摘要:

The central nervous system (CNS) pathology of HTLV‐I associated myelopathy or tropical spastic paraparesis (HAM/TSP) is reviewed, based mainly on 12 autopsy cases of Japanese HAM/TSP with a serological confirmation of HTLV‐I infection. The essential histopathological feature of HAM/TSP is a chronic progressive inflammatory process heralded by parenchymal infiltration of memory CD4 cells. The inflammation involves both the grey and white matter of the spinal cord, and progresses for more than three years after the onset of neurological symptoms, resulting in preferential degeneration of the white matter. In cases with a history of more than nine years, however, the spinal cord lesions appears degenerative rather than inflammatory. Both the inflammation and the white matter degeneration are most conspicuous in the lower thoracic cord. The lateral funiculus is always and most severely affected. Although the parenchymal tissue degeneration is not confined to any particular long tracts, symmetrical degeneration of the lateral pyramidal tract is evident in all cases. The involvement of the posterior and anterior funiculi is variable and neurons are relatively well preserved. Since evidence for HTLV‐I infection in the CNS is limited to detection of proviral DNA by the polymerase chain reaction (PCR) and isolation of the virus from CSF cells, autoimmune nature of the disease is suspected, but is supported by ample evidence for derangements of the host immune system compatible with those of autoimmune diseases. Recent studies on induction of white matter degeneration in the rat with a topographical similarity to human HAM/TSP is also briefly reviewed. However, in the rat disease, inflammatory cell infiltrations are inconspi

ISSN:1015-6305    

DOI:10.1111/j.1750-3639.1993.tb00719.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

The response of microglial cells to cortical spreading depression (CSD) was studied in rat brain by immunocytochemistry. CSD was elicited for one hour by the topical application of 4M potassium chloride solution and the microglial reaction examined immunocytochemically after 4, 16, 24 and 72 hours. CSD was sufficient to induce a microglial reaction throughout the cortex at 24 hours. Activated microglial cells furthermore showed a strikingde‐novoexpression of major histocompatibility complex class II antigens. In contrast, no microglial reaction was observed in the cortex of sham‐operated animals. This microglial reaction in response to CSD was not associated with histologically detectable neuronal damage. These results support the view that microglial cells are extremely sensitive to changes of the brain microenvironment. Their activation may be related to changes of ion homeostasis in the brain which are not sufficient to trigger neuronal inj

ISSN:1015-6305    

DOI:10.1111/j.1750-3639.1993.tb00720.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Glioblastoma multiforme is a clinically and histologically heterogeneous lesion; however, to date, it has not been possible to subdivide glioblastomas on a clinical, histopathological or biological basis. Previous studies have demonstrated that loss of portions of chromosomes 10 and 17 and amplification of the epidermal growth factor receptor (EGFR) gene are the most frequent genetic alterations in glioblastoma. We therefore examined 74 glioblastomas from 67 patients for loss of heterozygosity on chromosomes 10 and 17, and for amplification of the epidermal growth factor receptor gene, to determine whether glioblastomas can be subtyped on a genetic basis. Using Southern blot analysis we were able to detect different patterns of genomic alterations. Eighteen of 67 informative patients were characterized by a loss of heterozygosity on the short arm of chromosome 17 in the tumor tissue. Forty‐five of 64 informative patients showed a loss of heterozygosity on chromosome 10. Amplification of the epidermal growth factor receptor gene was noted in 25 of 67 patients and was restricted to those glioblastomas that had lost portions of chromosome 10. Epidermal growth factor receptor gene amplification occurred significantly more often in patients without chromosome 17p loss than in patients with chromosome 17p loss (p = 0.01). In addition, those glioblastomas with a loss of chromosome 17p occurred in patients significantly younger than those with glioblastomas characterized by EGFR gene amplification (p = 0.001). These data emphasize the genetic heterogeneity of glioblastoma and suggest the division of glioblastoma into genetic subset

ISSN:1015-6305    

DOI:10.1111/j.1750-3639.1993.tb00721.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

ISSN:1015-6305    

DOI:10.1111/j.1750-3639.1993.tb00722.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Neurofilament proteins are continuously modified during their lifetime by a succession of protein kinases and phosphatases. Site‐specific phosphorylation or dephosphorylation within different polypeptide domains of each neurofilament subunit is now believed to regulate such behaviors of neurofilaments as subunit polymerization and exchange, axonal transport, interactions with other cytoskeletal proteins and degradation. Local regulation of phosphorylation events could account for variations in the size, morphology and dynamics of the neurofilament network in different regions of the neuron. The apparent greater plasticity of the neurofilament network in regions like the perikaryon, initial segment and nodes along the axon may provide some insight into the vulnerability of these regions in neurofibrillary diseas

ISSN:1015-6305    

DOI:10.1111/j.1750-3639.1993.tb00723.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Tauprotein was a well‐studied molecule before it was discovered in the Alzheimer neurofibrillary tangles. As a microtubule‐associated protein (MAP), it continues to be of interest to microtubule biologists who have provided a rather rich knowledge about this protein. Recent work suggests thattau, a neuronal MAR is capable of generating some features of an axonal shape and an axon‐like organization of the cytoskeleton. The importance of tau in pathology stems from its relationship to Alzheimer paired helical filaments and dystrophic neurites.Tauwas first believed to be a component of paired helical filaments based upon immunocytochemical grounds (1–6) and then conclusively demonstrated by protein chemical techniques (7–9). Most recently it was shown that bacterially expressedtaufragments from the microtubule‐binding domain can self‐assemble into paired helical filaments that resemble those from the Alzheim

ISSN:1015-6305    

DOI:10.1111/j.1750-3639.1993.tb00724.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

The neuronal cytoskeleton is one of the most profoundly altered organelles in late life neurodegenerative disorders that are characterized by progressive impairments in cognitive abilities. The elucidation of the protein building blocks of these organelles as well as advances in understanding how these proteins become altered in Alzheimer's disease (AD) and other less common dementing illnesses, i.e., diffuse Lewy body disease (DLBD) or the Lewy body variant of AD (LBVAD), will provide insights into the molecular basis of these disorders. Within, we review evidence that normal adult humantauis abnormally phosphorylated and converted into the subunits of AD paired helical filaments (PHFs), and that Lewy bodies (LBs) represent accumulation of altered neurofilament (NF) triplet subunits. Although the precise biological consequences of PHF and LB formation in neurons is unknown, growing evidence suggests that the formation of PHFs and LBs from normal neuronal cytoskeletal proteins could have deleterious effects on neuronal function and survival. Finally, insights into the composition of PHFs and LBs could lead to the development of novel strategies for the timely and accurate diagnosis of AD, DLBD and the LBVAD.

ISSN:1015-6305    

DOI:10.1111/j.1750-3639.1993.tb00725.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Immunochemical staining to detect ubiquitin has become an essential technique in evaluating neurodegenerative processes. Age related staining is seen in myelin, in nerve processes in lysosome‐related dense bodies, and in corpora amylacea. There is a constant association between filamentous inclusions and the presence of ubiquitin. Intermediate filaments associated with ubiquitin, α B crystallin and enzymes of the ubiquitin pathway are the basis of Lewy bodies and Rosenthal fibres, as well as related bodies outside the nervous system. Neurofibrillary tangles in diverse diseases are associated with ubiquitin as are several othertaucontaining inclusions in both neurones and glia. Inclusions in motor neurones and non‐motor cortex characterizing amyotrophic lateral sclerosis (ALS) and certain related forms of frontal lobe dementia can only be readily detected by anti‐ubiquitin. Anti‐ubiquitin also identifies both filamentous and lysosomal structures in neuronal processes as well as in some swollen neurones. Involvement of ubiquitin‐containing elements of the lysosomal system appears important in pathogenesis of prion encephalopathies. Despite great advances in understanding cell biology of the ubiquitin pathway there are as yet few insights into the precise role played by ubiquitin in neuron

ISSN:1015-6305    

DOI:10.1111/j.1750-3639.1993.tb00726.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Ubiquitin modification of a variety of protein targets within the cell plays important roles in many cellular processes. Among these are regulation of gene expression, regulation of cell cycle and division, involvement in the cellular stress response, modification of cell surface receptors, DNA repair, and biogenesis of mitochondria and ribosomes. The best studied modification occurs in the ubiquitin‐dependent proteolytic pathway. Degradation of a protein by the ubiquitin system involves two discrete steps. Initially, multiple ubiquitin molecules are covalently linked in an ATP‐dependent mode to the protein substrate. The protein moiety of the conjugate is then degraded by a specific protease into free amino acids with the release of free and reutilizable ubiquitin. This process also requires energy. In addition, stable mono‐ubiquitin adducts are also found intracellularly, for example, those involving nucleosomal histories. Despite the considerable progress that has been made in elucidating the mode of action and roles of the ubiquitin system, many problems remain unsolved. For example, very little is known about the cellular substrates of the system and the signals that target them for conjugation and degradation. The scope of this review is to summarize briefly what is currently known on the role of the ubiquitin system in protein turnover, and to discuss in detail the mechanisms involved in selection of substrates for conjugation and in degradation of ubiquitin‐conjugated p

ISSN:1015-6305    

DOI:10.1111/j.1750-3639.1993.tb00727.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Complex sets of nervous system functions are dependent on proper working of the synaptic apparatus, and these functions are regulated by diverse synaptic proteins that are distributed in various subcellular compartments of the synapse. The most extensively studied synaptic proteins are synaptophysin, the synapsins, growth associated protein 43 (GAP‐43), SV‐2, and p65. Moreover, synaptic terminals contain a great number of other proteins involved in calcium transport, neurotransmission, signaling, growth and plasticity. Probes against various synaptic proteins have recently been used to study synaptic alterations in human disease, as well as in experimental models of neurological disorders. Such probes are useful markers of synaptic function and synaptic population density in the nervous system. For the present, we will review the role of synaptic proteins in the following conditions: Alzheimer's disease (AD) and other disorders including ischemia, disorders where synapse‐associated proteins are abnormally accumulated in the nerve terminals, synaptic proteins altered after denervation, and synaptic proteins as markers in neoplastic disorders. The study of the molecular alterations of the synapses and of plasticity might yield important clues as to the mechanisms of neurodegeneration in AD, and of the patterns of presynaptic and dendritic damage under diverse pathological condi

ISSN:1015-6305    

DOI:10.1111/j.1750-3639.1993.tb00728.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY