摘要:

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 th

ISSN:1015-6305    

DOI:10.1111/j.1750-3639.1995.tb00570.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Meningiomas are among the most common human brain tumors. Occasionally patients develop multiple meningiomas. While it has been surmised that these are multiple primary meningiomas, it is possible that they represent spread of a single primary tumor. Recently, the neurofibromatosis type 2 (NF2) tumor suppressor gene has been shown to carry mutations in meningiomas. In the present study we have analyzed multiple meningiomas from two patients for point mutations in the NF2 gene by SSCP analysis and direct sequencing. We detected point mutations in the meningiomas from both patients. The first patient from which six tumors were available had a three base pair deletion in the splice donor region of exon 7. All tumors showed the identical mutation. The second patient with two independent meningiomas had a nonsense mutation in exon 8 which was the same in both tumors. Analysis of constitutional DNA revealed a wildtype DNA sequence in both cases. There was no family history of neurofibromatosis type 2 in either patient. These data provide strong evidence for a monoclonal origin of multiple meningiomas. Early subarachnoid spread is the most likely mechanism for the formation of these tumors.

ISSN:1015-6305    

DOI:10.1111/j.1750-3639.1995.tb00571.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

This report describes clinical, neuropathological and molecular genetic findings in a Swiss family with four brain tumours in only two generations. The neoplasms observed covered a wide range of biologic behaviour, from a slowly growing lesion already apparent at birth, to anaplastic astrocytoma in a young adult and glioblastomas at the age of less then 10 years. The only non‐neural neoplasms in this family were a case of leukemia and an adrenocortical carcinoma. A germline deletion of codon 236 of thep53tumour suppressor gene was identified as an underlying cause and detected in all affected family members. This mutation has not previously been reported as germline transmission or in sporadic tumours. The unusual accumulation of CNS tumours may be due to a certain organ‐specific effect of this particularp53mutation or it may reflect the specific genetic back‐ground of this f

ISSN:1015-6305    

DOI:10.1111/j.1750-3639.1995.tb00572.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

ISSN:1015-6305    

DOI:10.1111/j.1750-3639.1995.tb00573.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

When their kinship was surmised 35 years ago, scrapie and kuru were linked mainly by their neuropathologic similarity. Most notable were neuronal degeneration and intense astrocytosis with little, if any, inflammation. Especially eye‐catching in kuru were the vacuolated neurons ‐ the histologic hallmark of scrapie that drew me to the human disease from the start. Because spongiform change in gray matter neuropil is variable and usually lacks prominence in both scrapie and kuru, it was not part of the resemblance I saw in them. Amyloid plaques, so characteristic of kuru, also did not figure in the similarity, for they had not yet been reported in scrapie. Despite the uncertainty at the time about the pathologic essence of scrapie, the two diseases still looked alike. Their eventual connection ‐ however tenuously held together initially by the few likenesses ‐ has survived as a tribute to morphologic observation. It provided the essential link that helped ensure the kinship a lasting place in comparative neuropa

ISSN:1015-6305    

DOI:10.1111/j.1750-3639.1995.tb00574.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Although typical cases of Creutzfeldt‐Jakob disease are readily recognized pathologically and clinically, variant forms often pose a diagnostic challenge. From the 1920's, when this disease was first characterized, until quite recently diagnosis relied heavily on morphologic changes. New advances in immunoassays and PrP gene analysis now provide important adjuncts in recognizing the spectrum of disorders of PrP metabolism associated with these transmissible encephalopathie

ISSN:1015-6305    

DOI:10.1111/j.1750-3639.1995.tb00575.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Fatal familial insomnia (FFI) and a subtype of familial Creutzfeldt‐Jakob disease (CJD178) are two prion diseases that have different clinical and pathological features, the same aspartic acid to asparagine mutation (D178N) at codon 178 of the prion protein (PrP) gene, but distinct genotypes generated by the methionine‐valine polymorphism at codon 129 (129M or 129V) in the mutant allele of the PrP gene. The D178N, 129M allele segregates with FFI while the D178N, 129V allele segregates with CJD178. The proteinase K resistant PrP (PrPres) isoforms present in FFI and CJD178differ in degree of glycosylation and size. Thus, the amino acid, methionine or valine, at position 129 of the mutant allele, in conjunction with D178N mutation results in significant alterations of PrPresin FFI and CJD178. The 129 polymorphic site also exerts influence through the normal allele: the course of the disease is shorter in the patients homozygous at codon 129 and other minor but consistent phenotypic differences occur between homozygous and heterozygous FFI patients. The comparative study of PrPresdistribution in FFI homozygotes and heterozygotes at codon 129 has lead to the conclusion that the phenotypic differences observed between these two FFI patient populations may be the result of different rates of conversion of normal PrP into PrPres, at least in some brain regi

ISSN:1015-6305    

DOI:10.1111/j.1750-3639.1995.tb00576.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Clinico‐pathological phenotypes of patients with prion diseases were compared with their PrP genotyes and transmission rate to mice. Sporadic and iatrogenic CJD patients without mutation and familial CJD patients with E200K showed uniform clinico‐pathological features, synaptic‐type deposition of PrPCJDand high rate of transmission of the disease to mice. GSS patients with P102L showed long duration of ataxia, numerous plaques in cerebellar cortex and transmitted the disease to mice in only one third of inoculated cases. Other mutations such as P105L, A117V, Y145stop, V180I, M232R and various insertions have particular phenotypes, distinct distribution patterns of PrPCJD, and untransmitted or inconclusive transmission to mice. Polymorphism at codon 129 may modify the phenotypes and transmission rate to mice. Therefore, prion diseases have a wide range from infectious disease to non‐infectious, hereditary metabolic

ISSN:1015-6305    

DOI:10.1111/j.1750-3639.1995.tb00577.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Gerstmann‐Sträussler‐Scheinker disease is an autosomal dominant disorder with a wide spectrum of clinical presentations including ataxia, spastic paraparesis, extrapyramidal signs, and dementia. The patients present with symptoms in the third to sixth decade of life and the mean duration of illness is five years. Mutations at codons 102, 105, 117, 145, 198 and 217 of the open reading frame of the prion protein gene have been associated with GSS disease. As a result of the mutations, a substitution at the corresponding residues of the prion protein occurs, or as in the case of the STOP mutation at codon 145, a truncated protein is produced. Neuropathologically, the common denominator is a cerebral prion protein amyloidosis; however, there is significant variability in the pattern of amyloid deposition in regions of the central nervous system among reported families. Amyloidosis coexists with severe spongiform degeneration in patients with the mutation at codon 102, and with neurofibrillary degeneration in the patients with mutation at codons 145, 198 and 217. The development of a transmissible spongiform encephalopathy in animals inoculated with brain tissue from affected subjects with mutation at codon 102 suggests that in some formsofgenetically‐determined Gerstmann‐Sträussler‐Scheinker disease, and particularly those characterized by severe spongiosis, amyloidogenesis and production of an infectious “agent” occur concomitantly via mechanisms that are only parti

ISSN:1015-6305    

DOI:10.1111/j.1750-3639.1995.tb00578.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

The concept that prions are novel pathogens which are different from both viroids and viruses has received increasing support from many avenues of investigation over the past decade. Enriching fractions from Syrian hamster (SHa) brain for scrapie prion infectivity led to the discovery of the prion protein (PrP). Prion diseases of animals include scrapie and “mad cow” disease; those of humans present as inherited, sporadic and infectious neurodegenerative disorders, two of which are called Creutzfeldt‐Jakob disease (CJD) and Gerstmann‐Sträussler‐Scheinker disease (GSS). The inherited human prion diseases are genetically linked to mutations in the PrP gene that result in non‐conservative amino acid substitutions. Transgenic (Tg) mice expressing PrP carrying a GSS mutation developed neurodegeneration spontaneously and produced prions de novo. In other studies, Tg mice expressing both SHa and mouse (Mo) PrP genes were used to demonstrate that the “species barrier” for scrapie prions resides in the primary structure of PrP. This concept was strengthened by the results of studies in which mice expressing chimeric Mo/human (Hu) PrP transgenes were constructed which differ from MoPrP by nine amino acids between residues 96 and 167. All of the Tg(MHu2M) mice developed neurologic disease ∼200 days after inoculation with brain homogenate from three patients who died of CJD. About 10% of Tg(HuPrP) mice expressing HuPrP and non‐Tg mice developed neurologic disease>500 days after inoculation with CJD prions. The different susceptibilities of Tg(HuPrP) and Tg(MHu2M) mice to human prions indicate that additional species specific factors such as chaperone proteins are involved in prion replication. Diagnosis, prevention and treatment of human prion diseases should be facilitated by study of Tg(MHu2M) mice. Our findings and those from other studies suggest that mutant and wtPrP interact, perhaps through a chaperone‐like protein, during the pathogenesis

ISSN:1015-6305    

DOI:10.1111/j.1750-3639.1995.tb00579.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY