100 results on '"Henry deF. Webster"'
Search Results
2. THE RELATIONSHIP BETWEEN SCHMIDT-LANTERMANN INCISURES AND MYELIN SEGMENTATION DURING WALLERIAN DEGENERATION*
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Henry deF. Webster
- Subjects
Pathology ,medicine.medical_specialty ,Wallerian degeneration ,Guinea Pigs ,General Biochemistry, Genetics and Molecular Biology ,Myelin ,History and Philosophy of Science ,Ranvier's Nodes ,medicine ,Animals ,Humans ,Myelin Sheath ,Nerve degeneration ,Chemistry ,Research ,General Neuroscience ,Brain ,medicine.disease ,Sciatic Nerve ,medicine.anatomical_structure ,Myelin sheath ,Nerve Degeneration ,Schwann Cells ,Sciatic nerve ,Nervous System Diseases ,Wallerian Degeneration ,Ranvier's node - Published
- 2006
3. The Early Development of the Neopallial Wall and Area Choroidea in Fetal Rats : A Light and Electron Microscopic Study
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Karl E. Aström, Henry deF. Webster, Karl E. Aström, and Henry deF. Webster
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- Neocortex, Choroid, Developmental neurobiology, Rats--Nervous system
- Abstract
Original study and a review of the pertinent literature are presented in this monograph on the early development of the neopallial wall and the choroidal area in vertebrates before the appearance of nerve cells. In the pre-neural period the telencephalic wall is a cohesive, non-stratified epithelial sheet of elongated, radially oriented, polarized cells. Although these cells, including the radial glial cells, differ from each other in various regions and change in shape, internal structure and phenotypic expression during development, they have a basic unity. The book draws attention to this unity and discusses the cells'morphogenesis and functions, and the mechanisms which help to shape the early cerebral hemispheres. The pre-neural period is of fundamental importance for the development of the cerebrum. The knowledge presented here of how cells differentiate during the early stages will help neuroscientists by providing a basis for comparisons with cultured cells and explants, and with cells seen in lineage studies and with microscopic observations of living animals in which dynamic events in the CNS can be seen directly. This work will improve our understanding of many developmental abnormalities of the nervous system.
- Published
- 2012
4. Basic FGF and FGF receptor 1 are expressed in microglia during experimental autoimmune encephalomyelitis: Temporally distinct expression of midkine and pleiotrophen
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Xia Liu, George A. Mashour, Andreas Kurtz, and Henry deF. Webster
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Midkine ,medicine.medical_specialty ,biology ,Microglia ,Encephalomyelitis ,Growth factor ,medicine.medical_treatment ,Experimental autoimmune encephalomyelitis ,Basic fibroblast growth factor ,medicine.disease ,Pleiotrophin ,Cell biology ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,medicine.anatomical_structure ,Endocrinology ,Neurology ,chemistry ,Internal medicine ,biology.protein ,medicine ,Neuroglia - Abstract
Heparin-binding growth factors have been implicated in central nervous system development, regeneration and pathology. To assess the expression pattern and possible function in multiple sclerosis, the heparin-binding growth factors pleiotrophin (PTN), midkine (MK), basic fibroblast growth factor (FGF-2) and one of its receptors (FGFR1/ flg) mRNA and protein levels were examined in an experimental autoimmune encephalomyelitis (EAE) model in the Lewis rat. We assessed the time course of expression of PTN, MK and FGF-2 during EAE and determined the cellular origin of FGF-2 and FGFR1 in normal spinal cord and during inflammatory demyelination. Basal expression of PTN and MK mRNAs in normal spinal cords was significantly upregulated after induction of EAE. MK expression was upregulated two to threefold correlating with disease progression, whereas PTN expression reached peak levels threefold above basal levels during the clinical recovery period. FGF-2 mRNA expression was low in normal spinal cord and dramatically increased in correlation with progressive demyelination. FGF-2 was confined to neurons in normal tissue and shifted dramatically to microglia, paralleling their activation during EAE. Double immunohistochemistry revealed co-localization of FGF-2 to activated microglia/ macrophages with strongest expression in the macrophage-rich perivascular core area and microglial expression at the edges of white and gray matter perivascular regions. FGFR1, like its ligand, was induced in activated macrophages/ microglia. Growth factor expression in demyelinating diseases could serve several functions, e.g., to modulate the activity of microglia/ macrophage in an autocrine fashion, to induce the expression of other factors like insulin-like growth factor 1 or plasminogen activator, which can effect regeneration or degeneration, respectively, and finally to stimulate directly localized proliferation and/ or regeneration of oligodendrocytes within the lesion area. GLIA 24:390–397, 1998. © 1998 Wiley-Liss, Inc.
- Published
- 1998
5. Growth factors and myelin regeneration in multiple sclerosis
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Henry deF. Webster
- Subjects
Encephalomyelitis, Autoimmune, Experimental ,Multiple Sclerosis ,Platelet-derived growth factor ,Cell Survival ,medicine.medical_treatment ,Nerve Tissue Proteins ,Ciliary neurotrophic factor ,Fibroblast growth factor ,03 medical and health sciences ,Myelin ,chemistry.chemical_compound ,0302 clinical medicine ,medicine ,Animals ,Humans ,Ciliary Neurotrophic Factor ,Nerve Growth Factors ,030212 general & internal medicine ,Insulin-Like Growth Factor I ,Growth Substances ,Myelin Sheath ,Platelet-Derived Growth Factor ,biology ,Growth factor ,Experimental autoimmune encephalomyelitis ,Brain ,Cell Differentiation ,medicine.disease ,Nerve Regeneration ,Cell biology ,Fibroblast Growth Factors ,Oligodendroglia ,medicine.anatomical_structure ,Nerve growth factor ,Spinal Cord ,Neurology ,chemistry ,Immunology ,biology.protein ,Neurology (clinical) ,Cell Division ,030217 neurology & neurosurgery ,Platelet-derived growth factor receptor - Abstract
Insulin-like growth factor-I (IGF-I), platelet-derived growth factor (PDGF), fibroblast growth factor (FGF) and ciliary neurotrophic factor (CNTF) are multifunctional growth factors which are found in the CNS. Oligodendroglia are the cells that form and maintain myelin sheaths and many in vitro experiments have shown that these growth factors promote the proliferation, differentiation and survival of cells in the oligodendroglial lineage. Since myelin breakdown is often severe in multiple sclerosis (MS), the possibility of growth factor use in the treatment of MS has been considered and recently, IGF-I treatment has been shown to reduce lesion severity and promote myelin regeneration in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. This review briefly summarizes the structural characteristics of these growth factors and the actions which might help reduce oligodendrocyte-myelin sheath injury in MS and promote myelin regeneration.
- Published
- 1997
6. Insulin-like growth factor-I treatment reduces immune cell responses in acute non-demyelinative experimental autoimmune encephalomyelitis
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Da-Lin Yao, C. Linnington, Xing-yan Liu, Georg W. Kreutzberg, Hartmut Wekerle, S. Lassmann, Henry deF. Webster, and Lynn D. Hudson
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Pathology ,medicine.medical_specialty ,biology ,business.industry ,Multiple sclerosis ,Growth factor ,medicine.medical_treatment ,Experimental autoimmune encephalomyelitis ,medicine.disease ,Myelin basic protein ,Lesion ,Cellular and Molecular Neuroscience ,Immune system ,biology.protein ,Medicine ,Antibody ,medicine.symptom ,business ,Immunostaining - Abstract
To test the effects of insulin-like growth factor-I (IGF-I) on clinical deficits, lesion severity, and immune cell response in acute, non-demyelinative experimental autoimmune encephalomyelitis (EAE), we induced EAE in Lewis rats by passive transfer of an MBP-reactive T lymphocyte line. Four days after receiving 5 x 10(5) MBPL-1 T cells intravenously, ten pairs of rats had the same mild degree of tail and hind limb weakness. Ten were given 300 micrograms IGF-I i.v. twice daily for 6 days, and the other 10 received the same volume of 0.89% NaCl. Pairs of rats were sacrificed after 4 days and 6 days of IGF-I and placebo treatment and spinal cord sections were processed for immunostaining, in situ hybridization, and morphological examination. IGF-I treatment decreased clinical deficits, lesion numbers, and lesion areas significantly. Numbers of CD4-positive T cells, alpha/beta TCR-positive cells, and ED-1-positive macrophages were also significantly reduced by IGF-I treatment. Similar reductions were found in our second trial, when 11 days of placebo and IGF-I injections began the day after transfer. No demyelination was observed in either toluidine blue-stained semithin sections or sections immunostained with an antibody raised against myelin basic protein (MBP). We conclude that IGF-I-induced reductions in immune cell responses can occur in the absence of demyelination and are of major importance in decreasing clinical deficits and lesion severity in EAE. If IGF-I has similar effects in multiple sclerosis, we think that it will be useful therapeutically.
- Published
- 1997
7. Insulin-like growth factor-I given subcutaneously reduces clinical deficits, decreases lesion severity and upregulates synthesis of myelin proteins in experimental autoimmune encephalomyelitis
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Xia Liu, Henry deF. Webster, Lynn D. Hudson, and Da-Lin Yao
- Subjects
Male ,medicine.medical_specialty ,Encephalomyelitis, Autoimmune, Experimental ,Proteolipid protein 1 ,medicine.medical_treatment ,Encephalomyelitis ,General Biochemistry, Genetics and Molecular Biology ,Lesion ,Insulin-like growth factor ,Myelin ,Internal medicine ,medicine ,Animals ,RNA, Messenger ,Insulin-Like Growth Factor I ,General Pharmacology, Toxicology and Pharmaceutics ,biology ,business.industry ,Multiple sclerosis ,Experimental autoimmune encephalomyelitis ,General Medicine ,medicine.disease ,Rats ,Up-Regulation ,Myelin basic protein ,Endocrinology ,medicine.anatomical_structure ,Rats, Inbred Lew ,Immunology ,biology.protein ,medicine.symptom ,business ,Myelin Proteins ,Demyelinating Diseases - Abstract
To extend our evaluation of insulin-like growth factor-I (IGF-I) treatment for human demyelinating diseases, we compared effects of s.c. and i.v. IGF-I in an in vivo model with lesions resembling those seen in multiple sclerosis. Experimental autoimmune encephalomyelitis (EAE) was induced in Lewis rats with an emulsion containing guinea pig spinal cord and treatment with placebo or with s.c. or i.v. IGF-I was started when definite clinical weakness was present. IGF-I given subcutaneously significantly reduced clinical deficits and lesion severity. The clinical improvement, as measured by clinical deficit scores, stride lengths and exercise wheel rotations, was evident in 48 hrs and was comparable to that produced by the same IGF-I dose administered intravenously. Subcutaneously administered IGF-I also increased relative mRNA levels of myelin basic protein (MBP), proteolipid protein (PLP) and 2′,3′ cyclic nucleotide 3′-phosphodiesterase (CNP), thereby promoting myelin regeneration. We conclude that s.c. IGF-I produces dramatic improvement in acute, demyelinating EAE. Our results also suggest that this growth factor may be useful in treating multiple sclerosis patients with active demyelination.
- Published
- 1996
8. Cryogenic spinal cord injury induces astrocytic gene expression of insulin-like growth factor I and insulin-like growth factor binding protein 2 during myelin regeneration
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West Nr, Michael Brenner, Lynn D. Hudson, Carolyn A. Bondy, Da-Lin Yao, Jian Zhou, Henry deF. Webster, and George H. Collins
- Subjects
medicine.medical_specialty ,medicine.medical_treatment ,Molecular Sequence Data ,Gene Expression ,Insulin-like growth factor-binding protein ,Rats, Sprague-Dawley ,Lesion ,Cellular and Molecular Neuroscience ,Myelin ,Insulin-like growth factor ,Somatomedins ,Internal medicine ,Freezing ,Glial Fibrillary Acidic Protein ,medicine ,Animals ,RNA, Messenger ,Insulin-Like Growth Factor I ,Remyelination ,In Situ Hybridization ,Myelin Sheath ,Spinal Cord Injuries ,Base Sequence ,Glial fibrillary acidic protein ,biology ,Myelin Basic Protein ,Immunohistochemistry ,Axons ,Nerve Regeneration ,Rats ,Myelin basic protein ,Microscopy, Electron ,medicine.anatomical_structure ,Endocrinology ,Astrocytes ,Immunology ,biology.protein ,Autoradiography ,Female ,medicine.symptom ,Carrier Proteins ,Insulin-Like Growth Factor Binding Protein 5 ,Astrocyte - Abstract
To study injury-induced astrocytic responses associated with regrowth of axons and regeneration of myelin, the method of Collins and colleagues was used to make focal cryogenic lesions in spinal cords of adult rats (Collins et al.: J Neuropathol Exp Neurol 45:742–757, 1986). The duration of cryogenic injury (CI), the size of the cryode, and its temperature were chosen to destroy all myelin sheaths and axons without producing cavities or hemorrhages. Messenger RNA and peptide distributions of insulin-like growth factor I (IGF-I), IGF-I receptor (IGFR-I), IGF binding protein 2 (IGFBP-2), glial fibrillary acidic protein (GFAP), and myelin basic protein (MBP) were studied 3–56 days after CI by in situ hybridization and immunocytochemistry. At 3 days, vimentin-positive, GFAP-negative astrocyte-Iike cells in the lesion expressed IGF-I mRNA and peptide and 7 days after CI, both were expressed by typical GFAP-positive, hypertrophic astrocytes, many of which also were vimentin-positive. Levels of IGF-I, IGFBP-2, and GFAP mRNA and peptide were higher in lesion astrocytes after 14 days. They attained maximum levels at 21–28 days before declining to near control levels at 56 days. Decreasing relative levels of oligodendroglial MBP mRNA were found in and around lesions 7–14 days after CI; subsequently, rising levels accompanied remyelination. At 28 and 56 days after CI, some transferrin-positive, oligodendroglia-like cells also were immunostained by anti-IGFR-I. Our findings suggest that early astrocytic production of IGF-I and IGFBP-2 may be involved in the myelin regeneration which occurs in this model of spinal cord injury. © 1995 Wiley-Liss, Inc.1
- Published
- 1995
9. Concentric sclerosis (Baló): Morphometric and in situ hybridization study of lesions in six patients
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Da-Lin Yao, Michael Brenner, Lynn D. Hudson, Duo-San Liu, Alfonso I. Escobar, Sámuel Komoly, and Henry deF. Webster
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Pathology ,medicine.medical_specialty ,Multiple sclerosis ,Immunocytochemistry ,Anatomy ,In situ hybridization ,Biology ,medicine.disease ,Lesion ,Central nervous system disease ,White matter ,Myelin ,medicine.anatomical_structure ,Neurology ,medicine ,Neurology (clinical) ,medicine.symptom ,Remyelination - Abstract
Brain tissues from 6 patients with concentric sclerosis (Balo) were examined by in situ hybridization, immunocytochemistry, morphometry, and histological methods. The patients were 24 to 48 years old and had progressive cerebral symptoms and signs that lasted 15 to 100 days. Large demyelinative lesions, most frequent in the frontal white matter, contained alternating bands of demyelinated and partly myelinated white matter that were arranged in concentric or mosaic patterns. In the areas of demyelination, axons were relatively well preserved and there were perivascular inflammatory infiltrates. In 2 specimens, lesions contained regions with the characteristic appearance of actively demyelinating multiple sclerosis plaques. Oligodendroglial densities were highest in normal-appearing white matter, lower in partially myelinated areas, and lowest in demyelinated areas, which also contained many hypertrophic astrocytes closely associated with oligodendroglia. Messenger RNA levels for myelin-related proteins followed the same pattern; they were lowest in demyelinated areas, higher in partially myelinated areas, and highest in normal-appearing white matter beyond lesion margins. Our findings suggest that concentric sclerosis is a variant of multiple sclerosis, that oligodendroglial loss is important in the pathogenesis of demyelination, and that partially myelinated areas probably represent stages of ongoing myelin breakdown rather than remyelination of previously demyelinated areas.
- Published
- 1994
10. Effects of Psychosine (Galactosylsphingosine) on the Survival and the Fine Structure of Cultured Schwann Cells
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Henry deF. Webster and Kaoru Tanaka
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Time Factors ,Cell Survival ,Cell ,Schwann cell ,Biology ,Pathology and Forensic Medicine ,Immunoenzyme Techniques ,Rats, Sprague-Dawley ,Cellular and Molecular Neuroscience ,Myelin ,medicine ,Animals ,Cytotoxic T cell ,Cytotoxicity ,Cells, Cultured ,Dose-Response Relationship, Drug ,S100 Proteins ,Psychosine ,General Medicine ,medicine.disease ,Immunohistochemistry ,Sciatic Nerve ,Mitochondria ,Rats ,Cell biology ,Kinetics ,Microscopy, Electron ,medicine.anatomical_structure ,Animals, Newborn ,nervous system ,Neurology ,Cytoplasm ,Cell culture ,Immunology ,Krabbe disease ,Schwann Cells ,Neurology (clinical) - Abstract
The cytotoxicity of psychosine (galactosylsphingosine) for cultured rat Schwann cells was studied by maintaining them in medium containing 1, 10, 50, 75 and 100 microM psychosine for 24, 48 and 72 hours (h). When incubated in 50-100 microM concentrations of psychosine for 24 h, 52-99% of cultured Schwann cells did not survive. Lower concentrations (1-10 microM) did not significantly reduce Schwann cell numbers for the first 24 h. However, only 43-69% of cultured Schwann cells survived in these low concentrations for 48 h, and substantially fewer remained after 72 h of incubation. During incubations in psychosine, bipolar processes of Schwann cells retracted; the resulting oval and rounded Schwann cells still were S-100 positive. When these Schwann cells were transferred into normal medium, their processes elongated quickly. When examined with the electron microscope, the cytoplasm of Schwann cells incubated in psychosine contained numerous membranous inclusions and fewer mitochondria, some of which were swollen. There also were fewer profiles of granular endoplasmic reticulum and some had widely dilated cisternae. These results suggest that 1) exogenous psychosine in concentrations of 1 microM and greater is cytotoxic for cultured rat Schwann cells; 2) psychosine has reversible toxic effects and its turnover is rapid; and 3) psychosine produces membranous inclusions and abnormalities in the mitochondria and granular endoplasmic reticulum of cultured Schwann cells. Our findings support the hypothesis that the accumulation of psychosine in human and murine globoid cell leukodystrophy is toxic for Schwann cells, produces changes in their capacity to maintain myelin, and leads to Schwann cell dysfunction.
- Published
- 1993
11. Growth factors, lesion repair and myelin regeneration
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Henry deF Webster
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Lesion ,Myelin ,Pathology ,medicine.medical_specialty ,medicine.anatomical_structure ,Regeneration (biology) ,medicine ,medicine.symptom ,Biology - Published
- 2010
12. Myelinated fiber regeneration after sciatic nerve crush: Morphometric observations in young adult and aging mice and the effects of macrophage suppression and conditioning lesions
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Qian-Lin Zhang, Henry deF. Webster, and Kaoru Tanaka
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Male ,Aging ,Nerve Crush ,Myelinated nerve fiber ,medicine.medical_treatment ,Biology ,Nerve Fibers, Myelinated ,Mice ,Myelin ,Developmental Neuroscience ,medicine ,Animals ,Axon ,Macrophages ,Anatomy ,Fascicle ,medicine.disease ,Adaptation, Physiological ,Sciatic Nerve ,Greater sciatic notch ,Nerve Regeneration ,Mice, Inbred C57BL ,Microscopy, Electron ,medicine.anatomical_structure ,nervous system ,Neurology ,Crush injury ,Sciatic nerve ,Axotomy - Abstract
To study myelinated nerve fiber regeneration during aging, the right sciatic nerves of 6- and 24-month-old mice were crushed at the sciatic notch. Two, 4, and 8 weeks later, both groups of mice were perfused. The sciatic nerves were processed so that the transverse sections of each nerve subsequently studied by light and electron microscopy included the entire posterior tibial fascicle 5 mm distal to the crush site. Two weeks after axotomy, fascicles of aging mice contained significantly fewer regenerated myelinated fibers than those of young adults. After 4 weeks, the difference in the number of myelinated fibers was less. However, measurements of myelinated fibers in fascicles of aging mice showed that areas of Schwann cell cytoplasm and myelin were significantly reduced at all intervals. In contrast, although axon diameters in aging mice were somewhat less 2 weeks after crushing, the difference decreased with time, suggesting that in nerves of aging mice, regenerative responses of Schwann cells were more affected than those of axons. Other experiments in young mice showed that myelinated fiber regeneration could be retarded by suppressing macrophage responses and was not significantly changed by conditioning lesions before crush injury.
- Published
- 1992
13. Brain vascular endothelial cells express JC virus large tumor antigen in immunocompetent and cyclophosphamide-treated hamsters
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H G Ressetar, Gerald L. Stoner, and Henry deF. Webster
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Antigens, Polyomavirus Transforming ,viruses ,JC virus ,Hamster ,Blood–brain barrier ,medicine.disease_cause ,Virus ,Immunoenzyme Techniques ,Antigen ,In vivo ,Cerebellum ,Cricetinae ,von Willebrand Factor ,medicine ,Animals ,Cyclophosphamide ,Multidisciplinary ,Mesocricetus ,biology ,virus diseases ,biology.organism_classification ,JC Virus ,Virology ,Tumor Virus Infections ,medicine.anatomical_structure ,nervous system ,Blood-Brain Barrier ,Endothelium, Vascular ,Immunostaining ,Research Article - Abstract
When injected intracerebrally into newborn hamsters, the human polyomavirus JC virus (JCV) establishes a nonproductive infection resulting in brain tumor formation. Using immunostaining methods to detect the JCV regulatory protein, large tumor antigen (T antigen), we have now demonstrated JCV infection of brain vascular endothelial cells (EC) in infected hamsters. JCV T antigen was detected in lectin-labeled EC as well as in von Willebrand factor-expressing EC in both cyclophosphamide-treated and nonimmunosuppressed hamster brains 16, 21, and 31 days after birth. Cyclophosphamide-treated hamsters exhibited a greater number of JCV-infected EC, whereas T-antigen expression in nonvascular cells was not affected. The influence of cyclophosphamide was most pronounced in the cerebellum where increased numbers of JCV-infected EC were located predominantly at the internal granular layer-white matter junction, also a prominent location for T-antigen-expressing neoplastic foci. The hamster model demonstrates in vivo infection of EC by a human polyomavirus and directs interest toward the role of these cells in human JCV infection.
- Published
- 1992
14. REVERSIBLE AND IRREVERSIBLE CHANGES IN THE FINE STRUCTURE OF NERVOUS TISSUE DURING OXYGEN AND GLUCOSE DEPRIVATION
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Adelbert Ames and Henry deF. Webster
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Retina ,Endoplasmic reticulum ,Nervous tissue ,Cell Biology ,Biology ,Golgi apparatus ,Synaptic vesicle ,Article ,Ganglion ,symbols.namesake ,medicine.anatomical_structure ,Biochemistry ,Organelle ,medicine ,Biophysics ,symbols ,sense organs ,Axon - Abstract
Rabbit retinas were fixed for electron microscopy immediately after removing the eye and after incubations in a control medium and in three different deprivation media that were identical with the control except for the omission of glucose, oxygen, or both. A systematic comparison was made of the electron microscopic appearance of the different retinas with particular attention to four regions: rod inner segments, rod synapses, bipolar cell bodies, and ganglion cell myelinated axons. Retinas fixed after 1 hour of incubation in the control medium appeared virtually identical with those fixed immediately after ocular removal. Retinas deprived of oxygen and glucose for only 3 minutes showed generalized swelling of mitochondria and alterations in the structure of the synapses with loss of synaptic vesicles. Extending the combined deprivation caused further mitochondrial swelling and synaptic changes and also led to progressive swelling of the Golgi membranes and the granular endoplasmic reticulum. All these changes were almost completely reversible for up to 20 minutes but were irreversible by 30 minutes, at which time multiple discontinuities had appeared in cell and organelle membranes. Anoxia alone produced alterations similar to those found after somewhat shorter periods of the combined deprivation, whereas glucose withdrawal produced only minor changes. These electron microscopic results correlate quite well with previously reported electrophysiological measurements.
- Published
- 2009
15. Gliogenesis: historical perspectives, 1839-1985
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Henry deF, Webster and Karl E, Aström
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Central Nervous System ,Tissue Culture Techniques ,Neural Tube ,Neuroanatomy ,Neurogenesis ,Glial Fibrillary Acidic Protein ,Animals ,Vimentin ,Epithelial Cells ,History, 19th Century ,History, 20th Century ,Neuroglia ,Myelin Sheath - Abstract
This historical review of gliogenesis begins with Schwann's introduction of the cell doctrine in 1839. Subsequent microscopic studies revealed the cellular structure of many organs and tissues, but the CNS was thought to be different. In 1864, Virchow created the concept that nerve cells are held together by a "Nervenkitte" which he called"glia" (for glue). He and his contemporaries thought that "glia" was an unstructured, connective tissue-like ground substance that separated nerve cells from each other and from blood vessels. Dieters, a pupil of Virchow, discovered that this ground substance contained cells, which he described and illustrated. Improvements in microscopes and discovery of metallic impregnation methods finally showed convincingly that the "glia" was not a binding substance. Instead, it was composed of cells, each separate and distinct from neighboring cells and each with its own characteristic array of processes. Light microscopic studies of developing and mature nervous tissue led to the discovery of different types of glial cells-astroglia, oligodendroglia, microglia, and ependymal cells in the CNS, and Schwann cells in the peripheral nervous system (PNS). Subsequent studies characterized the origins and development of each type of glial cell. A new era began with the introduction of electron microscopy, immunostaining, and in vitro maintenance of both central and peripheral nervous tissue. Other methods and models greatly expanded our understanding of how glia multiply, migrate, and differentiate. In 1985, almost a century and a half of study had produced substantial progress in our understanding of glial cells, including their origins and development. Major advances were associated with the discovery of new methods. These are summarized first. Then the origins and development of astroglia, oligodendroglia, microglia, ependymal cells, and Schwann cells are described and discussed. In general, morphology is emphasized. Findings related to cytodifferentiation, cellular interactions, functions, and regulation of developing glia have also been included.
- Published
- 2009
16. Po Glycoprotein mRNA distribution in myelin-forming Schwann cells of the developing rat trigeminal ganglion
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Lajos Lamperth, Laura Manuelidis, and Henry deF. Webster
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Histology ,General Neuroscience ,Endoplasmic reticulum ,Schwann cell ,Cell Biology ,Anatomy ,Biology ,Horseradish peroxidase ,Molecular biology ,Myelin ,Trigeminal ganglion ,Vibratome ,medicine.anatomical_structure ,nervous system ,Compact myelin ,Cytoplasm ,medicine ,biology.protein - Abstract
A biotinylated P0 cDNA was hybridized in situ to aldehyde-fixed vibratome sections of trigeminal ganglia from day 2, day 7, day 15, day 30 and adult rats. Nickel-enhanced horseradish peroxidase (HRP) was used in an antibody sandwich method to detect hybridization. After postfixation in osmium tetroxide, the sections were dehydrated in ethanol and embedded in epon. At each age, some vibratome sections were used to count the HRP-positive and HRP-negative myelin-forming Schwann cells. The percentage of HRP-positive myelin-forming Schwann cells in ganglia from day 2, 7, 15, 30, and adult rats were 31%, 56%, 47%, 12% and 3%. In sections of ganglia from 2-day-old rats, studied by light and electron microscopy, peroxidase reaction product localizing hybridized P0 mRNA was found on profiles of granular (rough) endoplasmic reticulum (RER) in perinuclear regions of Schwann cells which had formed two to three compact myelin lamellae. Peroxidase deposits were larger and more numerous in the cytoplasm cells with thicker myelin sheaths. At day 7, some Schwann cells had long external mesaxons; the cytoplasm between these mesaxons and the cell surface often contained abundant HRP-stained profiles of RER. In sections from day 7 and day 15 ganglia, substantially more reaction product was found. In each myelin-forming Schwann cell, the amount was generally proportional to the size of the newly formed myelin sheath. HRP deposits were observed all along the outer surfaces of myelin segments at these ages, and their distribution corresponded to that of the RER.(ABSTRACT TRUNCATED AT 250 WORDS)
- Published
- 1990
17. Preparation of fetal rat brains for light and electron microscopy
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Karl E. Åström and Henry deF. Webster
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Fetus ,Pathology ,medicine.medical_specialty ,Nucleoplasm ,Mesenchyme ,Embryo ,Anatomy ,Biology ,law.invention ,chemistry.chemical_compound ,medicine.anatomical_structure ,chemistry ,Osmium tetroxide ,law ,embryonic structures ,medicine ,Glutaraldehyde ,Electron microscope ,Fixation (histology) - Abstract
To study cellular shapes, growth patterns, and fine structure during early stages of CNS development in rat embryos, preparative procedures were evaluated and modified to meet two criteria: 1) Coronal semithin sections should reveal undeformed telencephalic hemispheres that were symmetrically expanded on both sides of midline structures and were surrounded by contiguous mesenchyme. 2) In electron micrographs, cells should have intact, undistorted surface membranes, evenly distributed nucleoplasm and well preserved cytoplasmic organelles. To meet these criteria, 378 fetuses with a gestational age of 11-20 days (E11-E20) were used to test and modify procedures for anesthesia, embryo removal and handling, dissection, fixation, dehydration, and embedding of the embryonic CNS. Most specimens were in an early stage of development (E11-E13), which, in case of the neopallial wall, is the preneural period. The tests produced methods that met the above criteria and identified the most common artifacts and their causes. Deformities of the cerebral hemispheres and separations between the brain and its coverings were usually caused by trauma during embryo removal and during handling before fixation. Changes in cellular volumes, especially swelling during fixation and dehydration, were the most important causes of histological artifacts. The procedures and methods that consistently produced the best light and electron microscopic preservation of the E11-E13 rat CNS are described. Fixation was best when the brains were treated with glutaraldehyde and s-collidine buffer, followed by osmium tetroxide in s-collidine buffer. A surprisingly beneficial effect of sodium chloride in the dehydrating alcohol was noted.
- Published
- 1990
18. Introduction
- Author
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HENRY DEF. WEBSTER
- Published
- 2005
19. Contributing Authors
- Author
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AMMAR AL-CHALABI, DORIS-EVA BAMIOU, ROBERT W. BANKS, RICHARD J. BAROHN, TIMOTHY J. BENSTEAD, ALAN R. BERGER, C.-H. BERTHOLD, ADIL E. BHARUCHA, ROLFE BIRCH, HERBERT L. BONKOVSKY, AUGUST M. BOOTH, E. PETER BOSCH, HUGH BOSTOCK, FRANK BRADKE, ROSCOE O. BRADY, STEPHEN BRIMIJOIN, DEBORAH BUCK, RICHARD P. BUNGE, DAVID BURKE, JAMES P. BURKE, TED M. BURNS, MICHAEL CAMILLERI, J. AIDAN CARNEY, COLIN CHALK, PHILLIP F. CHANCE, S.Y. CHIU, MICHAEL P. COLLINS, JOHN H. COOTE, JAMES J. CORBETT, DAVID R. CORNBLATH, T. COWEN, PAULA CUDIA, BASIL T. DARRAS, JENNY L. DAVIES, WILLIAM C. DE GROAT, ANGELA DISPENZIERI, MARY L. DOMBOVY, MICHAEL DONAGHY, PETER J. DYCK, P. JAMES B. DYCK, ANDREW G. ENGEL, JANEAN ENGELSTAD, MARK A. FERRANTE, JOHN P. FRAHER, MASON W. FREEMAN, ROY FREEMAN, THOMAS R. FRITSCHE, ANNEKE GABREëLS-FESTEN, ERNEST D. GARDNER, CATERINA GIANNINI, DONALD H. GILDEN, HANS H. GOEBEL, RALF GOLD, IAN A. GRANT, NORMAN A. GREGSON, JOHN W. GRIFFIN, MICHAEL J. GROVES, THOMAS M. HABERMANN, ANGELIKA F. HAHN, SUSAN HALL, JOHN R. HALLIWILL, MICHAEL G. HANNA, A.E. HARDING, HANS-PETER HARTUNG, STEVEN HERSKOVITZ, AHMET HöKE, RICHARD A.C. HUGHES, CLARE HUXLEY, ROBERT R. JACOBSON, ANN JACOBY, KRISTJÁN R. JESSEN, DAVID M. JOHNSON, H. ROYDEN JONES, MICHAEL J. JOYNER, BASHAR KATIRJI, KENTON R. KAUFMAN, JOHN J. KELLY, WILLIAM R. KENNEDY, MATTHEW C. KIERNAN, BERND C. KIESEIER, JUN KIMURA, R.H.M. KING, JOHN T. KISSEL, CAROLINE M. KLEIN, CHRISTOPHER J. KLEIN, KLEOPAS A. KLEOPA, CHRISTOPHER J. KLINGELE, DAVID L. KREULEN, ROBERT A. KYLE, CATHERINE LACROIX, TERRENCE D. LAGERLUND, EDWARD H. LAMBERT, SALLY N. LAWSON, JACQUELINE A. LEAVITT, P. NIGEL LEIGH, J.G. LLEWELYN, GLENN LOPATE, PHILLIP A. LOW, JAMES R. LUPSKI, LINDA M. LUXON, RUDOLF MARTINI, CHRISTOPHER J. MATHIAS, JUSTIN C. MCARTHUR, ELIZABETH S. MCDONALD, JAMES G. MCLEOD, PHILIP G. MCMANIS, L. JOSEPH MELTON, ALBEE MESSING, VIRGINIA V. MICHELS, RHONA MIRSKY, PETER C. O'BRIEN, GRAHAM M. O'HANLON, GILMORE N. O'NEILL, DAVID J. PATERSON, ALAN PESTRONK, DAVID PLEASURE, JOHN D. POLLARD, MICHAEL POLYDEFKIS, SUDHA POTTUMARTHY, MARY M. REILLY, ANDREA ROBERTSON, GUSTAVO C. ROMAN, MICHAEL C. ROWBOTHAM, MONIQUE M. RYAN, MARTIN RYDMARK, THOMAS D. SABIN, GÉRARD SAID, DAVID S. SAPERSTEIN, FRANCESCO SCARAVILLI, HERBERT H. SCHAUMBURG, STEVEN S. SCHERER, RAPHAEL SCHIFFMANN, MARTIN SCHMELZ, JON J.A. SCOTT, KAZIM SHEIKH, JOHN T. SHEPHERD, MICHAEL E. SHY, WOLFGANG SINGER, BENN E. SMITH, ERIC J. SORENSON, JUDITH M. SPIES, ERIK V. STÅLBERG, J. CLARKE STEVENS, GUIDO STOLL, GUILLERMO A. SUAREZ, UELI SUTER, THOMAS R. SWIFT, BRUCE V. TAYLOR, AYALEW TEFFERI, STEPHEN N. THIBODEAU, P.K. THOMAS, PHILIP D. THOMPSON, ERIK C. THORLAND, D.R. TOMLINSON, ERIK TOREBJÖRK, KLAUS V. TOYKA, JOŽE V. TRONTELJ, KENNETH L. TYLER, B. ULFHAKE, PAUL M. VANHOUTTE, ANNABEL K. WANG, LAURA E. WARNER, HENRY DEF. WEBSTER, ANANDA WEERASURIYA, GWEN WENDELSCHAFER-CRABB, EELCO F.M. WIJDICKS, ASA J. WILBOURN, HUGH J. WILLISON, ANTHONY J. WINDEBANK, HARALD WITTE, JACKIE D. WOOD, BRIAN R. YOUNGE, and DOUGLAS W. ZOCHODNE
- Published
- 2005
20. Global democratic consensus on neuropathological disease criteria
- Author
-
Bernd W. Scheithauer, Françoise Gray, Atsushi Sasaki, Yoh Matsumoto, Adriana Cardozo, Markus Tolnay, Manuel B. Graeber, Manuel Deprez, Yngve Olsson, Matti Haltia, Peter L. Lantos, James Lowe, Hans H. Goebel, David I. Graham, Georg W. Kreutzberg, John Q. Trojanowski, Matthew P. Frosch, Hitoshi Takahashi, Henry deF. Webster, Yoshio Hashizume, Rupert Egensperger, Kenji Ikeda, Dirk Troost, Charles Duyckaerts, Cristian Achim, Roland N. Auer, Catherine Bergeron, Margaret M. Esiri, Rob de Vos, Caterina Giannini, James W. Ironside, Samuel K. Ludwin, and Pathology
- Subjects
medicine.medical_specialty ,business.industry ,Brain Neoplasms ,media_common.quotation_subject ,Neurodegenerative Diseases ,Disease ,Democracy ,Phenotype ,Neurology ,Terminology as Topic ,medicine ,Humans ,Neurology (clinical) ,Nervous System Diseases ,Psychiatry ,business ,Neuroscience ,media_common - Published
- 2003
21. Persistence of neurotropic JC virus DNA in hamster tissues six months after intracerebral inoculation
- Author
-
H G Ressetar, Henry deF. Webster, and Gerald L. Stoner
- Subjects
Male ,Time Factors ,viruses ,JC virus ,Adrenal Gland Neoplasms ,Hamster ,Biology ,medicine.disease_cause ,law.invention ,Injections ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,Neuroblastoma ,Antigen ,Transcription (biology) ,law ,Virology ,Cricetinae ,medicine ,Animals ,Tissue Distribution ,Gonads ,Polymerase chain reaction ,Mesocricetus ,Papillomavirus Infections ,Brain ,Molecular biology ,JC Virus ,Reverse transcription polymerase chain reaction ,Tumor Virus Infections ,Viscera ,Neurology ,chemistry ,DNA, Viral ,Female ,Neurology (clinical) ,Immunostaining ,DNA - Abstract
Immunostaining and polymerase chain reaction (PCR) methods were used to examine tissues from 18 6-month-old hamsters intracerebrally inoculated with JC virus (JCV) as newborns. JCV DNA was detected in all hamster brains and urinary bladders, as well as in most kidney, adrenal gland and pancreas samples. While results from reverse transcription PCR (RNA PCR) and immunostaining suggest that T antigen transcription and protein expression were restricted to the brain, the DNA suggests that intracerebrally inoculated JCV enters the systemic circulation and latently infects organs in a tissue specific manner.
- Published
- 1997
22. Insulin-like growth factor I treatment reduces demyelination and up-regulates gene expression of myelin-related proteins in experimental autoimmune encephalomyelitis
- Author
-
Henry deF. Webster, Lynn D. Hudson, Da-Lin Yao, and Xia Liu
- Subjects
Male ,medicine.medical_specialty ,Proteolipid protein 1 ,Encephalomyelitis, Autoimmune, Experimental ,Encephalomyelitis ,Myelin ,Internal medicine ,medicine ,Animals ,RNA, Messenger ,Insulin-Like Growth Factor I ,Myelin Proteolipid Protein ,In Situ Hybridization ,Myelin Sheath ,Multidisciplinary ,biology ,Dose-Response Relationship, Drug ,Multiple sclerosis ,Experimental autoimmune encephalomyelitis ,Transferrin ,Myelin Basic Protein ,medicine.disease ,Immunohistochemistry ,Oligodendrocyte ,Myelin basic protein ,Myelin proteolipid protein ,Rats ,Oligodendroglia ,medicine.anatomical_structure ,Endocrinology ,Gene Expression Regulation ,Spinal Cord ,Rats, Inbred Lew ,Immunology ,biology.protein ,2',3'-Cyclic-Nucleotide Phosphodiesterases ,Cell Division ,Myelin Proteins ,Demyelinating Diseases ,Research Article - Abstract
To compare effects of insulin-like growth factor I (IGF-I) and placebo treatment on lesions that resemble those seen during active demyelination in multiple sclerosis, we induced experimental autoimmune encephalomyelitis in Lewis rats with an emulsion containing guinea pig spinal cord and Freund's adjuvant. On day 12-13, pairs of rats with the same degree of weakness were given either IGF-I or placebo intravenously twice daily for 8 days. After 8 days of placebo or IGF-I (200 micrograms/day or 1 mg/day) treatment, the spinal cord lesions were studied by in situ hybridization and with immunocytochemical and morphological methods. IGF-I produced significant reductions in numbers and areas of demyelinating lesions. These lesions contained axons surrounded by regenerating myelin segments instead of demyelinated axons seen in the placebo-treated rats. Relative mRNA levels for myelin basic protein, proteolipid protein (PLP), and 2',3'-cyclic nucleotide 3'-phosphodiesterase in lesions of IGF-I-treated rats were significantly higher than they were in placebo-treated rats. PLP mRNA-containing oligodendroglia also were more numerous and relative PLP mRNA levels per oligodendrocyte were higher in lesions of IGF-I-treated rats. Finally, a significantly higher proportion of proliferating cells were oligodendroglia-like cells in lesions of IGF-I-treated rats. We think that IGF-I effects on oligodendrocytes, myelin protein synthesis, and myelin regeneration reduced lesion severity and promoted clinical recovery in this experimental autoimmune encephalomyelitis model. These IGF-I actions may also benefit patients with multiple sclerosis.
- Published
- 1995
23. Astrocytes upregulate glial fibrillary acidic protein (GFAP), but not insulin-like growth factor-I (IGF-I) during experimental autoimmune neuritis (EAN)
- Author
-
Carolyn A. Bondy, Georg W. Kreutzberg, Bruno Bonetti, Da-Lin Yao, Jochen Gehrmann, Michael Brenner, Henry deF. Webster, and Hartmut Wekerle
- Subjects
Male ,T cell ,Immunocytochemistry ,Fluorescent Antibody Technique ,Biology ,Pathology and Forensic Medicine ,Receptor, IGF Type 1 ,Dorsal root ganglion ,Glial Fibrillary Acidic Protein ,medicine ,Animals ,RNA, Messenger ,Insulin-Like Growth Factor I ,In Situ Hybridization ,Microglia ,Glial fibrillary acidic protein ,General Neuroscience ,Brain ,Spinal cord ,GFAP stain ,Molecular biology ,Immunohistochemistry ,Neuritis, Autoimmune, Experimental ,Rats ,Up-Regulation ,Insulin-Like Growth Factor Binding Proteins ,Microglial cell activation ,medicine.anatomical_structure ,nervous system ,Spinal Cord ,Rats, Inbred Lew ,Astrocytes ,Immunology ,biology.protein ,Neurology (clinical) ,Carrier Proteins - Abstract
T cell-mediated autoimmune neuritis produces rapid activation of spinal cord microglia. To determine whether this microglial response upregulates astrocytic expression of IGF-related proteins, we induced EAN and used in situ hybridization and immunocytochemistry to examine the mRNAs and peptides for glial fibrillary acidic protein (GFAP), insulin-like growth factor-I (IGF-I), IGF-I receptor (IGFR-I) and IGF binding protein-2 (IGFBP-2). Relative levels of GFAP mRNA and peptide were highest in the lumbar spinal cord 4-10 d following T cell transfer and significant GFAP elevations were still present after three weeks. The astrocytes expressing GFAP mRNA and peptide were localized around motoneurons which were related topographically to axons in peripheral nerve inflammatory lesions. In the nucleus gracilis, where terminals of dorsal root ganglion neurons are located, astrocytic levels of GFAP mRNA and peptide rose later and did not reach their highest levels until 21 d after T cell transfer. Even though microglia were activated in both locations 2-4 d after transfer, astrocytic levels of IGF-I, IGFR-I and IGFBP-2 mRNA and peptide did not differ significantly from those observed in controls. The dissociation of GFAP and IGF-I expression in EAN suggests that these astrocytic responses may be independently regulated. We also suggest that the type and severity of remote neuronal injury are probably more important inducers and regulators of these astrocytic responses than microglial cell activation.
- Published
- 1995
24. Astrocytes express insulin-like growth factor-I (IGF-I) and its binding protein, IGFBP-2, during demyelination induced by experimental autoimmune encephalomyelitis
- Author
-
Carolyn A. Bondy, Henry deF. Webster, Michael Brenner, Lynn D. Hudson, Xiao Liu, Jian Zhou, and Da Lin Yao
- Subjects
Pathology ,medicine.medical_specialty ,Encephalomyelitis, Autoimmune, Experimental ,CNS demyelination ,Encephalomyelitis ,Guinea Pigs ,Molecular Sequence Data ,Biology ,Cellular and Molecular Neuroscience ,Myelin ,Glial Fibrillary Acidic Protein ,medicine ,Animals ,RNA, Messenger ,Remyelination ,Insulin-Like Growth Factor I ,Molecular Biology ,In Situ Hybridization ,Glial fibrillary acidic protein ,Base Sequence ,Experimental autoimmune encephalomyelitis ,Myelin Basic Protein ,Receptors, Somatomedin ,Cell Biology ,medicine.disease ,Immunohistochemistry ,Myelin basic protein ,Rats ,Insulin-Like Growth Factor Binding Protein 2 ,medicine.anatomical_structure ,Rats, Inbred Lew ,Astrocytes ,Molecular Probes ,Immunology ,biology.protein ,Carrier Proteins ,Astrocyte ,Demyelinating Diseases - Abstract
To assess the distribution of insulin-like growth-factor-related proteins during autoimmune CNS demyelination and remyelination, experimental autoimmune encephalomyelitis was produced by injecting Lewis rats with an emulsion containing guinea pig spinal cord and complete Freund's adjuvant. Tail weakness appeared at 10-12 days and was followed by hind and forelimb weakness. Paraplegia and incontinence were observed in some animals. From 8-40 days postinoculation (dpi), spinal cord sections were used to correlate lesion location and severity with mRNA distributions of insulin-like growth factor I (IGF-I), IGF-binding protein 2 (IGFBP-2), IGF-I-receptor (IGFR-I), glial fibrillary acidic protein (GFAP), and myelin basic protein (MBP). These were determined semiquantitatively by in situ hybridization. Fourteen dpi, there were inflammatory infiltrates and demyelination in both white matter (WM) and grey matter (GM). IGF-I and GFAP mRNAs were increased in these lesions and transcripts encoding myelin basic protein (MBP) were greatly reduced. Large lesions with extensive demyelination were evident in both WM and GM when mRNA levels of GFAP and IGF-I peaked 26 dpi. MBP mRNA levels began increasing 21 dpi and peaked 26 dpi, when a few thin regenerating myelin sheaths were found morphologically. Astrocytes, identified by their morphology and GFAP immunoreactivity, expressed very low levels of IGFBP-2 mRNA and peptide in normal controls; their levels were significantly higher 14 dpi, peaked 26 dpi, and then gradually decreased. Some neurons, as well as oligodendroglia in areas undergoing remyelination, expressed IGFR-I. Although levels of IGF-I, IGFBP-2, and GFAP mRNAs were highest in lesion areas, levels were also elevated around lesions and in some normal-appearing areas of WM and GM 14-40 dpi. The gene expression of both IGF-I and IGFBP-2 by hypertrophic GFAP-positive astrocytes was demonstrated 14-40 dpi by combined in situ hybridization and immunocytochemistry as well as by double immunostaining. Coexpression of IGF-I and IGFBP-2 in the same astrocyte was a frequent finding. Relative increases in both IGF-I, GFAP, IGFBP-2, IGFR-I, and MBP mRNAs peaked at about the same time. This suggests that during lesion progression and recovery, astrocytic expression of IGF-I-related peptides may reduce immune-mediated myelin injury. We also suggest that astrocytic IGFBP-2 in lesions may help target IGF-I to IGFR-I-expressing oligodendrocytes and promote remyelination of demyelinated axons.
- Published
- 1994
25. Human immunodeficiency virus (HIV) distribution in HIV encephalitis: study of 19 cases with combined use of in situ hybridization and immunocytochemistry
- Author
-
Lajos Lamperth, Georg Gosztonyi, Juan Artigas, and Henry deF. Webster
- Subjects
Transcription, Genetic ,Immunocytochemistry ,In situ hybridization ,Biology ,Virus ,Pathology and Forensic Medicine ,Cellular and Molecular Neuroscience ,Viral Proteins ,Antigen ,medicine ,Humans ,In Situ Hybridization ,Acquired Immunodeficiency Syndrome ,Base Sequence ,Brain ,HIV ,General Medicine ,medicine.disease ,Virology ,Immunohistochemistry ,Neurology ,Protein Biosynthesis ,Human Immunodeficiency Virus DNA ,Encephalitis ,Neurology (clinical) ,Viral disease - Abstract
Brains of 19 AIDS patients with HIV encephalitis were examined by immunohistochemistry and in situ hybridization using antisense HIV DNA and RNA probes. Double immunohistochemical labeling, using antibodies against viral and cell-type specific antigens, was utilized to study lesions in some brains. Other combined studies included use of in situ hybridization and immunohistochemical labeling of the same section, using antibodies against either viral or cell-type specific antigens. Hybridization signals were abundant and were concentrated mainly in the white matter. Heavy labeling was found in the subcortical white matter, the corpus callosum, the internal capsule, and white matter regions of the brainstem and cerebellum. Deeper cortical layers often contained cells with hybridized probe when the subcortical white matter was intensely labeled. HIV nucleic acid sequences were found almost exclusively in macrophages. Counts showed that 16-25% of macrophages contained viral antigens and exhibited hybridized HIV probe. Almost all of these macrophages contained proviral DNA, viral RNA and viral proteins; i.e. they were actively replicating HIV. We also examined brains from three AIDS cases without clinical or pathological evidence of HIV encephalitis; no HIV sequences or immunoreactive proteins were detected.
- Published
- 1994
26. Insulin-like growth factor I gene expression is induced in astrocytes during experimental demyelination
- Author
-
Henry deF. Webster, Sámuel Komoly, Lynn D. Hudson, and Carolyn A. Bondy
- Subjects
Male ,medicine.medical_specialty ,medicine.medical_treatment ,Proteolipids ,Gene Expression ,Nerve Tissue Proteins ,Receptors, Cell Surface ,Biology ,White matter ,Immunoenzyme Techniques ,Myelin ,Insulin-like growth factor ,Cuprizone ,Mice ,Cell surface receptor ,Internal medicine ,Gene expression ,Glial Fibrillary Acidic Protein ,medicine ,Animals ,RNA, Messenger ,Remyelination ,Insulin-Like Growth Factor I ,Multidisciplinary ,Nucleic Acid Hybridization ,Myelin Basic Protein ,Receptors, Somatomedin ,Oligodendrocyte ,Cell biology ,Endocrinology ,medicine.anatomical_structure ,Astrocytes ,2',3'-Cyclic-Nucleotide Phosphodiesterases ,Astrocyte ,Demyelinating Diseases ,Research Article - Abstract
To investigate insulin-like growth factor I (IGF-I) and IGF-I receptor gene expression during experimental demyelination and myelin regeneration, young mice were fed cuprizone (( bis(cyclohexanone) oxaldihydrazone )). This copper-chelating agent produces demyelination in the corpus callosum and superior cerebellar peduncles, and when treatment is stopped, there is rapid remyelination. At intervals during cuprizone treatment and recovery, brain sections were hybridized with specific probes and immunostained with antibodies to determine the localization and relative amounts of IGF-I and IGF-I receptor mRNAs and peptides. In untreated littermates, IGF-I and IGF-I receptor mRNAs and peptides were not detected in white matter. In cuprizone-treated mice, high levels of both IGF-I mRNA and peptide were expressed by astrocytes in areas of myelin breakdown. Astrocyte IGF-I expression decreased rapidly during recovery and oligodendroglial expression of myelin-related genes increased. In severely demyelinated areas, immature oligodendroglia exhibited a transient increase in IGF-I receptor mRNA and peptide immunoreactivity during early recovery. This highly specific pattern of IGF-I induction in astrocytes during demyelination and the expression of the IGF-I receptor in regenerating oligodendrocytes during recovery suggest that IGF-I functions in the regulation of oligodendrocyte and myelin metabolism in vivo.
- Published
- 1992
27. How international is the International Society of Neuropathology?
- Author
-
Henry deF. Webster, J. Hume Adams, and Samuel K. Ludwin
- Subjects
business.industry ,General Neuroscience ,International Cooperation ,Library science ,Neuropathology ,Pathology and Forensic Medicine ,Neuroanatomy ,Pathology ,Medicine ,Neurology (clinical) ,Periodicals as Topic ,business ,Developing Countries ,Societies, Medical - Published
- 1991
28. In vitro changes in the fine structure and protein composition of light myelin fractions isolated from guinea pig brain
- Author
-
M. G. Nunzi, K.-F. J. Chan, and Henry deF. Webster
- Subjects
Guinea Pigs ,Nerve Tissue Proteins ,Dithiothreitol ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,Myelin ,medicine ,Animals ,Protein phosphorylation ,Phosphorylation ,Incubation ,Myelin Sheath ,Gel electrophoresis ,HEPES ,Brain Chemistry ,biology ,Brain ,Myelin basic protein ,EGTA ,Microscopy, Electron ,medicine.anatomical_structure ,chemistry ,Biochemistry ,biology.protein ,Biophysics ,Electrophoresis, Polyacrylamide Gel - Abstract
To find out if in vitro maintenance produces changes in the electron microscopic appearance, protein composition and phosphorylation properties of guinea pig CNS myelin fractions, we incubated them for 10 min, 4 hr, 24 hr, and 48 hr in phosphate-buffered saline (pH 7.4) or in 20 mM Hepes, 2 mM EDTA, 0.5 mM EGTA, 0.5 mM dithiothreitol, and 20 mM NaCl at 4 and 30 degree C. Aliquots were processed for electron microscopic study, were analyzed for protein content by gel electrophoresis, and were assayed for endogenous protein phosphorylation. Before incubation, electron micrographs of fractions contained two types of multilamellar whorls with the periodicity of CNS myelin sheaths. The first type of whorl was separated from nearby whorls; the other type had surface lamellae that were connected to other multilayered membrane fragments. After incubation at 4 degree C for 24 hr, the number of both types of multilamellar whorls in micrographs had increased approximately 3- to 4- fold. Counts per unit area showed that the observed increase was both time- and temperature-dependent. In aliquots studied by gel electrophoresis, only minor degradation of myelin proteins was observed. The endogenous protein phosphorylation properties of the myelin fragments also remained functional, suggesting that the activities of protein phosphotransferases were not altered. We conclude that the incubation conditions described here favor interactions of proteins and lipids that lead to the formation of multilayered aggregates of CNS myelin membranes.
- Published
- 1991
29. Material and Methods
- Author
-
Karl Erik Åström and Henry deF. Webster
- Published
- 1991
30. Summary
- Author
-
Karl Erik Åström and Henry deF. Webster
- Published
- 1991
31. Discussion: Neopallial Wall
- Author
-
Henry deF. Webster and Karl E. Åström
- Subjects
Glial fibrillary acidic protein ,biology ,Neural tube ,Anatomy ,Columnar Cell ,Microfilament ,law.invention ,Neuroepithelial cell ,medicine.anatomical_structure ,law ,biology.protein ,medicine ,Basal lamina ,Electron microscope ,Growth cone - Abstract
The methods which were used in this study (Astrom and Webster 1990) have allowed us to examine whole brains of fetal rats in an early period of development (E11–13) and to use light and electron microscopy for studies of well-preserved cells within selected areas of the pallial wall. During this time period the selected regions (the neopallial wall and the area choroidea) have the same basic structure, which is that of a pseudostratified neuroepithelium. Like authors of previous studies, we found that the neuroepithelial cells are radially oriented and have an asymmetrical shape (His 1889; Sauer 1935b). They are joined by junctional complexes near the ventricles (Duncan 1957), they extend through the wall to the pial surface where the outer ends are covered by a basal lamina, and they have cytoskeletons composed of axial microtubules and microfilaments (Lyser 1964, 1968; Herman and Kauffman 1966). We have also confirmed previous observations on the fine anatomy of the columnar/radial glial cells in the telencephalic wall of mice (Meller et al. 1966; Hinds and Ruffett 1971; Choi 1988), in rats (Matsuyama et al. 1973; Peters and Feldman 1973; Rickmann and Wolff 1985), and in rabbits (Stensaas and Stensaas 1968). Earlier studies are concerned mainly with the radial glial cells which appear during the period of neuronal migration. This project is different in that it deals only with the columnar cells which are seen in the preneuronal period.
- Published
- 1991
32. Discussion: Area Choroidea
- Author
-
Karl E. Åström and Henry deF. Webster
- Subjects
Physics ,Germinal cell ,Coated vesicle ,Choroid plexus ,Cell biology - Abstract
The cells in the telencephalic roof, like those in the neopallial wall, give shape to the early brain, provide a framework for future development, limit the escape of CSF, and harbor a few germinal cells. We will now turn to features which are characteristic for cells in the two locations.
- Published
- 1991
33. Area Choroidea
- Author
-
Karl Erik Åström and Henry deF. Webster
- Published
- 1991
34. Neopallial Wall
- Author
-
Karl Erik Åström and Henry deF. Webster
- Published
- 1991
35. Introduction
- Author
-
Karl Erik Åström and Henry deF. Webster
- Published
- 1991
36. Nomenclature
- Author
-
Karl Erik Åström and Henry deF. Webster
- Published
- 1991
37. The Early Development of the Neopallial Wall and Area Choroidea in Fetal Rats
- Author
-
Karl E. Åström and Henry deF. Webster
- Subjects
Fetus ,Pathology ,medicine.medical_specialty ,medicine ,Biology - Published
- 1991
38. PREPARING MANUSCRIPTS ABOUT NEUROPATHOLOGY IN ENGLISH: A SUGGESTED APPROACH
- Author
-
Henry deF. Webster
- Subjects
Neurology (clinical) ,General Medicine ,Neuropathology ,Psychology ,Classics ,Pathology and Forensic Medicine - Published
- 1998
39. The International Society of Neuropathology: Past Accomplishments and Future Opportunities
- Author
-
Henry deF. Webster
- Subjects
Neuroanatomy ,business.industry ,International Cooperation ,General Neuroscience ,Pathology ,Medicine ,Engineering ethics ,Neurology (clinical) ,Neuropathology ,Periodicals as Topic ,business ,Societies, Medical ,Pathology and Forensic Medicine - Published
- 1990
40. Myelin damage and lipid peroxidation occur following hyperoxic cerebral reperfusion
- Author
-
Joseph F. Weiss, Giora Feurstein, Oliver Kempski, Henry deF. Webster, Dag von Lubitz, Yashesh N. Vaishnav, Joseph E. Parisi, and Hubert S. Mickel
- Subjects
Lipid peroxidation ,Myelin ,chemistry.chemical_compound ,medicine.medical_specialty ,medicine.anatomical_structure ,Endocrinology ,chemistry ,Biochemistry ,Physiology (medical) ,Internal medicine ,medicine - Published
- 1990
41. A novel fragmentation of human myelin basic protein: Identification of phosphorylated domains
- Author
-
K.-F. Jesse Chan, Gerald L. Stoner, Henry deF. Webster, and Mario A. Moscarello
- Subjects
Phosphopeptides ,medicine.medical_treatment ,Biophysics ,medicine.disease_cause ,Biochemistry ,Mole ,medicine ,Humans ,Amino Acid Sequence ,Phosphorylation ,Fragmentation (cell biology) ,Protein kinase A ,Molecular Biology ,Chromatography, High Pressure Liquid ,Protein Kinase C ,Protease ,biology ,Kinase ,Myelin Basic Protein ,Cell Biology ,Molecular biology ,Peptide Fragments ,Myelin basic protein ,Molecular Weight ,Staphylococcus aureus ,biology.protein ,Protein Kinases - Abstract
Human myelin basic protein (MBP) was fragmented into three major polypeptides comprised of a NH 2 -terminal domain (residues 1–83), a middle domain (residues 84–119) which contains an experimental allergic encephalitogenic determinant and a highly conserved triproline sequence, and a COOH-terminal domain (residues 120–170) by Staphylococcus aureus V8 protease at pH 4.0. These three polypeptides could be identified and purified by reversed-phase high-performance liquid chromatography. Analysis of the sites of phosphorylation of the component 1 of human MBP, the most cationic species, catalyzed by a purified Ca 2+ -activated and phospholipid-dependent protein kinase and cAMP-dependent protein kinase revealed that although these protein kinases could incorporate approximately 6 and 4 mol 32 P, respectively, into MBP, none of the potential sites were located within the middle domain.
- Published
- 1987
42. Myelin-associated glycoprotein (MAG) distribution in human central nervous tissue studied immunocytochemically with monoclonal antibody
- Author
-
Gerald L. Stoner, Christina G. Palkovits, Henry deF. Webster, Jacqueline T. Favilla, Donald E. Frail, and Peter E. Braun
- Subjects
Central Nervous System ,medicine.drug_class ,Immunology ,Immunocytochemistry ,Biology ,Monoclonal antibody ,Myelin ,medicine ,Humans ,Immunology and Allergy ,Tissue Distribution ,Nerve Tissue ,Antiserum ,Myelin-associated glycoprotein ,Histocytochemistry ,Immunochemistry ,Histological Techniques ,Antibodies, Monoclonal ,Molecular biology ,Myelin-Associated Glycoprotein ,medicine.anatomical_structure ,nervous system ,Neurology ,Paraffin ,Polyclonal antibodies ,Monoclonal ,biology.protein ,Neurology (clinical) ,Myelin Proteins ,Immunostaining - Abstract
Recent biochemical data show that myelin-associated glycoprotein (MAG) is the antigen for a monoclonal antibody found in sera of patients with IgM paraproteinemia and neuropathy (Braun et al. 1982). Immunoreactivity of this antibody with CNS has not been described. To study this, monoclonal anti-MAG was used in the avidin-biotin-peroxidase complex method (Hsu et al. 1981) to immunostain paraffin and epon sections of human CNS. Well characterized polyclonal MAG antiserum (Quarles et al. 1981) was employed in comparison tests. In paraffin sections of developing CNS, both monoclonal and polyclonal MAG antisera stained oligodendroglia and myelin. In adult CNS, periaxonal regions of myelin sheaths were immunostained in paraffin sections and semithin epon sections treated with monoclonal and polyclonal anti-MAG. In electron-microscopic experiments that included milder pretreatment of epon thin sections and more precise reaction product localization, entire thickness of myelin sheaths were immunostained. Thus, in electron micrographs, monoclonal and polyclonal anti-MAG immunoreactivity also have the same localization. In other electron-microscopic experiments, the same reaction product localization was observed with antiserum to myelin basic protein (MBP), a known constituent of compact myelin. Thus, results with this monoclonal anti-MAG provide important new evidence to support the localization of MAG in compact CNS myelin. Our data also suggest that monoclonal antibodies against MAG will be useful in studies of the pathogenesis of multiple sclerosis and other demyelinating diseases.
- Published
- 1984
43. LOCALIZATION OF MYELIN-ASSOCIATED GLYCOPROTEIN: EVIDENCE AND INTERPRETATIONS (Response by Henry DeF. Webster)
- Author
-
Henry deF. Webster
- Subjects
Cellular and Molecular Neuroscience ,Myelin-associated glycoprotein ,Biochemistry ,Chemistry ,Virology - Published
- 1984
44. Immunocytochemical localization of P0 protein in Golgi complex membranes and myelin of developing rat Schwann cells
- Author
-
Bruce D. Trapp, Richard H. Quarles, N H Sternberger, Henry deF. Webster, and Y. Itoyama
- Subjects
Cytoplasm ,Golgi Apparatus ,Biology ,Immunoenzyme Techniques ,symbols.namesake ,Myelin ,medicine ,Animals ,Myelin Sheath ,Antiserum ,Myelin glycoprotein ,Articles ,Cell Biology ,Anatomy ,Golgi apparatus ,Axons ,Mitochondria ,Rats ,Staining ,Cell biology ,medicine.anatomical_structure ,nervous system ,Peripheral nervous system ,symbols ,Schwann Cells ,Myelin P0 Protein ,Myelin Proteins ,Immunostaining - Abstract
P0 protein, the dominant protein in peripheral nervous system myelin, was studied immunocytochemically in both developing and mature Schwann cells. Trigeminal and sciatic nerves from newborn, 7-d, and adult rats were processed for transmission electron microscopy. Alternating 1-micrometer-thick Epon sections were stained with paraphenylenediamine (PD) or with P0 antiserum according to the peroxidase-antiperoxidase method. To localize P0 in Schwann cell cytoplasm and myelin membranes, the distribution of immunostaining observed in 1-micrometer sections was mapped on electron micrographs of identical areas found in adjacent thin sections. The first P0 staining was observed around axons and/or in cytoplasm of Schwann cells that had established a 1:1 relationship with axons. In newborn nerves, staining of newly formed myelin sheaths was detected more readily with P0 antiserum than with PD. Myelin sheaths with as few as three lamellae could be identified with the light microscope. Very thin sheaths often stained less intensely and part of their circumference frequently was unstained. Schmidt-Lanterman clefts found in more mature sheaths also were unstained. As myelination progressed, intensely stained myelin rings became much more numerous and, in adult nerves, all sheaths were intensely and uniformly stained. Particulate P0 staining also was observed in juxtanuclear areas of Schwann cell cytoplasm. It was most prominent during development, then decreased, but still was detected in adult nerves. The cytoplasmic areas stained by P0 antiserum were rich in Golgi complex membranes.
- Published
- 1981
45. JC papovavirus large tumor (T)-antigen expression in brain tissue of acquired immune deficiency syndrome (AIDS) and non-AIDS patients with progressive multifocal leukoencephalopathy
- Author
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Caroline F. Ryschkewitsch, Duard L. Walker, Henry deF. Webster, and Gerald L. Stoner
- Subjects
viruses ,Central nervous system ,Biology ,Virus ,Fixatives ,Antigen ,Immunopathology ,medicine ,Humans ,Antigens, Viral, Tumor ,Acquired Immunodeficiency Syndrome ,Multidisciplinary ,Progressive multifocal leukoencephalopathy ,Leukoencephalopathy, Progressive Multifocal ,JC Virus Infection ,Brain ,Cell Transformation, Viral ,medicine.disease ,biology.organism_classification ,JC Virus ,Virology ,medicine.anatomical_structure ,Viral disease ,Polyomavirus ,Papovavirus ,Research Article - Abstract
Progressive multifocal leukoencephalopathy (PML) is a JC papovavirus infection of the central nervous system in immunocompromised patients. It is well established that demyelination in PML is caused by JC virus infection of oligodendroglia, but whether the nonstructural regulatory protein, large tumor (T) antigen, is detectable in infected human tissue was not known. Using a modification of the peroxidase-antiperoxidase technique, we found T antigen expressed in the nuclei of cells in virus-infected sites in five cases of PML studied, including two with acquired immune deficiency syndrome (AIDS). PML occurs in AIDS at a much higher frequency than in other immunosuppressive disorders, and PML in AIDS may represent a more severe form of JC virus infection of the central nervous system.
- Published
- 1986
46. Fine structure of dividing astroglia and oligodendroglia during myelin formation in the developing mouse spinal cord
- Author
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Douglas L. Meinecke and Henry deF. Webster
- Subjects
General Neuroscience ,Central nervous system ,Anatomy ,Biology ,Spinal cord ,Cell biology ,White matter ,Mice ,Oligodendroglia ,Myelin ,medicine.anatomical_structure ,Animals, Newborn ,Spinal Cord ,nervous system ,Cytoplasm ,Astrocytes ,Neuropil ,medicine ,Ultrastructure ,Animals ,Neuroglia ,Cell Division ,Myelin Sheath - Abstract
To study the morphology and cellular relationships of dividing glial cells during myelin formation, were perfused newborn and 5-day mouse pups and embedded slices of cervical, thoracic, and lumbar cord for light and electron microscopic study. In semithin epon sections stained with toluidine blue, all levels of spinal cord at both ages contained mitotic glia in gray columns and funiculi. In electron micrographs of funiculi, dividing astroglia containing bundles of glial filaments, many glycogen granules, and had large processes extending into the surrounding neuropil. Cytoplasmic organelles of many immature interphase oligodendroglia and mitotic oligodendroblasts were similar and included microtubules, clusters of free ribosomes, and scattered profiles of granular endoplasmic reticulum. Unlike astroglia, dividing oligodendroblasts lacked large processes and in metaphase they were ellipsoids and had smooth plasma membranes. When these cells were studied in alternating serial thin and semithin sections over 10-15 micrometers distances, we did not identify connections between myelin sheaths and mitotic oligodendroblasts. Our findings indicate that oligodendroglia in developing white matter multiply before developing large processes. Our data also suggest that oligodendroglia do not divide while forming myelin.
- Published
- 1984
47. The penetration of fluorescein-conjugated and electron-dense tracer proteins into Xenopus tadpole optic nerves following perineural injection
- Author
-
Paul J. Reier, Takeshi Tabira, and Henry deF. Webster
- Subjects
Cell Membrane Permeability ,Xenopus ,CNS demyelination ,Horseradish peroxidase ,chemistry.chemical_compound ,Parenchyma ,Extracellular ,Animals ,Humans ,Fluorescein ,Molecular Biology ,Horseradish Peroxidase ,Myelin Sheath ,Glia limitans ,Right optic nerve ,biology ,General Neuroscience ,Optic Nerve ,Anatomy ,Fluoresceins ,Microscopy, Fluorescence ,chemistry ,Immunoglobulin G ,Larva ,Ferritins ,biology.protein ,Optic nerve ,Neurology (clinical) ,Developmental Biology - Abstract
The permeability of Xenopus tadpole optic nerves to macromolecules was studied in order to evaluate the usefulness of this system for studying mechanisms of serum-induced CNS demyelination in vivo. Single injections of either horseradish peroxidase (HRP), ferritin or fluorescein-conjugated human IgG were injected around the right optic nerve and tadpoles were then sacrificed between 15 min and 48 h. Each of the tracers had penetrated the nerve parenchyma by 30 min. Entry of HRP and ferritin occurred mainly via extracellular clefts between adjacent astrocytic endfeet in the glia limitans region. A similar mode of passage was suggested for IgG. Once within the nerve, the tracers became rapidly associated with myelinated axons. HRP was also seen in the periaxonal space but did not directly penetrate the myelin sheath. By 24 h, extracellular localization of tracer was virtually absent with nearly all of the tracer now being concentrated in vesicles within astrocytic processes and perikarya. The distribution of the tracers was not confined to the optic nerve on the injected side; some was seen in adjacent cranial peripheral nerves and surrounding extraocular musculature. Also, tracers eventually penetrated the pial sheath of the contralateral optic nerve. The results of this study indicate that tadpole optic nerves are permeable to a wide range of macromolecules. Furthermore, the distribution of these tracers to nearby cranial peripheral nerves may provide an important opportunity for testing the differential effect of various substances on central and peripheral myelin sheaths.
- Published
- 1976
48. Non myelin-forming perineuronal Schwann cells in rat trigeminal ganglia express P0 myelin glycoprotein mRNA during postnatal development
- Author
-
Laura Manuelidis, Henry deF. Webster, and Lajos Lamperth
- Subjects
Aging ,Schwann cell ,In situ hybridization ,Biology ,Horseradish peroxidase ,law.invention ,Cellular and Molecular Neuroscience ,Myelin ,law ,medicine ,Animals ,RNA, Messenger ,Trigeminal Nerve ,Molecular Biology ,Myelin Sheath ,Myelin glycoprotein ,Nucleic Acid Hybridization ,Rats, Inbred Strains ,DNA ,Anatomy ,Rats ,Cell biology ,Vibratome ,medicine.anatomical_structure ,Peripheral nervous system ,biology.protein ,Schwann Cells ,Electron microscope ,Myelin P0 Protein ,Myelin Proteins - Abstract
To determine whether P0 myelin glycoprotein mRNA is expressed in Schwann cells that ensheath neurons and do not form myelin, we probed aldehyde-fixed vibratome sections of developing and adult trigeminal ganglia with a biotinylated P0 cDNA. For probe detection, vibratome sections were treated with nickel-enhanced horseradish peroxidase (HRP). At each age, some vibratome sections were used to count numbers of HRP-positive and -negative satellite cells. The percentages of HRP-positive satellite cells at 2, 7, and 15 days were 22%, 30% and 14%. None was positive at 30 days or in the adult. Other vibratome sections were embedded for light and electron microscopic study. In semithin sections from ganglia removed from 2-day-old rats, small dot-like densities of HRP were located in perinuclear regions of a few perineuronal Schwann cells. In 7-day-old ganglia, more of these Schwann cells contained HRP. In thin sections studied with the electron microscope, peroxidase was found in cytoplasmic regions enriched in granular endoplasmic reticulum and ribosomes. At 2 and 7 days, HRP densities in perinuclear regions were larger and more numerous than at 15 days. No signal was detected in 30 day or adult perineuronal Schwann cells. The results show that early in postnatal development, P0 mRNA is expressed in some Schwann cells that ensheath neurons, that do not contain immunocytochemically detectable levels of P0 and that do not ever form myelin.
- Published
- 1989
49. Characterization of two subcellular fractions isolated from myelinated axons
- Author
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Michel Dolivo, Michèle Bény, Jean-Marie Matthieu, and Henry deF. Webster
- Subjects
Gel electrophoresis ,biology ,Chemistry ,General Neuroscience ,Fraction (chemistry) ,Lipids ,Axons ,Axolemma ,Cerebroside ,White matter ,Myelin ,medicine.anatomical_structure ,Biochemistry ,Compact myelin ,biology.protein ,medicine ,Animals ,Cytochrome c oxidase ,Rabbits ,Glycolipids ,Myelin Proteins ,Myelin Sheath ,Subcellular Fractions - Abstract
Myelin and a heavy membrane fraction ( 1.0 1.2 fraction) were isolated from rabbit white matter by a slight modification of the procedure for bovine CNS. The specific activities of acetylcholinesterase and Na + , K + -ATPase were higher in the 1.0 1.2 fraction than in myelin. In contrast, the cerebroside content and 2′, 3′-cyclic nucleotide 3′-phosphohydrolase activity in the 1.0 1.2 fraction were 4.5 and 3.4 times lower than in myelin. Total lipids accounted for only 30% of the 1.0 1.2 fraction's dry weight; for myelin, they represented 70%. Polacrylamide gel electrophoresis showed the presence of many high molecular weight proteins and glycoproteins in the 1.0 1.2 fraction but myelin components were practically missing. Cytochrome c oxidase and NADPH-cytochrome c reductase activities suggested about 15% contamination in the 1.0 1.2 fraction but less than 5% for myelin. In electron micrographs of the 1.0 1.2 fraction, there were many membraneous profiles that varied in size, some mitochondrial fragments, and only a few lamellar whorls of compact myelin. The results suggest that the 1.0 1.2 fraction is different from other myelin-related fractions and is probably enriched in axolemma.
- Published
- 1977
50. A double-label method detects both early (T-antigen) and late (capsid) proteins of JC virus in progressive multifocal leukoencephalopathy brain tissue from AIDS and non-AIDS patients
- Author
-
Duard L. Walker, Caroline F. Ryschkewitsch, Gerald L. Stoner, D. Soffer, and Henry deF. Webster
- Subjects
viruses ,Immunology ,JC virus ,medicine.disease_cause ,Virus ,Capsid ,Antigen ,medicine ,Humans ,Immunology and Allergy ,Antigens, Viral, Tumor ,Antiserum ,Acquired Immunodeficiency Syndrome ,biology ,Progressive multifocal leukoencephalopathy ,Leukoencephalopathy, Progressive Multifocal ,medicine.disease ,Immunohistochemistry ,JC Virus ,Virology ,Oligodendroglia ,Neurology ,Polyclonal antibodies ,biology.protein ,Neurology (clinical) ,Polyomavirus - Abstract
A new double-label immunocytochemical method detects JC virus (JCV) early (T-antigen) and late (capsid) proteins simultaneously in cryostat sections of progressive multifocal leukoencephalopathy (PML) brain tissue from both acquired immunodeficiency syndrome (AIDS) and non-AIDS patients. T-antigen is detected with a monoclonal antibody (PAb 416) followed by goat anti-mouse IgG and mouse Clono-PAP, while capsid proteins are detected by a rabbit polyclonal antiserum to capsid proteins followed by biotinylated goat anti-rabbit IgG and streptavidin-alkaline phosphatase conjugate. The substrates are 3,3'-diaminobenzidine and Vector Red I, respectively. With this method some infected glial cells stain for late (capsid) antigens in the nucleus, while others show early protein (large T-antigen) immunoreactivity. The latter are likely to be astrocytes infected abortively or oligodendrocytes in the early stages of a productive JCV infection.
- Published
- 1988
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