PubMed Health⌕ Search

Biomedical subjects

C Masters

Publications and source records attributed to C Masters.

At least 19 recordsLinked to original sources
PubMed2006

Mild memory impairment in healthy older adults is distinct from normal aging.

Mild memory impairment was detected in 28% of a sample of healthy community-dwelling older adults using the delayed recall trial of a word list learning task. Statistical analysis revealed that individuals with memory impairment also demonstrated relative deficits on other measures of memory, and tests of executive function, processing speed and global cognition, as measured by the CERAD and CogState batteries and CANTAB paired associate learning task. These relative deficits cannot be explained by age-related changes, education, intelligence, mood, health-related factors, or the individuals' ApoEepsilon4 status. Memory-impaired individuals (n = 30) did not recognize the extent of their memory and cognitive difficulties beyond the general complaints expressed by normal elderly (n = 77) within the study and their apparent difficulties did not appear to impact on their participation in life activities. These findings suggest it is unlikely that the memory and cognitive difficulties demonstrated by individuals with mild memory impairment reflect normal aging. Rather it is possible that such impairment may signal early neurodegenerative processes worthy of further investigation.

Aged↗
PubMed2004

Subtle memory decline over 12 months in mild cognitive impairment.

OBJECTIVE: Screening of normal older persons for progressive memory decline is a worthwhile strategy in the pursuit of the earliest possible stages of pre-clinical Alzheimer's disease (AD) or mild cognitive impairment (MCI). Reliable tests are needed to both detect MCI and measure the natural history of decline over months rather than years. We aimed to detect memory decline over 1 year in a group of older individuals with well-characterised amnestic MCI. METHODS: The continuous learning task (CLT) from the CogState test battery was administered 8 times in 12 months to 15 individuals with MCI and 35 controls matched for age, education, IQ and gender. All subjects were recruited from an ongoing aging study. The rate of change in CLT performance over the year was compared between groups and also compared to that detected with a word list learning task and a computerised paired associate learning task. RESULTS: At baseline, memory performance in the amnestic MCI group was significantly worse than controls on all memory tests. However, at 12 months the magnitude of the difference between the groups had increased significantly on the CLT due to decline in memory accuracy in the MCI group. No decline over 12 months was detectable on the routine memory tests. CONCLUSIONS: Subtle memory decline is detectable in amnestic MCI using reliable and sensitive tests of memory. Such measures may assist in the early identification of AD and also in trials of putative disease-modifying therapies to be conducted over as little as 12 months.

Aged↗
PubMed2002

Early onset autosomal dominant dementia with ataxia, extrapyramidal features, and epilepsy.

OBJECTIVE: To perform a clinical and molecular study of a large autosomal dominant family with a complex neurologic syndrome that comprises early-onset dementia, extrapyramidal and cerebellar features, and epilepsy. BACKGROUND: Early-onset forms of dementia often are caused by genetic factors. Mutations of three different genes-amyloid precursor protein (APP), presenilin 1 (PS-1), presenilin 2 (PS-2)-have been found in early-onset autosomal dominant forms of AD, of the human microtubule associated-protein tau gene (MAPT) in frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17), of the BRI gene in familial British dementia, of the PI12 gene in familial encephalopathy with neuroserpin inclusion bodies. Linkage to chromosome 3 has been found in familial nonspecific dementia (FND) and linkage to chromosome 20 has been found in Huntington disease (HD)-like neurodegenerative disease. Dementia may be a feature of other neurodegenerative diseases such as HD, dentatorubro-pallidoluysian atrophy (DRPLA), diseases caused by mutations of the prion protein gene (PRNP), spinocerebellar ataxias (SCA), and familial parkinsonism. METHODS: A southern Italian family with autosomal dominant dementia-plus was observed. The family includes 57 individuals in 5 generations (14 affected, 7 personally observed). The authors performed linkage analysis to APP, PS-1, PS-2, FTDP-17, BRI, PI12, FND, HD-like, SCA4, SCA5, SCA10, SCA11, SCA13, PARK1, PARK2, PARK3 loci; direct mutation analysis of HD, DRPLA, SCA1, SCA2, SCA3, SCA6, SCA7, SCA8, SCA12, and PRNP genes; and sequencing of the PRNP open reading frame. RESULTS: Linkage to the examined loci was excluded. All of the direct mutation analyses were negative excluding mutations in the examined genes. CONCLUSIONS: This family has a peculiar phenotype and molecular analyses excluded genes known to cause hereditary dementias.

Adult↗
PubMed2002

Variation at the APOE -491 promoter locus is associated with altered brain levels of apolipoprotein E.

The apolipoprotein E (APOE, gene; apoE, protein) type 4 isoform is a well-established risk factor for late-onset Alzheimer's disease (AD), and new data suggest that APOE promoter polymorphisms might also modulate AD risk, perhaps by altering transcription of the APOE gene. The current study was undertaken to determine whether the presence of the APOE promoter -491AA genotype (that appears to increase the risk for AD) is associated with an increase in the levels of apoE in brain tissue. Among 40 control and 20 autopsy-confirmed AD brain samples, levels of apoE were increased in the frontal cortex of AD cases (P < 0.001), consistent with the well-recognized up-regulation of APOE expression in reactive astrocytes. Among controls, the -491A allele appeared to impart a gene dose-dependent effect on the levels of apoE in frontal cortex. The levels of apoE in the brains of AD patients with the -491AA genotype were increased as compared to control subjects with the same genotype (P< 0.001). These data support the notion that the -491AA APOE promoter genotype is associated with elevated brain apolipoprotein E levels, suggesting that the risk for AD may be modulated by the apoE protein level as well as by the apoE protein isoform.

Age of Onset↗
PubMed2001

Alzheimer's disease: molecular concepts and therapeutic targets.

The beta amyloid peptide is the major component of the neuritic plaques, the characteristic lesions in Alzheimer's disease. Mutations in three genes (APP, PS-1, and PS-2) cause familial Alzheimer's disease by alteration of the rate of generation of amyloid peptide or the length of this peptide. However, in the 90% non-familial cases, other factors play a major pathogenetic role. These include the apolipoprotein E genotype, the "plaque-associated" proteins promoting the formation of toxic fibrillar aggregates or the chronic inflammatory responses. The aim of this review is to explain the steps in the complex cascade leading to Alzheimer's disease and, based on this, to report the current efforts to intervene in these different pathophysiological events in order to prevent progression of Alzheimer's disease. Whereas acetylcholine substitution is currently used in clinical practice, future therapeutical strategies to combat Alzheimer's disease may include anti-inflammatory treatments, vaccination against beta amyloid peptide, or treatment with cholesterol-lowering drugs.

Alzheimer Disease↗
PubMed1998

On the role of the peroxisome in cell differentiation and carcinogenesis.

This article reviews the currently available data on the role of peroxisomal function in relation to the processes of cell differentiation and carcinogenesis. In regard to tumourigenesis, both genotoxic and non-genotoxic processes have been considered, and the peroxisomal relationships with these phenomena and with differentiation are described at the level of organelle characteristics, enzyme contents, and the involvement of retinoids, steroid hormones, oxygen free radicals, growth factors, apoptosis, omega-3 polyunsaturated fatty acids and the cellular signalling networks. Overall these data serve to illustrate the unique and distinctive role of the peroxisome in differentiation and carcinogenesis, and point to the advantages of considering the peroxisomal involvement in the holistic context of the differentiation dedifferentiation continuum rather than the narrower focus of non-genotoxic carcinogenesis. The review also outlines the potential for medical benefit arising from a fuller understanding of these peroxisomal affiliations.

Animals↗
PubMed1998

The gel test: use in the identification of unexpected antibodies to blood group antigens.

The IgG GEL test was compared with the LISS tube test (Löw and Messeter's low-ionic-strength saline) for antibody identification. The suitability of red blood cells (RBCs) pretreated with ficin, dithiothreitol (DTT), or chloroquine diphosphate (CDP) also was assessed for use in the GEL test. In addition, time-in-motion studies were performed comparing GEL (12 panels per batch) with polyethylene glycol (PEG) tube tests (3 panels per batch). In 57 antibody identification studies, there were 63 GEL+ LISS+, 2 GEL+ LISS-, and 6 GEL-LISS+ antibodies. Among the GEL+ LISS+ antibodies were 19 that yielded stronger reactions in GEL than in LISS; by virtue of their specificity, 14 of these are considered potentially significant: D, 5 E, 2 e, 2 Jka, 2 S, K, and Fya. There were 38 antibodies that yielded equivalent results by both methods, including 31 that are considered potentially significant. Of six antibodies with significantly greater reactivity in LISS, there were three anti-Rh and three that are considered harmless with respect to transfusion management. The two GEL+ LISS- antibodies (anti-Jkb) were potentially significant. GEL- LISS+ reactions involved only harmless antibodies. Of the 50 antibodies of potential significance, GEL yielded equivalent or superior results in 47 (94%) instances. Additionally, GEL failed to detect 6 of 21 harmless antibodies. Expected results were obtained with normal serum or plasma and antibodies of known specificity in tests with RBCs treated with ficin, DTT, or CDP. Hands-on-time required for each GEL panel was 2 to 21/2 minutes compared with 12 minutes for PEG. These data document the suitability of GEL for use in antibody identification studies.

Journal Article↗
PubMed1997

Gluconeogenesis and the peroxisome.

In this article, the capabilities of peroxisomal involvement in the gluconeogenetic processes of vertebrate animals are reviewed in the light of recent findings on peroxisomal metabolism and proliferation. It is demonstrated that the participation of this organelle affords the potential of alternative pathways for the conversion of triacylglycerols to glucose, and for the conversion of amino acids and lactate to carbohydrate. Of interest in this connection, too, is that glyoxylate may act as a key intermediate in the gluconeogenetic functions of peroxisomes in both plants and animals. In addition, a close connection between peroxisomal function and the hormonal control of gluconeogenesis has been described, with these interrelationships extending to the associated phenomena of cellular signalling, gene expression, peroxisomal proliferation, and the function of insulin-like growth factors. The metabolic advantages of some of these alternative pathways for gluconeogenesis have been detailed, and suggestions made for the further testing of their quantitative relativities.

Amino Acids↗
PubMed1996

Omega-3 fatty acids and the peroxisome.

The interactions between the omega-3 unsaturated fatty acids and peroxisomal function have been reviewed, in order to update and integrate knowledge in this area. Following a brief retrospective of the major clinical involvements of these fatty acids, the participation of the peroxisome in their metabolism has been appraised-the peroxisome being shown to exert a major influence on both the synthesis and degradation of the omega-3 fatty acids, with these effects flowing on to the widespread physiological implications of the derivative eicosanoids. Interactions between the omega-3 and omega-6 families of fatty acids have been discussed, as have the interdependent phenomena of peroxisome proliferation, membrane remodelling and cellular signalling. Amongst the signalling involvements covered were those of steroid hormone receptor superfamily, the phosphatidylcholine cycle, and the regulatory influences of oxygen free radicals. Comment has also been included on the separate biological roles of the individual omega-3 fatty acids, their influence on differential gene function, and on the molecular mechanisms of their pharmacological effects. It is concluded that the peroxisome is intimately involved in directing the metabolism and physiological influence of the omega-3 unsaturated fatty acids, and that this organelle merits much greater emphasis in future research aimed at unravelling the profound biological effects of these unique and multipotent compounds.

Animals↗
PubMed1996

Recent developments in peroxisome biology.

Peroxisomes are subcellular organelles that are present in all eukaryotic organisms. These organelles are the focus of much contemporary interest among cellular and medical biologists--an interest which coincides with the realization of their vital role in higher organisms, their unique metabolic and biogenetic characteristics, and their widespread involvement in genetic and degenerative disease. This article reviews some of the major recent developments in peroxisome biology.

Animals↗
PubMed1996

Mitochondrial DNA polymorphism in substantia nigra.

Inefficiencies in mitochondrial respiration mainly affecting complex I and IV activities, occur with increasing age and have been suggested as a possible etiological factor in age-related neurodegenerative diseases. It has been suggested that this finding may be explained by an accumulation of mtDNA mutations. We hypothesise that some polymorphic mitochondrial genomes encode less efficient respiratory protein subunits and are therefore less tolerant of acquired mutations. If this hypothesis is correct, individuals with 'less efficient' mtDNA genotypes may be predisposed both to more rapid biological aging and to neurodegenerative disease. In this study we investigate the substantia nigra mtDNA composition from 4 elderly individuals (2 non-parkinsonian and 2 with idiopathic Parkinson's disease) to determine whether there is sufficient polymorphism to account for different possible respiratory efficiencies. THe mitochondrial tRNAArg, tRNAHis, tRNAScr, tRNALeu(CUN), ND4L, ND4 and ND5 genes as well as parts of the ND3 and ND6 subunit coding regions were analysed (4221 bp), revealing the presence of multiple deletions and 48 discrete polymorphic sites. These included 23 missense, two tRNA and one nonsense polymorphism. Eight of the missense polymorphisms caused nonconservative amino acid replacements at sites of moderate to high evolutionary constraint. These findings suggest that mtDNA diversity in the ageing brain may account for a range of bioenergetic outcomes. The variation in mtDNA genotype involves both inherited (fixed familial) polymorphism and superimposed acquired mutations.

Aged↗
PubMed1994

Alzheimer's disease and transgenic mice.

Transgenic mice overexpressing the three major neuronal isoforms of the human amyloid precursor protein (APP), APP695, APP751, APP770 may provide an animal model for the analysis of the mechanisms and risk factors leading to amyloid deposition in Alzheimer's disease (AD) and Downs syndrome (DS). We have therefore generated transgenic mice expressing these isoforms under the control of the strong metallothionin promoter. Although we can demonstrate expression of transgenic APP in several tissues including brain, expression levels never exceeded those of the endogenous mouse APP. So far we have not been able to detect pathological changes resembling those of AD and DS. However we could demonstrate significant changes in spatial navigation tasks and motor behavior in the transgenic mice. The question remains open whether overexpression of APP is sufficient to induce Alzheimer pathology.

Alzheimer Disease↗
PubMed1994

Apolipoprotein E-4 gene dose in clinically diagnosed Alzheimer's disease: prevalence, plasma cholesterol levels and cerebrovascular change.

The prevalence of the apolipoprotein E-4 allele (ApoE-4) was significantly higher in a referral population of 40 patients with clinically diagnosed Alzheimer's disease than in a sample of non-demented elderly controls (P < 0.01). The highest plasma cholesterol levels were found in demented patients homozygotic for Apo E-4, but no significant increases of glucose, triglycerides and thyroxine or of leuko-araiosis and brain infarcts were verified in this preliminary study.

Aged↗
PubMed1994

Developmental variations in the interactions of pyruvate kinase and glyceraldehyde-3-phosphate dehydrogenase with subcellular structure in cavian tissues.

The activities and interactions with cellular structure of glyceraldehyde-3-phosphate dehydrogenase and pyruvate kinase have been studied in the major tissues of the guinea pig during development. The extent of activity variation in these tissues is described along with the putative physiological determinants of these alterations in activity. As to binding, overall the present data provide a firm indication that the extent of enzyme-structure interactions is appreciable at all ontogenic stages, and when viewed in conjunction with other parallel studies on other enzymes and other animals, serve to confirm the broad biological significance of enzyme-structure associations in the compartmentation of glycolysis. The existence and significance of genetic and epigenetic modifications of these enzymes during development is also discussed.

Aging↗
PubMed1994

[Apolipoprotein E and Alzheimer dementia. Personal results and brief literature review].

The apolipoprotein E allele (Apo-E gene) status was determined in 147 individuals from a longitudinal study. 53 satisfied NINCDS-ADRDA criteria for probable or possible Alzheimer's disease (AD), 37 were non-demented healthy controls. 31 patients with AD had one or two Apo-E 4 alleles (phenotypes 1 x 4-2; 20 x 4-3; 10 x 4-4) compared with only 9 controls (8 x 4-3; 1 x 4-4). Within the AD group, patients homozygous for Apo-E 4 had an earlier onset of illness (7 of 10 cases were presenile) and more severe cognitive impairment at the time of examination after similar durations of illness as patients without Apo-E 4. This may reflect an influence of the Apo-E 4 gene dosage on the onset and course of illness, which is probably independent of chromosome 14 mutations.

Aged↗