Seventy-two hybridoma lines that produce monoclonal antibodies to molecules of a rat synaptosomal... more Seventy-two hybridoma lines that produce monoclonal antibodies to molecules of a rat synaptosomal plasma membrane fraction (SPM) were generated. The topographical distribution of the antigens in the cerebellum and other areas of the brain was studied by light microscopy immunocytochemistry. Some of the antibodies recognize exclusively neuronal antigens while others bind to specific glial molecules. Some of the antigens have a distribution limited to certain classes of neurons. There are antigens localized in both the cell bodies and processes while others are present only in the latter. Immunoblots of SPM proteins indicate that some antibodies react specifically with one or few of these proteins while other antibodies react with many. The latter antibodies also generally react with many brain cell types. Particularly interesting is the monoclonal antibody 8-6A2 which binds to many SPM proteins but only recognizes large neurons with long axons. A further characterization of the antigens was done by enzyme-linked immunosorbent assays and immunoblots of known purified proteins. The results indicate that antibody 8-2H5 binds specifically to clathrin, 8-7A5 to actin, 8-1E7 to the glial fibrillary acidic protein and both 8-3A5 and 7-2C12 to collagen. In contrast, the antibodies 4-4C3, 2-4H3, 4-4G7 and 6-6A8 bind to antigenic determinants present in many purified proteins.
The spectrum of neuropsychological features of familial Creutzfeldt-Jakob disease (CJD) have seld... more The spectrum of neuropsychological features of familial Creutzfeldt-Jakob disease (CJD) have seldom been reported, possibly because of (a) the rarity of this hereditary form of prion disease; (b) frequent delays in diagnosis, and; (c) the typically rapid demise of the patient, which affords little opportunity for comprehensive testing or serial analysis. Here we describe the neurobehavioral characteristics of a 48-year-old right-handed male (JD) who presented with complaints of poor depth perception, unsteady gait, and unusual sensory experiences in his face and neck. JD was followed serially over the final 4 months of his 5-month illness. Immediately following hospital admission, he underwent a neuropsychological evaluation that revealed moderate to severe impairment of delayed (30-minute) verbal memory, tactual performance in his right hand, and word-finding ability. In contrast, other abilities that are commonly classified within the verbal, visuospatial, and memory domains showed minimal or no compromise. Parallel studies of electroencephalographic activity revealed diffuse slowing and, later, 1-Hz rhythmical discharges over the left hemisphere, and mild prominence of the lateral ventricles and cerebral sulci on magnetic resonance imaging. Autopsy revealed spongiform changes and reactive astrocytosis, and genetic testing demonstrated a codon 200 mutation in the prion protein gene. These findings indicate that CJD can result in clinical manifestations compatible with multifocal asymmetric cerebral involvement before more diffuse neurodegeneration ensues, providing a strong impetus for the study of additional cases. This long-term understanding can help to determine whether
Current Hypotheses and Research Milestones in Alzheimer's Disease, 2009
Virtually all current hypotheses on the pathogenesis and pathophysiology of Alzheimer's ... more Virtually all current hypotheses on the pathogenesis and pathophysiology of Alzheimer's disease rely on an unvoiced “amorphous” concept of the brain that essentially ignores its highly complex organization at the systems neuroscience level. This is especially true for ...
Drug Dosage The authors and the publisher have exerted every effort to ensure that drug selection... more Drug Dosage The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text arc in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the con stant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any change in indications and dosage and for added warnings and precautions. This is particularly impor tant when the recommended agent is a new and/or infre quently employed drug All rights reserved. No part of this publication may be translated into other lan guages. reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying record ing. microcopying or by any information storage and re trieval system, without permission in writing from the pub lisher or. in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center (sec 'Infor mation for Readers and Subscribers').
This chapter discusses the importance of retina in aging and in Alzheimer's disease (AD). Def... more This chapter discusses the importance of retina in aging and in Alzheimer's disease (AD). Defective vision and visually guided behavior is a basic complaint in the elders and in patients with neurodegenerative disorders, which may result because of eye pathology whereby including the retina and a variety of processes that affect the central visual pathways. The basis for these deficits remains elusive because senile plaques (SP) and neuropil threads usually occur in multiple regions, which collectively mediate vision but not in the retina itself. The chapter focuses on one of the putative mechanisms for some of the clinical manifestations postulated on the basis of electroretinographic abnormalities, reduction in the number of cells, as well as axonal loss in the optic nerve of patients with AD. Because increasing attention is being paid to AD with visual manifestations, it would be rather helpful to have adequate information about eye abnormalities in patients in whom severe involvement of association with visual cortices has been fully recognized.
Development of positron emission tomography (PET) imaging agents capable of quantifying tau aggre... more Development of positron emission tomography (PET) imaging agents capable of quantifying tau aggregates in neurodegenerative disorders such as Alzheimer's disease (AD) is of enormous importance in the field of dementia research. The aim of the present study was to conduct first-inman imaging studies with the potential novel tau imaging agent [ 18 F]N-methyl lansoprazole ([ 18 F]NML). Herein we report validation of the synthesis of [ 18 F]NML for clinical use by labeling the trifluoromethyl group via radiofluorination of the corresponding gem-difluoro enol ether *
Identification and localization of biologically active peptides in the vertebrate retina. NC BREC... more Identification and localization of biologically active peptides in the vertebrate retina. NC BRECHA, W ELDRED, RO KULJIS, HJ KARTEN Progress in retinal research 3, 185-226, Pergamon Press, 1984. Rétine; Retina; Retina ...
This paper was designed to review some of the major aspects of the development of the human brain... more This paper was designed to review some of the major aspects of the development of the human brain for non-neuroscientists, as a preamble for discussions on ethical, legal, philosophical, and religious dilemmas posed by new reproductive technology. The present review is limited to the key biomedical aspects of brain development as they may be pertinent to current moral, legal, ethical, and other humanistic concerns raised about the potential of modern reproductive technology. For didactic purposes, the text is divided into four sections: (1) an overview of the neural substrate for human conscious experience and pain perception, the main goal of brain development, (2) the early events during the development of the nervous system, (3) the development of the cerebral cortex, and (4) concluding remarks.
Seventy-two hybridoma lines that produce monoclonal antibodies to molecules of a rat synaptosomal... more Seventy-two hybridoma lines that produce monoclonal antibodies to molecules of a rat synaptosomal plasma membrane fraction (SPM) were generated. The topographical distribution of the antigens in the cerebellum and other areas of the brain was studied by light microscopy immunocytochemistry. Some of the antibodies recognize exclusively neuronal antigens while others bind to specific glial molecules. Some of the antigens have a distribution limited to certain classes of neurons. There are antigens localized in both the cell bodies and processes while others are present only in the latter. Immunoblots of SPM proteins indicate that some antibodies react specifically with one or few of these proteins while other antibodies react with many. The latter antibodies also generally react with many brain cell types. Particularly interesting is the monoclonal antibody 8-6A2 which binds to many SPM proteins but only recognizes large neurons with long axons. A further characterization of the antigens was done by enzyme-linked immunosorbent assays and immunoblots of known purified proteins. The results indicate that antibody 8-2H5 binds specifically to clathrin, 8-7A5 to actin, 8-1E7 to the glial fibrillary acidic protein and both 8-3A5 and 7-2C12 to collagen. In contrast, the antibodies 4-4C3, 2-4H3, 4-4G7 and 6-6A8 bind to antigenic determinants present in many purified proteins.
The spectrum of neuropsychological features of familial Creutzfeldt-Jakob disease (CJD) have seld... more The spectrum of neuropsychological features of familial Creutzfeldt-Jakob disease (CJD) have seldom been reported, possibly because of (a) the rarity of this hereditary form of prion disease; (b) frequent delays in diagnosis, and; (c) the typically rapid demise of the patient, which affords little opportunity for comprehensive testing or serial analysis. Here we describe the neurobehavioral characteristics of a 48-year-old right-handed male (JD) who presented with complaints of poor depth perception, unsteady gait, and unusual sensory experiences in his face and neck. JD was followed serially over the final 4 months of his 5-month illness. Immediately following hospital admission, he underwent a neuropsychological evaluation that revealed moderate to severe impairment of delayed (30-minute) verbal memory, tactual performance in his right hand, and word-finding ability. In contrast, other abilities that are commonly classified within the verbal, visuospatial, and memory domains showed minimal or no compromise. Parallel studies of electroencephalographic activity revealed diffuse slowing and, later, 1-Hz rhythmical discharges over the left hemisphere, and mild prominence of the lateral ventricles and cerebral sulci on magnetic resonance imaging. Autopsy revealed spongiform changes and reactive astrocytosis, and genetic testing demonstrated a codon 200 mutation in the prion protein gene. These findings indicate that CJD can result in clinical manifestations compatible with multifocal asymmetric cerebral involvement before more diffuse neurodegeneration ensues, providing a strong impetus for the study of additional cases. This long-term understanding can help to determine whether
Current Hypotheses and Research Milestones in Alzheimer's Disease, 2009
Virtually all current hypotheses on the pathogenesis and pathophysiology of Alzheimer's ... more Virtually all current hypotheses on the pathogenesis and pathophysiology of Alzheimer's disease rely on an unvoiced “amorphous” concept of the brain that essentially ignores its highly complex organization at the systems neuroscience level. This is especially true for ...
Drug Dosage The authors and the publisher have exerted every effort to ensure that drug selection... more Drug Dosage The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text arc in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the con stant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any change in indications and dosage and for added warnings and precautions. This is particularly impor tant when the recommended agent is a new and/or infre quently employed drug All rights reserved. No part of this publication may be translated into other lan guages. reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying record ing. microcopying or by any information storage and re trieval system, without permission in writing from the pub lisher or. in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center (sec 'Infor mation for Readers and Subscribers').
This chapter discusses the importance of retina in aging and in Alzheimer's disease (AD). Def... more This chapter discusses the importance of retina in aging and in Alzheimer's disease (AD). Defective vision and visually guided behavior is a basic complaint in the elders and in patients with neurodegenerative disorders, which may result because of eye pathology whereby including the retina and a variety of processes that affect the central visual pathways. The basis for these deficits remains elusive because senile plaques (SP) and neuropil threads usually occur in multiple regions, which collectively mediate vision but not in the retina itself. The chapter focuses on one of the putative mechanisms for some of the clinical manifestations postulated on the basis of electroretinographic abnormalities, reduction in the number of cells, as well as axonal loss in the optic nerve of patients with AD. Because increasing attention is being paid to AD with visual manifestations, it would be rather helpful to have adequate information about eye abnormalities in patients in whom severe involvement of association with visual cortices has been fully recognized.
Development of positron emission tomography (PET) imaging agents capable of quantifying tau aggre... more Development of positron emission tomography (PET) imaging agents capable of quantifying tau aggregates in neurodegenerative disorders such as Alzheimer's disease (AD) is of enormous importance in the field of dementia research. The aim of the present study was to conduct first-inman imaging studies with the potential novel tau imaging agent [ 18 F]N-methyl lansoprazole ([ 18 F]NML). Herein we report validation of the synthesis of [ 18 F]NML for clinical use by labeling the trifluoromethyl group via radiofluorination of the corresponding gem-difluoro enol ether *
Identification and localization of biologically active peptides in the vertebrate retina. NC BREC... more Identification and localization of biologically active peptides in the vertebrate retina. NC BRECHA, W ELDRED, RO KULJIS, HJ KARTEN Progress in retinal research 3, 185-226, Pergamon Press, 1984. Rétine; Retina; Retina ...
This paper was designed to review some of the major aspects of the development of the human brain... more This paper was designed to review some of the major aspects of the development of the human brain for non-neuroscientists, as a preamble for discussions on ethical, legal, philosophical, and religious dilemmas posed by new reproductive technology. The present review is limited to the key biomedical aspects of brain development as they may be pertinent to current moral, legal, ethical, and other humanistic concerns raised about the potential of modern reproductive technology. For didactic purposes, the text is divided into four sections: (1) an overview of the neural substrate for human conscious experience and pain perception, the main goal of brain development, (2) the early events during the development of the nervous system, (3) the development of the cerebral cortex, and (4) concluding remarks.
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