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Biomedical subjects

M Landon

Publications and source records attributed to M Landon.

At least 91 records · Page 5Linked to original sources
PubMed1989

Diffuse Lewy body disease: an important differential diagnosis in dementia with extrapyramidal features.

Fifteen cases of diffuse Lewy body disease were identified in a systematic survey of all 216 brains referred to this hospital from a single health district in a single year. These cases presented with Parkinson's disease (40%), cognitive impairment (40%) and both (20%). Quantitative neuropathological studies using anti-ubiquitin immunocytochemistry revealed that dementia severity was related to cortical Lewy body density. The prevalence of diffuse Lewy body disease may have been underestimated in the past because of the neuropathological difficulties in making the diagnosis. Firstly, cortical Lewy bodies have a subtle appearance and are easy to overlook. Secondly, senile plaques are a common feature of diffuse Lewy body disease and may lead the unwary to make an erroneous diagnosis of Alzheimer's disease or "plaque-only Alzheimer's disease'. Diffuse Lewy body disease is a common and important cause of parkinsonian dementia, including the dementia of Parkinson's disease itself.

Alzheimer Disease↗
PubMed1988

A filamentous inclusion body within anterior horn neurones in motor neurone disease defined by immunocytochemical localisation of ubiquitin.

Using an immunocytochemical method to localise antibodies to ubiquitin, filamentous inclusion bodies were seen in spinal anterior horn neurones in cases of motor neurone disease (MND) but not in any control cases. These inclusion bodies appeared to be closely associated with classical Bunina bodies and immuno-electron microscopy suggested that they were based on arrays of straight 10-15 nm filaments together with some granular material. These observations link the protein ubiquitin with a chronic neurodegenerative disease and extend previous observations of a close association between filamentous inclusion bodies and ubiquitin. Ubiquitin-filament inclusions should be regarded as a new hallmark in the histological diagnosis of MND.

Adult↗
PubMed1988

Ubiquitin is a component of neurofibrillary tangles in a variety of neurodegenerative diseases.

Ubiquitin has been shown to be a component of neurofibrillary tangles in Alzheimer's disease. We now show immunocytochemically that it is also a component of neurofibrillary tangles in several other neurodegenerative diseases of diverse aetiology, including Down's syndrome, dementia pugilistica and postencephalitic parkinsonism, and in normal ageing. Ubiquitin immunoreactivity is not, however, generally found in the neurofibrillary tangles of progressive supranuclear palsy. These findings show that while associated ubiquitin is not a feature unique to the tangles of Alzheimer's disease, it is not simply a non-specific response to the presence of an inclusion body within the cell. The observations suggest that ubiquitin may have an important role in the formation of neurofibrillary tangles in a variety of neurodegenerative diseases.

Alzheimer Disease↗
PubMed1988

Ubiquitin is a common factor in intermediate filament inclusion bodies of diverse type in man, including those of Parkinson's disease, Pick's disease, and Alzheimer's disease, as well as Rosenthal fibres in cerebellar astrocytomas, cytoplasmic bodies in muscle, and mallory bodies in alcoholic liver disease.

Polyclonal antibodies were raised which have a high affinity for conjugated ubiquitin. Immunocytochemistry was performed on paraffin sections of tissues showing well-characterized inclusion bodies. Ubiquitin was found as a component of the intermediate filament inclusion bodies characteristic of several major diseases including Lewy bodies of Parkinson's disease, Pick bodies of Pick's disease, Mallory bodies of alcoholic liver disease, cytoplasmic bodies of a specific myopathy, and Rosenthal fibres within astrocytes. Ubiquitin was also present in the three histological lesions characteristic of Alzheimer's disease. These observations suggest a fundamental role for ubiquitin in the formation of intermediate filament inclusion bodies in man, and have implications regarding the pathogenesis of these important diseases.

Alzheimer Disease↗
PubMed1988

Immunohistochemical evidence for the derivation of a peptide ligand from the amyloid beta-protein precursor of Alzheimer disease.

A monoclonal antibody to a synthetic peptide consisting of residues 8-17 of the amyloid beta protein of Alzheimer disease was used in immunohistochemical studies to reveal binding sites for this peptide in vesicular elements in the islets of Langerhans of the pancreas and the zona reticularis of the adrenal gland. These binding sites may represent a specific membrane receptor. These results, together with similarities in structural features between the precursors for epidermal growth factor and beta protein, suggest that the beta-protein precursor may be processed to release an active peptide ligand rather than acting as a membrane receptor. In Alzheimer disease, abnormal processing of this active peptide precursor may result in the deposition of beta-protein amyloid fibrils in the brain.

Adrenal Glands↗
PubMed1988

CNS amyloid proteins in neurodegenerative diseases.

The amyloid plaques found in neurodegenerative diseases show considerable morphologic diversity. Two amyloidogenic proteins have been isolated from the brains of humans and animals with neurodegenerative diseases--beta-protein from Alzheimer's disease (AD) and Down's syndrome, and prion protein (PrP) from scrapie and Creutzfeldt-Jakob disease (CJD). Using monoclonal antibodies to a synthetic peptide corresponding to a portion of beta-protein and rabbit antiserum to hamster scrapie PrP 27-30, we examined in situ amyloid plaques on sections from cases of neurodegenerative diseases, including cases with a spectrum of plaque types. Anti-beta-peptide stained cerebrovascular and plaque core amyloid in all AD cases as well as cerebrovascular amyloid and senile plaque core amyloid in five elderly CJD cases. Anti-PrP stained plaques in CJD, kuru, and Gerstmann-Sträussler syndrome cases but not cerebrovascular amyloid or plaques in AD. Dual localization experiments showed that in cases with a mixture of plaque types, the antibodies identified different populations of plaques that showed anatomic heterogeneity. Colocalization of the two proteins was not observed in any plaque type. The data suggest that in neurodegenerative diseases two major plaque types exist, which have different etiologic origins. Our results emphasize the need for classification of CNS amyloids based not on their morphology but on the macromolecular components comprising these pathologic polymers.

Alzheimer Disease↗
PubMed1987

Immunogold labeling of cerebrovascular and neuritic plaque amyloid fibrils in Alzheimer's disease with an anti-beta protein monoclonal antibody.

A monoclonal antibody raised to a synthetic peptide consisting of residues 8 to 17 of the amyloid beta protein of Alzheimer's disease was employed for immunogold electron microscopic studies on amyloid fibrils of cerebrovascular walls and neuritic plaques in this disease. Electron microscopy revealed a specific gold labeling of the amyloid fibrils in these structures. This provides ultrastructural evidence that beta protein is intimately associated with the amyloid fibril. With previous chemical evidence, this observation supports the concentration that it is an intrinsic component of the fibril.

Alzheimer Disease↗
PubMed1986

Monoclonal antibodies raised against a subsequence of senile plaque core protein react with plaque cores, plaque periphery and cerebrovascular amyloid in Alzheimer's disease.

Four monoclonal antibodies (1D2/1/2, 1G10/2/3, 3B6/1/1, 4D12/2/6) were raised against a synthetic peptide consisting of residues 8-17 of a protein reported to be common to senile plaque cores, cerebrovascular amyloid and neurofibrillary tangles in Alzheimer's disease. In an immunoperoxidase study of Alzheimer brain tissue, these antibodies stained plaque and vascular amyloid but not tangles, suggesting that the polypeptide chain in the region of residues 8-17 is exposed in the former two but, if present, inaccessible in the latter. In addition, staining of granular material in the plaque periphery was observed. These antibodies will be useful tools for future work on the origin of this protein.

Alzheimer Disease↗
PubMed1986

Isolated senile plaque cores in Alzheimer's disease and Down's syndrome show differences in morphology.

Frontal and temporal cortical tissue from the brains of elderly cases of Down's syndrome was used to make preparations of neuronal cell bodies containing senile plaque cores. Polarisation microscopy revealed normal "classical" plaque cores, and also a high proportion of unusual "amorphous" plaque cores which we have not seen in Alzheimer's disease. These two forms were easily distinguished by electron microscopy. This suggests that late Down's syndrome may not be an exact model for Alzheimer's disease.

Alzheimer Disease↗
PubMed1985

Polypeptide components of bovine heart cytochrome c oxidase. Cross-identifications in two high-resolution polyacrylamide-gel electrophoresis systems.

Two-dimensional polyacrylamide-gel electrophoresis has been used to correlate polypeptide components of bovine heart cytochrome c oxidase that are resolved by two high resolution systems. The systems utilise chloral hydrate (2,2,2-trichloroethane-1,1-diol), which resolves fifteen components, and sodium dodecyl sulphate and urea, which resolves thirteen components. Seven components have been isolated and identified from their amino acid compositions in terms of polypeptides for which the amino acid sequence is known. Full resolution of all components present in this enzyme cannot be accomplished using any single-dimension system currently available.

Amino Acids↗
PubMed1985

Endogenous origin of microbiologically-inactive cobalamins (cobalamin analogues) in the human fetus.

The cobalamin content of placenta, maternal and fetal sera was assayed by methods which measure microbiologically-active and microbiologically-inactive cobalamins. Only microbiologically-active cobalamins were present in the placenta but both types were present in both maternal and fetal circulations. We conclude that only microbiologically-active cobalamins cross the placenta and that the microbiologically inactive cobalamins in the fetus must arise by metabolism in situ.

Blood Chemical Analysis↗
PubMed1983

The isolation and amino acid composition of senile plaque core protein.

A new method has been developed for the isolation of intact senile (neuritic) plaque cores from post-mortem brains of patients with Alzheimer's disease. The plaque cores were found to be insoluble in various protein denaturants. The amino acid composition of the plaque core protein does not resemble that of any known form of amyloid.

Aged↗
PubMed1982

Ion-exchange chromatography in the presence of the non-ionic dissociating agent chloral hydrate. Application to a membrane protein, bovine heart cytochrome c oxidase.

In previous work we have shown that aq. 100% (w/v) chloral hydrate (2,2,2-trichloroethane-1,1-diol) is a potent non-ionic protein dissociating agent. We have employed it in systems of polyacrylamide-gel electrophoresis and have demonstrated the presence of 15 components in a preparation of bovine heart cytochrome c oxidase [Griffin & Landon (1981) Biochem. J. 197, 333-344]. Here we describe the use of solutions containing aq. 100% (w/v) chloral hydrate in the ion-exchange column chromatographic separation on CM-cellulose of the alpha- and beta-chains of human haemoglobin, which we have employed as a model protein of known structure. We also describe the use of similar procedures in order to fractionate the polypeptide components of bovine heart cytochrome c oxidase. An effective separation has been obtained and we suggest that chloral hydrate-containing solutions could have general application in the ion-exchange-chromatographic analysis of membrane proteins, a procedure that has had restricted use owing to the inadequacy of non-ionic dissociating agents available previously.

Animals↗
PubMed1981

Transglutaminase-catalysed incorporation of putrescine into denatured cytochrome. Preparation of a mono-substituted derivative reactive with cytochrome c oxidase.

Guinea pig liver transglutaminase has been used to incorporate putrescine into horse heart cytochrome c. The native protein showed essentially no incorporation, while ethanol-denatured cytochrome c incorporated almost 1 mol putrescine per mol protein. No increase in this level of modification was obtained when maleylated cytochrome c and the tryptic peptides of cytochrome c were used as substrates. Analysis of the modified ethanol-denatured cytochrome c by tryptic cleavage and peptide isolation showed that glutamine-42 of the intact protein is the site of incorporation of radioactively labelled putrescine. Ethanol-denatured cytochrome c that was specifically modified at glutamine-42 by incorporated of putrescine could be readily renatured. The renatured modified protein showed reactivity with cytochrome c oxidase comparable to that of the original native protein.

Animals↗
PubMed1981

Additional components of bovine heart cytochrome c oxidase demonstrated by high-resolution polyacrylamide-gel electrophoresis in the presence of chloral hydrate.

We have shown that aq. 100% (w/v) chloral hydrate (2,2,2-trichloroethane-1,1-diol) dissociates bovine heart cytochrome c oxidase. We have developed new procedures of polyacrylamide-gel electrophoresis in the presence of chloral hydrate that permit variation in the pH of the separation, and, by using these procedures, we have observed 15 components in preparations of the enzyme. This number contrasts with the eight bands that were seen on electrophoresis in the presence of SDS (sodium dodecyl sulphate) and urea. We have isolated material from these eight bands and have characterized each by electrophoresis in the presence of chloral hydrate. Twelve of the fifteen components that were seen by electrophoresis in chloral hydrate were identified as constituents of the eight bands seen by electrophoresis in the presence of SDS and urea. Two-dimensional electrophoretic separations confirmed these identifications ans showed that the other three components which were resolved as discrete bands by electrophoresis in the presence of chloral hydrate appeared to be diffusely present in the electrophoretic separations performed in the presence of SDS and urea, which suggested anomalous behaviour in that detergent. Trypsin treatment of cytochrome c oxidase caused total loss, as observed by electrophoretic separations in the presence of chloral hydrate, of a number of components. The trypsin-sensitive components included all of those that behaved anomalously in the presence of SDS and urea. Chloral hydrate is a potent non-ionic dissociating agent for cytochrome c oxidase and its use in polyacrylamide-gel electrophoresis, with variation in the pH of the gel, permits charge-dependent separations that should have general application in the analysis of membrane proteins.

Animals↗