ISSN:1015-6305    

DOI:10.1111/j.1750-3639.1990.tb00629.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

In recent years much progress has been made toward a better understanding of the nature and function of microglial cells. This review summarizes new developments and attempts to provide a perspective for future avenues to take in microglial research. Microglia are considered to play an active role in a variety of neurological diseases. Their function in forming a network of immune competent cells within the CNS is discussed.

ISSN:1015-6305    

DOI:10.1111/j.1750-3639.1990.tb00630.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Cumulative evidence suggests that varicella‐zoster virus (VZV) can infect walls of CNS arteries, causing stroke in man. We review observations relating infection with this neurotropic virus to the development of arteritis in the CNS and note evidence supporting the hypothesis that VZV spreads from ganglionic reactivation sites to the arterial wall by neural pathways. Problems relating to the pathogenesis of arteritis and experimental approaches to their solution are suggeste

ISSN:1015-6305    

DOI:10.1111/j.1750-3639.1990.tb00631.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

ISSN:1015-6305    

DOI:10.1111/j.1750-3639.1990.tb00632.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Malignant gliomas and medulloblastomas which are the most common primary malignant brain tumours of adults and children, respectively, resemble other neurogenic tumours as they frequently contain gene amplification and show non‐random loss of specific chromosomal regions. In gliomas the gene which is most often amplified, is the epidermal growth factor receptor gene. In many cases the gene is rearranged as well, producing abnormally small epidermal growth factor receptor proteins. More than 80% of tumours have lost chromosome 10 and losses of 9p13, 17p and 22 occur in subgroups of cases. 17p loss is associated with point mutations of the p53 gene, but the relevant genes in the other chromosomal regions remain to be identified. For medulloblastoma the most frequent chromosomal abnormality is i (17q). Whether or not p53 gene mutations are the targets of 17p losses in these tumours remains to be determined. Approximately 5% of medulloblastoma biopsies contain gene amplification, although the incidence in medulloblastoma cell lines is more than 80%. c‐mycis the gene which is most frequently amplified in this tumour type. The relationship of these various molecular genetic abnormalities to the biology of the tumours and the course of the patients remains largely unexplo

ISSN:1015-6305    

DOI:10.1111/j.1750-3639.1990.tb00633.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

There are many findings which suggest that an individual may inherit a predisposition for developing a meningioma. The cytogenetics of meningiomas has been well known for some time with monosomy of chromosome 22 as the most characteristic finding. We have confirmed the cytogenetic findings in cultured cells, using molecular genetic techniques on primary tumour tissue. The only difference found between the results of the two techniques was the greater proportion of terminal deletions of the long arm of chromosome 22 detected by the molecular method. The minimal deletion common to 81 meningiomas, and thus the position of the tentative meningioma tumour suppressor gene (TSG), has been determined to lie distal to the myoglobin locus on the long arm of chromosome 22, corresponding to the region 22q12.3‐qter. All common histological types of meningioma show the same genetic abnormalities. Study of one tumour with areas of both meningothelial and anaplastic meningioma demonstrated the tumour to be clonal and a partial deletion of 22q to have occurred prior to the development of anaplasia. In order to map in more detail the position of, and finally identify, the TSG involved, a new series of 195 chromosome 22 genomic DNA fragments have been cloned. Current evidence suggests that the genes involved in neurofibromatosis type 2 and meningioma are located at different points on the long arm of chromosome 22 and thus are separate entitie

ISSN:1015-6305    

DOI:10.1111/j.1750-3639.1990.tb00634.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Retinoblastoma, the most common intraocular malignancy of children, has served as an important paradigm for understanding the events involved in neoplastic transformation. Much of the contemporary molecular description of human cancers stems directly from experimental approaches first developed to study this childhood tumour. This analytical methodology has demonstrated a major role for heritable predisposition in tumourigenesis, provided evidence for tissue pleiotropy of cancer genes, and revealed a more precise estimation of the number, activity, and location of other tumour suppressor loci.

ISSN:1015-6305    

DOI:10.1111/j.1750-3639.1990.tb00635.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Neurofibromatosis 1 and neurofibromatosis 2 are clinically distinct autosomal dominant disorders that affect an estimated 1.5 million individuals throughout the world. The genetic defect in each disorder has been mapped to different chromosomes, NF1 to chromosome 17 and NF2 to chromosome 22. Progress towards the cloning of the NF1 gene has proceeded rapidly. The NF1 locus was bracketed using genetic linkage analysis on NF1 affected pedigrees. Physical mapping methods were then used to precisely map the translocation breakpoints in each of two NF1 affected individuals who harbored constitutional chromosomal translocations in the putative NF1 region of chromosome 17. The region of DNA located between the two translocations has been cloned in cosmids and yeast artificial chromosomes and a number of RNA coding sequences have been identified. The identification of the NF1 gene will depend on finding mutations in the DNA of affected individuals. In the case of NF2, progress seems to have been less rapid, in part due to the lower availiability of NF2 affected pedigrees. The genetic defect has been mapped to the long arm of chromosome 22 by studies of chromosomal loss in the tumours associated with this disease. Subsequent genetic mapping has confirmed this location. Flanking DNA markers for the NF2 locus have been identified. The region of DNA between these markers is in the order of 5–10 Mb. The identification of chromosomal aberrations in patients with NF2 that involve chromosome 22 will play an important role in the identification of the NF2 gene in much the same way as they have in NF

ISSN:1015-6305    

DOI:10.1111/j.1750-3639.1990.tb00636.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Human neuroblastoma cells often carry non‐random chromosomal abnormalities signalling genetic alterations. Quite frequent are ‘double minutes’ (DMs) and homogeneously staining regions (HSRs), both cytogenetic manifestations of amplified DNA, and chromosome Ip‐deletions indicating loss of genetic information. With the identification of amplifiedMYCNand the demonstration of a consensus deletion spanning the chromosome 1p36.1–2 region it appears now likely that both amplification of a cellular oncogene and loss of a tumour‐suppressor gene play an important role in neuroblastoma. Amplification ofMYCNis an indicator for poor prognosis, even when classical morphological criteria would suggest a better outcome. Consequently, patients with amplification are subjected to more intensive therapeutic regimens. Amplification ofMYCNis a paradigm for the clinical use of an oncogene

ISSN:1015-6305    

DOI:10.1111/j.1750-3639.1990.tb00637.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

At least two genetic events have been identified which are characteristic of certain neuroblastomas. These are loss of a critical region on the short arm of chromosome 1, and amplification of theMYCNproto‐oncogene. Our studies suggest that the two genetic events may be related, and that loss of heterozygosity (LOH) for chromosome 1p may precede the development of amplification.RASgene mutations appear to be rare, and no other oncogene has been shown to be consistently activated by amplification or other mechanism. LOH for chromosome 14q has been identified recently, but its frequency and significance is not clear. Based on flow cytometric analysis of DNA content, tumour cytogenetics and molecular studies, three distinct genetic subsets of neuroblastomas are emerging. The first is characterized by a hyperdiploid or near‐triploid modal karyotype, with few if any cytogenetic rearrangements. These patients are generally less than one year of age with localized disease and a good prognosis. The second group is characterized by a near‐diploid or near‐tetraploid karyotype, with no consistent rearrangement identified to date. They are generally older patients with more advanced stages of disease that progress slowly and are ultimately fatal. The third group is characterized by a neardiploid or tetraploid karyotype, with deletions or LOH for chromosome 1p, amplification ofMYCN, or both. These patients are generally older with advanced stages of disease which is rapidly progressive. Thus, genetic analysis of neuroblastoma cells by karyotype, flow cytometry and determination ofMYCNcopy number provides information that has prognostic significance and can more appropriately direct the choice of treatment. A better understanding of these genetic abnormalities and the biochemical pathways that they effect may provide insights into malignant transformation and progression, as well as provide targets for future therapeutic app

ISSN:1015-6305    

DOI:10.1111/j.1750-3639.1990.tb00638.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY