摘要:

Primary central nervous system lymphomas (PCNSL) are uncommon neoplasms accounting for less than 2% of brain tumours. Their incidence appears to be increasing across a wide age range, in both immunocompetent and immunosuppressed populations. Particular risk groups include those with congenital and acquired immunodeficiencies and transplant recipients. The spread of the AIDS epidemic has seen large numbers of complicating PCNSL develop. Epstein‐Barr virus infection appears to play a role in the development of these lymphomas in the immunosuppressed population. The aetiology of these tumours in the immunocompetent is uncertain. Their tendency to remain within the nervous system is not well understood but may be a function of CMS binding molecules carried by lymphocytes. Clinically PCNSL may present with a wide variety of signs and symptoms and has a capacity to mimic many other neurological conditions. Radiologically they appear as hyperdense homogenous deposits in subcortical white matter. Although most lesions are intermediate or high grade B cell lymphomas, T cell lymphomas are being recognised with increasing frequency. Immunohistochemistry and genotypic analysis have an important role in accurately characterising PCNSL, particularly in stereotactic biopsies. Involvement of multiple areas of the neuraxis, the eye and multiple intracranial sites can occur in the absence of obvious systemic lymphoma. The role of surgery in their treatment is uncertain. A combination of radiotherapy and chemotherapy can increase the length of survival. The prognosis, however, remains poor in comparison with nodal lymphomas, and particularly so in those with AID

ISSN:1015-6305    

DOI:10.1111/j.1750-3639.1992.tb00677.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

ISSN:1015-6305    

DOI:10.1111/j.1750-3639.1992.tb00678.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Molecular genetics, biochemistry, immunology and morphology, are being applied in a coordinated fashion to unveil the molecular basis of the mitochondrial encephalomyopathies. Mutations of mitochondrial DNA (mtDNA) have been found in well characterized clinical groups of these disorders. New and old morphologic methods have been applied to investigate muscle biopsies from patients with mtDNA mutations. Important observations have been made on the cellular localization of normal and mutated mtDNA and on the expression of mtDNA‐encoded polypeptides. These observations have provided insight into the pathogenesis of respiratory chain enzyme deficiency at the level of individual muscle fibers. Application of immunocytochemical andin situhybridization techniques at the electron microscopic level will extend these studies to the level of individual mitochondri

ISSN:1015-6305    

DOI:10.1111/j.1750-3639.1992.tb00679.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

In the past few years several syndromes have been associated with lesions of the human mitochondrial DNA. MtDNA is a small, circular extra‐nuclear chromosome encoding essential components of the respiratory chain. MtDNA‐related syndromes can be divided into two groups: mitochondrial encephalomyopathies, characterized by the presence of ragged‐red fibres (RRF) as the morphological hallmark, or “pure” encephalopathies with no gross morphological abnormalities in muscle. The first group includes myoclonic epilepsy with ragged‐red fibres (MERRF), mitochondrial encephalomyopathy with lactic acidosis and stroke‐like episodes (MELAS), Kearns‐Sayre syndrome (KSS), chronic progressive external ophthalmoplegia (CPEO) and a new entity, maternally inherited myopathy and cardiomyopathy. The second group includes Leber's Hereditary Optic Neuroretinopathy (LHON) and the newly described ataxia‐retinitis pigmentosa‐dementia complex. Three kinds of molecular lesions have been identified: point mutations of protein encoding mtDNA‐genes (similar to yeastmit‐mutations); point mutations of mtDNA‐tRNA genes (similar to yeastsyn‐mutations); and large‐scale rearrangements of mtDNA (similar to yeast ρ‐ mutations). In general,“mit‐”mutations are responsible for non‐RRF encephalopathies, while“syn‐”and“ρ‐”mutations are associated with mitochondrial encephalomyopathies with RRF. Furthermore, point mutations [mit‐andsyn‐) are usually maternally‐ inherited, while large‐scale mtDNA rearrangements are either sporadic or inherited as mendelian traits. In most cases, the molecular detection of the known defects of mtDNA can be carried out by non‐invasive techniques, thus making it an easy and relatively inexpensive procedure in the differential diagnosis of the mitochon

ISSN:1015-6305    

DOI:10.1111/j.1750-3639.1992.tb00680.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Multiple deletions of mitochondrial DNA (mtDNA) have recently been described in a number of patients with neurological disorders. Most cases have been clinically characterized by autosomal dominant inheritance, adult onset, and a slowly progressive course with external ophthalmoplegia and muscle weakness. Some patients have had evidence of central or peripheral nervous system involvement or episodes of myoglobinuria. Muscle biopsy findings include ragged‐red fibres (RRF), muscle fibres with absent COX‐activity and abundant abnormal mitochondria with paracrystalline inclusions. Biochemically, a generalized reduction in the activities of mtDNA‐encoded enzymes is observed in skeletal muscle. Southern blotting or PCR analysis reveal multiple populations of deleted mtDNA. The deletions occur at multiple sites between the replication initiation sites, involving a large portion of mtDNA, and most deletions seem to be flanked by direct sequence repeats, shown to be “hot spots” in the case of single large deletions. Apparently, a defect in a nuclear gene results in multiple deletions of mtDNA. Both clinical, genetic and molecular genetic observations indicate heterogeneity of this new disease category, apparently based on a disturbance in the “cross‐talk” between the nuclear and the mitoch

ISSN:1015-6305    

DOI:10.1111/j.1750-3639.1992.tb00681.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Quantitative defects of mtDNA have been recently described in patients with fatal mitochondrial disease of early infancy or mitochondrial myopathy of childhood. There was variable tissue expression and depletion of up to 98% of mtDNA in affected tissues. Pedigree analysis was compatible with mendelian inheritance, suggesting faulty communication between nuclear and mitochondrial genomes, but the primary molecular lesion is unknown. In muscle, morphological studies allowed to correlate mtDNA depletion, absence of mtDNA‐encoded peptides, mitochondrial proliferation, and loss of cytochrome c oxidase (COX) activity in individual fiber

ISSN:1015-6305    

DOI:10.1111/j.1750-3639.1992.tb00682.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

This work reviews the role of mitochondria in the ageing process and summarizes pathomorphological biochemical and molecular genetic data. The pathophysiological mechanisms underlying the phenomenon of ageing are only partly understood. There is, however, increasing evidence that mitochondria are essentially involved. In various tissues of various species a decline in the respiratory chain capacity is seen with ageing. Enzyme histochemistry of cytochrome c oxidase (complex IV of the respiratory chain) has revealed an age‐related increase of randomly distributed defective fibres/cells in the skeletal and heart muscle the random pattern probably indicating cellular heterogeneity of the ageing process. Observed deletions of mitochondrial DNA during ageing may represent one causative factor. Similar to primary mitochondrial myopathies point mutations and depletion of the mtDNA are probably also involved. There is some evidence that damage of the mitochondrial genome and of other mitochondrial structures might be due to increased oxygen radical production during ageing. The role of nuclear influences on the degeneration of mitochondrial function remains, however, also to be determined. Nevertheless, the decline of respiratory chain function with ageing represents an important factor for the decline of functional organ reserve capacity in senescenc

ISSN:1015-6305    

DOI:10.1111/j.1750-3639.1992.tb00683.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

The term “mitochondrial diseases” encompasses a heterogeneous group of disorders in which a primary mitochondrial dysfunction is suspected or proven by morphologic, genetic, or biochemical criteria (1,2). Clinically, these progressive disorders usually affect muscle, either alone (mitochondrial myopathies) or in combination with other systems, most often brain (encephalomyopathies). Mitochondria are unique among intracellular organelles in that mitochondrial proteins are encoded by two genomes, nuclear DNA (nDNA) and mitochondrial DNA (mtDNA). The vast majority of mitochondrial proteins are encoded by the nuclear genome, whereas mtDNA (a circular, double stranded 16.5 kb molecule) encodes only 13 polypeptides, all of them subunits of respiratory chain complexes. In addition to structural genes, mtDNA also codes for 22 transfer RNAs and two ribosomal RNAs. Our understanding of mitochondrial diseases has grown at an impressive rate in the past few years, and most of the progress has been in the area of mtDNA genetics, where several mtDNA mutations have been associated with specific diseases (reviewed in this issue by Zeviani et al.). In comparison, our understanding of mitochondrial disorders due to nDNA lesions has lagged behind and, to date, molecular defects of nuclear genes have been documented in only a few patients. We will review which alterations in the nuclear genome can cause mitochondrial disorders and which criteria are useful in identifying such mutations. While several examples will be provided, this is not intended as a complete review of the subj

ISSN:1015-6305    

DOI:10.1111/j.1750-3639.1992.tb00684.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

ISSN:1015-6305    

DOI:10.1111/j.1750-3639.1992.tb00685.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

ISSN:1015-6305    

DOI:10.1111/j.1750-3639.1992.tb00686.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY