Search

Your search keyword '"Black K. L."' showing total 33 results
Start Over Author "Black K. L." Search Limiters Available in Library Collection
33 results on '"Black K. L."'

2. Age and sex impact plasma NFL and t-Tau trajectories in individuals with subjective memory complaints: a 3-year follow-up study

Author

Baldacci, F., Lista, S., Manca, M. L., Chiesa, P. A., Cavedo, E., Lemercier, P., Zetterberg, H., Blennow, K., Habert, M. -O., Potier, M. C., Dubois, B., Vergallo, A., Hampel, H., Bakardjian, H., Benali, H., Bertin, H., Bonheur, J., Boukadida, L., Boukerrou, N., Chiesa, P., Colliot, O., Dubois, M., Epelbaum, S., Gagliardi, G., Genthon, R., Houot, M., Kas, A., Lamari, F., Levy, M., Metzinger, C., Mochel, F., Nyasse, F., Poisson, C., Potier, M. -C., Revillon, M., Santos, A., Andrade, K. S., Sole, M., Surtee, M., de Schotten, M. T., Younsi, N., Afshar, M., Aguilar, L. F., Akman-Anderson, L., Arenas, J., Avila, J., Babiloni, C., Batrla, R., Benda, N., Black, K. L., Bokde, A. L. W., Bonuccelli, U., Broich, K., Cacciola, F., Caraci, F., Caruso, G., Castrillo, J., Ceravolo, R., Corbo, M., Corvol, J. -C., Claudio, A., Cummings, J. L., Depypere, H., Duggento, A., Emanuele, E., Escott-Price, V., Federoff, H., Ferretti, M. T., Fiandaca, M., Frank, R. A., Garaci, F., Geerts, H., Giacobini, E., Giorgi, F. S., Goetzl, E. J., Graziani, M., Haberkamp, M., Hanisch, B., Herholz, K., Hernandez, F., Imbimbo, B. P., Kapogiannis, D., Karran, E., Kiddle, S. J., Kim, S. H., Koronyo, Y., Koronyo-Hamaoui, M., Langevin, T., Lehericy, S., Llavero, F., Lorenceau, J., Lucia, A., Mango, D., Mapstone, M., Neri, C., Nistico, R., O'Bryant, S. E., Palermo, G., Perry, G., Ritchie, C., Rossi, S., Saidi, A., Santarnecchi, E., Schneider, L. S., Sporns, O., Toschi, N., Valenzuela, P. L., Vellas, B., Verdooner, S. R., Villain, N., Virecoulon Giudici, K., Watling, M., Welikovitch, L. A., Woodcock, J., Younesi, E., Zugaza, J. L., Alzheimer Precision Medicine [CHU Pitié-Salpétriêre] (GRC 21 AMP), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), University of Pisa - Università di Pisa, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Institut de la Mémoire et de la Maladie d'Alzheimer [Paris] (IM2A), Sorbonne Université (SU), Sahlgrenska Academy at University of Gothenburg [Göteborg], University College of London [London] (UCL), UK Dementia Research Institute (UK DRI), Laboratoire d'Imagerie Biomédicale (LIB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de médecine nucléaire [CHU Pitié-Salpétrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, BIOMARKER, 0301 basic medicine, Oncology, Aging, Neurology, [SDV]Life Sciences [q-bio], Disease, Neurodegenerative, Alzheimer's Disease, Medical and Health Sciences, lcsh:RC346-429, MESH: Cognitive Dysfunction, Alzheimer’s disease, Biomarkers, Mild cognitive impairment, Neurofilament light chain, Subjective memory complainers, Tau, 0302 clinical medicine, Neurofilament Proteins, Medicine and Health Sciences, BRAIN, MESH: Neurofilament Proteins, RISK, Settore FIS/07, NEURODEGENERATION, Cognition, ASSOCIATION, MESH: Follow-Up Studies, Alzheimer's disease, MESH: Amyloid beta-Peptides, MESH: tau Proteins, ALZHEIMERS-DISEASE, POSITIVITY, Neurological, Cohort, Biomarker (medicine), Female, medicine.medical_specialty, Cognitive Neuroscience, tau Proteins, Subjective, Affect (psychology), VALIDATION, lcsh:RC321-571, subjective memory complainers, mild cognitive impairment, biomarkers, s disease, 03 medical and health sciences, memory complainers, Clinical Research, Alzheimer Disease, Internal medicine, NEUROFILAMENT LIGHT-CHAIN, Acquired Cognitive Impairment, medicine, Humans, Cognitive Dysfunction, Vitamin B12, Allele, Alzheimer&#8217, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, lcsh:Neurology. Diseases of the nervous system, Amyloid beta-Peptides, MESH: Humans, business.industry, Research, Prevention, Neurosciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Alzheimer Precision Medicine Initiative, COGNITIVE IMPAIRMENT, MESH: Male, Brain Disorders, 030104 developmental biology, MESH: Biomarkers, Dementia, Neurology (clinical), business, INSIGHT-preAD study group, MESH: Female, MESH: Alzheimer Disease, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract

Background Plasma neurofilament light (NFL) and total Tau (t-Tau) proteins are candidate biomarkers for early stages of Alzheimer’s disease (AD). The impact of biological factors on their plasma concentrations in individuals with subjective memory complaints (SMC) has been poorly explored. We longitudinally investigate the effect of sex, age, APOE ε4 allele, comorbidities, brain amyloid-β (Aβ) burden, and cognitive scores on plasma NFL and t-Tau concentrations in cognitively healthy individuals with SMC, a condition associated with AD development. Methods Three hundred sixteen and 79 individuals, respectively, have baseline and three-time point assessments (at baseline, 1-year, and 3-year follow-up) of the two biomarkers. Plasma biomarkers were measured with an ultrasensitive assay in a mono-center cohort (INSIGHT-preAD study). Results We show an effect of age on plasma NFL, with women having a higher increase of plasma t-Tau concentrations compared to men, over time. The APOE ε4 allele does not affect the biomarker concentrations while plasma vitamin B12 deficiency is associated with higher plasma t-Tau concentrations. Both biomarkers are correlated and increase over time. Baseline NFL is related to the rate of Aβ deposition at 2-year follow-up in the left-posterior cingulate and the inferior parietal gyri. Baseline plasma NFL and the rate of change of plasma t-Tau are inversely associated with cognitive score. Conclusion We find that plasma NFL and t-Tau longitudinal trajectories are affected by age and female sex, respectively, in SMC individuals. Exploring the influence of biological variables on AD biomarkers is crucial for their clinical validation in blood.

Published
2020
Full Text
View/download PDF

3. β-Secretase1 biological markers for Alzheimer’s disease: state-of-art of validation and qualification

Author

Hampel, H., Lista, S., Vanmechelen, E., Zetterberg, H., Giorgi, F. S., Galgani, A., Blennow, K., Caraci, F., Das, B., Yan, R., Vergallo, A., Aguilar, L. F., Akman-Anderson, L., Arenas, J., Avila, J., Babiloni, C., Baldacci, F., Batrla, R., Benda, N., Black, K. L., Bokde, A. L. W., Bonuccelli, U., Broich, K., Cacciola, F., Caruso, G., Castrillo, J., Cavedo, E., Ceravolo, R., Chiesa, P. A., Corbo, M., Corvol, J. -C., Cuello, A. C., Cummings, J. L., Depypere, H., Dubois, B., Duggento, A., Emanuele, E., Escott-Price, V., Federoff, H., Ferretti, M. T., Fiandaca, M., Frank, R. A., Garaci, F., Geerts, H., Giacobini, E., Goetzl, E. J., Graziani, M., Haberkamp, M., Habert, M. -O., Hanisch, B., Herholz, K., Hernandez, F., Imbimbo, B. P., Kapogiannis, D., Karran, E., Kiddle, S. J., Kim, S. H., Koronyo, Y., Koronyo-Hamaoui, M., Langevin, T., Lehericy, S., Lemercier, P., Llavero, F., Lorenceau, J., Lucia, A., Mango, D., Mapstone, M., Neri, C., Nistico, R., O'Bryant, S. E., Palermo, G., Perry, G., Ritchie, C., Rossi, S., Saidi, A., Santarnecchi, E., Schneider, L. S., Sporns, O., Toschi, N., Valenzuela, P. L., Vellas, B., Verdooner, S. R., Villain, N., Virecoulon Giudici, K., Watling, M., Welikovitch, L. A., Woodcock, J., Younesi, E., and Zugaza, J. L.

Subjects
BIOMARKER, 0301 basic medicine, Aging, Neurology, Fluid biomarkers, Axonal damage, context of use, Review, Alzheimer’s disease, Amyloid-β pathway, BACE1, clinical trials, fluid biomarkers, neurodegeneration, Disease, Neurodegenerative, Bioinformatics, Medical and Health Sciences, lcsh:RC346-429, Clinical trials, 0302 clinical medicine, PP-BETA, Medicine and Health Sciences, Aspartic Acid Endopeptidases, Context of use, Neurodegeneration, Amyloid Precursor Protein Secretases, Amyloid beta-Peptides, Biomarkers, Humans, Alzheimer Disease, RISK, screening and diagnosis, CORRELATE, Settore FIS/07, AMYLOID-PRECURSOR PROTEIN, Alzheimer's disease, Detection, Neurological, State of art, Biomarker (medicine), EXPRESSION, medicine.medical_specialty, Cognitive Neuroscience, lcsh:RC321-571, 03 medical and health sciences, CEREBROSPINAL-FLUID, Clinical Research, BETA-SECRETASE BACE1, mental disorders, Acquired Cognitive Impairment, medicine, Adverse effect, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, lcsh:Neurology. Diseases of the nervous system, Mechanism (biology), business.industry, Prevention, Neurosciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Amyloid-beta pathway, medicine.disease, Brain Disorders, 4.1 Discovery and preclinical testing of markers and technologies, Clinical trial, Good Health and Well Being, 030104 developmental biology, Dementia, Alzheimer’s Precision Medicine Initiative, Neurology (clinical), TAU, business, 030217 neurology & neurosurgery, GENERATION
Abstract

β-Secretase1 (BACE1) protein concentrations and rates of enzyme activity, analyzed in human bodily fluids, are promising candidate biological markers for guidance in clinical trials investigating BACE1 inhibitors to halt or delay the dysregulation of the amyloid-β pathway in Alzheimer’s disease (AD). A robust body of evidence demonstrates an association between cerebrospinal fluid/blood BACE1 biomarkers and core pathophysiological mechanisms of AD, such as brain protein misfolding and aggregration, neurodegeneration, and synaptic dysfunction.In pharmacological trials, BACE1 candidate biomarkers may be applied to a wide set of contexts of use (CoU), including proof of mechanism, dose-finding, response and toxicity dose estimation. For clinical CoU, BACE1 biomarkers show good performance for prognosis and disease prediction.The roadmap toward validation and qualification of BACE1 biomarkers requires standardized pre-analytical and analytical protocols to reduce inter-site variance that may have contributed to inconsistent results.BACE1 biomarker-drug co-development programs, including biomarker-guided outcomes and endpoints, may support the identification of sub-populations with a higher probability to benefit from BACE1 inhibitors with a reduced risk of adverse effects, in line with the evolving precision medicine paradigm.

Published
2020
Full Text
View/download PDF

5. Differential default mode network trajectories in asymptomatic individuals at risk for Alzheimer's disease

Author

Chiesa P. A., Cavedo E., Vergallo A., Lista S., Potier M. -C., Habert M. -O., Dubois B., Thiebaut de Schotten M., Hampel H., Audrain C., Auffret A., Bakardjian H., Baldacci F., Batrancourt B., Benakki I., Benali H., Bertin H., Bertrand A., Boukadida L., Cacciamani F., Causse V., Cherif Touil S., Colliot O., Dalla Barba G., Depaulis M., Dos Santos A., Dubois M., Epelbaum S., Fontaine B., Francisque H., Gagliardi G., Genin A., Genthon R., Glasman P., Gombert F., Habert M. O., Hewa H., Houot M., Jungalee N., Kas A., Kilani M., La Corte V., Le Roy F., Lehericy S., Letondor C., Levy M., Lowrey M., Ly J., Makiese O., Masetti I., Mendes A., Metzinger C., Michon A., Mochel F., Nait Arab R., Nyasse F., Perrin C., Poirier F., Poisson C., Potier M. C., Ratovohery S., Revillon M., Rojkova K., Santos-Andrade K., Schindler R., Servera M. C., Seux L., Simon V., Skovronsky D., Uspenskaya O., Vlaincu M., Aguilar L. F., Babiloni C., Benda N., Black K. L., Bokde A. L. W., Bonuccelli U., Broich K., Cacciola F., Castrillo J., Ceravolo R., Corvol J. -C., Claudio Cuello A., Cummings J. L., Depypere H., Duggento A., Durrleman S., Escott-Price V., Federoff H., Teresa Ferretti M., Fiandaca M., Frank R. A., Garaci F., Geerts H., George N., Giorgi F. S., Graziani M., Haberkamp M., Herholz K., Karran E., Kim S. H., Koronyo Y., Koronyo-Hamaoui M., Lamari F., Langevin T., Lorenceau J., Mango D., Mapstone M., Neri C., Nistico R., O'Bryant S. E., Palermo G., Perry G., Ritchie C., Rossi S., Saidi A., Santarnecchi E., Schneider L. S., Sporns O., Toschi N., Verdooner S. R., Villain N., Welikovitch L. A., Woodcock J., Younesi E., Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Neuroradiologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Treat SVD, Laboratoire d'Imagerie Biomédicale (LIB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), sans affiliation, Institut de la Mémoire et de la Maladie d'Alzheimer [Paris] (IM2A), Sorbonne Université (SU), Algorithms, models and methods for images and signals of the human brain (ARAMIS), Sorbonne Université (SU)-Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Université de Bordeaux (UB), Service de neurologie 1 [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de médecine nucléaire [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre des Maladies Cognitives et Comportementales [Paris], Fraunhofer Center for Assistive Information and Communication Solutions [Porto] (Fraunhofer AICOS), Fraunhofer (Fraunhofer-Gesellschaft), Ariana Pharmaceuticals, McGill University = Université McGill [Montréal, Canada], Universidad Autonoma de Madrid (UAM), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], University of Pisa - Università di Pisa, Federal Institute of Drugs and Medical Devices [Bonn], Discipline of Psychiatry [Dublin], School of Medicine [Dublin], Trinity College Dublin-Trinity College Dublin, Universita degli Studi di Messina, University of Catania [Italy], University of Cambridge [UK] (CAM), Lou Ruvo Center for Brain Health [Las Vegas], Cleveland Clinic, Università degli Studi di Roma Tor Vergata [Roma], University of Pavia, Cardiff University, Universität Zürich [Zürich] = University of Zurich (UZH), University of California [Irvine] (UCI), University of California, Siemens Healthineers, Digital Services, Digital Technology and Innovation, In Silico Biosciences (ISB), Abdus Salam International Centre for Theoretical Physics [Trieste] (ICTP), University of California [San Francisco] (UCSF), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), University of Manchester [Manchester], National Institute on Aging [Bethesda, USA] (NIA), National Institutes of Health [Bethesda] (NIH), Abbvie Inc. [North Chicago], Institute of Psychiatry, Psychology & Neuroscience, King's College London, King‘s College London, University of Britsh Columbia [Vancouver], Cedars-Sinai Medical Center, Functional Neuromodulation, CIBER de Enfermedades Raras (CIBERER), Institut de la Vision, Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), European Brain Research Institute [Rome, Italy] (EBRI), Adaptation Biologique et Vieillissement = Biological Adaptation and Ageing (B2A), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institute for Aging and Alzheimer’s Disease Research [Fort Worth] (IAADR), University of North Texas Health Science Center [Fort Worth], University of Auckland [Auckland], University of Edinburgh, Università degli Studi di Siena = University of Siena (UNISI), Harvard Medical School [Boston] (HMS), Keck School of Medicine [Los Angeles], University of Southern California (USC), Indiana State University, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital [Boston]-Harvard Medical School [Boston] (HMS), NeuroVision Imaging, Fondation pour la Recherche sur Alzheimer, Center for Drug Evaluation and Research (CDER), European Society for Translational Medicine (EUSTM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service d'Explorations Fonctionnelles Neurologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de médecine nucléaire [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Fraunhofer AICOS [Porto], McGill University, Sapienza University [Rome], University of Zürich [Zürich] (UZH), Università degli Studi di Roma 'La Sapienza' [Rome], CHU Pitié-Salpêtrière [APHP], Service de neuro-radiologie [CHU Pitié-Salpêtrière], Università degli Studi di Siena (UNISI), Harvard Medical School [Boston] (HMS)-Massachusetts General Hospital [Boston], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de la Mémoire et de la Maladie d'Alzheimer [CHU Pitié-Salpétriêre] (IM2A), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Service de Médecine nucléaire [CHU Pitié-Salpétrière], Universidad Autónoma de Madrid (UAM), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Imagerie Biomédicale [Paris] (LIB), Sans affiliation, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Università degli Studi di Messina = University of Messina (UniMe), Università degli Studi di Pavia = University of Pavia (UNIPV), University of California [Irvine] (UC Irvine), University of California (UC), University of California [San Francisco] (UC San Francisco), University of British Columbia [Vancouver], Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Chiesa, P. A., Cavedo, E., Vergallo, A., Lista, S., Potier, M. -C., Habert, M. -O., Dubois, B., Thiebaut de Schotten, M., Hampel, H., Audrain, C., Auffret, A., Bakardjian, H., Baldacci, F., Batrancourt, B., Benakki, I., Benali, H., Bertin, H., Bertrand, A., Boukadida, L., Cacciamani, F., Causse, V., Cherif Touil, S., Colliot, O., Dalla Barba, G., Depaulis, M., Dos Santos, A., Dubois, M., Epelbaum, S., Fontaine, B., Francisque, H., Gagliardi, G., Genin, A., Genthon, R., Glasman, P., Gombert, F., Habert, M. O., Hewa, H., Houot, M., Jungalee, N., Kas, A., Kilani, M., La Corte, V., Le Roy, F., Lehericy, S., Letondor, C., Levy, M., Lowrey, M., Ly, J., Makiese, O., Masetti, I., Mendes, A., Metzinger, C., Michon, A., Mochel, F., Nait Arab, R., Nyasse, F., Perrin, C., Poirier, F., Poisson, C., Potier, M. C., Ratovohery, S., Revillon, M., Rojkova, K., Santos-Andrade, K., Schindler, R., Servera, M. C., Seux, L., Simon, V., Skovronsky, D., Uspenskaya, O., Vlaincu, M., Aguilar, L. F., Babiloni, C., Benda, N., Black, K. L., Bokde, A. L. W., Bonuccelli, U., Broich, K., Cacciola, F., Castrillo, J., Ceravolo, R., Corvol, J. -C., Claudio Cuello, A., Cummings, J. L., Depypere, H., Duggento, A., Durrleman, S., Escott-Price, V., Federoff, H., Teresa Ferretti, M., Fiandaca, M., Frank, R. A., Garaci, F., Geerts, H., George, N., Giorgi, F. S., Graziani, M., Haberkamp, M., Herholz, K., Karran, E., Kim, S. H., Koronyo, Y., Koronyo-Hamaoui, M., Lamari, F., Langevin, T., Lorenceau, J., Mango, D., Mapstone, M., Neri, C., Nistico, R., O'Bryant, S. E., Palermo, G., Perry, G., Ritchie, C., Rossi, S., Saidi, A., Santarnecchi, E., Schneider, L. S., Sporns, O., Toschi, N., Verdooner, S. R., Villain, N., Welikovitch, L. A., Woodcock, J., Younesi, E., and Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, Apolipoprotein E, Epidemiology, Brain activity and meditation, Precuneus, Disease, Neuropsychological Tests, Hippocampus, Cohort Studies, [SCCO]Cognitive science, 0302 clinical medicine, Medicine, Longitudinal Studies, Default mode network, ComputingMilieux_MISCELLANEOUS, Brain Mapping, Subjective memory complaints, Brain functional dynamic, Health Policy, Precision medicine, fMRI, Settore BIO/14, Brain, Brain functional dynamics, Alzheimer's disease, Magnetic Resonance Imaging, Temporal Lobe, Frontal Lobe, Psychiatry and Mental health, medicine.anatomical_structure, Cohort, Biomarker (medicine), Female, Amyloid, 03 medical and health sciences, Cellular and Molecular Neuroscience, Apolipoproteins E, Developmental Neuroscience, Alzheimer Disease, Humans, Aged, Resting state fMRI, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, 030104 developmental biology, Neurology (clinical), Geriatrics and Gerontology, business, Neuroscience, 030217 neurology & neurosurgery
Abstract

Introduction The longitudinal trajectories of functional brain dynamics and the impact of genetic risk factors in individuals at risk for Alzheimer's disease are poorly understood. Methods In a large-scale monocentric cohort of 224 amyloid stratified individuals at risk for Alzheimer's disease, default mode network (DMN) resting state functional connectivity (FC) was investigated between two serial time points across 2 years. Results Widespread DMN FC changes were shown in frontal and posterior areas, as well as in the right hippocampus. There were no cross-sectional differences, however, apolipoprotein E e4 (APOE e4) carriers demonstrated slower increase in FC in frontal lobes. There was no impact of individual brain amyloid load status. Discussion For the first time, we demonstrated that the pleiotropic biological effect of the APOE e4 allele impacts the dynamic trajectory of the DMN during aging. Dynamic functional biomarkers may become useful surrogate outcomes for the development of preclinical targeted therapeutic interventions.

Published
2019
Full Text
View/download PDF

7. Brain Aβ load association and sexual dimorphism of plasma BACE1 concentrations in cognitively normal individuals at risk for AD

Author

Vergallo, A., Houot, M., Cavedo, E., Lemercier, P., Vanmechelen, E., De Vos, A., Habert, M. -O., Potier, M. -C., Dubois, B., Lista, S., Hampel, H., Bakardjian, H., Benali, H., Bertin, H., Bonheur, J., Boukadida, L., Boukerrou, N., Chiesa, P., Colliot, O., Dubois, M., Epelbaum, S., Gagliardi, G., Genthon, R., Habert, M. O., Kas, A., Lamari, F., Levy, M., Metzinger, C., Mochel, F., Nyasse, F., Poisson, C., Potier, M. C., Revillon, M., Santos, A., Andrade, K. S., Sole, M., Surtee, M., Thiebaud de Schotten, M., Younsi, N., Afshar, M., Flores Aguilar, L., Akman-Anderson, L., Arenas, J., Avila, J., Babiloni, C., Baldacci, F., Batrla, R., Benda, N., Black, K. L., Bokde, A. L. W., Bonuccelli, U., Broich, K., Cacciola, F., Caraci, F., Castrillo, J., Ceravolo, R., Chiesa, P. A., Corvol, J. -C., Claudio Cuello, A., Cummings, J. L., Depypere, H., Duggento, A., Emanuele, E., Escott-Price, V., Federoff, H., Teresa Ferretti, M., Fiandaca, M., Frank, R. A., Garaci, F., Geerts, H., Giorgi, F. S., Goetzl, E. J., Graziani, M., Haberkamp, M., Marie-Odile, H., Herholz, K., Hernandez, F., Kapogiannis, D., Karran, E., Kiddle, S. J., Kim, S. H., Koronyo, Y., Koronyo-Hamaoui, M., Langevin, T., Lehericy, S., Lucia, A., Lorenceau, J., Mango, D., Mapstone, M., Neri, C., Nistico, R., O'Bryant, S. E., Palermo, G., Perry, G., Ritchie, C., Rossi, S., Saidi, A., Santarnecchi, E., Schneider, L. S., Sporns, O., Toschi, N., Verdooner, S. R., Villain, N., Welikovitch, L. A., Woodcock, J., Younesi, E., Alzheimer Precision Medicine [CHU Pitié-Salpétriêre] (GRC 21 AMP), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre d'investigation clinique Neurosciences [CHU Pitié Salpêtrière] (CIC Neurosciences), Laboratoire d'Imagerie Biomédicale (LIB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Service de médecine nucléaire [CHU Pitié-Salpétrière]

Subjects
Male, 0301 basic medicine, Apolipoprotein E, Epidemiology, [SDV]Life Sciences [q-bio], PROGRESSION, Disease, Cognition, 0302 clinical medicine, Amyloid precursor protein, Medicine and Health Sciences, Aspartic Acid Endopeptidases, medicine.diagnostic_test, biology, Health Policy, Settore BIO/14, Brain, Alzheimer's disease, Healthy Volunteers, 3. Good health, GENOTYPE, ALZHEIMERS-DISEASE, Psychiatry and Mental health, Positron emission tomography, Cohort, Biomarker (medicine), Female, EXPRESSION, medicine.medical_specialty, BIOMARKERS, Standardized uptake value, 03 medical and health sciences, Cellular and Molecular Neuroscience, Sexual dimorphism, Apolipoproteins E, Sex Factors, Developmental Neuroscience, Alzheimer Disease, Internal medicine, mental disorders, medicine, Humans, BACE1 biomarkers, Aged, Plasma BACE1, DECLINE, Amyloid beta-Peptides, business.industry, 030104 developmental biology, Endocrinology, Positron-Emission Tomography, Disease modifying, biology.protein, Neurology (clinical), Amyloid Precursor Protein Secretases, Geriatrics and Gerontology, business, Biomarkers, 030217 neurology & neurosurgery
Abstract

Introduction: Successful development of effective beta-site amyloid precursor protein cleaving enzyme 1 (BACE1)-targeted therapies for early stages of Alzheimer's disease requires biomarker-guided intervention strategies. Methods: We investigated whether key biological factors such as sex, apolipoprotein E (APOE epsilon 4) allele, and age affect longitudinal plasma BACE1 concentrations in a large monocenter cohort of individuals at risk for Alzheimer's disease. We explored the relationship between plasma BACE1 concentrations and levels of brain amyloid-beta (A beta) deposition, using positron emission tomography global standard uptake value ratios. Results: Baseline and longitudinal mean concentrations of plasma BACE1 were significantly higher in women than men. We also found a positive significant impact of plasma BACE1 on baseline A beta-positron emission tomography global standard uptake value ratios. Discussion: Our results suggest a sexual dimorphism in BACE1-related upstream mechanisms of brain A beta production and deposition. We argue that plasma BACE1 should be considered in further biomarker validation and qualification studies as well as in BACE1 clinical trials. (C) 2019 The Authors. Published by Elsevier Inc. on behalf of the Alzheimer's Association.

Published
2019
Full Text
View/download PDF

10. IMMUNOTHERAPY

Author

Hickey, M. J., primary, Malone, C. K., additional, Erickson, K. L., additional, Gerschenson, L. E., additional, Lin, A. H., additional, Inagaki, A., additional, Hiraoka, K., additional, Kasahara, N., additional, Mueller, B., additional, Kruse, C. A., additional, Kong, S., additional, Tyler, B., additional, Zhou, J., additional, Carter, B. S., additional, Brem, H., additional, Junghans, R. P., additional, Sampath, P., additional, Lai, R. K., additional, Recht, L. D., additional, Reardon, D. A., additional, Paleologos, N., additional, Groves, M., additional, Rosenfeld, M. R., additional, Davis, T., additional, Green, J., additional, Heimberger, A., additional, Sampson, J., additional, Hashimoto, N., additional, Tsuboi, A., additional, Chiba, Y., additional, Kijima, N., additional, Oka, Y., additional, Kinoshita, M., additional, Kagawa, N., additional, Fujimoto, Y., additional, Sugiyama, H., additional, Yoshimine, T., additional, Birks, S. M., additional, Burnet, M., additional, Pilkington, G. J., additional, Yu, J. S., additional, Wheeler, C. J., additional, Rudnick, J., additional, Mazer, M., additional, Wang, H. Q., additional, Nuno, M. A., additional, Richardson, J. E., additional, Fan, X., additional, Ji, J., additional, Chu, R. M., additional, Bender, J. G., additional, Hawkins, E. W., additional, Black, K. L., additional, Phuphanich, S., additional, Pollack, I. F., additional, Jakacki, R. I., additional, Butterfield, L. H., additional, Okada, H., additional, Hunt, M. A., additional, Pluhar, G. E., additional, Andersen, B. M., additional, Gallardo, J. L., additional, Seiler, C. O., additional, SantaCruz, K. S., additional, Ohlfest, J. R., additional, Bauer, D. F., additional, Lamb, L. S., additional, Harmon, D. K., additional, Zheng, X., additional, Romeo, A. K., additional, Gillespie, G. Y., additional, Parker, J. N., additional, Markert, J. M., additional, Jacobs, V. L., additional, Landry, R. P., additional, De Leo, J. A., additional, Bromberg, J. E., additional, Doorduijn, J., additional, Baars, J. W., additional, van Imhoff, G. W., additional, Enting, R., additional, van den Bent, M. J., additional, Murphy, K. A., additional, Bedi, J., additional, Epstein, A., additional, Olin, M., additional, Andersen, B., additional, Swier, L., additional, Ohlfest, J., additional, Litterman, A. J., additional, Zellmer, D. M., additional, Chiocca, E. A., additional, Aguilar, L. K., additional, Aguilar-Cordova, E., additional, Manzanera, A. G., additional, Harney, K. R., additional, Portnow, J., additional, Badie, B., additional, Lesniak, M., additional, Bell, S., additional, Ray-Chaudhuri, A., additional, Kaur, B., additional, Hardcastle, J., additional, Cavaliere, R., additional, McGregor, J., additional, Lo, S., additional, Chakarvarti, A., additional, Grecula, J., additional, Newton, H., additional, Trask, T. W., additional, Baskin, D. S., additional, New, P. Z., additional, Zeng, J., additional, See, A. P., additional, Phallen, J., additional, Belcaid, Z., additional, Durham, N., additional, Meyer, C., additional, Albesiano, E., additional, Pradilla, G., additional, Ford, E., additional, Hammers, H., additional, Tran, P. T., additional, Pardoll, D., additional, Drake, C. G., additional, Lim, M., additional, Ghazi, A., additional, Ashoori, A., additional, Hanley, P., additional, Salsman, V., additional, Schaffer, D. R., additional, Grada, Z., additional, Kew, Y., additional, Powell, S. Z., additional, Grossman, R., additional, Scheurer, M. E., additional, Leen, A. M., additional, Rooney, C. M., additional, Bollard, C. M., additional, Heslop, H. E., additional, Gottschalk, S., additional, Ahmed, N., additional, Hu, J., additional, Patil, C., additional, Nuno, M., additional, Wheeler, C., additional, Chu, R., additional, Black, K., additional, Yu, J., additional, Marabelle, A., additional, Kohrt, H., additional, Brody, J., additional, Luong, R., additional, Tse, V., additional, Levy, R., additional, Li, Y. M., additional, Jun, H., additional, Shahryar, M., additional, Daniel, V. A., additional, Walter, H. A., additional, Thaipisuttikul, I., additional, Avila, E., additional, Mitchell, D. A., additional, Archer, G. E., additional, Friedman, H. S., additional, Herndon, J. E., additional, Bigner, D. D., additional, Sampson, J. H., additional, Johnson, L. A., additional, Nair, S. K., additional, Schmittling, R., additional, Reap, E., additional, Knisely, J. P., additional, Kluger, H., additional, Flanigan, J., additional, Sznol, M., additional, Yu, J. B., additional, Chiang, V. L., additional, Prins, R. M., additional, Kim, W., additional, Soto, H., additional, Lisiero, D. N., additional, and Liau, L. M., additional

Published
2011
Full Text
View/download PDF

13. Immunotherapy

Author

Fujita, M., primary, Kohanbash, G., additional, McDonald, H. A., additional, Delamarre, L., additional, Decker, S. A., additional, Ohlfest, J. R., additional, Okada, H., additional, Kalinski, P., additional, Ueda, R., additional, Hoji, A., additional, Donegan, T. E., additional, Mintz, A. H., additional, Engh, J. A., additional, Bartlett, D. L., additional, Brown, C. K., additional, Zeh, H., additional, Holtzman, M. P., additional, Reinhart, T. A., additional, Whiteside, T. L., additional, Butterfield, L. H., additional, Hamilton, R. L., additional, Potter, D. M., additional, Pollack, I. F., additional, Salazar, A. M., additional, Lieberman, F. S., additional, Olin, M. R., additional, Andersen, B. M., additional, Grogan, P. T., additional, Hunt, M., additional, Popescu, F. E., additional, Xiong, Z. L., additional, Seiler, C., additional, Forster, C. L., additional, SantaCruz, K. S., additional, Chen, W., additional, Blazar, B. R., additional, Hu, J., additional, Wheeler, C. J., additional, Phuphanich, S., additional, Rudnick, J., additional, Nuno, M., additional, Serrano, N., additional, Dantis, J., additional, Richardson, J., additional, Mazer, M., additional, Wang, H. Q., additional, Chu, R., additional, Black, K. L., additional, Yu, J., additional, Li, Y. M., additional, Vallera, D. A., additional, Hall, W. A., additional, Rudnick, J. D., additional, Chu, R. M., additional, Wang, H., additional, Yu, J. S., additional, Yang, I., additional, Han, S., additional, Tihan, T., additional, Wrensch, M., additional, Parsa, A. T., additional, Hunt, M. A., additional, Gallardo, J. L., additional, Pluhar, G. E., additional, Brown, C. E., additional, Starr, R., additional, Martinez, C., additional, Bading, J., additional, Ressler, J. A., additional, Badie, B., additional, Jensen, M. C., additional, Glick, R. P., additional, Ksendzovsky, A., additional, Zengou, R., additional, Polak, P., additional, Simonini, V., additional, Lichtor, T., additional, Feinstein, D., additional, Chow, K. K., additional, Ahmed, N., additional, Salsman, V. S., additional, Kew, Y., additional, Powell, S., additional, Grossman, R., additional, Heslop, H. E., additional, Gottschalk, S., additional, Barnett, F. H., additional, Marchetti, V., additional, Wang, M., additional, Johnson, A., additional, Scheppke, L., additional, Jacobson, R., additional, Nemerow, G., additional, Friedlander, M., additional, Salsman, V., additional, Leen, A. M., additional, Bollard, C. M., additional, Rooney, C., additional, New, P. Z., additional, Salvoldo, B., additional, and Heslop, H., additional

Published
2010
Full Text
View/download PDF

14. The limits of treatment of malignant gliomas

Author

Black, K L and Ciacci, J R

Subjects
Adult, Brain Neoplasms, Chemotherapy, Adjuvant, Brachytherapy, Humans, Glioma, Prognosis, Combined Modality Therapy, Research Article, Aged
Published
1993

16. Brain tumors

Author

Black, K. L., Mazziotta, J. C., and Becker, D. P.

Subjects
Brain Chemistry, Radiography, Brain Neoplasms, Humans, Receptors, GABA-A, Magnetic Resonance Imaging, Research Article, Tomography, Emission-Computed
Abstract

Recent advances in experimental tumor biology are being applied to critical clinical problems of primary brain tumors. The expression of peripheral benzodiazepine receptors, which are sparse in normal brain, is increased as much as 20-fold in brain tumors. Experimental studies show promise in using labeled ligands to these receptors to identify the outer margins of malignant brain tumors. Whereas positron emission tomography has improved the dynamic understanding of tumors, the labeled selective tumor receptors with positron emitters will enhance the ability to specifically diagnose and greatly aid in the pretreatment planning for tumors. Modulation of these receptors will also affect tumor growth and metabolism. Novel methods to deliver antitumor agents to the brain and new approaches using biologic response modifiers also hold promise to further improve the management of brain tumors.

Published
1991

19. Association of cerebrospinal fluid α-synuclein with total and phospho-tau181 protein concentrations and brain amyloid load in cognitively normal subjective memory complainers stratified by Alzheimer's disease biomarkers

Author

Vergallo, A, Bun, R, Toschi, N, Baldacci, F, Zetterberg, H, Blennow, K, Cavedo, E, Lamari, F, Habert, M, Dubois, B, Floris, R, Garaci, F, Lista, S, Hampel, H, Audrain, C, Auffret, A, Bakardjian, H, Batrancourt, B, Benakki, I, Benali, H, Bertin, H, Bertrand, A, Boukadida, L, Cacciamani, F, Causse, V, Cherif Touil, S, Chiesa, Pa, Colliot, O, Dalla Barba, G, Depaulis, M, Dos Santos, A, Dubois, M, Epelbaum, S, Fontaine, B, Francisque, H, Gagliardi, G, Genin, A, Genthon, R, Glasman, P, Gombert, F, Habert, Mo, Hewa, H, Houot, M, Jungalee, N, Kas, A, Kilani, M, La Corte, V, Le Roy, F, Lehericy, S, Letondor, C, Levy, M, Lowrey, M, Ly, J, Makiese, O, Masetti, I, Mendes, A, Metzinger, C, Michon, A, Mochel, F, Nait Arab, R, Nyasse, F, Perrin, C, Poirier, F, Poisson, C, Potier, Mc, Ratovohery, S, Revillon, M, Rojkova, K, Santos-Andrade, K, Schindler, R, Servera, Mc, Seux, L, Simon, V, Skovronsky, D, Thiebaut, M, Uspenskaya, O, Vlaincu, M, Aguilar, Lf, Babiloni, C, Benda, N, Black, Kl, Bokde, Alw, Bonuccelli, U, Broich, K, Bun, Rs, Cacciola, F, Castrillo, J, Ceravolo, R, Coman, Cm, Corvol, Jc, Cuello, Ac, Cummings, Jl, Depypere, H, Duggento, A, Durrleman, S, Escott-Price, V, Federoff, H, Ferretti, Mt, Fiandaca, M, Frank, Ra, George, N, Giorgi, Fs, Graziani, M, Haberkamp, M, Herholz, K, Karran, E, Kim, Sh, Koronyo, Y, Koronyo-Hamaoui, M, Langevin, T, Lehéricy, S, Lorenceau, J, Mapstone, M, Neri, C, Nisticò, R, Nyasse-Messene, F, O'Bryant, Se, Perry, G, Ritchie, C, Rossi, S, Santarnecchi, E, Schneider, Ls, Sporns, O, Verdooner, Sr, Villain, N, Welikovitch, L, Woodcock, J, Younesi, E, Vergallo, A., Bun, R. -S., Toschi, N., Baldacci, F., Zetterberg, H., Blennow, K., Cavedo, E., Lamari, F., Habert, M. -O., Dubois, B., Floris, R., Garaci, F., Lista, S., Hampel, H., Audrain, C., Auffret, A., Bakardjian, H., Batrancourt, B., Benakki, I., Benali, H., Bertin, H., Bertrand, A., Boukadida, L., Cacciamani, F., Causse, V., Cherif Touil, S., Chiesa, P. A., Colliot, O., Dalla Barba, G., Depaulis, M., Dos Santos, A., Dubois, M., Epelbaum, S., Fontaine, B., Francisque, H., Gagliardi, G., Genin, A., Genthon, R., Glasman, P., Gombert, F., Habert, M. O., Hewa, H., Houot, M., Jungalee, N., Kas, A., Kilani, M., La Corte, V., Le Roy, F., Lehericy, S., Letondor, C., Levy, M., Lowrey, M., Ly, J., Makiese, O., Masetti, I., Mendes, A., Metzinger, C., Michon, A., Mochel, F., Nait Arab, R., Nyasse, F., Perrin, C., Poirier, F., Poisson, C., Potier, M. C., Ratovohery, S., Revillon, M., Rojkova, K., Santos-Andrade, K., Schindler, R., Servera, M. C., Seux, L., Simon, V., Skovronsky, D., Thiebaut, M., Uspenskaya, O., Vlaincu, M., Aguilar, L. F., Babiloni, C., Benda, N., Black, K. L., Bokde, A. L. W., Bonuccelli, U., Broich, K., Bun, R. S., Cacciola, F., Castrillo, J., Ceravolo, R., Coman, C. M., Corvol, J. C., Cuello, A. C., Cummings, J. L., Depypere, H., Duggento, A., Durrleman, S., Escott-Price, V., Federoff, H., Ferretti, M. T., Fiandaca, M., Frank, R. A., George, N., Giorgi, F. S., Graziani, M., Haberkamp, M., Herholz, K., Karran, E., Kim, S. H., Koronyo, Y., Koronyo-Hamaoui, M., Langevin, T., Lorenceau, J., Mapstone, M., Neri, C., Nistico, R., Nyasse-Messene, F., O'Bryant, S. E., Perry, G., Ritchie, C., Rossi, S., Santarnecchi, E., Schneider, L. S., Sporns, O., Verdooner, S. R., Villain, N., Welikovitch, L., Woodcock, J., and Younesi, E.

Subjects
0301 basic medicine, Epidemiology, Alzheimer's disease, Amyloid PET, Cerebrospinal fluid, Monocentric, Preclinical, Subjective memory complainers, SUVR, Synergistic, Tau protein, α-Synuclein, chemistry.chemical_compound, 0302 clinical medicine, biology, Health Policy, Settore FIS/07, Settore BIO/14, Pathophysiology, Psychiatry and Mental health, medicine.symptom, medicine.medical_specialty, Amyloid, Asymptomatic, 03 medical and health sciences, Cellular and Molecular Neuroscience, Developmental Neuroscience, Neurology (clinical), Geriatrics and Gerontology, Psychiatry and Mental Health, Internal medicine, mental disorders, medicine, Dementia, Alpha-synuclein, business.industry, Alzheimer's disease biomarkers, medicine.disease, 030104 developmental biology, Endocrinology, nervous system, chemistry, Subjective memory complainer, biology.protein, business, 030217 neurology & neurosurgery
Abstract

Introduction Several neurodegenerative brain proteinopathies, including Alzheimer's disease (AD), are associated with cerebral deposition of insoluble aggregates of α-synuclein. Previous studies reported a trend toward increased cerebrospinal fluid (CSF) α-synuclein (α-syn) concentrations in AD compared with other neurodegenerative diseases and healthy controls. Methods The pathophysiological role of CSF α-syn in asymptomatic subjects at risk of AD has not been explored. We performed a large-scale cross-sectional observational monocentric study of preclinical individuals at risk for AD (INSIGHT-preAD). Results We found a positive association between CSF α-syn concentrations and brain β-amyloid deposition measures as mean cortical standard uptake value ratios. We demonstrate positive correlations between CSF α-syn and both CSF t-tau and p-tau 181 concentrations. Discussion Animal models presented evidence, indicating that α-syn may synergistically and directly induce fibrillization of both tau and β-amyloid. Our data indicate an association of CSF α-syn with AD-related pathophysiological mechanisms, during the preclinical phase of the disease.

Published
2018

20. Overexpression of alpha4 chain-containing laminins in human glial tumors identified by gene microarray analysis.

Author

Ljubimova JY, Lakhter AJ, Loksh A, Yong WH, Riedinger MS, Miner JH, Sorokin LM, Ljubimov AV, and Black KL

Subjects
Adult, Aged, Brain metabolism, Brain pathology, Brain Neoplasms pathology, Female, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Glioblastoma genetics, Glioblastoma pathology, Glioma pathology, Humans, Male, Middle Aged, Oligonucleotide Array Sequence Analysis, Protein Isoforms genetics, RNA, Neoplasm genetics, RNA, Neoplasm metabolism, Reverse Transcriptase Polymerase Chain Reaction, Brain Neoplasms genetics, Glioma genetics, Laminin genetics
Abstract

Differential gene expression in tumors often involves growth factors and extracellular matrix/basement membrane components. Here, 11,000- gene microarray was used to identify gene expression profiles in brain tumors including high-grade gliomas [glioblastoma multiforme (GBM) and anaplastic astrocytoma], low-grade astrocytomas, or benign extra-axial brain tumors (meningioma) in comparison with normal brain tissue. Histologically normal tissues adjacent to GBMs were also studied. All GBMs studied overexpressed 14 known genes compared with normal human brain tissue. Overexpressed genes belonged to two broad groups: (a) growth factor-related genes; and (b) structural/extracellular matrix-related genes. For most of these 14 genes, expression levels were lower in low-grade astrocytoma than in GBM and were barely detectable in normal brain. Despite normal-appearing histology, gene expression patterns of tissues immediately adjacent to GBM were similar to those of their respective primary GBMs. Two genes were consistently up-regulated in both high-grade and low-grade gliomas, as well as in histologically normal tissues adjacent to GBMs. These genes coded for the epidermal growth factor receptor (previously reported to be overexpressed in gliomas) and for the alpha4 chain of laminin, a major blood vessel basement membrane component. Changes in expression of this laminin chain have not been previously associated with malignant tumors. Overexpression of laminin alpha4 chain in GBM and astrocytoma grade II by gene microarray analysis was confirmed by semiquantitive reverse transcription-PCR and immunohistochemistry. Importantly, an alpha4 chain-containing laminin isoform, laminin-8 (alpha4beta1gamma1), was expressed mainly in blood vessel walls of GBMs and histologically normal tissues adjacent to GBMs, whereas another alpha4 chain-containing laminin isoform, laminin-9 (alpha4beta2gamma1), was expressed mainly in blood vessel walls of low-grade tumors and normal brain. GBMs that overexpressed laminin-8 had a shorter mean time to tumor recurrence (4.3 months) than GBMs with overexpression of laminin-9 (9.7 months, P = 0.0007). Up-regulation of alpha4 chain-containing laminins could be important for the development of glioma-induced neovascularization and glial tumor progression. Overexpression of laminin-8 may be predictive of glioma recurrence.

Published
2001

21. A herpes simplex virus type 1 mutant deleted for gamma34.5 and LAT kills glioma cells in vitro and is inhibited for in vivo reactivation.

Author

Samoto K, Perng GC, Ehtesham M, Liu Y, Wechsler SL, Nesburn AB, Black KL, and Yu JS

Subjects
Animals, Antiviral Agents pharmacology, Brain Neoplasms pathology, Carrier Proteins metabolism, Cell Line, Cell Survival, Drug Resistance, Female, Ganciclovir pharmacology, Genetic Therapy, Glioma pathology, Green Fluorescent Proteins, Luminescent Proteins metabolism, Mice, Mutation, Phosphoproteins metabolism, Rabbits, Viral Proteins metabolism, Virulence genetics, Virus Latency genetics, Virus Replication genetics, Adaptor Proteins, Signal Transducing, Brain Neoplasms therapy, Carrier Proteins genetics, Gene Deletion, Genes, Viral, Glioma therapy, Herpesvirus 1, Human genetics, Membrane Proteins, Phosphoproteins genetics, Viral Proteins genetics, Virus Activation genetics
Abstract

To create an oncolytic herpes simplex virus type 1 (HSV-1) that is inhibited for reactivation, we constructed a novel herpes recombinant virus with deletions in the gamma34.5 and LAT genes. The LAT gene was replaced by the gene for green fluorescent protein, thereby allowing viral infection to be followed. This virus, designated DM33, is effective in killing primary and established human glioma cell lines in culture. DM33 is considerably less virulent following intracerebral inoculation of HSV-susceptible BALB/c mice than the wild-type HSV-1 strain McKrae. The safety of this virus is further supported by the retention of its sensitivity to ganciclovir and its relatively limited toxicity against cultured human neuronal cells, astrocytes, and endothelial cells. The ability of DM33 to spontaneously reactivate was tested in a rabbit ocular infection model that accurately depicts human herpes infection and reactivation. Following ocular infection of rabbits, spontaneous reactivation was detected in 83% (15/18) of the eyes infected with wild-type McKrae. In contrast, none of the eyes infected with DM33 had detectable reactivation. The efficacy of this virus in cultured human glioma cell lines, its safety, confirmed by its inability to reactivate, and its attenuated neurovirulence make DM33 a promising oncolytic agent for tumor therapy.

Published
2001
Full Text
View/download PDF

22. Vaccination of malignant glioma patients with peptide-pulsed dendritic cells elicits systemic cytotoxicity and intracranial T-cell infiltration.

Author

Yu JS, Wheeler CJ, Zeltzer PM, Ying H, Finger DN, Lee PK, Yong WH, Incardona F, Thompson RC, Riedinger MS, Zhang W, Prins RM, and Black KL

Subjects
Adult, Aged, Antigens, Neoplasm immunology, Astrocytoma therapy, Brain Neoplasms therapy, Cancer Vaccines adverse effects, Cancer Vaccines therapeutic use, Cytotoxicity, Immunologic, Dendritic Cells cytology, Dendritic Cells drug effects, Female, Glioblastoma therapy, Humans, Immunologic Memory immunology, Immunotherapy, Adoptive, Male, Middle Aged, T-Lymphocytes, Helper-Inducer immunology, Astrocytoma immunology, Brain Neoplasms immunology, Cancer Vaccines immunology, Dendritic Cells immunology, Glioblastoma immunology, Immunotherapy, Active, Lymphocytes, Tumor-Infiltrating immunology, T-Lymphocytes, Cytotoxic immunology
Abstract

In this Phase I trial, patients' peripheral blood dendritic cells were pulsed with peptides eluted from the surface of autologous glioma cells. Three biweekly intradermal vaccinations of peptide-pulsed dendritic cells were administered to seven patients with glioblastoma multiforme and two patients with anaplastic astrocytoma. Dendritic cell vaccination elicited systemic cytotoxicity in four of seven tested patients. Robust intratumoral cytotoxic and memory T-cell infiltration was detected in two of four patients who underwent reoperation after vaccination. This Phase I study demonstrated the feasibility, safety, and bioactivity of an autologous peptide-pulsed dendritic cell vaccine for patients with malignant glioma.

Published
2001

23. Treatment of a patient by vaccination with autologous dendritic cells pulsed with allogeneic major histocompatibility complex class I-matched tumor peptides. Case Report.

Author

Liau LM, Black KL, Martin NA, Sykes SN, Bronstein JM, Jouben-Steele L, Mischel PS, Belldegrun A, and Cloughesy TF

Subjects
Antigens, Neoplasm immunology, Brain Neoplasms immunology, Brain Neoplasms pathology, Cancer Vaccines administration & dosage, Cancer Vaccines immunology, Dendritic Cells transplantation, Fatal Outcome, Female, Glioblastoma immunology, Glioblastoma pathology, Humans, Magnetic Resonance Imaging, Middle Aged, Brain Neoplasms therapy, Dendritic Cells immunology, Glioblastoma therapy, Histocompatibility Antigens Class I immunology, Immunotherapy, Adoptive methods
Abstract

Dendritic cells (DCs) are antigen-presenting cells that play a central role in the initiation and modulation of antitumor immune responses. In this pilot study, we investigated the ability of autologous DCs pulsed ex vivo with allogeneic major histocompatibility complex class I-matched glioblastoma peptides to stimulate host antitumor immune responses when injected as a vaccine. A patient with recurrent brainstem glioblastoma multiforme (GBM) received a series of three intradermal immunizations of antigen-pulsed DCs on an outpatient basis following surgical debulking of her posterior fossa tumor. Dendritic cell vaccination was well tolerated, and no clinical signs of autoimmunity or experimental allergic encephalomyelitis were detected. She developed a measurable cellular immune response against the allogeneic glioblastoma peptides used in her vaccine preparation, as demonstrated by in vitro T-cell proliferation assays. In addition, increased T-cell infiltration was noted within the intracranial tumor site in the biopsy sample obtained following DC vaccination. An objective clinical response, however, was not evident, and this patient eventually died 21 months after her disease was diagnosed. To our knowledge, this is the first patient with brain cancer ever to be treated with DC-based immunotherapy. This case illustrates that vaccination with DCs pulsed with acid-eluted glioblastoma peptides is feasible and can induce systemic antigen-specific immunity in a patient with recurrent GBM. Additional studies are necessary to determine the optimum DC doses and antigen loading conditions that may translate into clinical effectiveness and survival benefit for patients with brain tumors. Phase I trials for malignant glioma are currently underway.

Published
2000
Full Text
View/download PDF

24. Novel human malignancy-associated gene (MAG) expressed in various tumors and in some tumor preexisting conditions.

Author

Ljubimova JY, Wilson SE, Petrovic LM, Ehrenman K, Ljubimov AV, Demetriou AA, Geller SA, and Black KL

Subjects
Adult, Amino Acid Sequence, Base Sequence, Brain metabolism, Brain Neoplasms genetics, Brain Neoplasms pathology, Carcinoma, Hepatocellular genetics, Carcinoma, Hepatocellular pathology, Embryo, Mammalian, Female, Glioblastoma genetics, Glioblastoma pathology, Hepatitis B genetics, Hepatitis B pathology, Hepatitis C genetics, Hepatitis C pathology, Humans, Liver metabolism, Liver Neoplasms genetics, Liver Neoplasms pathology, Male, Molecular Sequence Data, Neoplasm Proteins chemistry, Neoplasms pathology, Polymerase Chain Reaction, Precancerous Conditions pathology, Pregnancy, Reference Values, Retrospective Studies, Risk Factors, Transcription, Genetic, Tumor Cells, Cultured, Neoplasm Proteins genetics, Neoplasms genetics, Precancerous Conditions genetics
Abstract

We have identified a novel human malignancy-associated gene (MAG) expressed in various malignant tumors including glioblastomas and hepatocellular carcinomas (HCCs) and in tumor preexisting conditions such as hepatitis C virus- and hepatitis B virus-induced liver cirrhosis. The expression of MAG was characterized using reverse transcription-PCR (RT-PCR), rapid amplification of cDNA ends PCR, RNA dot blotting, RNase protection assay, and Northern blot analysis. Rapid amplification of cDNA ends PCR yielded a 536-bp MAG fragment in HCC, macroregenerative liver nodules with dysplasia, and liver cirrhosis but not in normal liver or placenta. By RT-PCR, MAG expression was not found in 12 different normal tissues but found in 46 of 51 (90%) premalignant and malignant tissues of various sites. Embryonic liver and brain were positive for MAG expression together with tumors from the same organs, but the corresponding normal adult tissues were negative. By RNase protection assay, MAG mRNA was expressed in the HepG2 liver tumor cell line and in an ovarian carcinoma but not in normal liver. The estimated transcript size from Northern blot analysis was 8.8 kb. This novel gene may play a role in the progression of premalignant conditions and in the development of HCC and other cancers.

Published
1998

25. Cyclic GMP-specific phosphodiesterase inhibition and intracarotid bradykinin infusion enhances permeability into brain tumors.

Author

Sugita M and Black KL

Subjects
3',5'-Cyclic-GMP Phosphodiesterases metabolism, Animals, Biological Transport drug effects, Brain Neoplasms pathology, Drug Synergism, Female, Glioma pathology, Rats, Rats, Wistar, 3',5'-Cyclic-GMP Phosphodiesterases antagonists & inhibitors, Bradykinin administration & dosage, Brain Neoplasms metabolism, Cell Membrane Permeability drug effects, Glioma metabolism, Phosphodiesterase Inhibitors administration & dosage, Purinones administration & dosage
Abstract

Intracarotid infusion of bradykinin selectively increases the delivery of compounds into brain tumors. This study sought to determine the role of cyclic GMP in increased permeability across the blood-tumor barrier (BTB) after infusion of bradykinin. In permeability studies, 186 Wistar rats with RG2 gliomas and C6 gliomas were used. Transport across the BTB was quantified by autoradiography and reported as a unidirectional transport, Ki, for [14C]dextran (Mr 70,000) and [14C]aminoisobutyric acid (Mr 103,000), with or without inhibition of cyclic GMP-specific phosphodiesterase or soluble guanylate cyclase. We also determined cyclic GMP levels in tumors and normal brain, with or without intracarotid bradykinin infusion, using RIA. Intracarotid infusion of bradykinin selectively increased permeability in RG2 tumors and C6 tumors for both tracers. Simultaneous infusion of bradykinin and a cyclic GMP-specific phosphodiesterase inhibitor, zaprinast (20 mg/kg), resulted in significantly increased permeability across the BTB, compared to intracarotid bradykinin infusion alone. Zaprinast also significantly prolonged the permeability effects of bradykinin. Pretreatment using i.v. infusion of the soluble guanylate cyclase inhibitor, LY-83583 (125 microg/kg), significantly attenuated the bradykinin effect of opening the BTB. Cyclic GMP levels in RG2 and C6 tumors were significantly increased after intracarotid bradykinin infusion (2.8- and 2.2-fold, respectively). Cyclic GMP levels in normal brain were not increased by bradykinin infusion. These results show that increasing cyclic GMP in tumor microvessels can increase permeability in response to bradykinin.

Published
1998

26. A multimedia database system for thermal ablation therapy of brain tumors.

Author

Dionisio JD, Cárdenas AF, Lufkin RB, DeSalles A, Black KL, Taira RK, and Chu WW

Subjects
Brain Neoplasms diagnosis, Humans, Magnetic Resonance Imaging, Reproducibility of Results, Brain Neoplasms surgery, Database Management Systems, Electrocoagulation methods, Image Processing, Computer-Assisted methods, Multimedia
Abstract

A prototype multimedia medical database is described for supporting thermal ablation therapy of brain tumors. Its design is motivated by the major need to manage and access multimedia information on the progress and reaction of tumors to various therapy protocols. The database links images to patient data in a way that permits the use to view and query medical information using alphanumeric, temporal, and feature-based predicates. Visualization programs permit the user to view or annotate the query results in various ways. These results support the wide variety of data types and presentation methods required by neuroradiologists to manage thermal ablation therapy data. The database satisfactorily meets the requirements defined by thermal ablation therapy. A similar approach is being undertaken for supporting different therapies of other types of tumors, thus showing the generality of our approach.

Published
1997
Full Text
View/download PDF

27. Increased brain tumor microvessel permeability after intracarotid bradykinin infusion is mediated by nitric oxide.

Author

Nakano S, Matsukado K, and Black KL

Subjects
Aminoisobutyric Acids pharmacokinetics, Animals, Arginine analogs & derivatives, Arginine pharmacology, Blood-Brain Barrier drug effects, Blotting, Western, Brain Neoplasms drug therapy, Brain Neoplasms metabolism, Carbon Radioisotopes, Dextrans pharmacokinetics, Enzyme Inhibitors pharmacology, Female, Glioma blood supply, Glioma drug therapy, Immunohistochemistry, Infusions, Intra-Arterial, NG-Nitroarginine Methyl Ester, Nitric Oxide Synthase antagonists & inhibitors, Nitric Oxide Synthase metabolism, Rats, Rats, Wistar, Tumor Cells, Cultured, Bradykinin pharmacology, Brain Neoplasms blood supply, Capillary Permeability drug effects, Nitric Oxide physiology
Abstract

Nitric oxide (NO), a free radical gas implicated in a wide variety of biological reactions, is a novel signaling molecule that may regulate vasodilation, cerebral blood flow, and vascular permeability. This study was performed to determine whether NO mediates the selective increase in brain tumor microvessel permeability after intracarotid infusion of bradykinin in the RG2 rat glioma model. Intracarotid infusion of bradykinin selectively increased the transport of radiolabeled alpha-aminoisobutyric acid and dextran into brain tumors. Transport into normal brain was not increased. The administration of an NO synthase inhibitor, NG-nitro-L-arginine methyl ester, significantly inhibited the increased transport into tumors for both tracers. The inhibitory effect of NG-nitro-L-arginine methyl ester on the response to bradykinin was reversed by L-arginine. The expression of two NO synthase (NOS) isoforms in cultured RG2 glioma cell lines and intracerebral RG2 glioma was examined by immunohistochemistry and Western blot analysis. High levels of expression of neuronal NOS were detected in cultured and intracerebral RG2 cells but not in normal brain tissue, except in rare neuronal cells. The endothelial form of NOS was also expressed in cultured RG2 cells, but not as strongly as neuronal NOS expression. In intracerebral RG2 gliomas, expression of endothelial NOS in the tumor was detected at higher levels than in normal brain. These findings indicate that RG2 rat gliomas express high levels of NOS, which regulate the production of NO, compared with normal brain. We suggest that the selective permeability increase in brain tumor microvessels after bradykinin infusion is mediated by NO. Furthermore, the absence of high levels of NOS in normal brain may account for the attenuated permeability response to bradykinin in normal brain microvessels.

Published
1996

28. Preliminary experience with MR-guided thermal ablation of brain tumors.

Author

Anzai Y, Lufkin R, DeSalles A, Hamilton DR, Farahani K, and Black KL

Subjects
Adenocarcinoma pathology, Adenocarcinoma secondary, Adenocarcinoma surgery, Adult, Aged, Aged, 80 and over, Brain Neoplasms pathology, Brain Neoplasms secondary, Contrast Media, Feasibility Studies, Feedback, Follow-Up Studies, Gadolinium, Glioblastoma pathology, Glioblastoma surgery, Humans, Image Enhancement, Middle Aged, Oligodendroglioma pathology, Oligodendroglioma surgery, Patient Care Planning, Treatment Outcome, Brain Neoplasms surgery, Magnetic Resonance Imaging methods, Radiology, Interventional, Radiosurgery methods
Abstract

Purpose: To evaluate the feasibility of a technique of MR-guided stereotactic radio frequency ablation, which was developed as a minimally invasive treatment for brain tumors, and to determine MR characteristics and sequential evolution of radio frequency lesions created to ablate brain tumors., Methods: Fourteen lesions in 12 patients with primary and metastatic brain tumors were treated with this technique and followed for up to 10 months. The stereotactic coordinates of the tumor and the angle of the radio frequency probe were calculated on MR imaging. The radio frequency lesion was generated in the awake patient by increasing the temperature to 80 degrees C within the tumor for 1 minute. This was repeated until the entire tumor volume was destroyed. MR imaging was performed before, during, and immediately after the radio frequency procedure, and sequential MR was obtained during clinical follow-up., Results: MR imaging clearly showed well-defined radio frequency lesions and provided feedback for treatment planning. The radio frequency lesion boundary was well identified as a dark signal rim on T2-weighted images and showed ring enhancement on contrast-enhanced T1-weighted images. The sequential MR imaging showed the radio frequency lesions decreased in volume in all cases, suggesting focal control., Conclusion: Stereotactic MR-guided radio frequency brain tumor ablation is a feasible and promising technique that can be an attractive brain tumor treatment alternative. MR provided not only accurate tumor location but also visualization of feedback of thermal tissue changes that reflected therapeutic effect.

Published
1995

29. The limits of treatment of malignant gliomas.

Author

Black KL and Ciacci JR

Subjects
Adult, Aged, Brachytherapy, Brain Neoplasms radiotherapy, Brain Neoplasms surgery, Chemotherapy, Adjuvant, Combined Modality Therapy, Glioma radiotherapy, Glioma surgery, Humans, Prognosis, Brain Neoplasms therapy, Glioma therapy
Published
1993

30. Blood-brain barrier and new approaches to brain drug delivery.

Author

Pardridge WM, Boado RJ, Black KL, and Cancilla PA

Subjects
Animals, Astrocytes physiology, Brain blood supply, Drug Carriers, Endothelium, Vascular physiology, Humans, Leukotrienes physiology, Monosaccharide Transport Proteins physiology, Blood-Brain Barrier physiology, Drug Delivery Systems, Peptides pharmacokinetics
Abstract

Morbidity caused by brain dysfunction affects more than 50 million persons in the United States. Although new neuropharmaceuticals have the potential for treating specific brain diseases, they may not effectively enter brain from blood. Safe strategies are needed for drug delivery through the brain capillary wall, which makes up the blood-brain barrier in vivo. Two of these strategies are reviewed, as are related new developments in the molecular and cell biology of the brain capillary endothelium. The production of chimeric peptides represents a physiologic-based strategy for drug delivery. It entails the covalent coupling of the neuropharmaceutical to a brain transport vector, allowing transportation through the blood-brain barrier. Another strategy is biochemical opening of the blood-brain barrier: intracarotid leukotriene infusion is a method for selectively increasing blood-brain barrier permeability in brain tumors without affecting barrier permeability in normal brain tissue.

Published
1992

31. Brain tumors.

Author

Black KL, Mazziotta JC, and Becker DP

Subjects
Brain Chemistry, Brain Neoplasms diagnostic imaging, Humans, Magnetic Resonance Imaging, Radiography, Tomography, Emission-Computed, Brain Neoplasms diagnosis, Receptors, GABA-A analysis
Abstract

Recent advances in experimental tumor biology are being applied to critical clinical problems of primary brain tumors. The expression of peripheral benzodiazepine receptors, which are sparse in normal brain, is increased as much as 20-fold in brain tumors. Experimental studies show promise in using labeled ligands to these receptors to identify the outer margins of malignant brain tumors. Whereas positron emission tomography has improved the dynamic understanding of tumors, the labeled selective tumor receptors with positron emitters will enhance the ability to specifically diagnose and greatly aid in the pretreatment planning for tumors. Modulation of these receptors will also affect tumor growth and metabolism. Novel methods to deliver antitumor agents to the brain and new approaches using biologic response modifiers also hold promise to further improve the management of brain tumors.

Published
1991

32. Thallium-201 SPECT imaging of brain tumors: methods and results.

Author

Kim KT, Black KL, Marciano D, Mazziotta JC, Guze BH, Grafton S, Hawkins RA, and Becker DP

Subjects
Astrocytoma classification, Astrocytoma metabolism, Brain Neoplasms classification, Brain Neoplasms metabolism, Glioblastoma classification, Glioblastoma metabolism, Humans, Astrocytoma diagnostic imaging, Brain Neoplasms diagnostic imaging, Glioblastoma diagnostic imaging, Thallium Radioisotopes pharmacokinetics, Tomography, Emission-Computed, Single-Photon
Abstract

Recent studies suggest that thallium-201 (201Tl) planar scans of brain tumors more accurately reflect viable tumor burden than CT, MRI, or radionuclide studies with other single-photon emitting compounds. We have previously reported the utility of 201Tl SPECT index in distinguishing low- from high-grade gliomas elsewhere. Here we describe the technical considerations of deriving a simple 201Tl index, based on uptake in the tumor normalized to homologous contralateral tissue, from SPECT images of brain tumors. We evaluated the importance of consistently correcting for tissue attenuation, as it may achieve better lesion discrimination on qualitative inspection, and the methodologic limitations imposed by partial volume effects at the limits of resolution.

Published
1990

33. Seizures and hemiparesis in a young woman 24 years after treatment of astrocytoma.

Author

Mazziotta JC, Jordan SE, Lones M, Black KL, Selch MT, Pignatti G, and Vinters HV

Subjects
Adult, Astrocytoma complications, Female, Humans, Motor Cortex pathology, Neoplasm Recurrence, Local complications, Skull Neoplasms etiology, Astrocytoma radiotherapy, Brain Neoplasms radiotherapy, Hemiplegia etiology, Neoplasms, Radiation-Induced complications, Osteosarcoma etiology, Seizures etiology
Abstract

An edited transcript of Neurology Grand Rounds held at the University of California, Los Angeles, Medical Center on January 27, 1988. John Mazziotta, MD, PhD, Professor of Neurology and Radiology, is the coordinator of these conferences. This conference was edited by Harry V. Vinters, MD.

Published
1989

Catalog

Books, media, physical & digital resources
See catalog results