy, and Fourier transform infrared spectroscopy. High-resolution transmission electron microscopy shows that the nanoparticles are mostly spherical in shape and monodispersed, with an average particle size of 15-20 nm. Notably, the OPE-synthesized AgNPs were stable up to 6 months without change in their properties. Low doses of OPE-AgNPs inhibited the growth of human pathogens Escherichia coli, Bacillus cereus, and Staphylococcus aureus. The minimum inhibitory concentration and minimum bactericidal concentration of AgNPs against selected pathogenic bacteria were determined. OPE-AgNPs exhibited strong antioxidant activity in terms of ABTS (2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid)) radical scavenging (IC 50 49.6 μg/mL) and DPPH (1,1-diphenyl-2-picrylhydrazyl) radical scavenging (IC 50 63.4 μg/mL). OPE-AgNPs showed dose-dependent response against rat glial tumor C6 cells (LD 50 60 μg/mL) showing a promising potential as anticancer agents. Overall, the current investigation highlighted a cheap green technology route to synthesize AgNPs using OPE byproducts and could potentially be utilized in biomedical, cosmetic, and pharmaceutical industry.

  20. Label-free imaging of brain and brain tumor specimens with combined two-photon excited fluorescence and second harmonic generation microscopy

    Science.gov (United States)

    Jiang, Liwei; Wang, Xingfu; Wu, Zanyi; Du, Huiping; Wang, Shu; Li, Lianhuang; Fang, Na; Lin, Peihua; Chen, Jianxin; Kang, Dezhi; Zhuo, Shuangmu

    2017-10-01

    Label-free imaging techniques are gaining acceptance within the medical imaging field, including brain imaging, because they have the potential to be applied to intraoperative in situ identifications of pathological conditions. In this paper, we describe the use of two-photon excited fluorescence (TPEF) and second harmonic generation (SHG) microscopy in combination for the label-free detection of brain and brain tumor specimens; gliomas. Two independently detecting channels were chosen to subsequently collect TPEF/SHG signals from the specimen to increase TPEF/SHG image contrasts. Our results indicate that the combined TPEF/SHG microscopic techniques can provide similar rat brain structural information and produce a similar resolution like conventional H&E staining in neuropathology; including meninges, cerebral cortex, white-matter structure corpus callosum, choroid plexus, hippocampus, striatum, and cerebellar cortex. It can simultaneously detect infiltrating human brain tumor cells, the extracellular matrix collagen fiber of connective stroma within brain vessels and collagen depostion in tumor microenvironments. The nuclear-to-cytoplasmic ratio and collagen content can be extracted as quantitative indicators for differentiating brain gliomas from healthy brain tissues. With the development of two-photon fiberscopes and microendoscope probes and their clinical applications, the combined TPEF and SHG microcopy may become an important multimodal, nonlinear optical imaging approach for real-time intraoperative histological diagnostics of residual brain tumors. These occur in various brain regions during ongoing surgeries through the method of simultaneously identifying tumor cells, and the change of tumor microenvironments, without the need for the removal biopsies and without the need for tissue labelling or fluorescent markers.

  1. Glial heterotopia of the orbit: a rare cause of proptosis.

    Science.gov (United States)

    Bakhti, Souad; Terkmani, Fella; Tighilt, Nabila; Benmouma, Youcef; Boumehdi, Nazim; Djennas, Mohamed

    2016-11-01

    Glial heterotopia is defined as presence of normal glial tissue in an unusual location without connection with the brain. It is a very rare clinical entity occuring mostly in the head and neck region which is generally present at birth. Orbital location is very rare. We report a case of a 4-month-old girl presenting congenital proptosis with progressive increase. CT scan revealed an intraorbital mass without bony defect. The patient was operated, and resection was subtotal. Histologically, the tumor was composed of glial tissue with plexus choroid and pathologist concluded glial heterotopia. The child is under constant medical supervision because recurrences can be observed after incomplete resection; she had no new clinical signs at 18 months follow-up.

  2. Neuronal-glial trafficking

    International Nuclear Information System (INIS)

    Bachelard, H.S.

    2001-01-01

    Full text: The name 'glia' originates from the Greek word for glue, because astro glia (or astrocytes) were thought only to provide an anatomical framework for the electrically-excitable neurones. However, awareness that astrocytes perform vital roles in protecting the neurones, which they surround, emerged from evidence that they act as neuroprotective K + -sinks, and that they remove potentially toxic extracellular glutamate from the vicinity of the neurones. The astrocytes convert the glutamate to non-toxic glutamine which is returned to the neurones and used to replenish transmitter glutamate. This 'glutamate-glutamine cycle' (established in the 1960s by Berl and his colleagues) also contributes to protecting the neurones against a build-up of toxic ammonia. Glial cells also supply the neurones with components for free-radical scavenging glutathione. Recent studies have revealed that glial cells play a more positive interactive role in furnishing the neurones with fuels. Studies using radioactive 14 C, 13 C-MRS and 15 N-GCMS have revealed that glia produce alanine, lactate and proline for consumption by neurones, with increased formation of neurotransmitter glutamate. On neuronal activation the release of NH 4 + and glutamate from the neurones stimulates glucose uptake and glycolysis in the glia to produce more alanine, which can be regarded as an 'alanine-glutamate cycle' Use of 14 C-labelled precursors provided early evidence that neurotransmitter GABA may be partly derived from glial glutamine, and this has been confirmed recently in vivo by MRS isotopomer analysis of the GABA and glutamine labelled from 13 C-acetate. Relative rates of intermediary metabolism in glia and neurones can be calculated using a combination of [1- 13 C] glucose and [1,2- 13 C] acetate. When glutamate is released by neurones there is a net neuronal loss of TCA intermediates which have to be replenished. Part of this is derived from carboxylation of pyruvate, (pyruvate carboxylase

  3. Percutaneous computed tomography-guided core needle biopsy of soft tissue tumors: results and correlation with surgical specimen analysis

    Energy Technology Data Exchange (ETDEWEB)

    Chojniak, Rubens; Grigio, Henrique Ramos; Bitencourt, Almir Galvao Vieira; Pinto, Paula Nicole Vieira; Tyng, Chiang J.; Cunha, Isabela Werneck da; Aguiar Junior, Samuel; Lopes, Ademar, E-mail: chojniak@uol.com.br [Hospital A.C. Camargo, Sao Paulo, SP (Brazil)

    2012-09-15

    Objective: To evaluate the efficacy of percutaneous computed tomography (CT)-guided core needle biopsy of soft tissue tumors in obtaining appropriate samples for histological analysis, and compare its diagnosis with the results of the surgical pathology as available. Materials and Methods: The authors reviewed medical records, imaging and histological reports of 262 patients with soft-tissue tumors submitted to CT-guided core needle biopsy in an oncologic reference center between 2003 and 2009. Results: Appropriate samples were obtained in 215 (82.1%) out of the 262 patients. The most prevalent tumors were sarcomas (38.6%), metastatic carcinomas (28.8%), benign mesenchymal tumors (20.5%) and lymphomas (9.3%). Histological grading was feasible in 92.8% of sarcoma patients, with the majority of them (77.9%) being classified as high grade tumors. Out of the total sample, 116 patients (44.3%) underwent surgical excision and diagnosis confirmation. Core biopsy demonstrated 94.6% accuracy in the identification of sarcomas, with 96.4% sensitivity and 89.5% specificity. A significant intermethod agreement about histological grading was observed between core biopsy and surgical resection (p < 0.001; kappa = 0.75). Conclusion: CT-guided core needle biopsy demonstrated a high diagnostic accuracy in the evaluation of soft tissue tumors as well as in the histological grading of sarcomas, allowing an appropriate therapeutic planning (author)

  4. Comparative study of pulsed-continuous arterial spin labeling and dynamic susceptibility contrast imaging by histogram analysis in evaluation of glial tumors.

    Science.gov (United States)

    Arisawa, Atsuko; Watanabe, Yoshiyuki; Tanaka, Hisashi; Takahashi, Hiroto; Matsuo, Chisato; Fujiwara, Takuya; Fujiwara, Masahiro; Fujimoto, Yasunori; Tomiyama, Noriyuki

    2018-06-01

    Arterial spin labeling (ASL) is a non-invasive perfusion technique that may be an alternative to dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) for assessment of brain tumors. To our knowledge, there have been no reports on histogram analysis of ASL. The purpose of this study was to determine whether ASL is comparable with DSC-MRI in terms of differentiating high-grade and low-grade gliomas by evaluating the histogram analysis of cerebral blood flow (CBF) in the entire tumor. Thirty-four patients with pathologically proven glioma underwent ASL and DSC-MRI. High-signal areas on contrast-enhanced T 1 -weighted images or high-intensity areas on fluid-attenuated inversion recovery images were designated as the volumes of interest (VOIs). ASL-CBF, DSC-CBF, and DSC-cerebral blood volume maps were constructed and co-registered to the VOI. Perfusion histogram analyses of the whole VOI and statistical analyses were performed to compare the ASL and DSC images. There was no significant difference in the mean values for any of the histogram metrics in both of the low-grade gliomas (n = 15) and the high-grade gliomas (n = 19). Strong correlations were seen in the 75th percentile, mean, median, and standard deviation values between the ASL and DSC images. The area under the curve values tended to be greater for the DSC images than for the ASL images. DSC-MRI is superior to ASL for distinguishing high-grade from low-grade glioma. ASL could be an alternative evaluation method when DSC-MRI cannot be used, e.g., in patients with renal failure, those in whom repeated examination is required, and in children.

  5. A Case of Nasal Glial Heterotopia in an Adult

    Directory of Open Access Journals (Sweden)

    Akira Hagiwara

    2014-01-01

    Full Text Available We report a rare case of nasal glial heterotopia in an adult. After the surgery, frontal lobe cerebral hemorrhage developed. A 58-year-old man had unilateral nasal obstruction that progressed for one year. He had been treated for hypertension, chronic heart failure, and cerebral infarction with aspirin and warfarin. A computed tomography scan showed that the tumor occupied the right nasal cavity and the sinuses with small defect in the cribriform plate. The tumor was removed totally with endoscopy. After the operation, the patient developed convulsions and frontal lobe cerebral hemorrhage. The hemorrhage site was located near a defect in the cribriform plate. Nasal glial heterotopia is a rare developmental abnormality, particularly rare in adult. Only few cases were reported. We could not find any report of adult nasal glial heterotopias that developed cerebral hemorrhage as a complication of the surgery.

  6. [Nasal glial heterotopia: Clinical and morphological characteristics].

    Science.gov (United States)

    Bykova, V P; Bakhtin, A A; Polyakov, D P; Yunusov, A S; Daikhes, N A

    The paper describes a case of nasal glial heterotopia in a 10-month-old girl with a mixed (intranasal and subcutaneous) localization, which is accompanied by the divergence of the nasal bones. Histological examination supplemented by immunohistochemical reactions with antibodies to vimentin, S100 protein, neuron-specific enolase, as well as Ki-67 and smooth muscle actin confirmed the neural nature of the tumor. Fields of mature astrocytic glia including individual cells with neuronal differentiation were found among the fibrous and fibrovascular tissues. The paper provides a brief overview of the discussed pathology.

  7. A Comparison of Fresh Frozen vs. Formalin-Fixed, Paraffin-Embedded Specimens of Canine Mammary Tumors via Branched-DNA Assay

    Directory of Open Access Journals (Sweden)

    Florenza Lüder Ripoli

    2016-05-01

    Full Text Available Mammary neoplasms are the tumors most affecting female dogs and women. Formalin-fixed, paraffin-embedded (FFPE tissues are an invaluable source of archived biological material. Fresh frozen (FF tissue is considered ideal for gene expression analysis. However, strategies based on FFPE material offer several advantages. Branched-DNA assays permit a reliable and fast workflow when analyzing gene expression. The aim of this study was to assess the comparability of the branched-DNA assay when analyzing certain gene expression patterns between FF and FFPE samples in canine mammary tumors. RNA was isolated from 109 FFPE samples and from 93 FF samples of different canine mammary tissues. Sixteen (16 target genes (Tp53; Myc; HMGA1; Pik3ca; Mcl1; MAPK3; FOXO3; PTEN; GATA4; PFDN5; HMGB1; MAPK1; BRCA2; BRCA1; HMGA2; and Her2 were analyzed via branched-DNA assay (b-DNA. ACTB, GAPDH, and HPRT1 were used as data normalizers. Overall, the relative gene expression of the two different origins of samples showed an agreement of 63%. Still, care should be taken, as FFPE specimens showed lower expression of the analyzed targets when compared to FF samples. The fact that the gene expression in FFPE proved to be lower than in FF specimens is likely to have been caused by the effect of storage time. ACTB had the best performance as a data normalizer.

  8. Cystic tumors of the pituitary infundibulum: seminal autopsy specimens (1899 to 1904) that allowed clinical-pathological craniopharyngioma characterization.

    Science.gov (United States)

    Pascual, José M; Prieto, Ruth; Rosdolsky, Maria; Strauss, Sewan; Castro-Dufourny, Inés; Hofecker, Verena; Winter, Eduard; Carrasco, Rodrigo; Ulrich, Walter

    2018-04-21

    A heterogeneous group of epithelial cystic tumors developed at the infundibulum and the third ventricle disconcerted pathologists at the dawn of the twentieth century. Very little was known at that time about the physiological role played by the pituitary gland, and there was almost complete ignorance regarding the function of the hypothalamus. Acromegaly, or enlargement of acral body parts, described in 1886 by Pierre Marie, was the only disease linked to primary hypertrophies of the pituitary gland, known as "pituitary strumas". A growing number of young patients manifesting an unexplained combination of physical and mental symptoms, including absent or delayed sexual maturation, progressive obesity, abnormal somnolence, and dementia-like changes in behavior were reported to present large solid-cystic tumors which characteristically expanded within the infundibulum and third ventricle, above an anatomically intact pituitary gland. Between 1899 and 1904, five seminal autopsy studies from different countries thoroughly described the anatomical relationships and histological features of this newly recognized type of infundibular tumors. These cases were instrumental in fostering the systematic investigation of similar lesions by the Austrian pathologist Jakob Erdheim (1874-1937), who in 1904 was able to classify these infundibulo-tuberal cysts under the common category of hypophyseal duct tumors. The pioneering American neurosurgeon Harvey Cushing (1869-1939) unsuccessfully attempted to surgically remove one of these cysts, for the first time in history, in 1902. The term "craniopharyngioma", chosen by Cushing in 1929 to designate these lesions, would eventually prevail over Erdheim's more accurate denomination, which linked their origin to squamous cell remnants derived from the embryological structures that give rise to the pituitary gland. This paper presents a comprehensive, renewed account of the five clinical-pathological reports which laid the groundwork for

  9. Imaging of brain tumors

    International Nuclear Information System (INIS)

    Gaensler, E.H.L.

    1995-01-01

    The contents are diagnostic approaches, general features of tumors -hydrocephalus, edema, attenuation and/or intensity value, hemorrhage, fat, contrast enhancement, intra-axial supratentorial tumors - tumors of glial origin, oligodendrogliomas, ependymomas, subependymomas, subependymal giant cell astrocytomas, choroid plexus papilloma; midline tumors - colloid cysts, craniopharyngiomas; pineal region tumors and miscellaneous tumors i.e. primary intracerebral lymphoma, primitive neuroectodermal tumors, hemangioblastomas; extraaxial tumors - meningiomas; nerve sheath tumors -schwannomas, epidermoids, dermoids, lipomas, arachnoid cysts; metastatic tumors (8 refs.)

  10. Imaging of brain tumors

    Energy Technology Data Exchange (ETDEWEB)

    Gaensler, E H.L. [California Univ., San Francisco, CA (United States). Dept. of Radiology

    1996-12-31

    The contents are diagnostic approaches, general features of tumors -hydrocephalus, edema, attenuation and/or intensity value, hemorrhage, fat, contrast enhancement, intra-axial supratentorial tumors - tumors of glial origin, oligodendrogliomas, ependymomas, subependymomas, subependymal giant cell astrocytomas, choroid plexus papilloma; midline tumors - colloid cysts, craniopharyngiomas; pineal region tumors and miscellaneous tumors i.e. primary intracerebral lymphoma, primitive neuroectodermal tumors, hemangioblastomas; extraaxial tumors - meningiomas; nerve sheath tumors -schwannomas, epidermoids, dermoids, lipomas, arachnoid cysts; metastatic tumors (8 refs.).

  11. {sup 18}F-fluorodeoxyglucose-PET/CT to evaluate tumor, nodal disease, and gross tumor volume of oropharyngeal and oral cavity cancer: comparison with MR imaging and validation with surgical specimen

    Energy Technology Data Exchange (ETDEWEB)

    Seitz, Oliver; Chambron-Pinho, Nicole; Sader, Rober [JW Goethe University, Department of Oromaxillofacial Surgery, Frankfurt (Germany); Middendorp, Markus [JW Goethe University, Department of Nuclear Medicine, Frankfurt (Germany); Mack, Martin; Vogl, Thomas J. [JW Goethe University, Department of Radiology, Frankfurt (Germany); Bisdas, Sotirios [Eberhard Karls University, Department of Neuroradiology, Tuebingen (Germany)

    2009-10-15

    The purpose of this paper is to evaluate the impact of adding combined {sup 18}F-PET/CT to MRI for T and N staging of the oral and oropharyngeal cancer and calculation of the gross tumor volume (GTV) having histopathology as reference standard. PET/CT and MRI were performed in 66 patients with suspected oral and oropharyngeal cancer (41 primary tumors/25 recurrent tumors) and nodal disease (114 nodes). Statistical analysis included the McNemar test, sensitivity, specificity for the diagnostic modalities as well as regression analysis, and Bland-Altman graphs for calculated tumor volumes. There was no statistically significant difference between the two modalities compared to pathological findings regarding detection of disease (P{>=}0.72). The sensitivity/specificity for tumor detection were 100/80% and 96.72/60% for MRI and PET/CT, respectively. The sensitivity/specificity for nodal metastases were 88.46/75% and 83.81/73.91% for MRI and PET/CT, respectively. In 18% of cases, the MRI-based T staging resulted in an overestimation of the pathologic tumor stage. The corresponding rate for PET/CT was 22%. Regarding the treated necks, both modalities showed 100% sensitivity for detection of the recurrent lesions. In necks with histologically N0 staging, MRI and PET/CT gave 22% and 26% false positive findings, respectively. The mean tumor volume in the pathologic specimen was 16.6{+-}18.6 ml, the mean volume derived by the MR imaging was 17.6{+-}19.1 ml while the estimated by PET/CT volume was 18.8{+-}18.1 ml (P{<=}0.007 between the three methods). The Bland-Altman analysis showed a better agreement between PET/CT and MRI. The diagnostic performance of FDG-PET/CT in the local staging of oral cancer is not superior to MRI. (orig.)

  12. 18F-fluorodeoxyglucose-PET/CT to evaluate tumor, nodal disease, and gross tumor volume of oropharyngeal and oral cavity cancer: comparison with MR imaging and validation with surgical specimen

    International Nuclear Information System (INIS)

    Seitz, Oliver; Chambron-Pinho, Nicole; Sader, Rober; Middendorp, Markus; Mack, Martin; Vogl, Thomas J.; Bisdas, Sotirios

    2009-01-01

    The purpose of this paper is to evaluate the impact of adding combined 18 F-PET/CT to MRI for T and N staging of the oral and oropharyngeal cancer and calculation of the gross tumor volume (GTV) having histopathology as reference standard. PET/CT and MRI were performed in 66 patients with suspected oral and oropharyngeal cancer (41 primary tumors/25 recurrent tumors) and nodal disease (114 nodes). Statistical analysis included the McNemar test, sensitivity, specificity for the diagnostic modalities as well as regression analysis, and Bland-Altman graphs for calculated tumor volumes. There was no statistically significant difference between the two modalities compared to pathological findings regarding detection of disease (P≥0.72). The sensitivity/specificity for tumor detection were 100/80% and 96.72/60% for MRI and PET/CT, respectively. The sensitivity/specificity for nodal metastases were 88.46/75% and 83.81/73.91% for MRI and PET/CT, respectively. In 18% of cases, the MRI-based T staging resulted in an overestimation of the pathologic tumor stage. The corresponding rate for PET/CT was 22%. Regarding the treated necks, both modalities showed 100% sensitivity for detection of the recurrent lesions. In necks with histologically N0 staging, MRI and PET/CT gave 22% and 26% false positive findings, respectively. The mean tumor volume in the pathologic specimen was 16.6±18.6 ml, the mean volume derived by the MR imaging was 17.6±19.1 ml while the estimated by PET/CT volume was 18.8±18.1 ml (P≤0.007 between the three methods). The Bland-Altman analysis showed a better agreement between PET/CT and MRI. The diagnostic performance of FDG-PET/CT in the local staging of oral cancer is not superior to MRI. (orig.)

  13. Erratum: Epigenetic silencing of miR-34a in human prostate cancer cells and tumor tissue specimens can be reversed by BR-DIM treatment.

    Science.gov (United States)

    Kong, D; Heath, E; Chen, W; Cher, M; Powell, I; Heilbrun, L; Li, Y; Ali, S; Sethi, S; Hassan, O; Hwang, C; Gupta, N; Chitale, D; Sakr, Wa; Menon, M; Sarkar, Fh

    2013-01-01

    Androgen Receptor (AR) signaling is critically important during the development and progression of prostate cancer (PCa). The AR signaling is also important in the development of castrate resistant prostate cancer (CRPC) where AR is functional even after androgen deprivation therapy (ADT); however, little is known regarding the transcriptional and functional regulation of AR in PCa. Moreover, treatment options for primary PCa for preventing the occurrence of CRPC is limited; therefore, novel strategy for direct inactivation of AR is urgently needed. In this study, we found loss of miR-34a, which targets AR, in PCa tissue specimens, especially in patients with higher Gleason grade tumors, consistent with increased expression of AR. Forced over-expression of miR-34a in PCa cell lines led to decreased expression of AR and prostate specific antigen (PSA) as well as the expression of Notch-1, another important target of miR-34a. Most importantly, BR-DIM intervention in PCa patients prior to radical prostatectomy showed reexpression of miR-34a, which was consistent with decreased expression of AR, PSA and Notch-1 in PCa tissue specimens. Moreover, BR-DIM intervention led to nuclear exclusion both in PCa cell lines and in tumor tissues. PCa cells treated with BR-DIM and 5-aza-dC resulted in the demethylation of miR-34a promoter concomitant with inhibition of AR and PSA expression in LNCaP and C4-2B cells. These results suggest, for the first time, epigenetic silencing of miR-34a in PCa, which could be reversed by BR-DIM treatment and, thus BR-DIM could be useful for the inactivation of AR in the treatment of PCa.[This corrects the article on p. 14 in vol. 4.].

  14. Systematic identification and validation of candidate genes for detection of circulating tumor cells in peripheral blood specimens of colorectal cancer patients.

    Science.gov (United States)

    Findeisen, Peter; Röckel, Matthias; Nees, Matthias; Röder, Christian; Kienle, Peter; Von Knebel Doeberitz, Magnus; Kalthoff, Holger; Neumaier, Michael

    2008-11-01

    The presence of tumor cells in peripheral blood is being regarded increasingly as a clinically relevant prognostic factor for colorectal cancer patients. Current molecular methods are very sensitive but due to low specificity their diagnostic value is limited. This study was undertaken in order to systematically identify and validate new colorectal cancer (CRC) marker genes for improved detection of minimal residual disease in peripheral blood mononuclear cells of colorectal cancer patients. Marker genes with upregulated gene expression in colorectal cancer tissue and cell lines were identified using microarray experiments and publicly available gene expression data. A systematic iterative approach was used to reduce a set of 346 candidate genes, reportedly associated with CRC to a selection of candidate genes that were then further validated by relative quantitative real-time RT-PCR. Analytical sensitivity of RT-PCR assays was determined by spiking experiments with CRC cells. Diagnostic sensitivity as well as specificity was tested on a control group consisting of 18 CRC patients compared to 12 individuals without malignant disease. From a total of 346-screened genes only serine (or cysteine) proteinase inhibitor, clade B (ovalbumin), member 5 (SERPINB5) showed significantly elevated transcript levels in peripheral venous blood specimens of tumor patients when compared to the nonmalignant control group. These results were confirmed by analysis of an enlarged collective consisting of 63 CRC patients and 36 control individuals without malignant disease. In conclusion SERPINB5 seems to be a promising marker for detection of circulating tumor cells in peripheral blood of colorectal cancer patients.

  15. Immunohistochemical demonstration of glial markers in retinoblastomas

    DEFF Research Database (Denmark)

    Schrøder, H D

    1987-01-01

    Twenty retinoblastomas were studied immunohistochemically in order to visualize glial cells. In the retina, the glial cells in the ganglion cell layer and the Müller cells were GFAP positive, while only the glial cells of the ganglion cell layer expressed S-100 reactivity. In the tumours S-100/GFAP...... cells reactive for both S-100 and GFAP were demonstrated. The latter findings may represent differentiation in a glial direction in the more mature parts of retinoblastoma....

  16. Profiling cancer gene mutations in clinical formalin-fixed, paraffin-embedded colorectal tumor specimens using targeted next-generation sequencing.

    Science.gov (United States)

    Zhang, Liangxuan; Chen, Liangjing; Sah, Sachin; Latham, Gary J; Patel, Rajesh; Song, Qinghua; Koeppen, Hartmut; Tam, Rachel; Schleifman, Erica; Mashhedi, Haider; Chalasani, Sreedevi; Fu, Ling; Sumiyoshi, Teiko; Raja, Rajiv; Forrest, William; Hampton, Garret M; Lackner, Mark R; Hegde, Priti; Jia, Shidong

    2014-04-01

    The success of precision oncology relies on accurate and sensitive molecular profiling. The Ion AmpliSeq Cancer Panel, a targeted enrichment method for next-generation sequencing (NGS) using the Ion Torrent platform, provides a fast, easy, and cost-effective sequencing workflow for detecting genomic "hotspot" regions that are frequently mutated in human cancer genes. Most recently, the U.K. has launched the AmpliSeq sequencing test in its National Health Service. This study aimed to evaluate the clinical application of the AmpliSeq methodology. We used 10 ng of genomic DNA from formalin-fixed, paraffin-embedded human colorectal cancer (CRC) tumor specimens to sequence 46 cancer genes using the AmpliSeq platform. In a validation study, we developed an orthogonal NGS-based resequencing approach (SimpliSeq) to assess the AmpliSeq variant calls. Validated mutational analyses revealed that AmpliSeq was effective in profiling gene mutations, and that the method correctly pinpointed "true-positive" gene mutations with variant frequency >5% and demonstrated high-level molecular heterogeneity in CRC. However, AmpliSeq enrichment and NGS also produced several recurrent "false-positive" calls in clinically druggable oncogenes such as PIK3CA. AmpliSeq provided highly sensitive and quantitative mutation detection for most of the genes on its cancer panel using limited DNA quantities from formalin-fixed, paraffin-embedded samples. For those genes with recurrent "false-positive" variant calls, caution should be used in data interpretation, and orthogonal verification of mutations is recommended for clinical decision making.

  17. Nasal Glial Heterotopia with Cleft Palate.

    Science.gov (United States)

    Chandna, Sudhir; Mehta, Milind A; Kulkarni, Abhishek Kishore

    2018-01-01

    Congenital midline nasal masses are rare anomalies of which nasal glial heterotopia represents an even rarer subset. We report a case of a 25-day-old male child with nasal glial heterotopia along with cleft palate suggesting embryonic fusion anomaly which was treated with excision and primary closure for nasal mass followed by palatal repair at later date.

  18. Glial heterotopia of maxilla: A clinical surprise

    Directory of Open Access Journals (Sweden)

    Santosh Kumar Mahalik

    2011-01-01

    Full Text Available Glial heterotopia is a rare congenital mass lesion which often presents as a clinical surprise. We report a case of extranasal glial heterotopia in a neonate with unusual features. The presentation, management strategy, etiopathogenesis and histopathology of the mass lesion has been reviewed.

  19. Nasal glial heterotopia with cleft palate

    Directory of Open Access Journals (Sweden)

    Sudhir Chandna

    2018-01-01

    Full Text Available Congenital midline nasal masses are rare anomalies of which nasal glial heterotopia represents an even rarer subset. We report a case of a 25-day-old male child with nasal glial heterotopia along with cleft palate suggesting embryonic fusion anomaly which was treated with excision and primary closure for nasal mass followed by palatal repair at later date.

  20. Pediatric Glial Heterotopia in the Medial Canthus.

    Science.gov (United States)

    Kim, Soung Min; Amponsah, Emmanuel Kofi; Eo, Mi Young; Cho, Yun Ju; Lee, Suk Keun

    2017-11-01

    Glial heterotopias are rare, benign, congenital, midline, and nonteratomatous extracranial glial tissue. They may be confused as encephalocele or dermoid cysts and are mostly present in the nose.An 8-month-old African female child presented with a slow growing paranasal mass. The mass had been present at the left upper medial canthus since birth and had slowly and progressively enlarged. There was no communication between the mass and the cranial cavity during the operational procedure. The mass was immunohistochemically positive for S-100 protein as well as for glial fibrillary acidic protein, but negative for proliferating cell nuclear antigen. This suggested that the mass was composed of benign glial tissues with many astrocytes.The purpose of this report is to demonstrate the first patient with pediatric glial heterotopic tissue in the medial canthus and to report the clinical importance of its immunohistochemical findings.

  1. Telmisartan Modulates Glial Activation: In Vitro and In Vivo Studies.

    Directory of Open Access Journals (Sweden)

    Nofar Torika

    Full Text Available The circulating renin-angiotensin system (RAS, including the biologically active angiotensin II, is a fundamental regulatory mechanism of blood pressure conserved through evolution. Angiotensin II components of the RAS have also been identified in the brain. In addition to pro-inflammatory cytokines, neuromodulators, such as angiotensin II can induce (through angiotensin type 1 receptor (AT1R some of the inflammatory actions of brain glial cells and influence brain inflammation. Moreover, in Alzheimer's disease (AD models, where neuroinflammation occurs, increased levels of cortical AT1Rs have been shown. Still, the precise role of RAS in neuroinflammation is not completely clear. The overall aim of the present study was to elucidate the role of RAS in the modulation of glial functions and AD pathology. To reach this goal, the specific aims of the present study were a. to investigate the long term effect of telmisartan (AT1R blocker on tumor necrosis factor-α (TNF-α, interleukin 1-β (IL1-β and nitric oxide (NO release from glial cells. b. to examine the effect of intranasally administered telmisartan on amyloid burden and microglial activation in 5X familial AD (5XFAD mice. Telmisartan effects in vivo were compared to those of perindopril (angiotensin converting enzyme inhibitor. Long-term-exposure of BV2 microglia to telmisartan significantly decreased lipopolysaccharide (LPS -induced NO, inducible NO synthase, TNF-α and IL1-β synthesis. The effect of Telmisartan on NO production in BV2 cells was confirmed also in primary neonatal rat glial cells. Intranasal administration of telmisartan (1 mg/kg/day for up to two months significantly reduced amyloid burden and CD11b expression (a marker for microglia both in the cortex and hipoccampus of 5XFAD. Based on the current view of RAS and our data, showing reduced amyloid burden and glial activation in the brains of 5XFAD transgenic mice, one may envision potential intervention with the

  2. Nasal glial heterotopia or congenital hemangioma? A case report.

    Science.gov (United States)

    Lartizien, R; Durand, C; Blaise, S; Morand, B

    2017-10-01

    Nasal glial heterotopia (NGH) is a rare benign tumor of the median line. We describe the case of a child presenting a lateral nasal mass. The characteristics of the prenatal ultrasound and the postnatal clinical examination argued in favor of a congenital hemangioma (CH). The MRI performed at 6 weeks of life suggested glial heterotopia. This diagnosis was confirmed by the pathological analysis. Congenital hemangiomas and nasal glial heterotopies have similar clinical presentations. Prenatal ultrasound diagnosis between NGH and CH is difficult. Fetal MRI is not yet highly specific for these two lesions, but it can eliminate an intracerebral connection in cases of NGH. Postnatal exams are more specific. Flow on the Doppler exam is rapid for CH and slow for NGH. On MRI, these two lesions appear as a hypersignal on T2-weighted sequences, but less intense for NGH than for CH. Distinguishing between NGH and CH can be difficult. This does not have a direct incidence on treatment because it is surgical in both cases. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  3. Risk factors for oligodendroglial tumors: a pooled international study

    DEFF Research Database (Denmark)

    McCarthy, Bridget J; Rankin, Kristin M; Aldape, Ken

    2011-01-01

    Oligodendroglial tumors are rare subtypes of brain tumors and are often combined with other glial tumors in epidemiological analyses. However, different demographic associations and clinical characteristics suggest potentially different risk factors. The purpose of this study was to investigate p...

  4. Neuron-glial communication mediated by TNF-α and glial activation in dorsal root ganglia in visceral inflammatory hypersensitivity.

    Science.gov (United States)

    Song, Dan-dan; Li, Yong; Tang, Dong; Huang, Li-ya; Yuan, Yao-zong

    2014-05-01

    Communication between neurons and glia in the dorsal root ganglia (DRG) and the central nervous system is critical for nociception. Both glial activation and proinflammatory cytokine induction underlie this communication. We investigated whether satellite glial cell (SGC) and tumor necrosis factor-α (TNF-α) activation in DRG participates in a 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced rat model of visceral hyperalgesia. In TNBS-treated rats, TNF-α expression increased in DRG and was colocalized to SGCs enveloping a given neuron. These SGCs were activated as visualized under electron microscopy: they had more elongated processes projecting into the connective tissue space and more gap junctions. When nerves attached to DRG (L6-S1) were stimulated with a series of electrical stimulations, TNF-α were released from DRG in TNBS-treated animals compared with controls. Using a current clamp, we noted that exogenous TNF-α (2.5 ng/ml) increased DRG neuron activity, and visceral pain behavioral responses were reversed by intrathecal administration of anti-TNF-α (10 μg·kg(-1)·day(-1)). Based on our findings, TNF-α and SGC activation in neuron-glial communication are critical in inflammatory visceral hyperalgesia.

  5. Glial heterotopia of the oral cavity

    Directory of Open Access Journals (Sweden)

    Radhames E. Lizardo

    2015-07-01

    Full Text Available We report an unusual case of a glial heterotopia arising from the oral cavity of an African neonate. The patient presented with an external pedunculated oral mass which was connected to the anterior hard palate by a firm, rubbery stalk of mucosal tissue. While the mass appeared painless, it interfered with the infant's feeding and was disturbing to the parents. After a computed tomography scan excluded an intracranial connection, the mass was excised at its base and sent for biopsy. Histopathology examination confirmed glial heterotopia. Glial heterotopias should be included in the differential diagnosis of congenital masses in the oral region.

  6. Analytical validation of the PAM50-based Prosigna Breast Cancer Prognostic Gene Signature Assay and nCounter Analysis System using formalin-fixed paraffin-embedded breast tumor specimens

    International Nuclear Information System (INIS)

    Nielsen, Torsten; Storhoff, James; Wallden, Brett; Schaper, Carl; Ferree, Sean; Liu, Shuzhen; Gao, Dongxia; Barry, Garrett; Dowidar, Naeem; Maysuria, Malini

    2014-01-01

    NanoString’s Prosigna™ Breast Cancer Prognostic Gene Signature Assay is based on the PAM50 gene expression signature. The test outputs a risk of recurrence (ROR) score, risk category, and intrinsic subtype (Luminal A/B, HER2-enriched, Basal-like). The studies described here were designed to validate the analytical performance of the test on the nCounter Analysis System across multiple laboratories. Analytical precision was measured by testing five breast tumor RNA samples across 3 sites. Reproducibility was measured by testing replicate tissue sections from 43 FFPE breast tumor blocks across 3 sites following independent pathology review at each site. The RNA input range was validated by comparing assay results at the extremes of the specified range to the nominal RNA input level. Interference was evaluated by including non-tumor tissue into the test. The measured standard deviation (SD) was less than 1 ROR unit within the analytical precision study and the measured total SD was 2.9 ROR units within the reproducibility study. The ROR scores for RNA inputs at the extremes of the range were the same as those at the nominal input level. Assay results were stable in the presence of moderate amounts of surrounding non-tumor tissue (<70% by area). The analytical performance of NanoString’s Prosigna assay has been validated using FFPE breast tumor specimens across multiple clinical testing laboratories

  7. Human iPSC Glial Mouse Chimeras Reveal Glial Contributions to Schizophrenia

    DEFF Research Database (Denmark)

    Windrem, Martha S.; Osipovitch, Mikhail; Liu, Zhengshan

    2017-01-01

    with childhood-onset SCZ. After neonatal implantation into myelin-deficient shiverer mice, SCZ GPCs showed premature migration into the cortex, leading to reduced white matter expansion and hypomyelination relative to controls. The SCZ glial chimeras also showed delayed astrocytic differentiation and abnormal...... astrocytic morphologies. When established in myelin wild-type hosts, SCZ glial mice showed reduced prepulse inhibition and abnormal behavior, including excessive anxiety, antisocial traits, and disturbed sleep. RNA-seq of cultured SCZ human glial progenitor cells (hGPCs) revealed disrupted glial...

  8. Glial Tissue Mechanics and Mechanosensing by Glial Cells

    OpenAIRE

    Katarzyna Pogoda; Katarzyna Pogoda; Paul A. Janmey

    2018-01-01

    Understanding the mechanical behavior of human brain is critical to interpret the role of physical stimuli in both normal and pathological processes that occur in CNS tissue, such as development, inflammation, neurodegeneration, aging, and most common brain tumors. Despite clear evidence that mechanical cues influence both normal and transformed brain tissue activity as well as normal and transformed brain cell behavior, little is known about the links between mechanical signals and their bio...

  9. NMDA Receptors in Glial Cells: Pending Questions.

    Science.gov (United States)

    Dzamba, David; Honsa, Pavel; Anderova, Miroslava

    2013-05-01

    Glutamate receptors of the N-methyl-D-aspartate (NMDA) type are involved in many cognitive processes, including behavior, learning and synaptic plasticity. For a long time NMDA receptors were thought to be the privileged domain of neurons; however, discoveries of the last 25 years have demonstrated their active role in glial cells as well. Despite the large number of studies in the field, there are many unresolved questions connected with NMDA receptors in glia that are still a matter of debate. The main objective of this review is to shed light on these controversies by summarizing results from all relevant works concerning astrocytes, oligodendrocytes and polydendrocytes (also known as NG2 glial cells) in experimental animals, further extended by studies performed on human glia. The results are divided according to the study approach to enable a better comparison of how findings obtained at the mRNA level correspond with protein expression or functionality. Furthermore, special attention is focused on the NMDA receptor subunits present in the particular glial cell types, which give them special characteristics different from those of neurons - for example, the absence of Mg(2+) block and decreased Ca(2+) permeability. Since glial cells are implicated in important physiological and pathophysiological roles in the central nervous system (CNS), the last part of this review provides an overview of glial NMDA receptors with respect to ischemic brain injury.

  10. Glioblastoma models reveal the connection between adult glial progenitors and the proneural phenotype.

    Directory of Open Access Journals (Sweden)

    Liang Lei

    Full Text Available Tumor heterogeneity is a major obstacle for finding effective treatment of Glioblastoma (GBM. Based on global expression analysis, GBM can be classified into distinct subtypes: Proneural, Neural, Classical and Mesenchymal. The signatures of these different tumor subtypes may reflect the phenotypes of cells giving rise to them. However, the experimental evidence connecting any specific subtype of GBM to particular cells of origin is lacking. In addition, it is unclear how different genetic alterations interact with cells of origin in determining tumor heterogeneity. This issue cannot be addressed by studying end-stage human tumors.To address this issue, we used retroviruses to deliver transforming genetic lesions to glial progenitors in adult mouse brain. We compared the resulting tumors to human GBM. We found that different initiating genetic lesions gave rise to tumors with different growth rates. However all mouse tumors closely resembled the human Proneural GBM. Comparative analysis of these mouse tumors allowed us to identify a set of genes whose expression in humans with Proneural GBM correlates with survival.This study offers insights into the relationship between adult glial progenitors and Proneural GBM, and allows us to identify molecular alterations that lead to more aggressive tumor growth. In addition, we present a new preclinical model that can be used to test treatments directed at a specific type of GBM in future studies.

  11. Neocortical glial cell numbers in human brains

    DEFF Research Database (Denmark)

    Pelvig, D.P.; Pakkenberg, H.; Stark, A.K.

    2008-01-01

    Stereological cell counting was applied to post-mortem neocortices of human brains from 31 normal individuals, age 18-93 years, 18 females (average age 65 years, range 18-93) and 13 males (average age 57 years, range 19-87). The cells were differentiated in astrocytes, oligodendrocytes, microglia...... while the total astrocyte number is constant through life; finally males have a 28% higher number of neocortical glial cells and a 19% higher neocortical neuron number than females. The overall total number of neocortical neurons and glial cells was 49.3 billion in females and 65.2 billion in males...... and neurons and counting were done in each of the four lobes. The study showed that the different subpopulations of glial cells behave differently as a function of age; the number of oligodendrocytes showed a significant 27% decrease over adult life and a strong correlation to the total number of neurons...

  12. Glial K(+) Clearance and Cell Swelling

    DEFF Research Database (Denmark)

    Macaulay, Nanna; Zeuthen, Thomas

    2012-01-01

    An important feature of neuronal signalling is the increased concentration of K(+) in the extracellular space. The K(+) concentration is restored to its original basal level primarily by uptake into nearby glial cells. The molecular mechanisms by which K(+) is transferred from the extracellular...... space into the glial cell are debated. Although spatial buffer currents may occur, their quantitative contribution to K(+) clearance is uncertain. The concept of spatial buffering of K(+) precludes intracellular K(+) accumulation and is therefore (i) difficult to reconcile with the K(+) accumulation...

  13. Glial Tissue Mechanics and Mechanosensing by Glial Cells

    Directory of Open Access Journals (Sweden)

    Katarzyna Pogoda

    2018-02-01

    Full Text Available Understanding the mechanical behavior of human brain is critical to interpret the role of physical stimuli in both normal and pathological processes that occur in CNS tissue, such as development, inflammation, neurodegeneration, aging, and most common brain tumors. Despite clear evidence that mechanical cues influence both normal and transformed brain tissue activity as well as normal and transformed brain cell behavior, little is known about the links between mechanical signals and their biochemical and medical consequences. A multi-level approach from whole organ rheology to single cell mechanics is needed to understand the physical aspects of human brain function and its pathologies. This review summarizes the latest achievements in the field.

  14. Urine culture - catheterized specimen

    Science.gov (United States)

    Culture - urine - catheterized specimen; Urine culture - catheterization; Catheterized urine specimen culture ... urinary tract infections may be found in the culture. This is called a contaminant. You may not ...

  15. 40 CFR 79.67 - Glial fibrillary acidic protein assay.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 16 2010-07-01 2010-07-01 false Glial fibrillary acidic protein assay... Glial fibrillary acidic protein assay. (a) Purpose. Chemical-induced injury of the nervous system, i.e... paragraph (e)(3) in this section). Assays of glial fibrillary acidic protein (GFAP), the major intermediate...

  16. Wen-Luo-Tong Prevents Glial Activation and Nociceptive Sensitization in a Rat Model of Oxaliplatin-Induced Neuropathic Pain.

    Science.gov (United States)

    Deng, Bo; Jia, Liqun; Pan, Lin; Song, Aiping; Wang, Yuanyuan; Tan, Huangying; Xiang, Qing; Yu, Lili; Ke, Dandan

    2016-01-01

    One of the main dose-limiting complications of the chemotherapeutic agent oxaliplatin (OXL) is painful neuropathy. Glial activation and nociceptive sensitization may be responsible for the mechanism of neuropathic pain. The Traditional Chinese Medicine (TCM) Wen-luo-tong (WLT) has been widely used in China to treat chemotherapy induced neuropathic pain. However, there is no study on the effects of WLT on spinal glial activation induced by OXL. In this study, a rat model of OXL-induced chronic neuropathic pain was established and WLT was administrated. Pain behavioral tests and morphometric examination of dorsal root ganglia (DRG) were conducted. Glial fibrillary acidic protein (GFAP) immunostaining was performed, glial activation was evaluated, and the excitatory neurotransmitter substance P (SP) and glial-derived proinflammatory cytokine tumor necrosis factor-α (TNF-α) were analyzed. WLT treatment alleviated OXL-induced mechanical allodynia and mechanical hyperalgesia. Changes in the somatic, nuclear, and nucleolar areas of neurons in DRG were prevented. In the spinal dorsal horn, hypertrophy and activation of GFAP-positive astrocytes were averted, and the level of GFAP mRNA decreased significantly. Additionally, TNF-α mRNA and protein levels decreased. Collectively, these results indicate that WLT reversed both glial activation in the spinal dorsal horn and nociceptive sensitization during OXL-induced chronic neuropathic pain in rats.

  17. Glial-glial and glial-neuronal interfaces in radiation-induced, glia-depleted spinal cord

    International Nuclear Information System (INIS)

    Gilmore, S.A.; Sims, T.J.

    1997-01-01

    This review summarises some of the major findings derived from studies using the model of a glia-depleted environment developed and characterised in this laboratory. Glial depletion is achieved by exposure of the immature rodent spinal cord to x-radiation which markedly reduces both astrocyte and oligodendrocyte populations and severely impairs myelination. This glia-depleted, hypomylinated state presents a unique opportunity to examine aspects of spinal cord maturation in the absence of a normal glial population. An associated sequela within 2-3 wk following irradiation is the appearance of Schwann cells in the dorsal portion of the spinal cord. Characteristics of these intraspinal Schwann cells, their patterns of myelination or ensheathment, and their interrelations with the few remaining central glia have been examined. A later sequela is the development of Schwann cells in the ventral aspect of the spinal cord where they occur predominantly in the grey matter. (author)

  18. White Matter Glial Pathology in Autism

    Science.gov (United States)

    2015-11-01

    AWARD NUMBER: W81XWH-12-1-0302 TITLE: White Matter Glial Pathology in Autism PRINCIPAL INVESTIGATOR: Gregory A. Ordway, Ph.D. CONTRACTING...Pathology in Autism 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-12-1-0302 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Gregory A. Ordway, Ph.D...Approved for Public Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Methods used to directly study the autism brain include brain

  19. Neocortical glial cell numbers in human brains.

    Science.gov (United States)

    Pelvig, D P; Pakkenberg, H; Stark, A K; Pakkenberg, B

    2008-11-01

    Stereological cell counting was applied to post-mortem neocortices of human brains from 31 normal individuals, age 18-93 years, 18 females (average age 65 years, range 18-93) and 13 males (average age 57 years, range 19-87). The cells were differentiated in astrocytes, oligodendrocytes, microglia and neurons and counting were done in each of the four lobes. The study showed that the different subpopulations of glial cells behave differently as a function of age; the number of oligodendrocytes showed a significant 27% decrease over adult life and a strong correlation to the total number of neurons while the total astrocyte number is constant through life; finally males have a 28% higher number of neocortical glial cells and a 19% higher neocortical neuron number than females. The overall total number of neocortical neurons and glial cells was 49.3 billion in females and 65.2 billion in males, a difference of 24% with a high biological variance. These numbers can serve as reference values in quantitative studies of the human neocortex.

  20. Primary culture of glial cells from mouse sympathetic cervical ganglion: a valuable tool for studying glial cell biology.

    Science.gov (United States)

    de Almeida-Leite, Camila Megale; Arantes, Rosa Maria Esteves

    2010-12-15

    Central nervous system glial cells as astrocytes and microglia have been investigated in vitro and many intracellular pathways have been clarified upon various stimuli. Peripheral glial cells, however, are not as deeply investigated in vitro despite its importance role in inflammatory and neurodegenerative diseases. Based on our previous experience of culturing neuronal cells, our objective was to standardize and morphologically characterize a primary culture of mouse superior cervical ganglion glial cells in order to obtain a useful tool to study peripheral glial cell biology. Superior cervical ganglia from neonatal C57BL6 mice were enzymatically and mechanically dissociated and cells were plated on diluted Matrigel coated wells in a final concentration of 10,000cells/well. Five to 8 days post plating, glial cell cultures were fixed for morphological and immunocytochemical characterization. Glial cells showed a flat and irregular shape, two or three long cytoplasm processes, and round, oval or long shaped nuclei, with regular outline. Cell proliferation and mitosis were detected both qualitative and quantitatively. Glial cells were able to maintain their phenotype in our culture model including immunoreactivity against glial cell marker GFAP. This is the first description of immunocytochemical characterization of mouse sympathetic cervical ganglion glial cells in primary culture. This work discusses the uses and limitations of our model as a tool to study many aspects of peripheral glial cell biology. Copyright © 2010 Elsevier B.V. All rights reserved.

  1. The role of glial cells in neuronal acetylcholine synthesis

    International Nuclear Information System (INIS)

    Kasa, P.

    1986-01-01

    This paper presents data on the role of glial cells in neuronal ACh synthesis. It is noted that central neurons fare better in cultures when in contact with non-neuronal cells, and especially glial cells. Since neither the fate of the Ch released from the glial cells nor the role of the contact between glial cells and neurons has yet been elucidated, the author investigates these phenomena. Glial cells from 14-day-old chickbrain were cultured for 14 days. ( 14 C) - choline incorporated into lipids, phosphocholine, betaine and ACh, as well as the free ( 14 C) -choline, were determined in the pure glial cell cultures after 24 h, and in the combined cultures after 7 days. The ( 14 C) - choline influx into the incubation medium and the uptake by the neurons were measured. Results are presented

  2. Nasopharyngeal glial heterotopia with delayed postoperative meningitis.

    Science.gov (United States)

    Maeda, Kenichi; Furuno, Kenji; Chong, Pin Fee; Morioka, Takato

    2017-06-22

    A male infant, who underwent radical resection of a large glial heterotopia at the nasopharynx at 8 days, developed delayed postoperative bacterial meningitis at 9 months. Neuroradiological examination clearly demonstrated that meningitis had occurred because of the intracranial and extracranial connections, which were scarcely seen in the perioperative period. A transsphenoidal extension of hypothalamic hamartoma is possible because the connection started from the right optic nerve, running through the transsphenoidal canal in the sphenoid bone and terminating at the recurrent mass in the nasopharyngeal region. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  3. Cerebral radiation necrosis: vascular and glial features

    Energy Technology Data Exchange (ETDEWEB)

    Husain, M M; Garcia, J H

    1976-12-21

    Glial and vascular abnormalities in brain, simulating intracranial neoplasia, are described in a patient who received radiation to the pituitary region for treatment of an adenoma, 13 months before death. In addition to the expected changes of cerebral radionecrosis, four interesting features are cited: (1) diffuse hyperplasia of capillaries in the cerebral cortex with marked endothelial hypertrophy; (2) abundant, large multipolar bizarre cells in the perivascular connective tissues; (3) focal astrocytic proliferation with many cells resembling either Alzheimer type I astrocytes or neoplastic cells, and (4) radiation changes in the non-irradiated brain.

  4. Long term follow-up in a patient with papillary glioneuronal tumor Seguimento tardio de paciente com tumor papilar glioneuronal

    Directory of Open Access Journals (Sweden)

    Guilherme Borges

    2004-09-01

    Full Text Available We report a case of a young female patient with a rare and recently described form of brain tumor. This patient had a history of headache, hemiparesis and motor simple partial seizures. Her investigation revealed a brain tumor involving the left frontal and parietal lobes. The radiological images showed a cystic mass with multiple nodular masses and a rim of contrast enhancement extending from the right parietal cortex to the ipsilateral ventricle and corpus callosum. The patient underwent gross resection of the lesion and the histological analysis of the surgical specimen revealed a pseudopapillary structure formed by delicate vessels intermixed with a fibrillary pattern and bordered by intense astrocytic reaction with Rosenthal fibers. These features correspond to the recently described mixed neuronal-glial neoplasm, the papillary glioneuronal tumor. The patient has been followed for five years since the surgical treatment, without evidence of tumor recurrence, confirming the indolent behavior of this type of tumor.Relatamos o caso de uma jovem paciente com um tumor cerebral raro e recentemente descrito. Essa paciente apresentou-se com queixas de cefaléia, hemiparesia e crises epiléticas parciais simples. Sua investigação revelou um tumor cerebral envolvendo os lobos frontal e parietal esquerdos. As imagens radiológicas mostraram uma massa cística com massas nodulares múltiplas e reforço anelar de contraste estendendo do córtex parietal direito aos ventrículo lateral e corpo caloso ipsilaterais. A paciente se submeteu à ressecção do tumor e a análise histológica da lesão revelou uma estrutura pseudopapilar formada por vasos delicados entremeados com um padrão fibrilar e emoldurada por intensa reação astrocítica com fibras de Rosenthal. Essas características correspondem a uma forma de neoplasia mista glial-neuronal recentemente descrita, o tumor papilar glioneuronal. A paciente está em seguimento desde a cirurgia sem evid

  5. Laparoscopic specimen retrieval bags.

    Science.gov (United States)

    Smorgick, Noam

    2014-10-01

    Specimen retrieval bags have long been used in laparoscopic gynecologic surgery for contained removal of adnexal cysts and masses. More recently, the concerns regarding spread of malignant cells during mechanical morcellation of myoma have led to an additional use of specimen retrieval bags for contained "in-bag" morcellation. This review will discuss the indications for use retrieval bags in gynecologic endoscopy, and describe the different specimen bags available to date.

  6. Georeferencing Animal Specimen Datasets

    NARCIS (Netherlands)

    van Erp, M.G.J.; Hensel, R.; Ceolin, D.; van der Meij, M.

    2014-01-01

    For biodiversity research, the field of study that is concerned with the richness of species of our planet, it is of the utmost importance that the location of an animal specimen find is known with high precision. Due to specimens often having been collected over the course of many years, their

  7. Glial heterotopia in an adult: A rare orbital mass

    Directory of Open Access Journals (Sweden)

    Divya Dabir Sundaresh

    2016-01-01

    Full Text Available Heterotopic glial tissue is very rare in the orbit. Our case was an adult, which is unique since most cases reported in literature involve children. We describe a case of a 60-year-old man who presented with an orbital mass, which histopathologically revealed heterotopic glial tissue.

  8. Glial heterotopia in an adult: A rare orbital mass.

    Science.gov (United States)

    Sundaresh, Divya Dabir; Mangala Gouri, S R

    2016-11-01

    Heterotopic glial tissue is very rare in the orbit. Our case was an adult, which is unique since most cases reported in literature involve children. We describe a case of a 60-year-old man who presented with an orbital mass, which histopathologically revealed heterotopic glial tissue.

  9. Glial Cells: The Other Cells of the Nervous System

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 7; Issue 1. Glial Cells: The Other Cells of the Nervous System - An Introduction to Glial Cells. Medha S Rajadhyaksha Yasmin Khan. Series Article Volume 7 Issue 1 January 2002 pp 4-10 ...

  10. Glial heterotopia of the lip: A rare presentation.

    Science.gov (United States)

    Dadaci, Mehmet; Bayram, Fazli Cengiz; Ince, Bilsev; Bilgen, Fatma

    2016-01-01

    Glial heterotopia represents collections of normal glial tissue in an abnormal location distant to the central nervous system or spinal canal with no intracranial connectivity. Nasal gliomas are non-neoplastic midline tumours, with limited growth potential and no similarity to the central nervous system gliomas. The nose and the nasopharynx are the most common sites of location. Existence of glial heterotopia in the lip region is a rare developmental disorder. We report a case of large glial heterotopia in the upper lip region in a full-term female newborn which had intracranial extension with a fibrotic band. After the surgery, there was no recurrence in the follow-up period of 3 years. When glial heterotopia, which is a rare midline anomaly, is suspected, possible intracranial connection and properties of the mass should be evaluated by magnetic resonance imaging. By this way, lower complication rate and better aesthetic results can be achieved with early diagnosis and proper surgery.

  11. Glial heterotopia of the lip: A rare presentation

    Directory of Open Access Journals (Sweden)

    Mehmet Dadaci

    2016-01-01

    Full Text Available Glial heterotopia represents collections of normal glial tissue in an abnormal location distant to the central nervous system or spinal canal with no intracranial connectivity. Nasal gliomas are non-neoplastic midline tumours, with limited growth potential and no similarity to the central nervous system gliomas. The nose and the nasopharynx are the most common sites of location. Existence of glial heterotopia in the lip region is a rare developmental disorder. We report a case of large glial heterotopia in the upper lip region in a full-term female newborn which had intracranial extension with a fibrotic band. After the surgery, there was no recurrence in the follow-up period of 3 years. When glial heterotopia, which is a rare midline anomaly, is suspected, possible intracranial connection and properties of the mass should be evaluated by magnetic resonance imaging. By this way, lower complication rate and better aesthetic results can be achieved with early diagnosis and proper surgery.

  12. Pediatric brain tumors of neuroepithelial tissue

    International Nuclear Information System (INIS)

    Papanagiotou, P.; Politi, M.; Bergmann, M.; Pekrun, A.; Juergens, K.U.

    2014-01-01

    Tumors of neuroepithelial tissue represent the largest group of pediatric brain tumors by far and has therefore been divided into several discrete tumor subtypes each corresponding to a specific component of the neuropil. The neuropil contains several subtypes of glial cells, including astrocytes, oligodendrocytes, ependymal cells and modified ependymal cells that form the choroid plexus. This review discusses the imaging aspects of the most common pediatric tumors of neuroepithelial tissue. (orig.) [de

  13. Radiation adaptive response for the growth of cultured glial cells

    International Nuclear Information System (INIS)

    Suzuki, S.; Miura, Y.; Kano, M.; Toda, T.; Urano, S.

    2003-01-01

    Full text: To examine the molecular mechanism of radiation adaptive response (RAR) for the growth of cultured glial cells and to investigate the influence of aging on the response, glial cells were cultured from young and aged rats (1 month and 24 months old). RAR for the growth of glial cells conditioned with a low dose of X-rays and subsequently exposed to a high dose of X-rays was examined for cell number and BrdU incorporation. Involvement of the subcellular signaling pathway factors in RAR was investigated using their inhibitors, activators and mutated glial cells. RAR was observed in cells cultured from young rats, but was not in cells from aged rats. The inhibitors of protein kinase C (PKC) and DNA-dependent protein kinase (DNA-PK) or phosphatidylinositol 3-kinase (PI3K) suppressed RAR. The activators of PKC instead of low dose irradiation also caused RAR. Moreover, glial cells cultured from severe combined immunodeficiency (scid) mice (CB-17 scid) and ataxia-telangiectasia (AT) cells from AT patients showed no RAR. These results indicated that PKC, ATM, DNAPK and/or PI3K were involved in RAR for growth and BrdU incorporation of cultured glial cells and RAR decreased with aging. Proteomics data of glial cells exposed to severe stress of H 2 O 2 or X-rays also will be presented in the conference since little or no difference has not been observed with slight stress yet

  14. Modeling cognition and disease using human glial chimeric mice

    DEFF Research Database (Denmark)

    Goldman, Steven A.; Nedergaard, Maiken; Windrem, Martha S.

    2015-01-01

    , oligodendrocytes as well. As a result, the recipient brains may become inexorably humanized with regards to their resident glial populations, yielding human glial chimeric mouse brains. These brains provide us a fundamentally new tool by which to assess the species-specific attributes of glia in modulating human...... for studying the human-specific contributions of glia to psychopathology, as well as to higher cognition. As such, the assessment of human glial chimeric mice may provide us new insight into the species-specific contributions of glia to human cognitive evolution, as well as to the pathogenesis of human...

  15. An exceptional collision tumor: gastric calcified stromal tumor and ...

    African Journals Online (AJOL)

    The authors report an exceptional case of collision tumor comprised of a gastric calcified stromal tumor and a pancreatic adenocarcinoma. The pancreatic tumor was detected fortuitously on the histological exam of resection specimen. Key words: Collision tumor, stromal tumor, adenocarcinoma ...

  16. Controlled Environment Specimen Transfer

    DEFF Research Database (Denmark)

    Damsgaard, Christian Danvad; Zandbergen, Henny W.; Hansen, Thomas Willum

    2014-01-01

    an environmental transmission electron microscope to an in situ X-ray diffractometer through a dedicated transmission electron microscope specimen transfer holder, capable of sealing the specimen in a gaseous environment at elevated temperatures. Two catalyst material systems have been investigated; Cu/ZnO/Al2O3...... transferred in a reactive environment to the environmental transmission electron microscope where further analysis on the local scale were conducted. The Co/Al2O3 catalyst was reduced in the environmental microscope and successfully kept reduced outside the microscope in a reactive environment. The in situ......Specimen transfer under controlled environment conditions, such as temperature, pressure, and gas composition, is necessary to conduct successive complementary in situ characterization of materials sensitive to ambient conditions. The in situ transfer concept is introduced by linking...

  17. Glial cell biology in the Great Lakes region.

    Science.gov (United States)

    Feinstein, Douglas L; Skoff, Robert P

    2016-03-31

    We report on the tenth bi-annual Great Lakes Glial meeting, held in Traverse City, Michigan, USA, September 27-29 2015. The GLG meeting is a small conference that focuses on current research in glial cell biology. The array of functions that glial cells (astrocytes, microglia, oligodendrocytes, Schwann cells) play in health and disease is constantly increasing. Despite this diversity, GLG meetings bring together scientists with common interests, leading to a better understanding of these cells. This year's meeting included two keynote speakers who presented talks on the regulation of CNS myelination and the consequences of stress on Schwann cell biology. Twenty-two other talks were presented along with two poster sessions. Sessions covered recent findings in the areas of microglial and astrocyte activation; age-dependent changes to glial cells, Schwann cell development and pathology, and the role of stem cells in glioma and neural regeneration.

  18. Complex and differential glial responses in Alzheimer's disease and ageing.

    Science.gov (United States)

    Rodríguez, José J; Butt, Arthur M; Gardenal, Emanuela; Parpura, Vladimir; Verkhratsky, Alexei

    2016-01-01

    Glial cells and their association with neurones are fundamental for brain function. The emergence of complex neurone-glial networks assures rapid information transfer, creating a sophisticated circuitry where both types of neural cells work in concert, serving different activities. All glial cells, represented by astrocytes, oligodendrocytes, microglia and NG2-glia, are essential for brain homeostasis and defence. Thus, glia are key not only for normal central nervous system (CNS) function, but also to its dysfunction, being directly associated with all forms of neuropathological processes. Therefore, the progression and outcome of neurological and neurodegenerative diseases depend on glial reactions. In this review, we provide a concise account of recent data obtained from both human material and animal models demonstrating the pathological involvement of glia in neurodegenerative processes, including Alzheimer's disease (AD), as well as physiological ageing.

  19. Glial Cells: The Other Cells of the Nervous System

    Indian Academy of Sciences (India)

    nervous system and that glial cells were a mere glue holding neurons in place, Schleich ... fact that these cells did not show any electrical activity like neurons or muscles ... membrane potential higher than that of the surrounding neu- rons.

  20. Quantitation of glial fibrillary acidic protein in human brain tumours

    DEFF Research Database (Denmark)

    Rasmussen, S; Bock, E; Warecka, K

    1980-01-01

    The glial fibrillary acidic protein (GFA) content of 58 human brain tumours was determined by quantitative immunoelectrophoresis, using monospecific antibody against GFA. Astrocytomas, glioblastomas, oligodendrogliomas, spongioblastomas, ependymomas and medulloblastomas contained relatively high...

  1. Glial Cells: The Other Cells of the Nervous System

    Indian Academy of Sciences (India)

    secrete growth factors that act on neurons and other glial cells. from activated microglia. .... Microglia in Alzheimer's disease: Alzheimer's disease is charac- terized by deposition of ... trigger the recruitment ofT lymphocytes into the inflammatory.

  2. Glial hemichannels and their involvement in aging and neurodegenerative diseases.

    Science.gov (United States)

    Orellana, Juan A; von Bernhardi, Rommy; Giaume, Christian; Sáez, Juan C

    2012-01-26

    During the last two decades, it became increasingly evident that glial cells accomplish a more important role in brain function than previously thought. Glial cells express pannexins and connexins, which are member subunits of two protein families that form membrane channels termed hemichannels. These channels communicate intra- and extracellular compartments and allow the release of autocrine/paracrine signaling molecules [e.g., adenosine triphosphate (ATP), glutamate, nicotinamide adenine dinucleotide, and prostaglandin E2] to the extracellular milieu, as well as the uptake of small molecules (e.g., glucose). An increasing body of evidence has situated glial hemichannels as potential regulators of the beginning and maintenance of homeostatic imbalances observed in diverse brain diseases. Here, we review and discuss the current evidence about the possible role of glial hemichannels on neurodegenerative diseases. A subthreshold pathological threatening condition leads to microglial activation, which keeps active defense and restores the normal function of the central nervous system. However, if the stimulus is deleterious, microglial cells and the endothelium become overactivated, both releasing bioactive molecules (e.g., glutamate, cytokines, prostaglandins, and ATP), which increase the activity of glial hemichannels, reducing the astroglial neuroprotective functions, and further reducing neuronal viability. Because ATP and glutamate are released via glial hemichannels in neurodegenerative conditions, it is expected that they contribute to neurotoxicity. More importantly, toxic molecules released via glial hemichannels could increase the Ca2+ entry in neurons also via neuronal hemichannels, leading to neuronal death. Therefore, blockade of hemichannels expressed by glial cells and/or neurons during neuroinflammation might prevent neurodegeneration.

  3. Preserve specimens for reproducibility

    Czech Academy of Sciences Publication Activity Database

    Krell, F.-T.; Klimeš, Petr; Rocha, L. A.; Fikáček, M.; Miller, S. E.

    2016-01-01

    Roč. 539, č. 7628 (2016), s. 168 ISSN 0028-0836 Institutional support: RVO:60077344 Keywords : reproducibility * specimen * biodiversity Subject RIV: EH - Ecology, Behaviour Impact factor: 40.137, year: 2016 http://www.nature.com/nature/journal/v539/n7628/full/539168b.html

  4. Radiotherapy of pineal tumors

    International Nuclear Information System (INIS)

    Danoff, B.; Sheline, G.E.

    1984-01-01

    Radiotherapy has universally been used in the treatment of pineal tumors and suprasellar germinomas. Recently however, major technical advances related to the use of the operating microscope and development of microsurgical techniques have prompted a renewed interest in the direct surgical approach for biopsy and/or excision. This interest has resulted in a controversy regarding the role of surgery prior to radiotherapy. Because of the heterogeneity of tumors occurring in the pineal region (i.e., germ cell tumors, pineal parenchymal tumors, glial tumors, and cysts) and their differing biological behavior, controversy also surrounds aspects of radiotherapy such as: the optimal radiation dose, the volume to be irradiated, and indications for prophylactic spinal irradiation. A review of the available data is presented in an attempt to answer these questions

  5. Biaxial Creep Specimen Fabrication

    International Nuclear Information System (INIS)

    JL Bump; RF Luther

    2006-01-01

    This report documents the results of the weld development and abbreviated weld qualification efforts performed by Pacific Northwest National Laboratory (PNNL) for refractory metal and superalloy biaxial creep specimens. Biaxial creep specimens were to be assembled, electron beam welded, laser-seal welded, and pressurized at PNNL for both in-pile (JOYO reactor, O-arai, Japan) and out-of-pile creep testing. The objective of this test campaign was to evaluate the creep behavior of primary cladding and structural alloys under consideration for the Prometheus space reactor. PNNL successfully developed electron beam weld parameters for six of these materials prior to the termination of the Naval Reactors program effort to deliver a space reactor for Project Prometheus. These materials were FS-85, ASTAR-811C, T-111, Alloy 617, Haynes 230, and Nirnonic PE16. Early termination of the NR space program precluded the development of laser welding parameters for post-pressurization seal weldments

  6. Biaxial Creep Specimen Fabrication

    Energy Technology Data Exchange (ETDEWEB)

    JL Bump; RF Luther

    2006-02-09

    This report documents the results of the weld development and abbreviated weld qualification efforts performed by Pacific Northwest National Laboratory (PNNL) for refractory metal and superalloy biaxial creep specimens. Biaxial creep specimens were to be assembled, electron beam welded, laser-seal welded, and pressurized at PNNL for both in-pile (JOYO reactor, O-arai, Japan) and out-of-pile creep testing. The objective of this test campaign was to evaluate the creep behavior of primary cladding and structural alloys under consideration for the Prometheus space reactor. PNNL successfully developed electron beam weld parameters for six of these materials prior to the termination of the Naval Reactors program effort to deliver a space reactor for Project Prometheus. These materials were FS-85, ASTAR-811C, T-111, Alloy 617, Haynes 230, and Nirnonic PE16. Early termination of the NR space program precluded the development of laser welding parameters for post-pressurization seal weldments.

  7. Expression of Zonulin, c-kit, and Glial Fibrillary Acidic Protein in Human Gliomas.

    Science.gov (United States)

    Skardelly, Marco; Armbruster, Franz Paul; Meixensberger, Jürgen; Hilbig, Heidegard

    2009-08-18

    The hallmarks of human malignant gliomas are their marked invasiveness and vascularity. Because angiogenesis and tumor invasion have been associated with extracellular matrix degradation and intercellular tight junctions, the involvement of zonulin in glioma biology is in the focus. We selected for histological examination five cases of glioblastoma WHO IV (nomenclature of the World Health Organization) and one case each from astrocytoma WHO III, meningioma WHO III, and meningioma WHO I as control samples. The meningioma WHO I is regarded as benign, whereas the meningioma WHO III is recognized as the transition form of malignant tumors in humans. The visualization of a newly designed antibody against human zonulin was studied in triple-labeling studies using fluorescence immunocytochemistry and compared with the expression of c-kit and glial fibrillary acidic protein in differently developed human gliomas. We found that increasing the expression of c-kit is accompanied by an increase of zonulin expression. Both are correlated to the degree of malignancy of human brain tumors. The expression of zonulin is correlated to the degradation of the blood-brain barrier as revealed by Griffonia simplicifolia lectin. In differently graded tumors, we found differently graded involvement of blood vessels in the tumor development, explaining patients' survival.

  8. Glial Heterotopia of the orbit: A rare presentation

    Science.gov (United States)

    2011-01-01

    Background Glial heterotopias are rare, benign, congenital, midline, non-teratomatous extracranial glial tissue. They may masquerade as encephalocoele or dermoid cyst and mostly present in nose. Herein, we present an unusual case of glial heterotopia of the orbit with unilateral blindness. Case presentation A 6 year-old-boy presented with a progressive painless mass over the nose and medial aspect of the left eye noticed since birth. On examination, the globe was displaced laterally by a firm, regular, mobile, non-pulsatile and non-tender medial mass. The affected eye had profound loss of vision. Computed tomography scan showed a large hypodense mass in the extraconal space with no intracranial connectivity and bony erosion. The child underwent total surgical excision of the mass and histopathological examination confirmed glial heterotopia of the orbit. Conclusion Though the incidence of this condition is rare, the need of appropriate diagnosis and management of such mass to prevent the visual and cosmetic deterioration is warranted. To our knowledge this is the first reported case of Glial heterotopia of orbit causing unilateral blindness. PMID:22088230

  9. Glial Heterotopia of the orbit: A rare presentation

    Directory of Open Access Journals (Sweden)

    Sitaula Ranju

    2011-11-01

    Full Text Available Abstract Background Glial heterotopias are rare, benign, congenital, midline, non-teratomatous extracranial glial tissue. They may masquerade as encephalocoele or dermoid cyst and mostly present in nose. Herein, we present an unusual case of glial heterotopia of the orbit with unilateral blindness. Case presentation A 6 year-old-boy presented with a progressive painless mass over the nose and medial aspect of the left eye noticed since birth. On examination, the globe was displaced laterally by a firm, regular, mobile, non-pulsatile and non-tender medial mass. The affected eye had profound loss of vision. Computed tomography scan showed a large hypodense mass in the extraconal space with no intracranial connectivity and bony erosion. The child underwent total surgical excision of the mass and histopathological examination confirmed glial heterotopia of the orbit. Conclusion Though the incidence of this condition is rare, the need of appropriate diagnosis and management of such mass to prevent the visual and cosmetic deterioration is warranted. To our knowledge this is the first reported case of Glial heterotopia of orbit causing unilateral blindness.

  10. Identification of raw as a regulator of glial development.

    Directory of Open Access Journals (Sweden)

    Diana Luong

    Full Text Available Glial cells perform numerous functions to support neuron development and function, including axon wrapping, formation of the blood brain barrier, and enhancement of synaptic transmission. We have identified a novel gene, raw, which functions in glia of the central and peripheral nervous systems in Drosophila. Reducing Raw levels in glia results in morphological defects in the brain and ventral nerve cord, as well as defects in neuron function, as revealed by decreased locomotion in crawling assays. Examination of the number of glia along peripheral nerves reveals a reduction in glial number upon raw knockdown. The reduced number of glia along peripheral nerves occurs as a result of decreased glial proliferation. As Raw has been shown to negatively regulate Jun N-terminal kinase (JNK signaling in other developmental contexts, we examined the expression of a JNK reporter and the downstream JNK target, matrix metalloproteinase 1 (mmp1, and found that raw knockdown results in increased reporter activity and Mmp1 levels. These results are consistent with previous studies showing increased Mmp levels lead to nerve cord defects similar to those observed upon raw knockdown. In addition, knockdown of puckered, a negative feedback regulator of JNK signaling, also causes a decrease in glial number. Thus, our studies have resulted in the identification of a new regulator of gliogenesis, and demonstrate that increased JNK signaling negatively impacts glial development.

  11. The Purinergic System and Glial Cells: Emerging Costars in Nociception

    Directory of Open Access Journals (Sweden)

    Giulia Magni

    2014-01-01

    Full Text Available It is now well established that glial cells not only provide mechanical and trophic support to neurons but can directly contribute to neurotransmission, for example, by release and uptake of neurotransmitters and by secreting pro- and anti-inflammatory mediators. This has greatly changed our attitude towards acute and chronic disorders, paving the way for new therapeutic approaches targeting activated glial cells to indirectly modulate and/or restore neuronal functions. A deeper understanding of the molecular mechanisms and signaling pathways involved in neuron-to-glia and glia-to-glia communication that can be pharmacologically targeted is therefore a mandatory step toward the success of this new healing strategy. This holds true also in the field of pain transmission, where the key involvement of astrocytes and microglia in the central nervous system and satellite glial cells in peripheral ganglia has been clearly demonstrated, and literally hundreds of signaling molecules have been identified. Here, we shall focus on one emerging signaling system involved in the cross talk between neurons and glial cells, the purinergic system, consisting of extracellular nucleotides and nucleosides and their membrane receptors. Specifically, we shall summarize existing evidence of novel “druggable” glial purinergic targets, which could help in the development of innovative analgesic approaches to chronic pain states.

  12. Molecular markers: Implications for cytopathology and specimen collection.

    Science.gov (United States)

    VanderLaan, Paul A

    2015-08-01

    Cytologic specimens obtained through minimally invasive biopsy techniques are increasingly being used as principle diagnostic specimens for tumors arising in multiple sites. The number and scope of ancillary tests performed on these specimens have grown substantially over the past decade, including many molecular markers that not only can aid in formulating accurate and specific diagnoses but also can provide prognostic or therapeutic information to help direct clinical decisions. Thus, the cytopathologist needs to ensure that adequate material is collected and appropriately processed for the study of relevant molecular markers, many of which are specific to tumor site. This brief review covers considerations for effective cytologic specimen collection and processing to ensure diagnostic and testing success. In addition, a general overview is provided of molecular markers pertinent to tumors from a variety of sites. The recognition of these established and emerging molecular markers by cytopathologists is an important step toward realizing the promise of personalized medicine. © 2015 American Cancer Society.

  13. Pathway analyses implicate glial cells in schizophrenia.

    Directory of Open Access Journals (Sweden)

    Laramie E Duncan

    Full Text Available The quest to understand the neurobiology of schizophrenia and bipolar disorder is ongoing with multiple lines of evidence indicating abnormalities of glia, mitochondria, and glutamate in both disorders. Despite high heritability estimates of 81% for schizophrenia and 75% for bipolar disorder, compelling links between findings from neurobiological studies, and findings from large-scale genetic analyses, are only beginning to emerge.Ten publically available gene sets (pathways related to glia, mitochondria, and glutamate were tested for association to schizophrenia and bipolar disorder using MAGENTA as the primary analysis method. To determine the robustness of associations, secondary analyses were performed with: ALIGATOR, INRICH, and Set Screen. Data from the Psychiatric Genomics Consortium (PGC were used for all analyses. There were 1,068,286 SNP-level p-values for schizophrenia (9,394 cases/12,462 controls, and 2,088,878 SNP-level p-values for bipolar disorder (7,481 cases/9,250 controls.The Glia-Oligodendrocyte pathway was associated with schizophrenia, after correction for multiple tests, according to primary analysis (MAGENTA p = 0.0005, 75% requirement for individual gene significance and also achieved nominal levels of significance with INRICH (p = 0.0057 and ALIGATOR (p = 0.022. For bipolar disorder, Set Screen yielded nominally and method-wide significant associations to all three glial pathways, with strongest association to the Glia-Astrocyte pathway (p = 0.002.Consistent with findings of white matter abnormalities in schizophrenia by other methods of study, the Glia-Oligodendrocyte pathway was associated with schizophrenia in our genomic study. These findings suggest that the abnormalities of myelination observed in schizophrenia are at least in part due to inherited factors, contrasted with the alternative of purely environmental causes (e.g. medication effects or lifestyle. While not the primary purpose of our study

  14. NASA Biological Specimen Repository

    Science.gov (United States)

    McMonigal, K. A.; Pietrzyk, R. A.; Sams, C. F.; Johnson, M. A.

    2010-01-01

    The NASA Biological Specimen Repository (NBSR) was established in 2006 to collect, process, preserve and distribute spaceflight-related biological specimens from long duration ISS astronauts. This repository provides unique opportunities to study longitudinal changes in human physiology spanning may missions. The NBSR collects blood and urine samples from all participating ISS crewmembers who have provided informed consent. These biological samples are collected once before flight, during flight scheduled on flight days 15, 30, 60, 120 and within 2 weeks of landing. Postflight sessions are conducted 3 and 30 days after landing. The number of in-flight sessions is dependent on the duration of the mission. Specimens are maintained under optimal storage conditions in a manner that will maximize their integrity and viability for future research The repository operates under the authority of the NASA/JSC Committee for the Protection of Human Subjects to support scientific discovery that contributes to our fundamental knowledge in the area of human physiological changes and adaptation to a microgravity environment. The NBSR will institute guidelines for the solicitation, review and sample distribution process through establishment of the NBSR Advisory Board. The Advisory Board will be composed of representatives of all participating space agencies to evaluate each request from investigators for use of the samples. This process will be consistent with ethical principles, protection of crewmember confidentiality, prevailing laws and regulations, intellectual property policies, and consent form language. Operations supporting the NBSR are scheduled to continue until the end of U.S. presence on the ISS. Sample distribution is proposed to begin with selections on investigations beginning in 2017. The availability of the NBSR will contribute to the body of knowledge about the diverse factors of spaceflight on human physiology.

  15. Rotating specimen rack repair

    International Nuclear Information System (INIS)

    Miller, G.E.; Rogers, P.J.; Nabor, W.G.; Bair, H.

    1984-01-01

    In 1980, an operator at the UCI TRIGA Reactor noticed difficulties with the rotation of the specimen rack. Investigations showed that the drive bearing in the rack had failed and allowed the bearings to enter the rack. After some time of operation in static mode it was decided that installation of a bearing substitute - a graphite sleeve - would be undertaken. Procedures were written and approved for removal of the rack, fabrication and installation of the sleeve, and re-installation of the rack. This paper describes these procedures in some detail. Detailed drawings of the necessary parts may be obtained from the authors

  16. Method for thinning specimen

    Science.gov (United States)

    Follstaedt, David M.; Moran, Michael P.

    2005-03-15

    A method for thinning (such as in grinding and polishing) a material surface using an instrument means for moving an article with a discontinuous surface with an abrasive material dispersed between the material surface and the discontinuous surface where the discontinuous surface of the moving article provides an efficient means for maintaining contact of the abrasive with the material surface. When used to dimple specimens for microscopy analysis, a wheel with a surface that has been modified to produce a uniform or random discontinuous surface significantly improves the speed of the dimpling process without loss of quality of finish.

  17. Glial progenitor cell-based treatment of the childhood leukodystrophies

    DEFF Research Database (Denmark)

    Osório, M. Joana; Goldman, Steven A.

    2016-01-01

    stem cell-derived human neural or glial progenitor cells may comprise a promising strategy for both structural remyelination and metabolic rescue. A broad variety of pediatric white matter disorders, including the primary hypomyelinating disorders, the lysosomal storage disorders, and the broader group...... genetic editing of pluripotent stem cells. Yet these challenges notwithstanding, the promise of glial progenitor cell-based treatment of the childhood myelin disorders offers hope to the many victims of this otherwise largely untreatable class of disease....... and astrocytes are the major affected cell populations, and are either structurally impaired or metabolically compromised through cell-intrinsic pathology, or are the victims of mis-accumulated toxic byproducts of metabolic derangement. In either case, glial cell replacement using implanted tissue or pluripotent...

  18. Custom-Designed MLPA Using Multiple Short Synthetic Probes Application to Methylation Analysis of Five Promoter CpG Islands in Tumor and Urine Specimens from Patients with Bladder Cancer

    DEFF Research Database (Denmark)

    Serizawa, R.R.; Ralfkiaer, U.; Dahl, C.

    2010-01-01

    this assay to analyze DNA from tumor tissue and corresponding urine samples from patients with bladder cancer. Our data show that the use of multiple short synthetic probes provides a simple means for custom-designed MS-MLPA analysis. (J Mol Diagn 2010, 12:402-408; DOI: 10.2353/jmoldx.2010.090152)...

  19. Giant Glial Cell: New Insight Through Mechanism-Based Modeling

    DEFF Research Database (Denmark)

    Postnov, D. E.; Ryazanova, L. S.; Brazhe, Nadezda

    2008-01-01

    The paper describes a detailed mechanism-based model of a tripartite synapse consisting of P- and R-neurons together with a giant glial cell in the ganglia of the medical leech (Hirudo medicinalis), which is a useful object for experimental studies in situ. We describe the two main pathways...... of the glial cell activation: (1) via IP3 production and Ca2+ release from the endoplasmic reticulum and (2) via increase of the extracellular potassium concentration, glia depolarization, and opening of voltage-dependent Ca2+ channels. We suggest that the second pathway is the more significant...

  20. Cathepsin D and Its Prognostic Value in Neuroepithelial Brain Tumors

    OpenAIRE

    Pigac, Biserka; Dmitrović, Branko; Marić, Svjetlana; Mašić, Silvija

    2012-01-01

    Expression of Cathepsin D (Cath D) in some primary neuroepithelial brain tumors and its prognostic value were studied. The research included 65 samples of human primary neuroepithelial brain tumors. There were 50 glial tumors (10 diffuse astrocytomas (DA), 15 anaplastic astrocytomas (AA), 25 glioblastomas (GB), 15 embryonic tumors (15 medulloblastomas (MB) as well as 5 samples of normal brain tissue. Immunohistochemical method was applied to monitor diffuse positive reaction in the cytoplasm ...

  1. Multimodal MRI in the characterization of glial neoplasms: the combined role of single-voxel MR spectroscopy, diffusion imaging and echo-planar perfusion imaging

    International Nuclear Information System (INIS)

    Zonari, Paolo; Baraldi, Patrizia; Crisi, Girolamo

    2007-01-01

    Diffusion-weighted imaging (DWI), perfusion-weighted imaging (PWI) and MR spectroscopy (MRS) provide useful data for tumor evaluation. To assess the contribution of these multimodal techniques in grading glial neoplasms, we compared the value of DWI, PWI and MRS in the evaluation of histologically proven high- and low-grade gliomas in a population of 105 patients. Independently for each modality, the following variables were used to compare the tumors: minimum apparent diffusion coefficient (ADC) and maximum relative cerebral blood volume (rCBV) normalized values between tumor and healthy tissue, maximum Cho/Cr ratio and minimum NAA/Cr ratio in tumor, and scored lactate and lipid values in tumor. The Mann-Whitney and Wilcoxon tests were employed to compare DWI, PWI and MRS between tumor types. Logistic regression analysis was used to determine which parameters best increased the diagnostic accuracy in terms of sensitivity, specificity, and positive and negative predictive values. ROC curves were determined for parameters with high sensitivity and specificity to identify threshold values to separate high- from low-grade lesions. Statistically significant differences were found for rCBV tumor/normal tissue ratio, and NAA/Cr ratio in tumor and Cho/Cr ratio in tumor between low- and high-grade tumors. The best performing single parameter for group classification was the normalized rCBV value; including all parameters, statistical significance was reached by rCBV tumor/normal tissue ratio, NAA/Cr tumor ratio and lactate. From the ROC curves, a high probability for a neoplasm to be a high-grade lesion was associated with a rCBV tumor/normal tissue ratio of >1.16 and NAA/Cr tumor ratio of <0.44. Combining PWI and MRS with conventional MR imaging increases the accuracy of the attribution of malignancy to glial neoplasms. The best performing parameter was found to be the perfusion level. (orig.)

  2. A neuropathology-based approach to epilepsy surgery in brain tumors and proposal for a new terminology use for long-term epilepsy-associated brain tumors

    NARCIS (Netherlands)

    Blumcke, Ingmar; Aronica, Eleonora; Urbach, Horst; Alexopoulos, Andreas; Gonzalez-Martinez, Jorge A.

    2014-01-01

    Every fourth patient submitted to epilepsy surgery suffers from a brain tumor. Microscopically, these neoplasms present with a wide-ranging spectrum of glial or glio-neuronal tumor subtypes. Gangliogliomas (GG) and dysembryoplastic neuroepithelial tumors (DNTs) are the most frequently recognized

  3. Progenitor cell-based treatment of glial disease

    DEFF Research Database (Denmark)

    Goldman, Steven A

    2017-01-01

    -based neurodegenerative conditions may now be compelling targets for cell-based therapy. As such, glial cell-based therapies may offer potential benefit to a broader range of diseases than ever before contemplated, including disorders such as Huntington's disease and the motor neuron degeneration of amyotrophic lateral...

  4. Glial Cells - The Key Elements of Alzheimer's Disease

    Czech Academy of Sciences Publication Activity Database

    Džamba, Dávid; Harantová, Lenka; Butenko, Olena; Anděrová, Miroslava

    2016-01-01

    Roč. 13, č. 8 (2016), s. 894-911 ISSN 1567-2050 R&D Projects: GA ČR(CZ) GBP304/12/G069 Institutional support: RVO:68378041 Keywords : alzheimer 's disease * astrocytes * glial cells Subject RIV: ED - Physiology Impact factor: 2.952, year: 2016

  5. A series of parapharyngeal glial heterotopia mimicking lymphatic malformation.

    Science.gov (United States)

    Haloob, Nora; Pepper, Christopher; Hartley, Benjamin

    2015-12-01

    Otolaryngologists will most frequently encounter extra-cranial glial tissue within the nasal cavity, where it is known as a 'nasal glioma', and may communicate with the dura. However, glial tissue can also present extra-nasally in the form of a neck mass with no intracranial connection. In these rare cases, they can present soon after birth as an enlarging neck mass, causing compressive symptoms with airway obstruction and feeding difficulties. In this way, it is often initially misdiagnosed as a more common lesion such as a lymphatic malformation, teratoma, branchial anomaly or vascular malformation. As with many congenital head and neck masses, offering the most the appropriate management relies heavily on radiological imaging and, where possible, histopathology from a diagnostic biopsy. Once the diagnosis of extra-nasal glial heterotopia has been confirmed, the gold standard management is complete surgical excision. We review three cases of extra-nasal glial heterotopia presenting to our institution over an eleven year period as a large neck mass, which mimicked other congenital neck lumps, and discuss them in the context of those in the literature. We highlight how their clinical and radiological features can easily be confused with lymphatic malformations, and the potential implications of misdiagnosis. Raising awareness of this diagnostic confusion will highlight the need for management of these cases within an appropriate paediatric multidisciplinary setting. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  6. Rapid method for culturing embryonic neuron-glial cell cocultures

    DEFF Research Database (Denmark)

    Svenningsen, Åsa Fex; Shan, Wei-Song; Colman, David R

    2003-01-01

    neurons is seen after 3 weeks (2 weeks in ascorbic acid), suggesting that basal lamina production is important even for glial ensheathment in the enteric nervous system. No overgrowth of fibroblasts or other nonneuronal cells was noted in any cultures, and myelination of the peripheral nervous system...

  7. Peripheral Glial Cells in the Development of Diabetic Neuropathy

    Science.gov (United States)

    Gonçalves, Nádia Pereira; Vægter, Christian Bjerggaard; Pallesen, Lone Tjener

    2018-01-01

    The global prevalence of diabetes is rapidly increasing, affecting more than half a billion individuals within the next few years. As diabetes negatively affects several physiological systems, this dramatic increase represents not only impaired quality of life on the individual level but also a huge socioeconomic challenge. One of the physiological consequences affecting up to half of diabetic patients is the progressive deterioration of the peripheral nervous system, resulting in spontaneous pain and eventually loss of sensory function, motor weakness, and organ dysfunctions. Despite intense research on the consequences of hyperglycemia on nerve functions, the biological mechanisms underlying diabetic neuropathy are still largely unknown, and treatment options lacking. Research has mainly focused directly on the neuronal component, presumably from the perspective that this is the functional signal-transmitting unit of the nerve. However, it is noteworthy that each single peripheral sensory neuron is intimately associated with numerous glial cells; the neuronal soma is completely enclosed by satellite glial cells and the length of the longest axons covered by at least 1,000 Schwann cells. The glial cells are vital for the neuron, but very little is still known about these cells in general and especially how they respond to diabetes in terms of altered neuronal support. We will discuss current knowledge of peripheral glial cells and argue that increased research in these cells is imperative for a better understanding of the mechanisms underlying diabetic neuropathy. PMID:29770116

  8. Understanding the NG2 glial scar after spinal cord injury

    Directory of Open Access Journals (Sweden)

    Amber R Hackett

    2016-11-01

    Full Text Available NG2 cells, also known as oligodendrocyte progenitor cells, are located throughout the central nervous system and serve as a pool of progenitors to differentiate into oligodendrocytes. In response to spinal cord injury, NG2 cells increase their proliferation and differentiation into remyelinating oligodendrocytes. While astrocytes are typically associated with being the major cell type in the glial scar, many NG2 cells also accumulate within the glial scar but their function remains poorly understood. Similar to astrocytes, these cells hypertrophy, upregulate expression of chondroitin sulfate proteoglycans, inhibit axon regeneration, contribute to the glial-fibrotic scar border, and some even differentiate into astrocytes. Whether NG2 cells also have a role in other astrocyte functions, such as preventing the spread of infiltrating leukocytes and expression of inflammatory cytokines, is not yet known. Thus, NG2 cells are not only important for remyelination after spinal cord injury, but are also a major component of the glial scar with functions that overlap with astrocytes in this region. In this review, we describe the signaling pathways important for the proliferation and differentiation of NG2 cells, as well as the role of NG2 cells in scar formation and tissue repair.

  9. Cytokine-induced activation of glial cells in the mouse brain is enhanced at an advanced age.

    Science.gov (United States)

    Deng, X-H; Bertini, G; Xu, Y-Z; Yan, Z; Bentivoglio, M

    2006-08-25

    Numerous neurological diseases which include neuroinflammatory components exhibit an age-related prevalence. The aging process is characterized by an increase of inflammatory mediators both systemically and in the brain, which may prime glial cells. However, little information is available on age-related changes in the glial response of the healthy aging brain to an inflammatory challenge. This problem was here examined using a mixture of the proinflammatory cytokines interferon-gamma and tumor necrosis factor-alpha, which was injected intracerebroventricularly in young (2-3.5 months), middle-aged (10-11 months) and aged (18-21 months) mice. Vehicle (phosphate-buffered saline) was used as control. After a survival of 1 or 2 days (all age groups) or 4 days (young and middle-aged animals), immunohistochemically labeled astrocytes and microglia were investigated both qualitatively and quantitatively. In all age groups, astrocytes were markedly activated in periventricular as well as in deeper brain regions 2 days following cytokine treatment, whereas microglia activation was already evident at 24 h. Interestingly, cytokine-induced activation of both astrocytes and microglia was significantly more marked in the brain of aged animals, in which it included numerous ameboid microglia, than of younger age groups. Moderate astrocytic activation was also seen in the hippocampal CA1 field of vehicle-treated aged mice. FluoroJade B histochemistry and the terminal deoxynucleotidyl transferase-mediated UTP nick-end labeling technique, performed at 2 days after cytokine administration, did not reveal ongoing cell death phenomena in young or aged animals. This indicated that glial cell changes were not secondary to neuronal death. Altogether, the findings demonstrate for the first time enhanced activation of glial cells in the old brain, compared with young and middle-aged subjects, in response to cytokine exposure. Interestingly, the results also suggest that such enhancement

  10. Distinct types of glial cells populate the Drosophila antenna

    Directory of Open Access Journals (Sweden)

    Jhaveri Dhanisha

    2005-11-01

    Full Text Available Abstract Background The development of nervous systems involves reciprocal interactions between neurons and glia. In the Drosophila olfactory system, peripheral glial cells arise from sensory lineages specified by the basic helix-loop-helix transcription factor, Atonal. These glia wrap around the developing olfactory axons early during development and pattern the three distinct fascicles as they exit the antenna. In the moth Manduca sexta, an additional set of central glia migrate to the base of the antennal nerve where axons sort to their glomerular targets. In this work, we have investigated whether similar types of cells exist in the Drosophila antenna. Results We have used different P(Gal4 lines to drive Green Fluorescent Protein (GFP in distinct populations of cells within the Drosophila antenna. Mz317::GFP, a marker for cell body and perineural glia, labels the majority of peripheral glia. An additional ~30 glial cells detected by GH146::GFP do not derive from any of the sensory lineages and appear to migrate into the antenna from the brain. Their appearance in the third antennal segment is regulated by normal function of the Epidermal Growth Factor receptor and small GTPases. We denote these distinct populations of cells as Mz317-glia and GH146-glia respectively. In the adult, processes of GH146-glial cells ensheath the olfactory receptor neurons directly, while those of the Mz317-glia form a peripheral layer. Ablation of GH146-glia does not result in any significant effects on the patterning of the olfactory receptor axons. Conclusion We have demonstrated the presence of at least two distinct populations of glial cells within the Drosophila antenna. GH146-glial cells originate in the brain and migrate to the antenna along the newly formed olfactory axons. The number of cells populating the third segment of the antenna is regulated by signaling through the Epidermal Growth Factor receptor. These glia share several features of the sorting

  11. Splitting tests on rock specimens

    Energy Technology Data Exchange (ETDEWEB)

    Davies, J D; Stagg, K G

    1970-01-01

    Splitting tests are described for a square-section sandstone specimens line loaded through steel or timber packings on the top face and supported on the bottom face either on similar packings (type A specimen) or directly on the lower platen plate of the testing machine (type B specimens). The stress distribution across the vertical central plane and the horizontal central plane were determined from a linear elastic finite element analysis for both types. Two solutions were obtained for the type B specimen: one assuming no friction between the base of the specimen and the platen plate and the other assuming no relative slip between the surfaces. Vertical and horizontal strains were measured at the center of the specimens for all loads up to failure.

  12. Janka hardness using nonstandard specimens

    Science.gov (United States)

    David W. Green; Marshall Begel; William Nelson

    2006-01-01

    Janka hardness determined on 1.5- by 3.5-in. specimens (2×4s) was found to be equivalent to that determined using the 2- by 2-in. specimen specified in ASTM D 143. Data are presented on the relationship between Janka hardness and the strength of clear wood. Analysis of historical data determined using standard specimens indicated no difference between side hardness...

  13. Analytical Validation of a Highly Quantitative, Sensitive, Accurate, and Reproducible Assay (HERmark® for the Measurement of HER2 Total Protein and HER2 Homodimers in FFPE Breast Cancer Tumor Specimens

    Directory of Open Access Journals (Sweden)

    Jeffrey S. Larson

    2010-01-01

    Full Text Available We report here the results of the analytical validation of assays that measure HER2 total protein (H2T and HER2 homodimer (H2D expression in Formalin Fixed Paraffin Embedded (FFPE breast cancer tumors as well as cell line controls. The assays are based on the VeraTag technology platform and are commercially available through a central CAP-accredited clinical reference laboratory. The accuracy of H2T measurements spans a broad dynamic range (2-3 logs as evaluated by comparison with cross-validating technologies. The measurement of H2T expression demonstrates a sensitivity that is approximately 7–10 times greater than conventional immunohistochemistry (IHC (HercepTest. The HERmark assay is a quantitative assay that sensitively and reproducibly measures continuous H2T and H2D protein expression levels and therefore may have the potential to stratify patients more accurately with respect to response to HER2-targeted therapies than current methods which rely on semiquantitative protein measurements (IHC or on indirect assessments of gene amplification (FISH.

  14. Sleep and immune function: glial contributions and consequences of aging.

    Science.gov (United States)

    Ingiosi, Ashley M; Opp, Mark R; Krueger, James M

    2013-10-01

    The reciprocal interactions between sleep and immune function are well-studied. Insufficient sleep induces innate immune responses as evidenced by increased expression of pro-inflammatory mediators in the brain and periphery. Conversely, immune challenges upregulate immunomodulator expression, which alters central nervous system-mediated processes and behaviors, including sleep. Recent studies indicate that glial cells, namely microglia and astrocytes, are active contributors to sleep and immune system interactions. Evidence suggests glial regulation of these interactions is mediated, in part, by adenosine and adenosine 5'-triphosphate actions at purinergic type 1 and type 2 receptors. Furthermore, microglia and astrocytes may modulate declines in sleep-wake behavior and immunity observed in aging. Copyright © 2013. Published by Elsevier Ltd.

  15. Tumors of the pineal region: radiological findings

    International Nuclear Information System (INIS)

    Roman, G.; Delgado, F.; Cano, A.; Vicente, J.; Ramos, M.

    1997-01-01

    To consider the different radiological findings that, together with age, sex, clinical picture and serum markers, indicate a presumed or even definitive diagnosis in tumors of the pineal region. We reviewed retrospectively 18 patients diagnosed as having pineal region tumors. The lesions in this series consisted of seven germinoma, three meningiomas, one pineoblastoma. two ependymomas, one teratoma, two glial cysts, and arachnoid cyst and a lipoma. All but the arachnoid cysts and the lipoma were confirmed histologically. We took into account mainly the epidemiological data, tumor markers and CT and MR features. The germinoma was the most common lesions, representing 38.8% of the tumors in our series. All developed in men (mean age: 21 years). Small non tumoral calcifications were present in pineal gland in six of these cases. This tumor usually invades adjacent structures and produces metastatic seeding in CSF. The pineoblastoma contained prominent tumor calcifications. Meningiomas were detected only in middle-aged women. In addition to the fact that the behavior of these lesions was typical of that meningiomas in other locations, meningeal enhancement in the vicinity of the extraaxial tumor aided in the diagnosis. The teratoma showed variable attenuation, ranging from a fatty substance to calcium, and elevated fetoprotein levels. The glial cyst is a cyst lesion that does not be-have exactly like the CSF, while the arachnoid cyst was isointense with respect to the CSF in all sequences. Enhancement was observed in the glial cysts, one peripheral and the other nodular. The assessment of age, sex, clinical picture and tumor markers, together with the features observed in CT an MR images are suggestive of the histological diagnosis of pineal region tumors. We recommend the use of CT because of its availability and its ability detect calcifications, thus indicating a specific histological type, and of MR because of its greater anatomical definition and its, ability to

  16. Glial activation colocalizes with structural abnormalities in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Alshikho, Mohamad J; Zürcher, Nicole R; Loggia, Marco L; Cernasov, Paul; Chonde, Daniel B; Izquierdo Garcia, David; Yasek, Julia E; Akeju, Oluwaseun; Catana, Ciprian; Rosen, Bruce R; Cudkowicz, Merit E; Hooker, Jacob M; Atassi, Nazem

    2016-12-13

    In this cross-sectional study, we aimed to evaluate brain structural abnormalities in relation to glial activation in the same cohort of participants. Ten individuals with amyotrophic lateral sclerosis (ALS) and 10 matched healthy controls underwent brain imaging using integrated MR/PET and the radioligand [ 11 C]-PBR28. Diagnosis history and clinical assessments including Upper Motor Neuron Burden Scale (UMNB) were obtained from patients with ALS. Diffusion tensor imaging (DTI) analyses including tract-based spatial statistics and tractography were applied. DTI metrics including fractional anisotropy (FA) and diffusivities (mean, axial, and radial) were measured in regions of interest. Cortical thickness was assessed using surface-based analysis. The locations of structural changes, measured by DTI and the areas of cortical thinning, were compared to regional glial activation measured by relative [ 11 C]-PBR28 uptake. In this cohort of individuals with ALS, reduced FA and cortical thinning colocalized with regions demonstrating higher radioligand binding. [ 11 C]-PBR28 binding in the left motor cortex was correlated with FA (r = -0.68, p < 0.05) and cortical thickness (r = -0.75, p < 0.05). UMNB was correlated with glial activation (r = +0.75, p < 0.05), FA (r = -0.77, p < 0.05), and cortical thickness (r = -0.75, p < 0.05) in the motor cortex. Increased uptake of the glial marker [ 11 C]-PBR28 colocalizes with changes in FA and cortical thinning. This suggests a link between disease mechanisms (gliosis and inflammation) and structural changes (cortical thinning and white and gray matter changes). In this multimodal neuroimaging work, we provide an in vivo model to investigate the pathogenesis of ALS. © 2016 American Academy of Neurology.

  17. Measuring Glial Metabolism in Repetitive Brain Trauma and Alzheimers Disease

    Science.gov (United States)

    2017-09-01

    4: Correlate the glial and glutamate metabolic rates with additional measures obtained in the parent studies including of a) serum, CSF, and genetic...resonances as a linear combination model. Note the high SNR of glutamate and its separation from other metabolites that would overlap at 3 Tesla. 3.3... separate protocol offered to participants in the study but will not be mandatory and thus will not impact this study in any way. 3.4. Results

  18. Peripheral nerve injury induces glial activation in primary motor cortex

    OpenAIRE

    Julieta Troncoso; Julieta Troncoso; Efraín Buriticá; Efraín Buriticá

    2015-01-01

    Preliminary evidence suggests that peripheral facial nerve injuries are associated with sensorimotor cortex reorganization. We have characterized facial nerve lesion-induced structural changes in primary motor cortex layer 5 pyramidal neurons and their relationship with glial cell density using a rodent facial paralysis model. First, we used adult transgenic mice expressing green fluorescent protein in microglia and yellow fluorescent protein in pyramidal neurons which were subjected to eithe...

  19. Connecting Malfunctioning Glial Cells and Brain Degenerative Disorders.

    Science.gov (United States)

    Kaminsky, Natalie; Bihari, Ofer; Kanner, Sivan; Barzilai, Ari

    2016-06-01

    The DNA damage response (DDR) is a complex biological system activated by different types of DNA damage. Mutations in certain components of the DDR machinery can lead to genomic instability disorders that culminate in tissue degeneration, premature aging, and various types of cancers. Intriguingly, malfunctioning DDR plays a role in the etiology of late onset brain degenerative disorders such as Parkinson's, Alzheimer's, and Huntington's diseases. For many years, brain degenerative disorders were thought to result from aberrant neural death. Here we discuss the evidence that supports our novel hypothesis that brain degenerative diseases involve dysfunction of glial cells (astrocytes, microglia, and oligodendrocytes). Impairment in the functionality of glial cells results in pathological neuro-glial interactions that, in turn, generate a "hostile" environment that impairs the functionality of neuronal cells. These events can lead to systematic neural demise on a scale that appears to be proportional to the severity of the neurological deficit. Copyright © 2016 The Authors. Production and hosting by Elsevier Ltd.. All rights reserved.

  20. Imaging of intracranial neuronal and mixed neuronal-glial tumours

    International Nuclear Information System (INIS)

    Cui Shimin; Qin Jinxi; Zhang Leili; Liu Meili; Jin Song; Yan Shixin; Liu Li; Dai Weiying; Li Tao; Gao Man

    2001-01-01

    Objective: To investigate the characteristic clinical, imaging , and pathologic findings of intracranial neuronal and mixed neuronal-glial tumours. Methods: The imaging findings of surgery and pathobiology proved intracranial neuronal and mixed neuronal-glial tumours in 14 cases (7 male and 7 female, ranging in age from 6-56 years; mean age 33.8 years) were retrospectively analyzed. Results: Eight gangliogliomas were located in the frontal lobe (4 cases), temporal lobe (1 case), front- temporal lobe (2 cases), and pons (1 case). They appeared as iso-or low density on CT, iso-or low signal intensity on T 1 WI, and high signal intensity on T 2 WI on MR imaging. Two central neurocytomas were located in the supratentorial ventricles. Four desmoplastic gangliogliomas were seen as cystic masses, appearing as low signal intensity on T 1 WI and high signal intensity on T 2 WI. Conclusion: Intracranial neuronal and mixed neuronal-glial tumours had imaging characteristics. Combined with clinical history, it was possible to make a tendency preoperative diagnosis using CT or MR

  1. Responses of fibroblasts and glial cells to nanostructured platinum surfaces

    Energy Technology Data Exchange (ETDEWEB)

    Pennisi, C P; Sevcencu, C; Yoshida, K [Center for Sensory-Motor Interaction (SMI), Aalborg University, Aalborg (Denmark); Dolatshahi-Pirouz, A; Foss, M; Larsen, A Nylandsted; Besenbacher, F [Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Aarhus (Denmark); Hansen, J Lundsgaard [Department of Physics and Astronomy, Aarhus University, Aarhus (Denmark); Zachar, V, E-mail: cpennisi@hst.aau.d [Laboratory for Stem Cell Research, Aalborg University (Denmark)

    2009-09-23

    The chronic performance of implantable neural prostheses is affected by the growth of encapsulation tissue onto the stimulation electrodes. Encapsulation is associated with activation of connective tissue cells at the electrode's metallic contacts, usually made of platinum. Since surface nanotopography can modulate the cellular responses to materials, the aim of the present work was to evaluate the 'in vitro' responses of connective tissue cells to platinum strictly by modulating its surface nanoroughness. Using molecular beam epitaxy combined with sputtering, we produced platinum nanostructured substrates consisting of irregularly distributed nanopyramids and investigated their effect on the proliferation, cytoskeletal organization and cellular morphology of primary fibroblasts and transformed glial cells. Cells were cultured on these substrates and their responses to surface roughness were studied. After one day in culture, the fibroblasts were more elongated and their cytoskeleton less mature when cultured on rough substrates. This effect increased as the roughness of the surface increased and was associated with reduced cell proliferation throughout the observation period (4 days). Morphological changes also occurred in glial cells, but they were triggered by a different roughness scale and did not affect cellular proliferation. In conclusion, surface nanotopography modulates the responses of fibroblasts and glial cells to platinum, which may be an important factor in optimizing the tissue response to implanted neural electrodes.

  2. Connecting Malfunctioning Glial Cells and Brain Degenerative Disorders

    Directory of Open Access Journals (Sweden)

    Natalie Kaminsky

    2016-06-01

    Full Text Available The DNA damage response (DDR is a complex biological system activated by different types of DNA damage. Mutations in certain components of the DDR machinery can lead to genomic instability disorders that culminate in tissue degeneration, premature aging, and various types of cancers. Intriguingly, malfunctioning DDR plays a role in the etiology of late onset brain degenerative disorders such as Parkinson’s, Alzheimer’s, and Huntington’s diseases. For many years, brain degenerative disorders were thought to result from aberrant neural death. Here we discuss the evidence that supports our novel hypothesis that brain degenerative diseases involve dysfunction of glial cells (astrocytes, microglia, and oligodendrocytes. Impairment in the functionality of glial cells results in pathological neuro-glial interactions that, in turn, generate a “hostile” environment that impairs the functionality of neuronal cells. These events can lead to systematic neural demise on a scale that appears to be proportional to the severity of the neurological deficit.

  3. Technical validation of an RT-qPCR in vitro diagnostic test system for the determination of breast cancer molecular subtypes by quantification of ERBB2, ESR1, PGR and MKI67 mRNA levels from formalin-fixed paraffin-embedded breast tumor specimens.

    Science.gov (United States)

    Laible, Mark; Schlombs, Kornelia; Kaiser, Katharina; Veltrup, Elke; Herlein, Stefanie; Lakis, Sotiris; Stöhr, Robert; Eidt, Sebastian; Hartmann, Arndt; Wirtz, Ralph M; Sahin, Ugur

    2016-07-07

    MammaTyper is a novel CE-marked in vitro diagnostic RT-qPCR assay which assigns routinely processed breast cancer specimens into the molecular subtypes Luminal A-like, Luminal B-like (HER2 positive or negative), HER2 positive (non-luminal) and Triple negative (ductal) according to the mRNA expression of ERBB2, ESR1, PGR and MKI67 and the St Gallen consensus surrogate clinical definition. Until now and regarding formalin-fixed, paraffin-embedded material (FFPE), this has been a task mostly accomplished by immunohistochemistry (IHC). However the discrepancy rates of IHC for the four breast cancer biomarkers are frequently under debate, especially for Ki-67 which carries the highest degree of inter- and even intra-observer variability. Herein we describe a series of studies in FFPE specimens which aim to fully validate the analytical performance of the MammaTyper assay, including the site to site reproducibility of the individual marker measurements. Tumor RNA was extracted with the novel RNXtract RNA extraction kit. Synthetic RNA was used to assess the sensitivity of the RNXtract kit. DNA and RNA specific qPCR assays were used so as to determine analyte specificity of RNXtract. For the assessment of limit of blank, limit of detection, analytical measurement range and PCR efficiency of the MammaTyper kit serial dilutions of samples were used. Analytical precision studies of MammaTyper were built around two different real time PCR platforms and involved breast tumor samples belonging to different subtypes analyzed across multiple sites and under various stipulated conditions. The MammaTyper assay robustness was tested against RNA input variations, alternative extraction methods and tumor cell content. Individual assays were linear up to at least 32.33 and 33.56 Cqs (quantification cycles) for the two qPCR platforms tested. PCR efficiency ranged from 99 to 109 %. In qPCR platform 1, estimates for assay specific inter-site standard deviations (SD) were between 0.14 and

  4. Technical validation of an RT-qPCR in vitro diagnostic test system for the determination of breast cancer molecular subtypes by quantification of ERBB2, ESR1, PGR and MKI67 mRNA levels from formalin-fixed paraffin-embedded breast tumor specimens

    International Nuclear Information System (INIS)

    Laible, Mark; Schlombs, Kornelia; Kaiser, Katharina; Veltrup, Elke; Herlein, Stefanie; Lakis, Sotiris; Stöhr, Robert; Eidt, Sebastian; Hartmann, Arndt; Wirtz, Ralph M.; Sahin, Ugur

    2016-01-01

    MammaTyper is a novel CE-marked in vitro diagnostic RT-qPCR assay which assigns routinely processed breast cancer specimens into the molecular subtypes Luminal A-like, Luminal B-like (HER2 positive or negative), HER2 positive (non-luminal) and Triple negative (ductal) according to the mRNA expression of ERBB2, ESR1, PGR and MKI67 and the St Gallen consensus surrogate clinical definition. Until now and regarding formalin-fixed, paraffin-embedded material (FFPE), this has been a task mostly accomplished by immunohistochemistry (IHC). However the discrepancy rates of IHC for the four breast cancer biomarkers are frequently under debate, especially for Ki-67 which carries the highest degree of inter- and even intra-observer variability. Herein we describe a series of studies in FFPE specimens which aim to fully validate the analytical performance of the MammaTyper assay, including the site to site reproducibility of the individual marker measurements. Tumor RNA was extracted with the novel RNXtract RNA extraction kit. Synthetic RNA was used to assess the sensitivity of the RNXtract kit. DNA and RNA specific qPCR assays were used so as to determine analyte specificity of RNXtract. For the assessment of limit of blank, limit of detection, analytical measurement range and PCR efficiency of the MammaTyper kit serial dilutions of samples were used. Analytical precision studies of MammaTyper were built around two different real time PCR platforms and involved breast tumor samples belonging to different subtypes analyzed across multiple sites and under various stipulated conditions. The MammaTyper assay robustness was tested against RNA input variations, alternative extraction methods and tumor cell content. Individual assays were linear up to at least 32.33 and 33.56 Cqs (quantification cycles) for the two qPCR platforms tested. PCR efficiency ranged from 99 to 109 %. In qPCR platform 1, estimates for assay specific inter-site standard deviations (SD) were between 0.14 and 0

  5. Primary glia expressing the G93A-SOD1 mutation present a neuroinflammatory phenotype and provide a cellular system for studies of glial inflammation

    Directory of Open Access Journals (Sweden)

    Qi Min

    2006-01-01

    Full Text Available Abstract Detailed study of glial inflammation has been hindered by lack of cell culture systems that spontaneously demonstrate the "neuroinflammatory phenotype". Mice expressing a glycine → alanine substitution in cytosolic Cu, Zn-superoxide dismutase (G93A-SOD1 associated with familial amyotrophic lateral sclerosis (ALS demonstrate age-dependent neuroinflammation associated with broad-spectrum cytokine, eicosanoid and oxidant production. In order to more precisely study the cellular mechanisms underlying glial activation in the G93A-SOD1 mouse, primary astrocytes were cultured from 7 day mouse neonates. At this age, G93A-SOD1 mice demonstrated no in vivo hallmarks of neuroinflammation. Nonetheless astrocytes cultured from G93A-SOD1 (but not wild-type human SOD1-expressing transgenic mouse pups demonstrated a significant elevation in either the basal or the tumor necrosis alpha (TNFα-stimulated levels of proinflammatory eicosanoids prostaglandin E2 (PGE2 and leukotriene B4 (LTB4; inducible nitric oxide synthase (iNOS and •NO (indexed by nitrite release into the culture medium; and protein carbonyl products. Specific cytokine- and TNFα death-receptor-associated components were similarly upregulated in cultured G93A-SOD1 cells as assessed by multiprobe ribonuclease protection assays (RPAs for their mRNA transcripts. Thus, endogenous glial expression of G93A-SOD1 produces a metastable condition in which glia are more prone to enter an activated neuroinflammatory state associated with broad-spectrum increased production of paracrine-acting substances. These findings support a role for active glial involvement in ALS and may provide a useful cell culture tool for the study of glial inflammation.

  6. Screen-film specimen radiography

    International Nuclear Information System (INIS)

    Shepard, S.J.; Hogan, J.; Schreck, B.

    1990-01-01

    This paper reports on the reproducibility and quality of biopsy specimen radiographs, a unique phototimed cabinet x-ray system is being developed. The system utilizes specially modified Kodal Min-R cassettes and will be compatible with current mammographic films. Tube voltages are in the 14-20-kVp range with 0.1-1.0-second exposure times. A top-hat type compression device is used (1) to compress the specimen to uniform thickness, (2) to measure the specimen thickness and determine optimum kVp, and (3) to superimpose a grid over the specimen for identification of objects of radiographic interest. The phototiming circuit developed specifically for this purpose will be described along with the modified Min-R cassette. Characteristics of the generator and cabinet will also be described. Tests will be performed on phantoms to evaluate the system limitations

  7. 3D volume reconstruction from serial breast specimen radiographs for mapping between histology and 3D whole specimen imaging

    NARCIS (Netherlands)

    Mertzanidou, T.; Hipwell, J.H.; Reis, S.; Hawkes, D.J.; Ehteshami Bejnordi, B.; Dalmis, M.U.; Vreemann, S.; Platel, B.; Laak, J.A. van der; Karssemeijer, N.; Hermsen, M.; Bult, P.; Mann, R.M.

    2017-01-01

    PURPOSE: In breast imaging, radiological in vivo images, such as x-ray mammography and magnetic resonance imaging (MRI), are used for tumor detection, diagnosis, and size determination. After excision, the specimen is typically sliced into slabs and a small subset is sampled. Histopathological

  8. DNA extraction from herbarium specimens.

    Science.gov (United States)

    Drábková, Lenka Záveská

    2014-01-01

    With the expansion of molecular techniques, the historical collections have become widely used. Studying plant DNA using modern molecular techniques such as DNA sequencing plays an important role in understanding evolutionary relationships, identification through DNA barcoding, conservation status, and many other aspects of plant biology. Enormous herbarium collections are an important source of material especially for specimens from areas difficult to access or from taxa that are now extinct. The ability to utilize these specimens greatly enhances the research. However, the process of extracting DNA from herbarium specimens is often fraught with difficulty related to such variables as plant chemistry, drying method of the specimen, and chemical treatment of the specimen. Although many methods have been developed for extraction of DNA from herbarium specimens, the most frequently used are modified CTAB and DNeasy Plant Mini Kit protocols. Nine selected protocols in this chapter have been successfully used for high-quality DNA extraction from different kinds of plant herbarium tissues. These methods differ primarily with respect to their requirements for input material (from algae to vascular plants), type of the plant tissue (leaves with incrustations, sclerenchyma strands, mucilaginous tissues, needles, seeds), and further possible applications (PCR-based methods or microsatellites, AFLP).

  9. Central nervous system tumors

    International Nuclear Information System (INIS)

    Gavin, P.R.; Fike, J.R.; Hoopes, P.J.

    1995-01-01

    Central nervous system (CNS) tumors are relatively common in veterinary medicine, with most diagnoses occurring in the canine and feline species. Numerous tumor types from various cells or origins have been identified with the most common tumors being meningiomas and glial cell tumors. Radiation therapy is often used as an aid to control the clinical signs associated with these neoplasms. In general, these tumors have a very low metastatic potential, such that local control offers substantial benefit. Experience in veterinary radiation oncology would indicate that many patients benefit from radiation treatment. Current practice indicates the need for computed tomography or magnetic resonance imaging studies. These highly beneficial studies are used for diagnosis, treatment planning, and to monitor treatment response. Improvements in treatment planning and radiation delivered to the tumor, while sparing the normal tissues, should improve local control and decrease potential radiation related problems to the CNS. When possible, multiple fractions of 3 Gy or less should be used. The tolerance dose to the normal tissue with this fractionation schedule is 50 to 55 Gy. The most common and serious complications of radiation for CNS tumors is delayed radiation myelopathy and necrosis. Medical management of the patient during radiation therapy requires careful attention to anesthetic protocols, and medications to reduce intracranial pressure that is often elevated in these patients. Canine brain tumors have served as an experimental model to test numerous new treatments. Increased availability of advanced imaging modalities has spawned increased detection of these neoplasms. Early detection of these tumors with appropriate aggressive therapy should prove beneficial to many patients

  10. Comparative study of muscarinic acetylcholine receptors of human and rat cortical glial cells

    International Nuclear Information System (INIS)

    Demushkin, V.P.; Burbaeva, G.S.; Dzhaliashvili, T.A.; Plyashkevich, Y.G.

    1985-01-01

    The aim of the present investigation was a comparative studyof muscarinic acetylcholine receptors in human and rat glial cells. ( 3 H)Quinuclidinyl-benzylate (( 3 H)-QB), atropine, platiphylline, decamethonium, carbamylcholine, tubocurarine, and nicotine were used. The glial cell fraction was obtained from the cerebral cortex of rats weighing 130-140 g and from the frontal pole of the postmortem brain from men aged 60-70 years. The use of the method of radioimmune binding of ( 3 H)-QB with human and rat glial cell membranes demonstrated the presence of a muscarinic acetylcholine receptor in the glial cells

  11. An in vitro clonogenic assay to assess radiation damage in rat CNS glial progenitor cells

    International Nuclear Information System (INIS)

    Maazen, R.W.M. van der; Verhagen, I.; Kogel, A.J. van der

    1990-01-01

    Normal glial progenitor cells can be isolated from the rat central nervous system (CNS) and cultured in vitro on a monolayer of type-1 astrocytes. These monolayers are able to support and stimulate explanted glial progenitor cells to proliferate. Employing these in vitro interactions of specific glial cell types, an in vivo-in vitro clonogenic assay has been developed. This method offers the possibility to study the intrinsic radiosensitivity, repair and regeneration of glial progenitor cells after in vitro or in vivo irradiation. (author)

  12. Neuroinflammation induces glial aromatase expression in the uninjured songbird brain

    Directory of Open Access Journals (Sweden)

    Saldanha Colin J

    2011-07-01

    Full Text Available Abstract Background Estrogens from peripheral sources as well as central aromatization are neuroprotective in the vertebrate brain. Under normal conditions, aromatase is only expressed in neurons, however following anoxic/ischemic or mechanical brain injury; aromatase is also found in astroglia. This increased glial aromatization and the consequent estrogen synthesis is neuroprotective and may promote neuronal survival and repair. While the effects of estradiol on neuroprotection are well studied, what induces glial aromatase expression remains unknown. Methods Adult male zebra finches (Taeniopygia guttata were given a penetrating injury to the entopallium. At several timepoints later, expression of aromatase, IL-1β-like, and IL-6-like were examined using immunohisotchemistry. A second set of zebra birds were exposed to phytohemagglutinin (PHA, an inflammatory agent, directly on the dorsal surface of the telencephalon without creating a penetrating injury. Expression of aromatase, IL-1β-like, and IL-6-like were examined using both quantitative real-time polymerase chain reaction to examine mRNA expression and immunohistochemistry to determine cellular expression. Statistical significance was determined using t-test or one-way analysis of variance followed by the Tukey Kramers post hoc test. Results Following injury in the zebra finch brain, cytokine expression occurs prior to aromatase expression. This temporal pattern suggests that cytokines may induce aromatase expression in the damaged zebra finch brain. Furthermore, evoking a neuroinflammatory response characterized by an increase in cytokine expression in the uninjured brain is sufficient to induce glial aromatase expression. Conclusions These studies are among the first to examine a neuroinflammatory response in the songbird brain following mechanical brain injury and to describe a novel neuroimmune signal to initiate aromatase expression in glia.

  13. Allergic Inflammation Leads to Neuropathic Pain via Glial Cell Activation.

    Science.gov (United States)

    Yamasaki, Ryo; Fujii, Takayuki; Wang, Bing; Masaki, Katsuhisa; Kido, Mizuho A; Yoshida, Mari; Matsushita, Takuya; Kira, Jun-Ichi

    2016-11-23

    Allergic and atopic disorders have increased over the past few decades and have been associated with neuropsychiatric conditions, such as autism spectrum disorder and asthmatic amyotrophy. Myelitis presenting with neuropathic pain can occur in patients with atopic disorder; however, the relationship between allergic inflammation and neuropathic pain, and the underlying mechanism, remains to be established. We studied whether allergic inflammation affects the spinal nociceptive system. We found that mice with asthma, atopic dermatitis, or atopic diathesis had widespread and significantly more activated microglia and astroglia in the spinal cord than those without atopy, and displayed tactile allodynia. Microarray analysis of isolated microglia revealed a dysregulated phenotype showing upregulation of M1 macrophage markers and downregulation of M2 markers in atopic mice. Among the cell surface protein genes, endothelin receptor type B (EDNRB) was most upregulated. Immunohistochemical analysis revealed that EDNRB expression was enhanced in microglia and astroglia, whereas endothelin-1, an EDNRB ligand, was increased in serum, lungs, and epidermis of atopic mice. No EDNRA expression was found in the spinal cord. Expression of FBJ murine osteosarcoma viral oncogene homolog B was significantly higher in the dorsal horn neurons of asthma mice than nonatopic mice. The EDNRB antagonist BQ788 abolished glial and neural activation and allodynia. We found increased serum endothelin-1 in atopic patients with myelitis and neuropathic pain, and activation of spinal microglia and astroglia with EDNRB upregulation in an autopsied case. These results suggest that allergic inflammation induces diffuse glial activation, influencing the nociceptive system via the EDNRB pathway. The prevalence of allergic disorders has markedly increased over the past few decades. Allergic disorders are associated with neuropsychiatric conditions; however, the relationship between allergic inflammation

  14. Minocycline blocks glial cell activation and ventilatory acclimatization to hypoxia.

    Science.gov (United States)

    Stokes, Jennifer A; Arbogast, Tara E; Moya, Esteban A; Fu, Zhenxing; Powell, Frank L

    2017-04-01

    Ventilatory acclimatization to hypoxia (VAH) is the time-dependent increase in ventilation, which persists upon return to normoxia and involves plasticity in both central nervous system respiratory centers and peripheral chemoreceptors. We investigated the role of glial cells in VAH in male Sprague-Dawley rats using minocycline, an antibiotic that inhibits microglia activation and has anti-inflammatory properties, and barometric pressure plethysmography to measure ventilation. Rats received either minocycline (45mg/kg ip daily) or saline beginning 1 day before and during 7 days of chronic hypoxia (CH, Pi O 2  = 70 Torr). Minocycline had no effect on normoxic control rats or the hypercapnic ventilatory response in CH rats, but minocycline significantly ( P minocycline administration during only the last 3 days of CH did not reverse VAH. Microglia and astrocyte activation in the nucleus tractus solitarius was quantified from 30 min to 7 days of CH. Microglia showed an active morphology (shorter and fewer branches) after 1 h of hypoxia and returned to the control state (longer filaments and extensive branching) after 4 h of CH. Astrocytes increased glial fibrillary acidic protein antibody immunofluorescent intensity, indicating activation, at both 4 and 24 h of CH. Minocycline had no effect on glia in normoxia but significantly decreased microglia activation at 1 h of CH and astrocyte activation at 24 h of CH. These results support a role for glial cells, providing an early signal for the induction but not maintenance of neural plasticity underlying ventilatory acclimatization to hypoxia. NEW & NOTEWORTHY The signals for neural plasticity in medullary respiratory centers underlying ventilatory acclimatization to chronic hypoxia are unknown. We show that chronic hypoxia activates microglia and subsequently astrocytes. Minocycline, an antibiotic that blocks microglial activation and has anti-inflammatory properties, also blocks astrocyte activation in respiratory

  15. Indoxyl Sulfate Affects Glial Function Increasing Oxidative Stress and Neuroinflammation in Chronic Kidney Disease: Interaction between Astrocytes and Microglia

    Directory of Open Access Journals (Sweden)

    Simona Adesso

    2017-06-01

    Full Text Available Indoxyl sulfate (IS is a protein-bound uremic toxin resulting from the metabolism of dietary tryptophan which accumulates in patients with impaired renal function, such as chronic kidney disease (CKD. IS is a well-known nephrovascular toxin but little is known about its effects on central nervous system (CNS cells. Considering the growing interest in the field of CNS comorbidities in CKD, we studied the effect of IS on CNS cells. IS (15–60 μM treatment in C6 astrocyte cells increased reactive oxygen species release and decreased nuclear factor (erythroid-derived 2-like 2 (Nrf2 activation, and heme oxygenase-1 (HO-1 and NAD(PH dehydrogenase quinone 1 expression. Moreover, IS increased Aryl hydrocarbon Receptor (AhR and Nuclear Factor-kB (NF-kB activation in these cells. Similiar observations were made in primary mouse astrocytes and mixed glial cells. Inducible nitric oxide synthase and cyclooxygenase-2 (COX-2 expression, tumor necrosis factor-α and interleukin-6 release and nitrotyrosine formation were increased by IS (15–60 μM in primary mouse astrocytes and mixed glial cells. IS increased AhR and NF-kB nuclear translocation and reduced Nrf2 translocation and HO-1 expression in primary glial cells. In addition, IS induced cell death in neurons in a dose dependent fashion. Injection of IS (800 mg/kg, i.p. into mice induced histological changes and increased COX-2 expression and nitrotyrosine formation in thebrain tissue. Taken together, our results show a significant contribution of IS in generating a neurotoxic enviroment and it could also have a potential role in neurodegeneration. IS could be considered also a potential therapeutical target for CKD-associated neurodegenerative complications.

  16. Transcriptional differences between normal and glioma-derived glial progenitor cells identify a core set of dysregulated genes.

    Science.gov (United States)

    Auvergne, Romane M; Sim, Fraser J; Wang, Su; Chandler-Militello, Devin; Burch, Jaclyn; Al Fanek, Yazan; Davis, Danielle; Benraiss, Abdellatif; Walter, Kevin; Achanta, Pragathi; Johnson, Mahlon; Quinones-Hinojosa, Alfredo; Natesan, Sridaran; Ford, Heide L; Goldman, Steven A

    2013-06-27

    Glial progenitor cells (GPCs) are a potential source of malignant gliomas. We used A2B5-based sorting to extract tumorigenic GPCs from human gliomas spanning World Health Organization grades II-IV. Messenger RNA profiling identified a cohort of genes that distinguished A2B5+ glioma tumor progenitor cells (TPCs) from A2B5+ GPCs isolated from normal white matter. A core set of genes and pathways was substantially dysregulated in A2B5+ TPCs, which included the transcription factor SIX1 and its principal cofactors, EYA1 and DACH2. Small hairpin RNAi silencing of SIX1 inhibited the expansion of glioma TPCs in vitro and in vivo, suggesting a critical and unrecognized role of the SIX1-EYA1-DACH2 system in glioma genesis or progression. By comparing the expression patterns of glioma TPCs with those of normal GPCs, we have identified a discrete set of pathways by which glial tumorigenesis may be better understood and more specifically targeted. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

  17. Glial processes at the Drosophila larval neuromuscular junction match synaptic growth.

    Directory of Open Access Journals (Sweden)

    Deidre L Brink

    Full Text Available Glia are integral participants in synaptic physiology, remodeling and maturation from blowflies to humans, yet how glial structure is coordinated with synaptic growth is unknown. To investigate the dynamics of glial development at the Drosophila larval neuromuscular junction (NMJ, we developed a live imaging system to establish the relationship between glia, neuronal boutons, and the muscle subsynaptic reticulum. Using this system we observed processes from two classes of peripheral glia present at the NMJ. Processes from the subperineurial glia formed a blood-nerve barrier around the axon proximal to the first bouton. Processes from the perineurial glial extended beyond the end of the blood-nerve barrier into the NMJ where they contacted synapses and extended across non-synaptic muscle. Growth of the glial processes was coordinated with NMJ growth and synaptic activity. Increasing synaptic size through elevated temperature or the highwire mutation increased the extent of glial processes at the NMJ and conversely blocking synaptic activity and size decreased the presence and size of glial processes. We found that elevated temperature was required during embryogenesis in order to increase glial expansion at the nmj. Therefore, in our live imaging system, glial processes at the NMJ are likely indirectly regulated by synaptic changes to ensure the coordinated growth of all components of the tripartite larval NMJ.

  18. Honeybee retinal glial cells transform glucose and supply the neurons with metabolic substrate

    International Nuclear Information System (INIS)

    Tsacopoulos, M.; Evequoz-Mercier, V.; Perrottet, P.; Buchner, E.

    1988-01-01

    The retina of the honeybee drone is a nervous tissue in which glial cells and photoreceptor cells (sensory neurons) constitute two distinct metabolic compartments. Retinal slices incubated with 2-deoxy[ 3 H]glucose convert this glucose analogue to 2-deoxy[ 3 H]glucose 6-phosphate, but this conversion is made only in the glial cells. Hence, glycolysis occurs only in glial cells. In contrast, the neurons consume O 2 and this consumption is sustained by the hydrolysis of glycogen, which is contained in large amounts in the glia. During photostimulation the increased oxidative metabolism of the neurons is sustained by a higher supply of carbohydrates from the glia. This clear case of metabolic interaction between neurons and glial cells supports Golgi's original hypothesis, proposed nearly 100 years ago, about the nutritive function of glial cells in the nervous system

  19. Honeybee Retinal Glial Cells Transform Glucose and Supply the Neurons with Metabolic Substrate

    Science.gov (United States)

    Tsacopoulos, M.; Evequoz-Mercier, V.; Perrottet, P.; Buchner, E.

    1988-11-01

    The retina of the honeybee drone is a nervous tissue in which glial cells and photoreceptor cells (sensory neurons) constitute two distinct metabolic compartments. Retinal slices incubated with 2-deoxy[3H]glucose convert this glucose analogue to 2-deoxy[3H]glucose 6-phosphate, but this conversion is made only in the glial cells. Hence, glycolysis occurs only in glial cells. In contrast, the neurons consume O2 and this consumption is sustained by the hydrolysis of glycogen, which is contained in large amounts in the glia. During photostimulation the increased oxidative metabolism of the neurons is sustained by a higher supply of carbohydrates from the glia. This clear case of metabolic interaction between neurons and glial cells supports Golgi's original hypothesis, proposed nearly 100 years ago, about the nutritive function of glial cells in the nervous system.

  20. Tissue engineered tumor models.

    Science.gov (United States)

    Ingram, M; Techy, G B; Ward, B R; Imam, S A; Atkinson, R; Ho, H; Taylor, C R

    2010-08-01

    Many research programs use well-characterized tumor cell lines as tumor models for in vitro studies. Because tumor cells grown as three-dimensional (3-D) structures have been shown to behave more like tumors in vivo than do cells growing in monolayer culture, a growing number of investigators now use tumor cell spheroids as models. Single cell type spheroids, however, do not model the stromal-epithelial interactions that have an important role in controlling tumor growth and development in vivo. We describe here a method for generating, reproducibly, more realistic 3-D tumor models that contain both stromal and malignant epithelial cells with an architecture that closely resembles that of tumor microlesions in vivo. Because they are so tissue-like we refer to them as tumor histoids. They can be generated reproducibly in substantial quantities. The bioreactor developed to generate histoid constructs is described and illustrated. It accommodates disposable culture chambers that have filled volumes of either 10 or 64 ml, each culture yielding on the order of 100 or 600 histoid particles, respectively. Each particle is a few tenths of a millimeter in diameter. Examples of histological sections of tumor histoids representing cancers of breast, prostate, colon, pancreas and urinary bladder are presented. Potential applications of tumor histoids include, but are not limited to, use as surrogate tumors for pre-screening anti-solid tumor pharmaceutical agents, as reference specimens for immunostaining in the surgical pathology laboratory and use in studies of invasive properties of cells or other aspects of tumor development and progression. Histoids containing nonmalignant cells also may have potential as "seeds" in tissue engineering. For drug testing, histoids probably will have to meet certain criteria of size and tumor cell content. Using a COPAS Plus flow cytometer, histoids containing fluorescent tumor cells were analyzed successfully and sorted using such criteria.

  1. Central nervous system tumors: a hospital based analysis

    International Nuclear Information System (INIS)

    Ayaz, B.; Lodhi, F.; Hasan, M.

    2011-01-01

    Objective: To assess the spectrum of CNS tumors and provide benchmark data for future studies assessing data in continuum. Patients and Methods: One hundred cases fulfilling the inclusion criteria were included between the ages of 1-85 years belonging to both genders. Results: Majority of the cases were seen in the year 2008 with the most commonly encountered lesion being the glial tumors followed by the meningiothelial neoplasms. Our findings were similar to previous similar studies in our setup with little change in trends. Conclusion: Glial tumors appear to be more common in our setup whereas the popularly believed Meningiothelial tumors though common came next. Our study can form the benchmark data upon which future studies can be conducted. (author)

  2. Peripheral nerve injury induces glial activation in primary motor cortex

    Directory of Open Access Journals (Sweden)

    Julieta Troncoso

    2015-02-01

    Full Text Available Preliminary evidence suggests that peripheral facial nerve injuries are associated with sensorimotor cortex reorganization. We have characterized facial nerve lesion-induced structural changes in primary motor cortex layer 5 pyramidal neurons and their relationship with glial cell density using a rodent facial paralysis model. First, we used adult transgenic mice expressing green fluorescent protein in microglia and yellow fluorescent protein in pyramidal neurons which were subjected to either unilateral lesion of the facial nerve or sham surgery. Two-photon excitation microscopy was then used for evaluating both layer 5 pyramidal neurons and microglia in vibrissal primary motor cortex (vM1. It was found that facial nerve lesion induced long-lasting changes in dendritic morphology of vM1 layer 5 pyramidal neurons and in their surrounding microglia. Pyramidal cells’ dendritic arborization underwent overall shrinkage and transient spine pruning. Moreover, microglial cell density surrounding vM1 layer 5 pyramidal neurons was significantly increased with morphological bias towards the activated phenotype. Additionally, we induced facial nerve lesion in Wistar rats to evaluate the degree and extension of facial nerve lesion-induced reorganization processes in central nervous system using neuronal and glial markers. Immunoreactivity to NeuN (neuronal nuclei antigen, GAP-43 (growth-associated protein 43, GFAP (glial fibrillary acidic protein, and Iba 1 (Ionized calcium binding adaptor molecule 1 were evaluated 1, 3, 7, 14, 28 and 35 days after either unilateral facial nerve lesion or sham surgery. Patches of decreased NeuN immunoreactivity were found bilaterally in vM1 as well as in primary somatosensory cortex (CxS1. Significantly increased GAP-43 immunoreactivity was found bilaterally after the lesion in hippocampus, striatum, and sensorimotor cortex. One day after lesion GFAP immunoreactivity increased bilaterally in hippocampus, subcortical white

  3. Sox2 promotes survival of satellite glial cells in vitro

    International Nuclear Information System (INIS)

    Koike, Taro; Wakabayashi, Taketoshi; Mori, Tetsuji; Hirahara, Yukie; Yamada, Hisao

    2015-01-01

    Sox2 is a transcriptional factor expressed in neural stem cells. It is known that Sox2 regulates cell differentiation, proliferation and survival of the neural stem cells. Our previous study showed that Sox2 is expressed in all satellite glial cells of the adult rat dorsal root ganglion. In this study, to examine the role of Sox2 in satellite glial cells, we establish a satellite glial cell-enriched culture system. Our culture method succeeded in harvesting satellite glial cells with the somata of neurons in the dorsal root ganglion. Using this culture system, Sox2 was downregulated by siRNA against Sox2. The knockdown of Sox2 downregulated ErbB2 and ErbB3 mRNA at 2 and 4 days after siRNA treatment. MAPK phosphorylation, downstream of ErbB, was also inhibited by Sox2 knockdown. Because ErbB2 and ErbB3 are receptors that support the survival of glial cells in the peripheral nervous system, apoptotic cells were also counted. TUNEL-positive cells increased at 5 days after siRNA treatment. These results suggest that Sox2 promotes satellite glial cell survival through the MAPK pathway via ErbB receptors. - Highlights: • We established satellite glial cell culture system. • Function of Sox2 in satellite glial cell was examined using siRNA. • Sox2 knockdown downregulated expression level of ErbB2 and ErbB3 mRNA. • Sox2 knockdown increased apoptotic satellite glial cell. • Sox2 promotes satellite glial cell survival through ErbB signaling

  4. Sox2 promotes survival of satellite glial cells in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Koike, Taro, E-mail: koiket@hirakata.kmu.ac.jp; Wakabayashi, Taketoshi; Mori, Tetsuji; Hirahara, Yukie; Yamada, Hisao

    2015-08-14

    Sox2 is a transcriptional factor expressed in neural stem cells. It is known that Sox2 regulates cell differentiation, proliferation and survival of the neural stem cells. Our previous study showed that Sox2 is expressed in all satellite glial cells of the adult rat dorsal root ganglion. In this study, to examine the role of Sox2 in satellite glial cells, we establish a satellite glial cell-enriched culture system. Our culture method succeeded in harvesting satellite glial cells with the somata of neurons in the dorsal root ganglion. Using this culture system, Sox2 was downregulated by siRNA against Sox2. The knockdown of Sox2 downregulated ErbB2 and ErbB3 mRNA at 2 and 4 days after siRNA treatment. MAPK phosphorylation, downstream of ErbB, was also inhibited by Sox2 knockdown. Because ErbB2 and ErbB3 are receptors that support the survival of glial cells in the peripheral nervous system, apoptotic cells were also counted. TUNEL-positive cells increased at 5 days after siRNA treatment. These results suggest that Sox2 promotes satellite glial cell survival through the MAPK pathway via ErbB receptors. - Highlights: • We established satellite glial cell culture system. • Function of Sox2 in satellite glial cell was examined using siRNA. • Sox2 knockdown downregulated expression level of ErbB2 and ErbB3 mRNA. • Sox2 knockdown increased apoptotic satellite glial cell. • Sox2 promotes satellite glial cell survival through ErbB signaling.

  5. Differentiation of Inflammation-Responsive Astrocytes from Glial Progenitors Generated from Human Induced Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Renata Santos

    2017-06-01

    Full Text Available Astrocyte dysfunction and neuroinflammation are detrimental features in multiple pathologies of the CNS. Therefore, the development of methods that produce functional human astrocytes represents an advance in the study of neurological diseases. Here we report an efficient method for inflammation-responsive astrocyte generation from induced pluripotent stem cells (iPSCs and embryonic stem cells. This protocol uses an intermediate glial progenitor stage and generates functional astrocytes that show levels of glutamate uptake and calcium activation comparable with those observed in human primary astrocytes. Stimulation of stem cell-derived astrocytes with interleukin-1β or tumor necrosis factor α elicits a strong and rapid pro-inflammatory response. RNA-sequencing transcriptome profiling confirmed that similar gene expression changes occurred in iPSC-derived and primary astrocytes upon stimulation with interleukin-1β. This protocol represents an important tool for modeling in-a-dish neurological diseases with an inflammatory component, allowing for the investigation of the role of diseased astrocytes in neuronal degeneration.

  6. Differentiation of Inflammation-Responsive Astrocytes from Glial Progenitors Generated from Human Induced Pluripotent Stem Cells.

    Science.gov (United States)

    Santos, Renata; Vadodaria, Krishna C; Jaeger, Baptiste N; Mei, Arianna; Lefcochilos-Fogelquist, Sabrina; Mendes, Ana P D; Erikson, Galina; Shokhirev, Maxim; Randolph-Moore, Lynne; Fredlender, Callie; Dave, Sonia; Oefner, Ruth; Fitzpatrick, Conor; Pena, Monique; Barron, Jerika J; Ku, Manching; Denli, Ahmet M; Kerman, Bilal E; Charnay, Patrick; Kelsoe, John R; Marchetto, Maria C; Gage, Fred H

    2017-06-06

    Astrocyte dysfunction and neuroinflammation are detrimental features in multiple pathologies of the CNS. Therefore, the development of methods that produce functional human astrocytes represents an advance in the study of neurological diseases. Here we report an efficient method for inflammation-responsive astrocyte generation from induced pluripotent stem cells (iPSCs) and embryonic stem cells. This protocol uses an intermediate glial progenitor stage and generates functional astrocytes that show levels of glutamate uptake and calcium activation comparable with those observed in human primary astrocytes. Stimulation of stem cell-derived astrocytes with interleukin-1β or tumor necrosis factor α elicits a strong and rapid pro-inflammatory response. RNA-sequencing transcriptome profiling confirmed that similar gene expression changes occurred in iPSC-derived and primary astrocytes upon stimulation with interleukin-1β. This protocol represents an important tool for modeling in-a-dish neurological diseases with an inflammatory component, allowing for the investigation of the role of diseased astrocytes in neuronal degeneration. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  7. How do glial cells contribute to motor control?

    DEFF Research Database (Denmark)

    Christensen, Rasmus Kordt; Petersen, Anders Victor; Perrier, Jean-Francois Marie

    2013-01-01

    that glia play an active role in several physiological functions. The discovery that a bidirectional communication takes place between astrocytes (the star shaped glial cell of the brain) and neurons, was a major breakthrough in the field of synaptic physiology. Astrocytes express receptors that get...... activated by neurotransmitters during synaptic transmission. In turn they release other transmitters - called gliotransmitters - that bind to neuronal receptors and modulate synaptic transmission. This feedback, which led to the concept of the tripartite synapse, has been reported with various transmitters...... including glutamate, ATP, GABA or serine. In the present review we will focus on astrocytes and review the evidence suggesting and demonstrating their role in motor control. Rhythmic motor behaviors such as locomotion, swimming or chewing are generated by networks of neurons termed central pattern...

  8. Regulation of radial glial survival by signals from the meninges.

    Science.gov (United States)

    Radakovits, Randor; Barros, Claudia S; Belvindrah, Richard; Patton, Bruce; Müller, Ulrich

    2009-06-17

    Radial glial cells (RGCs) in the developing cerebral cortex are progenitors for neurons and glia, and their processes serve as guideposts for migrating neurons. So far, it has remained unclear whether RGC processes also control the function of RGCs more directly. Here, we show that RGC numbers and cortical size are reduced in mice lacking beta1 integrins in RGCs. TUNEL stainings and time-lapse video recordings demonstrate that beta1-deficient RGCs processes detach from the meningeal basement membrane (BM) followed by apoptotic death of RGCs. Apoptosis is also induced by surgical removal of the meninges. Finally, mice lacking the BM components laminin alpha2 and alpha4 show defects in the attachment of RGC processes at the meninges, a reduction in cortical size, and enhanced apoptosis of RGC cells. Our findings demonstrate that attachment of RGC processes at the meninges is important for RGC survival and the control of cortical size.

  9. CSF glial markers correlate with survival in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Süssmuth, S D; Sperfeld, A D; Hinz, A; Brettschneider, J; Endruhn, S; Ludolph, A C; Tumani, H

    2010-03-23

    In neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), CSF biomarkers are increasingly studied to evaluate their relevance for differential diagnosis, disease progression, and understanding of pathophysiologic processes. To identify a biomarker profile of neuronal and glial CSF proteins to discriminate ALS from other motor neuron diseases (MND) and to assess whether baseline levels of CSF measures in ALS are associated with the course of the disease. A total of 122 consecutive subjects with MND were included in this cross-sectional study (ALS, n = 75; lower motor neuron syndrome, n = 39; upper motor neuron diseases, n = 8). Clinical follow-up included 76 patients. We determined baseline levels of protein tau and astroglial S100beta in CSF and microglial sCD14 in CSF and serum in relation to diagnosis, duration of disease, and survival. CSF tau was significantly elevated in ALS and upper motor neuron diseases as compared to lower motor neuron diseases and controls. CSF S100beta levels were significantly lower in lower motor neuron diseases as compared to other MND. CSF concentrations of S100beta and sCD14 correlated with the survival time in patients with ALS. In motor neuron diseases, CSF tau elevation indicates the degeneration of upper motor neurons, while S100 beta and sCD14 may indicate the activation of CNS glial cells. Because S100beta and sCD14 concentrations correlate with survival in amyotrophic lateral sclerosis (ALS), we suppose that the combination of both markers may be useful to obtain prognostic information in patients with ALS.

  10. Depression as a Glial-Based Synaptic Dysfunction

    Directory of Open Access Journals (Sweden)

    Daniel eRial

    2016-01-01

    Full Text Available Recent studies combining pharmacological, behavioral, electrophysiological and molecular approaches indicate that depression results from maladaptive neuroplastic processing occurring in defined frontolimbic circuits responsible for emotional processing such as the prefrontal cortex, hippocampus, amygdala and ventral striatum. However, the exact mechanisms controlling synaptic plasticity that are disrupted to trigger depressive conditions have not been elucidated. Since glial cells (astrocytes and microglia tightly and dynamically interact with synapses, engaging a bi-directional communication critical for the processing of synaptic information, we now revisit the role of glial cells in the etiology of depression focusing on a dysfunction of the ‘quad-partite’ synapse. This interest is supported by the observations that depressive-like conditions are associated with a decreased density and hypofunction of astrocytes and with an increase microglia ‘activation’ in frontolimbic regions, which is expected to contribute for the synaptic dysfunction present in depression. Furthermore, the traditional culprits of depression (glucocorticoids, biogenic amines, BDNF affect glia functioning, whereas antidepressant treatments (SSRIs, electroshock, deep brain stimulation recover glia functioning. In this context of a quad-partite synapse, systems modulating glia-synapse bidirectional communication - such as the purinergic neuromodulation system operated by ATP and adenosine - emerge as promising candidates to re-normalize synaptic function by combining direct synaptic effects with an ability to also control astrocyte and microglia function. This proposed triple action of purines to control aberrant synaptic function illustrates the rationale to consider the interference with glia dysfunction as a mechanism of action driving the design of future pharmacological tools to manage depression.

  11. Bone tumor

    Science.gov (United States)

    Tumor - bone; Bone cancer; Primary bone tumor; Secondary bone tumor; Bone tumor - benign ... The cause of bone tumors is unknown. They often occur in areas of the bone that grow rapidly. Possible causes include: Genetic defects ...

  12. Measuring ERCC1 protein expression in cancer specimens

    DEFF Research Database (Denmark)

    Smith, David Hersi; Fiehn, Anne-Marie Kanstrup; Fogh, Louise

    2014-01-01

    Platinum chemotherapy remains part of standard therapies in the management of a variety of cancers. Severe side effects and a high degree of resistance to platinum drugs have led numerous researchers to search for predictive biomarkers, which could aid in identifying patients that are the most......, the specificity of antibody 4F9 was tested by immunoblotting, immunohistochemistry and immunofluorescence. Scoring guidelines to aid in the evaluation of ERCC1 tumor expression were developed and evaluated in archival formalin-fixed paraffin embedded colorectal cancer specimens. Antibody 4F9 was found...... to be specific by all methods applied and it was possible to evaluate the ERCC1 expression in the majority (85%) of colorectal cancer tumor specimens....

  13. The Drosophila blood-brain barrier: Development and function of a glial endothelium

    Directory of Open Access Journals (Sweden)

    Stefanie eLimmer

    2014-11-01

    Full Text Available The efficacy of neuronal function requires a well-balanced extracellular ion homeostasis and a steady supply with nutrients and metabolites. Therefore, all organisms equipped with a complex nervous system developed a so-called blood-brain barrier, protecting it from an uncontrolled entry of solutes, metabolites or pathogens. In higher vertebrates, this diffusion barrier is established by polarized endothelial cells that form extensive tight junctions, whereas in lower vertebrates and invertebrates the blood-brain barrier is exclusively formed by glial cells. Here, we review the development and function of the glial blood-brain barrier of Drosophila melanogaster. In the Drosophila nervous system, at least seven morphologically distinct glial cell classes can be distinguished. Two of these glial classes form the blood-brain barrier. Perineurial glial cells participate in nutrient uptake and establish a first diffusion barrier. The subperineurial glial cells form septate junctions, which block paracellular diffusion and thus seal the nervous system from the hemolymph. We summarize the molecular basis of septate junction formation and address the different transport systems expressed by the blood-brain barrier forming glial cells.

  14. Sodium channels in axons and glial cells of the optic nerve of Necturus maculosa.

    Science.gov (United States)

    Tang, C M; Strichartz, G R; Orkand, R K

    1979-11-01

    Experiments investigating both the binding of radioactively labelled saxitoxin (STX) and the electrophysiological response to drugs that increase the sodium permeability of excitable membranes were conducted in an effort to detect sodium channels in glial cells of the optic nerve of Necturus maculosa, the mudpuppy. Glial cells in nerves from chronically enucleated animals, which lack optic nerve axons, show no saturable uptake of STX whereas a saturable uptake is clearly present in normal optic nerves. The normal nerve is depolarized by aconitine, batrachotoxin, and veratridine (10(-6)-10(-5) M), whereas the all-glial preparation is only depolarized by veratridine and at concentrations greater than 10(-3) M. Unlike the depolarization caused by veratridine in normal nerves, the response in the all-glial tissue is not blocked by tetrodotoxin nor enhanced by scorpion venom (Leiurus quinquestriatus). In glial cells of the normal nerve, where axons are also present, the addition of 10(-5) M veratridine does lead to a transient depolarization; however, it is much briefer than the axonal response to veratridine in this same tissue. This glial response to veratridine could be caused by the efflux of K+ from the drug-depolarized axons, and is similar to the glial response to extracellular K+ accumulation resulting from action potentials in the axon.

  15. The Drosophila blood-brain barrier: development and function of a glial endothelium.

    Science.gov (United States)

    Limmer, Stefanie; Weiler, Astrid; Volkenhoff, Anne; Babatz, Felix; Klämbt, Christian

    2014-01-01

    The efficacy of neuronal function requires a well-balanced extracellular ion homeostasis and a steady supply with nutrients and metabolites. Therefore, all organisms equipped with a complex nervous system developed a so-called blood-brain barrier, protecting it from an uncontrolled entry of solutes, metabolites or pathogens. In higher vertebrates, this diffusion barrier is established by polarized endothelial cells that form extensive tight junctions, whereas in lower vertebrates and invertebrates the blood-brain barrier is exclusively formed by glial cells. Here, we review the development and function of the glial blood-brain barrier of Drosophila melanogaster. In the Drosophila nervous system, at least seven morphologically distinct glial cell classes can be distinguished. Two of these glial classes form the blood-brain barrier. Perineurial glial cells participate in nutrient uptake and establish a first diffusion barrier. The subperineurial glial (SPG) cells form septate junctions, which block paracellular diffusion and thus seal the nervous system from the hemolymph. We summarize the molecular basis of septate junction formation and address the different transport systems expressed by the blood-brain barrier forming glial cells.

  16. Macrophage-Mediated Glial Cell Elimination in the Postnatal Mouse Cochlea

    Directory of Open Access Journals (Sweden)

    LaShardai N. Brown

    2017-12-01

    Full Text Available Hearing relies on the transmission of auditory information from sensory hair cells (HCs to the brain through the auditory nerve. This relay of information requires HCs to be innervated by spiral ganglion neurons (SGNs in an exclusive manner and SGNs to be ensheathed by myelinating and non-myelinating glial cells. In the developing auditory nerve, mistargeted SGN axons are retracted or pruned and excessive cells are cleared in a process referred to as nerve refinement. Whether auditory glial cells are eliminated during auditory nerve refinement is unknown. Using early postnatal mice of either sex, we show that glial cell numbers decrease after the first postnatal week, corresponding temporally with nerve refinement in the developing auditory nerve. Additionally, expression of immune-related genes was upregulated and macrophage numbers increase in a manner coinciding with the reduction of glial cell numbers. Transient depletion of macrophages during early auditory nerve development, using transgenic CD11bDTR/EGFP mice, resulted in the appearance of excessive glial cells. Macrophage depletion caused abnormalities in myelin formation and transient edema of the stria vascularis. Macrophage-depleted mice also showed auditory function impairment that partially recovered in adulthood. These findings demonstrate that macrophages contribute to the regulation of glial cell number during postnatal development of the cochlea and that glial cells play a critical role in hearing onset and auditory nerve maturation.

  17. An Adenosine-Mediated Glial-Neuronal Circuit for Homeostatic Sleep.

    Science.gov (United States)

    Bjorness, Theresa E; Dale, Nicholas; Mettlach, Gabriel; Sonneborn, Alex; Sahin, Bogachan; Fienberg, Allen A; Yanagisawa, Masashi; Bibb, James A; Greene, Robert W

    2016-03-30

    Sleep homeostasis reflects a centrally mediated drive for sleep, which increases during waking and resolves during subsequent sleep. Here we demonstrate that mice deficient for glial adenosine kinase (AdK), the primary metabolizing enzyme for adenosine (Ado), exhibit enhanced expression of this homeostatic drive by three independent measures: (1) increased rebound of slow-wave activity; (2) increased consolidation of slow-wave sleep; and (3) increased time constant of slow-wave activity decay during an average slow-wave sleep episode, proposed and validated here as a new index for homeostatic sleep drive. Conversely, mice deficient for the neuronal adenosine A1 receptor exhibit significantly decreased sleep drive as judged by these same indices. Neuronal knock-out of AdK did not influence homeostatic sleep need. Together, these findings implicate a glial-neuronal circuit mediated by intercellular Ado, controlling expression of homeostatic sleep drive. Because AdK is tightly regulated by glial metabolic state, our findings suggest a functional link between cellular metabolism and sleep homeostasis. The work presented here provides evidence for an adenosine-mediated regulation of sleep in response to waking (i.e., homeostatic sleep need), requiring activation of neuronal adenosine A1 receptors and controlled by glial adenosine kinase. Adenosine kinase acts as a highly sensitive and important metabolic sensor of the glial ATP/ADP and AMP ratio directly controlling intracellular adenosine concentration. Glial equilibrative adenosine transporters reflect the intracellular concentration to the extracellular milieu to activate neuronal adenosine receptors. Thus, adenosine mediates a glial-neuronal circuit linking glial metabolic state to neural-expressed sleep homeostasis. This indicates a metabolically related function(s) for this glial-neuronal circuit in the buildup and resolution of our need to sleep and suggests potential therapeutic targets more directly related to

  18. DNA synthesis during development and proliferation of glial cells in organotypic rat cerebellar culture

    International Nuclear Information System (INIS)

    Renkawek, K.

    1977-01-01

    DNA synthesis was investigated in glial cells in vitro with 3 H thymidine in concentration 1 μCi/ml medium. Incorporation of isotope into the glial nuclei has been found both in the explant (7-21%) and in the outgrowth (22-56%). DNA synthesis was dependent on the age of culture and due to the contact inhibition in the outgrowth. Results point out that marked DNA synthesis is a characteristic feature of glia differentiation and of reactive character of glial cells in vitro. (author)

  19. Riding the glial monorail: a common mechanism for glial-guided neuronal migration in different regions of the developing mammalian brain.

    Science.gov (United States)

    Hatten, M E

    1990-05-01

    In vitro studies from our laboratory indicate that granule neurons, purified from early postnatal mouse cerebellum, migrate on astroglial fibers by forming a 'migration junction' with the glial fiber along the length of the neuronal soma and extending a motile 'leading process' in the direction of migration. Similar dynamics are seen for hippocampal neurons migrating along hippocampal astroglial fibers in vitro. In heterotypic recombinations of neurons and glia from mouse cerebellum and rat hippocampus, neurons migrate on astroglial processes with a cytology and neuron-glia relationship identical to that of homotypic neuronal migration in vitro. In all four cases, the migrating neuron presents a stereotyped posture, speed and mode of movement, suggesting that glial fibers provide a generic pathway for neuronal migration in developing brain. Studies on the molecular basis of glial-guided migration suggest that astrotactin, a neuronal antigen that functions as a neuron-glia ligand, is likely to play a crucial role in the locomotion of the neuron along glial fibers. The navigation of neurons from glial fibers into cortical layers, in turn, is likely to involve neuron-neuron adhesion ligands.

  20. Magnetic resonance imaging-based detection of glial brain tumors in mice after antiangiogenic treatment.

    NARCIS (Netherlands)

    Claes, A.; Gambarota, G.; Hamans, B.C.; Tellingen, O. van; Wesseling, P.; Maass, C.N.; Heerschap, A.; Leenders, W.P.J.

    2008-01-01

    Proper delineation of gliomas using contrast-enhanced magnetic resonance imaging (CE-MRI) poses a problem in neuro-oncology. The blood brain barrier (BBB) in areas of diffuse-infiltrative growth may be intact, precluding extravasation and subsequent MR-based detection of the contrast agent

  1. Glial tumors in brodmann area 6: spread pattern and relationships to motor areas.

    Science.gov (United States)

    Shah, Komal B; Hayman, L Anne; Chavali, Lakshmi S; Hamilton, Jackson D; Prabhu, Sujit S; Wangaryattawanich, Pattana; Kumar, Vinodh A; Kumar, Ashok J

    2015-01-01

    The posterior frontal lobe of the brain houses Brodmann area 4, which is the primary motor cortex, and Brodmann area 6, which consists of the supplementary motor area on the medial portion of the hemisphere and the premotor cortex on the lateral portion. In this area, safe resection is dependent on accurate localization of the motor cortex and the central sulcus, which can usually be achieved by using thin-section imaging and confirmed by using other techniques. The most reliable anatomic landmarks are the "hand knob" area and the marginal ramus of the cingulate sulcus. Postoperatively, motor deficits can occur not only because of injury to primary motor cortex but also because of injury to the supplementary motor area. Unlike motor cortex injury, the supplementary motor area syndrome is transient, if it occurs at all. On the lateral hemisphere, motor and language deficits can also occur because of premotor cortex injury, but a dense motor deficit would indicate subcortical injury to the corticospinal tract. The close relationship of the subcortical motor fibers and premotor cortex is illustrated. In contrast to the more constant landmarks of the central sulcus and marginal ramus, which aid in preoperative localization, the variable interruptions in the precentral and cingulate sulci of the posterior frontal lobe seem to provide "cortical bridges" for spread of infiltrating gliomas. (©)RSNA, 2015.

  2. Carboplatin hypersensitivity in children with glial tumors: a report of two cases

    Directory of Open Access Journals (Sweden)

    Tugce Kazgan

    2016-12-01

    Full Text Available Carboplatin, commonly used chemotherapeutic agent in treatment of pediatric cancers, can cause life-threatening hypersensitivty reactions. Carboplatin hypersensitivity is protocol-specific and associated with repeated doses and prolonged use of the drug. Vincristin and carboplatin combination is used efficiently in treatment of pediatric low-grade gliomas. However, hypersensitivity reactions are frequently observed during usage of this protocol. Desensitization strategies with variable success rates were reported. Failure of these strategies may lead to cessation of carboplatin Here, we report two cases with carboplatin hypersensitivity treated with epinephrine administration, in whom carboplatin was discontinued after hypersensitivity reaction. [Cukurova Med J 2016; 41(4.000: 796-798

  3. Social Behavior in Medulloblastoma: Functional Analysis of Tumor-Supporting Glial Cells

    Science.gov (United States)

    2015-10-01

    the manuscript with inputs from all authors. All authors reviewed the manuscript. Acknowledgements We thank Chris Doe, David Rowitch, and Praveen...201–208. Goodrich, L.V., Milenković, L., Higgins , K.M., and Scott, M.P. (1997). Altered Neural Cell Fates and Medulloblastoma in Mouse patched...Genes & Development 27, 98–115. Goodrich, L.V., Milenković, L., Higgins , K.M., and Scott, M.P. (1997). Altered Neural Cell Fates and Medulloblastoma in

  4. HER2 testing on core needle biopsy specimens from primary breast cancers: interobserver reproducibility and concordance with surgically resected specimens

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    Yamamoto Sohei

    2010-10-01

    Full Text Available Abstract Background Accurate evaluation of human epidermal growth factor receptor type-2 (HER2 status based on core needle biopsy (CNB specimens is mandatory for identification of patients with primary breast cancer who will benefit from primary systemic therapy with trastuzumab. The aim of the present study was to validate the application of HER2 testing with CNB specimens from primary breast cancers in terms of interobserver reproducibility and comparison with surgically resected specimens. Methods A total of 100 pairs of archival formalin-fixed paraffin-embedded CNB and surgically resected specimens of invasive breast carcinomas were cut into sections. All 100 paired sections were subjected to HER2 testing by immunohistochemistry (IHC and 27 paired sections were subjected to that by fluorescence in situ hybridization (FISH, the results being evaluated by three and two observers, respectively. Interobserver agreement levels in terms of judgment and the concordance of consensus scores between CNB samples and the corresponding surgically resected specimens were estimated as the percentage agreement and κ statistic. Results In CNB specimens, the percentage interobserver agreement of HER2 scoring by IHC was 76% (κ = 0.71 for 3 × 3 categories (0-1+ versus 2+ versus 3+ and 90% (κ = 0.80 for 2 × 2 categories (0-2+ versus 3+. These levels were close to the corresponding ones for the surgically resected specimens: 80% (κ = 0.77 for 3 × 3 categories and 92% (κ = 0.88 for 2 × 2 categories. Concordance of consensus for HER2 scores determined by IHC between CNB and the corresponding surgical specimens was 87% (κ = 0.77 for 3 × 3 categories, and 94% (κ = 0.83 for 2 × 2 categories. Among the 13 tumors showing discordance in the mean IHC scores between the CNB and surgical specimens, the results of consensus for FISH results were concordant in 11. The rate of successful FISH analysis and the FISH positivity rate in cases with a HER2 IHC score of

  5. HER2 testing on core needle biopsy specimens from primary breast cancers: interobserver reproducibility and concordance with surgically resected specimens

    International Nuclear Information System (INIS)

    Tsuda, Hitoshi; Kurosumi, Masafumi; Umemura, Shinobu; Yamamoto, Sohei; Kobayashi, Takayuki; Osamura, Robert Yoshiyuki

    2010-01-01

    Accurate evaluation of human epidermal growth factor receptor type-2 (HER2) status based on core needle biopsy (CNB) specimens is mandatory for identification of patients with primary breast cancer who will benefit from primary systemic therapy with trastuzumab. The aim of the present study was to validate the application of HER2 testing with CNB specimens from primary breast cancers in terms of interobserver reproducibility and comparison with surgically resected specimens. A total of 100 pairs of archival formalin-fixed paraffin-embedded CNB and surgically resected specimens of invasive breast carcinomas were cut into sections. All 100 paired sections were subjected to HER2 testing by immunohistochemistry (IHC) and 27 paired sections were subjected to that by fluorescence in situ hybridization (FISH), the results being evaluated by three and two observers, respectively. Interobserver agreement levels in terms of judgment and the concordance of consensus scores between CNB samples and the corresponding surgically resected specimens were estimated as the percentage agreement and κ statistic. In CNB specimens, the percentage interobserver agreement of HER2 scoring by IHC was 76% (κ = 0.71) for 3 × 3 categories (0-1+ versus 2+ versus 3+) and 90% (κ = 0.80) for 2 × 2 categories (0-2+ versus 3+). These levels were close to the corresponding ones for the surgically resected specimens: 80% (κ = 0.77) for 3 × 3 categories and 92% (κ = 0.88) for 2 × 2 categories. Concordance of consensus for HER2 scores determined by IHC between CNB and the corresponding surgical specimens was 87% (κ = 0.77) for 3 × 3 categories, and 94% (κ = 0.83) for 2 × 2 categories. Among the 13 tumors showing discordance in the mean IHC scores between the CNB and surgical specimens, the results of consensus for FISH results were concordant in 11. The rate of successful FISH analysis and the FISH positivity rate in cases with a HER2 IHC score of 2+ differed among specimens processed at

  6. Clinicopathologic features of incidental prostatic adenocarcinoma in radical cystoprostatectomy specimens

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    Vuruskan Hakan

    2011-07-01

    Full Text Available Abstract Background The aim of this study is to review all features of incidentally discovered prostate adenocarcinoma in patients undergoing radical cystoprostatectomy for bladder cancer. Methods The medical charts of 300 male patients who underwent radical cystoprostatectomy for bladder cancer between 1997 and 2005 were retrospectively reviewed. The mean age of the patients was 62 (range 51-75 years. Results Prostate adenocarcinoma was present in 60 (20% of 300 specimens. All were acinar adenocarcinoma. Of these, 40 (66.7% were located in peripheral zone, 20 (33.3% had pT2a tumor, 12 (20% had pT2b tumor, 22(36.7% had pT2c and, 6 (10% had pT3a tumor. Gleason score was 6 or less in 48 (80% patients. Surgical margins were negative in 54 (90% patients, and tumor volume was less than 0.5 cc in 23 (38.3% patients. Of the 60 incidentally detected cases of prostate adenocarcinoma 40 (66.7% were considered clinically significant. Conclusion Incidentally detected prostate adenocarcinoma is frequently observed in radical cystoprostatectomy specimens. The majority are clinically significant.

  7. A New Outlook on Mental Illnesses: Glial Involvement Beyond the Glue

    KAUST Repository

    Elsayed, Maha

    2015-12-16

    Mental illnesses have long been perceived as the exclusive consequence of abnormalities in neuronal functioning. Until recently, the role of glial cells in the pathophysiology of mental diseases has largely been overlooked. However recently, multiple lines of evidence suggest more diverse and significant functions of glia with behavior-altering effects. The newly ascribed roles of astrocytes, oligodendrocytes and microglia have led to their examination in brain pathology and mental illnesses. Indeed, abnormalities in glial function, structure and density have been observed in postmortem brain studies of subjects diagnosed with mental illnesses. In this review, we discuss the newly identified functions of glia and highlight the findings of glial abnormalities in psychiatric disorders. We discuss these preclinical and clinical findings implicating the involvement of glial cells in mental illnesses with the perspective that these cells may represent a new target for treatment.

  8. Injury-induced ctgfa directs glial bridging and spinal cord regeneration in zebrafish

    Science.gov (United States)

    Mokalled, Mayssa H.; Patra, Chinmoy; Dickson, Amy L.; Endo, Toyokazu; Stainier, Didier Y. R.; Poss, Kenneth D.

    2016-01-01

    Unlike mammals, zebrafish efficiently regenerate functional nervous system tissue after major spinal cord injury. Whereas glial scarring presents a roadblock for mammalian spinal cord repair, glial cells in zebrafish form a bridge across severed spinal cord tissue and facilitate regeneration, a relatively unexplored process. Here, we performed a genome-wide profiling screen for secreted factors that are upregulated during zebrafish spinal cord regeneration. We find that connective tissue growth factor a (ctgfa) is induced in and around glial cells that participate in initial bridging events. Mutations in ctgfa disrupt spinal cord repair, while transgenic ctgfa overexpression and local human CTGF recombinant protein delivery accelerate bridging and functional regeneration. Our study reveals that CTGF is necessary and sufficient to stimulate glial bridging and natural spinal cord regeneration. PMID:27811277

  9. A New Outlook on Mental Illnesses: Glial Involvement Beyond the Glue

    KAUST Repository

    Elsayed, Maha; Magistretti, Pierre J.

    2015-01-01

    Mental illnesses have long been perceived as the exclusive consequence of abnormalities in neuronal functioning. Until recently, the role of glial cells in the pathophysiology of mental diseases has largely been overlooked. However recently, multiple lines of evidence suggest more diverse and significant functions of glia with behavior-altering effects. The newly ascribed roles of astrocytes, oligodendrocytes and microglia have led to their examination in brain pathology and mental illnesses. Indeed, abnormalities in glial function, structure and density have been observed in postmortem brain studies of subjects diagnosed with mental illnesses. In this review, we discuss the newly identified functions of glia and highlight the findings of glial abnormalities in psychiatric disorders. We discuss these preclinical and clinical findings implicating the involvement of glial cells in mental illnesses with the perspective that these cells may represent a new target for treatment.

  10. Innovations in macroscopic evaluation of pancreatic specimens and radiologic correlation

    Directory of Open Access Journals (Sweden)

    Charikleia Triantopoulou

    2016-01-01

    Full Text Available The purpose of this study was to evaluate the feasibility of a novel dissection technique of surgical specimens in different cases of pancreatic tumors and provide a radiologic pathologic correlation. In our hospital, that is a referral center for pancreatic diseases, the macroscopic evaluation of the pancreatectomy specimens is performed by the pathologists using the axial slicing technique (instead of the traditional procedure with longitudinal opening of the main pancreatic and/or common bile duct and slicing along the plane defined by both ducts. The specimen is sliced in an axial plane that is perpendicular to the longitudinal axis of the descending duodenum. The procedure results in a large number of thin slices (3–4 mm. This plane is identical to that of CT or MRI and correlation between pathology and imaging is straightforward. We studied 70 cases of suspected different solid and cystic pancreatic tumors and we correlated the tumor size and location, the structure—consistency (areas of necrosis—hemorrhage—fibrosis—inflammation, the degree of vessels’ infiltration, the size of pancreatic and common bile duct and the distance from resection margins. Missed findings by imaging or pitfalls were recorded and we tried to explain all discrepancies between radiology evaluation and the histopathological findings. Radiologic-pathologic correlation is extremely important, adding crucial information on imaging limitations and enabling quality assessment of surgical specimens. The deep knowledge of different pancreatic tumors’ consistency and way of extension helps to improve radiologists’ diagnostic accuracy and minimize the radiological-surgical mismatching, preventing patients from unnecessary surgery.

  11. TDP-43 causes differential pathology in neuronal versus glial cells in the mouse brain.

    Science.gov (United States)

    Yan, Sen; Wang, Chuan-En; Wei, Wenjie; Gaertig, Marta A; Lai, Liangxue; Li, Shihua; Li, Xiao-Jiang

    2014-05-15

    Mutations in TAR DNA-binding protein 43 (TDP-43) are associated with familial forms of amyotrophic lateral sclerosis and frontotemporal lobar degeneration. Although recent studies have revealed that mutant TDP-43 in neuronal and glial cells is toxic, how mutant TDP-43 causes primarily neuronal degeneration in an age-dependent manner remains unclear. Using adeno-associated virus (AAV) that expresses mutant TDP-43 (M337V) ubiquitously, we found that mutant TDP-43 accumulates preferentially in neuronal cells in the postnatal mouse brain. We then ubiquitously or selectively expressed mutant TDP-43 in neuronal and glial cells in the striatum of adult mouse brains via stereotaxic injection of AAV vectors and found that it also preferentially accumulates in neuronal cells. Expression of mutant TDP-43 in neurons in the striatum causes more severe degeneration, earlier death and more robust symptoms in mice than expression of mutant TDP-43 in glial cells; however, aging increases the expression of mutant TDP-43 in glial cells, and expression of mutant TDP-43 in older mice caused earlier onset of phenotypes and more severe neuropathology than that in younger mice. Although expression of mutant TDP-43 in glial cells via stereotaxic injection does not lead to robust neurological phenotypes, systemic inhibition of the proteasome activity via MG132 in postnatal mice could exacerbate glial TDP-43-mediated toxicity and cause mice to die earlier. Consistently, this inhibition increases the expression of mutant TDP-43 in glial cells in mouse brains. Thus, the differential accumulation of mutant TDP-43 in neuronal versus glial cells contributes to the preferential toxicity of mutant TDP-43 in neuronal cells and age-dependent pathology.

  12. Implications of glial nitric oxyde in neurodegenerative diseases

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    Jose Enrique eYuste

    2015-08-01

    Full Text Available Nitric oxide (NO is a pleiotropic janus-faced molecule synthesized by nitric oxide synthases (NOS which plays a critical role in a number of physiological and pathological processes in humans. The physiological roles of NO depend on its local concentrations, as well as its availability and the nature of downstream target molecules. Its double-edged sword action has been linked to neurodegenerative disorders. Excessive NO production, as the evoked by inflammatory signals, has been identified as one of the major causative reasons for the pathogenesis of several neurodegenerative diseases. Moreover, excessive NO synthesis under neuroinflammation leads to the formation of reactive nitrogen species and neuronal cell death. There is an intimate relation between microglial activation, NO and neuroinflammation in the human brain. The role of NO in neuroinflammation has been defined in animal models where this neurotransmitter can modulate the inflammatory process acting on key regulatory pathways, such as those associated with excitotoxicity processes induced by glutamate accumulation and microglial activation. Activated glia express inducible NOS and produce NO that triggers calcium mobilization from the endoplasmic reticulum, activating the release of vesicular glutamate from astroglial cells resulting in neuronal death. This change in microglia potentially contributes to the increased age-associated susceptibility and neurodegeneration. In the current review, information is provided about the role of NO, glial activation and age-related processes in the central nervous system (CNS that may be helpful in the isolation of new therapeutic targets for aging and neurodegenerative diseases.

  13. Endothelium in brain: Receptors, mitogenesis, and biosynthesis in glial cells

    International Nuclear Information System (INIS)

    MacCumber, M.W.; Ross, C.A.; Snyder, S.H.

    1990-01-01

    The authors have explored the cellular loci of endothelin (ET) actions and formation in the brain, using cerebellar mutant mice was well as primary and continuous cell cultures. A glial role is favored by several observations: (1) mutant mice lacking neuronal Purkinje cells display normal ET receptor binding and enhanced stimulation by ET of inositolphospholipid turnover; (ii) in weaver mice lacking neuronal granule cells, ET stimulation of inositolphospholipid turnover is not significantly diminished; (iii) C 6 glioma cells and primary cultures of cerebellar astroglia exhibit substantial ET receptor binding and ET-induced stimulation of inositolphospholipid turnover; (iv) ET promotes mitogenesis of C 6 glioma cells and primary cerebellar astroglia; and (v) primary cultures of cerebellar astroglia contain ET mRNA. ET also appears to have a neuronal role, since it stimulates inositolphospholipid turnover in primary cultures of cerebellar granule cells, and ET binding declines in granule cell-deficient mice. Thus, ET can be produced by glia and act upon both glia and neurons in a paracrine fashion

  14. Proliferation of differentiated glial cells in the brain stem

    Directory of Open Access Journals (Sweden)

    P.C. Barradas

    1998-02-01

    Full Text Available Classical studies of macroglial proliferation in muride rodents have provided conflicting evidence concerning the proliferating capabilities of oligodendrocytes and microglia. Furthermore, little information has been obtained in other mammalian orders and very little is known about glial cell proliferation and differentiation in the subclass Metatheria although valuable knowledge may be obtained from the protracted period of central nervous system maturation in these forms. Thus, we have studied the proliferative capacity of phenotypically identified brain stem oligodendrocytes by tritiated thymidine radioautography and have compared it with known features of oligodendroglial differentiation as well as with proliferation of microglia in the opossum Didelphis marsupialis. We have detected a previously undescribed ephemeral, regionally heterogeneous proliferation of oligodendrocytes expressing the actin-binding, ensheathment-related protein 2'3'-cyclic nucleotide 3'-phosphodiesterase (CNPase, that is not necessarily related to the known regional and temporal heterogeneity of expression of CNPase in cell bodies. On the other hand, proliferation of microglia tagged by the binding of Griffonia simplicifolia B4 isolectin, which recognizes an alpha-D-galactosyl-bearing glycoprotein of the plasma membrane of macrophages/microglia, is known to be long lasting, showing no regional heterogeneity and being found amongst both ameboid and differentiated ramified cells, although at different rates. The functional significance of the proliferative behavior of these differentiated cells is unknown but may provide a low-grade cell renewal in the normal brain and may be augmented under pathological conditions.

  15. Bone tumors

    International Nuclear Information System (INIS)

    Unni, K.K.

    1988-01-01

    This book contains the proceedings on bone tumors. Topics covered include: Bone tumor imaging: Contribution of CT and MRI, staging of bone tumors, perind cell tumors of bone, and metastatic bone disease

  16. Stereotactic Radiosurgery for Intracranial Tumors : Early Experience with Linear Accelerator

    Energy Technology Data Exchange (ETDEWEB)

    Shu, Chang Ok; Chung, Sang Sup; Chu, Sung Sil; Kim, Young Soo; Yoon, Do Heum; Kim, Sun Ho; Loh, John Juhn; Kim, Gwi Eon [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    1992-06-15

    Between August 1988 and December 1991, 24 patients with intracranial tumors were treated with stereotactic radiosurgery(RS) using a 10 MV linear accelerator at Severance Hospital, Yonsei University College of Medicine. There were 5 meningiomas, 3 craniopharyngiomas, 9 glial tumors, 2 solitary metastases, 2 acoustic neurinomas, 2 pineal tumors, and 1 non-Hodgkin Iymphoma. Ten patients were treated as primary treatment after diagnosis with stereotactic biopsy or neuroimaging study. Nine patients underwent RS for post-op. residual tumors and three patients as a salvage treatment for recurrence after external irradiation. Two patients received RS as a boost followed by fractionated conventional radiotherapy. Among sixteen patients who were followed more than 6 months with neuroimage, seven patients (2 meningiomas, 4 benign glial tumors, one non-Hodgkin lymphoma) showed complete response on neuroimage after RS and nine patients showed decreased tumor size. There was no acute treatment related side reaction. Late complications include three patients with symptomatic peritumoral braid edema and one craniopharyngioma with optic chiasmal injury. Through this early experience, we conclude that stereotactically directed single high doses of irradiation to the small intracranial tumors is effective for tumor control. However, in order to define the role of radiosurgery in the management of intracranial tumors, we should get the long-term results available to demonstrate the benefits versus potential complications of this therapeutic modality.

  17. Collagen Quantification in Tissue Specimens.

    Science.gov (United States)

    Coentro, João Quintas; Capella-Monsonís, Héctor; Graceffa, Valeria; Wu, Zhuning; Mullen, Anne Maria; Raghunath, Michael; Zeugolis, Dimitrios I

    2017-01-01

    Collagen is the major extracellular protein in mammals. Accurate quantification of collagen is essential in the biomaterials (e.g., reproducible collagen scaffold fabrication), drug discovery (e.g., assessment of collagen in pathophysiologies, such as fibrosis), and tissue engineering (e.g., quantification of cell-synthesized collagen) fields. Although measuring hydroxyproline content is the most widely used method to quantify collagen in biological specimens, the process is very laborious. To this end, the Sircol™ Collagen Assay is widely used due to its inherent simplicity and convenience. However, this method leads to overestimation of collagen content due to the interaction of Sirius red with basic amino acids of non-collagenous proteins. Herein, we describe the addition of an ultrafiltration purification step in the process to accurately determine collagen content in tissues.

  18. The glia doctrine: addressing the role of glial cells in healthy brain ageing.

    Science.gov (United States)

    Nagelhus, Erlend A; Amiry-Moghaddam, Mahmood; Bergersen, Linda H; Bjaalie, Jan G; Eriksson, Jens; Gundersen, Vidar; Leergaard, Trygve B; Morth, J Preben; Storm-Mathisen, Jon; Torp, Reidun; Walhovd, Kristine B; Tønjum, Tone

    2013-10-01

    Glial cells in their plurality pervade the human brain and impact on brain structure and function. A principal component of the emerging glial doctrine is the hypothesis that astrocytes, the most abundant type of glial cells, trigger major molecular processes leading to brain ageing. Astrocyte biology has been examined using molecular, biochemical and structural methods, as well as 3D brain imaging in live animals and humans. Exosomes are extracelluar membrane vesicles that facilitate communication between glia, and have significant potential for biomarker discovery and drug delivery. Polymorphisms in DNA repair genes may indirectly influence the structure and function of membrane proteins expressed in glial cells and predispose specific cell subgroups to degeneration. Physical exercise may reduce or retard age-related brain deterioration by a mechanism involving neuro-glial processes. It is most likely that additional information about the distribution, structure and function of glial cells will yield novel insight into human brain ageing. Systematic studies of glia and their functions are expected to eventually lead to earlier detection of ageing-related brain dysfunction and to interventions that could delay, reduce or prevent brain dysfunction. Copyright © 2013 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  19. Chronic lead intoxication affects glial and neural systems and induces hypoactivity in adult rat.

    Science.gov (United States)

    Sansar, Wafa; Ahboucha, Samir; Gamrani, Halima

    2011-10-01

    Lead is an environmental toxin and its effects are principally manifested in the brain. Glial and neuronal changes have been described during development following chronic or acute lead intoxication, however, little is known about the effects of chronic lead intoxication in adults. In this study we evaluated immunohistochemically the glial and dopaminergic systems in adult male Wistar rats. 0.5% (v/v) lead acetate in drinking water was administrated chronically over a 3-month period. Hypertrophic immunoreactive astrocytes were observed in the frontal cortex and other brain structures of the treated animals. Analysis of the astroglial features showed increased number of astrocyte cell bodies and processes in treated rats, an increase confirmed by Western blot. Particular distribution of glial fibrillary acidic protein immunoreactivity was observed within the blood vessel walls in which dense immunoreactive glial processes emanate from astrocytes. Glial changes in the frontal cortex were concomitant with reduced tyrosine hydroxylase immunoreactive neuronal processes, which seem to occur as a consequence of significantly reduced dopaminergic neurons within the nucleus of origin in the substantia nigra. These glial and neuronal changes following lead intoxication may affect animal behavior as evidenced by reduced locomotor activity in an open field test. These findings demonstrate that chronic lead exposure induces astroglial changes, which may compromise neuronal function and consequently animal behavior. Copyright © 2010 Elsevier GmbH. All rights reserved.

  20. Opioid-Induced Glial Activation: Mechanisms of Activation and Implications for Opioid Analgesia, Dependence, and Reward

    Directory of Open Access Journals (Sweden)

    Mark R. Hutchinson

    2007-01-01

    Full Text Available This review will introduce the concept of toll-like receptor (TLR–mediated glial activation as central to all of the following: neuropathic pain, compromised acute opioid analgesia, and unwanted opioid side effects (tolerance, dependence, and reward. Attenuation of glial activation has previously been demonstrated both to alleviate exaggerated pain states induced by experimental pain models and to reduce the development of opioid tolerance. Here we demonstrate that selective acute antagonism of TLR4 results in reversal of neuropathic pain as well as potentiation of opioid analgesia. Attenuating central nervous system glial activation was also found to reduce the development of opioid dependence, and opioid reward at a behavioral (conditioned place preference and neurochemical (nucleus accumbens microdialysis of morphine-induced elevations in dopamine level of analysis. Moreover, a novel antagonism of TLR4 by (+- and (˗-isomer opioid antagonists has now been characterized, and both antiallodynic and morphine analgesia potentiating activity shown. Opioid agonists were found to also possess TLR4 agonistic activity, predictive of glial activation. Targeting glial activation is a novel and as yet clinically unexploited method for treatment of neuropathic pain. Moreover, these data indicate that attenuation of glial activation, by general or selective TLR antagonistic mechanisms, may also be a clinical method for separating the beneficial (analgesia and unwanted (tolerance, dependence, and reward actions of opioids, thereby improving the safety and efficacy of their use.

  1. Ethanol-Induced Neurodegeneration and Glial Activation in the Developing Brain

    Directory of Open Access Journals (Sweden)

    Mariko Saito

    2016-08-01

    Full Text Available Ethanol induces neurodegeneration in the developing brain, which may partially explain the long-lasting adverse effects of prenatal ethanol exposure in fetal alcohol spectrum disorders (FASD. While animal models of FASD show that ethanol-induced neurodegeneration is associated with glial activation, the relationship between glial activation and neurodegeneration has not been clarified. This review focuses on the roles of activated microglia and astrocytes in neurodegeneration triggered by ethanol in rodents during the early postnatal period (equivalent to the third trimester of human pregnancy. Previous literature indicates that acute binge-like ethanol exposure in postnatal day 7 (P7 mice induces apoptotic neurodegeneration, transient activation of microglia resulting in phagocytosis of degenerating neurons, and a prolonged increase in glial fibrillary acidic protein-positive astrocytes. In our present study, systemic administration of a moderate dose of lipopolysaccharides, which causes glial activation, attenuates ethanol-induced neurodegeneration. These studies suggest that activation of microglia and astrocytes by acute ethanol in the neonatal brain may provide neuroprotection. However, repeated or chronic ethanol can induce significant proinflammatory glial reaction and neurotoxicity. Further studies are necessary to elucidate whether acute or sustained glial activation caused by ethanol exposure in the developing brain can affect long-lasting cellular and behavioral abnormalities observed in the adult brain.

  2. Distinct angiotensin II receptor in primary cultures of glial cells from rat brain

    International Nuclear Information System (INIS)

    Raizada, M.K.; Phillips, M.I.; Crews, F.T.; Sumners, C.

    1987-01-01

    Angiotensin II (Ang-II) has profound effects on the brain. Receptors for Ang-II have been demonstrated on neurons, but no relationship between glial cells and Agn-II has been established. Glial cells (from the hypothalamus and brain stem of 1-day-old rat brains) in primary culture have been used to demonstrate the presence of specific Ang-II receptors. Binding of 125 I-Ang-II to glial cultures was rapid, reversible, saturable, and specific for Ang-II. The rank order of potency of 125 I-Ang-II binding was determined. Scatchard analysis revealed a homogeneous population of high-affinity binding sites with a B/sub max/ of 110 fmol/mg of protein. Light-microscopic autoradiography of 125 I-Ang-II binding supported the kinetic data, documenting specific Ang-II receptors on the glial cells. Ang-II stimulated a dose-dependent hydrolysis of phosphatidylinositols in glial cells, an effect mediated by Ang-II receptors. However, Ang-II failed to influence [ 3 H] norepinephrine uptake, and catecholamines failed to regulate Ang-II receptors, effects that occur in neurons. These observations demonstrate the presence of specific Ang-II receptors on the glial cells in primary cultures derived from normotensive rat brain. The receptors are kinetically similar to, but functionally distinct from, the neuronal Ang-II receptors

  3. Notch effects in uniaxial tension specimens

    International Nuclear Information System (INIS)

    Delph, T.J.

    1979-03-01

    Results of a literature survey on the effect of notches on the time-dependent failure of uniaxial tension specimens at elevated temperatures are presented. Particular attention is paid to the failure of notched specimens containing weldments

  4. Measurements and Counts for Notacanthidae Specimens

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Taxonomic data were collected for specimens of deep-sea spiny eels (Notacanthidae) from the Hawaiian Ridge by Bruce C. Mundy. Specimens were collected off the north...

  5. Innovations in macroscopic evaluation of pancreatic specimens and radiologic correlation

    International Nuclear Information System (INIS)

    Triantopoulou, Charikleia; Papaparaskeva, Kleo; Agalianos, Christos; Dervenis, Christos

    2016-01-01

    •The axial slicing technique offers many advantages in accurate estimation of tumors extend and staging.•Cross-sectional axial imaging is the best technique for accurate radiologic-pathologic correlation.•Correlation may explain any discrepancies between radiological and histopathological findings.•Pathology correlation may offer a better understanding of the missed findings by imaging or pitfalls The axial slicing technique offers many advantages in accurate estimation of tumors extend and staging. Cross-sectional axial imaging is the best technique for accurate radiologic-pathologic correlation. Correlation may explain any discrepancies between radiological and histopathological findings. Pathology correlation may offer a better understanding of the missed findings by imaging or pitfalls The purpose of this study was to evaluate the feasibility of a novel dissection technique of surgical specimens in different cases of pancreatic tumors and provide a radiologic pathologic correlation. In our hospital, that is a referral center for pancreatic diseases, the macroscopic evaluation of the pancreatectomy specimens is performed by the pathologists using the axial slicing technique (instead of the traditional procedure with longitudinal opening of the main pancreatic and/or common bile duct and slicing along the plane defined by both ducts). The specimen is sliced in an axial plane that is perpendicular to the longitudinal axis of the descending duodenum. The procedure results in a large number of thin slices (3–4 mm). This plane is identical to that of CT or MRI and correlation between pathology and imaging is straightforward. We studied 70 cases of suspected different solid and cystic pancreatic tumors and we correlated the tumor size and location, the structure—consistency (areas of necrosis—hemorrhage—fibrosis—inflammation), the degree of vessels’ infiltration, the size of pancreatic and common bile duct and the distance from resection margins

  6. Protein kinase A and Epac activation by cAMP regulates the expression of glial fibrillary acidic protein in glial cells

    Directory of Open Access Journals (Sweden)

    Sugimoto Naotoshi

    2016-01-01

    Full Text Available Cyclic adenosine monophosphate (cAMP controls differentiation in several types of cells during brain development. However, the molecular mechanism of cAMP-controlled differentiation is not fully understood. We investigated the role of protein kinase A (PKA and exchange protein directly activated by cAMP (Epac on cAMP-induced glial fibrillary acidic protein (GFAP, an astrocyte marker, in cultured glial cells. B92 glial cells were treated with cAMP-elevating drugs, an activator of adenylate cyclase, phosphodiesterase inhibitor and a ß adrenal receptor agonist. These cAMP-elevating agents induced dramatic morphological changes and expression of GFAP. A cAMP analog, 8-Br-cAMP, which activates Epac as well as PKA, induced GFAP expression and morphological changes, while another cAMP analog, 8-CPT-cAMP, which activates Epac with greater efficacy when compared to PKA, induced GFAP expression but very weak morphological changes. Most importantly, the treatment with a PKA inhibitor partially reduced cAMP-induced GFAP expression. Taken together, these results indicate that cAMP-elevating drugs lead to the induction of GFAP via PKA and/or Epac activation in B92 glial cells.

  7. Mathematical modeling of chemotaxis and glial scarring around implanted electrodes

    International Nuclear Information System (INIS)

    Silchenko, Alexander N; Tass, Peter A

    2015-01-01

    It is well known that the implantation of electrodes for deep brain stimulation or microelectrode probes for the recording of neuronal activity is always accompanied by the response of the brain’s immune system leading to the formation of a glial scar around the implantation sites. The implantation of electrodes causes massive release of adenosine-5′-triphosphate (ATP) and different cytokines into the extracellular space and activates the microglia. The released ATP and the products of its hydrolysis, such as ADP and adenosine, become the main elements mediating chemotactic sensitivity and motility of microglial cells via subsequent activation of P2Y 2,12 as well as A3A/A2A adenosine receptors. The size and density of an insulating sheath around the electrode, formed by microglial cells, are important criteria for the optimization of the signal-to-noise ratio during microelectrode recordings or parameters of electrical current delivered to the brain tissue. Here, we study a purinergic signaling pathway underlying the chemotactic motion of microglia towards implanted electrodes as well as the possible impact of an anti-inflammatory coating consisting of the interleukin-1 receptor antagonist. We present a model describing the formation of a stable aggregate around the electrode due to the joint chemo-attractive action of ATP and ADP and the mixed influence of extracellular adenosine. The bioactive coating is modeled as a source of chemo-repellent located near the electrode surface. The obtained analytical and numerical results allowed us to reveal the dependences of size and spatial location of the insulating sheath on the amount of released ATP and estimate the impact of immune suppressive coating on the scarring process. (paper)

  8. Development of Reconstitution Technology for Surveillance Specimens

    International Nuclear Information System (INIS)

    Yasushi Atago; Shunichi Hatano; Eiichiro Otsuka

    2002-01-01

    The Japan Power Engineering and Inspection Corporation (JAPEIC) has been carrying out the project titled 'Nuclear Power Plant Integrated Management Technology (PLIM)' consigned by Japanese Ministry of Economy, Trade and Industry (METI) since 1996FY as a 10-years project. As one of the project themes, development of reconstitution technology for reactor pressure vessel (RPV/RV) surveillance specimens, which are installed in RPVs to monitor the neutron irradiation embrittlement on RPV/RV materials, is now on being carried out to deal with the long-term operation of nuclear power plants. The target of this theme is to establish the technical standard for applicability of reconstituted surveillance specimens including the reconstitution of the Charpy specimens and Compact Tension (CT) specimens. With the Charpy specimen reconstitution, application of 10 mm length inserts is used, which enables the conversion of tests from the LT-direction to the TL-direction. This paper presents the basic data from Charpy and CT specimens of RPV materials using the surveillance specimens obtained for un-irradiated materials including the following. 1) Reconstitution Technology of Charpy Specimens. a) The interaction between plastic zone and Heat Affected Zone (HAZ). b) The effects of the possible deviations from the standard specimens for the reconstituted specimens. 2) Reconstitution Technology of CT specimens. a) The correlation between fracture toughness and plastic zone width. Because the project is now in progress, this paper describes the outline of the results obtained as of the end of 2000 FY. (authors)

  9. Quantification of tumor extension in prostate biopsies: importance in the identification of confined tumors

    Directory of Open Access Journals (Sweden)

    Leite Kátia R.M.

    2003-01-01

    Full Text Available OBJECTIVE: To assess the importance of quantifying the adenocarcinoma in prostate biopsies when determining the tumor's final stage in patients who undergo radical prostatectomy. To identify the best methodology for obtaining such data. PATIENTS AND METHODS: Prostate biopsies from 132 patients were examined, with determination of Gleason histological grade and tumor volume in number of involved fragments, tumor extent of the fragment mostly affected by the tumor and the total percentage of tumor in the specimen. Theses parameters were statistically correlated with the neoplasia's final stage following the evaluation of radical prostatectomy specimens. RESULTS: An average of 12 and a median of 14 biopsy fragments were evaluated per patient. In the univariate analysis the Gleason histological grade, the largest tumor extent in one fragment and the total percentage of tumor in the specimen were correlated with tumor stage of the surgical specimen. In the multivariate analysis, the Gleason histological grade and the total percentage of tumor were strongly correlated with the neoplasia's final stage. The risk of the tumor not being confined was 3 for Gleason 7 tumors and 10.6 for Gleason 8 tumors or above. In cases where the tumor involved more than 60% of the specimen, the risk of non-confined disease was 4.4 times. Among 19 patients with unfavorable histological parameters, Gleason > 7 and extension greater than 60% the tumor final stage was pT3 in 95%. CONCLUSION: When associated to the Gleason histological grade, tumor quantification in prostate biopsies is an important factor for determining organ-confined disease, and among the methods, total percentage of tumor is the most informative one. Such data should be included in the pathological report and must be incorporated in future nomograms.

  10. Ghrelin is involved in the paracrine communication between neurons and glial cells.

    Science.gov (United States)

    Avau, B; De Smet, B; Thijs, T; Geuzens, A; Tack, J; Vanden Berghe, P; Depoortere, I

    2013-09-01

    Ghrelin is the only known peripherally active orexigenic hormone produced by the stomach that activates vagal afferents to stimulate food intake and to accelerate gastric emptying. Vagal sensory neurons within the nodose ganglia are surrounded by glial cells, which are able to receive and transmit chemical signals. We aimed to investigate whether ghrelin activates or influences the interaction between both types of cells. The effect of ghrelin was compared with that of leptin and cholecystokinin (CCK). Cultures of rat nodose ganglia were characterized by immunohistochemistry and the functional effects of peptides, neurotransmitters, and pharmacological blockers were measured by Ca(2+) imaging using Fluo-4-AM as an indicator. Neurons responded to KCl and were immunoreactive for PGP-9.5 whereas glial cells responded to lysophosphatidic acid and had the typical SOX-10-positive nuclear staining. Neurons were only responsive to CCK (31 ± 5%) whereas glial cells responded equally to the applied stimuli: ghrelin (27 ± 2%), leptin (21 ± 2%), and CCK (30 ± 2%). In contrast, neurons stained more intensively for the ghrelin receptor than glial cells. ATP induced [Ca(2+) ]i rises in 90% of the neurons whereas ACh and the NO donor, SIN-1, mainly induced [Ca(2+) ]i changes in glial cells (41 and 51%, respectively). The percentage of ghrelin-responsive glial cells was not affected by pretreatment with suramin, atropine, hexamethonium or 1400 W, but was reduced by l-NAME and by tetrodotoxin. Neurons were shown to be immunoreactive for neuronal NO-synthase (nNOS). Our data show that ghrelin induces Ca(2+) signaling in glial cells of the nodose ganglion via the release of NO originating from the neurons. © 2013 John Wiley & Sons Ltd.

  11. Breast cancer: determining the genetic profile from ultrasound-guided percutaneous biopsy specimens obtained during the diagnostic workups.

    Science.gov (United States)

    López Ruiz, J A; Zabalza Estévez, I; Mieza Arana, J A

    2016-01-01

    To evaluate the possibility of determining the genetic profile of primary malignant tumors of the breast from specimens obtained by ultrasound-guided percutaneous biopsies during the diagnostic imaging workup. This is a retrospective study in 13 consecutive patients diagnosed with invasive breast cancer by B-mode ultrasound-guided 12 G core needle biopsy. After clinical indication, the pathologist decided whether the paraffin block specimens seemed suitable (on the basis of tumor size, validity of the sample, and percentage of tumor cells) before sending them for genetic analysis with the MammaPrint® platform. The size of the tumors on ultrasound ranged from 0.6cm to 5cm. In 11 patients the preserved specimen was considered valid and suitable for use in determining the genetic profile. In 1 patient (with a 1cm tumor) the pathologist decided that it was necessary to repeat the core biopsy to obtain additional samples. In 1 patient (with a 5cm tumor) the specimen was not considered valid by the genetic laboratory. The percentage of tumor cells in the samples ranged from 60% to 70%. In 11/13 cases (84.62%) it was possible to do the genetic analysis on the previously diagnosed samples. In most cases, regardless of tumor size, it is possible to obtain the genetic profile from tissue specimens obtained with ultrasound-guided 12 G core biopsy preserved in paraffin blocks. Copyright © 2015 SERAM. Published by Elsevier España, S.L.U. All rights reserved.

  12. Astrocyte-like glial cells physiologically regulate olfactory processing through the modification of ORN-PN synaptic strength in Drosophila.

    Science.gov (United States)

    Liu, He; Zhou, Bangyu; Yan, Wenjun; Lei, Zhengchang; Zhao, Xiaoliang; Zhang, Ke; Guo, Aike

    2014-09-01

    Astrocyte-like glial cells are abundant in the central nervous system of adult Drosophila and exhibit morphology similar to astrocytes of mammals. Previous evidence has shown that astrocyte-like glial cells are strongly associated with synapses in the antennal lobe (AL), the first relay of the olfactory system, where olfactory receptor neurons (ORNs) transmit information into projection neurons (PNs). However, the function of astrocyte-like glia in the AL remains obscure. In this study, using in vivo calcium imaging, we found that astrocyte-like glial cells exhibited spontaneous microdomain calcium elevations. Using simultaneous manipulation of glial activity and monitoring of neuronal function, we found that the astrocyte-like glial activation, but not ensheathing glial activation, could inhibit odor-evoked responses of PNs. Ensheathing glial cells are another subtype of glia, and are of functional importance in the AL. Electrophysiological experiments indicated that astrocyte-like glial activation decreased the amplitude and slope of excitatory postsynaptic potentials evoked through electrical stimulation of the antennal nerve. These results suggest that astrocyte-like glial cells may regulate olfactory processing through negative regulation of ORN-PN synaptic strength. Beyond the antennal lobe we observed astrocyte-like glial spontaneous calcium activities in the ventromedial protocerebrum, indicating that astrocyte-like glial spontaneous calcium elevations might be general in the adult fly brain. Overall, our study demonstrates a new function for astrocyte-like glial cells in the physiological modulation of olfactory information transmission, possibly through regulating ORN-PN synapse strength. © 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  13. Histopathologic analysis of appendectomy specimens

    Directory of Open Access Journals (Sweden)

    R Shrestha

    2012-03-01

    Full Text Available Background: Acute appendicitis is one of the common conditions requiring emergency surgery. A retrospective study was performed to determine various histopathological diagnoses, their demographics and the rates of perforated appendicitis, negative appendectomy and incidental appendectomy. Materials and Methods: Histopathological records of resected appendices submitted to histopathology department Chitwan medical college teaching hospital over the period of 2 yrs from May, 2009 to April 2011 were reviewed retrospectively. Results: Out of 930 specimens of appendix, appendicitis accounted for 88.8% with peak age incidence in the age group of 11 to 30 yrs in both sexes. Histopathologic diagnoses included acute appendicitis (45.6%, acute suppurative (20.8%, gangrenous (16.3%, perforated (1.7%, resolving /recurrent/non specific chronic appendicitis (2.5%, acute eosinophilic appendicitis (1.2%, periappendicitis (0.2%, and carcinoid tumour (0.1%. Other important coexisting pathologies were parasitic infestation (0.2% and Meckel’s diverticulum (0.2%. Negative appendectomy rate was 10.8% and three times more common in females with peak occurrence in the age group of 21-30 yrs. There were 10 cases of acute appendicitis in incidental appendectomies (2.5%, 24 cases with 7 times more common in females of age group of 31- 60 yrs. Conclusion: There is a high incidence of appendicitis in adolescents and young adults in central south region of Nepal. Negative appendectomy is also very common in females. Incidental appendectomy in elderly females may have preventive value. DOI: http://dx.doi.org/10.3126/jpn.v2i3.6025 JPN 2012; 2(3: 215-219

  14. Specimen size effects in Charpy impact testing

    International Nuclear Information System (INIS)

    Alexander, D.J.; Klueh, R.L.

    1989-01-01

    Full-size , half-size, and third-size specimens from several different steels have been tested as part of an ongoing alloy development program. The smaller specimens permit more specimens to be made from small trail heats and are much more efficient for irradiation experiments. The results of several comparisons between the different specimen sizes have shown that the smaller specimens show qualitatively similar behavior to large specimens, although the upper-shelf energy level and ductile-to-ductile transition temperature are reduced. The upper-shelf energy levels from different specimen sizes can be compared by using a simple volume normalization method. The effect of specimen size and geometry on the ductile-to-ductile transition temperature is more difficult to predict, although the available data suggest a simple shift in the transition temperature due to specimen size changes.The relatively shallower notch used in smaller specimens alters the deformation pattern, and permits yielding to spread back to the notched surface as well as through to the back. This reduces the constraint and the peak stresses, and thus the initiation of cleavage is more difficult. A better understanding of the stress and strain distributions is needed. 19 refs., 3 figs., 3 tabs

  15. Preliminary investigation of candidate specimens for the Egyptian environmental specimen bank

    International Nuclear Information System (INIS)

    Shawky, S.; Amer, H.; Schladot, J.D.; Ostapczuk, P.; Emons, H.; Abou El-Nour, F.

    2000-01-01

    In the frame of establishing an environmental monitoring program related to environmental specimen banking in egypt, some candidate specimens from the aquatic environment (Fish muscle, fish liver; mussels) were investigated. The selection of specimens and sampling sites is described. Specimens are chemically characterised with respect to some major and trace elements and the results are compared with data obtained from comparable specimens collected in aquatic ecosystems of germany

  16. [Trace elements of bone tumors].

    Science.gov (United States)

    Kalashnikov, V M; Zaĭchik, V E; Bizer, V A

    1983-01-01

    Due to activation analysis involving the use of neutrons from a nuclear reactor, the concentrations of 11 trace elements: scandium, iron, cobalt, mercury, rubidium, selenium, silver, antimony, chrome, zinc and terbium in intact bone and skeletal tumors were measured. 76 specimens of bioptates and resected material of operations for bone tumors and 10 specimens of normal bone tissue obtained in autopsies of cases of sudden death were examined. The concentrations of trace elements and their dispersion patterns in tumor tissue were found to be significantly higher than those in normal bone tissue. Also, the concentrations of some trace elements in tumor differed significantly from those in normal tissue; moreover, they were found to depend on the type and histogenesis of the neoplasm.

  17. The effects of centrally administered fluorocitrate via inhibiting glial cells on working memory in rats

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Although prefrontal and hippocampal neurons are critical for spatial working memory,the function of glial cells in spatial working memory remains uncertain.In this study we investigated the function of glial cells in rats’ working memory.The glial cells of rat brain were inhibited by intracerebroventricular(icv) injection of fluorocitrate(FC).The effects of FC on the glial cells were examined by using electroencephalogram(EEG) recordings and delayed spatial alternation tasks.After icv injection of 10 μL of 0.5 nmol/L or 5 nmol/L FC,the EEG power spectrum recorded from the hippocampus increased,but the power spectrum for the prefrontal cortex did not change,and working memory was unaffected.Following an icv injection of 10 μL of 20 nmol/L FC,the EEG power spectra in both the prefrontal cortex and the hippocampus increased,and working memory improved.The icv injection of 10 μL of 50 nmol/L FC,the EEG power spectra in both the prefrontal cortex and in the hippocampus decreased,and working memory was impaired.These results suggest that spatial working memory is affected by centrally administered FC,but only if there are changes in the EEG power spectrum in the prefrontal cortex.Presumably,the prefrontal glial cells relate to the working memory.

  18. Plasticity of Neuron-Glial Transmission: Equipping Glia for Long-Term Integration of Network Activity

    Directory of Open Access Journals (Sweden)

    Wayne Croft

    2015-01-01

    Full Text Available The capacity of synaptic networks to express activity-dependent changes in strength and connectivity is essential for learning and memory processes. In recent years, glial cells (most notably astrocytes have been recognized as active participants in the modulation of synaptic transmission and synaptic plasticity, implicating these electrically nonexcitable cells in information processing in the brain. While the concept of bidirectional communication between neurons and glia and the mechanisms by which gliotransmission can modulate neuronal function are well established, less attention has been focussed on the computational potential of neuron-glial transmission itself. In particular, whether neuron-glial transmission is itself subject to activity-dependent plasticity and what the computational properties of such plasticity might be has not been explored in detail. In this review, we summarize current examples of plasticity in neuron-glial transmission, in many brain regions and neurotransmitter pathways. We argue that induction of glial plasticity typically requires repetitive neuronal firing over long time periods (minutes-hours rather than the short-lived, stereotyped trigger typical of canonical long-term potentiation. We speculate that this equips glia with a mechanism for monitoring average firing rates in the synaptic network, which is suited to the longer term roles proposed for astrocytes in neurophysiology.

  19. Neuronal-glial interactions in rats fed a ketogenic diet.

    Science.gov (United States)

    Melø, Torun Margareta; Nehlig, Astrid; Sonnewald, Ursula

    2006-01-01

    Glucose is the preferred energy substrate for the adult brain. However, during periods of fasting and consumption of a high fat, low carbohydrate (ketogenic) diet, ketone bodies become major brain fuels. The present study was conducted to investigate how the ketogenic diet influences neuronal-glial interactions in amino acid neurotransmitter metabolism. Rats were kept on a standard or ketogenic diet. After 21 days all animals received an injection of [1-(13)C]glucose plus [1,2-(13)C]acetate, the preferential substrates of neurons and astrocytes, respectively. Extracts from cerebral cortex and plasma were analyzed by (13)C and (1)H nuclear magnetic resonance spectroscopy and HPLC. Increased amounts of valine, leucine and isoleucine and a decreased amount of glutamate were found in the brains of rats receiving the ketogenic diet. Glycolysis was decreased in ketotic rats compared with controls, evidenced by the reduced amounts of [3-(13)C]alanine and [3-(13)C]lactate. Additionally, neuronal oxidative metabolism of [1-(13)C]glucose was decreased in ketotic rats compared with controls, since amounts of [4-(13)C]glutamate and [4-(13)C]glutamine were lower than those of controls. Although the amount of glutamate from [1-(13)C]glucose was decreased, this was not the case for GABA, indicating that relatively more [4-(13)C]glutamate is converted to GABA. Astrocytic metabolism was increased in response to ketosis, shown by increased amounts of [4,5-(13)C]glutamine, [4,5-(13)C]glutamate, [1,2-(13)C]GABA and [3,4-(13)C]-/[1,2-(13)C]aspartate derived from [1,2-(13)C]acetate. The pyruvate carboxylation over dehydrogenation ratio for glutamine was increased in the ketotic animals compared to controls, giving further indication of increased astrocytic metabolism. Interestingly, pyruvate recycling was higher in glutamine than in glutamate in both groups of animals. An increase in this pathway was detected in glutamate in response to ketosis. The decreased glycolysis and oxidative

  20. Value of apparent diffusion coefficients in patients with brain tumors

    International Nuclear Information System (INIS)

    De Luca, Silvina; Stoisa, Daniela; Mondello, Eduardo; Vietti, Julio; Casas, Gabriel; Florenzano, Nestor; Eyheremendy, Eduardo; Martinez Boero, Macarena

    2004-01-01

    Purpose: To determine the utility of ADC values for the diagnosis of encephalic tumors. Material and method: Forty patients with encephalic tumors histopathologically confirmed, have been studied by conventional MR, diffusion and ADC maps. The intensities were measured in the solid tumor portion and the normal white matter, ratios were obtained and correlated in 13 patients with their respective cellularity indexes. Results: Seventeen were glial tumors, with lower ADC values in cases of greater malignancy. In 12 patients the diagnosis was secondary lesions in which the lowest ADC values were obtained. This feature was shared by the epidermoid cyst. The hamartomas, neurinomas, oligodendrogliomas and ependymomas have shown intermediate ADC values. Conclusion: The ADC map is a complement of conventional MR which provides additional information for the diagnosis of encephalic tumors. Low ADC values correlated with high grade malignant tumors. (author)

  1. Rosette-forming glioneuronal tumor of the fourth ventricle.

    Science.gov (United States)

    Preusser, Matthias; Dietrich, Wolfgang; Czech, Thomas; Prayer, Daniela; Budka, Herbert; Hainfellner, Johannes A

    2003-11-01

    Rosette-forming glioneuronal tumor (RGNT) of the fourth ventricle has been reported recently as a novel type of primary CNS neoplasm. We present the case of a 35-year-old male patient with RGNT of the fourth ventricle. The tumor was found incidentally; the patient did not suffer from any neurological symptoms. The tumor mass involved the caudal cerebellar vermis, filled the fourth ventricle and protruded into the caudal part of the mesencephalic aquaeduct. Smaller tumor nodules were visible in the adjacent right cerebellar hemisphere. Histologically, prominent neurocytic rosettes with synaptophysin expression were embedded in a glial tumor component resembling pilocytic astrocytoma. Clinicopathological features of our case closely resemble those reported in the original description. Thus, our case confirms RGNT as a new distinct type of primary CNS neoplasm. Due to its distinct features, adoption of RGNT as a new entity into the WHO classification of tumors should be considered.

  2. The soft mechanical signature of glial scars in the central nervous system

    Science.gov (United States)

    Moeendarbary, Emad; Weber, Isabell P.; Sheridan, Graham K.; Koser, David E.; Soleman, Sara; Haenzi, Barbara; Bradbury, Elizabeth J.; Fawcett, James; Franze, Kristian

    2017-03-01

    Injury to the central nervous system (CNS) alters the molecular and cellular composition of neural tissue and leads to glial scarring, which inhibits the regrowth of damaged axons. Mammalian glial scars supposedly form a chemical and mechanical barrier to neuronal regeneration. While tremendous effort has been devoted to identifying molecular characteristics of the scar, very little is known about its mechanical properties. Here we characterize spatiotemporal changes of the elastic stiffness of the injured rat neocortex and spinal cord at 1.5 and three weeks post-injury using atomic force microscopy. In contrast to scars in other mammalian tissues, CNS tissue significantly softens after injury. Expression levels of glial intermediate filaments (GFAP, vimentin) and extracellular matrix components (laminin, collagen IV) correlate with tissue softening. As tissue stiffness is a regulator of neuronal growth, our results may help to understand why mammalian neurons do not regenerate after injury.

  3. Advancements in the Underlying Pathogenesis of Schizophrenia: Implications of DNA Methylation in Glial Cells.

    Science.gov (United States)

    Chen, Xing-Shu; Huang, Nanxin; Michael, Namaka; Xiao, Lan

    2015-01-01

    Schizophrenia (SZ) is a chronic and severe mental illness for which currently there is no cure. At present, the exact molecular mechanism involved in the underlying pathogenesis of SZ is unknown. The disease is thought to be caused by a combination of genetic, biological, psychological, and environmental factors. Recent studies have shown that epigenetic regulation is involved in SZ pathology. Specifically, DNA methylation, one of the earliest found epigenetic modifications, has been extensively linked to modulation of neuronal function, leading to psychiatric disorders such as SZ. However, increasing evidence indicates that glial cells, especially dysfunctional oligodendrocytes undergo DNA methylation changes that contribute to the pathogenesis of SZ. This review primarily focuses on DNA methylation involved in glial dysfunctions in SZ. Clarifying this mechanism may lead to the development of new therapeutic interventional strategies for the treatment of SZ and other illnesses by correcting abnormal methylation in glial cells.

  4. Advancements in the Underlying Pathogenesis of Schizophrenia: Implications of DNA Methylation in Glial Cells

    Directory of Open Access Journals (Sweden)

    Xin-Shu eChen

    2015-12-01

    Full Text Available Schizophrenia (SZ)is a chronic and severe mental illness for which currently there is no cure. At present, the exact molecular mechanism involved in the underlying pathogenesis of SZ is unknown. The disease is thought to be caused by a combination of genetic, biological, psychological, and environmental factors. Recent studies have shown that epigenetic regulation is involved in SZ pathology. Specifically, DNA methylation, one of the earliest found epigenetic modifications, has been extensively linked to modulation of neuronal function, leading to psychiatric disorders such as SZ. However, increasing evidence indicates that glial cells, especially dysfunctional oligodendrocytes undergo DNA methylation changes that contribute to the pathogenesis of SZ. This review primarily focuses on DNA methylation involved in glial dysfunctions in SZ. Clarifying this mechanism may lead to the development of new therapeutic interventional strategies for the treatment of SZ and other illnesses by correcting abnormal methylation in glial cells.

  5. Opioid-dependent growth of glial cultures: Suppression of astrocyte DNA synthesis by met-enkephalin

    International Nuclear Information System (INIS)

    Stiene-Martin, A.; Hauser, K.F.

    1990-01-01

    The action of met-enkephalin on the growth of astrocytes in mixed-glial cultures was examined. Primary, mixed-glial cultures were isolated from 1 day-old mouse cerebral hemispheres and continuously treated with either basal growth media, 1 μM met-enkephalin, 1 μM met-enkephalin plus the opioid antagonist naloxone, or naloxone alone. Absolute numbers of neural cells were counted in unstained preparations, while combined [ 3 H]-thymidine autoradiography and glial fibrillary acid protein (GFAP) immunocytochemistry was performed to identify specific changes in astrocytes. When compared to control and naloxone treated cultures, met-enkephalin caused a significant decrease in both total cell numbers, and in [ 3 H]-thymidine incorporation by GFAP-positive cells with flat morphology. These results indicate that met-enkephalin suppresses astrocyte growth in culture

  6. Opioid-dependent growth of glial cultures: Suppression of astrocyte DNA synthesis by met-enkephalin

    Energy Technology Data Exchange (ETDEWEB)

    Stiene-Martin, A.; Hauser, K.F. (Univ. of Kentucky, Lexington (USA))

    1990-01-01

    The action of met-enkephalin on the growth of astrocytes in mixed-glial cultures was examined. Primary, mixed-glial cultures were isolated from 1 day-old mouse cerebral hemispheres and continuously treated with either basal growth media, 1 {mu}M met-enkephalin, 1 {mu}M met-enkephalin plus the opioid antagonist naloxone, or naloxone alone. Absolute numbers of neural cells were counted in unstained preparations, while combined ({sup 3}H)-thymidine autoradiography and glial fibrillary acid protein (GFAP) immunocytochemistry was performed to identify specific changes in astrocytes. When compared to control and naloxone treated cultures, met-enkephalin caused a significant decrease in both total cell numbers, and in ({sup 3}H)-thymidine incorporation by GFAP-positive cells with flat morphology. These results indicate that met-enkephalin suppresses astrocyte growth in culture.

  7. Spatial organization of NG2 glial cells and astrocytes in rat hippocampal CA1 region.

    Science.gov (United States)

    Xu, Guangjin; Wang, Wei; Zhou, Min

    2014-04-01

    Similar to astrocytes, NG2 glial cells are uniformly distributed in the central nervous system (CNS). However, little is known about the interspatial relationship, nor the functional interactions between these two star-shaped glial subtypes. Confocal morphometric analysis showed that NG2 immunostained cells are spatially organized as domains in rat hippocampal CA1 region and that each NG2 glial domain occupies a spatial volume of ∼178, 364 μm(3) . The processes of NG2 glia and astrocytes overlap extensively; each NG2 glial domain interlaces with the processes deriving from 5.8 ± 0.4 neighboring astrocytes, while each astrocytic domain accommodates processes stemming from 4.5 ± 0.3 abutting NG2 glia. In CA1 stratum radiatum, the cell bodies of morphologically identified glial cells often appear to make direct somatic-somata contact, termed as doublets. We used dual patch recording and postrecording NG2/GFAP double staining to determine the glial identities of these doublets. We show that among 44 doublets, 50% were NG2 glia-astrocyte pairs, while another 38.6% and 11.4% were astrocyte-astrocyte and NG2 glia-NG2 glia pairs, respectively. In dual patch recording, neither electrical coupling nor intercellular biocytin transfer was detected in astrocyte-NG2 glia or NG2 glia-NG2 glia doublets. Altogether, although NG2 glia and astrocytes are not gap junction coupled, their cell bodies and processes are interwoven extensively. The anatomical and physiological relationships revealed in this study should facilitate future studies to understand the metabolic coupling and functional communication between NG2 glia and astrocytes. Copyright © 2013 Wiley Periodicals, Inc.

  8. Glial modulation by N-acylethanolamides in brain injury and neurodegeneration

    Directory of Open Access Journals (Sweden)

    María Inés Herrera

    2016-04-01

    Full Text Available Neuroinflammation involves the activation of glial cells and represents a key element in normal aging and pathophysiology of brain damage. N-acylethanolamides (NAEs, naturally occurring amides, are known for their pro-homeostatic effects. An increase of NAEs has been reported in vivo and in vitro in the aging brain and in brain injury. Treatment with NAEs may promote neuroprotection and exert anti-inflammatory actions via PPARα activation and/or by counteracting gliosis. This review aims to provide an overview of endogenous and exogenous properties of NAEs in neuroinflammation and to discuss their interaction with glial cells.

  9. 7 CFR 97.8 - Specimen requirements.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 3 2010-01-01 2010-01-01 false Specimen requirements. 97.8 Section 97.8 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards... required by the examiner to furnish representative specimens of the variety, or its flower, fruit, or seeds...

  10. Temporal profiles of age-dependent changes in cytokine mRNA expression and glial cell activation after status epilepticus in postnatal rat hippocampus.

    Science.gov (United States)

    Järvelä, Juha T; Lopez-Picon, Francisco R; Plysjuk, Anna; Ruohonen, Saku; Holopainen, Irma E

    2011-04-08

    Status epilepticus (SE) is proposed to lead to an age-dependent acute activation of a repertoire of inflammatory processes, which may contribute to neuronal damage in the hippocampus. The extent and temporal profiles of activation of these processes are well known in the adult brain, but less so in the developing brain. We have now further elucidated to what extent inflammation is activated by SE by investigating the acute expression of several cytokines and subacute glial reactivity in the postnatal rat hippocampus. SE was induced by an intraperitoneal (i.p.) injection of kainic acid (KA) in 9- and 21-day-old (P9 and P21) rats. The mRNA expression of interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), interleukin-10 (IL-10), matrix metalloproteinase-9 (MMP-9), glial-derived neurotrophic factor (GDNF), interferon gamma (IFN-γ), and transforming growth factor-beta 1 (TGF-β1) were measured from 4 h up to 3 days after KA injection with real-time quantitative PCR (qPCR). IL-1β protein expression was studied with ELISA, GFAP expression with western blotting, and microglial and astrocyte morphology with immunohistochemistry 3 days after SE. SE increased mRNA expression of IL-1β, TNF-α and IL-10 mRNA in hippocampus of both P9 and P21 rats, their induction being more rapid and pronounced in P21 than in P9 rats. MMP-9 expression was augmented similarly in both age groups and GDNF expression augmented only in P21 rats, whereas neither IFN-γ nor TGF-β1 expression was induced in either age group. Microglia and astrocytes exhibited activated morphology in the hippocampus of P21 rats, but not in P9 rats 3 d after SE. Microglial activation was most pronounced in the CA1 region and also detected in the basomedial amygdala. Our results suggest that SE provokes an age-specific cytokine expression in the acute phase, and age-specific glial cell activation in the subacute phase as verified now in the postnatal rat hippocampus. In the juvenile hippocampus

  11. DMPD: Multifunctional effects of bradykinin on glial cells in relation to potentialanti-inflammatory effects. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 17669557 Multifunctional effects of bradykinin on glial cells in relation to potent... Epub 2007 Jun 27. (.png) (.svg) (.html) (.csml) Show Multifunctional effects of bradykinin on glial cells i...n relation to potentialanti-inflammatory effects. PubmedID 17669557 Title Multifunction

  12. Recent advances on Charpy specimen reconstitution techniques

    Energy Technology Data Exchange (ETDEWEB)

    Andrade, Arnaldo H.P.; Lobo, Raquel M.; Miranda, Carlos Alexandre J., E-mail: aandrade@ipen.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2017-07-01

    Charpy specimen reconstitution is widely used around the world as a tool to enhance or supplement surveillance programs of nuclear reactor pressure vessels. The reconstitution technique consists in the incorporation of a small piece from a previously tested specimen into a compound specimen, allowing to increase the number of tests. This is especially important if the available materials is restricted and fracture mechanics parameter have to be determined. The reconstitution technique must fulfill some demands, among them tests results like the original standard specimens and the loaded material of the insert must not be influenced by the welding and machining procedure. It is known that reconstitution of Charpy specimens may affect the impact energy in a consequence of the constraint of plastic deformation by the hardened weldment and HAZ. This paper reviews some recent advances of the reconstitution technique and its applications. (author)

  13. Recent advances on Charpy specimen reconstitution techniques

    International Nuclear Information System (INIS)

    Andrade, Arnaldo H.P.; Lobo, Raquel M.; Miranda, Carlos Alexandre J.

    2017-01-01

    Charpy specimen reconstitution is widely used around the world as a tool to enhance or supplement surveillance programs of nuclear reactor pressure vessels. The reconstitution technique consists in the incorporation of a small piece from a previously tested specimen into a compound specimen, allowing to increase the number of tests. This is especially important if the available materials is restricted and fracture mechanics parameter have to be determined. The reconstitution technique must fulfill some demands, among them tests results like the original standard specimens and the loaded material of the insert must not be influenced by the welding and machining procedure. It is known that reconstitution of Charpy specimens may affect the impact energy in a consequence of the constraint of plastic deformation by the hardened weldment and HAZ. This paper reviews some recent advances of the reconstitution technique and its applications. (author)

  14. Sixth nerve palsy - Window to a dreaded brain tumor in children (pontine glioma

    Directory of Open Access Journals (Sweden)

    Sujit Das

    2017-01-01

    Full Text Available Pontine glioma is a rare tumor and exclusively occurs in children. It originates from the glial (connective/supporting cells of the brain. In children, they are the leading cause of deaths from brain tumors. The usual age of presentation is later half of first decade. Most of the children die within 18 months of diagnosis. It mostly affects 6th and 7th cranial nerves along with hearing defect.

  15. LPTR irradiation of LLL vanadium tensile specimens and LLL Nb--1Zr tensile specimens

    International Nuclear Information System (INIS)

    MacLean, S.C.; Rowe, C.L.

    1977-01-01

    The LPTR irradiation of 14 LLL vanadium tensile specimens and 14 LLL Nb-1Zr tensile specimens is described. Sample packaging, the irradiation schedule and neutron fluences for three energy ranges are given

  16. Significance of microscopic extention from 1162 esophageal carcinoma specimens

    International Nuclear Information System (INIS)

    Wang Jun; Zhu Shuchai; Han Chun; Zhang Xin; Xiao Aiqin; Ma Guoxin

    2007-01-01

    Objective: To examine the subclinical microscopic tumor extention along the long axis in 1162 specimens of esophageal carcinoma so as to help define the clinical target volume(CTV) according to the degree of microscopic extention(ME) for radiotherapy for esophageal carcinoma. Methods: 1162 resected esophageal carcinoma specimens originally located in the neck and thorax were studied with special reference to the correlation between upper and lower resection length from the tumor and positive microscopic margin. Another 52 resected esophageal carcinoma specimens were made into pathological giant sections: the actual resection length of upper and para-esophageal normal tissues was compared with that of the lower nor- mal tissues from the tumor, there by, the ratio of shrinkage was obtained and compared. Results: After fixation, microscopic positive margin ratio of the upper resection border in length ≤0.5 cm group was higher than that in length > 0.5 cm group (16.4% vs 4.1%, P=0.000). Microscopic positive margin ratio of the lower resection border in length ≤1.5 cm group was higher than that in length > 1.5 cm group( 8.1% vs 0.4%, P = 0.000). This showed that the positive margin ratio of the upper border was higher than that of the lower border in resection length > 1.5 cm group(3.5% vs 0.4%, P=0. 000). The actual length of upper and lower normal esophageal tissue after having been made into pathological giant sections in 52 patients, was 30% ± 14% and 44% ± 19% of that measured in the operation. Conclusions: Considering the shrinkage of the normal esophagus during fixation, a CTV margin of 2.0 cm along the upper long axis and 3.5 cm along the lower long axis should be chosen for radiotherapy for esophageal carcinoma, according to the ratio of shrinkage. Ascending invasion proportion is higher than the descending invasion in that tumor. (authors)

  17. 16 CFR Figure 3 to Part 1610 - Specimen Holder Supported in Specimen Rack

    Science.gov (United States)

    2010-01-01

    ... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Specimen Holder Supported in Specimen Rack 3 Figure 3 to Part 1610 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FLAMMABLE FABRICS ACT... Holder Supported in Specimen Rack ER25MR08.002 ...

  18. Evidence that stress activates glial lactate formation in vivo assessed with rat hippocampus lactography

    NARCIS (Netherlands)

    Elekes, O; Venema, K; Postema, F; Dringen, R; Hamprecht, B; Korf, J

    1996-01-01

    Extracellular lactate of the rat hippocampus is inter alia increased by immobilization stress. The origin of lactate is, however, not well established, so it is not known whether it is mainly derived form neurons or glial cells. Dialysates were collected shortly (1 or 2 days) or with a delay (14 or

  19. Electron microscopy of glial cells of the central nervous system in the crab Ucides cordatus

    Directory of Open Access Journals (Sweden)

    Allodi S.

    1999-01-01

    Full Text Available Invertebrate glial cells show a variety of morphologies depending on species and location. They have been classified according to relatively general morphological or functional criteria and also to their location. The present study was carried out to characterize the organization of glial cells and their processes in the zona fasciculata and in the protocerebral tract of the crab Ucides cordatus. We performed routine and cytochemical procedures for electron microscopy analysis. Semithin sections were observed at the light microscope. The Thiéry procedure indicated the presence of carbohydrates, particularly glycogen, in tissue and in cells. To better visualize the axonal ensheathment at the ultrastructural level, we employed a method to enhance the unsaturated fatty acids present in membranes. Our results showed that there are at least two types of glial cells in these nervous structures, a light one and a dark one. Most of the dark cell processes have been mentioned in the literature as extracellular matrix, but since they presented an enveloping membrane, glycogen and mitochondria - intact and with different degrees of disruption - they were considered to be glial cells in the present study. We assume that they correspond to the perineurial cells on the basis of their location. The light cells must correspond to the periaxonal cells. Some characteristics of the axons such as their organization, ensheathment and subcellular structures are also described.

  20. Involvement of glial cells in the neurotoxicity of parathion and chlorpyrifos

    International Nuclear Information System (INIS)

    Zurich, M.-G.; Honegger, P.; Schilter, B.; Costa, L.G.; Monnet-Tschudi, F.

    2004-01-01

    An in vitro model, the aggregating brain cell culture of fetal rat telencephalon, has been used to investigate the influence of glial cells on the neurotoxicity of two organophosphorus pesticides (OPs), chlorpyrifos and parathion. Mixed-cell aggregate cultures were treated continuously for 10 days between DIV 5 and 15. Parathion induced astrogliosis at concentration at which MAP-2 immunostaining, found here to be more sensitive than neuron-specific enzyme activities, was not affected. In contrast, chlorpyrifos induced a comparatively weak gliotic reaction, and only at concentrations at which neurons were already affected. After similar treatments, increased neurotoxicity of parathion and chlorpyrifos was found in aggregate cultures deprived of glial cells. These results suggest that glial cells provide neuroprotection against OPs toxicity. To address the question of the difference in toxicity between parathion and chlorpyrifos, the toxic effects of their leaving groups, p-nitrophenol and trichloropyridinol, were studied in mixed-cell aggregates. General cytotoxicity was more pronounced for trichloropyridinol and both compounds had similar toxic effects on neuron-specific enzyme activities. In contrast, trichloropyridinol induced a much stronger decrease in glutamine synthetase activity, the enzymatic marker of astrocytes. Trichloropyridinol may exert a toxic effect on astrocytes, compromising their neuroprotective function, thus exacerbating the neurotoxicity of chlorpyrifos. This is in line with the suggestion that glial cells may contribute to OPs neurotoxicity, and with the view that OPs may exert their neurotoxic effects through different mechanisms

  1. Flavonoids Modulate the Proliferation of Neospora caninum in Glial Cell Primary Cultures

    Science.gov (United States)

    Barbosa de Matos, Rosan; Braga-de-Souza, Suzana; Pena Seara Pitanga, Bruno; Amaral da Silva, Victor Diógenes; Viana de Jesus, Erica Etelvina; Morales Pinheiro, Alexandre; Dias Costa, Maria de Fátima; dos Santos El-Bacha, Ramon; de Oliveira Ribeiro, Cátia Suse

    2014-01-01

    Neospora caninum (Apicomplexa; Sarcocystidae) is a protozoan that causes abortion in cattle, horses, sheep, and dogs as well as neurological and dermatological diseases in dogs. In the central nervous system of dogs infected with N. caninum, cysts were detected that exhibited gliosis and meningitis. Flavonoids are polyphenolic compounds that exhibit antibacterial, antiparasitic, antifungal, and antiviral properties. In this study, we investigated the effects of flavonoids in a well-established in vitro model of N. caninum infection in glial cell cultures. Glial cells were treated individually with 10 different flavonoids, and a subset of cultures was also infected with the NC-1 strain of N. caninum. All of the flavonoids tested induced an increase in the metabolism of glial cells and many of them increased nitrite levels in cultures infected with NC-1 compared to controls and uninfected cultures. Among the flavonoids tested, 3',4'-dihydroxyflavone, 3',4',5,7-tetrahydroxyflavone (luteolin), and 3,3',4',5,6-pentahydroxyflavone (quercetin), also inhibited parasitophorous vacuole formation. Taken together, our findings show that flavonoids modulate glial cell responses, increase NO secretion, and interfere with N. caninum infection and proliferation. PMID:25548412

  2. Dampak Hipoksia Sistemik terhadap Malondialdehida, Glial Fibrillary Acidic Protein dan Aktivitas Asetilkolin Esterase Otak Tikus

    OpenAIRE

    Andriani Andriani; Ani Retno Prijanti; Ninik Mudjihartini; Sri Widia A. Jusman

    2016-01-01

    Hipoksia sistemik menyebabkan berkurangnya oksigen dan energi di otak sehingga memicupenglepasan neurotransmiter asetilkolin, meningkatkan radikal bebas dan glial fibrillary acidic protein (GFAP)yang berfungsi menjaga kekuatan membran. Tujuan penelitian untuk melihat gambaran adaptasi otak padahipoksia sistemik terhadap fungsi asetilkolin esterase, kerusakan membran sel neuron dan astrosit. Penelitiandilakukan di Laboratorium Biokimia & Biologi Molekuler FK Universitas Indonesia, pada ta...

  3. Controlled adhesion and growth of long term glial and neuronal cultures on Parylene-C.

    Directory of Open Access Journals (Sweden)

    Evangelos Delivopoulos

    Full Text Available This paper explores the long term development of networks of glia and neurons on patterns of Parylene-C on a SiO(2 substrate. We harvested glia and neurons from the Sprague-Dawley (P1-P7 rat hippocampus and utilized an established cell patterning technique in order to investigate cellular migration, over the course of 3 weeks. This work demonstrates that uncontrolled glial mitosis gradually disrupts cellular patterns that are established early during culture. This effect is not attributed to a loss of protein from the Parylene-C surface, as nitrogen levels on the substrate remain stable over 3 weeks. The inclusion of the anti-mitotic cytarabine (Ara-C in the culture medium moderates glial division and thus, adequately preserves initial glial and neuronal conformity to underlying patterns. Neuronal apoptosis, often associated with the use of Ara-C, is mitigated by the addition of brain derived neurotrophic factor (BDNF. We believe that with the right combination of glial inhibitors and neuronal promoters, the Parylene-C based cell patterning method can generate structured, active neural networks that can be sustained and investigated over extended periods of time. To our knowledge this is the first report on the concurrent application of Ara-C and BDNF on patterned cell cultures.

  4. Glial Cells: The Other Cells of the Nervous System-Microglia–The ...

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 7; Issue 10. Glial Cells: The Other Cells of the Nervous System - Microglia – The Guardians of the CNS. Medha S Rajadhyaksha Daya Manghani. Series Article Volume 7 Issue 10 October 2002 pp 23-29 ...

  5. Gemfibrozil, a Lipid-lowering Drug, Induces Suppressor of Cytokine Signaling 3 in Glial Cells

    Science.gov (United States)

    Ghosh, Arunava; Pahan, Kalipada

    2012-01-01

    Glial inflammation is an important feature of several neurodegenerative disorders. Suppressor of cytokine signaling (SOCS) proteins play a crucial role in inhibiting cytokine signaling and inflammatory gene expression in various cell types, including glial cells. However, mechanisms by which SOCS genes could be up-regulated are poorly understood. This study underlines the importance of gemfibrozil, a Food and Drug Administration-approved lipid-lowering drug, in up-regulating the expression of SOCS3 in glial cells. Gemfibrozil increased the expression of Socs3 mRNA and protein in mouse astroglia and microglia in both a time- and dose-dependent manner. Interestingly, gemfibrozil induced the activation of type IA phosphatidylinositol (PI) 3-kinase and AKT. Accordingly, inhibition of PI 3-kinase and AKT by chemical inhibitors abrogated gemfibrozil-mediated up-regulation of SOCS3. Furthermore, we demonstrated that gemfibrozil induced the activation of Krüppel-like factor 4 (KLF4) via the PI 3-kinase-AKT pathway and that siRNA knockdown of KLF4 abrogated gemfibrozil-mediated up-regulation of SOCS3. Gemfibrozil also induced the recruitment of KLF4 to the distal, but not proximal, KLF4-binding site of the Socs3 promoter. This study delineates a novel property of gemfibrozil in up-regulating SOCS3 in glial cells via PI 3-kinase-AKT-mediated activation of KLF4 and suggests that gemfibrozil may find therapeutic application in neuroinflammatory and neurodegenerative disorders. PMID:22685291

  6. Multiscale Vision Model Highlights Spontaneous Glial Calcium Waves Recorded by 2-Photon Imaging in Brain Tissue

    DEFF Research Database (Denmark)

    Brazhe, Alexey; Mathiesen, Claus; Lauritzen, Martin

    2013-01-01

    Intercellular glial calcium waves constitute a signaling pathway which can be visualized by fluorescence imaging of cytosolic Ca2+ changes. However, there is a lack of procedures for sensitive and reliable detection of calcium waves in noisy multiphoton imaging data. Here we extend multiscale...

  7. Glial GABA Transporters as Modulators of Inhibitory Signalling in Epilepsy and Stroke

    DEFF Research Database (Denmark)

    Lie, Maria E K; Al-Khawaja, Anas; Damgaard, Maria

    2017-01-01

    is to provide an overview of glial GATs in regulating tonic inhibition, especially in epilepsy and stroke. This entails a comprehensive summary of changes known to occur in GAT expression levels and signalling following epileptic and ischemic insults. Further, we discuss the accumulating pharmacological...

  8. Axon Guidance of Sympathetic Neurons to Cardiomyocytes by Glial Cell Line-Derived Neurotrophic Factor (GDNF)

    NARCIS (Netherlands)

    Miwa, Keiko; Lee, Jong-Kook; Takagishi, Yoshiko; Opthof, Tobias; Fu, Xianming; Hirabayashi, Masumi; Watabe, Kazuhiko; Jimbo, Yasuhiko; Kodama, Itsuo; Komuro, Issei

    2013-01-01

    Molecular signaling of cardiac autonomic innervation is an unresolved issue. Here, we show that glial cell line-derived neurotrophic factor (GDNF) promotes cardiac sympathetic innervation in vitro and in vivo. In vitro, ventricular myocytes (VMs) and sympathetic neurons (SNs) isolated from neonatal

  9. Chemokine expression by glial cells directs leukocytes to sites of axonal injury in the CNS

    DEFF Research Database (Denmark)

    Babcock, Alicia A; Kuziel, William A; Rivest, Serge

    2003-01-01

    Innate responses in the CNS are critical to first line defense against infection and injury. Leukocytes migrate to inflammatory sites in response to chemokines. We studied leukocyte migration and glial chemokine expression within the denervated hippocampus in response to axonal injury caused by e...

  10. Handling of biological specimens for electron microscopy

    International Nuclear Information System (INIS)

    Bullock, G.

    1987-01-01

    There are many different aspects of specimen preparation procedure which need to be considered in order to achieve good results. Whether using the scanning or transmission microscope, the initial handling procedures are very similar and are selected for the information required. Handling procedures and techniques described are: structural preservation; immuno-and histo-chemistry; x-ray microanalysis and autoradiography; dehydration and embedding; mounting and coating specimens for scanning electron microscopy; and sectioning of resin embedded material. With attention to detail and careful choice of the best available technique, excellent results should be obtainable whatever the specimen. 6 refs

  11. Evaluation of irradiated coating material specimens

    International Nuclear Information System (INIS)

    Lee, Yong Jin; Nam, Seok Woo; Cho, Lee Moon

    2007-12-01

    Evaluation result of irradiated coating material specimens - Coating material specimens radiated Gamma Energy(Co 60) in air condition. - Evaluation conditions was above 1 X 10 4 Gy/hr, and radiated TID 2.0 X 10 6 Gy. - The radiated coating material specimens, No Checking, Cracking, Flaking, Delamination, Peeling and Blistering. - Coating system at the Kori no. 1 and APR 1400 Nuclear power plant, evaluation of irradiated coating materials is in accordance with owner's requirement(2.0 X 10 6 Gy)

  12. Ammonia modifies enteric neuromuscular transmission through glial γ-aminobutyric acid signaling.

    Science.gov (United States)

    Fried, David E; Watson, Ralph E; Robson, Simon C; Gulbransen, Brian D

    2017-12-01

    Impaired gut motility may contribute, at least in part, to the development of systemic hyperammonemia and systemic neurological disorders in inherited metabolic disorders, or in severe liver and renal disease. It is not known whether enteric neurotransmission regulates intestinal luminal and hence systemic ammonia levels by induced changes in motility. Here, we propose and test the hypothesis that ammonia acts through specific enteric circuits to influence gut motility. We tested our hypothesis by recording the effects of ammonia on neuromuscular transmission in tissue samples from mice, pigs, and humans and investigated specific mechanisms using novel mutant mice, selective drugs, cellular imaging, and enzyme-linked immunosorbent assays. Exogenous ammonia increased neurogenic contractions and decreased neurogenic relaxations in segments of mouse, pig, and human intestine. Enteric glial cells responded to ammonia with intracellular Ca 2+ responses. Inhibition of glutamine synthetase and the deletion of glial connexin-43 channels in hGFAP :: Cre ER T2+/- /connexin43 f/f mice potentiated the effects of ammonia on neuromuscular transmission. The effects of ammonia on neuromuscular transmission were blocked by GABA A receptor antagonists, and ammonia drove substantive GABA release as did the selective pharmacological activation of enteric glia in GFAP::hM3Dq transgenic mice. We propose a novel mechanism whereby local ammonia is operational through GABAergic glial signaling to influence enteric neuromuscular circuits that regulate intestinal motility. Therapeutic manipulation of these mechanisms may benefit a number of neurological, hepatic, and renal disorders manifesting hyperammonemia. NEW & NOTEWORTHY We propose that local circuits in the enteric nervous system sense and regulate intestinal ammonia. We show that ammonia modifies enteric neuromuscular transmission to increase motility in human, pig, and mouse intestine model systems. The mechanisms underlying the

  13. Neuronal and glial release of (3H)GABA from the rat olfactory bulb

    Energy Technology Data Exchange (ETDEWEB)

    Jaffe, E.H.; Cuello, A.C.

    1981-12-01

    Neuronal versus glial components of the (3H)gamma-aminobutyric acid ((3H)GABA) release studies were performed with two different microdissected layers of the olfactory bulb of the rat. In some experiments substantia nigra was used as a GABAergic axonal system and the trigeminal ganglia as a peripheral glial model. Spontaneous release of (3H)GABA was always lower in neuronal elements as compared with glial cells. A veratridine-evoked release was observed from the ONL but not from the trigeminal ganglia. Tetrodotoxin (TTX) abolished the veratridine-evoked release from the ONL, which also showed a partial inhibition when high magnesium concentrations were used in a Ca2+-free solution. beta-Alanine was strongly exchanged with (3H)GABA from the ONL of animals with the olfactory nerve lesioned and from animals with no lesion; but only a small heteroexchange was found from the external plexiform layer. The beta-alanine heteroexchange was able to deplete the releasable GABA store from the ONL of lesioned animals. In nonlesioned animals and the external plexiform layer, the veratridine-stimulated release of (3H)GABA was not significantly reduced after the beta-alanine heteroexchange. Stimulation of the (3H)GABA release by high concentrations of potassium elicited a higher release rate from axonal terminals than from dendrites or glia. Neurones and glia showed a similar inhibition of (3H)GABA release when a high magnesium concentration was added to a calcium-free solution. When D-600 was used as a calcium-flux blocker no inhibition of the release was observed in glial cells, whereas an almost complete blockage was found in both neuronal preparations (substantia nigra and EPL). These results provide further evidence for differential release mechanisms of GABA from CNS neurones and glial cells.

  14. Transglial transmission at the dorsal root ganglion sandwich synapse: glial cell to postsynaptic neuron communication.

    Science.gov (United States)

    Rozanski, Gabriela M; Li, Qi; Stanley, Elise F

    2013-04-01

    The dorsal root ganglion (DRG) contains a subset of closely-apposed neuronal somata (NS) separated solely by a thin satellite glial cell (SGC) membrane septum to form an NS-glial cell-NS trimer. We recently reported that stimulation of one NS with an impulse train triggers a delayed, noisy and long-lasting response in its NS pair via a transglial signaling pathway that we term a 'sandwich synapse' (SS). Transmission could be unidirectional or bidirectional and facilitated in response to a second stimulus train. We have shown that in chick or rat SS the NS-to-SGC leg of the two-synapse pathway is purinergic via P2Y2 receptors but the second SGC-to-NS synapse mechanism remained unknown. A noisy evoked current in the target neuron, a reversal potential close to 0 mV, and insensitivity to calcium scavengers or G protein block favored an ionotropic postsynaptic receptor. Selective block by D-2-amino-5-phosphonopentanoate (AP5) implicated glutamatergic transmission via N-methyl-d-aspartate receptors. This agent also blocked NS responses evoked by puff of UTP, a P2Y2 agonist, directly onto the SGC cell, confirming its action at the second synapse of the SS transmission pathway. The N-methyl-d-aspartate receptor NR2B subunit was implicated by block of transmission with ifenprodil and by its immunocytochemical localization to the NS membrane, abutting the glial septum P2Y2 receptor. Isolated DRG cell clusters exhibited daisy-chain and branching NS-glial cell-NS contacts, suggestive of a network organization within the ganglion. The identification of the glial-to-neuron transmitter and receptor combination provides further support for transglial transmission and completes the DRG SS molecular transmission pathway. © 2013 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  15. 50 CFR 14.24 - Scientific specimens.

    Science.gov (United States)

    2010-10-01

    ..., POSSESSION, TRANSPORTATION, SALE, PURCHASE, BARTER, EXPORTATION, AND IMPORTATION OF WILDLIFE AND PLANTS... international mail system. Provided, that this exception will not apply to any specimens or parts thereof taken...

  16. Impact of specimen adequacy on the assessment of renal allograft biopsy specimens.

    Science.gov (United States)

    Cimen, S; Geldenhuys, L; Guler, S; Imamoglu, A; Molinari, M

    2016-01-01

    The Banff classification was introduced to achieve uniformity in the assessment of renal allograft biopsies. The primary aim of this study was to evaluate the impact of specimen adequacy on the Banff classification. All renal allograft biopsies obtained between July 2010 and June 2012 for suspicion of acute rejection were included. Pre-biopsy clinical data on suspected diagnosis and time from renal transplantation were provided to a nephropathologist who was blinded to the original pathological report. Second pathological readings were compared with the original to assess agreement stratified by specimen adequacy. Cohen's kappa test and Fisher's exact test were used for statistical analyses. Forty-nine specimens were reviewed. Among these specimens, 81.6% were classified as adequate, 6.12% as minimal, and 12.24% as unsatisfactory. The agreement analysis among the first and second readings revealed a kappa value of 0.97. Full agreement between readings was found in 75% of the adequate specimens, 66.7 and 50% for minimal and unsatisfactory specimens, respectively. There was no agreement between readings in 5% of the adequate specimens and 16.7% of the unsatisfactory specimens. For the entire sample full agreement was found in 71.4%, partial agreement in 20.4% and no agreement in 8.2% of the specimens. Statistical analysis using Fisher's exact test yielded a P value above 0.25 showing that - probably due to small sample size - the results were not statistically significant. Specimen adequacy may be a determinant of a diagnostic agreement in renal allograft specimen assessment. While additional studies including larger case numbers are required to further delineate the impact of specimen adequacy on the reliability of histopathological assessments, specimen quality must be considered during clinical decision making while dealing with biopsy reports based on minimal or unsatisfactory specimens.

  17. Specimen environments in thermal neutron scattering experiments

    International Nuclear Information System (INIS)

    Cebula, D.J.

    1980-11-01

    This report is an attempt to collect into one place outline information concerning the techniques used and basic design of sample environment apparatus employed in neutron scattering experiments. Preliminary recommendations for the specimen environment programme of the SNS are presented. The general conclusion reached is that effort should be devoted towards improving reliability and efficiency of operation of specimen environment apparatus and developing systems which are robust and easy to use, rather than achieving performance at the limits of technology. (author)

  18. Thermal property testing technique on micro specimen

    International Nuclear Information System (INIS)

    Baba, Tetsuya; Kishimoto, Isao; Taketoshi, Naoyuki

    2000-01-01

    This study aims at establishment of further development on some testing techniques on the nuclear advanced basic research accumulated by the National Research Laboratory of Metrology for ten years. For this purpose, a technology to test heat diffusion ratio and specific heat capacity of less than 3 mm in diameter and 1 mm in thickness of micro specimen and technology to test heat diffusion ratio at micro area of less than 1 mm in area along cross section of less than 10 mm in diameter of column specimen were developed to contribute to common basic technology supporting the nuclear power field. As a result, as an element technology to test heat diffusion ratio and specific heat capacity of the micro specimen, a specimen holding technique stably to hold a micro specimen with 3 mm in diameter could be developed. And, for testing the specific heat capacity by using the laser flush differential calorimetry, a technique to hold two specimen of 5 mm in diameter at their proximities was also developed. In addition, by promoting development of thermal property data base capable of storing thermal property data obtained in this study and with excellent workability in this 1998 fiscal year a data in/out-put program with graphical user interface could be prepared. (G.K.)

  19. Comparative study on Charpy specimen reconstitution techniques

    International Nuclear Information System (INIS)

    Bourdiliau, B.; Decroix, G.-M.; Averty, X.; Wident, P.; Bienvenu, Y.

    2011-01-01

    Highlights: → Welding processes are used to reconstitute previously tested Charpy specimens. → Stud welding is preferred for a quick installation, almost immediately operational. → Friction welding produces better quality welds, but requires a development effort. - Abstract: Reconstitution techniques are often used to allow material from previously fractured Charpy-V specimens to be reused for additional experiments. This paper presents a comparative experimental study of various reconstitution techniques and evaluates the feasibility of these methods for future use in shielded cells. The following techniques were investigated: arc stud welding, 6.0 kW CO 2 continuous wave laser welding, 4.5 kW YAG continuous wave laser welding and friction welding. Subsize Charpy specimens were reconstituted using a 400 W YAG pulsed wave laser. The best result was obtained with arc stud welding; the resilience of the reconstituted specimens and the load-displacement curves agreed well with the reference specimens, and the temperature elevation caused by the welding process was limited to the vicinity of the weld. Good results were also obtained with friction welding; this process led to the best quality welds. Laser welding seems to have affected the central part of the specimens, thus leading to different resilience values and load-displacement curves.

  20. Studies on diagnostic value of CT images for hypopharyngeal cancer by comparing with sliced specimens

    International Nuclear Information System (INIS)

    Fujimura, Akiko

    1988-01-01

    The findings of preoperative CT were compared with extirpated specimens in 11 patients to evaluate the value of CT in diagnosing the extent of hypopharyngeal cancer. CT was capable of detecting tumor extent to the submucosal fibrofatty tissue, except for the case of tumor extent to the laryngeal ventricle that contains many mucous glands and is usually depicted as a dense shadow. When the margin of ossified cortex of the thyroid cartilage was irregular and surrounded by tumor shadow, or when the margin of the cricoid cartilage was irregular and accompanied by increased medullary concentration, the invasion of the tumor into these cartilages was histopathologically demonstrated. Tumor extension next to these ossified cartilages did not indicate histopathological invasion of the tumor whenever their margins were smooth and regular. The intrinsic laryngeal muscle and the inferior pharyngeal constrictor muscle were identified on CT. Tumor extent to these muscles was well correlated to histologically demonstrated tumor invasion. When vocal cord fixation was present, CT showed tumor extent either to the paralaryngeal space only or to the paralaryngeal space and thyroarytenoid muscle or posterior cricoarytenoid muscle. Extraluminal spread through the thyrohyoid membrane was depicted on CT as a distinctive shadow in the visceral space that surrounds the hypopharyngeal cavity. Computed tomography overestimated tumor invation into the submucosal layer, muscles, or laryngeal cartilages. (Namekawa, K.)

  1. Bilateral malignant phyllodes tumor of the breast | Odik | Nigerian ...

    African Journals Online (AJOL)

    ... biphasic tumors, arising from the intra-lobular breast stroma. It constitutes less than 1%of all breast tumors. Bilateralmalignant phyllodes tumor is uncommon.We report a case of 32-year oldmultiparouswoman who died of multi-organ metastatic disease. The diagnosis was based on histology report of the breast specimen.

  2. Sinus Tumors

    Science.gov (United States)

    ... RESOURCES Medical Societies Patient Education About this Website Font Size + - Home > CONDITIONS > Sinus Tumors Adult Sinusitis Pediatric ... and they vary greatly in location, size and type. Care for these tumors is individualized to each ...

  3. Tumors markers

    International Nuclear Information System (INIS)

    Yamaguchi-Mizumoto, N.H.

    1989-01-01

    In order to study blood and cell components alterations (named tumor markers) that may indicate the presence of a tumor, several methods are presented. Aspects as diagnostic, prognostic, therapeutic value and clinical evaluation are discussed. (M.A.C.)

  4. Wilms tumor

    Science.gov (United States)

    ... suggested. Alternative Names Nephroblastoma; Kidney tumor - Wilms Images Kidney anatomy Wilms tumor References Babaian KN, Delacroix SE, Wood CG, Jonasch E. Kidney cancer. In: Skorecki K, Chertow GM, Marsden PA, ...

  5. Radiation-induced reduction of the glial population during development disrupts the formation of olfactory glomeruli in an insect

    International Nuclear Information System (INIS)

    Oland, L.A.; Tolbert, L.P.; Mossman, K.L.

    1988-01-01

    Interactions between neurons and between neurons and glial cells have been shown by a number of investigators to be critical for normal development of the nervous system. In the olfactory system of Manduca sexta, sensory axons have been shown to induce the formation of synaptic glomeruli in the antennal lobe of the brain. Oland and Tolbert (1987) found that the growth of sensory axons into the developing antennal lobe causes changes in glial shape and disposition that presage the establishment of glomeruli, each surrounded by a glial envelope. Several lines of evidence lead us to hypothesize that the glial cells of the lobe may be acting as intermediaries in developmental interactions between sensory axons and neurons of the antennal lobe. In the present study, we have tested this hypothesis by using gamma-radiation to reduce the number of glial cells at a time when neurons of the antennal system are postmitotic but glomeruli have not yet developed. When glial numbers are severely reduced, the neuropil of the resulting lobe lacks glomeruli. Despite the presence of afferent axons, the irradiated lobe has many of the features of a lobe that developed in the absence of afferent axons. Our findings indicate that the glial cells must play a necessary role in the inductive influence of the afferent axons

  6. Operative outcomes of conventional specimen radiography versus in-operating room specimen radiography in radioactive seed-localized segmental mastectomies.

    Science.gov (United States)

    Rhee, Daniel; Pockaj, Barbara; Wasif, Nabil; Stucky, Chee-Chee; Pizzitola, Victor; Giurescu, Marina; Patel, Bhavika; McCarthy, Janice; Gray, Richard

    2018-01-01

    In-operating room specimen radiography (ORSR) has not been studied among women undergoing radioactive seed localization (RSL) for breast cancer surgery and had the potential to decrease operative time and perhaps improve intraoperative margin management. One hundred consecutive RSL segmental mastectomies among 98 patients using ORSR were compared to 100 consecutive segmental mastectomies among 98 patients utilizing conventional radiography (CSR) prior to the initiation of ORSR from December 2013 to January 2015 after radioactive seed localization. Final pathologic margins were considered to be 10 mm for all cases of no residual disease after biopsy or neoadjuvant therapy, but such patients were excluded from analyses involving tumor size. All patients' specimens were subjected to intraoperative pathologic consultation in addition to ORSR or CSR. The median age of the cohort was 65 years (range 36-97), and the median tumor size was 1 cm. There were no differences between the ORSR and CSR groups in age, tumor size, percentage of cases with only DCIS, and percentage of cases with microcalcifications. The ORSR group had a statistically significant lower BMI. Mean operative time from cut-to-close was not significantly different (ORSR 77 min, SD 24.8 vs CSR 76 min, SD 24.8, p = 0.75). There was no statistical difference in mean closest final pathologic margin (4.99 mm, SD 3.3 vs 4.88 mm, SD 3.5, p = 0.9). The percentage undergoing intraoperative margin re-excision (ORSR 40%, CR 47%, p = 0.31) and the mean total number of margins excised intraoperatively (ORSR 0.9, CR 1.0 p = 0.65) were similar. The rate of any margin CSR; this difference was not statistically significant (p = 0.25). The mean ratio of segmental mastectomy volume to maximum tumor diameter was less for ORSR (82.7cm2 vs 139.4cm2, p = 0.014). ORSR for RSL breast surgery, in the setting of routine intraoperative pathology consultation, does not significantly impact operative time, the rate or

  7. Stereotaxic microsurgical procedures of cerebral intracranial tumors guided by image and attended by computer

    International Nuclear Information System (INIS)

    Lopez Flores, Gerardo; Guerra Figueredo, Eritk; Ochoa Zaldivar, Luis

    2000-01-01

    It is reported that spatial guidance during microsurgery is an essential element. This application of stereotaxic surgery is shown at the International Center of Neurological Restoration (Cirene) from May, 1994, to February, 1998, on describing the performance of 65 microsurgical procedures under stereotaxic conditions among 62 patients with cerebral intracranial tumors. The procedure was divided into 3 stages: image acquisition, Cat, surgical planning , with Stasis planning system, and microsurgical procedures that included the Leksell, Micromar and Esteroflex stereotaxic systems. 27 of the total of patients presented glial tumors; 33, non-glial; and only 2 non-neoplastic lesions of diverse localization and size. 30 total resections We're made. Surgical morbidity was minimum and there was no surgical mortality. The main advantages of this method are: exact localization of the craniotomy, easy spatial guidance, and the opportunity to distinguish the limits between the tumor and the sound tissue. The possibility to apply Esteroflex to cerebral microsurgery was demonstrated

  8. Spinal Cord Glioneuronal Tumor with Rosetted Neuropil-Like Islands in Pediatric Age Group

    Directory of Open Access Journals (Sweden)

    Nil Comunoglu

    2014-01-01

    Full Text Available Glioneuronal neoplasms are rare tumors. Recently, an unusual glioneuronal tumor histologically showing neuropil-like islands has been described. Here, we present such a tumor originating from spinal cord of a 14-year-old girl, who has scoliosis and urinary incontinence. Microscopically, the glial component was chiefly fibrillary astrocytic, punctuated by neuropil-like islands. Immunohistochemically, glial tissue was GFAP positive, and neuropil-like areas and big neurons were synaptophysin reactive. For astrocytic component Ki-67 proliferation index was 1% and p53 was immunonegative. This case is unique in that in the literature it is the second reported case in pediatric age group that is located at spinal cord.

  9. Spinal tumors

    International Nuclear Information System (INIS)

    Goethem, J.W.M. van; Hauwe, L. van den; Oezsarlak, Oe.; Schepper, A.M.A. de; Parizel, P.M.

    2004-01-01

    Spinal tumors are uncommon lesions but may cause significant morbidity in terms of limb dysfunction. In establishing the differential diagnosis for a spinal lesion, location is the most important feature, but the clinical presentation and the patient's age and gender are also important. Magnetic resonance (MR) imaging plays a central role in the imaging of spinal tumors, easily allowing tumors to be classified as extradural, intradural-extramedullary or intramedullary, which is very useful in tumor characterization. In the evaluation of lesions of the osseous spine both computed tomography (CT) and MR are important. We describe the most common spinal tumors in detail. In general, extradural lesions are the most common with metastasis being the most frequent. Intradural tumors are rare, and the majority is extramedullary, with meningiomas and nerve sheath tumors being the most frequent. Intramedullary tumors are uncommon spinal tumors. Astrocytomas and ependymomas comprise the majority of the intramedullary tumors. The most important tumors are documented with appropriate high quality CT or MR images and the characteristics of these tumors are also summarized in a comprehensive table. Finally we illustrate the use of the new World Health Organization (WHO) classification of neoplasms affecting the central nervous system

  10. Brain Tumors

    Science.gov (United States)

    A brain tumor is a growth of abnormal cells in the tissues of the brain. Brain tumors can be benign, with no cancer cells, ... cancer cells that grow quickly. Some are primary brain tumors, which start in the brain. Others are ...

  11. Urogenital tumors

    Energy Technology Data Exchange (ETDEWEB)

    Weller, R.E.

    1994-03-01

    An overview is provided for veterinary care of urogenital tumors in companion animals, especially the dog. Neoplasms discussed include tumors of the kidney, urinary bladder, prostate, testis, ovary, vagina, vulva and the canine transmissible venereal tumor. Topics addressed include description, diagnosis and treatment.

  12. Closeout of JOYO-1 Specimen Fabrication Efforts

    International Nuclear Information System (INIS)

    ME Petrichek; JL Bump; RF Luther

    2005-01-01

    Fabrication was well under way for the JOYO biaxial creep and tensile specimens when the NR Space program was canceled. Tubes of FS-85, ASTAR-811C, and T-111 for biaxial creep specimens had been drawn at True Tube (Paso Robles, CA), while tubes of Mo-47.5 Re were being drawn at Rhenium Alloys (Cleveland, OH). The Mo-47.5 Re tubes are now approximately 95% complete. Their fabrication and the quantities produced will be documented at a later date. End cap material for FS-85, ASTAR-811C, and T-111 had been swaged at Pittsburgh Materials Technology, Inc. (PMTI) (Large, PA) and machined at Vangura (Clairton, PA). Cutting of tubes, pickling, annealing, and laser engraving were in process at PMTI. Several biaxial creep specimen sets of FS-85, ASTAR-811C, and T-111 had already been sent to Pacific Northwest National Laboratory (PNNL) for weld development. In addition, tensile specimens of FS-85, ASTAR-811C, T-111, and Mo-47.5 Re had been machined at Kin-Tech (North Huntington, PA). Actual machining of the other specimen types had not been initiated. Flowcharts 1-3 detail the major processing steps each piece of material has experienced. A more detailed description of processing will be provided in a separate document [B-MT(SRME)-51]. Table 1 lists the in-process materials and finished specimens. Also included are current metallurgical condition of these materials and specimens. The available chemical analyses for these alloys at various points in the process are provided in Table 2

  13. Correlation of histopathological factor of brain tumor and high thallium-201 uptake in single photon emission computed tomography

    International Nuclear Information System (INIS)

    Yoshii, Yoshihiko; Moritake, Takashi; Yamamoto, Tetsuya; Takano, Shingo; Tsuboi, Koji; Hyodo, Akio; Nose, Tadao; Satou, Motohiro

    1996-01-01

    This study was undertaken to investigate the relationship between several histological features and the degree of Tl-201 uptake in brain tumors. Tl-201 SPECT was performed on 52 patients with intracranial lesions. Histological examinations were carried out to determine the gradation of tumor cell density, vascularization, small-cell density, and matrix loosening, and the presence of necrosis, atypia, mitoses, and endothelial proliferation. The histological findings were classified into three categories. While the early uptake of Tl-201 depended on the degree of necrosis of glial tumor, the delayed Tl-201 uptake was closely related to the degree of necrosis, tumor cell density, and small-cell density, and may thus be of value for estimating the viability and degree of malignancy of glial tumors. In the non-glial tumors, the early and delayed Tl-201 uptakes were closely related to all histological parameters, with the increase of necrosis and vascularization in the tumor tissue being particularly closely related to high uptake levels. (author)

  14. Central nervous system tumors: Radiologic pathologic correlation and diagnostic approach

    Directory of Open Access Journals (Sweden)

    Ishita Pant

    2015-01-01

    Full Text Available Objective: This study was conducted to formulate location-wise radiologic diagnostic algorithms and assess their concordance with the final histopathological diagnosis so as to evaluate their utility in a rural setting where only basic facilities are available. Materials and Methods: A retrospective analysis to assess the concordance of radiology (primarily MRI with final histopathology report was done. Based on the most common incidence of tumor location and basic radiology findings, diagnostic algorithms were prepared. Results: For supratentorial intraaxial parenchymal location concordance was seen in all high-grade astrocytomas, low- and high-grade oligodendrogliomas, metastatic tumors, primitive neuroectodermal tumors, high-grade ependymomas, neuronal and mixed neuro-glial tumors and tumors of hematopoietic system. Lowest concordance was seen in low-grade astrocytomas. In the supratentorial intraaxial ventricular location, agreement was observed in choroid plexus tumors, ependymomas, low-grade astrocytomas and meningiomas; in the supratentorial extraaxial location, except for the lack of concordance in the only case of metastatic tumor, concordance was observed in meningeal tumors, tumors of the sellar region, tumors of cranial and paraspinal nerves; the infratentorial intraaxial parenchymal location showed agreement in low- as well as high-grade astrocytomas, metastatic tumors, high-grade ependymoma, embryonal tumors and hematopoietic tumors; in the infratentorial intraaxial ventricular location, except for the lack of concordance in one case of low-grade astrocytoma and two cases of medulloblastomas, agreement was observed in low- and high-grade ependymoma; infratentorial extraaxial tumors showed complete agreement in all tumors of cranial and paraspinal nerves, meningiomas, and hematopoietic tumors. Conclusion: A location-based approach to central nervous system (CNS tumors is helpful in establishing an appropriate differential diagnosis.

  15. Glial Draper Rescues Aβ Toxicity in a Drosophila Model of Alzheimer's Disease.

    Science.gov (United States)

    Ray, Arpita; Speese, Sean D; Logan, Mary A

    2017-12-06

    Pathological hallmarks of Alzheimer's disease (AD) include amyloid-β (Aβ) plaques, neurofibrillary tangles, and reactive gliosis. Glial cells offer protection against AD by engulfing extracellular Aβ peptides, but the repertoire of molecules required for glial recognition and destruction of Aβ are still unclear. Here, we show that the highly conserved glial engulfment receptor Draper/MEGF10 provides neuroprotection in an AD model of Drosophila (both sexes). Neuronal expression of human Aβ42 arc in adult flies results in robust Aβ accumulation, neurodegeneration, locomotor dysfunction, and reduced lifespan. Notably, all of these phenotypes are more severe in draper mutant animals, whereas enhanced expression of glial Draper reverses Aβ accumulation, as well as behavioral phenotypes. We also show that the signal transducer and activator of transcription (Stat92E), c-Jun N-terminal kinase (JNK)/AP-1 signaling, and expression of matrix metalloproteinase-1 (Mmp1) are activated downstream of Draper in glia in response to Aβ42 arc exposure. Furthermore, Aβ42-induced upregulation of the phagolysosomal markers Atg8 and p62 was notably reduced in draper mutant flies. Based on our findings, we propose that glia clear neurotoxic Aβ peptides in the AD model Drosophila brain through a Draper/STAT92E/JNK cascade that may be coupled to protein degradation pathways such as autophagy or more traditional phagolysosomal destruction methods. SIGNIFICANCE STATEMENT Alzheimer's disease (AD) and similar dementias are common incurable neurodegenerative disorders in the aging population. As the primary immune responders in the brain, glial cells are implicated as key players in the onset and progression of AD and related disorders. Here we show that the glial engulfment receptor Draper is protective in a Drosophila model of AD, reducing levels of amyloid β (Aβ) peptides, reversing locomotor defects, and extending lifespan. We further show that protein degradation pathways are

  16. Dampak Hipoksia Sistemik terhadap Malondialdehida, Glial Fibrillary Acidic Protein dan Aktivitas Asetilkolin Esterase Otak Tikus

    Directory of Open Access Journals (Sweden)

    Andriani Andriani

    2016-09-01

    Full Text Available Hipoksia sistemik menyebabkan berkurangnya oksigen dan energi di otak sehingga memicupenglepasan neurotransmiter asetilkolin, meningkatkan radikal bebas dan glial fibrillary acidic protein (GFAPyang berfungsi menjaga kekuatan membran. Tujuan penelitian untuk melihat gambaran adaptasi otak padahipoksia sistemik terhadap fungsi asetilkolin esterase, kerusakan membran sel neuron dan astrosit. Penelitiandilakukan di Laboratorium Biokimia & Biologi Molekuler FK Universitas Indonesia, pada tahun 2013.Penelitian ekperimental ini menggunakan hewan coba tikus spraque dawley yang diinduksi hipoksia sistemikyang diambil jaringan otak bagian korteks dan plasma tikus. Kelompok tikus terdiri atas kelompok kontrol,kelompok perlakuan induksi hipoksia hari ke-1, 3 hari, 5 hari dan hari ke-7. Parameter yang diukur adalahkadar malondialdehida (MDA otak dan plasma, aktivitas spesifik enzim AChE jaringan otak serta kadar GFAPjaringan otak. Hasil menunjukkan bahwa hipoksia sistemik tidak meningkatkankadar MDA otak dan plasma.Induksi hipoksia sistemik meningkatkan aktivitas spesifik enzim AChE dan kadar GFAP jaringan otak secarabermakna. Pada plasma tidak terjadi peningkatan kadar GFAP. Hipoksia sistemik selama hari ke-7 belummenyebabkan kerusakan oksidatif, namun memperlihatkan peningkatan aktivitas AChe dan adaptasi astrositmelalui peningkatan GFAP. Kata kunci: hipoksia, astrosit, glial fibrillary acidic protein, malondialdehida, asetilkolin esterase   Systemic Hypoxia Effect on Rat Brain Malondialdehyde, Glial FibrillaryAcidic Protein, and Acetylcholine Esterase Activity Abstract Sistemic hypoxia causes lack of oxygen and energy in brain that trigger the release of acetylcholine,free radical and Glial fibrillary acidic protein (GFAP, a specific protein in astrocyte cells that act to strenghtenastrocite membrane. The aim of the research was to evaluate the damages of brain in systemic hypoxiathrough activity of acetylcholine esterase, neuron and astrocyte membran

  17. SUMO-1 is associated with a subset of lysosomes in glial protein aggregate diseases.

    Science.gov (United States)

    Wong, Mathew B; Goodwin, Jacob; Norazit, Anwar; Meedeniya, Adrian C B; Richter-Landsberg, Christiane; Gai, Wei Ping; Pountney, Dean L

    2013-01-01

    Oligodendroglial inclusion bodies characterize a subset of neurodegenerative diseases. Multiple system atrophy (MSA) is characterized by α-synuclein glial cytoplasmic inclusions and progressive supranuclear palsy (PSP) is associated with glial tau inclusions. The ubiquitin homologue, SUMO-1, has been identified in inclusion bodies in MSA, located in discrete sub-domains in α-synuclein-positive inclusions. We investigated SUMO-1 associated with oligodendroglial inclusion bodies in brain tissue from MSA and PSP and in glial cell models. We examined MSA and PSP cases and compared to age-matched normal controls. Fluorescence immunohistochemistry revealed frequent SUMO-1 sub-domains within and surrounding inclusions bodies in both diseases and showed punctate co-localization of SUMO-1 and the lysosomal marker, cathepsin D, in affected brain regions. Cell counting data revealed that 70-75 % of lysosomes in inclusion body-positive oligodendrocytes were SUMO-1-positive consistently across MSA and PSP cases, compared to 20 % in neighbouring inclusion body negative oligodendrocytes and 10 % in normal brain tissue. Hsp90 co-localized with some SUMO-1 puncta. We examined the SUMO-1 status of lysosomes in 1321N1 human glioma cells over-expressing α-synuclein and in immortalized rat oligodendrocyte cells over-expressing the four repeat form of tau following treatment with the proteasome inhibitor, MG132. We also transfected 1321N1 cells with the inherently aggregation-prone huntingtin exon 1 mutant, HttQ74-GFP. Each cell model showed the association of SUMO-1-positive lysosomes around focal cytoplasmic accumulations of α-synuclein, tau or HttQ74-GFP, respectively. Association of SUMO-1 with lysosomes was also detected in glial cells bearing α-synuclein aggregates in a rotenone-lesioned rat model. SUMO-1 labelling of lysosomes showed a major increase between 24 and 48 h post-incubation of 1321N1 cells with MG132 resulting in an increase in a 90 kDa SUMO-1-positive band

  18. In Vitro Efficient Expansion of Tumor Cells Deriving from Different Types of Human Tumor Samples

    Directory of Open Access Journals (Sweden)

    Ilaria Turin

    2014-03-01

    Full Text Available Obtaining human tumor cell lines from fresh tumors is essential to advance our understanding of antitumor immune surveillance mechanisms and to develop new ex vivo strategies to generate an efficient anti-tumor response. The present study delineates a simple and rapid method for efficiently establishing primary cultures starting from tumor samples of different types, while maintaining the immuno-histochemical characteristics of the original tumor. We compared two different strategies to disaggregate tumor specimens. After short or long term in vitro expansion, cells analyzed for the presence of malignant cells demonstrated their neoplastic origin. Considering that tumor cells may be isolated in a closed system with high efficiency, we propose this methodology for the ex vivo expansion of tumor cells to be used to evaluate suitable new drugs or to generate tumor-specific cytotoxic T lymphocytes or vaccines.

  19. Tumor immunology

    International Nuclear Information System (INIS)

    Otter, W. den

    1987-01-01

    Tumor immunology, the use of immunological techniques for tumor diagnosis and approaches to immunotherapy of cancer are topics covered in this multi-author volume. Part A, 'Tumor Immunology', deals with present views on tumor-associated antigens, the initiation of immune reactions of tumor cells, effector cell killing, tumor cells and suppression of antitumor immunity, and one chapter dealing with the application of mathematical models in tumor immunology. Part B, 'Tumor Diagnosis and Imaging', concerns the use of markers to locate the tumor in vivo, for the histological diagnosis, and for the monitoring of tumor growth. In Part C, 'Immunotherapy', various experimental approaches to immunotherapy are described, such as the use of monoclonal antibodies to target drugs, the use of interleukin-2 and the use of drugs inhibiting suppression. In the final section, the evaluation, a pathologist and a clinician evaluate the possibilities and limitations of tumor immunology and the extent to which it is useful for diagnosis and therapy. refs.; figs.; tabs

  20. Clinical evaluation of a mobile digital specimen radiography system for intraoperative specimen verification.

    Science.gov (United States)

    Wang, Yingbing; Ebuoma, Lilian; Saksena, Mansi; Liu, Bob; Specht, Michelle; Rafferty, Elizabeth

    2014-08-01

    Use of mobile digital specimen radiography systems expedites intraoperative verification of excised breast specimens. The purpose of this study was to evaluate the performance of a such a system for verifying targets. A retrospective review included 100 consecutive pairs of breast specimen radiographs. Specimens were imaged in the operating room with a mobile digital specimen radiography system and then with a conventional digital mammography system in the radiology department. Two expert reviewers independently scored each image for image quality on a 3-point scale and confidence in target visualization on a 5-point scale. A target was considered confidently verified only if both reviewers declared the target to be confidently detected. The 100 specimens contained a total of 174 targets, including 85 clips (49%), 53 calcifications (30%), 35 masses (20%), and one architectural distortion (1%). Although a significantly higher percentage of mobile digital specimen radiographs were considered poor quality by at least one reviewer (25%) compared with conventional digital mammograms (1%), 169 targets (97%), were confidently verified with mobile specimen radiography; 172 targets (98%) were verified with conventional digital mammography. Three faint masses were not confidently verified with mobile specimen radiography, and conventional digital mammography was needed for confirmation. One faint mass and one architectural distortion were not confidently verified with either method. Mobile digital specimen radiography allows high diagnostic confidence for verification of target excision in breast specimens across target types, despite lower image quality. Substituting this modality for conventional digital mammography can eliminate delays associated with specimen transport, potentially decreasing surgical duration and increasing operating room throughput.

  1. Sequencing historical specimens: successful preparation of small specimens with low amounts of degraded DNA.

    Science.gov (United States)

    Sproul, John S; Maddison, David R

    2017-11-01

    Despite advances that allow DNA sequencing of old museum specimens, sequencing small-bodied, historical specimens can be challenging and unreliable as many contain only small amounts of fragmented DNA. Dependable methods to sequence such specimens are especially critical if the specimens are unique. We attempt to sequence small-bodied (3-6 mm) historical specimens (including nomenclatural types) of beetles that have been housed, dried, in museums for 58-159 years, and for which few or no suitable replacement specimens exist. To better understand ideal approaches of sample preparation and produce preparation guidelines, we compared different library preparation protocols using low amounts of input DNA (1-10 ng). We also explored low-cost optimizations designed to improve library preparation efficiency and sequencing success of historical specimens with minimal DNA, such as enzymatic repair of DNA. We report successful sample preparation and sequencing for all historical specimens despite our low-input DNA approach. We provide a list of guidelines related to DNA repair, bead handling, reducing adapter dimers and library amplification. We present these guidelines to facilitate more economical use of valuable DNA and enable more consistent results in projects that aim to sequence challenging, irreplaceable historical specimens. © 2017 John Wiley & Sons Ltd.

  2. Effects of X-irradiation on glial cells in the developing rat brain

    International Nuclear Information System (INIS)

    Ferrer, I.; Borras, D.

    1994-01-01

    Sprague-Dawley rats were given a single dose of 2Gy X-rays when 1 or 3 days of age. Dying cells in the germinal layer of the telencephalon reached peak values 6h after irradiation; dead cells were cleared 48h later. These effects were almost abolished with the injection of cyclohexamide (1 μg/g body weight) given at the time of irradiation. PCNA-immunoreactive cells (cells in late G 1 and S phases of the cell cycle) and PCNA-negative cells were sensitive to X-rays. Long-term effects on glial cell populations in the subcortical white matter of the cingulum were examined in irradiated rats, killed at postnatal day 30 (P30), by means of glial fibrillary acidic protein, vimentin and S-100 immunohistochemistry, as well as with anti-TGF-α (transformerly growth factor) antibodies that are used as putative oligodendrogial cell markers in the white matter of rat. (author)

  3. Enteric glial cells and their role in gastrointestinal motor abnormalities: Introducing the neuro-gliopathies

    Institute of Scientific and Technical Information of China (English)

    Gabrio Bassotti; Vincenzo Villanacci; Simona Fisogni; Elisa Rossi; Paola Baronio; Carlo Clerici; Christoph A Maurer; Gieri Cathomas; Elisabetta Antonelli

    2007-01-01

    The role of enteric glial cells has somewhat changed from that of mere mechanical support elements, gluing together the various components of the enteric nervous system, to that of active participants in the complex interrelationships of the gut motor and inflammatory events. Due to their multiple functions, spanning from supporting elements in the myenteric plexuses to neurotransmitters, to neuronal homeostasis, to antigen presenting cells, this cell population has probably more intriguing abilities than previously thought. Recently,some evidence has been accumulating that shows how these cells may be involved in the pathophysiological aspects of some diseases. This review will deal with the properties of the enteric glial cells more strictly related to gastrointestinal motor function and the human pathological conditions in which these cells may play a role, suggesting the possibility of enteric neurogliopathies.

  4. [Activity of glial cells in trigeminal nervous system in rats with experimental pulpitis].

    Science.gov (United States)

    Gu, Bin; Liu, Na; Liu, Hongchen

    2014-04-29

    To observe the activity change of astrocyte in related nucleus caused by acute pulpitis in rats. Rat acute pulpitis model was induced by lipopolysaccharides (LPS). And, according to processing time, a total of 30 rats were divided into 5 groups of control, 6, 12, 24 and 48 h. Immunohistochemistry and Western blot were employed to detect the dynamic expression of glial fibrillary acidic protein (GFAP) in spinal nucleus of trigeminal nerve (Vc). The relative gray value of ipsilateral Vc GFAP expression in experimental groups was 153 ± 11 at 12 h. And it significantly increased versus the control group (100 ± 4)(P pulpitis model, activated glial cells are probably involved in the processes of pulpitis and hyperalgesia.

  5. Reappraisal of Bergmann glial cells as modulators of cerebellar circuit function

    Directory of Open Access Journals (Sweden)

    Chris I De Zeeuw

    2015-07-01

    Full Text Available Just as there is a huge morphological and functional diversity of neuron types specialized for specific aspects of information processing in the brain, astrocytes have equally distinct morphologies and functions that aid optimal functioning of the circuits in which they are embedded. One type of astrocyte, the Bergmann glial cell of the cerebellum, is a prime example of a highly diversified astrocyte type, the architecture of which is adapted to the cerebellar circuit and facilitates an impressive range of functions that optimize information processing in the adult brain. In this review we expand on the function of the Bergmann glial cell in the cerebellum to highlight the importance of astrocytes not only in housekeeping functions, but also in contributing to plasticity and information processing in the cerebellum.

  6. Restraining reactive oxygen species in Listeria monocytogenes promotes the apoptosis of glial cells.

    Science.gov (United States)

    Li, Sen; Li, Yixuan; Chen, Guowei; Zhang, Jingchen; Xu, Fei; Wu, Man

    2017-07-01

    Listeria monocytogenes is a facultative anaerobic foodborne pathogen that can traverse the blood-brain barrier and cause brain infection. L. monocytogenes infection induces host cell apoptosis in several cell types. In this study, we investigated the apoptosis of human glioma cell line U251 invaded by L. monocytogenes and evaluated the function of bacterial reactive oxygen species (ROS) during infection. Bacterial ROS level was reduced by carrying out treatment with N-acetyl cysteine (NAC) and diphenyleneiodonium chloride (DPI). After infection, the apoptosis of U251 cells was examined by flow cytometry assay and propidium iodide staining. DPI and NAC efficiently decreased ROS level in L. monocytogenes without affecting bacterial growth. Moreover, the apoptosis of glial cells was enhanced upon invasion of DPI- and NAC-pretreated L. monocytogenes. Results indicate that the apoptosis of glial cells can be induced by L. monocytogenes, and that the inhibition of bacterial ROS increases the apoptosis of host cells.

  7. HIV-1 Tat protein induces glial cell autophagy through enhancement of BAG3 protein levels.

    Science.gov (United States)

    Bruno, Anna Paola; De Simone, Francesca Isabella; Iorio, Vittoria; De Marco, Margot; Khalili, Kamel; Sariyer, Ilker Kudret; Capunzo, Mario; Nori, Stefania Lucia; Rosati, Alessandra

    2014-01-01

    BAG3 protein has been described as an anti-apoptotic and pro-autophagic factor in several neoplastic and normal cells. We previously demonstrated that BAG3 expression is elevated upon HIV-1 infection of glial and T lymphocyte cells. Among HIV-1 proteins, Tat is highly involved in regulating host cell response to viral infection. Therefore, we investigated the possible role of Tat protein in modulating BAG3 protein levels and the autophagic process itself. In this report, we show that transfection with Tat raises BAG3 levels in glioblastoma cells. Moreover, BAG3 silencing results in highly reducing Tat- induced levels of LC3-II and increasing the appearance of sub G0/G1 apoptotic cells, in keeping with the reported role of BAG3 in modulating the autophagy/apoptosis balance. These results demonstrate for the first time that Tat protein is able to stimulate autophagy through increasing BAG3 levels in human glial cells.

  8. MALDI mass spectrometry based molecular phenotyping of CNS glial cells for prediction in mammalian brain tissue

    DEFF Research Database (Denmark)

    Hanrieder, Jørg; Wicher, Grzegorz; Bergquist, Jonas

    2011-01-01

    . Complementary proteomic experiments revealed the identity of these signature proteins that were predominantly expressed in the different glial cell types, including histone H4 for oligodendrocytes and S100-A10 for astrocytes. MALDI imaging MS was performed, and signature masses were employed as molecular...... tracers for prediction of oligodendroglial and astroglial localization in brain tissue. The different cell type specific protein distributions in tissue were validated using immunohistochemistry. ICMS of intact neuroglia is a simple and straightforward approach for characterization and discrimination...

  9. Differentiation of a bipotential glial progenitor cell in a single cell microculture.

    Science.gov (United States)

    Temple, S; Raff, M C

    Although it is known that most cells of the vertebrate central nervous system (CNS) are derived from the neuroepithelial cells of the neural tube, the factors determining whether an individual neuroepithelial cell develops into a particular type of neurone or glial cell remain unknown. A promising model for studying this problem is the bipotential glial progenitor cell in the developing rat optic nerve; this cell differentiates into a particular type of astrocyte (a type-2 astrocyte) if cultured in 10% fetal calf serum (FCS) and into an oligodendrocyte if cultured in serum-free medium. As the oligodendrocyte-type-2 astrocyte (0-2A) progenitor cell can differentiate along either glial pathway in neurone-free cultures, living axons clearly are not required for its differentiation, at least in vitro. However, the studies on 0-2A progenitor cells were carried out in bulk cultures of optic nerve, and so it was possible that other cell-cell interactions were required for differentiation in culture. We show here that 0-2A progenitor cells can differentiate into type-2 astrocytes or oligodendrocytes when grown as isolated cells in microculture, indicating that differentiation along either glial pathway in vitro does not require signals from other CNS cells, apart from the signals provided by components of the culture medium. We also show that single 0-2A progenitor cells can differentiate along either pathway without dividing, supporting our previous studies using 3H-thymidine and suggesting that DNA replication is not required for these cells to choose between the two differentiation programmes.

  10. Substance P spinal signaling induces glial activation and nociceptive sensitization after fracture

    OpenAIRE

    Li, Wen-Wu; Guo, Tian-Zhi; Shi, Xiaoyou; Sun, Yuan; Wei, Tzuping; Clark, David J; Kingery, Wade S

    2015-01-01

    Tibia fracture in rodents induces substance P (SP)-dependent keratinocyte activation and inflammatory changes in the hindlimb, similar to those seen in complex regional pain syndrome (CRPS). In animal pain models spinal glial cell activation results in nociceptive sensitization. This study tested the hypothesis that limb fracture triggers afferent C-fiber SP release in the dorsal horn, resulting in chronic glia activation and central sensitization. At 4 weeks after tibia fracture and casting ...

  11. Possible role of glial cells in the relationship between thyroid dysfunction and mental disorders

    OpenAIRE

    Noda, Mami

    2015-01-01

    It is widely accepted that there is a close relationship between the endocrine system and the central nervous system (CNS). Among hormones closely related to the nervous system, thyroid hormones (THs) are critical for the development and function of the CNS; not only for neuronal cells but also for glial development and differentiation. Any impairment of TH supply to the developing CNS causes severe and irreversible changes in the overall architecture and function of the human brain, leading ...

  12. Sex- and age-dependent effects of thyroid hormone on glial morphology and function

    OpenAIRE

    Noda, Mami; Mori, Yuki; Yoshioka, Yusaku

    2016-01-01

    Thyroid hormones (THs) are essential for the development and function of the central nervous system (CNS), not only for neuronal cells but also for glial development and differentiation. In adult CNS, both hypo- and hyper-thyroidism may affect psychological condition and potentially increase the risk of cognitive impairment and neurodegeneration including Alzheimer’s disease (AD). We have reported non-genomic effects of tri-iodothyronine (T3) on microglial functions and its signaling in vitro...

  13. Measuring Glial Metabolism in Repetitive Brain Trauma and Alzheimer’s Disease

    Science.gov (United States)

    2016-09-01

    stages of repetitive brain trauma as well. Current methods of measure brain glutamate using proton spectroscopy is not specific to different cell...covering a representative range of clinical cases: a young female , young male , middle-aged male (all healthy volunteers) and a male patient with...AWARD NUMBER: W81XWH-15-1-0412 TITLE: Measuring Glial Metabolism in Repetitive Brain Trauma and Alzheimer’s Disease PRINCIPAL INVESTIGATOR

  14. Effect of glial cell line-derived neurotrophic factor on retinal function after experimental branch retinal vein occlusion

    DEFF Research Database (Denmark)

    Ejstrup, Rasmus; Dornonville de la Cour, Morten; Kyhn, Maria Voss

    2012-01-01

    The objective of the study was to investigate the effect of glial cell line-derived neurotrophic factor (GDNF) on the multifocal electroretinogram (mfERG) following an induced branch retinal vein occlusion (BRVO) in pigs.......The objective of the study was to investigate the effect of glial cell line-derived neurotrophic factor (GDNF) on the multifocal electroretinogram (mfERG) following an induced branch retinal vein occlusion (BRVO) in pigs....

  15. Characteristics of Glial Reaction in the Perinatal Rat Cortex: Effect of Lesion Size in the ‘Critical Period’

    Directory of Open Access Journals (Sweden)

    Mihály Kálmán

    2000-01-01

    tissue defect plus reactive gliosis; and (iii healing always with reactive gliosis. The age limits between them were at P0 and P5. The glial reactivity seemingly appears after the end of the neuronal migration and just precedes the massive transformation of the radial glia into astrocytes. Estimating the position of the appearance of glial reactivity among the events of cortical maturation can help to adapt the experimental results to humans.

  16. A novel and efficient gene transfer strategy reduces glial reactivity and improves neuronal survival and axonal growth in vitro

    OpenAIRE

    Desclaux, Mathieu; Teigell, Marisa; Amar, Lahouari; Vogel, Roland; Giménez y Ribotta, Minerva; Privát, Alain M.; Mallet, Jacques

    2009-01-01

    Background: The lack of axonal regeneration in the central nervous system is attributed among other factors to the formation of a glial scar. This cellular structure is mainly composed of reactive astrocytes that overexpress two intermediate filament proteins, the glial fibrillary acidic protein (GFAP) and vimentin. Indeed, in vitro, astrocytes lacking GFAP or both GFAP and vimentin were shown to be the substrate for increased neuronal plasticity. Moreover, double knockout mice lacking both G...

  17. [The effect of hyperthyroidism on the cognition processes and the state of the glial intermediate filaments in the rat brain].

    Science.gov (United States)

    Nedzvets'kyĭ, V S; Nerush, P O

    2010-01-01

    The effects of hyperthyreosis on oxidative stress, state of glial intermediate filaments and memory were investigated. We observed a significant increase in lipid peroxidation products into both hippocampus and cortex and memory worsening. The changes of GFAP polypeptides was observed in hippocampus and cortex. In group of rats with hyperthyreosis, the content of GFAP in both soluble and filamentous fractions was increased in hippocampus. This data shows, that glial cytoskeleton is reconstructed under thyroid hormone effects.

  18. The central nervous system of sea cucumbers (Echinodermata: Holothuroidea shows positive immunostaining for a chordate glial secretion

    Directory of Open Access Journals (Sweden)

    Grondona Jesus M

    2009-06-01

    Full Text Available Abstract Background Echinoderms and chordates belong to the same monophyletic taxon, the Deuterostomia. In spite of significant differences in body plan organization, the two phyla may share more common traits than was thought previously. Of particular interest are the common features in the organization of the central nervous system. The present study employs two polyclonal antisera raised against bovine Reissner's substance (RS, a secretory product produced by glial cells of the subcomissural organ, to study RS-like immunoreactivity in the central nervous system of sea cucumbers. Results In the ectoneural division of the nervous system, both antisera recognize the content of secretory vacuoles in the apical cytoplasm of the radial glia-like cells of the neuroepithelium and in the flattened glial cells of the non-neural epineural roof epithelium. The secreted immunopositive material seems to form a thin layer covering the cell apices. There is no accumulation of the immunoreactive material on the apical surface of the hyponeural neuroepithelium or the hyponeural roof epithelium. Besides labelling the supporting cells and flattened glial cells of the epineural roof epithelium, both anti-RS antisera reveal a previously unknown putative glial cell type within the neural parenchyma of the holothurian nervous system. Conclusion Our results show that: a the glial cells of the holothurian tubular nervous system produce a material similar to Reissner's substance known to be synthesized by secretory glial cells in all chordates studied so far; b the nervous system of sea cucumbers shows a previously unrealized complexity of glial organization. Our findings also provide significant clues for interpretation of the evolution of the nervous system in the Deuterostomia. It is suggested that echinoderms and chordates might have inherited the RS-producing radial glial cell type from the central nervous system of their common ancestor, i.e., the last common

  19. Hippocampal kindling alters the concentration of glial fibrillary acidic protein and other marker proteins in rat brain

    DEFF Research Database (Denmark)

    Hansen, A; Jørgensen, Ole Steen; Bolwig, T G

    1990-01-01

    The effect of hippocampal kindling on neuronal and glial marker proteins was studied in the rat by immunochemical methods. In hippocampus, pyriform cortex and amygdala there was an increase in glial fibrillary acidic protein (GFAP), indicating reactive gliosis, and an increase in the glycolytic...... enzyme NSE, suggesting increased anaerobic metabolism. Neuronal cell adhesion molecule (NCAM) decreased in pyriform cortex and amygdala of kindled rats, indicating neuronal degeneration....

  20. Glial cell morphological and density changes through the lifespan of rhesus macaques.

    Science.gov (United States)

    Robillard, Katelyn N; Lee, Kim M; Chiu, Kevin B; MacLean, Andrew G

    2016-07-01

    How aging impacts the central nervous system (CNS) is an area of intense interest. Glial morphology is known to affect neuronal and immune function as well as metabolic and homeostatic balance. Activation of glia, both astrocytes and microglia, occurs at several stages during development and aging. The present study analyzed changes in glial morphology and density through the entire lifespan of rhesus macaques, which are physiologically and anatomically similar to humans. We observed apparent increases in gray matter astrocytic process length and process complexity as rhesus macaques matured from juveniles through adulthood. These changes were not attributed to cell enlargement because they were not accompanied by proportional changes in soma or process volume. There was a decrease in white matter microglial process length as rhesus macaques aged. Aging was shown to have a significant effect on gray matter microglial density, with a significant increase in aged macaques compared with adults. Overall, we observed significant changes in glial morphology as macaques age indicative of astrocytic activation with subsequent increase in microglial density in aged macaques. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Stereological analysis of neuron, glial and endothelial cell numbers in the human amygdaloid complex.

    Directory of Open Access Journals (Sweden)

    María García-Amado

    Full Text Available Cell number alterations in the amygdaloid complex (AC might coincide with neurological and psychiatric pathologies with anxiety imbalances as well as with changes in brain functionality during aging. This stereological study focused on estimating, in samples from 7 control individuals aged 20 to 75 years old, the number and density of neurons, glia and endothelial cells in the entire AC and in its 5 nuclear groups (including the basolateral (BL, corticomedial and central groups, 5 nuclei and 13 nuclear subdivisions. The volume and total cell number in these territories were determined on Nissl-stained sections with the Cavalieri principle and the optical fractionator. The AC mean volume was 956 mm(3 and mean cell numbers (x10(6 were: 15.3 neurons, 60 glial cells and 16.8 endothelial cells. The numbers of endothelial cells and neurons were similar in each AC region and were one fourth the number of glial cells. Analysis of the influence of the individuals' age at death on volume, cell number and density in each of these 24 AC regions suggested that aging does not affect regional size or the amount of glial cells, but that neuron and endothelial cell numbers respectively tended to decrease and increase in territories such as AC or BL. These accurate stereological measures of volume and total cell numbers and densities in the AC of control individuals could serve as appropriate reference values to evaluate subtle alterations in this structure in pathological conditions.

  2. How Does Transcranial Magnetic Stimulation Influence Glial Cells in the Central Nervous System?

    Directory of Open Access Journals (Sweden)

    Carlie L Cullen

    2016-04-01

    Full Text Available Transcranial magnetic stimulation (TMS is widely used in the clinic, and while it has a direct effect on neuronal excitability, the beneficial effects experienced by patients are likely to include the indirect activation of other cell types. Research conducted over the past two decades has made it increasingly clear that a population of non-neuronal cells, collectively known as glia, respond to and facilitate neuronal signalling. Each glial cell type has the ability to respond to electrical activity directly or indirectly, making them likely cellular effectors of TMS. TMS has been shown to enhance adult neural stem and progenitor cell proliferation, but the effect on cell survival and differentiation is less certain. Furthermore there is limited information regarding the response of astrocytes and microglia to TMS, and a complete paucity of data relating to the response of oligodendrocyte-lineage cells to this treatment. However, due to the critical and yet multifaceted role of glial cells in the CNS, the influence that TMS has on glial cells is certainly an area that warrants careful examination.

  3. Long term effects of lipopolysaccharide on satellite glial cells in mouse dorsal root ganglia

    Energy Technology Data Exchange (ETDEWEB)

    Blum, E. [Laboratory of Experimental Surgery, Hadassah-Hebrew University Medical Center, Mount Scopus, Jerusalem 91240 (Israel); Procacci, P.; Conte, V.; Sartori, P. [Dipartimento di Scienze Biomediche per la Salute, University of Milan, via Mangiagalli 14, I-20133 Milano (Italy); Hanani, M., E-mail: hananim@cc.huji.ac.il [Laboratory of Experimental Surgery, Hadassah-Hebrew University Medical Center, Mount Scopus, Jerusalem 91240 (Israel)

    2017-01-01

    Lipopolysaccharide (LPS) has been used extensively to study neuroinflammation, but usually its effects were examined acutely (24 h<). We have shown previously that a single intraperitoneal LPS injection activated satellite glial cells (SGCs) in mouse dorsal root ganglia (DRG) and altered several functional parameters in these cells for at least one week. Here we asked whether the LPS effects would persist for 1 month. We injected mice with a single LPS dose and tested pain behavior, assessed SGCs activation in DRG using glial fibrillary acidic protein (GFAP) immunostaining, and injected a fluorescent dye intracellularly to study intercellular coupling. Electron microscopy was used to quantitate changes in gap junctions. We found that at 30 days post-LPS the threshold to mechanical stimulation was lower than in controls. GFAP expression, as well as the magnitude of dye coupling among SGCs were greater than in controls. Electron microscopy analysis supported these results, showing a greater number of gap junctions and an abnormal growth of SGC processes. These changes were significant, but less prominent than at 7 days post-LPS. We conclude that a single LPS injection exerts long-term behavioral and cellular changes. The results are consistent with the idea that SGC activation contributes to hyperalgesia. - Highlights: • A single lipopolysaccharides injection activated glia in mouse dorsal root ganglia for 30 days. • This was accompanied by increased communications by gap junctions among glia and by hyperalgesia. • Glial activation and coupling may contribute to chronic pain.

  4. Electrogenic glutamate uptake is a major current carrier in the membrane of axolotl retinal glial cells

    Science.gov (United States)

    Brew, Helen; Attwell, David

    1987-06-01

    Glutamate is taken up avidly by glial cells in the central nervous system1. Glutamate uptake may terminate the transmitter action of glutamate released from neurons1, and keep extracellular glutamate at concentrations below those which are neurotoxic. We report here that glutamate evokes a large inward current in retinal glial cells which have their membrane potential and intracellular ion concentrations controlled by the whole-cell patch-clamp technique2. This current seems to be due to an electrogenic glutamate uptake carrier, which transports at least two sodium ions with every glutamate anion carried into the cell. Glutamate uptake is strongly voltage-dependent, decreasing at depolarized potentials: when fully activated, it contributes almost half of the conductance in the part of the glial cell membrane facing the retinal neurons. The spatial localization, glutamate affinity and magnitude of the uptake are appropriate for terminating the synaptic action of glutamate released from photoreceptors and bipolar cells. These data challenge present explanations of how the b-wave of the electroretinogram is generated, and suggest a mechanism for non-vesicular voltage-dependent release of glutamate from neurons.

  5. Enteric Glial Cells: A New Frontier in Neurogastroenterology and Clinical Target for Inflammatory Bowel Diseases.

    Science.gov (United States)

    Ochoa-Cortes, Fernando; Turco, Fabio; Linan-Rico, Andromeda; Soghomonyan, Suren; Whitaker, Emmett; Wehner, Sven; Cuomo, Rosario; Christofi, Fievos L

    2016-02-01

    The word "glia" is derived from the Greek word "γλoια," glue of the enteric nervous system, and for many years, enteric glial cells (EGCs) were believed to provide mainly structural support. However, EGCs as astrocytes in the central nervous system may serve a much more vital and active role in the enteric nervous system, and in homeostatic regulation of gastrointestinal functions. The emphasis of this review will be on emerging concepts supported by basic, translational, and/or clinical studies, implicating EGCs in neuron-to-glial (neuroglial) communication, motility, interactions with other cells in the gut microenvironment, infection, and inflammatory bowel diseases. The concept of the "reactive glial phenotype" is explored as it relates to inflammatory bowel diseases, bacterial and viral infections, postoperative ileus, functional gastrointestinal disorders, and motility disorders. The main theme of this review is that EGCs are emerging as a new frontier in neurogastroenterology and a potential therapeutic target. New technological innovations in neuroimaging techniques are facilitating progress in the field, and an update is provided on exciting new translational studies. Gaps in our knowledge are discussed for further research. Restoring normal EGC function may prove to be an efficient strategy to dampen inflammation. Probiotics, palmitoylethanolamide (peroxisome proliferator-activated receptor-α), interleukin-1 antagonists (anakinra), and interventions acting on nitric oxide, receptor for advanced glycation end products, S100B, or purinergic signaling pathways are relevant clinical targets on EGCs with therapeutic potential.

  6. Stereological analysis of neuron, glial and endothelial cell numbers in the human amygdaloid complex.

    Science.gov (United States)

    García-Amado, María; Prensa, Lucía

    2012-01-01

    Cell number alterations in the amygdaloid complex (AC) might coincide with neurological and psychiatric pathologies with anxiety imbalances as well as with changes in brain functionality during aging. This stereological study focused on estimating, in samples from 7 control individuals aged 20 to 75 years old, the number and density of neurons, glia and endothelial cells in the entire AC and in its 5 nuclear groups (including the basolateral (BL), corticomedial and central groups), 5 nuclei and 13 nuclear subdivisions. The volume and total cell number in these territories were determined on Nissl-stained sections with the Cavalieri principle and the optical fractionator. The AC mean volume was 956 mm(3) and mean cell numbers (x10(6)) were: 15.3 neurons, 60 glial cells and 16.8 endothelial cells. The numbers of endothelial cells and neurons were similar in each AC region and were one fourth the number of glial cells. Analysis of the influence of the individuals' age at death on volume, cell number and density in each of these 24 AC regions suggested that aging does not affect regional size or the amount of glial cells, but that neuron and endothelial cell numbers respectively tended to decrease and increase in territories such as AC or BL. These accurate stereological measures of volume and total cell numbers and densities in the AC of control individuals could serve as appropriate reference values to evaluate subtle alterations in this structure in pathological conditions.

  7. Connexin43 Hemichannels in Satellite Glial Cells, Can They Influence Sensory Neuron Activity?

    Directory of Open Access Journals (Sweden)

    Mauricio A. Retamal

    2017-11-01

    Full Text Available In this review article, we summarize the current insight on the role of Connexin- and Pannexin-based channels as modulators of sensory neurons. The somas of sensory neurons are located in sensory ganglia (i.e., trigeminal and nodose ganglia. It is well known that within sensory ganglia, sensory neurons do not form neither electrical nor chemical synapses. One of the reasons for this is that each soma is surrounded by glial cells, known as satellite glial cells (SGCs. Recent evidence shows that connexin43 (Cx43 hemichannels and probably pannexons located at SGCs have an important role in paracrine communication between glial cells and sensory neurons. This communication may be exerted via the release of bioactive molecules from SGCs and their subsequent action on receptors located at the soma of sensory neurons. The glio-neuronal communication seems to be relevant for the establishment of chronic pain, hyperalgesia and pathologies associated with tissue inflammation. Based on the current literature, it is possible to propose that Cx43 hemichannels expressed in SGCs could be a novel pharmacological target for treating chronic pain, which need to be directly evaluated in future studies.

  8. The Comparative Utility of Viromer RED and Lipofectamine for Transient Gene Introduction into Glial Cells

    Directory of Open Access Journals (Sweden)

    Sudheendra Rao

    2015-01-01

    Full Text Available The introduction of genes into glial cells for mechanistic studies of cell function and as a therapeutic for gene delivery is an expanding field. Though viral vector based systems do exhibit good delivery efficiency and long-term production of the transgene, the need for transient gene expression, broad and rapid gene setup methodologies, and safety concerns regarding in vivo application still incentivize research into the use of nonviral gene delivery methods. In the current study, aviral gene delivery vectors based upon cationic lipid (Lipofectamine 3000 lipoplex or polyethylenimine (Viromer RED polyplex technologies were examined in cell lines and primary glial cells for their transfection efficiencies, gene expression levels, and toxicity. The transfection efficiencies of polyplex and lipoplex agents were found to be comparable in a limited, yet similar, transfection setting, with or without serum across a number of cell types. However, differential effects on cell-specific transgene expression and reduced viability with cargo loaded polyplex were observed. Overall, our data suggests that polyplex technology could perform comparably to the market dominant lipoplex technology in transfecting various cells lines including glial cells but also stress a need for further refinement of polyplex reagents to minimize their effects on cell viability.

  9. Virus isolation: Specimen type and probable transmission

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. Virus isolation: Specimen type and probable transmission. Over 500 CHIK virus isolations were made. 4 from male Ae. Aegypti (?TOT). 6 from CSF (neurological involvement). 1 from a 4-day old child (transplacental transmission.

  10. Some recent innovations in small specimen testing

    International Nuclear Information System (INIS)

    Odette, G.R.; He, M.; Gragg, D.; Klingensmith, D.; Lucas, G.E.

    2002-01-01

    New innovative small specimen test techniques are described. Finite element simulations show that combinations of cone indentation pile-up geometry and load-penetration depth relations can be used to determine both the yield stress and strain-hardening behavior of a material. Techniques for pre-cracking and testing sub-miniaturized fracture toughness bend bars, with dimensions of 1.65x1.65x9 mm 3 , or less, are described. The corresponding toughness-temperature curves have a very steep transition slope, primarily due to rapid loss of constraint, which has advantages in some experiments to characterize the effects of specified irradiation variables. As one example of using composite specimens, an approach to evaluating helium effects is proposed, involving diffusion bonding small wires of a 54 Fe-based ferritic-martensitic alloy to a surrounding fracture specimen composed of an elemental Fe-based alloy. Finally, we briefly outline some potential approaches to multipurpose specimens and test automation

  11. Progress in Tissue Specimens Alternative for the Driver Genes Testing of Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Yan SUN

    2015-06-01

    Full Text Available Target treatment based on driver genes in advanced non-small cell lung cancer is very important currently. Tumor tissues is the gold standard for driver genes testing. However, most of patients could not get the gene information for lack of enough tissues. To explore the tissue specimens alternatives is a hot spot in clinical work. This report reviews the tissue specimen alternatives of driver gene testing in non-small cell lung cancer.

  12. Rehydration of forensically important larval Diptera specimens.

    Science.gov (United States)

    Sanford, Michelle R; Pechal, Jennifer L; Tomberlin, Jeffery K

    2011-01-01

    Established procedures for collecting and preserving evidence are essential for all forensic disciplines to be accepted in court and by the forensic community at large. Entomological evidence, such as Diptera larvae, are primarily preserved in ethanol, which can evaporate over time, resulting in the dehydration of specimens. In this study, methods used for rehydrating specimens were compared. The changes in larval specimens with respect to larval length and weight for three forensically important blow fly (Diptera: Calliphoridae) species in North America were quantified. Phormia regina (Meigen), Cochliomyia macellaria (F.), and Chrysomya rufifacies (Macquart) third-instar larvae were collected from various decomposing animals and preserved with three preservation methods (80% ethanol, 70% isopropyl alcohol, and hot-water kill then 80% ethanol). Preservative solutions were allowed to evaporate. Rehydration was attempted with either of the following: 80% ethanol, commercial trisodium phosphate substitute solution, or 0.5% trisodium phosphate solution. All three methods partially restored weight and length of specimens recorded before preservation. Analysis of variance results indicated that effects of preservation, rehydration treatment, and collection animal were different in each species. The interaction between preservative method and rehydration treatment had a significant effect on both P. regina and C. macellaria larval length and weight. In addition, there was a significant interaction effect of collection animal on larval C. macellaria measurements. No significant effect was observed in C. rufifacies larval length or weight among the preservatives or treatments. These methods could be used to establish a standard operating procedure for dealing with dehydrated larval specimens in forensic investigations.

  13. Morphological variants of renal carcinoma in radical nephrectomy specimens

    International Nuclear Information System (INIS)

    Humera, A.; Kehar, I.

    2015-01-01

    To determine the morphological variants of Renal Cell Carcinoma (RCC) to detect the commonest histopathological type with special focus to the newly introduced entity Clear Cell Papillary Renal Cell Carcinoma (CCPRCC). Study Design: Case series. Place and Duration of Study: Department of Pathology, Basic Medical Sciences Institute, JPMC, Karachi, from January 2007 to December 2012. Methodology: Paraffin embedded blocks of 32 cases of radical nephrectomy specimens for renal mass were selected from records of Pathology Department, BMSI. Cases were excluded due to inadequate biopsies. Remaining 30 cases of renal cell carcinoma were included in study. H and E staining was done for all cases and PAS stain was employed for a few cases. All cases were reviewed under light microscope. Results: The 30 cases of renal cell carcinoma included 21 (70%) clear cell renal cell carcinoma, 03 (10%) clear cell papillary renal cell carcinoma, 02 (6.6%) papillary renal cell carcinoma and 04 (13.33%) hybrid tumors. Majority of cases (53.3%) found in age range between 40 - 60 years while 23.33% cases were found in 7th and 6.6% in 8th decade of life. While 16.66% cases were in younger age group that is between 31 - 40 years of age. Sixty percent cases of right radical nephrectomies and 40% cases of left radical nephrectomies. Conclusion: CCRCC was most common histopathologic type followed by CCPRCC, hybrid tumors and PRCC. (author)

  14. Noonan syndrome, PTPN11 mutations, and brain tumors. A clinical report and review of the literature.

    Science.gov (United States)

    Siegfried, Aurore; Cances, Claude; Denuelle, Marie; Loukh, Najat; Tauber, Maïté; Cavé, Hélène; Delisle, Marie-Bernadette

    2017-04-01

    Noonan syndrome (NS), an autosomal dominant disorder, is characterized by short stature, congenital heart defects, developmental delay, and facial dysmorphism. PTPN11 mutations are the most common cause of NS. PTPN11 encodes a non-receptor protein tyrosine phosphatase, SHP2. Hematopoietic malignancies and solid tumors are associated with NS. Among solid tumors, brain tumors have been described in children and young adults but remain rather rare. We report a 16-year-old boy with PTPN11-related NS who, at the age of 12, was incidentally found to have a left temporal lobe brain tumor and a cystic lesion in the right thalamus. He developed epilepsy 2 years later. The temporal tumor was surgically resected because of increasing crises and worsening radiological signs. Microscopy showed nodules with specific glioneuronal elements or glial nodules, leading to the diagnosis of dysembryoplastic neuroepithelial tumor (DNT). Immunohistochemistry revealed positive nuclear staining with Olig2 and pERK in small cells. SHP2 plays a key role in RAS/MAPK pathway signaling which controls several developmental cell processes and oncogenesis. An amino-acid substitution in the N-terminal SHP2 domain disrupts the self-locking conformation and leads to ERK activation. Glioneuronal tumors including DNTs and pilocytic astrocytomas have been described in NS. This report provides further support for the relation of DNTs with RASopathies and for the implication of RAS/MAPK pathways in sporadic low-grade glial tumors including DNTs. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  15. Theissenolactone C Exhibited Ocular Protection of Endotoxin-Induced Uveitis by Attenuating Ocular Inflammatory Responses and Glial Activation

    Directory of Open Access Journals (Sweden)

    Fan-Li Lin

    2018-04-01

    Full Text Available The aim of this study was to investigate the effects of a natural component, theissenolactone C (LC53, on the ocular inflammation of experimental endotoxin-induced uveitis (EIU and its related mechanisms in microglia. Evaluation of the severity of anterior uveitis indicated that LC53 treatment significantly decreased iridal hyperemia and restored the clinical scores. Additionally, the deficient retina functions of electroretinography were improved by LC53. LC53 significantly reduced levels of tumor necrosis factor (TNF-α, monocyte chemoattractant protein-1, protein leakage and activation of matrix metalloproteinases in the anterior section during EIU. Moreover, LC53 treatment decreased the oxidative stress as well as neuroinflammatory reactivities of GFAP and Iba-1 in the posterior section. Furthermore, LC53 decreased the phosphorylation of p65, expression of HSP90, Bax, and cleaved-caspase-3 in EIU. According to the microglia studies, LC53 significantly abrogated the productions of TNF-α, PGE2, NO and ROS, as well as inducible NO synthase and cyclooxygenase-2 expression in LPS-stimulated microglial BV2 cells. The microglial activation of IKKβ, p65 phosphorylation and nuclear phosphorylated p65 translocation were strongly attenuated by LC53. On the other hand, LC53 exhibited the inhibitory effects on JNK and ERK MAPKs activation. Our findings indicated that LC53 exerted the ocular-protective effect through its inhibition on neuroinflammation, glial activation, and apoptosis in EIU, suggesting a therapeutic potential with down-regulation of the NF-κB signaling for uveitis and retinal inflammatory diseases.

  16. Simultaneous specimen and stage cleaning device for analytical electron microscope

    Science.gov (United States)

    Zaluzec, Nestor J.

    1996-01-01

    An improved method and apparatus are provided for cleaning both a specimen stage, a specimen and an interior of an analytical electron microscope (AEM). The apparatus for cleaning a specimen stage and specimen comprising a plasma chamber for containing a gas plasma and an air lock coupled to the plasma chamber for permitting passage of the specimen stage and specimen into the plasma chamber and maintaining an airtight chamber. The specimen stage and specimen are subjected to a reactive plasma gas that is either DC or RF excited. The apparatus can be mounted on the analytical electron microscope (AEM) for cleaning the interior of the microscope.

  17. Effect of all-trans retinoic acid on the proliferation and differentiation of brain tumor stem cells

    Directory of Open Access Journals (Sweden)

    Niu Chao

    2010-08-01

    Full Text Available Abstract Objective To investigate the effect of all-trans retinoic acid(ATRA on the proliferation and differentiation of brain tumor stem cells(BTSCs in vitro. Methods Limiting dilution and clonogenic assay were used to isolate and screen BTSCs from the fresh specimen of human brain glioblastoma. The obtained BTSCs, which were cultured in serum-free medium, were classified into four groups in accordance with the composition of the different treatments. The proliferation of the BTSCs was evaluated by MTT assay. The BTSCs were induced to differentiate in serum-containing medium, and classified into the ATRA group and control group. On the 10th day of induction, the expressions of CD133 and glial fibrillary acidic protein (GFAP in the differentiated BTSCs were detected by immunofluorescence. The differentiated BTSCs were cultured in serum-free medium, the percentage and the time required for formation of brain tumor spheres (BTS were observed. Results BTSCs obtained by limiting dilution were all identified as CD133-positive by immunofluorescence. In serum-free medium, the proliferation of BTSCs in the ATRA group was observed significantly faster than that in the control group, but slower than that in the growth factor group and ATRA/growth factor group, and the size of the BTS in the ATRA group was smaller than that in the latter two groups(P P P P Conclusion ATRA can promote the proliferation and induce the differentiation of BTSCs, but the differentiation is incomplete, terminal differentiation cannot be achieved and BTSs can be formed again.

  18. Accuracy of computed tomography in determining pancreatic cancer tumor size

    International Nuclear Information System (INIS)

    Aoki, Kazunori; Okada, Shuichi; Moriyama, Noriyuki

    1994-01-01

    We compared tumor sizes determined by computed tomography (CT) with those of the resected specimens in 26 patients with pancreatic cancer in order to clarify whether or not the size of a pancreatic tumor can be accurately determined by CT. From the precontrast, postcontrast and arterial dominant phases of dynamic CT, the arterial dominant phase was found to yield the highest correlation between CT measured tumor size and that of the resected specimens (p<0.01). The correlation coefficient was, however, not high (r=0.67). CT alone may therefore be insufficient to determine tumor size in pancreatic cancer accurately. (author)

  19. Automated detection of breast cancer in resected specimens with fluorescence lifetime imaging

    Science.gov (United States)

    Phipps, Jennifer E.; Gorpas, Dimitris; Unger, Jakob; Darrow, Morgan; Bold, Richard J.; Marcu, Laura

    2018-01-01

    Re-excision rates for breast cancer lumpectomy procedures are currently nearly 25% due to surgeons relying on inaccurate or incomplete methods of evaluating specimen margins. The objective of this study was to determine if cancer could be automatically detected in breast specimens from mastectomy and lumpectomy procedures by a classification algorithm that incorporated parameters derived from fluorescence lifetime imaging (FLIm). This study generated a database of co-registered histologic sections and FLIm data from breast cancer specimens (N  =  20) and a support vector machine (SVM) classification algorithm able to automatically detect cancerous, fibrous, and adipose breast tissue. Classification accuracies were greater than 97% for automated detection of cancerous, fibrous, and adipose tissue from breast cancer specimens. The classification worked equally well for specimens scanned by hand or with a mechanical stage, demonstrating that the system could be used during surgery or on excised specimens. The ability of this technique to simply discriminate between cancerous and normal breast tissue, in particular to distinguish fibrous breast tissue from tumor, which is notoriously challenging for optical techniques, leads to the conclusion that FLIm has great potential to assess breast cancer margins. Identification of positive margins before waiting for complete histologic analysis could significantly reduce breast cancer re-excision rates.

  20. Tumoral tracers

    International Nuclear Information System (INIS)

    Camargo, E.E.

    1979-01-01

    Direct tumor tracers are subdivided in the following categories:metabolite tracers, antitumoral tracers, radioactive proteins and cations. Use of 67 Ga-citrate as a clinically important tumoral tracer is emphasized and gallium-67 whole-body scintigraphy is discussed in detail. (M.A.) [pt

  1. Animal tumors

    International Nuclear Information System (INIS)

    Gillette, E.L.

    1983-01-01

    There are few trained veterinary radiation oncologists and the expense of facilities has limited the extent to which this modality is used. In recent years, a few cobalt teletherapy units and megavoltage x-ray units have been employed in larger veterinary institutions. In addition, some radiation oncologists of human medical institutions are interested and willing to cooperate with veterinarians in the treatment of animal tumors. Carefully designed studies of the response of animal tumors to new modalities serve two valuable purposes. First, these studies may lead to improved tumor control in companion animals. Second, these studies may have important implications to the improvement of therapy of human tumors. Much remains to be learned of animal tumor biology so that appropriate model systems can be described for such studies. Many of the latter studies can be sponsored by agencies interested in the improvement of cancer management

  2. Standard guide for preparation of metallographic specimens

    CERN Document Server

    American Society for Testing and Materials. Philadelphia

    2011-01-01

    1.1 The primary objective of metallographic examinations is to reveal the constituents and structure of metals and their alloys by means of a light optical or scanning electron microscope. In special cases, the objective of the examination may require the development of less detail than in other cases but, under nearly all conditions, the proper selection and preparation of the specimen is of major importance. Because of the diversity in available equipment and the wide variety of problems encountered, the following text presents for the guidance of the metallographer only those practices which experience has shown are generally satisfactory; it cannot and does not describe the variations in technique required to solve individual specimen preparation problems. Note 1—For a more extensive description of various metallographic techniques, refer to Samuels, L. E., Metallographic Polishing by Mechanical Methods, American Society for Metals (ASM) Metals Park, OH, 3rd Ed., 1982; Petzow, G., Metallographic Etchin...

  3. Natural History Specimen Digitization: Challenges and Concerns

    Directory of Open Access Journals (Sweden)

    Ana Vollmar

    2010-10-01

    Full Text Available A survey on the challenges and concerns invovled with digitizing natural history specimens was circulated to curators, collections managers, and administrators in the natural history community in the Spring of 2009, with over 200 responses received. The overwhelming barrier to digitizing collections was a lack of funding, based on a limited number of sources, leaving institutions mostly responsible for providing the necessary support. The uneven digitization landscape leads to a patchy accumulation of records at varying qualities, and based on different priorities, ulitimately influencing the data's fitness for use. The survey also found that although the kind of specimens found in collections and their storage can be quite varible, there are many similar challenges when digitizing including imaging, automated text scanning and parsing, geo-referencing, etc. Thus, better communication between domains could foster knowledge on digitization leading to efficiencies that could be disseminated through documentation of best practices and training.

  4. Thermal endurance tests on silicone rubber specimens

    International Nuclear Information System (INIS)

    Warburton, C.

    1977-07-01

    Thermal endurance tests have been performed on a range of silicone rubber specimens at temperature above 300 0 C. It is suggested that the rubber mix A2426, the compound from which Wylfa sealing rings are manufactured, will fail at temperatures above 300 0 C within weeks. Hardness measurements show that this particular rubber performs in a similar manner to Walker's S.I.L./60. (author)

  5. The working procedure of human autopsy specimens

    International Nuclear Information System (INIS)

    Chen Rusong; Liu Guodong

    2000-01-01

    In order to perform the Coordinated Research Program for the Reference Asian Man (phase 2): Ingestion and body content of trace elements of importance in Radiation Protection, study on elemental content in organs of normal Chinese has been worked by China Institute for Radiation Protection and Institute of Radiation Medicine - CAMS in recent two years. Sampling and sample collection of human tissues and the procedures of sample preparation of human autopsy specimens are enlisted

  6. Bireflectance imaging of coal and carbon specimens

    Energy Technology Data Exchange (ETDEWEB)

    Crelling, J.C. [Department of Geology, 1259 Lincoln Drive, Southern Illinois University, Carbondale, Illinois 62901 (United States); Glasspool, I.J.; Gibbins, J.R.; Seitz, M. [Department of Mechanical Engineering, Imperial College, Exhibition Road, London, SW7 2BX (United Kingdom)

    2005-11-10

    Although bireflectance measurements are routine, to date they have been limited to selected single point measurements. This study uses a 360{sup o} rotating polarizer in the incident light path combined with digital imaging to map the optical bireflectance of a polished specimen over the complete field of view, a system herein referred to as 'Bireflectance Imaging of Coal and Carbon Specimens' (BRICCS). True maximum reflectance maps and maps of polarizer angle for maximum reflectance (to identify co-ordered regions) are obtainable from the same data. A variety of coal, coke, char, graphite, and carbon/carbon specimens have been examined with the BRICCS system and the results demonstrate that the system can produce accurate maximum and apparent minimum reflectance, bireflectance, and extinction angle images. For example, flakes of natural graphite show no bireflectance along their long axis except in areas that have been strained. The images are maps showing the value of every pixel that has been calibrated by mineral reflectance standards. The maps are unique in that they show fields of view that cannot be seen by normal viewing through the microscope. For example, the bireflectance maps show the maximum difference between the maximum and apparent minimum reflectance for each of the million pixels at twenty orientations of the polarizer. (author)

  7. Specimen loading list for the varying temperature experiment

    International Nuclear Information System (INIS)

    Qualls, A.L.; Sitterson, R.G.

    1998-01-01

    The varying temperature experiment HFIR-RB-13J has been assembled and inserted in the reactor. Approximately 5300 specimens were cleaned, inspected, matched, and loaded into four specimen holders. A listing of each specimen loaded into the steady temperature holder, its position in the capsule, and the identification of the corresponding specimen loaded into the varying temperature holder is presented in this report

  8. HMSRP Hawaiian Monk Seal Specimen Data (includes physical specimens, collection information, status, storage locations, and laboratory results associated with individual specimens)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data set includes physical specimens, paper logs and Freezerworks database of all logged information on specimens collected from Hawaiian monk seals since 1975....

  9. Use of globally unique identifiers (GUIDs) to link herbarium specimen records to physical specimens.

    Science.gov (United States)

    Nelson, Gil; Sweeney, Patrick; Gilbert, Edward

    2018-02-01

    With the advent of the U.S. National Science Foundation's Advancing Digitization of Biodiversity Collections program and related worldwide digitization initiatives, the rate of herbarium specimen digitization in the United States has expanded exponentially. As the number of electronic herbarium records proliferates, the importance of linking these records to the physical specimens they represent as well as to related records from other sources will intensify. Although a rich and diverse literature has developed over the past decade that addresses the use of specimen identifiers for facilitating linking across the internet, few implementable guidelines or recommended practices for herbaria have been advanced. Here we review this literature with the express purpose of distilling a specific set of recommendations especially tailored to herbarium specimen digitization, curation, and management. We argue that associating globally unique identifiers (GUIDs) with physical herbarium specimens and including these identifiers in all electronic records about those specimens is essential to effective digital data curation. We also address practical applications for ensuring these associations.

  10. Cellular characterization of the peritumoral edema zone in malignant brain tumors

    International Nuclear Information System (INIS)

    Engelhorn, T.; Schwarz, M.A.; Savaskan, N.E.

    2009-01-01

    Brain edema is a hallmark of human malignant brain tumors and contributes to the clinical course and outcome of brain tumor patients. The so-called perifocal edema or brain swelling imposes in T2-weighted MR scans as high intensity areas surrounding the bulk tumor mass. The mechanisms of this increased fluid attraction and the cellular composition of the microenvironment are only partially understood. In this study, we focus on imaging perifocal edema in orthotopically implanted gliomas in rodents and correlate perifocal edema with immunohistochemical markers. We identified that areas of perifocal edema not only include the tumor invasion zone, but also are associated with increased glial fibrillary acidic protein (GFAP) and aquaporin-4 expression surrounding the bulk tumor mass. Moreover, a high number of activated microglial cells expressing CD11b and macrophage migration inhibitory factor (MIF) accumulate at the tumor border. Thus, the area of perifocal edema is mainly dominated by reactive changes of vital brain tissue. These data corroborate that perifocal edema identified in T2-weighted MR scans are characterized with alterations in glial cell distribution and marker expression forming an inflammatory tumor microenvironment. (author)

  11. Development of fatigue life evaluation technique using miniature specimen

    International Nuclear Information System (INIS)

    Nogami, Shuhei; Nishimura, Arata; Fujiwara, Masaharu; Hisaka, Tomoaki

    2012-01-01

    To develop the fatigue life evaluation technique using miniature specimen, the investigation of the effect of specimen size and specimen shape on the fatigue life and the development of the fatigue testing machine, especially the extensometer, were carried out. The effect of specimen size on the fatigue life was almost negligible for the round-bar specimens. The shorter fatigue life at relatively low strain range conditions for the hourglass specimen that the standard specimen were observed. Therefore the miniature round-bar specimen was considered to be adequate for the fatigue life evaluation using small specimen. Several types of the extensometer system using a strain gauge and a laser has been developed for realizing the fatigue test of the miniature round-bar specimen at high temperature in vacuum. (author)

  12. Tumor initiating cells in malignant gliomas: biology and implications for therapy.

    Science.gov (United States)

    Hadjipanayis, Costas G; Van Meir, Erwin G

    2009-04-01

    A rare subpopulation of cells within malignant gliomas, which shares canonical properties with neural stem cells (NSCs), may be integral to glial tumor development and perpetuation. These cells, also known as tumor initiating cells (TICs), have the ability to self-renew, develop into any cell in the overall tumor population (multipotency), and proliferate. A defining property of TICs is their ability to initiate new tumors in immunocompromised mice with high efficiency. Mounting evidence suggests that TICs originate from the transformation of NSCs and their progenitors. New findings show that TICs may be more resistant to chemotherapy and radiation than the bulk of tumor cells, thereby permitting recurrent tumor formation and accounting for the failure of conventional therapies. The development of new therapeutic strategies selectively targeting TICs while sparing NSCs may provide for more effective treatment of malignant gliomas.

  13. Gene discovery in glioma in the context of molecular reclassification of tumors

    Directory of Open Access Journals (Sweden)

    Khushboo Irshad

    2015-12-01

    Full Text Available Conventional classification of tumors, especially in terms of staging and grading is of immense importance for both prognostication as well as management strategies. However it is not a perfect system and there are many instances where tumor behaviour does not correspond to what is expected. In addition, with the onset of targeted therapy, the identification of the distinct molecular target in a subset of tumors becomes a marker of tumor behaviour as well as a target of therapy. This leads to the concept of molecular subclassification of tumors where molecular markers further refine and in some cases, alter conventional classification. We would be presenting this concept in relation to glial tumors, especially in the context of molecular markers discovered in our laboratory.

  14. [Protective measures in laparoscopic resection for upper or mid rectal cancer and sigmoid colon cancer with transrectal specimen extraction surgery].

    Science.gov (United States)

    Fu, Chuangang; Zhou, Zhuqing; Han, Junyi; Lu, Bin; Gao, Wei; Zhu, Zhe; Jiang, Qixin; Ji, Fang; Du, Tao

    2017-10-25

    To introduce the use of a self-made specimen protective sleeve in laparoscopic resection for upper or mid rectal cancer and sigmoid colon cancer with transrectal specimen extraction surgery and the improvement of implantation method, so as to avoid and reduce bacterial contamination and tumor cell dissemination in abdominal cavity. During June 2015 and May 2017, 48 cases of high located rectal or sigmoid colon cancer were operated laparoscopically with natural orifices specimen extraction surgery (NOSES) using a self-made specimen protecting sleeve. Operation indication: (1) Rectum and sigmoid colon cancer with the distance of more than 6 cm from tumor inferior margin to dentate line. (2) The maximum diameter of intestine together with mesangial and tumor <7 cm by intraoperative judgment. (3) No anal and distal rectal surgery, no anorectal stenosis or lack of expansion capacity caused by trauma. (4) No ulcerative colitis, Crohn's disease or radiation proctitis. After transecting the rectum, the specimen protective sleeve was inserted through the right lower 12 mm main Trocar (This sleeve was tailored from the laparoscopic protective sleeve produced by China 3L Corporation, which was intercepted with 25-35 cm from one end of the sleeve according to the length of distal rectal retention. One end was ligated and the other was open with a ligature band. About 5 ml paraffin oil was used to rinse and lubricate during the operation). The rectal stump retained 7-8 cm in abdominal cavity. The transanal ligation part of the protective sleeve was cut off, then the stapler nail seat was inserted and specimen was pull out through the sleeve and rectum. There were 30 males and 18 females. The average age was (64.5±14.1) years, the BMI was (25.4±3.9) kg/m 2 , the tumor diameter was (3.3±1.1) cm, the maximum diameter of specimen was (5.4±1.5) cm and the length of specimen was (18.6±4.3) cm. Among these 48 cases, specimens of 36 patients were pulled out through inside of the

  15. Hyperthyreosis effects on the learning and glial intermediate filaments of rat brain

    Directory of Open Access Journals (Sweden)

    S. V. Kyrychenko

    2014-03-01

    Full Text Available The influence of hyperthyreosis on oxidative stress, state of glial intermediate filaments and memotry was investigated. Significant increasing of lipid peroxidation products into both hippocampus and cortex and change for the worse of memory was observed. Analysis of the behavioral reactions of rats in the test of passive avoidance conditioned reflex showed that the acquisition of skills of all groups of animals did not differ by time waiting period (latent period. Time saving memory test conditioned reflex of passive avoidance was excellent in the group of rats treated with thyroxine compared with controls. The change of polypeptide GFAP was observed in hippocampus and cortex. Both soluble and filamentous forms of GFAP increased in hippocampus of rat with hyperthyreosis. In filament fractions, increase in the intensity of 49 kDa polypeptide band was found. In the same fraction of insoluble cytoskeleton proteins degraded HFKB polypeptides with molecular weight in the region of 46–41 kDa appeared. Marked increase of degraded polypeptides was found in the soluble fraction of the brain stem. The intensity of the intact polypeptide (49 kDa, as well as in the filament fraction, significantly increased. It is possible that increasing concentrations of soluble subunits glial filaments may be due to dissociation of own filaments during the reorganization of cytoskeleton structures. Given the results of Western blotting for filament fraction, increased content of soluble intact 49 kDa polypeptide is primarily the result of increased expression of HFKB and only partly due to redistribution of existing filament structures. Calculation and analysis of indicators showed high correlation between the increase in content and peroxidation products of HFKB. These results indicate the important role of oxidative stress in the induction of astroglial reactive response under conditions of hyperthyroidism. This data shows the possibility of the glial cell

  16. The glial scar-monocyte interplay: a pivotal resolution phase in spinal cord repair.

    Directory of Open Access Journals (Sweden)

    Ravid Shechter

    Full Text Available The inflammatory response in the injured spinal cord, an immune privileged site, has been mainly associated with the poor prognosis. However, recent data demonstrated that, in fact, some leukocytes, namely monocytes, are pivotal for repair due to their alternative anti-inflammatory phenotype. Given the pro-inflammatory milieu within the traumatized spinal cord, known to skew monocytes towards a classical phenotype, a pertinent question is how parenchymal-invading monocytes acquire resolving properties essential for healing, under such unfavorable conditions. In light of the spatial association between resolving (interleukin (IL-10 producing monocytes and the glial scar matrix chondroitin sulfate proteoglycan (CSPG, in this study we examined the mutual relationship between these two components. By inhibiting the de novo production of CSPG following spinal cord injury, we demonstrated that this extracellular matrix, mainly known for its ability to inhibit axonal growth, serves as a critical template skewing the entering monocytes towards the resolving phenotype. In vitro cell culture studies demonstrated that this matrix alone is sufficient to induce such monocyte polarization. Reciprocal conditional ablation of the monocyte-derived macrophages concentrated at the lesion margins, using diphtheria toxin, revealed that these cells have scar matrix-resolving properties. Replenishment of monocytic cell populations to the ablated mice demonstrated that this extracellular remodeling ability of the infiltrating monocytes requires their expression of the matrix-degrading enzyme, matrix metalloproteinase 13 (MMP-13, a property that was found here to be crucial for functional recovery. Altogether, this study demonstrates that the glial scar-matrix, a known obstacle to regeneration, is a critical component skewing the encountering monocytes towards a resolving phenotype. In an apparent feedback loop, monocytes were found to regulate scar resolution. This

  17. Soman poisoning increases neural progenitor proliferation and induces long-term glial activation in mouse brain

    International Nuclear Information System (INIS)

    Collombet, Jean-Marc; Four, Elise; Bernabe, Denis; Masqueliez, Catherine; Burckhart, Marie-France; Baille, Valerie; Baubichon, Dominique; Lallement, Guy

    2005-01-01

    To date, only short-term glial reaction has been extensively studied following soman or other warfare neurotoxicant poisoning. In a context of cell therapy by neural progenitor engraftment to repair brain damage, the long-term effect of soman on glial reaction and neural progenitor division was analyzed in the present study. The effect of soman poisoning was estimated in mouse brains at various times ranging from 1 to 90 days post-poisoning. Using immunochemistry and dye staining techniques (hemalun-eosin staining), the number of degenerating neurons, the number of dividing neural progenitors, and microglial, astroglial or oligodendroglial cell activation were studied. Soman poisoning led to rapid and massive (post-soman day 1) death of mature neurons as assessed by hemalun-eosin staining. Following this acute poisoning phase, a weak toxicity effect on mature neurons was still observed for a period of 1 month after poisoning. A massive short-termed microgliosis peaked on day 3 post-poisoning. Delayed astrogliosis was observed from 3 to 90 days after soman poisoning, contributing to glial scar formation. On the other hand, oligodendroglial cells or their precursors were practically unaffected by soman poisoning. Interestingly, neural progenitors located in the subgranular zone of the dentate gyrus (SGZ) or in the subventricular zone (SVZ) of the brain survived soman poisoning. Furthermore, soman poisoning significantly increased neural progenitor proliferation in both SGZ and SVZ brain areas on post-soman day 3 or day 8, respectively. This increased proliferation rate was detected up to 1 month after poisoning

  18. Pituitary Tumors

    Science.gov (United States)

    ... Association (ABTA) International RadioSurgery Association National Brain Tumor Society National Institute of Child Health and Human Development ... Definition The pituitary is a small, bean-sized gland ...

  19. Hypothalamic tumor

    Science.gov (United States)

    ... in the brain to reduce spinal fluid pressure. Risks of radiation therapy include damage to healthy brain cells when tumor cells are destroyed. Common side effects from chemotherapy include loss of appetite, nausea and vomiting, and fatigue.

  20. Pseudoangiomatous Stromal Hyperplasia in Core Needle Biopsies of Breast Specimens.

    Science.gov (United States)

    Kelten Talu, Canan; Boyaci, Ceren; Leblebici, Cem; Hacihasanoglu, Ezgi; Bozkurt, Erol Rustu

    2017-02-01

    Pseudoangiomatous stromal hyperplasia (PASH) is a benign lesion of myofibroblasts that is composed of a network of slit-like channels that resemble vascular spaces. The aims of this study were to document the frequency of PASH in core needle biopsy specimens (CNBS) of the breast, to describe which histopathologic findings coexist with PASH and to examine any endothelial cell differentiation. We reevaluated hematoxylin and eosin-stained sections of all CNBS that were obtained during a 1-year period. First, we performed CD34 and CD31 immunostainings to highlight the areas of PASH, then performed D2-40/podoplanin (lymphatic endothelial marker) and Fli-1 (vascular endothelial cell marker) immunostains. The total number of CNBS was 412. Areas of PASH were noted in 37 of the 412 cases (9%), with a mean age of 38.5 years. The lesions that were described in association with PASH were "benign breast parenchyma with stromal fibrosis" (17/37; 46%), "fibroepithelial tumors" (17/37; 46%), "columnar cell changes (CCC)" (2/37; 5%), and "invasive carcinoma" (1/37; 3%). There were 2 cases of CCC within the foci of PASH (direct contact with PASH), and 8 additional cases of CCC that coexisted in the same specimen but were not in direct contact. There was no staining for D2-40 or Fli-1 within PASH foci. PASH lesions occurred with a frequency of 9% in CNBS and were mostly in association with benign breast lesions in premenopausal women. CCC was determined as an accompanying epithelial lesion within or near PASH areas. No obvious immunopositivity compatible with endothelial cell differentiation was revealed.

  1. The impact of the glial spatial buffering on the K(+) Nernst potential.

    Science.gov (United States)

    Noori, H R

    2011-09-01

    Astrocytes play a critical role in CNS metabolism, regulation of volume and ion homeostasis of the interstitial space. Of special relevance is their clearance of K(+) that is released by active neurons into the extracellular space. Mathematical analysis of a modified Nernst equation for the electrochemical equilibrium of neuronal plasma membranes, suggests that K(+) uptake by glial cells is not only relevant during neuronal activity but also has a non-neglectable impact on the basic electrical membrane properties, specifically the resting membrane potential, of neurons and might be clinically valuable as a factor in the genetics and epigenetics of the epilepsy and tuberous sclerosis complex.

  2. Human glial chimeric mice reveal astrocytic dependence of JC virus infection

    DEFF Research Database (Denmark)

    Kondo, Yoichi; Windrem, Martha S; Zou, Lisa

    2014-01-01

    with humanized white matter by engrafting human glial progenitor cells (GPCs) into neonatal immunodeficient and myelin-deficient mice. Intracerebral delivery of JCV resulted in infection and subsequent demyelination of these chimeric mice. Human GPCs and astrocytes were infected more readily than...... that was chimeric for human astrocytes and GPCs. JCV effectively propagated in these mice, which indicates that astroglial infection is sufficient for JCV spread. Sequencing revealed progressive mutation of the JCV capsid protein VP1 after infection, suggesting that PML may evolve with active infection...

  3. Several synthetic progestins disrupt the glial cell specific-brain aromatase expression in developing zebra fish

    International Nuclear Information System (INIS)

    Cano-Nicolau, Joel; Garoche, Clémentine; Hinfray, Nathalie; Pellegrini, Elisabeth; Boujrad, Noureddine; Pakdel, Farzad; Kah, Olivier; Brion, François

    2016-01-01

    The effects of some progestins on fish reproduction have been recently reported revealing the hazard of this class of steroidal pharmaceuticals. However, their effects at the central nervous system level have been poorly studied until now. Notwithstanding, progesterone, although still widely considered primarily a sex hormone, is an important agent affecting many central nervous system functions. Herein, we investigated the effects of a large set of synthetic ligands of the nuclear progesterone receptor on the glial-specific expression of the zebrafish brain aromatase (cyp19a1b) using zebrafish mechanism-based assays. Progesterone and 24 progestins were first screened on transgenic cyp19a1b-GFP zebrafish embryos. We showed that progesterone, dydrogesterone, drospirenone and all the progesterone-derived progestins had no effect on GFP expression. Conversely, all progestins derived from 19-nortesterone induced GFP in a concentration-dependent manner with EC 50 ranging from the low nM range to hundreds nM. The 19-nortestosterone derived progestins levonorgestrel (LNG) and norethindrone (NET) were further tested in a radial glial cell context using U251-MG cells co-transfected with zebrafish ER subtypes (zfERα, zfERβ1 or zfERβ2) and cyp19a1b promoter linked to luciferase. Progesterone had no effect on luciferase activity while NET and LNG induced luciferase activity that was blocked by ICI 182,780. Zebrafish-ERs competition assays showed that NET and LNG were unable to bind to ERs, suggesting that the effects of these compounds on cyp19a1b require metabolic activation prior to elicit estrogenic activity. Overall, we demonstrate that 19-nortestosterone derived progestins elicit estrogenic activity by inducing cyp19a1b expression in radial glial cells. Given the crucial role of radial glial cells and neuro-estrogens in early development of brain, the consequences of exposure of fish to these compounds require further investigation. - Highlights: • P4 + 24 progestins

  4. Several synthetic progestins disrupt the glial cell specific-brain aromatase expression in developing zebra fish

    Energy Technology Data Exchange (ETDEWEB)

    Cano-Nicolau, Joel [Team NEED, Institut de recherche en Santé Environnement et Travail (Irset), INSERM U1085, Université de Rennes 1, Campus de Beaulieu, SFR Biosit, 35042 Rennes cedex (France); Garoche, Clémentine; Hinfray, Nathalie [Unité d' Ecotoxicologie in vitro et in vivo , Institut National de l' Environnement Industriel et des Risques (INERIS), BP 2, 60550 Verneuil-en-Halatte (France); Pellegrini, Elisabeth [Team NEED, Institut de recherche en Santé Environnement et Travail (Irset), INSERM U1085, Université de Rennes 1, Campus de Beaulieu, SFR Biosit, 35042 Rennes cedex (France); Boujrad, Noureddine; Pakdel, Farzad [TREK, Institut de recherche en Santé Environnement et Travail (Irset), INSERM U1085, Université de Rennes 1, Campus de Beaulieu, SFR Biosit, 35042 Rennes cedex (France); Kah, Olivier, E-mail: oliver.kah@univ-rennes1.fr [Team NEED, Institut de recherche en Santé Environnement et Travail (Irset), INSERM U1085, Université de Rennes 1, Campus de Beaulieu, SFR Biosit, 35042 Rennes cedex (France); Brion, François, E-mail: francois.brion@ineris.fr [Unité d' Ecotoxicologie in vitro et in vivo , Institut National de l' Environnement Industriel et des Risques (INERIS), BP 2, 60550 Verneuil-en-Halatte (France)

    2016-08-15

    The effects of some progestins on fish reproduction have been recently reported revealing the hazard of this class of steroidal pharmaceuticals. However, their effects at the central nervous system level have been poorly studied until now. Notwithstanding, progesterone, although still widely considered primarily a sex hormone, is an important agent affecting many central nervous system functions. Herein, we investigated the effects of a large set of synthetic ligands of the nuclear progesterone receptor on the glial-specific expression of the zebrafish brain aromatase (cyp19a1b) using zebrafish mechanism-based assays. Progesterone and 24 progestins were first screened on transgenic cyp19a1b-GFP zebrafish embryos. We showed that progesterone, dydrogesterone, drospirenone and all the progesterone-derived progestins had no effect on GFP expression. Conversely, all progestins derived from 19-nortesterone induced GFP in a concentration-dependent manner with EC{sub 50} ranging from the low nM range to hundreds nM. The 19-nortestosterone derived progestins levonorgestrel (LNG) and norethindrone (NET) were further tested in a radial glial cell context using U251-MG cells co-transfected with zebrafish ER subtypes (zfERα, zfERβ1 or zfERβ2) and cyp19a1b promoter linked to luciferase. Progesterone had no effect on luciferase activity while NET and LNG induced luciferase activity that was blocked by ICI 182,780. Zebrafish-ERs competition assays showed that NET and LNG were unable to bind to ERs, suggesting that the effects of these compounds on cyp19a1b require metabolic activation prior to elicit estrogenic activity. Overall, we demonstrate that 19-nortestosterone derived progestins elicit estrogenic activity by inducing cyp19a1b expression in radial glial cells. Given the crucial role of radial glial cells and neuro-estrogens in early development of brain, the consequences of exposure of fish to these compounds require further investigation. - Highlights: • P4 + 24

  5. In Vivo Imaging of Glial Activation after Unilateral Labyrinthectomy in the Rat: A [18F]GE180-PET Study

    Directory of Open Access Journals (Sweden)

    Andreas Zwergal

    2017-12-01

    Full Text Available The functional relevance of reactive gliosis for recovery from acute unilateral vestibulopathy is unknown. In the present study, glial activation was visualized in vivo by [18F]GE180-PET in a rat model of unilateral labyrinthectomy (UL and compared to behavioral vestibular compensation (VC overtime. 14 Sprague-Dawley rats underwent a UL by transtympanic injection of bupivacaine/arsenilate, 14 rats a SHAM UL (injection of normal saline. Glial activation was depicted with [18F]GE180-PET and ex vivo autoradiography at baseline and 7, 15, 30 days after UL/SHAM UL. Postural asymmetry and nystagmus were registered at 1, 2, 3, 7, 15, 30 days after UL/SHAM UL. Signs of vestibular imbalance were found only after UL, which significantly decreased until days 15 and 30. In parallel, [18F]GE180-PET and ex vivo autoradiography depicted glial activation in the ipsilesional vestibular nerve and nucleus on days 7 and 15 after UL. Correlation analysis revealed a strong negative association of [18F]GE180 uptake in the ipsilesional vestibular nucleus on day 7 with the rate of postural recovery (R = −0.90, p < 0.001, suggesting that glial activation accelerates VC. In conclusion, glial activation takes place in the ipsilesional vestibular nerve and nucleus within the first 30 days after UL in the rat and can be visualized in vivo by [18F]GE180-PET.

  6. Histological evaluation of 400 cholecystectomy specimens

    Directory of Open Access Journals (Sweden)

    H Kumar

    2015-09-01

    Full Text Available Background: A majority of gallbladder specimens show changes associated with chronic cholecystitis; however few harbour a highly lethal carcinoma. This study was conducted to review the significant histopathological findings encountered in gallbladder specimens received in our laboratory.Materials and Methods: Four hundred cholecystectomy specimens were studied over a period of five years (May, 2002 to April, 2007 received at department of pathology, Kasturba Medical College, Mangalore, India. Results: Gallstones and associated diseases were more common in women in the 4th to 5th decade as compared to men with M: F ratio of 1:1.33. Maximum number of patients (28.25% being 41 to 50 years old. Histopathologically, the most common diagnosis was chronic cholecystitis (66.75%, followed by chronic active cholecystitis (20.25%, acute cholecystitis (6%, gangrenous cholecystitis (2.25%,xanthogranulomatous cholecystitis (0.50%, empyema (1%, mucocele (0.25%, choledochal cyst (0.25%, adenocarcinoma gallbladder (1.25% and  normal  gallbladders (1%.Conclusion: All lesions were found more frequently in women except chronic active cholecystitis. Gallstones were present in (80.25% cases, and significantly associated with various lesions (P value 0.009. Pigment stones were most common, followed by cholesterol stones and mixed stones. Adequate  sectioning  is  mandatory  in  all  cases  to  assess  epithelial changes arising from cholelithiasis and chronic cholecystitis as it has been known to progress to malignancy in some cases.

  7. Wildlife specimen collection, preservation, and shipment

    Science.gov (United States)

    White, C. LeAnn; Dusek, Robert J.; Franson, J. Christian; Friend, Milton; Gibbs, Samantha E.J.; Wild, Margaret A.

    2015-01-01

    Specimens are used to provide supporting information leading to the determination of the cause of disease or death in wildlife and for disease monitoring or surveillance. Commonly used specimens for wildlife disease investigations include intact carcasses, tissues from carcasses, euthanized or moribund animals, parasites, ingested food, feces, or environmental samples. Samples from live animals or the environment (e.g., contaminated feed) in the same vicinity as a mortality event also may be helpful. The type of specimen collected is determined by availability of samples and biological objectives. Multiple fresh, intact carcasses from affected species are the most useful in establishing a cause for a mortality event. Submission of entire carcasses allows observation of gross lesions and abnormalities, as well as disease testing of multiple tissues. Samples from live animals may be more appropriate when sick animals cannot be euthanized (e.g., threatened or endangered species) or for research and monitoring projects examining disease or agents circulating in apparently healthy animals or those not exhibiting clinical signs. Samples from live animals may include collections of blood, hair, feathers, feces, or ectoparasites, or samples obtained by swabbing lesions or orifices. Photographs and videos are useful additions for recording field and clinical signs and conveying conditions at the site. Collection of environmental samples (e.g., feces, water, feed, or soil) may be appropriate when animals cannot be captured for sampling or the disease agent may persist in the environment. If lethal collection is considered necessary, biologists should refer to the policies, procedures, and permit requirements of their institution/facility and the agency responsible for species management (U.S. Fish and Wildlife Service or State natural resource agency) prior to use in the field. If threatened or endangered species are found dead, or there is evidence of illegal take, field

  8. Bright field electron microscopy of biological specimens

    International Nuclear Information System (INIS)

    Johansen, B.V.

    1976-01-01

    A preirradiation procedure is described which preserves negatively stained morphological features in bright field electron micrographs to a resolution of about 1.2 nm. Prior to microscopy the pre-irradiation dose (1.6 x 10 -3 C cm -2 ) is given at low electron optical magnification at five different areas on the grid (the centre plus four 'corners'). This pre-irradiation can be measured either with a Faraday cage or through controlled exposure-developing conditions. Uranyl formate stained T2 bacteriophages and stacked disk aggregates of Tobacco Mosaic Virus (TMV) protein served as test objects. A comparative study was performed on specimens using either the pre-irradiation procedure or direct irradiation by the 'minimum beam exposure' technique. Changes in the electron diffraction pattern of the stain-protein complex and the disappearance of certain morphological features in the specimens were both used in order to compare the pre-irradiation method with the direct exposure technique. After identical electron exposures the pre-irradiation approach gave a far better preservation of specimen morphology. Consequently this procedure gives the microscopist more time to select and focus appropriate areas for imaging before deteriorations take place. The investigation also suggested that microscopy should be carried out between 60,000 and 100,000 times magnification. Within this magnification range, it is possible to take advantage of the phase contrast transfer characteristics of the objective lens while the electron load on the object is kept at a moderate level. Using the pre-irradiation procedure special features of the T2 bacteriophage morphology could be established. (author)

  9. A Century of Shope Papillomavirus in Museum Rabbit Specimens.

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    Clara Escudero Duch

    Full Text Available Sylvilagus floridanus Papillomavirus (SfPV causes growth of large horn-like tumors on rabbits. SfPV was described in cottontail rabbits (probably Sylvilagus floridanus from Kansas and Iowa by Richard Shope in 1933, and detected in S. audubonii in 2011. It is known almost exclusively from the US Midwest. We explored the University of Kansas Natural History Museum for historical museum specimens infected with SfPV, using molecular techniques, to assess if additional wild species host SfPV, and whether SfPV occurs throughout the host range, or just in the Midwest. Secondary aims were to detect distinct strains, and evidence for strain spatio-temporal specificity. We found 20 of 1395 rabbits in the KU collection SfPV symptomatic. Three of 17 lagomorph species (S. nuttallii, and the two known hosts were symptomatic, while Brachylagus, Lepus and eight additional Sylvilagus species were not. 13 symptomatic individuals were positive by molecular testing, including the first S. nuttallii detection. Prevalence of symptomatic individuals was significantly higher in Sylvilagus (1.8% than Lepus. Half of these specimens came from Kansas, though new molecular detections were obtained from Jalisco-Mexico's first-and Nebraska, Nevada, New Mexico, and Texas, USA. We document the oldest lab-confirmed case (Kansas, 1915, pre-dating Shope's first case. SfPV amplification was possible from 63.2% of symptomatic museum specimens. Using multiple methodologies, rolling circle amplification and, multiple isothermal displacement amplification in addition to PCR, greatly improved detection rates. Short sequences were obtained from six individuals for two genes. L1 gene sequences were identical to all previously detected sequences; E7 gene sequences, were more variable, yielding five distinct SfPV1 strains that differing by less than 2% from strains circulating in the Midwest and Mexico, between 1915 and 2005. Our results do not clarify whether strains are host species

  10. Tumor Types: Understanding Brain Tumors

    Science.gov (United States)

    ... May cause excessive secretion of hormones Common among men and women in their 50s-80s Accounts for about 13 percent of all brain tumors Symptoms Headache Depression Vision loss Nausea or vomiting Behavioral and cognitive ...

  11. Development of fatigue life evaluation method using small specimen

    International Nuclear Information System (INIS)

    Nogami, Shuhei; Nishimura, Arata; Wakai, Eichi; Tanigawa, Hiroyasu; Itoh, Takamoto; Hasegawa, Akira

    2013-01-01

    For developing the fatigue life evaluation method using small specimen, the effect of specimen size and shape on the fatigue life of the reduced activation ferritic/martensitic steels (F82H-IEA, F82H-BA07 and JLF-1) was investigated by the fatigue test at room temperature in air using round-bar and hourglass specimens with various specimen sizes (test section diameter: 0.85–10 mm). The round-bar specimen showed no specimen size and no specimen shape effects on the fatigue life, whereas the hourglass specimen showed no specimen size effect and obvious specimen shape effect on it. The shorter fatigue life of the hourglass specimen observed under low strain ranges could be attributed to the shorter micro-crack initiation life induced by the stress concentration dependent on the specimen shape. On the basis of this study, the small round-bar specimen was an acceptable candidate for evaluating the fatigue life using small specimen

  12. Environmental stress, ageing and glial cell senescence: a novel mechanistic link to Parkinson's disease?

    Science.gov (United States)

    Chinta, S J; Lieu, C A; Demaria, M; Laberge, R-M; Campisi, J; Andersen, J K

    2013-05-01

    Exposure to environmental toxins is associated with a variety of age-related diseases including cancer and neurodegeneration. For example, in Parkinson's disease (PD), chronic environmental exposure to certain toxins has been linked to the age-related development of neuropathology. Neuronal damage is believed to involve the induction of neuroinflammatory events as a consequence of glial cell activation. Cellular senescence is a potent anti-cancer mechanism that occurs in a number of proliferative cell types and causes the arrest of proliferation of cells at risk of malignant transformation following exposure to potentially oncogenic stimuli. With age, senescent cells accumulate and express a senescence-associated secretory phenotype (SASP; that is the robust secretion of many inflammatory cytokines, growth factors and proteases). Whereas cell senescence in peripheral tissues has been causally linked to a number of age-related pathologies, little is known about the induction of cellular senescence and the SASP in the brain. On the basis of recently reported findings, we propose that environmental stressors associated with PD may act in part by eliciting senescence and the SASP within non neuronal glial cells in the ageing brain, thus contributing to the characteristic decline in neuronal integrity that occurs in this disorder. © 2013 The Association for the Publication of the Journal of Internal Medicine.

  13. Environmental stress, ageing and glial cell senescence: a novel mechanistic link to Parkinson’s disease?

    Science.gov (United States)

    Chinta, Shankar J; Lieu, Christopher A; DeMaria, Marco; Laberge, Remi-Martin; Campisi, Judith; Andersen, Julie K

    2013-01-01

    Exposure to environmental toxins is associated with a variety of age-related diseases including cancer and neurodegeneration. For example, in Parkinson’s disease (PD), chronic environmental exposure to certain toxins has been linked to the age-related development of neuropathology. Neuronal damage is believed to involve the induction of neuroinflammatory events as a consequence of glial cell activation. Cellular senescence is a potent anti-cancer mechanism that occurs in a number of proliferative cell types and causes the arrest of proliferation of cells at risk of malignant transformation following exposure to potentially oncogenic stimuli. With age, senescent cells accumulate and express a senescence-associated secretory phenotype (SASP; i.e. the robust secretion of many inflammatory cytokines, growth factors and proteases). Whereas cell senescence in peripheral tissues has been causally linked to a number of age-related pathologies, little is known about the induction of cellular senescence and the SASP in the brain. Based on recently reported findings, we propose that environmental stressors associated with PD may act in part by eliciting senescence and the SASP within non-neuronal glial cells in the ageing brain, thus contributing to the characteristic decline in neuronal integrity that occurs in this disorder. PMID:23600398

  14. Activation of Satellite Glial Cells in Rat Trigeminal Ganglion after Upper Molar Extraction

    International Nuclear Information System (INIS)

    Gunjigake, Kaori K.; Goto, Tetsuya; Nakao, Kayoko; Kobayashi, Shigeru; Yamaguchi, Kazunori

    2009-01-01

    The neurons in the trigeminal ganglion (TG) are surrounded by satellite glial cells (SGCs), which passively support the function of the neurons, but little is known about the interactions between SGCs and TG neurons after peripheral nerve injury. To examine the effect of nerve injury on SGCs, we investigated the activation of SGCs after neuronal damage due to the extraction of the upper molars in rats. Three, 7, and 10 days after extraction, animals were fixed and the TG was removed. Cryosections of the ganglia were immunostained with antibodies against glial fibrillary acidic protein (GFAP), a marker of activated SGCs, and ATF3, a marker of damaged neurons. After tooth extraction, the number of ATF3-immunoreactive (IR) neurons enclosed by GFAP-IR SGCs had increased in a time-dependent manner in the maxillary nerve region of the TG. Although ATF3-IR neurons were not detected in the mandibular nerve region, the number of GFAP-IR SGCs increased in both the maxillary and mandibular nerve regions. Our results suggest that peripheral nerve injury affects the activation of TG neurons and the SGCs around the injured neurons. Moreover, our data suggest the existence of a neuronal interaction between maxillary and mandibular neurons via SGC activation

  15. Resveratrol confers protection against rotenone-induced neurotoxicity by modulating myeloperoxidase levels in glial cells.

    Directory of Open Access Journals (Sweden)

    Chi Young Chang

    Full Text Available Myeloperoxidase (MPO functions as a key molecular component of the host defense system against diverse pathogens. We have previously reported that increased MPO levels and activity is a distinguishing feature of rotenone-exposed glial cells, and that either overactivation or deficiency of MPO leads to pathological conditions in the brain. Here, we provide that modulation of MPO levels in glia by resveratrol confers protective effects on rotenone-induced neurotoxicity. We show that resveratrol significantly reduced MPO levels but did not trigger abnormal nitric oxide (NO production in microglia and astrocytes. Resveratrol-induced down-regulation of MPO, in the absence of an associated overproduction of NO, markedly attenuated rotenone-triggered inflammatory responses including phagocytic activity and reactive oxygen species production in primary microglia and astrocytes. In addition, impaired responses of primary mixed glia from Mpo (-/- mice to rotenone were relieved by treatment with resveratrol. We further show that rotenone-induced neuronal injury, particularly dopaminergic cell death, was attenuated by resveratrol in neuron-glia co-cultures, but not in neurons cultured alone. Similar regulatory effects of resveratrol on MPO levels were observed in microglia treated with MPP(+, another Parkinson's disease-linked neurotoxin, supporting the beneficial effects of resveratrol on the brain. Collectively, our findings provide that resveratrol influences glial responses to rotenone by regulating both MPO and NO, and thus protects against rotenone-induced neuronal injury.

  16. Possible role of glial cells in the relationship between thyroid dysfunction and mental disorders

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    Mami eNoda

    2015-06-01

    Full Text Available It is widely accepted that there is a close relationship between the endocrine system and the central nervous system (CNS. Among hormones closely related to the nervous system, thyroid hormones (THs are critical for the development and function of the CNS; not only for neuronal cells but also for glial development and differentiation. Any impairment of TH supply to the developing CNS causes severe and irreversible changes in the overall architecture and function of human brain, leading to various neurological dysfunctions. In adult brain, impairment of THs, such as hypothyroidism and hyperthyroidism, can cause psychiatric disorders such as schizophrenia, bipolar disorder, anxiety and depression. Though hypothyroidism impairs synaptic transmission and plasticity, its effect on glial cells and cellular mechanisms are unknown. This mini-review article summarizes how THs are transported to the brain, metabolized in astrocytes and affect microglia and oligodendrocytes, showing an example of glioendocrine system. It may help to understand physiological and/or pathophysiological functions of THs in the CNS and how hypo- and hyper-thyroidism may cause mental disorders.

  17. Titanium dioxide nanoparticles inhibit proliferation and induce morphological changes and apoptosis in glial cells

    International Nuclear Information System (INIS)

    Márquez-Ramírez, Sandra Gissela; Delgado-Buenrostro, Norma Laura; Chirino, Yolanda Irasema; Iglesias, Gisela Gutiérrez; López-Marure, Rebeca

    2012-01-01

    Titanium dioxide nanoparticles (TiO 2 NPs) are widely used in the chemical, electrical and electronic industries. TiO 2 NPs can enter directly into the brain through the olfactory bulb and be deposited in the hippocampus region. We determined the effect of TiO 2 NPs on rat and human glial cells, C6 and U373, respectively. We evaluated proliferation by crystal violet staining, internalization of TiO 2 NPs, and cellular morphology by TEM analysis, as well as F-actin distribution by immunostaining and cell death by detecting active caspase-3 and DNA fragmentation. TiO 2 NPs inhibited proliferation and induced morphological changes that were related with a decrease in immuno-location of F-actin fibers. TiO 2 NPs were internalized and formation of vesicles was observed. TiO 2 NPs induced apoptosis after 96 h of treatment. Hence, TiO 2 NPs had a cytotoxic effect on glial cells, suggesting that exposure to TiO 2 NPs could cause brain injury and be hazardous to health.

  18. Glial degeneration with oxidative damage drives neuronal demise in MPSII disease.

    Science.gov (United States)

    Zalfa, Cristina; Verpelli, Chiara; D'Avanzo, Francesca; Tomanin, Rosella; Vicidomini, Cinzia; Cajola, Laura; Manara, Renzo; Sala, Carlo; Scarpa, Maurizio; Vescovi, Angelo Luigi; De Filippis, Lidia

    2016-08-11

    Mucopolysaccharidosis type II (MPSII) is a lysosomal storage disorder due to the deficit of the iduronate 2-sulfatase (IDS) enzyme, causing progressive neurodegeneration in patients. Neural stem cells (NSCs) derived from the IDS-ko mouse can recapitulate MPSII pathogenesis in vitro. In differentiating IDS-ko NSCs and in the aging IDS-ko mouse brain, glial degeneration precedes neuronal degeneration. Here we show that pure IDS-ko NSC-derived astrocytes are selectively able to drive neuronal degeneration when cocultured with healthy neurons. This phenotype suggests concurrent oxidative damage with metabolic dysfunction. Similar patterns were observed in murine IDS-ko animals and in human MPSII brains. Most importantly, the mutant phenotype of IDS-ko astrocytes was reversed by low oxygen conditions and treatment with vitamin E, which also reversed the toxic effect on cocultured neurons. Moreover, at very early stages of disease we detected in vivo the development of a neuroinflammatory background that precedes astroglial degeneration, thus suggesting a novel model of MPSII pathogenesis, with neuroinflammation preceding glial degeneration, which is finally followed by neuronal death. This hypothesis is also consistent with the progression of white matter abnormalities in MPSII patients. Our study represents a novel breakthrough in the elucidation of MPSII brain pathogenesis and suggests the antioxidant molecules as potential therapeutic tools to delay MPSII onset and progression.

  19. Lipid metabolism in myelinating glial cells: lessons from human inherited disorders and mouse models.

    Science.gov (United States)

    Chrast, Roman; Saher, Gesine; Nave, Klaus-Armin; Verheijen, Mark H G

    2011-03-01

    The integrity of central and peripheral nervous system myelin is affected in numerous lipid metabolism disorders. This vulnerability was so far mostly attributed to the extraordinarily high level of lipid synthesis that is required for the formation of myelin, and to the relative autonomy in lipid synthesis of myelinating glial cells because of blood barriers shielding the nervous system from circulating lipids. Recent insights from analysis of inherited lipid disorders, especially those with prevailing lipid depletion and from mouse models with glia-specific disruption of lipid metabolism, shed new light on this issue. The particular lipid composition of myelin, the transport of lipid-associated myelin proteins, and the necessity for timely assembly of the myelin sheath all contribute to the observed vulnerability of myelin to perturbed lipid metabolism. Furthermore, the uptake of external lipids may also play a role in the formation of myelin membranes. In addition to an improved understanding of basic myelin biology, these data provide a foundation for future therapeutic interventions aiming at preserving glial cell integrity in metabolic disorders.

  20. GABA and glutamate uptake and metabolism in retinal glial (Müller cells

    Directory of Open Access Journals (Sweden)

    Andreas eBringmann

    2013-04-01

    Full Text Available Müller cells, the principal glial cells of the retina, support the synaptic activity by the uptake and metabolization of extracellular neurotransmitters. Müller cells express uptake and exchange systems for various neurotransmitters including glutamate and -aminobutyric acid (GABA. Müller cells remove the bulk of extracellular glutamate in the inner retina and contribute to the glutamate clearance around photoreceptor terminals. By the uptake of glutamate, Müller cells are involved in the shaping and termination of the synaptic activity, particularly in the inner retina. Reactive Müller cells are neuroprotective, e.g., by the clearance of excess extracellular glutamate, but may also contribute to neuronal degeneration by a malfunctioning or even reversal of glial glutamate transporters, or by a downregulation of the key enzyme, glutamine synthetase. This review summarizes the present knowledge about the role of Müller cells in the clearance and metabolization of extracellular glutamate and GABA. Some major pathways of GABA and glutamate metabolism in Müller cells are described; these pathways are involved in the glutamate-glutamine cycle of the retina, in the defense against oxidative stress via the production of glutathione, and in the production of substrates for the neuronal energy metabolism.

  1. New Implications for the Melanocortin System in Alcohol Drinking Behavior in Adolescents: The Glial Dysfunction Hypothesis

    Science.gov (United States)

    Orellana, Juan A.; Cerpa, Waldo; Carvajal, Maria F.; Lerma-Cabrera, José M.; Karahanian, Eduardo; Osorio-Fuentealba, Cesar; Quintanilla, Rodrigo A.

    2017-01-01

    Alcohol dependence causes physical, social, and moral harms and currently represents an important public health concern. According to the World Health Organization (WHO), alcoholism is the third leading cause of death worldwide, after tobacco consumption and hypertension. Recent epidemiologic studies have shown a growing trend in alcohol abuse among adolescents, characterized by the consumption of large doses of alcohol over a short time period. Since brain development is an ongoing process during adolescence, short- and long-term brain damage associated with drinking behavior could lead to serious consequences for health and wellbeing. Accumulating evidence indicates that alcohol impairs the function of different components of the melanocortin system, a major player involved in the consolidation of addictive behaviors during adolescence and adulthood. Here, we hypothesize the possible implications of melanocortins and glial cells in the onset and progression of alcohol addiction. In particular, we propose that alcohol-induced decrease in α-MSH levels may trigger a cascade of glial inflammatory pathways that culminate in altered gliotransmission in the ventral tegmental area and nucleus accumbens (NAc). The latter might potentiate dopaminergic drive in the NAc, contributing to increase the vulnerability to alcohol dependence and addiction in the adolescence and adulthood. PMID:28424592

  2. Modeling glial contributions to seizures and epileptogenesis: cation-chloride cotransporters in Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    Zeid M Rusan

    Full Text Available Flies carrying a kcc loss-of-function mutation are more seizure-susceptible than wild-type flies. The kcc gene is the highly conserved Drosophila melanogaster ortholog of K+/Cl- cotransporter genes thought to be expressed in all animal cell types. Here, we examined the spatial and temporal requirements for kcc loss-of-function to modify seizure-susceptibility in flies. Targeted RNA interference (RNAi of kcc in various sets of neurons was sufficient to induce severe seizure-sensitivity. Interestingly, kcc RNAi in glia was particularly effective in causing seizure-sensitivity. Knockdown of kcc in glia or neurons during development caused a reduction in seizure induction threshold, cell swelling, and brain volume increase in 24-48 hour old adult flies. Third instar larval peripheral nerves were enlarged when kcc RNAi was expressed in neurons or glia. Results suggest that a threshold of K+/Cl- cotransport dysfunction in the nervous system during development is an important determinant of seizure-susceptibility in Drosophila. The findings presented are the first attributing a causative role for glial cation-chloride cotransporters in seizures and epileptogenesis. The importance of elucidating glial cell contributions to seizure disorders and the utility of Drosophila models is discussed.

  3. Comparison of contrast in brightness mode and strain ultrasonography of glial brain tumours

    International Nuclear Information System (INIS)

    Selbekk, Tormod; Brekken, Reidar; Indergaard, Marit; Solheim, Ole; Unsgård, Geirmund

    2012-01-01

    Image contrast between normal tissue and brain tumours may sometimes appear to be low in intraoperative ultrasound. Ultrasound imaging of strain is an image modality that has been recently explored for intraoperative imaging of the brain. This study aims to investigate differences in image contrast between ultrasound brightness mode (B-mode) images and ultrasound strain magnitude images of brain tumours. Ultrasound radiofrequency (RF) data was acquired during surgery in 15 patients with glial tumours. The data were subsequently processed to provide strain magnitude images. The contrast in the B-mode images and the strain images was determined in assumed normal brain tissue and tumour tissue at selected regions of interest (ROI). Three measurements of contrast were done in the ultrasound data for each patient. The B-mode and strain contrasts measurements were compared using the paired samples t- test. The statistical analysis of a total of 45 measurements shows that the contrasts in the strain magnitude images are significantly higher than in the conventional ultrasound B-mode images (P < 0.0001). The results indicate that ultrasound strain imaging provides better discrimination between normal brain tissue and glial tumour tissue than conventional ultrasound B-mode imaging. Ultrasound imaging of tissue strain therefore holds the potential of becoming a valuable adjunct to conventional intraoperative ultrasound imaging in brain tumour surgery

  4. Functional protease profiling with reporter peptides in serum specimens of colorectal cancer patients: demonstration of its routine diagnostic applicability.

    Science.gov (United States)

    Findeisen, Peter; Costina, Victor; Yepes, Diego; Hofheinz, Ralf; Neumaier, Michael

    2012-06-08

    The progression of many solid tumors is characterized by the release of tumor-associated proteases and the detection of tumor specific proteolytic activity in serum specimens is a promising diagnostic tool in oncology. Here we describe a mass spectrometry-based functional proteomic profiling approach that tracks the ex-vivo degradation of a synthetic endoprotease substrate in serum specimens of colorectal tumor patients. A reporter peptide (RP) with the amino acid sequence WKPYDAAD was synthesized that has a known cleavage site for the cysteine-endopeptidase cancer procoagulant (EC 3.4.22.26). The RP was added to serum specimens from colorectal cancer patients (n = 30), inflammatory controls (n = 30) and healthy controls (n = 30) and incubated under strictly standardized conditions. The proteolytic fragment of the RP was quantified with liquid chromatography / mass spectrometry (LC/MS). RP-spiking showed good intra- and inter-day reproducibility with coefficients of variation (CVs) that did not exceed a value of 10%. The calibration curve for the anchor peptide was linear in the concentration range of 0.4 - 50 μmol/L. The median concentration of the RP-fragment in serum specimens from tumor patients (TU: 17.6 μmol/L, SD 9.0) was significantly higher when compared to non-malignant inflammatory controls (IC: 11.1 μmol/L, SD 6.1) and healthy controls (HC: 10.3 μmol/L, SD 3.1). Highest area under receiver operating characteristic (AUROC) values were seen for discrimination of TU versus HC (0.89) followed by TU versus IC (0.77). IC and HC could barely be separated indicated by an AUROC value of 0.57. The proteolytic activity towards the RP was conserved in serum specimens that were kept at room temperature for up to 24 hours prior to the analysis. The proteolytic cleavage of reporter peptides is a surrogate marker for tumor associated proteolytic activity in serum specimens of cancer patients. A simple, robust and highly reproducible LC/MS method has

  5. Functional protease profiling with reporter peptides in serum specimens of colorectal cancer patients: demonstration of its routine diagnostic applicability

    Directory of Open Access Journals (Sweden)

    Findeisen Peter

    2012-06-01

    Full Text Available Abstract Background The progression of many solid tumors is characterized by the release of tumor-associated proteases and the detection of tumor specific proteolytic activity in serum specimens is a promising diagnostic tool in oncology. Here we describe a mass spectrometry-based functional proteomic profiling approach that tracks the ex-vivo degradation of a synthetic endoprotease substrate in serum specimens of colorectal tumor patients. Methods A reporter peptide (RP with the amino acid sequence WKPYDAAD was synthesized that has a known cleavage site for the cysteine-endopeptidase cancer procoagulant (EC 3.4.22.26. The RP was added to serum specimens from colorectal cancer patients (n = 30, inflammatory controls (n = 30 and healthy controls (n = 30 and incubated under strictly standardized conditions. The proteolytic fragment of the RP was quantified with liquid chromatography / mass spectrometry (LC/MS. Results RP-spiking showed good intra- and inter-day reproducibility with coefficients of variation (CVs that did not exceed a value of 10%. The calibration curve for the anchor peptide was linear in the concentration range of 0.4 – 50 μmol/L. The median concentration of the RP-fragment in serum specimens from tumor patients (TU: 17.6 μmol/L, SD 9.0 was significantly higher when compared to non-malignant inflammatory controls (IC: 11.1 μmol/L, SD 6.1 and healthy controls (HC: 10.3 μmol/L, SD 3.1. Highest area under receiver operating characteristic (AUROC values were seen for discrimination of TU versus HC (0.89 followed by TU versus IC (0.77. IC and HC could barely be separated indicated by an AUROC value of 0.57. The proteolytic activity towards the RP was conserved in serum specimens that were kept at room temperature for up to 24 hours prior to the analysis. Conclusion The proteolytic cleavage of reporter peptides is a surrogate marker for tumor associated proteolytic activity in serum specimens of cancer patients. A

  6. Tumor immunology.

    Science.gov (United States)

    Mocellin, Simone; Lise, Mario; Nitti, Donato

    2007-01-01

    Advances in tumor immunology are supporting the clinical implementation of several immunological approaches to cancer in the clinical setting. However, the alternate success of current immunotherapeutic regimens underscores the fact that the molecular mechanisms underlying immune-mediated tumor rejection are still poorly understood. Given the complexity of the immune system network and the multidimensionality of tumor/host interactions, the comprehension of tumor immunology might greatly benefit from high-throughput microarray analysis, which can portrait the molecular kinetics of immune response on a genome-wide scale, thus accelerating the discovery pace and ultimately catalyzing the development of new hypotheses in cell biology. Although in its infancy, the implementation of microarray technology in tumor immunology studies has already provided investigators with novel data and intriguing new hypotheses on the molecular cascade leading to an effective immune response against cancer. Although the general principles of microarray-based gene profiling have rapidly spread in the scientific community, the need for mastering this technique to produce meaningful data and correctly interpret the enormous output of information generated by this technology is critical and represents a tremendous challenge for investigators, as outlined in the first section of this book. In the present Chapter, we report on some of the most significant results obtained with the application of DNA microarray in this oncology field.

  7. Pancreatic islet cell tumor

    Science.gov (United States)

    ... cell tumors; Islet of Langerhans tumor; Neuroendocrine tumors; Peptic ulcer - islet cell tumor; Hypoglycemia - islet cell tumor ... stomach acid. Symptoms may include: Abdominal pain Diarrhea ... and small bowel Vomiting blood (occasionally) Glucagonomas make ...

  8. Recent advances in FIB-TEM specimen preparation techniques

    International Nuclear Information System (INIS)

    Li Jian; Malis, T.; Dionne, S.

    2006-01-01

    Preparing high-quality transmission electron microscopy (TEM) specimens is of paramount importance in TEM studies. The development of the focused ion beam (FIB) microscope has greatly enhanced TEM specimen preparation capabilities. In recent years, various FIB-TEM foil preparation techniques have been developed. However, the currently available techniques fail to produce TEM specimens from fragile and ultra-fine specimens such as fine fibers. In this paper, the conventional FIB-TEM specimen preparation techniques are reviewed, and their advantages and shortcomings are compared. In addition, a new technique suitable to prepare TEM samples from ultra-fine specimens is demonstrated

  9. Downregulation of DmMANF in Glial Cells Results in Neurodegeneration and Affects Sleep and Lifespan in Drosophila melanogaster

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    Lucyna Walkowicz

    2017-11-01

    Full Text Available In Drosophila melanogaster, mesencephalic astrocyte-derived neurotrophic factor (DmMANF is an evolutionarily conserved ortholog of mammalian MANF and cerebral dopamine neurotrophic factor (CDNF, which have been shown to promote the survival of dopaminergic neurons in the brain. We observed especially high levels of DmMANF in the visual system of Drosophila, particularly in the first optic neuropil (lamina. In the lamina, DmMANF was found in glial cells (surface and epithelial glia, photoreceptors and interneurons. Interestingly, silencing of DmMANF in all neurons or specifically in photoreceptors or L2 interneurons had no impact on the structure of the visual system. However, downregulation of DmMANF in glial cells induced degeneration of the lamina. Remarkably, this degeneration in the form of holes and/or tightly packed membranes was observed only in the lamina epithelial glial cells. Those membranes seem to originate from the endoplasmic reticulum, which forms autophagosome membranes. Moreover, capitate projections, the epithelial glia invaginations into photoreceptor terminals that are involved in recycling of the photoreceptor neurotransmitter histamine, were less numerous after DmMANF silencing either in neurons or glial cells. The distribution of the alpha subunit of Na+/K+-ATPase protein in the lamina cell membranes was also changed. At the behavioral level, silencing of DmMANF either in neurons or glial cells affected the daily activity/sleep pattern, and flies showed less activity during the day but higher activity during the night than did controls. In the case of silencing in glia, the lifespan of flies was also shortened. The obtained results showed that DmMANF regulates many functions in the brain, particularly those dependent on glial cells.

  10. Age-Related Changes in the Expression of the Circadian Clock Protein PERIOD in Drosophila Glial Cells

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    Dani M. Long

    2018-01-01

    Full Text Available Circadian clocks consist of molecular negative feedback loops that coordinate physiological, neurological, and behavioral variables into “circa” 24-h rhythms. Rhythms in behavioral and other circadian outputs tend to weaken during aging, as evident in progressive disruptions of sleep-wake cycles in aging organisms. However, less is known about the molecular changes in the expression of clock genes and proteins that may lead to the weakening of circadian outputs. Western blot studies have demonstrated that the expression of the core clock protein PERIOD (PER declines in the heads of aged Drosophila melanogaster flies. This age-related decline in PER does not occur in the central pacemaker neurons but has been demonstrated so far in retinal photoreceptors. Besides photoreceptors, clock proteins are also expressed in fly glia, which play important roles in neuronal homeostasis and are further categorized into subtypes based on morphology and function. While previous studies of mammalian glial cells have demonstrated the presence of functional clocks in astrocytes and microglia, it is not known which glial cell types in Drosophila express clock proteins and how their expression may change in aged individuals. Here, we conducted immunocytochemistry experiments to identify which glial subtypes express PER protein suggestive of functional circadian clocks. Glial cell subtypes that showed night-time accumulation and day-time absence in PER consistent with oscillations reported in the pacemaker neurons were selected to compare the level of PER protein between young and old flies. Our data demonstrate that some glial subtypes show rhythmic PER expression and the relative PER levels become dampened with advanced age. Identification of glial cell types that display age-related dampening of PER levels may help to understand the cellular changes that contribute to the loss of homeostasis in the aging brain.

  11. Poly-thymidine oligonucleotides mediate activation of murine glial cells primarily through TLR7, not TLR8.

    Directory of Open Access Journals (Sweden)

    Min Du

    Full Text Available The functional role of murine TLR8 in the inflammatory response of the central nervous system (CNS remains unclear. Murine TLR8 does not appear to respond to human TLR7/8 agonists, due to a five amino acid deletion in the ectodomain. However, recent studies have suggested that murine TLR8 may be stimulated by alternate ligands, which include vaccinia virus DNA, phosphothioate oligodeoxynucleotides (ODNs or the combination of phosphothioate poly-thymidine oligonucleotides (pT-ODNs with TLR7/8 agonists. In the current study, we analyzed the ability of pT-ODNs to induce activation of murine glial cells in the presence or absence of TLR7/8 agonists. We found that TLR7/8 agonists induced the expression of glial cell activation markers and induced the production of multiple proinflammatory cytokines and chemokines in mixed glial cultures. In contrast, pT-ODNs alone induced only low level expression of two cytokines, CCL2 and CXCL10. The combination of pT-ODNs along with TLR7/8 agonists induced a synergistic response with substantially higher levels of proinflammatory cytokines and chemokines compared to CL075. This enhancement was not due to cellular uptake of the agonist, indicating that the pT-ODN enhancement of cytokine responses was due to effects on an intracellular process. Interestingly, this response was also not due to synergistic stimulation of both TLR7 and TLR8, as the loss of TLR7 abolished the activation of glial cells and cytokine production. Thus, pT-ODNs act in synergy with TLR7/8 agonists to induce strong TLR7-dependent cytokine production in glial cells, suggesting that the combination of pT-ODNs with TLR7 agonists may be a useful mechanism to induce pronounced glial activation in the CNS.

  12. Evidence of female-specific glial deficits in the hippocampus in a mouse model of prenatal stress.

    LENUS (Irish Health Repository)

    Behan, Aine T

    2011-01-01

    Prenatal stress (PS) has been associated with an increased incidence of numerous neuropsychiatric disorders, including depression, anxiety, schizophrenia, and autism. To determine the effects of PS on hippocampal-dependent behaviour hippocampal morphology, we examined behavioural responses and hippocampal cytoarchitecture of a maternal restraint stress paradigm of PS in C57BL6 mice. Female offspring only showed a reduction in hippocampal glial count in the pyramidal layer following PS. Additionally, only PS females showed increased depressive-like behaviour with cognitive deficits predominantly in female offspring when compared to males. This data provides evidence for functional female-specific glial deficits within the hippocampus as a consequence of PS.

  13. Evidence of female-specific glial deficits in the hippocampus in a mouse model of prenatal stress.

    LENUS (Irish Health Repository)

    Behan, Aine T

    2012-02-01

    Prenatal stress (PS) has been associated with an increased incidence of numerous neuropsychiatric disorders, including depression, anxiety, schizophrenia, and autism. To determine the effects of PS on hippocampal-dependent behaviour hippocampal morphology, we examined behavioural responses and hippocampal cytoarchitecture of a maternal restraint stress paradigm of PS in C57BL6 mice. Female offspring only showed a reduction in hippocampal glial count in the pyramidal layer following PS. Additionally, only PS females showed increased depressive-like behaviour with cognitive deficits predominantly in female offspring when compared to males. This data provides evidence for functional female-specific glial deficits within the hippocampus as a consequence of PS.

  14. Classification of breast cancer cytological specimen using convolutional neural network

    Science.gov (United States)

    Żejmo, Michał; Kowal, Marek; Korbicz, Józef; Monczak, Roman

    2017-01-01

    The paper presents a deep learning approach for automatic classification of breast tumors based on fine needle cytology. The main aim of the system is to distinguish benign from malignant cases based on microscopic images. Experiment was carried out on cytological samples derived from 50 patients (25 benign cases + 25 malignant cases) diagnosed in Regional Hospital in Zielona Góra. To classify microscopic images, we used convolutional neural networks (CNN) of two types: GoogLeNet and AlexNet. Due to the very large size of images of cytological specimen (on average 200000 × 100000 pixels), they were divided into smaller patches of size 256 × 256 pixels. Breast cancer classification usually is based on morphometric features of nuclei. Therefore, training and validation patches were selected using Support Vector Machine (SVM) so that suitable amount of cell material was depicted. Neural classifiers were tuned using GPU accelerated implementation of gradient descent algorithm. Training error was defined as a cross-entropy classification loss. Classification accuracy was defined as the percentage ratio of successfully classified validation patches to the total number of validation patches. The best accuracy rate of 83% was obtained by GoogLeNet model. We observed that more misclassified patches belong to malignant cases.

  15. Molecular changes preceding endometrial and ovarian cancer: a study of consecutive endometrial specimens from Lynch syndrome surveillance.

    Science.gov (United States)

    Niskakoski, Anni; Pasanen, Annukka; Lassus, Heini; Renkonen-Sinisalo, Laura; Kaur, Sippy; Mecklin, Jukka-Pekka; Bützow, Ralf; Peltomäki, Päivi

    2018-03-27

    Molecular alterations preceding endometrial and ovarian cancer and the sequence of events are unknown. Consecutive specimens from lifelong surveillance for Lynch syndrome provides a natural setting to address such questions. To molecularly define the multistep gynecological tumorigenesis, DNA mismatch repair gene mutation carriers with endometrial or ovarian carcinoma or endometrial hyperplasia were identified from a nation-wide registry and endometrial biopsy specimens taken from these individuals during 20 years of screening were collected. A total of 213 endometrial and ovarian specimens from Lynch syndrome individuals and 197 histology-matched (non-serous) samples from sporadic cases were available for this investigation. The specimens were profiled for markers linked to endometrial and ovarian tumorigenesis, including ARID1A protein expression, mismatch repair status, and tumor suppressor gene promoter methylation. In Lynch syndrome-associated endometrial and ovarian carcinomas, ARID1A protein was lost in 61-100% and mismatch repair was deficient in 97-100%, compared to 0-17% and 14-44% in sporadic cases (P = 0.000). ARID1A loss appeared in complex hyperplasia and deficient mismatch repair and tumor suppressor gene promoter methylation in histologically normal endometrium. Despite quantitative differences between Lynch syndrome and sporadic cases, ARID1A expression, mismatch repair, and tumor suppressor gene promoter methylation divided endometrial samples from both patient groups into three categories of increasing abnormality, comprising normal endometrium and simple hyperplasia (I), complex hyperplasia with or without atypia (II), and endometrial cancer (III). Complex hyperplasias without vs. with atypia were molecularly indistinguishable. In conclusion, surveillance specimens from Lynch syndrome identify mismatch repair deficiency, tumor suppressor gene promoter methylation, and ARID1A loss as early changes in tumor development. Our findings are

  16. T3 receptors in human pituitary tumors.

    Science.gov (United States)

    Machiavelli, Gloria A; Pauni, Micaela; Heredia Sereno, Gastón M; Szijan, Irene; Basso, Armando; Burdman, José A

    2009-11-01

    The purpose of this work was to investigate the synthesis of T3 receptors in human tumors of the anterior pituitary gland, its relationship with the hormone synthesized and/or secreted by the tumor and the post-surgical evolution of the patient. Patients were evaluated clinically and by magnetic nuclear resonance to classify the adenoma according to their size. Hormonal concentrations in sera were determined by radioimmunoassay. Immunohistochemistry of the pituitary hormones was performed in the tumors. Tumors were obtained at surgery and immediately frozen in ice, transported to the laboratory and stored at -70 degrees C. Reverse transcription was performed with purified RNA from the tumors. Out of 33 pituitary tumors, 29 had RNA for T3 receptors synthesis (88%). They were present in different histological specimens, the tumors were grades 1-4 according to their size, and there was no relationship between the size of the tumor and the presence of T3 receptor RNAs. The post-surgical evolution of the patient was mostly dependent on the size and not on the presence of T3 receptors. The presence of thyroid hormone receptors in pituitary tumors is in line with two important characteristics of these tumors: they are histologically benign and well differentiated.

  17. Investigations on contribution of glial inwardly-rectifying K+ current to membrane potential and ion flux: An experimental and theoretical study

    Directory of Open Access Journals (Sweden)

    Sheng-Nan Wu

    2015-01-01

    Full Text Available The inwardly rectifying K+ current [IK(IR] allows large inward K+ currents at potentials negative to K+ equilibrium potential (EK and it becomes small outward K+ currents at those positive to EK. How changes of such currents enriched in glial cells can influence the functions of glial cell, neurons, or both is not clearly defined, although mutations of Kir4.1 channels have been demonstrated to cause serious neurological disorders. In this study, we identified the presence of IK(IR in human glioma cells (U373 and U87 cells. The amplitude of IK(IR in U373 cells was subject to inhibition by amitriptyline, arecoline, or BaCl2. The activity of inwardly rectifying K+ channels was also clearly detected, and single-channel conductance of these channels was calculated to be around 23 pS. Moreover, based on a simulation model derived from neuron–glial interaction mediated by ion flux, we further found out that incorporation of glial IK(IR conductance into the model can significantly contribute to regulation of extracellular K+ concentrations and glial resting potential, particularly during high-frequency stimulation. Glial cells and neurons can mutually modulate their expression of ion channels through K+ ions released into the extracellular space. It is thus anticipated that glial IK(IR may be a potential target utilized to influence the activity of neuronal and glial cells as well as their interaction.

  18. Anti-inflammatory effect by lentiviral-mediated overexpression of IL-10 or IL-1 receptor antagonist in rat glial cells and macrophages

    NARCIS (Netherlands)

    van Strien, N.M.; Mercier, D.; Drukarch, B.; Breve, J.J.P.; Poole, S.; Binnekade, R.; Bol, J.G.J.M.; Blits, B.; Verhaagen, J.; van Dam, A.M.W.

    2010-01-01

    Neuroinflammation, as defined by activation of local glial cells and production of various inflammatory mediators, is an important feature of many neurological disorders. Expression of pro-inflammatory mediators produced by glial cells in the central nervous system (CNS) is considered to contribute

  19. Preoperative intraluminal irradiation of the extrahepatic bile duct tumor

    International Nuclear Information System (INIS)

    Kamada, Tadashi; Tsujii, Hirohiko; Arimoto, Takuro; Irie, Goro.

    1991-01-01

    From 1984 through 1986, six patients with extrahepatic bile duct tumor were treated preoperatively with intraluminal irradiation of the bile duct. There were no unresectable cases and pathological examination of the surgical specimens showed moderate to remarkable tumor regression in all cases. Postoperative biliary tract hemorrhage occurred in 2 of 3 patients who received 60 Gy at a point 7.5 mm from the center of the source. With accurate preoperative diagnosis of the tumor extent and careful setting of the target area of intraluminal irradiation, improved local tumor control of extrahepatic bile duct tumor can be expected with this method. (author)

  20. Corrosion testing of uranium silicide fuel specimens

    International Nuclear Information System (INIS)

    Bourns, W.T.

    1968-09-01

    U 3 Si is the most promising high density natural uranium fuel for water-cooled power reactors. Power reactors fuelled with this material are expected to produce cheaper electricity than those fuelled with uranium dioxide. Corrosion tests in 300 o C water preceded extensive in-reactor performance tests of fuel elements and bundles. Proper heat-treatment of U-3.9 wt% Si gives a U 3 5i specimen which corrodes at less than 2 mg/cm 2 h in 300 o C water. This is an order of magnitude lower than the maximum corrosion rate tolerable in a water-cooled reactor. U 3 Si in a defected unbonded Zircaloy-2 sheath showed only a slow uniform sheath expansion in 300 o C water. All tests were done under isothermal conditions in an out-reactor loop. (author)

  1. A system for mapping radioactive specimens

    International Nuclear Information System (INIS)

    Britten, R.J.; Davidson, E.H.

    1988-01-01

    A system for mapping radioactive specimens comprises an avalanche counter, an encoder, pre-amplifier circuits, sample and hold circuits and a programmed computer. The parallel plate counter utilizes avalanche event counting over a large area with the ability to locate radioactive sources in two dimensions. When a beta ray, for example, enters a chamber, an ionization event occurs and the avalanche effect multiplies the event and results in charge collection on the anode surface for a limited period of time before the charge leaks away. The encoder comprises a symmetrical array of planar conductive surfaces separated from the anode by a dielectric material. The encoder couples charge currents, the amlitudes of which define the relative position of the ionization event. The amplitude of coupled current, delivered to pre-amplifiers, defines the location of the event. (author) 12 figs

  2. Corrosion testing of uranium silicide fuel specimens

    Energy Technology Data Exchange (ETDEWEB)

    Bourns, W T

    1968-09-15

    U{sub 3}Si is the most promising high density natural uranium fuel for water-cooled power reactors. Power reactors fuelled with this material are expected to produce cheaper electricity than those fuelled with uranium dioxide. Corrosion tests in 300{sup o}C water preceded extensive in-reactor performance tests of fuel elements and bundles. Proper heat-treatment of U-3.9 wt% Si gives a U{sub 3}5i specimen which corrodes at less than 2 mg/cm{sup 2} h in 300{sup o}C water. This is an order of magnitude lower than the maximum corrosion rate tolerable in a water-cooled reactor. U{sub 3}Si in a defected unbonded Zircaloy-2 sheath showed only a slow uniform sheath expansion in 300{sup o}C water. All tests were done under isothermal conditions in an out-reactor loop. (author)

  3. Targeting Tumor Oct4 to Deplete Prostate Tumor and Metastasis Initiating Cells

    Science.gov (United States)

    2017-12-01

    is associated with androgen receptor (AR). We detected Oct4 protein expression in prostate cancer cells as well as in tumor tissue specimens...unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Identification of genes driving prostate carcinogenesis will lead to new cancer treatment. The human...a pseudogene of embryonic Oct4 (POU5F1). A recent study found that tumor Oct4 found in prostate cancer cells is due to the gene expression of POU5F1B

  4. Intratumor microvessel density in biopsy specimens predicts local response of hypopharyngeal cancer to radiotherapy

    International Nuclear Information System (INIS)

    Zhang, Shi-Chuan; Miyamoto, Shin-ichi; Hasebe, Takahiro; Ishii, Genichiro; Ochiai, Atsushi; Kamijo, Tomoyuki; Hayashi, Ryuichi; Fukayama, Masashi

    2003-01-01

    The aim of this retrospective study was to identify reliable predictive factors for local control of hypopharyngeal cancer (HPC) treated by radiotherapy. A cohort of 38 patients with HPC treated by radical radiotherapy at the National Cancer Center Hospital East between 1992 and 1999 were selected as subjects for the present study. Paraffin-embedded pre-therapy biopsy specimens from these patients were used for immunostaining to evaluate the relationships between local tumor control and expression of the following previously reported predictive factors for local recurrence of head and neck cancer treated by radiotherapy: Ki-67, Cyclin D1, CDC25B, VEGF, p53, Bax and Bcl-2. The predictive power of microvessel density (MVD) in biopsy specimens and of clinicopathologic factors (age, gender and clinical tumor-node-metastasis stage) was also statistically analyzed. Twenty-five patients developed tumor recurrence at the primary site. Univariate analysis indicated better local control of tumors with high microvessel density [MVD≥median (39 vessels/field)] than with low MVD (< median, P=0.042). There were no significant associations between local control and expression of Ki-67 (P=0.467), Bcl-2 (P=0.127), Bax (P=0.242), p53 (P=0.262), Cyclin D1 (P=0.245), CDC25B (P=0.511) or VEGF (P=0.496). Clinicopathologic factors were also demonstrated to have no significant influence on local control (age, P=0.974; gender, P=0.372; T factor, P=0.602; N factor, P=0.530; Stage, P=0.499). MVD in biopsy specimens was closely correlated with local control of HPC treated by radiotherapy. (author)

  5. 10 CFR 26.165 - Testing split specimens and retesting single specimens.

    Science.gov (United States)

    2010-01-01

    ... (c), as applicable. If the specimen in Bottle A is free of any evidence of drugs or drug metabolites... suitable inquiry conducted under the provisions of § 26.63 or to any other inquiry or investigation... records must be provided to personnel conducting reviews, inquiries into allegations, or audits under the...

  6. A non-destructive DNA sampling technique for herbarium specimens.

    Science.gov (United States)

    Shepherd, Lara D

    2017-01-01

    Herbarium specimens are an important source of DNA for plant research but current sampling methods require the removal of material for DNA extraction. This is undesirable for irreplaceable specimens such as rare species or type material. Here I present the first non-destructive sampling method for extracting DNA from herbarium specimens. DNA was successfully retrieved from robust leaves and/or stems of herbarium specimens up to 73 years old.

  7. Miniature tensile test specimens for fusion reactor irradiation studies

    International Nuclear Information System (INIS)

    Klueh, R.L.

    1985-01-01

    Three miniature sheet-type tensile specimens and a miniature rod-type specimen are being used to determine irradiated tensile properties for alloy development for fusion reactors. The tensile properties of type 316 stainless steel were determined with these different specimens, and the results were compared. Reasonably good agreement was observed. However, there were differences that led to recommendations on which specimens are preferred. 4 references, 9 figures, 6 tables

  8. Elastic-plastic analysis of the SS-3 tensile specimen

    International Nuclear Information System (INIS)

    Majumdar, S.

    1998-01-01

    Tensile tests of most irradiated specimens of vanadium alloys are conducted using the miniature SS-3 specimen which is not ASTM approved. Detailed elastic-plastic finite element analysis of the specimen was conducted to show that, as long as the ultimate to yield strength ratio is less than or equal to 1.25 (which is satisfied by many irradiated materials), the stress-plastic strain curve obtained by using such a specimen is representative of the true material behavior

  9. Bone tumors

    International Nuclear Information System (INIS)

    Moylan, D.J.; Yelovich, R.M.

    1991-01-01

    Primary bone malignancies are relatively rare with less than 4,000 new cases per year. Multiple myeloma (more correctly a hematologic malignancy) accounts for 40%; osteosarcomas, 28%; chondrosarcomas, 13%; fibrosarcomas arising in bone, 4%; and Ewing's sarcoma, 7%. The authors discuss various treatments for bone tumors, including radiotherapy, chemotherapy and surgery

  10. Wilms Tumor

    Science.gov (United States)

    ... a child's general health and to detect any adverse side effects (such as low red or white blood cell ... medicine needed, which helps reduce long-term side effects. The most common ... can be completely removed by surgery. About 41% of all Wilms tumors are stage ...

  11. Nephrogenic tumors

    International Nuclear Information System (INIS)

    Wiesbauer, P.

    2008-01-01

    Nephroblastomas are the most common malignant renal tumors in childhood. According to the guidelines of the SIOP (Societe Internationale d'Oncologie Pediatrique) and GPOH (Gesellschaft fuer Paediatrische Onkologie und Haematologie) pre-operative chemotherapy can be started without histological confirmation and thus initial imaging studies, in particular ultrasound, play an outstanding role for diagnostic purposes

  12. Pleomorphic rhabdomyosarcoma arising in the anterior mediastinum: A case report with cytological features of imprint and liquid-based cytology specimens.

    Science.gov (United States)

    Nishijima, Yoshimi; Hirato, Junko; Fukuda, Toshio

    2017-04-01

    We herein report the cytological features of a very rare case of pleomorphic rhabdomyosarcoma arising in the anterior mediastinum on imprint and liquid-based cytology (LBC) specimens. A 58-year-old man had an approximately 10-cm tumor in the anterior mediastinum as shown on computed tomography. Thymectomy with complete resection of the left lung was performed. The fresh cut surface of the tumor was used to prepare imprint and LBC specimens. The imprint specimens showed four types of tumor cells dispersed on a background of hemorrhage, necrosis, and mucus. On the other hand, only two types of tumor cells (spindle-shaped and spiderweb cells) were scattered or present in clusters in the LBC specimens. Immunocytologically, both of these cell types were positive for desmin and myoglobin, negative for pan-keratin and epithelial membrane antigen. Cytological and immunocytological features are useful for the correct diagnosis of pleomorphic rhabdomyosarcoma, and LBC specimens show clearer results than do imprint specimens. Diagn. Cytopathol. 2017;45:333-338. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  13. Molecular Auditing: An Evaluation of Unsuspected Tissue Specimen Misidentification.

    Science.gov (United States)

    Demetrick, Douglas J

    2018-06-18

    Context Specimen misidentification is the most significant error in laboratory medicine, potentially accounting for hundreds of millions of dollars in extra health care expenses and significant morbidity in patient populations in the United States alone. New technology allows the unequivocal documentation of specimen misidentification or contamination; however, the value of this technology currently depends on suspicion of the specimen integrity by a pathologist or other health care worker. Objective To test the hypothesis that there is a detectable incidence of unsuspected tissue specimen misidentification among cases submitted for routine surgical pathology examination. Design To test this hypothesis, we selected specimen pairs that were obtained at different times and/or different hospitals from the same patient, and compared their genotypes using standardized microsatellite markers used commonly for forensic human DNA comparison in order to identify unsuspected mismatches between the specimen pairs as a trial of "molecular auditing." We preferentially selected gastrointestinal, prostate, and skin biopsies because we estimated that these types of specimens had the greatest potential for misidentification. Results Of 972 specimen pairs, 1 showed an unexpected discordant genotype profile, indicating that 1 of the 2 specimens was misidentified. To date, we are unable to identify the etiology of the discordance. Conclusions These results demonstrate that, indeed, there is a low level of unsuspected tissue specimen misidentification, even in an environment with careful adherence to stringent quality assurance practices. This study demonstrates that molecular auditing of random, routine biopsy specimens can identify occult misidentified specimens, and may function as a useful quality indicator.

  14. [Fuzzing pattern recognition study on Raman spectrum of tumor peripheral tissue].

    Science.gov (United States)

    Luo, Lei; Zhao, Yuan-li; Ge, Xiang-hong; Zhang, Xiao-dong; Hao, Zhi-fang; Lü, Jing

    2006-06-01

    On the basis of some theories about fuzzing pattern recognition, the present article studied the data preprocessing of the Raman spectrum of tumor peripheral tissue, and feature extraction and selection. According to these features the authors improved the leaning towards the bigger membership function of trapezoidal distribution. The authors built the membership function of Raman spectrum of tumor peripheral tissue which belongs to malignant tumor on the basis of 40 specimens, and designed the classifier. The test of other 40 specimens showed that the discrimination of malignant tumor is 82.4%, while that of beginning tumor is 73.9%.

  15. Glial cell activity is maintained during prolonged inflammatory challenge in rats

    Energy Technology Data Exchange (ETDEWEB)

    Borges, B.C.; Rorato, R.; Antunes-Rodrigues, J.; Elias, L.L.K. [Departamento de Fisiologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto SP (Brazil)

    2012-05-04

    We evaluated the expression of glial fibrillary acidic protein (GFAP), glutamine synthetase (GS), ionized calcium binding adaptor protein-1 (Iba-1), and ferritin in rats after single or repeated lipopolysaccharide (LPS) treatment, which is known to induce endotoxin tolerance and glial activation. Male Wistar rats (200-250 g) received ip injections of LPS (100 µg/kg) or saline for 6 days: 6 saline (N = 5), 5 saline + 1 LPS (N = 6) and 6 LPS (N = 6). After the sixth injection, the rats were perfused and the brains were collected for immunohistochemistry. After a single LPS dose, the number of GFAP-positive cells increased in the hypothalamic arcuate nucleus (ARC; 1 LPS: 35.6 ± 1.4 vs control: 23.1 ± 2.5) and hippocampus (1 LPS: 165.0 ± 3.0 vs control: 137.5 ± 2.5), and interestingly, 6 LPS injections further increased GFAP expression in these regions (ARC = 52.5 ± 4.3; hippocampus = 182.2 ± 4.1). We found a higher GS expression only in the hippocampus of the 6 LPS injections group (56.6 ± 0.8 vs 46.7 ± 1.9). Ferritin-positive cells increased similarly in the hippocampus of rats treated with a single (49.2 ± 1.7 vs 28.1 ± 1.9) or repeated (47.6 ± 1.1 vs 28.1 ± 1.9) LPS dose. Single LPS enhanced Iba-1 in the paraventricular nucleus (PVN: 92.8 ± 4.1 vs 65.2 ± 2.2) and hippocampus (99.4 ± 4.4 vs 73.8 ± 2.1), but had no effect in the retrochiasmatic nucleus (RCA) and ARC. Interestingly, 6 LPS increased the Iba-1 expression in these hypothalamic and hippocampal regions (RCA: 57.8 ± 4.6 vs 36.6 ± 2.2; ARC: 62.4 ± 6.0 vs 37.0 ± 2.2; PVN: 100.7 ± 4.4 vs 65.2 ± 2.2; hippocampus: 123.0 ± 3.8 vs 73.8 ± 2.1). The results suggest that repeated LPS treatment stimulates the expression of glial activation markers, protecting neuronal activity during prolonged inflammatory challenges.

  16. Clinicopathological characteristics of duodenal epithelial neoplasms: Focus on tumors with a gastric mucin phenotype (pyloric gland-type tumors.

    Directory of Open Access Journals (Sweden)

    Takehiro Mitsuishi

    Full Text Available Epithelial tumors less commonly occur in the duodenum than in the stomach or large intestine. The clinicopathological characteristics of duodenal epithelial tumors remain a matter of debate. We therefore studied resected specimens to investigate the clinicopathological characteristics of duodenal epithelial tumors.Among duodenal epithelial tumors resected endoscopically or surgically in our hospital, we studied the clinicopathological characteristics of 110 adenomas or intramucosal carcinomas. The grade of atypia of all tumors was classified into 3 groups according to the World Health Organization (WHO 2010 classification. The tumors were immunohistochemically evaluated to determine the frequency of differentiation toward fundic glands.As for patient characteristics, there were 76 men (75.2% and 25 women (24.8%, with a median age of 65 years (range, 34 to 84. The tumors most commonly arose in the first to second part of the duodenum. Many lesions were flat, and the median tumor diameter was 8.0 mm. The lesions were classified into 2 types according to mucin phenotype: intestinal-type tumors (98 lesions, 89.1% and gastric-type tumors (12 lesions, 10.9%. Intestinal-type tumors were subdivided into 2 groups: tubular-type tumors (91 lesions, 82.7% and tubulovillous-type tumors (7 lesions, 6.4%. Gastric-type tumors were classified into 2 types: foveolar type (3 lesions, 2.7% and pyloric gland-type (PG tumors (9 lesions, 8.2%. The grade of atypia was significantly higher in gastric-type tumors (p<0.01. PG tumors were gastric-type tumors characterized by pyloric glands and findings suggesting differentiation toward fundic glands.About 10% of the duodenal tumors had a gastric-type mucin phenotype. Gastric-type tumors showed high-grade atypia. In particular, PG tumors showed similarities to PG tumors of the stomach, such as differentiation toward fundic glands.

  17. Inhalation exposure to white spirit causes region-dependent alterations in the levels of glial fibrillary acidic protein

    DEFF Research Database (Denmark)

    Lam, Henrik Rye; Ladefoged, Ole; østergaard, G.

    2000-01-01

    Enhanced expression of glial fibrillary acidic protein (GFAP) is known to be associated with toxicant-induced gliosis, a homotypic response of the central nervous system to neural injury. A variety of neurochemical and neurophysiological effects have been observed in experimental animals exposed ...

  18. Late effects of radiation on the central nervous system: role of vascular endothelial damage and glial stem cell survival.

    NARCIS (Netherlands)

    Coderre, J.A.; Morris, G.M.; Micca, P.L.; Hopewell, J.W.; Verhagen, I.; Kleiboer, B.J.; Kogel, A.J. van der

    2006-01-01

    Selective irradiation of the vasculature of the rat spinal cord was used in this study, which was designed specifically to address the question as to whether it is the endothelial cell or the glial progenitor cell that is the target responsible for late white matter necrosis in the CNS. Selective

  19. A competitive advantage by neonatally engrafted human glial progenitors yields mice whose brains are chimeric for human glia

    DEFF Research Database (Denmark)

    Windrem, Martha S; Schanz, Steven J; Morrow, Carolyn

    2014-01-01

    Neonatally transplanted human glial progenitor cells (hGPCs) densely engraft and myelinate the hypomyelinated shiverer mouse. We found that, in hGPC-xenografted mice, the human donor cells continue to expand throughout the forebrain, systematically replacing the host murine glia. The differentiat...

  20. Gemfibrozil, a lipid-lowering drug, induces suppressor of cytokine signaling 3 in glial cells: implications for neurodegenerative disorders.

    Science.gov (United States)

    Ghosh, Arunava; Pahan, Kalipada

    2012-08-03

    Glial inflammation is an important feature of several neurodegenerative disorders. Suppressor of cytokine signaling (SOCS) proteins play a crucial role in inhibiting cytokine signaling and inflammatory gene expression in various cell types, including glial cells. However, mechanisms by which SOCS genes could be up-regulated are poorly understood. This study underlines the importance of gemfibrozil, a Food and Drug Administration-approved lipid-lowering drug, in up-regulating the expression of SOCS3 in glial cells. Gemfibrozil increased the expression of Socs3 mRNA and protein in mouse astroglia and microglia in both a time- and dose-dependent manner. Interestingly, gemfibrozil induced the activation of type IA phosphatidylinositol (PI) 3-kinase and AKT. Accordingly, inhibition of PI 3-kinase and AKT by chemical inhibitors abrogated gemfibrozil-mediated up-regulation of SOCS3. Furthermore, we demonstrated that gemfibrozil induced the activation of Krüppel-like factor 4 (KLF4) via the PI 3-kinase-AKT pathway and that siRNA knockdown of KLF4 abrogated gemfibrozil-mediated up-regulation of SOCS3. Gemfibrozil also induced the recruitment of KLF4 to the distal, but not proximal, KLF4-binding site of the Socs3 promoter. This study delineates a novel property of gemfibrozil in up-regulating SOCS3 in glial cells via PI 3-kinase-AKT-mediated activation of KLF4 and suggests that gemfibrozil may find therapeutic application in neuroinflammatory and neurodegenerative disorders.

  1. Sleep disturbances and severe stress as glial activators: key targets for treating central sensitization in chronic pain patients?

    Science.gov (United States)

    Nijs, Jo; Loggia, Marco L; Polli, Andrea; Moens, Maarten; Huysmans, Eva; Goudman, Lisa; Meeus, Mira; Vanderweeën, Luc; Ickmans, Kelly; Clauw, Daniel

    2017-08-01

    The mechanism of sensitization of the central nervous system partly explains the chronic pain experience in many patients, but the etiological mechanisms of this central nervous system dysfunction are poorly understood. Recently, an increasing number of studies suggest that aberrant glial activation takes part in the establishment and/or maintenance of central sensitization. Areas covered: This review focused on preclinical work and mostly on the neurobiochemistry studied in animals, with limited human studies available. Glial overactivation results in a low-grade neuroinflammatory state, characterized by high levels of BDNF, IL-1β, TNF-α, which in turn increases the excitability of the central nervous system neurons through mechanisms like long-term potentiation and increased synaptic efficiency. Aberrant glial activity in chronic pain might have been triggered by severe stress exposure, and/or sleeping disturbances, each of which are established initiating factors for chronic pain development. Expert opinion: Potential treatment avenues include several pharmacological options for diminishing glial activity, as well as conservative interventions like sleep management, stress management and exercise therapy. Pharmacological options include propentofylline, minocycline, β -adrenergic receptor antagonists, and cannabidiol. Before translating these findings from basic science to clinical settings, more human studies exploring the outlined mechanisms in chronic pain patients are needed.

  2. Prefrontal changes in the glutamate-glutamine cycle and neuronal/glial glutamate transporters in depression with and without suicide

    NARCIS (Netherlands)

    Zhao, J.; Verwer, R.W.H.; van Wamelen, D.J.; Qi, X.R.; Gao, S.F.; Lucassen, P.J.; Swaab, D.F.

    2016-01-01

    There are indications for changes in glutamate metabolism in relation to depression or suicide. The glutamate-glutamine cycle and neuronal/glial glutamate transporters mediate the uptake of the glutamate and glutamine. The expression of various components of the glutamate-glutamine cycle and the

  3. The contribution of spinal glial cells to chronic pain behaviour in the monosodium iodoacetate model of osteoarthritic pain

    Directory of Open Access Journals (Sweden)

    Sagar Devi

    2011-11-01

    Full Text Available Abstract Background Clinical studies of osteoarthritis (OA suggest central sensitization may contribute to the chronic pain experienced. This preclinical study used the monosodium iodoacetate (MIA model of OA joint pain to investigate the potential contribution of spinal sensitization, in particular spinal glial cell activation, to pain behaviour in this model. Experimental OA was induced in the rat by the intra-articular injection of MIA and pain behaviour (change in weight bearing and distal allodynia was assessed. Spinal cord microglia (Iba1 staining and astrocyte (GFAP immunofluorescence activation were measured at 7, 14 and 28 days post MIA-treatment. The effects of two known inhibitors of glial activation, nimesulide and minocycline, on pain behaviour and activation of microglia and astrocytes were assessed. Results Seven days following intra-articular injection of MIA, microglia in the ipsilateral spinal cord were activated (p Conclusions Here we provide evidence for a contribution of spinal glial cells to pain behaviour, in particular distal allodynia, in this model of osteoarthritic pain. Our data suggest there is a potential role of glial cells in the central sensitization associated with OA, which may provide a novel analgesic target for the treatment of OA pain.

  4. Dopamine D1 receptor activation regulates the expression of the estrogen synthesis gene aromatase B in radial glial cell

    Directory of Open Access Journals (Sweden)

    Lei eXing

    2015-09-01

    Full Text Available Radial glial cells (RGCs are abundant stem-like non-neuronal progenitors that are important for adult neurogenesis and brain repair, yet little is known about their regulation by neurotransmitters. Here we provide evidence for neuronal-glial interactions via a novel role for dopamine to stimulate RGC function. Goldfish were chosen as the model organism due to the abundance of RGCs and regenerative abilities of the adult central nervous system. A close anatomical relationship was observed between tyrosine hydroxylase-positive catecholaminergic cell bodies and axons and dopamine-D1 receptor expressing RGCs along the ventricular surface of telencephalon, a site of active neurogenesis. A primary cell culture model was established and immunofluorescence analysis indicates that in vitro RGCs from female goldfish retain their major characteristics in vivo, including expression of glial fibrillary acidic protein and brain lipid binding protein. The estrogen synthesis enzyme aromatase B is exclusively found in RGCs, but this is lost as cells differentiate to neurons and other glial types in adult teleost brain. Pharmacological experiments using the cultured RGCs established that specific activation of dopamine D1 receptors up-regulates aromatase B mRNA through a cyclic adenosine monophosphate-dependent molecular mechanism. These data indicate that dopamine enhances the steroidogenic function of this neuronal progenitor cell.

  5. Specimen holder for an electron microscope and device and method for mounting a specimen in an electron microscope

    NARCIS (Netherlands)

    Zandbergen, H.W.; Latenstein van Voorst, A.; Westra, C.; Hoveling, G.H.

    1996-01-01

    A specimen holder for an electron microscope, comprising a bar-shaped body provided adjacent one end with means for receiving a specimen, with means being present for screening the specimen from the environment at least temporarily in airtight and moisture-proof manner in a first position, which

  6. Lipoic Acid Treatment after Brain Injury: Study of the Glial Reaction

    Directory of Open Access Journals (Sweden)

    Brenda Rocamonde

    2013-01-01

    Full Text Available After trauma brain injury, oxidative substances released to the medium provoke an enlargement of the initial lesion, increasing glial cell activation and, occasionally, an influx of immune cells into the central nervous system, developing the secondary damage. In response to these stimuli, microglia are activated to perform upregulation of intracellular enzymes and cell surface markers to propagate the immune response and phagocytosis of cellular debris. The phagocytosis of debris and dead cells is essential to limit the inflammatory reaction and potentially prevent extension of the damage to noninjured regions. Lipoic acid has been reported as a neuroprotectant by acting as an antioxidant and anti-inflammatory agent. Furthermore, angiogenic effect promoted by lipoic acid has been recently shown by our group as a crucial process for neural regeneration after brain injury. In this work, we focus our attention on the lipoic acid effect on astroglial and microglial response after brain injury.

  7. Mactosylceramide Prevents Glial Cell Overgrowth by Inhibiting Insulin and Fibroblast Growth Factor Receptor Signaling

    DEFF Research Database (Denmark)

    Gerdøe-Kristensen, Stine; Lund, Viktor K; Wandall, Hans H

    2017-01-01

    , in which the mannosyltransferase Egghead controls conversion of glucosylceramide (GlcCer) to mactosylceramide (MacCer). Lack of elongated GSL in egghead (egh) mutants causes overgrowth of subperineurial glia (SPG), largely due to aberrant activation of phosphatidylinositol 3-kinase (PI3K). However, to what...... of the Drosophila Insulin Receptor (InR) and the FGFR homolog Heartless (Htl) in wild type SPG, and is suppressed by inhibiting Htl and InR activity in egh. Knockdown of GlcCer synthase in the SPG fails to suppress glial overgrowth in egh nerves, and slightly promotes overgrowth in wild type, suggesting that RTK...... hyperactivation is caused by absence of MacCer and not by GlcCer accumulation. We conclude that an early product in GSL biosynthesis, MacCer, prevents inappropriate activation of Insulin and Fibroblast Growth Factor Receptors in Drosophila glia. This article is protected by copyright. All rights reserved....

  8. Distinctive response of CNS glial cells in oro-facial pain associated with injury, infection and inflammation

    Directory of Open Access Journals (Sweden)

    Ribeiro-da-Silva Alfredo

    2010-11-01

    Full Text Available Abstract Oro-facial pain following injury and infection is frequently observed in dental clinics. While neuropathic pain evoked by injury associated with nerve lesion has an involvement of glia/immune cells, inflammatory hyperalgesia has an exaggerated sensitization mediated by local and circulating immune mediators. To better understand the contribution of central nervous system (CNS glial cells in these different pathological conditions, in this study we sought to characterize functional phenotypes of glial cells in response to trigeminal nerve injury (loose ligation of the mental branch, infection (subcutaneous injection of lipopolysaccharide-LPS and to sterile inflammation (subcutaneous injection of complete Freund's adjuvant-CFA on the lower lip. Each of the three insults triggered a specific pattern of mechanical allodynia. In parallel with changes in sensory response, CNS glial cells reacted distinctively to the challenges. Following ligation of the mental nerve, both microglia and astrocytes in the trigeminal nuclear complex were highly activated, more prominent in the principal sensory nucleus (Pr5 and subnucleus caudalis (Sp5C area. Microglial response was initiated early (days 3-14, followed by delayed astrocytes activation (days 7-28. Although the temporal profile of microglial and astrocyte reaction corresponded respectively to the initiation and chronic stage of neuropathic pain, these activated glial cells exhibited a low profile of cytokine expression. Local injection of LPS in the lower lip skin also triggered a microglial reaction in the brain, which started in the circumventricular organs (CVOs at 5 hours post-injection and diffused progressively into the brain parenchyma at 48 hours. This LPS-induced microglial reaction was accompanied by a robust induction of IκB-α mRNA and pro-inflammatory cytokines within the CVOs. However, LPS induced microglial activation did not specifically occur along the pain signaling pathway. In

  9. Neuroendocrine Tumors of the Lung

    Energy Technology Data Exchange (ETDEWEB)

    Fisseler-Eckhoff, Annette, E-mail: Annette.Fisseler-Eckhoff@hsk-wiesbaden.de; Demes, Melanie [Department of Pathology und Cytology, Dr. Horst-Schmidt-Kliniken (HSK), Wiesbaden 65199 (Germany)

    2012-07-31

    Neuroendocrine tumors may develop throughout the human body with the majority being found in the gastrointestinal tract and bronchopulmonary system. Neuroendocrine tumors are classified according to the grade of biological aggressiveness (G1–G3) and the extent of differentiation (well-differentiated/poorly-differentiated). The well-differentiated neoplasms comprise typical (G1) and atypical (G2) carcinoids. Large cell neuroendocrine carcinomas as well as small cell carcinomas (G3) are poorly-differentiated. The identification and differentiation of atypical from typical carcinoids or large cell neuroendocrine carcinomas and small cell carcinomas is essential for treatment options and prognosis. Pulmonary neuroendocrine tumors are characterized according to the proportion of necrosis, the mitotic activity, palisading, rosette-like structure, trabecular pattern and organoid nesting. The given information about the histopathological assessment, classification, prognosis, genetic aberration as well as treatment options of pulmonary neuroendocrine tumors are based on own experiences and reviewing the current literature available. Most disagreements among the classification of neuroendocrine tumor entities exist in the identification of typical versus atypical carcinoids, atypical versus large cell neuroendocrine carcinomas and large cell neuroendocrine carcinomas versus small cell carcinomas. Additionally, the classification is restricted in terms of limited specificity of immunohistochemical markers and possible artifacts in small biopsies which can be compressed in cytological specimens. Until now, pulmonary neuroendocrine tumors have been increasing in incidence. As compared to NSCLCs, only little research has been done with respect to new molecular targets as well as improving the classification and differential diagnosis of neuroendocrine tumors of the lung.

  10. Effects of reactive oxygen species on metabolism monitored by longitudinal 1H single voxel MRS follow-up in patients with mitochondrial disease or cerebral tumors

    International Nuclear Information System (INIS)

    Constans, J M; Collet, S; Hossu, G; Courtheoux, P; Guillamo, J S; Lechapt-Zalcman, E; Valable, S; Lacombe, S; Houee Levin, C; Gauduel, Y A; Dou, W; Ruan, S; Barre, L; Rioult, F; Derlon, J M; Chapon, F; Fong, V; Kauffmann, F

    2011-01-01

    Free radicals, or Reactive Oxygen Species (ROS), have an effect on energy and glycolytic metabolism, mitochondrial function, lipid metabolism, necrosis and apoptosis, cell proliferation, and infiltration. These changes could be monitored longitudinally (every 4 months over 6 years) in humans with glial brain tumors (low and high grade) after therapy, using conventional magnetic resonance imaging (MRI) and spectroscopy (MRS) and MR perfusion. Some examples of early clinical data from longitudinal follow-up monitoring in humans of energy and glycolytic metabolism, lipid metabolism, necrosis, proliferation, and infiltration measured by conventional MRI, MRS and perfusion, and positron emission tomography (PET) are shown in glial brain tumors after therapy. Despite the difficulty, the variability and unknown factors, these repeated measurements give us a better insight into the nature of the different processes, tumor progression and therapeutic response.

  11. Effects of reactive oxygen species on metabolism monitored by longitudinal {sup 1}H single voxel MRS follow-up in patients with mitochondrial disease or cerebral tumors

    Energy Technology Data Exchange (ETDEWEB)

    Constans, J M; Collet, S; Hossu, G; Courtheoux, P [MRI Unit, Caen University Hospital, Caen, Normandy (France); Guillamo, J S; Lechapt-Zalcman, E; Valable, S [CERVOxy Group, CI-NAPS, UMR 6232 CI-NAPS, Cyceron, Caen, Normandy (France); Lacombe, S; Houee Levin, C [Paris-Sud 11 University-CNRS, Orsay (France); Gauduel, Y A [LOA, Ecole Polytechnique - ENSTA ParisTech, Palaiseau (France); Dou, W [Tsinghua University, Beijing (China); Ruan, S [CReSTIC EA 3804, IUT Troyes, Troyes (France); Barre, L [GDMTEP, Group CI-NAPS, UMR 6232 CI-NAPS, Cyceron, Caen (France); Rioult, F [CNRS UMR 6072, GREYC, Caen, Normandy (France); Derlon, J M [Neurosurgery and Neurology, Caen University Hospital, Caen, Normandy (France); Chapon, F [Pathology, Caen University Hospital, Caen, Normandy (France); Fong, V [Caen University (France); Kauffmann, F, E-mail: constans-jm@chu-caen.fr [Mathematics LMNO CNRS UMR 6139, Caen University, Caen, Normandy (France)

    2011-01-01

    Free radicals, or Reactive Oxygen Species (ROS), have an effect on energy and glycolytic metabolism, mitochondrial function, lipid metabolism, necrosis and apoptosis, cell proliferation, and infiltration. These changes could be monitored longitudinally (every 4 months over 6 years) in humans with glial brain tumors (low and high grade) after therapy, using conventional magnetic resonance imaging (MRI) and spectroscopy (MRS) and MR perfusion. Some examples of early clinical data from longitudinal follow-up monitoring in humans of energy and glycolytic metabolism, lipid metabolism, necrosis, proliferation, and infiltration measured by conventional MRI, MRS and perfusion, and positron emission tomography (PET) are shown in glial brain tumors after therapy. Despite the difficulty, the variability and unknown factors, these repeated measurements give us a better insight into the nature of the different processes, tumor progression and therapeutic response.

  12. NG2/CSPG4 and progranulin in the posttraumatic glial scar.

    Science.gov (United States)

    Schäfer, Michael K E; Tegeder, Irmgard

    2018-08-01

    Traumatic injury of the central nervous system is one of the leading causes of death and disability in young adults. Failure of regeneration is caused by autonomous neuronal obstacles and by formation of the glial scar, which is essential to seal the injury but also constitutes a barrier for regrowing axons. The scar center is highly inflammatory and populated by NG2+ glia, whereas astrocytes form the sealing border and trap regrowing axons, suggesting that the non-permissive environment of activated astrocytes and extracellular matrix components is one of the reasons for the regenerative failure. Particularly, secreted chondroitin-sulfate proteoglycans, CSPGs, of the lectican family hinder axonal regrowth. In contrast, the transmembrane CSPG, NG2/CSPG4, appears to be functionally closer related to axon growth permissive heparan sulfate proteoglycans, HSPGs, and synaptic adhesion molecules, which all regulate synaptic signaling and plasticity upon alpha-secretase mediated shedding. Consequently, knockout of NG2/CSPG4 aggravates tissue loss, inflammation and neurologic deficits after brain injury, a phenotype partly mimicked by deletion of HSPG-binding proteins such as the HSPG2/perlecan-interacting protein, progranulin that is also a functional ligand of Notch and Eph2a. Indeed, structural features or progranulin's targets and NG2 may point to direct reciprocal regulations that may act in concert to overcome injury-evoked inflammation and neuronal dystrophy. This review provides an overview of the pathophysiology of the glial scar after brain injury, with a specific focus on NG2/CSPG4, its functions before and after shedding and putative reciprocal influences with the glycoprotein progranulin. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Effects of aging and sensory loss on glial cells in mouse visual and auditory cortices

    Science.gov (United States)

    Tremblay, Marie-Ève; Zettel, Martha L.; Ison, James R.; Allen, Paul D.; Majewska, Ania K.

    2011-01-01

    Normal aging is often accompanied by a progressive loss of receptor sensitivity in hearing and vision, whose consequences on cellular function in cortical sensory areas have remained largely unknown. By examining the primary auditory (A1) and visual (V1) cortices in two inbred strains of mice undergoing either age-related loss of audition (C57BL/6J) or vision (CBA/CaJ), we were able to describe cellular and subcellular changes that were associated with normal aging (occurring in A1 and V1 of both strains) or specifically with age-related sensory loss (only in A1 of C57BL/6J or V1 of CBA/CaJ), using immunocytochemical electron microscopy and light microscopy. While the changes were subtle in neurons, glial cells and especially microglia were transformed in aged animals. Microglia became more numerous and irregularly distributed, displayed more variable cell body and process morphologies, occupied smaller territories, and accumulated phagocytic inclusions that often displayed ultrastructural features of synaptic elements. Additionally, evidence of myelination defects were observed, and aged oligodendrocytes became more numerous and were more often encountered in contiguous pairs. Most of these effects were profoundly exacerbated by age-related sensory loss. Together, our results suggest that the age-related alteration of glial cells in sensory cortical areas can be accelerated by activity-driven central mechanisms that result from an age-related loss of peripheral sensitivity. In light of our observations, these age-related changes in sensory function should be considered when investigating cellular, cortical and behavioral functions throughout the lifespan in these commonly used C57BL/6J and CBA/CaJ mouse models. PMID:22223464

  14. Glial response in the central nervous system of cats with feline infectious peritonitis.

    Science.gov (United States)

    Mesquita, Leonardo P; Hora, Aline S; de Siqueira, Adriana; Salvagni, Fernanda A; Brandão, Paulo E; Maiorka, Paulo C

    2016-12-01

    The aim of the study was to evaluate central nervous system (CNS) lesions in non-effusive and effusive cases of feline infectious peritonitis (FIP) regarding aspects related to astrocytic and microglial reactions. Five necropsied cats that were naturally infected with FIP virus, confirmed by reverse transcriptase polymerase chain reaction and immunohistochemistry, with different intensities of CNS lesions, were studied. Brain and cerebellum were evaluated by light microscopy and immunohistochemistry for glial fibrillary acidic protein (GFAP) and vimentin to assess astrocytic morphology, and lectin histochemistry for Ricinus communis agglutinin-I (RCA-I) to detect microglia was performed to evaluate the glial response in the CNS of cats with FIP. An important astrocytic response in many areas of the CNS of all cats, including the periventricular areas of lateral ventricles and fourth ventricle, the molecular layer of the cerebellum and cerebral cortex, was visualized. This astrocytic reactivity was associated with areas of granulomatous or pyogranulomatous vasculitis/perivasculitis in most cases, and it was characterized by multifocal to coalescing astrocytosis and astrogliosis with an increase in the expression of intermediate filaments, such as GFAP. However, astrocytes exhibited strong vimentin expression in neuroparenchyma with severe inflammatory and necrotic changes, but GFAP expression was mild or absent in these cases. A microglial response was present only in severe lesions, and RCA-I expression was detected primarily in gitter cells and resting microglia. The present study indicates a strong astrocytic response, including the presence of many less differentiated vimentin-positive astrocytes and gitter cells positive for RCA-1 in severe lesions in the CNS of cats with FIP. © The Author(s) 2015.

  15. Prolonged Minocycline Treatment Impairs Motor Neuronal Survival and Glial Function in Organotypic Rat Spinal Cord Cultures

    Science.gov (United States)

    Pinkernelle, Josephine; Fansa, Hisham; Ebmeyer, Uwe; Keilhoff, Gerburg

    2013-01-01

    Background Minocycline, a second-generation tetracycline antibiotic, exhibits anti-inflammatory and neuroprotective effects in various experimental models of neurological diseases, such as stroke, Alzheimer’s disease, amyotrophic lateral sclerosis and spinal cord injury. However, conflicting results have prompted a debate regarding the beneficial effects of minocycline. Methods In this study, we analyzed minocycline treatment in organotypic spinal cord cultures of neonatal rats as a model of motor neuron survival and regeneration after injury. Minocycline was administered in 2 different concentrations (10 and 100 µM) at various time points in culture and fixed after 1 week. Results Prolonged minocycline administration decreased the survival of motor neurons in the organotypic cultures. This effect was strongly enhanced with higher concentrations of minocycline. High concentrations of minocycline reduced the number of DAPI-positive cell nuclei in organotypic cultures and simultaneously inhibited microglial activation. Astrocytes, which covered the surface of the control organotypic cultures, revealed a peripheral distribution after early minocycline treatment. Thus, we further analyzed the effects of 100 µM minocycline on the viability and migration ability of dispersed primary glial cell cultures. We found that minocycline reduced cell viability, delayed wound closure in a scratch migration assay and increased connexin 43 protein levels in these cultures. Conclusions The administration of high doses of minocycline was deleterious for motor neuron survival. In addition, it inhibited microglial activation and impaired glial viability and migration. These data suggest that especially high doses of minocycline might have undesired affects in treatment of spinal cord injury. Further experiments are required to determine the conditions for the safe clinical administration of minocycline in spinal cord injured patients. PMID:23967343

  16. Design of specimen for weld residual stress simulation

    International Nuclear Information System (INIS)

    Kim, Jin Weon; Park, Jong Sun; Lee, Kyung Soo

    2008-01-01

    The objective of this study is to design a laboratory specimen for simulating residual stress of circumferential butt welding of pipe. Specimen type and method for residual stress generation were proposed based on the review of prior studies and parametric finite element simulation. To prove the proposed specimen type and loading method, the residual stress was generated using the designed specimen by applying proposed method and was measured. The measured residual stress using X-ray diffraction reasonably agreed with the results of finite element simulation considered in the specimen design. Comparison of residual strains measured at several locations of specimen and given by finite element simulation also showed good agreement. Therefore, it is indicated that the designed specimen can reasonably simulate the residual stress of circumferential butt welding of pipe

  17. Optimum slicing of radical prostatectomy specimens for correlation between histopathology and medical images

    International Nuclear Information System (INIS)

    Chen, Li Hong; Ng, Wan Sing; Ho, Henry; Yuen, John; Cheng, Chris; Lazaro, Richie; Thng, Choon Hua

    2010-01-01

    There is a need for methods which enable precise correlation of histologic sections with in vivo prostate images. Such methods would allow direct comparison between imaging features and functional or histopathological heterogeneity of tumors. Correlation would be particularly useful for validating the accuracy of imaging modalities, developing imaging techniques, assessing image-guided therapy, etc. An optimum prostate slicing method for accurate correlation between the histopathological and medical imaging planes in terms of section angle, thickness and level was sought. Literature review (51 references from 1986-2009 were cited) was done on the various sectioning apparatus or techniques used to slice the prostate specimen for accurate correlation between histopathological data and medical imaging. Technology evaluation was performed with review and discussion of various methods used to section other organs and their possible applications for sectioning prostatectomy specimens. No consensus has been achieved on how the prostate should be dissected to achieve a good correlation. Various customized sectioning instruments and techniques working with different mechanism are used in different research institutes to improve the correlation. Some of the methods have convincingly shown significant potential for improving image-specimen correlation. However, the semisolid consistent property of prostate tissue and the lack of identifiable landmarks remain challenges to be overcome, especially for fresh prostate sectioning and microtomy without external fiducials. A standardized optimum protocol to dissect prostatectomy specimens is needed for the validation of medical imaging modalities by histologic correlation. These standards can enhance disease management by improving the comparability between different modalities. (orig.)

  18. "Cancer tumor".

    Science.gov (United States)

    Bronshtehn, V. A.

    The title is a phrase borrowed from a speech by a Leningrad pressman, V. E. Lvov, who called upon those attending a theoretical conference on ideological issues in astronomy held by the Leningrad Branch of the All-Union Astronomic and Geodetic Society (13 - 4 December 1948), "to make a more radical emphasis on the negative role of relativistic cosmology which is a cancer tumor disintegrating the contemporary astronomy theory, and a major ideological enemy of a materialist astronomy".

  19. Schwann cell-mediated delivery of glial cell line-derived neurotrophic factor restores erectile function after cavernous nerve injury.

    Science.gov (United States)

    May, Florian; Buchner, Alexander; Schlenker, Boris; Gratzke, Christian; Arndt, Christian; Stief, Christian; Weidner, Norbert; Matiasek, Kaspar

    2013-03-01

    To evaluate the time-course of functional recovery after cavernous nerve injury using glial cell line-derived neurotrophic factor-transduced Schwann cell-seeded silicon tubes. Sections of the cavernous nerves were excised bilaterally (5 mm), followed by immediate bilateral surgical repair. A total of 20 study nerves per group were reconstructed by interposition of empty silicon tubes and silicon tubes seeded with either glial cell line-derived neurotrophic factor-overexpressing or green fluorescent protein-expressing Schwann cells. Control groups were either sham-operated or received bilateral nerve transection without nerve reconstruction. Erectile function was evaluated by relaparotomy, electrical nerve stimulation and intracavernous pressure recording after 2, 4, 6, 8 and 10 weeks. The animals underwent re-exploration only once, and were killed afterwards. The nerve grafts were investigated for the maturation state of regenerating nerve fibers and the fascular composition. Recovery of erectile function took at least 4 weeks in the current model. Glial cell line-derived neurotrophic factor-transduced Schwann cell grafts restored erectile function better than green fluorescent protein-transduced controls and unseeded conduits. Glial cell line-derived neurotrophic factor-transduced grafts promoted an intact erectile response (4/4) at 4, 6, 8 and 10 weeks that was overall significantly superior to negative controls (P cell line-derived neurotrophic factor-transduced grafts compared with negative controls (P = 0.018) and unseeded tubes (P = 0.034). Return of function was associated with the electron microscopic evidence of preganglionic myelinated nerve fibers and postganglionic unmyelinated axons. Schwann cell-mediated delivery of glial cell line-derived neurotrophic factor presents a viable approach for the treatment of erectile dysfunction after cavernous nerve injury. © 2013 The Japanese Urological Association.

  20. A novel and efficient gene transfer strategy reduces glial reactivity and improves neuronal survival and axonal growth in vitro.

    Directory of Open Access Journals (Sweden)

    Mathieu Desclaux

    Full Text Available BACKGROUND: The lack of axonal regeneration in the central nervous system is attributed among other factors to the formation of a glial scar. This cellular structure is mainly composed of reactive astrocytes that overexpress two intermediate filament proteins, the glial fibrillary acidic protein (GFAP and vimentin. Indeed, in vitro, astrocytes lacking GFAP or both GFAP and vimentin were shown to be the substrate for increased neuronal plasticity. Moreover, double knockout mice lacking both GFAP and vimentin presented lower levels of glial reactivity in vivo, significant axonal regrowth and improved functional recovery in comparison with wild-type mice after spinal cord hemisection. From these results, our objective was to develop a novel therapeutic strategy for axonal regeneration, based on the targeted suppression of astroglial reactivity and scarring by lentiviral-mediated RNA-interference (RNAi. METHODS AND FINDINGS: In this study, we constructed two lentiviral vectors, Lv-shGFAP and Lv-shVIM, which allow efficient and stable RNAi-mediated silencing of endogenous GFAP or vimentin in vitro. In cultured cortical and spinal reactive astrocytes, the use of these vectors resulted in a specific, stable and highly significant decrease in the corresponding protein levels. In a second model -- scratched primary cultured astrocytes -- Lv-shGFAP, alone or associated with Lv-shVIM, decreased astrocytic reactivity and glial scarring. Finally, in a heterotopic coculture model, cortical neurons displayed higher survival rates and increased neurite growth when cultured with astrocytes in which GFAP and vimentin had been invalidated by lentiviral-mediated RNAi. CONCLUSIONS: Lentiviral-mediated knockdown of GFAP and vimentin in astrocytes show that GFAP is a key target for modulating reactive gliosis and monitoring neuron/glia interactions. Thus, manipulation of reactive astrocytes with the Lv-shGFAP vector constitutes a promising therapeutic strategy for

  1. A novel and efficient gene transfer strategy reduces glial reactivity and improves neuronal survival and axonal growth in vitro.

    Science.gov (United States)

    Desclaux, Mathieu; Teigell, Marisa; Amar, Lahouari; Vogel, Roland; Gimenez Y Ribotta, Minerva; Privat, Alain; Mallet, Jacques

    2009-07-14

    The lack of axonal regeneration in the central nervous system is attributed among other factors to the formation of a glial scar. This cellular structure is mainly composed of reactive astrocytes that overexpress two intermediate filament proteins, the glial fibrillary acidic protein (GFAP) and vimentin. Indeed, in vitro, astrocytes lacking GFAP or both GFAP and vimentin were shown to be the substrate for increased neuronal plasticity. Moreover, double knockout mice lacking both GFAP and vimentin presented lower levels of glial reactivity in vivo, significant axonal regrowth and improved functional recovery in comparison with wild-type mice after spinal cord hemisection. From these results, our objective was to develop a novel therapeutic strategy for axonal regeneration, based on the targeted suppression of astroglial reactivity and scarring by lentiviral-mediated RNA-interference (RNAi). In this study, we constructed two lentiviral vectors, Lv-shGFAP and Lv-shVIM, which allow efficient and stable RNAi-mediated silencing of endogenous GFAP or vimentin in vitro. In cultured cortical and spinal reactive astrocytes, the use of these vectors resulted in a specific, stable and highly significant decrease in the corresponding protein levels. In a second model -- scratched primary cultured astrocytes -- Lv-shGFAP, alone or associated with Lv-shVIM, decreased astrocytic reactivity and glial scarring. Finally, in a heterotopic coculture model, cortical neurons displayed higher survival rates and increased neurite growth when cultured with astrocytes in which GFAP and vimentin had been invalidated by lentiviral-mediated RNAi. Lentiviral-mediated knockdown of GFAP and vimentin in astrocytes show that GFAP is a key target for modulating reactive gliosis and monitoring neuron/glia interactions. Thus, manipulation of reactive astrocytes with the Lv-shGFAP vector constitutes a promising therapeutic strategy for increasing glial permissiveness and permitting axonal regeneration

  2. Temporomandibular joint inflammation activates glial and immune cells in both the trigeminal ganglia and in the spinal trigeminal nucleus

    Directory of Open Access Journals (Sweden)

    Jasmin Luc

    2010-12-01

    Full Text Available Abstract Background Glial cells have been shown to directly participate to the genesis and maintenance of chronic pain in both the sensory ganglia and the central nervous system (CNS. Indeed, glial cell activation has been reported in both the dorsal root ganglia and the spinal cord following injury or inflammation of the sciatic nerve, but no data are currently available in animal models of trigeminal sensitization. Therefore, in the present study, we evaluated glial cell activation in the trigeminal-spinal system following injection of the Complete Freund's Adjuvant (CFA into the temporomandibular joint, which generates inflammatory pain and trigeminal hypersensitivity. Results CFA-injected animals showed ipsilateral mechanical allodynia and temporomandibular joint edema, accompanied in the trigeminal ganglion by a strong increase in the number of GFAP-positive satellite glial cells encircling neurons and by the activation of resident macrophages. Seventy-two hours after CFA injection, activated microglial cells were observed in the ipsilateral trigeminal subnucleus caudalis and in the cervical dorsal horn, with a significant up-regulation of Iba1 immunoreactivity, but no signs of reactive astrogliosis were detected in the same areas. Since the purinergic system has been implicated in the activation of microglial cells during neuropathic pain, we have also evaluated the expression of the microglial-specific P2Y12 receptor subtype. No upregulation of this receptor was detected following induction of TMJ inflammation, suggesting that any possible role of P2Y12 in this paradigm of inflammatory pain does not involve changes in receptor expression. Conclusions Our data indicate that specific glial cell populations become activated in both the trigeminal ganglia and the CNS following induction of temporomandibular joint inflammation, and suggest that they might represent innovative targets for controlling pain during trigeminal nerve sensitization.

  3. Risk Factors Associated with Discordant Ki-67 Levels between Preoperative Biopsy and Postoperative Surgical Specimens in Breast Cancers.

    Directory of Open Access Journals (Sweden)

    Hyung Sun Kim

    Full Text Available The Ki-67 labelling index is significant for the management of breast cancer. However, the concordance of Ki-67 expression between preoperative biopsy and postoperative surgical specimens has not been well evaluated. This study aimed to find the correlation in Ki-67 expression between biopsy and surgical specimens and to determine the clinicopathological risk factors associated with discordant values.Ki-67 levels were immunohistochemically measured using paired biopsy and surgical specimens in 310 breast cancer patients between 2008 and 2013. ΔKi-67 was calculated by postoperative Ki-67 minus preoperative levels. The outliers of ΔKi-67 were defined as [lower quartile of ΔKi-67-1.5 × interquartile range (IQR] or (upper quartile + 1.5 × IQR and were evaluated according to clinicopathological parameters by logistic regression analysis.The median preoperative and postoperative Ki-67 levels were 10 (IQR, 15 and 10 (IQR, 25, respectively. Correlation of Ki-67 levels between the two specimens indicated a moderately positive relationship (coefficient = 0.676. Of 310 patients, 44 (14.2% showed outliers of ΔKi-67 (range, ≤-20 or ≥28. A significant association with poor prognostic factors was found among these patients. Multivariate analysis determined that significant risk factors for outliers of ΔKi-67 were tumor size >1 cm, negative progesterone receptor (PR expression, grade III cancer, and age ≤35 years. Among 171 patients with luminal human epidermal growth factor receptor 2-negative tumors, breast cancer subtype according to preoperative or postoperative Ki-67 levels discordantly changed in 46 (26.9% patients and a significant proportion of patients with discordant cases had ≥1 risk factor.Ki-67 expression showed a substantial concordance between biopsy and surgical specimens. Extremely discordant Ki-67 levels may be associated with aggressive tumor biology. In patients with luminal subtype disease, clinical application of Ki-67

  4. Functional imaging for brain tumors (perfusion, DTI and MR spectroscopy)

    International Nuclear Information System (INIS)

    Essig, M.; Giesel, F.; Stieltjes, B.; Weber, M.A.

    2007-01-01

    This contribution considers the possibilities involved with using functional methods in magnetic resonance imaging (MRI) diagnostics for brain tumors. Of the functional methods available, we discuss perfusion MRI (PWI), diffusion MRI (DWI and DTI) and MR spectroscopy (H-MRS). In cases of brain tumor, PWI aids in grading and better differentiation in diagnostics as well as for pre-therapeutic planning. In addition, the course of treatment, both after chemo- as well as radiotherapy in combination with surgical treatment, can be optimized. PWI allows better estimates of biological activity and aggressiveness in low grade brain tumors, and in the case of WHO grade II astrocytoma showing anaplastically transformed tumor areas, allows more rapid visualization and a better prediction of the course of the disease than conventional MRI diagnostics. Diffusion MRI, due to the directional dependence of the diffusion, can illustrate the course and direction of the nerve fibers, as well as reconstructing the nerve tracts in the cerebrum, pons and cerebellum 3-dimensionally. Diffusion imaging can be used for describing brain tumors, for evaluating contralateral involvement and the course of the nerve fibers near the tumor. Due to its operator dependence, DTI based fiber tracking for defining risk structures is controversial. DWI can also not differentiate accurately between cystic and necrotic brain tumors, or between metastases and brain abscesses. H-MRS provides information on cell membrane metabolism, neuronal integrity and the function of neuronal structures, energy metabolism and the formation of tumors and brain tissue necroses. Diagnostic problems such as the differentiation between neoplastic and non-neoplastic lesions, grading cerebral glioma and distinguishing between primary brain tumors and metastases can be resolved. An additional contribution will discuss the control of the course of glial tumors after radiotherapy. (orig.)

  5. Biobanking of fresh frozen tissue from clinical surgical specimens: transport logistics, sample selection, and histologic characterization.

    Science.gov (United States)

    Botling, Johan; Micke, Patrick

    2011-01-01

    Access to high-quality fresh frozen tissue is critical for translational cancer research and molecular -diagnostics. Here we describe a workflow for the collection of frozen solid tissue samples derived from fresh human patient specimens after surgery. The routines have been in operation at Uppsala University Hospital since 2001. We have integrated cryosection and histopathologic examination of each biobank sample into the biobank manual. In this way, even small, macroscopically ill-defined lesions can be -procured without a diagnostic hazard due to the removal of uncharacterized tissue from a clinical -specimen. Also, knowledge of the histomorphology of the frozen tissue sample - tumor cell content, stromal components, and presence of necrosis - is pivotal before entering a biobank case into costly molecular profiling studies.

  6. Understanding Brain Tumors

    Science.gov (United States)

    ... to Know About Brain Tumors . What is a Brain Tumor? A brain tumor is an abnormal growth
 ... Tumors” from Frankly Speaking Frankly Speaking About Cancer: Brain Tumors Download the full book Questions to ask ...

  7. Brain tumor - primary - adults

    Science.gov (United States)

    ... Vestibular schwannoma (acoustic neuroma) - adults; Meningioma - adults; Cancer - brain tumor (adults) ... Primary brain tumors include any tumor that starts in the brain. Primary brain tumors can start from brain cells, ...

  8. Brain tumor - children

    Science.gov (United States)

    ... children; Neuroglioma - children; Oligodendroglioma - children; Meningioma - children; Cancer - brain tumor (children) ... The cause of primary brain tumors is unknown. Primary brain tumors may ... (spread to nearby areas) Cancerous (malignant) Brain tumors ...

  9. Adrenal Gland Tumors: Statistics

    Science.gov (United States)

    ... Gland Tumor: Statistics Request Permissions Adrenal Gland Tumor: Statistics Approved by the Cancer.Net Editorial Board , 03/ ... primary adrenal gland tumor is very uncommon. Exact statistics are not available for this type of tumor ...

  10. Improvement of rotary specimen rack design

    International Nuclear Information System (INIS)

    Batch, J.M.; Gietzen, A.J.

    1978-01-01

    A redesign and verification test program has been completed on a new Rotary Specimen Rack ('Lazy Susan') design for the TRIGA Mark III. The purpose of the redesign was to solve a rotation problem which occurred at power levels of about 1 MW and above. The previous redesign effort on the Mark II-type lazy susan was made in 1967 when the bearing was changed to use stellite balls, spring-type separators and stainless-steel bearing races. An extensive test program at that time showed that the design gave excellent service under all anticipated operating conditions. Fifteen of these units have been installed in the past ten years and have been essentially trouble-free. Although the bearing design for the Mark III was very similar, the component layout was such that irradiation-induced heating with associated thermal expansion resulted in decreased bearing clearance and an increase in the required driving torque. The solution involved redesign and re-arrangement of the rack drive mechanism. A series of stringent operational proof tests were made under high temperature and temperature differential conditions which proved successful operation of the new design. The severe conditions under which these tests were performed uncovered further difficulties with the bearing and led to a re-evaluation of the bearing design. A new design was developed in which the spring separators were replaced by similar sized, cylindrical graphite spacers. The entire series of operational and life tests were repeated and the performance was outstanding. Acceptable wear characteristics of the spacers were verified and the bearing was noticeably smoother and quieter than with previous designs. A Mark III lazy susan of this new design was installed in a TRIGA about one year ago and operated at power levels up to 2 MW with excellent performance. The Mark II design has now been changed to incorporate the new drive and bearing design proven for the Mark III. (author)

  11. Pediatric brain tumors

    Energy Technology Data Exchange (ETDEWEB)

    Poussaint, Tina Y. [Department of Radiology, Boston, MA (United States); Panigrahy, Ashok [Children' s Hospital of Pittsburgh of University of Pittsburgh Medical Center, Department of Radiology, Pittsburgh, PA (United States); Huisman, Thierry A.G.M. [Charlotte R. Bloomberg Children' s Center, Johns Hopkins Hospital, Division of Pediatric Radiology and Pediatric Neuroradiology, Baltimore, MD (United States)

    2015-09-15

    Among all causes of death in children from solid tumors, pediatric brain tumors are the most common. This article includes an overview of a subset of infratentorial and supratentorial tumors with a focus on tumor imaging features and molecular advances and treatments of these tumors. Key to understanding the imaging features of brain tumors is a firm grasp of other disease processes that can mimic tumor on imaging. We also review imaging features of a common subset of tumor mimics. (orig.)

  12. Technique of manufacturing specimen of irradiated fuel rods

    International Nuclear Information System (INIS)

    Min, Duck Seok; Seo, Hang Seok; Min, Duck Kee; Koo, Dae Seo; Lee, Eun Pyo; Yang, Song Yeol

    1999-04-01

    Technique of manufacturing specimen of irradiated fuel rods to perform efficient PIE is developed by analyzing the relation between requiring time of manufacturing specimen and manufacturing method in irradiated fuel rods. It takes within an hour to grind 1 mm of specimen thickness under 150 rpm in speed of grinding, 600 g gravity in force using no.120, no.240, no.320 of grinding paper. In case of no.400 of grinding paper, it takes more an hour to grind the same thickness as above. It takes up to a quarter to grind 80-130 μm in specimen thickness using no.400 of grinding paper. When grinding time goes beyond 15 minutes, the grinding thickness of specimen does not exist. The polishing of specimen with 150 Rpms in speed of grinding machine, 600 g gravity in force, 10 minutes in polishing time using diamond paste 15 μm on polishing cloths amounts to 50 μm in specimen thickness. In case of diamond paste 9 μm on polishing cloth, the polishing of specimen amounts to 20 μm. The polishing thickness of specimen with 15 minutes in polishing time using 6 μm, 3 μm, 1 μm, 1/4 μm does not exist. Technique of manufacturing specimen of irradiated fuel rods will have application to the destructive examination of PIE. (author). 6 refs., 1 tab., 10 figs

  13. Lack of connexin43-mediated Bergmann glial gap junctional coupling does not affect cerebellar long-term depression, motor coordination, or eyeblink conditioning

    Directory of Open Access Journals (Sweden)

    Mika Tanaka

    2008-04-01

    Full Text Available Bergmann glial cells are specialized astrocytes in the cerebellum. In the mature cerebellar molecular layer, Bergmann glial processes are closely associated with Purkinje cells, enclosing Purkinje cell dendritic synapses with a glial sheath. There is intensive gap junctional coupling between Bergmann glial processes, but their significance in cerebellar functions is not known. Connexin43 (Cx43, a major component of astrocytic gap junction channels, is abundantly expressed in Bergmann glial cells. To examine the role of Cx43-mediated gap junctions between Bergmann glial cells in cerebellar functions, we generated Cx43 conditional knockout mice with the S100b-Cre transgenic line (Cx43fl/fl:S100b-Cre, which exhibited a significant loss of Cx43 in the Bergmann glial cells and astrocytes in the cerebellum with a postnatal onset. The Cx43fl/fl:S100b-Cre mice had normal cerebellar architecture. Although gap junctional coupling between the Bergmann glial cells measured by spreading of microinjected Lucifer yellow was virtually abolished in Cx43fl/fl:S100b-Cre mice, electrophysiologic analysis revealed that cerebellar long-term depression could be induced and maintained normally in thier cerebellar slices. In addition, at the behavioral level, Cx43fl/fl:S100b-Cre mice had normal motor coordination in the rotarod task and normal conditioned eyelid response. Our findings suggest that Cx43-mediated gap junctional coupling between Bergmann glial cells is not necessary for the neuron-glia interactions required for cerebellum-dependent motor coordination and motor learning.

  14. Testis tumors

    International Nuclear Information System (INIS)

    White, R.L.; Maier, J.G.

    1987-01-01

    Clinical trials are evaluating new combinations of drugs with the goal of diminishing the toxicity associated with the current regimens while not compromising the chance for cure. The evolution of information and staging studies such as tumor markers, CT scanning and MR scanning has made possible the detection of residual metastatic disease while obviating the need for surgical staging procedures. This has made less treatment possible for a large number of patients. The regularity of follow-up studies has made early detection of recurrences a possibility, so that effective and curative treatment is generally possible

  15. The study on linac stereotactic radiosurgery for acoustic tumors

    International Nuclear Information System (INIS)

    Ohishi, Hitoshi

    1995-01-01

    We have designed and manufactured a new type of device for stereotactic radiosurgery characterized by the combined use of a rotatory chair and a linear accelerator. In this study, 20 acoustic tumors treated by our modality were evaluated by serial neuroimaging, neurofunctional outcome and, in a few cases, pathological findings of surgical specimens. Because tumor size usually changed very slowly after radiosurgery, 12 cases that had a minimum of 12 months of follow-up were employed in the analysis of tumor size. Serial neuroimaging studies revealed the reduction of tumor size in 3 cases and prevention of tumor growth in 7 cases, therefore, the rate of tumor control was evaluated as 83%. Growth of tumor size occurred in 3 cases, two were cases harbouring a large cyst in the tumor and another was a case of neurofibromatosis type 2. In 13 cases (68%), loss of the gadolinium enhancement effect inside the tumor was observed. This is a characteristic change after radiosurgery for acoustic tumors, and attributable to a necrotic change. Cranial nerve neuropathies as a complication also occurred (facial nerve palsy in 2 and trigeminal nerve dysfunction in 1). Adjacent parenchymal change appeared in 1 case. This patient had two prior operations and the tumor had an irregular shape, therefore, planning for radiosurgery encountered some difficulty. Hydrocephalus occurred in 1 case. Surgical specimens in 2 cases in which microsurgery was undertaken for growing tumors, revealed a necrotic tumor tissue and proliferation of fibrous tissue. In conclusion, our new device for stereotactic radiosurgery is particularly useful for the treatment of acoustic tumors. Similar therapeutic results of the gamma knife have been achieved. Radiosurgery is a recommendable treatment for acoustic tumors. However, the superiority of radiosurgery over microsurgery is still controversial and needs a longer term follow-up and multivariate analysis for a final conclusion. (author)

  16. Preoperative measurement of canine primary bone tumors, using radiography and bone scintigraphy

    International Nuclear Information System (INIS)

    Lamb, C.R.; Berg, J.; Bengston, A.E.

    1990-01-01

    Specimens of 20 canine primary bone tumors (18 osteosarcoma, 2 fibrosarcoma) were examined to compare the maximal axial length of gross tumor with the length of the lesion seen on preoperative radiographs and 99mTc methylene diphosphonate bone scintigraphic images. Radiographs defined the length of the tumor to within +/- 10% of the gross measurement for 6 (30%), underestimated it for 12 (60%), and overestimated it for 2 (10%) specimens. Bone scintigraphy defined tumor length within +/- 10% for 8 (40%), underestimated it for 1 (5%), and overestimated it for the remaining 11 (55%) specimens. Use of radiographic evaluation alone could result in underestimation of the diaphyseal extent of a primary bone tumor, with risk of incomplete resection. Bone scan images tend to overestimate tumor length and, therefore, may provide safer resection guidelines

  17. Studying the glial cell response to biomaterials and surface topography for improving the neural electrode interface

    Science.gov (United States)

    Ereifej, Evon S.

    Neural electrode devices hold great promise to help people with the restoration of lost functions, however, research is lacking in the biomaterial design of a stable, long-term device. Current devices lack long term functionality, most have been found unable to record neural activity within weeks after implantation due to the development of glial scar tissue (Polikov et al., 2006; Zhong and Bellamkonda, 2008). The long-term effect of chronically implanted electrodes is the formation of a glial scar made up of reactive astrocytes and the matrix proteins they generate (Polikov et al., 2005; Seil and Webster, 2008). Scarring is initiated when a device is inserted into brain tissue and is associated with an inflammatory response. Activated astrocytes are hypertrophic, hyperplastic, have an upregulation of intermediate filaments GFAP and vimentin expression, and filament formation (Buffo et al., 2010; Gervasi et al., 2008). Current approaches towards inhibiting the initiation of glial scarring range from altering the geometry, roughness, size, shape and materials of the device (Grill et al., 2009; Kotov et al., 2009; Kotzar et al., 2002; Szarowski et al., 2003). Literature has shown that surface topography modifications can alter cell alignment, adhesion, proliferation, migration, and gene expression (Agnew et al., 1983; Cogan et al., 2005; Cogan et al., 2006; Merrill et al., 2005). Thus, the goals of the presented work are to study the cellular response to biomaterials used in neural electrode fabrication and assess surface topography effects on minimizing astrogliosis. Initially, to examine astrocyte response to various materials used in neural electrode fabrication, astrocytes were cultured on platinum, silicon, PMMA, and SU-8 surfaces, with polystyrene as the control surface. Cell proliferation, viability, morphology and gene expression was measured for seven days in vitro. Results determined the cellular characteristics, reactions and growth rates of astrocytes

  18. Teratoid Wilms′ tumor - A rare renal tumor

    Directory of Open Access Journals (Sweden)

    Biswanath Mukhopadhyay

    2011-01-01

    Full Text Available Teratoid Wilms′ tumor is an extremely rare renal tumor. We report a case of unilateral teratoid Wilms′ tumor in a 4-year-old girl. The patient was admitted with a right-sided abdominal mass. The mass was arising from the right kidney. Radical nephrectomy was done and the patient had an uneventful recovery. Histopathology report showed teratoid Wilms′ tumor.

  19. An epidemiologic survey on brain tumors in Kerman from 1997 to 2001

    Directory of Open Access Journals (Sweden)

    Hamed Reihani kermani

    2004-09-01

    Full Text Available Central nervous system tumors contain neoplastic and nonneoplastic lesions. Incidence of brain tumors has increased in all age groups in recent 20 years. Developments of medical devices such as CT scan, MRI and varying of classification are important causes of this raising. The present study evaluates epidemiology of brain tumors from 1997 to 2001 in Kerman. In a cross sectional study all files of neurosurgery department, in Kerman Bahonar Hospital and from 1997 to 2001, were inquired. Variables such as age, sex and histological considerations were evaluated. A total of 338 tumors were studied. The most common tumor was glial (35%, and meningioma was the second common tumor (26.3%. The other tumors were anaplastic astrocytoma, astrocytoma, pituitary adenoma, aucostic neorinoma, medulloblastoma, ependymoma, choroid plexus carcinoma, craniopharyngioma, lymphoma, sarcoma and anaplastic ependymoma. There was statistical significant difference between tumors and sex and age (p<0.05. Age and sex distribution of brain tumors is compatible with other studies in many countries. These findings suggest that prevalence of brain tumors in Kerman has increased in recent years because of diagnostic methods have improved and other medical devices are available.

  20. Expression and Significance of CYR61 Expression in Breast Cancer Tumor Specimens

    National Research Council Canada - National Science Library

    Lupu, Ruth

    2002-01-01

    Breast cancer often progresses from an estrogen (ER)-dependent, non-metastatic, antiestrogen-sensitive phenotype to an ER-independent, antiestrogen-resistant, highly invasive, and metastatic phenotype...

  1. Metastatic prostatic adenocarcinoma diagnosed in a bronchoalveolar lavage specimen: An unusual presentation of a common tumor

    Directory of Open Access Journals (Sweden)

    Adrienne E Moul

    2016-01-01

    Full Text Available Metastatic prostatic adenocarcinoma presenting as a primary lung disease is rare. We present a 52-year-old male with a 3-month history of cough, shortness of breath, and weight loss with clinical and radiological findings suggestive of a primary lung disease: Bilateral interstitial and alveolar opacities with blunting of the costophrenic angles, multiple diffuse foci of consolidations and nodules, predominantly subpleural and located in the lower lobes, and diffuse interlobular septal thickening and peribronchial thickening. The patient underwent bronchoscopy and bronchoalveolar lavage (BAL was obtained. Cytospin smears were diagnostic for a low-grade adenocarcinoma. Clinically, the patient had elevated serum prostate-specific antigen (PSA levels greater than 5,000 ng/mL. Because of this, immunocytochemistry for PSA was performed which was positive, confirming the diagnosis of metastatic prostatic adenocarcinoma. This unusual case of metastatic adenocarcinoma of the prostate first diagnosed by BAL highlights the significance of available clinical information and the use of immunocytochemistry for proper diagnosis.

  2. Biopsy in Musculoskeletal Tumors

    Directory of Open Access Journals (Sweden)

    Mohammad Gharehdaghi

    2014-09-01

    proximity to the skin incision, because this tract is also contaminated and must be excised with the surgical specimen. Imaging-guided core needle biopsy is a well-established technique for the diagnosis of bone and soft tissue tumors and tumor-like lesions in specialized orthopedic oncology centers. Although large lesions of the limbs can easily be biopsied without image guidance, lesions in the spine, para spinal area, and pelvis are difficult to target, therefore taking the advantage of C.T. guidance will improve the accuracy of targeting the lesion for biopsy purposes. We can benefit from image intensifiers for targeting limb lesions rather than C.T. guidance. Also sonographic guide can be applied for soft tissue lesions (Figure D, E, F. In soft tissue tumors, the results of percutaneous CNB are relatively inferior compared to open biopsy whereas almost equal results are expected for bony tumors except for low-grade chondrosarcoma. CNB is a safe, minimally invasive, and cost effective technique for the diagnosis of bone lesions if done by an experienced orthopedic oncologic surgeon and be evaluated by an experienced anatomical bone pathologist (1, 3. For soft tissue tumors, CNB results depend on the size of the lesion, its location and amount of tumor necrosis. Guided needle biopsy have become the standard technique in most orthopedic oncologic centers. The accuracy of this method in our center is more than 90% for bone tumors. Cores should be taken in different directions including areas of central necrotic tissues but from a single well planned entrance. The procedure is quick, especially for bone CNB or soft tissue FNA and CNB, and the diagnosis can be achieved within 24 – 48 hours. The material should be sufficient for immunohistochemistry evaluations as well (1-3. Because I have seen 3 cases of tumor implantation at the towel clips puncture site including 2 chondrosarcomas and a case of malignant schowanoma, so I highly suggest that never crush the skin by towel

  3. Pediatric brain tumors of neuroepithelial tissue; Hirntumoren des neuroepithelialen Gewebes im Kindesalter

    Energy Technology Data Exchange (ETDEWEB)

    Papanagiotou, P.; Politi, M. [Klinikum Bremen-Mitte/Bremen-Ost, Klinik fuer Diagnostische und Interventionelle Neuroradiologie, Bremen (Germany); Bergmann, M. [Klinikum Bremen-Mitte, Institut fuer Klinische Neuropathologie, Bremen (Germany); Pekrun, A. [Klinikum Bremen-Mitte, Klinik fuer Kinder- und Jugendmedizin, paed. Haematologie/Onkologie, Neonatologie, Bremen (Germany); Juergens, K.U. [Klinikum Bremen-Mitte, ZEMODI-Zentrum fuer moderne Diagnostik, MRT, Nuklearmedizin und PET-CT, Bremen (Germany)

    2014-08-15

    Tumors of neuroepithelial tissue represent the largest group of pediatric brain tumors by far and has therefore been divided into several discrete tumor subtypes each corresponding to a specific component of the neuropil. The neuropil contains several subtypes of glial cells, including astrocytes, oligodendrocytes, ependymal cells and modified ependymal cells that form the choroid plexus. This review discusses the imaging aspects of the most common pediatric tumors of neuroepithelial tissue. (orig.) [German] Tumoren des neuroepithelialen Gewebes stellen die mit Abstand groesste Gruppe der paediatrischen Hirntumoren dar und werden je nach deren Ursprung in diversen Subtypen unterteilt. Das Neuropil beinhaltet diverse Subtypen von Gliazellen: Astrozyten, Oligodendrozyten, ependymale Zellen und modifizierte ependymale Zellen, die den Plexus choroideus formen. In diesem Review werden die bildgebenden Aspekte mittels CT und MRT der haeufigsten Tumoren des neuroepithelialen Gewebes diskutiert. (orig.)

  4. Laboratory specimens and genetic privacy: evolution of legal theory.

    Science.gov (United States)

    Lewis, Michelle Huckaby

    2013-03-01

    Although laboratory specimens are an important resource for biomedical research, controversy has arisen when research has been conducted without the knowledge or consent of the individuals who were the source of the specimens. This paper summarizes the most important litigation regarding the research use of laboratory specimens and traces the evolution of legal theory from property claims to claims related to genetic privacy interests. © 2013 American Society of Law, Medicine & Ethics, Inc.

  5. Location specific in situ TEM straining specimens made using FIB

    International Nuclear Information System (INIS)

    Field, R.D.; Papin, P.A.

    2004-01-01

    A method has been devised and demonstrated for producing in situ straining specimens for the transmission electron microscope (TEM) from specific locations in a sample using a dual-beam focused ion beam (FIB) instrument. The specimen is removed from a polished surface in the FIB using normal methods and then attached to a pre-fabricated substrate in the form of a modified TEM tensile specimen. In this manner, specific features of the microstructure of a polished optical mount can be selected for in situ tensile straining. With the use of electron backscattered diffraction (EBSD), this technique could be extended to select specific orientations of the specimen as well

  6. Uniaxial compression tests on diesel contaminated frozen silty soil specimens

    International Nuclear Information System (INIS)

    Chenaf, D.; Stampli, N.; Bathurst, R.; Chapuis, R.P.

    1999-01-01

    Results of a uniaxial, unconfined compression test on artificial diesel-contaminated and uncontaminated frozen silty soils are discussed. The testing program involved 59 specimens. The results show that for the same fluid content, diesel contamination reduced the strength of the frozen specimens by increasing the unfrozen water content. For example, in specimens containing 50 per cent diesel oil of the fluid content by weight the maximum strength was reduced by 95 per cent compared to the strength of an uncontaminated specimen. Diesel contamination was also shown to contribute to the slippage between soil particles by acting as a lubricant, thus accelerating the loss of compressive strength.13 refs., 18 figs

  7. Quantitative X-ray microanalysis of biological specimens

    International Nuclear Information System (INIS)

    Roomans, G.M.

    1988-01-01

    Qualitative X-ray microanalysis of biological specimens requires an approach that is somewhat different from that used in the materials sciences. The first step is deconvolution and background subtraction on the obtained spectrum. The further treatment depends on the type of specimen: thin, thick, or semithick. For thin sections, the continuum method of quantitation is most often used, but it should be combined with an accurate correction for extraneous background. However, alternative methods to determine local mass should also be considered. In the analysis of biological bulk specimens, the ZAF-correction method appears to be less useful, primarily because of the uneven surface of biological specimens. The peak-to-local background model may be a more adequate method for thick specimens that are not mounted on a thick substrate. Quantitative X-ray microanalysis of biological specimens generally requires the use of standards that preferably should resemble the specimen in chemical and physical properties. Special problems in biological microanalysis include low count rates, specimen instability and mass loss, extraneous contributions to the spectrum, and preparative artifacts affecting quantitation. A relatively recent development in X-ray microanalysis of biological specimens is the quantitative determination of local water content

  8. Drone Transport of Microbes in Blood and Sputum Laboratory Specimens.

    Science.gov (United States)

    Amukele, Timothy K; Street, Jeff; Carroll, Karen; Miller, Heather; Zhang, Sean X

    2016-10-01

    Unmanned aerial vehicles (UAVs) could potentially be used to transport microbiological specimens. To examine the impact of UAVs on microbiological specimens, blood and sputum culture specimens were seeded with usual pathogens and flown in a UAV for 30 ± 2 min. Times to recovery, colony counts, morphologies, and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS)-based identifications of the flown and stationary specimens were similar for all microbes studied. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  9. A Debonded Sandwich Specimen Under Mixed Mode Bending (MMB)

    DEFF Research Database (Denmark)

    Quispitupa, Amilcar; Berggreen, Christian; Carlsson, Leif A.

    2008-01-01

    Face/core interface crack propagation in sandwich specimens is analyzed. A thorough analysis of the typical failure modes in sandwich composites was performed in order to design the MMB specimen to promote face/core debond fracture. Displacement, compliance and energy release rate expressions...... for the MMB specimen were derived from a superposition analysis. An experimental verification of the methodology proposed was performed using MMB sandwich specimens with H100 PVC foam core and E-glass/polyester non-crimp quadro-axial [0/45/90/-45]s DBLT-850 faces. Different mixed mode loadings were applied...

  10. TEM specimen preparation of semiconductor-PMMA-metal interfaces

    International Nuclear Information System (INIS)

    Thangadurai, P.; Lumelsky, Yulia; Silverstein, Michael S.; Kaplan, Wayne D.

    2008-01-01

    Transmission electron microscopy (TEM) cross-section specimens of PMMA in contact with gold and Si were prepared by focused ion beam (FIB) and compared with plan-view PMMA specimens prepared by a dip-coating technique. The specimens were characterized by TEM and electron energy loss spectroscopy (EELS). In the cross-section specimens, the thin films of PMMA were located in a Si-PMMA-Au multilayer. Different thicknesses of PMMA films were spin-coated on the Si substrates. The thickness of the TEM specimens prepared by FIB was estimated using EELS to be 0.65 of the plasmon mean-free-path. Along the PMMA-Au interface, Au particle diffusion into the PMMA was observed, and the size of the Au particles was in the range of 2-4 nm. Dip-coating of PMMA directly on Cu TEM grids resulted in thin specimens with a granular morphology, with a thickness of 0.58 of the plasmon mean-free-path. The dip-coated specimens were free from ion milling induced artifacts, and thus serve as control specimens for comparison with the cross-sectioned specimens prepared by FIB

  11. Primary microglia isolation from mixed glial cell cultures of neonatal rat brain tissue.

    Science.gov (United States)

    Tamashiro, Tami T; Dalgard, Clifton Lee; Byrnes, Kimberly R

    2012-08-15

    Microglia account for approximately 12% of the total cellular population in the mammalian brain. While neurons and astrocytes are considered the major cell types of the nervous system, microglia play a significant role in normal brain physiology by monitoring tissue for debris and pathogens and maintaining homeostasis in the parenchyma via phagocytic activity. Microglia are activated during a number of injury and disease conditions, including neurodegenerative disease, traumatic brain injury, and nervous system infection. Under these activating conditions, microglia increase their phagocytic activity, undergo morpohological and proliferative change, and actively secrete reactive oxygen and nitrogen species, pro-inflammatory chemokines and cytokines, often activating a paracrine or autocrine loop. As these microglial responses contribute to disease pathogenesis in neurological conditions, research focused on microglia is warranted. Due to the cellular heterogeneity of the brain, it is technically difficult to obtain sufficient microglial sample material with high purity during in vivo experiments. Current research on the neuroprotective and neurotoxic functions of microglia require a routine technical method to consistently generate pure and healthy microglia with sufficient yield for study. We present, in text and video, a protocol to isolate pure primary microglia from mixed glia cultures for a variety of downstream applications. Briefly, this technique utilizes dissociated brain tissue from neonatal rat pups to produce mixed glial cell cultures. After the mixed glial cultures reach confluency, primary microglia are mechanically isolated from the culture by a brief duration of shaking. The microglia are then plated at high purity for experimental study. The principle and protocol of this methodology have been described in the literature. Additionally, alternate methodologies to isolate primary microglia are well described. Homogenized brain tissue may be separated

  12. Sex cord-gonadal stromal tumor of the rete testis.

    Science.gov (United States)

    Sajadi, Kamran P; Dalton, Rory R; Brown, James A

    2009-01-01

    A 34-year-old tetraplegic patient with suppurative epididymitis was found on follow-up examination and ultrasonography to have a testicular mass. The radical orchiectomy specimen contained an undifferentiated spindled sex cord-stromal tumor arising in the rete testis. Testicular sex cord-stromal tumors are far less common than germ cell neoplasms and are usually benign. The close relationship between sex cords and ductules of the rete testis during development provides the opportunity for these uncommon tumors to arise anatomically within the rete tesis. This undifferentiated sex cord-stromal tumor, occurring in a previously unreported location, is an example of an unusual lesion mimicking an intratesticular malignant neoplasm.

  13. Alkaloids from Prosopis juliflora leaves induce glial activation, cytotoxicity and stimulate NO production.

    Science.gov (United States)

    Silva, A M M; Silva, A R; Pinheiro, A M; Freitas, S R V B; Silva, V D A; Souza, C S; Hughes, J B; El-Bachá, R S; Costa, M F D; Velozo, E S; Tardy, M; Costa, S L

    2007-04-01

    Prosopis juliflora is used for feeding cattle and humans. Intoxication with the plant has been reported, and is characterized by neuromuscular alterations and gliosis. Total alkaloidal extract (TAE) was obtained using acid/basic-modified extraction and was fractionated. TAE and seven alkaloidal fractions, at concentrations ranging 0.03-30 microg/ml, were tested for 24h on astrocyte primary cultures derived from the cortex of newborn Wistar rats. The MTT test and the measure of LDH activity on the culture medium, revealed that TAE and fractions F29/30, F31/33, F32 and F34/35 were cytotoxic to astrocytes. The EC(50) values for the most toxic compounds, TAE, F31/33 and F32 were 2.87 2.82 and 3.01 microg/ml, respectively. Morphological changes and glial cells activation were investigated through Rosenfeld's staining, by immunocytochemistry for the protein OX-42, specific of activated microglia, by immunocytochemistry and western immunoblot for GFAP, the marker of reactive and mature astrocytes, and by the production of nitric oxide (NO). We observed that astrocytes exposed to 3 microg/ml TAE, F29/30 or F31/33 developed compact cell body with many processes overexpressing GFAP. Treatment with 30 microg/ml TAE and fractions, induced cytotoxicity characterized by a strong cell body contraction, very thin and long processes and condensed chromatin. We also observed that when compared with the control (+/-1.34%), the proportion of OX-42 positive cells was increased in cultures treated with 30 microg/ml TAE or F29/30, F31/33, F32 and F34/35, with values raging from 7.27% to 28.74%. Moreover, incubation with 3 microg/ml F32, 30 microg/ml TAE, F29/30, F31/33 or F34/35 induced accumulation of nitrite in culture medium indicating induction of NO production. Taken together these results show that TAE and fractionated alkaloids from P. juliflora act directly on glial cells, inducing activation and/or cytotoxicity, stimulating NO production, and may have an impact on neuronal

  14. Tumor Macroenvironment and Metabolism

    OpenAIRE

    Al-Zhoughbi, Wael; Huang, Jianfeng; Paramasivan, Ganapathy S.; Till, Holger; Pichler, Martin; Guertl-Lackner, Barbara; Hoefler, Gerald

    2014-01-01

    In this review we introduce the concept of the tumor macroenvironment and explore it in the context of metabolism. Tumor cells interact with the tumor microenvironment including immune cells. Blood and lymph vessels are the critical components that deliver nutrients to the tumor and also connect the tumor to the macroenvironment. Several factors are then released from the tumor itself but potentially also from the tumor microenvironment, influencing the metabolism of distant tissues and organ...

  15. Application of subsize specimens in nuclear plant life extension

    International Nuclear Information System (INIS)

    Rosinski, S.T.; Kumar, A.S.; Cannon, N.S.; Hamilton, M.L.

    1993-01-01

    The US Department of Energy is sponsoring a research effort through Sandia National Laboratories and the University of Missouri-Rolla to test a correlation for the upper shelf energy (USE) values obtained from the impact testing of subsize Charpy V-notch specimens to those obtained from the testing of full-size samples. The program involves the impact testing of unirradiated and irradiated full-, half-, and third-size Charpy V-notch specimens. To verify the applicability of the correlation on LWR materials, unirradiated and irradiated full-, half-, and third-size Charpy V-notch specimens of a commercial pressure vessel steel (ASTM A533 Grade B) will be tested. The correlation methodology is based on the partitioning of the USE into crack initiation and crack propagation energies. To accomplish this partition, both precracked and notched-only specimens will be used. Whereas the USE of notched-only specimens is the sum of both crack initiation and crack propagation energies, the USE of precracked specimens reflects only the crack propagation component. The difference in the USE of the two types of specimens represents a measure of the crack initiation energy. Normalizing the values of the crack initiation energy to the fracture volume of the sample produces similar values for the full-, half-, and third-size specimens. In addition, the ratios of the USE and the crack propagation energy are also in agreement for full-, half-, and third-size specimens. These two observations will be used to predict the USE of full-size specimens based on subsize USE data. This paper provides details of the program and presents results obtained from the application of the developed correlation methodology to the impact testing of the unirradiated full-, half-, and third-size A533 Grade B Charpy V-notch specimens

  16. Swift Acetate Glial Assay (SAGA): an accelerated human ¹³C MRS brain exam for clinical diagnostic use.

    Science.gov (United States)

    Sailasuta, Napapon; Tran, Thao T; Harris, Kent C; Ross, B D

    2010-12-01

    We demonstrate a robust procedure for the quantitative characterization of glial metabolism in human brain. In the past, the slope of the uptake and production of enriched label at steady state were used to determine metabolic rates, requiring the patient to be in the magnet for 120-160 min. In the present method, (13)C cerebral metabolite profiles were acquired at steady state alone on a routine clinical MR scanner in 25.6 min. Results obtained from the new short method (SAGA) were comparable to those achieved in a conventional, long method and effective for determination of glial metabolic rate in posterior-parietal and frontal brain regions. Copyright © 2010 Elsevier Inc. All rights reserved.

  17. Flow Cytometric Detection of PrPSc in Neurons and Glial Cells from Prion-Infected Mouse Brains.

    Science.gov (United States)

    Yamasaki, Takeshi; Suzuki, Akio; Hasebe, Rie; Horiuchi, Motohiro

    2018-01-01

    In prion diseases, an abnormal isoform of prion protein (PrP Sc ) accumulates in neurons, astrocytes, and microglia in the brains of animals affected by prions. Detailed analyses of PrP Sc -positive neurons and glial cells are required to clarify their pathophysiological roles in the disease. Here, we report a novel method for the detection of PrP Sc in neurons and glial cells from the brains of prion-infected mice by flow cytometry using PrP Sc -specific staining with monoclonal antibody (MAb) 132. The combination of PrP Sc staining and immunolabeling of neural cell markers clearly distinguished neurons, astrocytes, and microglia that were positive for PrP Sc from those that were PrP Sc negative. The flow cytometric analysis of PrP Sc revealed the appearance of PrP Sc -positive neurons, astrocytes, and microglia at 60 days after intracerebral prion inoculation, suggesting the presence of PrP Sc in the glial cells, as well as in neurons, from an early stage of infection. Moreover, the kinetic analysis of PrP Sc revealed a continuous increase in the proportion of PrP Sc -positive cells for all cell types with disease progression. Finally, we applied this method to isolate neurons, astrocytes, and microglia positive for PrP Sc from a prion-infected mouse brain by florescence-activated cell sorting. The method described here enables comprehensive analyses specific to PrP Sc -positive neurons, astrocytes, and microglia that will contribute to the understanding of the pathophysiological roles of neurons and glial cells in PrP Sc -associated pathogenesis. IMPORTANCE Although formation of PrP Sc in neurons is associated closely with neurodegeneration in prion diseases, the mechanism of neurodegeneration is not understood completely. On the other hand, recent studies proposed the important roles of glial cells in PrP Sc -associated pathogenesis, such as the intracerebral spread of PrP Sc and clearance of PrP Sc from the brain. Despite the great need for detailed analyses

  18. Focal Transplantation of Human iPSC-Derived Glial-Rich Neural Progenitors Improves Lifespan of ALS Mice

    Directory of Open Access Journals (Sweden)

    Takayuki Kondo

    2014-08-01

    Full Text Available Transplantation of glial-rich neural progenitors has been demonstrated to attenuate motor neuron degeneration and disease progression in rodent models of mutant superoxide dismutase 1 (SOD1-mediated amyotrophic lateral sclerosis (ALS. However, translation of these results into a clinical setting requires a renewable human cell source. Here, we derived glial-rich neural progenitors from human iPSCs and transplanted them into the lumbar spinal cord of ALS mouse models. The transplanted cells differentiated into astrocytes, and the treated mouse group showed prolonged lifespan. Our data suggest a potential therapeutic mechanism via activation of AKT signal. The results demonstrated the efficacy of cell therapy for ALS by the use of human iPSCs as cell source.

  19. Genetic deletion of afadin causes hydrocephalus by destruction of adherens junctions in radial glial and ependymal cells in the midbrain.

    Directory of Open Access Journals (Sweden)

    Hideaki Yamamoto

    Full Text Available Adherens junctions (AJs play a role in mechanically connecting adjacent cells to maintain tissue structure, particularly in epithelial cells. The major cell-cell adhesion molecules at AJs are cadherins and nectins. Afadin binds to both nectins and α-catenin and recruits the cadherin-β-catenin complex to the nectin-based cell-cell adhesion site to form AJs. To explore the role of afadin in radial glial and ependymal cells in the brain, we generated mice carrying a nestin-Cre-mediated conditional knockout (cKO of the afadin gene. Newborn afadin-cKO mice developed hydrocephalus and died neonatally. The afadin-cKO brain displayed enlarged lateral ventricles and cerebral aqueduct, resulting from stenosis of the caudal end of the cerebral aqueduct and obliteration of the ventral part of the third ventricle. Afadin deficiency further caused the loss of ependymal cells from the ventricular and aqueductal surfaces. During development, radial glial cells, which terminally differentiate into ependymal cells, scattered from the ventricular zone and were replaced by neurons that eventually covered the ventricular and aqueductal surfaces of the afadin-cKO midbrain. Moreover, the denuded ependymal cells were only occasionally observed in the third ventricle and the cerebral aqueduct of the afadin-cKO midbrain. Afadin was co-localized with nectin-1 and N-cadherin at AJs of radial glial and ependymal cells in the control midbrain, but these proteins were not concentrated at AJs in the afadin-cKO midbrain. Thus, the defects in the afadin-cKO midbrain most likely resulted from the destruction of AJs, because AJs in the midbrain were already established before afadin was genetically deleted. These results indicate that afadin is essential for the maintenance of AJs in radial glial and ependymal cells in the midbrain and is required for normal morphogenesis of the cerebral aqueduct and ventral third ventricle in the midbrain.

  20. Lithium and brain plasticity - studies on glial cell changes and electroconvulsive treatment-induced amnesia in rats

    OpenAIRE

    Orre, Karin

    2013-01-01

    Depression and bipolar disorder, collectively known as mood disorders, are devastating, common and often chronic illnesses. Imaging studies of patients with mood disorders have demonstrated structural changes in several brain regions implicated in mood regulation. Furthermore, bipolar disorder is associated with white matter abnormalities and post mortem analysis of brain tissue from patients with mood disorders have shown glial cell pathology. Electroconvulsive therapy (ECT) and pharmacologi...

  1. Glial alterations from early to late stages in a model of Alzheimer's disease: Evidence of autophagy involvement in Aβ internalization.

    Science.gov (United States)

    Pomilio, Carlos; Pavia, Patricio; Gorojod, Roxana Mayra; Vinuesa, Angeles; Alaimo, Agustina; Galvan, Veronica; Kotler, Monica Lidia; Beauquis, Juan; Saravia, Flavia

    2016-02-01

    Alzheimer's disease (AD) is a progressive neurodegenerative disease without effective therapy. Brain amyloid deposits are classical histopathological hallmarks that generate an inflammatory reaction affecting neuronal and glial function. The identification of early cell responses and of brain areas involved could help to design new successful treatments. Hence, we studied early alterations of hippocampal glia and their progression during the neuropathology in PDAPP-J20 transgenic mice, AD model, at 3, 9, and 15 months (m) of age. At 3 m, before deposits formation, microglial Iba1+ cells from transgenic mice already exhibited signs of activation and larger soma size in the hilus, alterations appearing later on stratum radiatum. Iba1 immunohistochemistry revealed increased cell density and immunoreactive area in PDAPP mice from 9 m onward selectively in the hilus, in coincidence with prominent amyloid Congo red + deposition. At pre-plaque stages, GFAP+ astroglia showed density alterations while, at an advanced age, the presence of deposits was associated with important glial volume changes and apparently being intimately involved in amyloid degradation. Astrocytes around plaques were strongly labeled for LC3 until 15 m in Tg mice, suggestive of increased autophagic flux. Moreover, β-Amyloid fibrils internalization by astrocytes in in vitro conditions was dependent on autophagy. Co-localization of Iba1 with ubiquitin or p62 was exclusively found in microglia contacting deposits from 9 m onward, suggesting torpid autophagy. Our work characterizes glial changes at early stages of the disease in PDAPP-J20 mice, focusing on the hilus as an especially susceptible hippocampal subfield, and provides evidence that glial autophagy could play a role in amyloid processing at advanced stages. © 2015 Wiley Periodicals, Inc.

  2. Corvitin restores metallothionein and glial fibrillary acidic protein levels in rat brain affected by pituitrin-izadrin

    OpenAIRE

    H. N. Shiyntum; O. O. Dovban; Y. P. Kovalchuk; T. Ya. Yaroshenko2; G. A. Ushakova1

    2017-01-01

    In this research, we investigated the effect of pituitrin-izadrin induced injury on the levels of metallothionein (MT) and soluble and filament forms of glial fibrillary acidic protein (GFAP) in the hippocampus, cerebellum, thalamus, and the cerebral cortex, and examined the effect of corvitin on the brain under the noted changes. Our results showed oppositely directed changes – a decrease in the level of MT and an increase in GFAP in the rat brain, with a tendency to astrogliosis development...

  3. Radiosensitivity of glial progenitor cells of the perinatal and adult rat optic nerve studied by an in vitro clonogenic assay

    International Nuclear Information System (INIS)

    Maazen, R.W.M. van der; Verhagen, I.; Kleiboer, B.J.; Kogel, A.J. van der

    1991-01-01

    The cellular basis of radiation-induced demyelination and white matter necrosis of the central nervous system (CNS), is poorly understood. Glial cells responsible for myelination in the CNS might be the target cells of this type of damage. Glial cells with stem cell properties derived from the perinatal and adult rat CNS can be cultured in vitro. These cells are able to differentiate into oligodendrocytes or type-2 astrocytes (O-2A) depending on the culture conditions. Growth factors produced by monolayers of type-1 astrocytes inhibit premature differentiation of O-2A progenitor cells and allow colony formation. A method which employs these monolayers of type-1 astrocytes to culture O-2A progenitor cells has been adapted to allow the analysis of colonies of surviving cells after X-irradiation. In vitro survival curves were obtained for glial progenitor cells derived from perinatal and adult optic nerves. The intrinsic radiosensitivity of perinatal and adult O-2A progenitor cells showed a large difference. Perinatal O-2A progenitor cells are quite radiosensitive, in contrast to adult O-2A progenitor cells. For both cell types an inverse relationship was found between the dose and the size of colonies derived from surviving cells. Surviving O-2A progenitor cells maintain their ability to differentiate into oligo-dendrocytes or type-2 astrocytes. This system to assess radiation-induced damage to glial progenitor cells in vitro systems to have a great potential in unraveling the cellular basis of radiation-induced demyelinating syndromes of the CNS. (author). 28 refs.; 4 figs.; 1 tab

  4. Glial and Neuronal Glutamate Transporters Differ in the Na+ Requirements for Activation of the Substrate-Independent Anion Conductance

    Directory of Open Access Journals (Sweden)

    Christopher B. Divito

    2017-05-01

    Full Text Available Excitatory amino acid transporters (EAATs are secondary active transporters of L-glutamate and L- or D-aspartate. These carriers also mediate a thermodynamically uncoupled anion conductance that is gated by Na+ and substrate binding. The activation of the anion channel by binding of Na+ alone, however, has only been demonstrated for mammalian EAAC1 (EAAT3 and EAAT4. To date, no difference has been observed for the substrate dependence of anion channel gating between the glial, EAAT1 and EAAT2, and the neuronal isoforms EAAT3, EAAT4 and EAAT5. Here we describe a difference in the Na+-dependence of anion channel gating between glial and neuronal isoforms. Chloride flux through transporters without glutamate binding has previously been described as substrate-independent or “leak” channel activity. Choline or N-methyl-D-glucamine replacement of external Na+ ions significantly reduced or abolished substrate-independent EAAT channel activity in EAAT3 and EAAT4 yet has no effect on EAAT1 or EAAT2. The interaction of Na+ with the neuronal carrier isoforms was concentration dependent, consistent with previous data. The presence of substrate and Na+-independent open states in the glial EAAT isoforms is a novel finding in the field of EAAT function. Our results reveal an important divergence in anion channel function between glial and neuronal glutamate transporters and highlight new potential roles for the EAAT-associated anion channel activity based on transporter expression and localization in the central nervous system.

  5. Glial reaction in visual centers upon whole-body combined irradiation with microwaves and x-radiation

    International Nuclear Information System (INIS)

    Logvinov, S.V.

    1989-01-01

    A single whole-body preirradiation with thermogenous microwaves modifies the dynamics of the glial reactions of visual centers of ginea pigs induced by median lethal X-radiation doses. A combination of the two factors products the synergistic effect, estimated by the degree of alteration of astrocytes and oligodendroglyocytes at early times after exposure, leads to early activation of microglia, and reduces radiation-induced alterations in glia at later times (25-60 days)

  6. Multivoxel 1H-MR spectroscopy in evaluating perienhancement region of brain tumors

    International Nuclear Information System (INIS)

    Xu Maosheng; Pan Zhiyong; Cao Zhijian; Wang Wei; Zheng Meijun; Ni Guibao

    2003-01-01

    Objective: To investigate the predictive value of multivoxel proton magnetic resonance spectroscopy (MRS) in evaluating the metabolic changes in perienhancement area of brain tumors. Methods: Fifty-one intracranial tumor patients were recruited in this study with 24 astrocytomas [grade II(8), III(7), IV(9)], 15 metastases, and 12 meningiomas. Multivoxel proton MRS was performed on a 1.5 TMR scanner using point-resolved spectroscopy (PRESS) sequence with TE of 144 ms and TR of 1000 ms. Spectra of three voxels were taken from A) enhanced, solid part of the tumor, B) perienhancement region (PER, with T 2 hyperintense areas), and C) corresponding contralateral normal appearing white matter, and those regions were evaluated in every patients. Fitted areas in the spectrum for N-acetylaspartate (NAA), choline (Cho), creatine (Cr), lipid/ lactate, and myo-Inositol (mI) metabolite peaks were measured and NAA/Cho, NAA/Cr, Cho/Cho (normal), Cho/Cr (n) ratios were calculated for each voxel (0.562 cm 3 in size). One way ANOVA (SPSS 11.0 for windows, Chicago, Ill.) was used for statistical analysis in metabolic ratio's difference among the brain tumors. Results: In voxel A (MRS from the solid enhanced part of the lesion), the ratios of NAA/Cho and Cho/Cho (n) changed significantly by comparing with that of normal control brain tissues, but there was no significant difference among gliomas, metastases, and meningiomas (P>0.05). On the contrary, in voxel B of MRS from perienhancement region, NAA/Cho, Cho/Cho (n), and Cho/Cr (n) ratios revealed strong correlations between metabolite concentrations and tumor types, allowing the differentiation of glial tumors from both metastases and meningiomas (P<0.05). The mean values of PER for glial tumor, metastasis, and meningiomas were 0.89, 1.31, and 1.32 for NAA/Cho; 1.54, 1.78, and 1.87 for NAA/Cr; 1.47, 1.01, and 0.96 for Cho/Cho (n); and 1.75, 1.13 and, 1.21 for Cho/Cr (n), respectively. Conclusion: Evaluation of brain tumors and

  7. Pathophysiology of NG2-glia:a ‘Chicken and Egg’ scenario of altered neurotransmission and disruption of NG2-glial cell function

    OpenAIRE

    Rivera, Andrea Domenico; De La Rocha, Irene Chacon; Neville, Rebekah; Butt, Arthur Morgan

    2016-01-01

    Classically, the central nervous system (CNS) was considered to contain neurons and three main types of glial cells - astrocytes, oligodendrocytes, and microglia. Now, it has been clearly established that NG2-glia are a fourth glial cell type that are defined by their expression of the NG2 chondroitin sulfate proteoglycan (Cspg4). NG2-glia are also known as oligodendrocyte precursor cells (OPCs) and express the alpha receptor for platelet-derived growth factor (Pdgfra) as well as other oligod...

  8. 46 CFR 57.06-4 - Production testing specimen requirements.

    Science.gov (United States)

    2010-10-01

    ... WELDING AND BRAZING Production Tests § 57.06-4 Production testing specimen requirements. (a) For test... 46 Shipping 2 2010-10-01 2010-10-01 false Production testing specimen requirements. 57.06-4... to welding shall not throw the finished test plate out of line by an angle of over 5°. (c) Where the...

  9. Structural analysis of 177-FA redesigned surveillance specimen holder tube

    International Nuclear Information System (INIS)

    Pryor, C.W.; Thoren, D.E.; Vames, G.J.; Harris, R.J.

    1976-08-01

    Because of in-service operational problems, the surveillance specimen holder tubes described in B and W topical report BAW-10051 have been redesigned. This report describes the new design and structural analysis for normal operation and upset loading conditions. The results of the analysis demonstrate the adequacy of the new surveillance specimen holder tubes for their design life of 40 years

  10. Feasibility Study of Laser Cutting for Fabrication of Tensile Specimen

    International Nuclear Information System (INIS)

    Jin, Y. G.; Baik, S. J.; Kim, G. S.; Heo, G. S.; Yoo, B. O.; Ahn, S. B.; Chun, Y. B.

    2015-01-01

    The specimen fabrication technique was established to machine the specimen from the irradiated materials. The wire cut EDM(electric discharge machine) was modified to fabricate the mechanical testing specimens from irradiated components and fuel claddings. The oxide layer removal system was also developed because the oxide layer on the surface of the irradiated components and claddings interrupted the applying the electric current during the processing. However, zirconium oxide is protective against further corrosion as well as beneficial to mechanical strength for the tensile deformation of the cladding. Thus, it is important to fabricate the irradiated specimens without removal of oxide layer on the surface of the irradiated structural components and claddings. In the present study, laser cutting system was introduced to fabricate the various mechanical testing specimens from the unirradiated fuel cladding and the feasibility of the laser cutting system was studied for the fabrication of various types of irradiated specimens in a hot cell at IMEF (Irradiated Materials Examination Facility) of KAERI. Laser beam machining system was introduced to fabricate the various mechanical testing specimens from the unirradiated fuel cladding and the dimensions were compared for the feasibility of the laser cutting system. The effect of surface oxide layer was also investigated for machining process of the zircaloy-4 fuel cladding and it was found that laser beam machining could be a useful tool to fabricate the specimens with surface oxide layer

  11. Feasibility Study of Laser Cutting for Fabrication of Tensile Specimen

    Energy Technology Data Exchange (ETDEWEB)

    Jin, Y. G.; Baik, S. J.; Kim, G. S.; Heo, G. S.; Yoo, B. O.; Ahn, S. B.; Chun, Y. B. [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2015-05-15

    The specimen fabrication technique was established to machine the specimen from the irradiated materials. The wire cut EDM(electric discharge machine) was modified to fabricate the mechanical testing specimens from irradiated components and fuel claddings. The oxide layer removal system was also developed because the oxide layer on the surface of the irradiated components and claddings interrupted the applying the electric current during the processing. However, zirconium oxide is protective against further corrosion as well as beneficial to mechanical strength for the tensile deformation of the cladding. Thus, it is important to fabricate the irradiated specimens without removal of oxide layer on the surface of the irradiated structural components and claddings. In the present study, laser cutting system was introduced to fabricate the various mechanical testing specimens from the unirradiated fuel cladding and the feasibility of the laser cutting system was studied for the fabrication of various types of irradiated specimens in a hot cell at IMEF (Irradiated Materials Examination Facility) of KAERI. Laser beam machining system was introduced to fabricate the various mechanical testing specimens from the unirradiated fuel cladding and the dimensions were compared for the feasibility of the laser cutting system. The effect of surface oxide layer was also investigated for machining process of the zircaloy-4 fuel cladding and it was found that laser beam machining could be a useful tool to fabricate the specimens with surface oxide layer.

  12. Design Analysis of the Mixed Mode Bending Sandwich Specimen

    DEFF Research Database (Denmark)

    Quispitupa, Amilcar; Berggreen, Christian; Carlsson, Leif A.

    2010-01-01

    A design analysis of the mixed mode bending (MMB) sandwich specimen for face–core interface fracture characterization is presented. An analysis of the competing failure modes in the foam cored sandwich specimens is performed in order to achieve face–core debond fracture prior to other failure modes...... for the chosen geometries and mixed mode loading conditions....

  13. Blood specimen labelling errors: Implications for nephrology nursing practice.

    Science.gov (United States)

    Duteau, Jennifer

    2014-01-01

    Patient safety is the foundation of high-quality health care, as recognized both nationally and worldwide. Patient blood specimen identification is critical in ensuring the delivery of safe and appropriate care. The practice of nephrology nursing involves frequent patient blood specimen withdrawals to treat and monitor kidney disease. A critical review of the literature reveals that incorrect patient identification is one of the major causes of blood specimen labelling errors. Misidentified samples create a serious risk to patient safety leading to multiple specimen withdrawals, delay in diagnosis, misdiagnosis, incorrect treatment, transfusion reactions, increased length of stay and other negative patient outcomes. Barcode technology has been identified as a preferred method for positive patient identification leading to a definitive decrease in blood specimen labelling errors by as much as 83% (Askeland, et al., 2008). The use of a root cause analysis followed by an action plan is one approach to decreasing the occurrence of blood specimen labelling errors. This article will present a review of the evidence-based literature surrounding blood specimen labelling errors, followed by author recommendations for completing a root cause analysis and action plan. A failure modes and effects analysis (FMEA) will be presented as one method to determine root cause, followed by the Ottawa Model of Research Use (OMRU) as a framework for implementation of strategies to reduce blood specimen labelling errors.

  14. On a specimen of Lumbricus terrestris, L. with bifurcated tail

    NARCIS (Netherlands)

    Horst, R.

    1886-01-01

    In the last number of the »Annals and Magazine of Nat. History” (Dec. 1885), I find a notice of Prof. Jeffrey Bell about two Lumbrici with bifid hinder ends, one specimen belonging to L. terrestris, the other to L. foetidus; moreover he mentions a specimen, presenting a similar remarquable

  15. A cylindrical specimen holder for electron cryo-tomography

    International Nuclear Information System (INIS)

    Palmer, Colin M.; Löwe, Jan

    2014-01-01

    The use of slab-like flat specimens for electron cryo-tomography restricts the range of viewing angles that can be used. This leads to the “missing wedge” problem, which causes artefacts and anisotropic resolution in reconstructed tomograms. Cylindrical specimens provide a way to eliminate the problem, since they allow imaging from a full range of viewing angles around the tilt axis. Such specimens have been used before for tomography of radiation-insensitive samples at room temperature, but never for frozen-hydrated specimens. Here, we demonstrate the use of thin-walled carbon tubes as specimen holders, allowing the preparation of cylindrical frozen-hydrated samples of ribosomes, liposomes and whole bacterial cells. Images acquired from these cylinders have equal quality at all viewing angles, and the accessible tilt range is restricted only by the physical limits of the microscope. Tomographic reconstructions of these specimens demonstrate that the effects of the missing wedge are substantially reduced, and could be completely eliminated if a full tilt range was used. The overall quality of these tomograms is still lower than that obtained by existing methods, but improvements are likely in future. - Highlights: • The missing wedge is a serious problem for electron cryo-tomography. • Cylindrical specimens allow the missing wedge to be eliminated. • Carbon nanopipettes can be used as cylindrical holders for tomography of frozen-hydrated specimens. • Cryo-tomography of cylindrical biological samples demonstrates a reduction of deleterious effects associated with the missing wedge

  16. Thermal Cycling of Uranium Dioxide - Tungsten Cermet Fuel Specimens

    Energy Technology Data Exchange (ETDEWEB)

    Gripshover, P.J.; Peterson, J.H.

    1969-12-08

    In phase I tungsten clad cermet fuel specimens were thermal cycled, to study the effects of fuel loading, fuel particle size, stablized fuel, duplex coatings, and fabrication techniques on dimensional stability during thermal cycling. In phase II the best combination of the factors studies in phase I were combined in one specimen for evaluation.

  17. Radial glial dependent and independent dynamics of interneuronal migration in the developing cerebral cortex.

    Directory of Open Access Journals (Sweden)

    Yukako Yokota

    2007-08-01

    Full Text Available Interneurons originating from the ganglionic eminence migrate tangentially into the developing cerebral wall as they navigate to their distinct positions in the cerebral cortex. Compromised connectivity and differentiation of interneurons are thought to be an underlying cause in the emergence of neurodevelopmental disorders such as schizophrenia. Previously, it was suggested that tangential migration of interneurons occurs in a radial glia independent manner. Here, using simultaneous imaging of genetically defined populations of interneurons and radial glia, we demonstrate that dynamic interactions with radial glia can potentially influence the trajectory of interneuronal migration and thus the positioning of interneurons in cerebral cortex. Furthermore, there is extensive local interneuronal migration in tangential direction opposite to that of pallial orientation (i.e., in a medial to lateral direction from cortex to ganglionic eminence all across the cerebral wall. This counter migration of interneurons may be essential to locally position interneurons once they invade the developing cerebral wall from the ganglionic eminence. Together, these observations suggest that interactions with radial glial scaffold and localized migration within the expanding cerebral wall may play essential roles in the guidance and placement of interneurons in the developing cerebral cortex.

  18. Brain glutamine synthesis requires neuronal-born aspartate as amino donor for glial glutamate formation.

    Science.gov (United States)

    Pardo, Beatriz; Rodrigues, Tiago B; Contreras, Laura; Garzón, Miguel; Llorente-Folch, Irene; Kobayashi, Keiko; Saheki, Takeyori; Cerdan, Sebastian; Satrústegui, Jorgina

    2011-01-01

    The glutamate-glutamine cycle faces a drain of glutamate by oxidation, which is balanced by the anaplerotic synthesis of glutamate and glutamine in astrocytes. De novo synthesis of glutamate by astrocytes requires an amino group whose origin is unknown. The deficiency in Aralar/AGC1, the main mitochondrial carrier for aspartate-glutamate expressed in brain, results in a drastic fall in brain glutamine production but a modest decrease in brain glutamate levels, which is not due to decreases in neuronal or synaptosomal glutamate content. In vivo (13)C nuclear magnetic resonance labeling with (13)C(2)acetate or (1-(13)C) glucose showed that the drop in brain glutamine is due to a failure in glial glutamate synthesis. Aralar deficiency induces a decrease in aspartate content, an increase in lactate production, and lactate-to-pyruvate ratio in cultured neurons but not in cultured astrocytes, indicating that Aralar is only functional in neurons. We find that aspartate, but not other amino acids, increases glutamate synthesis in both control and aralar-deficient astrocytes, mainly by serving as amino donor. These findings suggest the existence of a neuron-to-astrocyte aspartate transcellular pathway required for astrocyte glutamate synthesis and subsequent glutamine formation. This pathway may provide a mechanism to transfer neuronal-born redox equivalents to mitochondria in astrocytes.

  19. Clonal Heterogeneity in the Neuronal and Glial Differentiation of Dental Pulp Stem/Progenitor Cells

    Directory of Open Access Journals (Sweden)

    Fraser I. Young

    2016-01-01

    Full Text Available Cellular heterogeneity presents an important challenge to the development of cell-based therapies where there is a fundamental requirement for predictable and reproducible outcomes. Transplanted Dental Pulp Stem/Progenitor Cells (DPSCs have demonstrated early promise in experimental models of spinal cord injury and stroke, despite limited evidence of neuronal and glial-like differentiation after transplantation. Here, we report, for the first time, on the ability of single cell-derived clonal cultures of murine DPSCs to differentiate in vitro into immature neuronal-like and oligodendrocyte-like cells. Importantly, only DPSC clones with high nestin mRNA expression levels were found to successfully differentiate into Map2 and NF-positive neuronal-like cells. Neuronally differentiated DPSCs possessed a membrane capacitance comparable with primary cultured striatal neurons and small inward voltage-activated K+ but not outward Na+ currents were recorded suggesting a functionally immature phenotype. Similarly, only high nestin-expressing clones demonstrated the ability to adopt Olig1, Olig2, and MBP-positive immature oligodendrocyte-like phenotype. Together, these results demonstrate that appropriate markers may be used to provide an early indication of the suitability of a cell population for purposes where differentiation into a specific lineage may be beneficial and highlight that further understanding of heterogeneity within mixed cellular populations is required.

  20. Major Shifts in Glial Regional Identity Are a Transcriptional Hallmark of Human Brain Aging

    Directory of Open Access Journals (Sweden)

    Lilach Soreq

    2017-01-01

    Full Text Available Gene expression studies suggest that aging of the human brain is determined by a complex interplay of molecular events, although both its region- and cell-type-specific consequences remain poorly understood. Here, we extensively characterized aging-altered gene expression changes across ten human brain regions from 480 individuals ranging in age from 16 to 106 years. We show that astrocyte- and oligodendrocyte-specific genes, but not neuron-specific genes, shift their regional expression patterns upon aging, particularly in the hippocampus and substantia nigra, while the expression of microglia- and endothelial-specific genes increase in all brain regions. In line with these changes, high-resolution immunohistochemistry demonstrated decreased numbers of oligodendrocytes and of neuronal subpopulations in the aging brain cortex. Finally, glial-specific genes predict age with greater precision than neuron-specific genes, thus highlighting the need for greater mechanistic understanding of neuron-glia interactions in aging and late-life diseases.

  1. Oxidative Glial Cell Damage Associated with White Matter Lesions in the Aging Human Brain.

    Science.gov (United States)

    Al-Mashhadi, Sufana; Simpson, Julie E; Heath, Paul R; Dickman, Mark; Forster, Gillian; Matthews, Fiona E; Brayne, Carol; Ince, Paul G; Wharton, Stephen B

    2015-09-01

    White matter lesions (WML) are common in brain aging and are associated with dementia. We aimed to investigate whether oxidative DNA damage and occur in WML and in apparently normal white matter in cases with lesions. Tissue from WML and control white matter from brains with lesions (controls lesional) and without lesions (controls non-lesional) were obtained, using post-mortem magnetic resonance imaging-guided sampling, from the Medical Research Council Cognitive Function and Ageing Study. Oxidative damage was assessed by immunohistochemistry to 8-hydroxy-2'-deoxoguanosine (8-OHdG) and Western blotting for malondialdehyde. DNA response was assessed by phosphorylated histone H2AX (γH2AX), p53, senescence markers and by quantitative Reverse transcription polymerase chain reaction (RT-PCR) panel for candidate DNA damage-associated genes. 8-OHdG was expressed in glia and endothelium, with increased expression in both WML and controls lesional compared with controls non-lesional (P glial dysfunction. Their expression in apparently normal white matter in cases with WML suggests that white matter dysfunction is not restricted to lesions. The role of this field-effect lesion pathogenesis and cognitive impairment are areas to be defined. © 2014 The Authors. Brain Pathology published by John Wiley & Sons Ltd on behalf of International Society of Neuropathology.

  2. Astrocytes from adult Wistar rats aged in vitro show changes in glial functions.

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    Souza, Débora Guerini; Bellaver, Bruna; Raupp, Gustavo Santos; Souza, Diogo Onofre; Quincozes-Santos, André

    2015-11-01

    Astrocytes, the most versatile cells of the central nervous system, play an important role in the regulation of neurotransmitter homeostasis, energy metabolism, antioxidant defenses and the anti-inflammatory response. Recently, our group characterized cortical astrocyte cultures from adult Wistar rats. In line with that work, we studied glial function using an experimental in vitro model of aging astrocytes (30 days in vitro after reaching confluence) from newborn (NB), adult (AD) and aged (AG) Wistar rats. We evaluated metabolic parameters, such as the glucose uptake, glutamine synthetase (GS) activity, and glutathione (GSH) content, as well as the GFAP, GLUT-1 and xCT expression. AD and AG astrocytes take up less glucose than NB astrocytes and had decreased GLUT1 expression levels. Furthermore, AD and AG astrocytes exhibited decreased GS activity compared to NB cells. Simultaneously, AD and AG astrocytes showed an increase in GSH levels, along with an increase in xCT expression. NB, AD and AG astrocytes presented similar morphology; however, differences in GFAP levels were observed. Taken together, these results improve the knowledge of cerebral senescence and represent an innovative tool for brain studies of aging. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Major Shifts in Glial Regional Identity Are a Transcriptional Hallmark of Human Brain Aging.

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    Soreq, Lilach; Rose, Jamie; Soreq, Eyal; Hardy, John; Trabzuni, Daniah; Cookson, Mark R; Smith, Colin; Ryten, Mina; Patani, Rickie; Ule, Jernej

    2017-01-10

    Gene expression studies suggest that aging of the human brain is determined by a complex interplay of molecular events, although both its region- and cell-type-specific consequences remain poorly understood. Here, we extensively characterized aging-altered gene expression changes across ten human brain regions from 480 individuals ranging in age from 16 to 106 years. We show that astrocyte- and oligodendrocyte-specific genes, but not neuron-specific genes, shift their regional expression patterns upon aging, particularly in the hippocampus and substantia nigra, while the expression of microglia- and endothelial-specific genes increase in all brain regions. In line with these changes, high-resolution immunohistochemistry demonstrated decreased numbers of oligodendrocytes and of neuronal subpopulations in the aging brain cortex. Finally, glial-specific genes predict age with greater precision than neuron-specific genes, thus highlighting the need for greater mechanistic understanding of neuron-glia interactions in aging and late-life diseases. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  4. Glial responses, neuron death and lesion resolution after intracerebral hemorrhage in young vs. aged rats.

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    Wasserman, Jason K; Yang, Helen; Schlichter, Lyanne C

    2008-10-01

    Intracerebral hemorrhage (ICH) usually affects older humans but almost no experimental studies have assessed aged animals. We address how aging alters inflammation, neuron death and lesion resolution after a hemorrhage in the rat striatum. In the normal aged brain, microglia displayed a 'dystrophic' phenotype, with shorter cellular processes and large gaps between adjacent cells, and there was more astrocyte reactivity. The ICH injury was monitored as hematoma volume and number of dying neurons at 1 and 3 days, and the volume of the residual lesion, ventricles and lost tissue at 28 days. Inflammation at 1 and 3 days was assessed from densities of microglia with resting vs. activated morphologies, or expressing the lysosomal marker ED1. Despite an initial delay in neuron death in aged animals, by 28 days, there was no difference in neuron density or volume of tissue lost. However, lesion resolution was impaired in aged animals and there was less compensatory ventricular expansion. At 1 day after ICH, there were fewer activated microglia/macrophages in the aged brain, but by 3 days there were more of these cells at the edge of the hematoma and in the surrounding parenchyma. In both age groups a glial limitans had developed by 3 days, but astrocyte reactivity and the spread of activated microglia/macrophages into the surrounding parenchyma was greater in the aged. These findings have important implications for efforts to reduce secondary injury after ICH and to develop anti-inflammatory therapies to treat ICH in aged humans.

  5. [Alterations of glial fibrillary acidic protein in rat brain after gamma knife irradiation].

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    Ma, Z M; Jiang, B; Ma, J R

    2001-08-28

    To study glial fibrillary acidic protein (GFAP) immunoreactivity in different time and water content of the rat brain treated with gamma knife radiotherapy and to understand the alteration course of the brain lesion after a single high dose radiosurgical treatment. In the brains of the normal rats were irradiated by gamma knife with 160 Gy-high dose. The irradiated rats were then killed on the 1st day, 7th day, 14th day, and 28th day after radiotherapy, respectively. The positive cells of GFAP in brain tissue were detected by immunostaining; the water content of the brain tissue was measured by microgravimetry. The histological study of the irradiated brain tissue was performed with H.E. and examined under light microscope. The numbers of GFAP-positive astrocytes began to increase on the 1st day after gamma knife irradiation. It was enlarged markedly in the number and size of GFAP-stained astrocytes over the irradiated areas. Up to the 28th day, circumscribed necrosis foci (4 mm in diameter) was seen in the central area of the target. In the brain tissue around the necrosis, GFAP-positive astrocytes significantly increased (P gravity in the irradiated brain tissue the 14th and 28th day after irradiation. The results suggest that GFAP can be used as a marker for the radiation-induced brain injury. The brain edema and disruption of brain-blood barrier can be occurred during the acute stage after irradiation.

  6. Occlusion of retinal capillaries caused by glial cell proliferation in chronic ocular inflammation.

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    Bianchi, E; Ripandelli, G; Feher, J; Plateroti, A M; Plateroti, R; Kovacs, I; Plateroti, P; Taurone, S; Artico, M

    2015-01-01

    The inner blood-retinal barrier is a gliovascular unit in which glial cells surround capillary endothelial cells and regulate retinal capillaries by paracrine interactions. During chronic ocular inflammation, microvascular complications can give rise to vascular proliferative lesions, which compromise visual acuity. This pathologic remodelling caused by proliferating Müller cells determines occlusion of retinal capillaries. The aim of the present study was to identify qualitative and quantitative alterations in the retinal capillaries in patients with post-traumatic chronic ocular inflammation or post-thrombotic vascular glaucoma. Moreover, we investigated the potential role of vascular endothelial growth factor (VEGF) and pro-inflammatory cytokines in retinal inflammation. Our electron microscopy findings demonstrated that during chronic ocular inflammation, thickening of the basement membrane, loss of pericytes and endothelial cells and proliferation of Müller cells occur with irreversible occlusion of retinal capillaries. Angiogenesis takes place as part of a regenerative reaction that results in fibrosis. We believe that VEGF and pro-inflammatory cytokines may be potential therapeutic targets in the treatment of this disease although further studies are required to confirm these findings.

  7. Proliferative reactive gliosis is compatible with glial metabolic support and neuronal function

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    Fero Matthew

    2011-10-01

    Full Text Available Abstract Background The response of mammalian glial cells to chronic degeneration and trauma is hypothesized to be incompatible with support of neuronal function in the central nervous system (CNS and retina. To test this hypothesis, we developed an inducible model of proliferative reactive gliosis in the absence of degenerative stimuli by genetically inactivating the cyclin-dependent kinase inhibitor p27Kip1 (p27 or Cdkn1b in the adult mouse and determined the outcome on retinal structure and function. Results p27-deficient Müller glia reentered the cell cycle, underwent aberrant migration, and enhanced their expression of intermediate filament proteins, all of which are characteristics of Müller glia in a reactive state. Surprisingly, neuroglial interactions, retinal electrophysiology, and visual acuity were normal. Conclusion The benign outcome of proliferative reactive Müller gliosis suggests that reactive glia display context-dependent, graded and dynamic phenotypes and that reactivity in itself is not necessarily detrimental to neuronal function.

  8. Acquisition of glial cells missing 2 enhancers contributes to a diversity of ionocytes in zebrafish.

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    Takanori Shono

    Full Text Available Glial cells missing 2 (gcm2 encoding a GCM-motif transcription factor is expressed in the parathyroid in amniotes. In contrast, gcm2 is expressed in pharyngeal pouches (a homologous site of the parathyroid, gills, and H(+-ATPase-rich cells (HRCs, a subset of ionocytes on the skin surface of the teleost fish zebrafish. Ionocytes are specialized cells that are involved in osmotic homeostasis in aquatic vertebrates. Here, we showed that gcm2 is essential for the development of HRCs and Na(+-Cl(- co-transporter-rich cells (NCCCs, another subset of ionocytes in zebrafish. We also identified gcm2 enhancer regions that control gcm2 expression in ionocytes of zebrafish. Comparisons of the gcm2 locus with its neighboring regions revealed no conserved elements between zebrafish and tetrapods. Furthermore, We observed gcm2 expression patterns in embryos of the teleost fishes Medaka (Oryzias latipes and fugu (Fugu niphobles, the extant primitive ray-finned fishes Polypterus (Polypterus senegalus and sturgeon (a hybrid of Huso huso × Acipenser ruhenus, and the amphibian Xenopus (Xenopus laevis. Although gcm2-expressing cells were observed on the skin surface of Medaka and fugu, they were not found in Polypterus, sturgeon, or Xenopus. Our results suggest that an acquisition of enhancers for the expression of gcm2 contributes to a diversity of ionocytes in zebrafish during evolution.

  9. Chemokines in neuron-glial cell interaction and pathogenesis of neuropathic pain.

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    Zhang, Zhi-Jun; Jiang, Bao-Chun; Gao, Yong-Jing

    2017-09-01

    Neuropathic pain resulting from damage or dysfunction of the nervous system is a highly debilitating chronic pain state and is often resistant to currently available treatments. It has become clear that neuroinflammation, mainly mediated by proinflammatory cytokines and chemokines, plays an important role in the establishment and maintenance of neuropathic pain. Chemokines were originally identified as regulators of peripheral immune cell trafficking and were also expressed in neurons and glial cells in the central nervous system. In recent years, accumulating studies have revealed the expression, distribution and function of chemokines in the spinal cord under chronic pain conditions. In this review, we provide evidence showing that several chemokines are upregulated after peripheral nerve injury and contribute to the pathogenesis of neuropathic pain via different forms of neuron-glia interaction in the spinal cord. First, chemokine CX3CL1 is expressed in primary afferents and spinal neurons and induces microglial activation via its microglial receptor CX3CR1 (neuron-to-microglia signaling). Second, CCL2 and CXCL1 are expressed in spinal astrocytes and act on CCR2 and CXCR2 in spinal neurons to increase excitatory synaptic transmission (astrocyte-to-neuron signaling). Third, we recently identified that CXCL13 is highly upregulated in spinal neurons after spinal nerve ligation and induces spinal astrocyte activation via receptor CXCR5 (neuron-to-astrocyte signaling). Strategies that target chemokine-mediated neuron-glia interactions may lead to novel therapies for the treatment of neuropathic pain.

  10. Treatment with glial derived neurotropic factor (GDNF attenuates oxidative damages of spinal

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    Tao Li

    2016-05-01

    Full Text Available Spinal cord injury (SCI is a serious and debilitating issue being suffered by wide population worldwide. Extensive treatment approaches have been tested and being verified for their efficacy. Owing to the nature of central nervous system (CNS, the resident stem cells would be triggered in response to any sort of trauma with nerve factors as their communication signals. Apart from physical injuries, damages due to oxidative stress also need to be addressed while CNS repair mechanism takes place. This study looks at the potential of glial derived nerve factor (GDNF in addressing the SCI in regard to oxidative damages. A total of 60 Wistar rats were clustered into five groups and GDNF at various concentrations was tested in each group. Assessments in terms of oxidative stress parameters were noted and analyzed accordingly. It was noted that GDNF had reduced oxidative damages and increased the levels of anti-oxidants in dose-dependent manner (p < 0.05. Though treatment with 10 mg/mL and 20 mg/mL showed significant changes as compared to control group, these treatment modalities remained insignificant among each other. In conclusion, we demonstrated that GDNF exerted a neuro-protective effect on CNS by inducing anti-oxidants and reducing the levels of oxidative stress in SCI induced rat models.

  11. The glial response to intracerebrally delivered therapies for neurodegenerative disorders: Is this a critical issue?

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    Francesca eCicchetti

    2014-07-01

    Full Text Available The role of glial cells in the pathogenesis of many neurodegenerative conditions of the central nervous system (CNS is now well established (as is discussed in other reviews in this special issue of Frontiers in Neuropharmacology. What is less clear is whether there are changes in these same cells in terms of their behaviour and function in response to invasive experimental therapeutic interventions for these diseases. This has, and will continue to, become more of an issue as we enter a new era of novel treatments which require the agent to be directly placed/infused into the CNS such as deep brain stimulation, cell transplants, gene therapies and growth factor infusions. To date, all of these treatments have produced variable outcomes and the reasons for this have been widely debated but the host astrocytic and/or microglial response induced by such invasively delivered agents has not been discussed in any detail. In this review, we have attempted to summarise the limited published data on this, in particular we discuss the small number of human post-mortem studies reported in this field. By so doing, we hope to provide a better description and understanding of the extent and nature of both the astrocytic and microglial response, which in turn could lead to modifications in the way these therapeutic interventions are delivered.

  12. Combined treatment with ribavirin and tiazofurin attenuates response of glial cells in experimental autoimmune encephalomyelitis

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    Nedeljković Nadežda

    2012-01-01

    Full Text Available Experimental autoimmune encephalomyelitis (EAE is an animal model of multiple sclerosis (MS, a human inflammatory and demyelinating disease. Microglia and astrocytes are glial cells of the central nervous system (CNS that play a dual role in MS and EAE pathology. The aim of this study was to examine the effect of combined treatment with two nucleoside analogues, ribavirin and tiazofurin, on microglia and astrocytes in actively induced EAE. Therapeutic treatment with a combination of these two nucleoside analogues reduced disease severity, mononuclear cell infiltration and demyelination. The obtained histological results indicate that ribavirin and tiazofurin changed activated microglia into an inactive type and attenuated astrocyte reactivity at the end of the treatment period. Since reduction of reactive microgliosis and astrogliosis correlated with EAE suppression, the present study also suggests that the obtained beneficial effect of ribavirin and tiazofurin could be a consequence of their action inside as well as outside the CNS. [Acknowledgments. This work was supported by the Serbian Ministry of Education and Science, Project No: III41014.

  13. Intracellular recordings from isolated rabbit retinal Müller (glial) cells.

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    Reichenbach, A; Eberhardt, W

    1986-09-01

    Müller (glial) cells were isolated from rabbit retinae by papaine and mechanical dissociation. The cells were fixed on a gelatine-covered glass slide by means of concanavalin A, and the slide was mounted in a perfusion chamber under a light microscope with modified optics. Besides the recording microelectrode, two other micropipettes could be adjusted with their tips near the cell. These micropipettes were used for application of test solutions into the environment of the cells. On application of high K+ solutions, the cell depolarized strongly but during prolonged application there was a marked repolarization. After the end of high K+ application the cells showed a hyperpolarization which was enhanced in both amplitude and duration with prolongation of the K+ exposure. Both repolarization and afterhyperpolarization disappeared under ouabain. Ouabain application itself caused a small reversible depolarization. Na+ free solution caused hyperpolarization. The results suggest the existence of an active membrane pump mechanism in our cells. This pump seems to be electrogenic under our experimental conditions and seems to be activated even in the absence of sodium. The cell membrane is demonstrated to contain a significant Na+ conductance.

  14. Efficient K+ buffering by mammalian retinal glial cells is due to cooperation of specialized ion channels.

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    Nilius, B; Reichenbach, A

    1988-06-01

    Radial glial (Müller) cells were isolated from rabbit retinae by papaine and mechanical dissociation. Regional membrane properties of these cells were studied by using the patch-clamp technique. In the course of our experiments, we found three distinct types of large K+ conducting channels. The vitread process membrane was dominated by high conductance inwardly rectifying (HCR) channels which carried, in the open state, inward currents along a conductance of about 105 pS (symmetrical solutions with 140 mM K+) but almost no outward currents. In the membrane of the soma and the proximal distal process, we found low conductance inwardly rectifying (LCR) channels which had an open state-conductance of about 60 pS and showed rather weak rectification. The endfoot membrane, on the other hand, was found to contain non-rectifying very high conductance (VHC) channels with an open state-conductance of about 360 pS (same solutions). These results suggest that mammalian Müller cells express regional membrane specializations which are optimized to carry spatial buffering currents of excess K+ ions.

  15. A three dimensional in vitro glial scar model to investigate the local strain effects from micromotion around neural implants.

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    Spencer, Kevin C; Sy, Jay C; Falcón-Banchs, Roberto; Cima, Michael J

    2017-02-28

    Glial scar formation remains a significant barrier to the long term success of neural probes. Micromotion coupled with mechanical mismatch between the probe and tissue is believed to be a key driver of the inflammatory response. In vitro glial scar models present an intermediate step prior to conventional in vivo histology experiments as they enable cell-device interactions to be tested on a shorter timescale, with the ability to conduct broader biochemical assays. No established in vitro models have incorporated methods to assess device performance with respect to mechanical factors. In this study, we describe an in vitro glial scar model that combines high-precision linear actuators to simulate axial micromotion around neural implants with a 3D primary neural cell culture in a collagen gel. Strain field measurements were conducted to visualize the local displacement within the gel in response to micromotion. Primary brain cell cultures were found to be mechanically responsive to micromotion after one week in culture. Astrocytes, as determined by immunohistochemical staining, were found to have significantly increased in cell areas and perimeters in response to micromotion compared to static control wells. These results demonstrate the importance of micromotion when considering the chronic response to neural implants. Going forward, this model provides advantages over existing in vitro models as it will enable critical mechanical design factors of neural implants to be evaluated prior to in vivo testing.

  16. A competitive advantage by neonatally engrafted human glial progenitors yields mice whose brains are chimeric for human glia.

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    Windrem, Martha S; Schanz, Steven J; Morrow, Carolyn; Munir, Jared; Chandler-Militello, Devin; Wang, Su; Goldman, Steven A

    2014-11-26

    Neonatally transplanted human glial progenitor cells (hGPCs) densely engraft and myelinate the hypomyelinated shiverer mouse. We found that, in hGPC-xenografted mice, the human donor cells continue to expand throughout the forebrain, systematically replacing the host murine glia. The differentiation of the donor cells is influenced by the host environment, such that more donor cells differentiated as oligodendrocytes in the hypomyelinated shiverer brain than in myelin wild-types, in which hGPCs were more likely to remain as progenitors. Yet in each recipient, both the number and relative proportion of mouse GPCs fell as a function of time, concomitant with the mitotic expansion and spread of donor hGPCs. By a year after neonatal xenograft, the forebrain GPC populations of implanted mice were largely, and often entirely, of human origin. Thus, neonatally implanted hGPCs outcompeted and ultimately replaced the host population of mouse GPCs, ultimately generating mice with a humanized glial progenitor population. These human glial chimeric mice should permit us to define the specific contributions of glia to a broad variety of neurological disorders, using human cells in vivo. Copyright © 2014 the authors 0270-6474/14/3416153-09$15.00/0.

  17. Progressive supranuclear palsy: neuronal and glial cytoskeletal pathology in the higher order processing autonomic nuclei of the lower brainstem.

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    Rüb, U; Del Tredici, K; Schultz, C; de Vos, R A I; Jansen Steur, E N H; Arai, K; Braak, H

    2002-02-01

    The medial and lateral parabrachial nuclei (MPB, LPB), the gigantocellular reticular nucleus (GI), the raphes magnus (RMG) and raphes obscurus nuclei (ROB), as well as the intermediate reticular zone (IRZ) represent pivotal subordinate brainstem centres, all of which control autonomic functions. In this study, we investigated the occurrence and severity of the neuronal and glial cytoskeletal pathology in these six brainstem nuclei from 17 individuals with clinically diagnosed and neuropathologically confirmed progressive supranuclear palsy (PSP). The association between the severity of the pathology and the duration of the disease was investigated by means of correlation analysis. The brainstem nuclei in all of the PSP cases were affected by the neuronal cytoskeletal pathology, with the IRZ and GI regularly showing severe involvement, the MPB, RMG, and ROB marked involvement, and the LPB mild involvement. In the six nuclear greys studied, glial cells undergo alterations of their cytoskeleton on an irregular basis, whereby diseased oligodendrocytes predominantly presented as coiled bodies and affected astrocytes as thorn-shaped astrocytes. In all six nuclei, the severity of the neuronal or glial cytoskeletal pathology showed no correlation with the duration of PSP. In view of their functional role, the neuronal pathology in the nuclei studied offers a possible explanation for the autonomic dysfunctions that eventually develop in the course of PSP.

  18. CNS development under altered gravity: cerebellar glial and neuronal protein expression in rat neonates exposed to hypergravity

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    Nguon, K.; Li, G.-H.; Sajdel-Sulkowska, E. M.

    2004-01-01

    The future of space exploration depends on a solid understanding of the developmental process under microgravity, specifically in relation to the central nervous system (CNS). We have previously employed a hypergravity paradigm to assess the impact of altered gravity on the developing rat cerebellum [Exp. Biol. Med. 226 (2000) 790]. The present study addresses the molecular mechanisms involved in the cerebellar response to hypergravity. Specifically, the study focuses on the expression of selected glial and neuronal cerebellar proteins in rat neonates exposed to hypergravity (1.5 G) from embryonic day (E)11 to postnatal day (P)6 or P9 (the time of maximal cerebellar changes) comparing them against their expression in rat neonates developing under normal gravity. Proteins were analyzed by quantitative Western blots of cerebellar homogenates; RNA analysis was performed in the same samples using quantitative PCR. Densitometric analysis of Western blots suggested a reduction in glial (glial acidic protein, GFAP) and neuronal (neuronal cell adhesion moiecule, NCAM-L1, synaptophysin) proteins, but the changes in individual cerebellar proteins in hypergravity-exposed neonates appeared both age- and gender-specific. RNA analysis suggested a reduction in GFAP and synaptophysin mRNAs on P6. These data suggest that exposure to hypergravity may interfere with the expression of selected cerebellar proteins. These changes in protein expression may be involved in mediating the effect of hypergravity on the developing rat cerebellum.

  19. Nuclear progesterone receptors are up-regulated by estrogens in neurons and radial glial progenitors in the brain of zebrafish.

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    Nicolas Diotel

    Full Text Available In rodents, there is increasing evidence that nuclear progesterone receptors are transiently expressed in many regions of the developing brain, notably outside the hypothalamus. This suggests that progesterone and/or its metabolites could be involved in functions not related to reproduction, particularly in neurodevelopment. In this context, the adult fish brain is of particular interest, as it exhibits constant growth and high neurogenic activity that is supported by radial glia progenitors. However, although synthesis of neuroprogestagens has been documented recently in the brain of zebrafish, information on the presence of progesterone receptors is very limited. In zebrafish, a single nuclear progesterone receptor (pgr has been cloned and characterized. Here, we demonstrate that this pgr is widely distributed in all regions of the zebrafish brain. Interestingly, we show that Pgr is strongly expressed in radial glial cells and more weakly in neurons. Finally, we present evidence, based on quantitative PCR and immunohistochemistry, that nuclear progesterone receptor mRNA and proteins are upregulated by estrogens in the brain of adult zebrafish. These data document for the first time the finding that radial glial cells are preferential targets for peripheral progestagens and/or neuroprogestagens. Given the crucial roles of radial glial cells in adult neurogenesis, the potential effects of progestagens on their activity and the fate of daughter cells require thorough investigation.

  20. Nutritional State-Dependent Ghrelin Activation of Vasopressin Neurons via Retrograde Trans-Neuronal–Glial Stimulation of Excitatory GABA Circuits

    Science.gov (United States)

    Haam, Juhee; Halmos, Katalin C.; Di, Shi

    2014-01-01

    Behavioral and physiological coupling between energy balance and fluid homeostasis is critical for survival. The orexigenic hormone ghrelin has been shown to stimulate the secretion of the osmoregulatory hormone vasopressin (VP), linking nutritional status to the control of blood osmolality, although the mechanism of this systemic crosstalk is unknown. Here, we show using electrophysiological recordings and calcium imaging in rat brain slices that ghrelin stimulates VP neurons in the hypothalamic paraventricular nucleus (PVN) in a nutritional state-dependent manner by activating an excitatory GABAergic synaptic input via a retrograde neuronal–glial circuit. In slices from fasted rats, ghrelin activation of a postsynaptic ghrelin receptor, the growth hormone secretagogue receptor type 1a (GHS-R1a), in VP neurons caused the dendritic release of VP, which stimulated astrocytes to release the gliotransmitter adenosine triphosphate (ATP). ATP activation of P2X receptors excited presynaptic GABA neurons to increase GABA release, which was excitatory to the VP neurons. This trans-neuronal–glial retrograde circuit activated by ghrelin provides an alternative means of stimulation of VP release and represents a novel mechanism of neuronal control by local neuronal–glial circuits. It also provides a potential cellular mechanism for the physiological integration of energy and fluid homeostasis. PMID:24790191