PubMed Health⌕ Search

Biomedical subjects

R Nicholls

Publications and source records attributed to R Nicholls.

14 recordsLinked to original sources
PubMed2000

Fine-mapping of the type 1 diabetes locus (IDDM4) on chromosome 11q and evaluation of two candidate genes (FADD and GALN) by affected sibpair and linkage-disequilibrium analyses.

Previous studies have identified a susceptibility region for insulin-dependent (type 1) diabetes mellitus on chromosome 11q13 (IDDM4). In this study, 15 polymorphic markers were analyzed for 382 affected sibpair (ASP) families with type 1 diabetes. Our analyses provided additional evidence for linkage for IDDM4 (a peak LOD score of 3.4 at D11S913). The markers with strong linkage evidence are located within an interval of approximately 6 cM between D11S4205 and GALN. We also identified polymorphisms in two candidate genes, Fas-associated death domain protein (FADD) and galanin (GALN). Analyses of the data by transmission/disequilibrium test (TDT) and extended TDT (ETDT) did not provide any evidence for association/linkage with these candidate genes. However, ETDT did reveal significant association/linkage with the marker D11S987 (P=0.0004) within the IDDM4 interval defined by ASP analyses, suggesting that IDDM4 may be in the close proximity of D11S987.

Bacterial Proteins↗
PubMed1999

Changing hospitals.

Explore the source record for details and available documents.

Economics, Hospital↗
PubMed1999

Microsatellite abnormalities in plasma of patients with breast carcinoma: concordance with the primary tumour.

AIMS: To detect microsatellite abnormalities in the primary tumours and plasma of patients with breast carcinoma. METHODS: Plasma was obtained from 17 breast carcinoma patients before surgery. Corresponding tumour and benign lymph node (control) samples for each of the carcinoma patients were obtained from paraffin blocks. DNA was extracted from the plasma samples and the paraffin embedded tissue using previously described methods. RESULTS: The 17 primary tumours showed two examples of loss of heterozygosity and three examples of microsatellite instability; the 17 plasma samples showed three and one, respectively. Many of the longer microsatellites (over 200 base pairs) were difficult to amplify from plasma. The investigations suggested that this was because of the highly fragmented nature of plasma DNA. Only one example of loss of heterozygosity and one example of microsatellite instability showed a concordant pattern in both primary tumour and plasma. These were both in the same patient. CONCLUSIONS: DNA mutations concordant with those in the primary carcinomas can occasionally be detected in the plasma of patients with breast carcinoma. However, the frequency would have to be markedly improved before this could be of any diagnostic value.

Biomarkers, Tumor↗
PubMed1992

Modification of proteins and other biological molecules by acetaldehyde: adduct structure and functional significance.

1. Chronic ethanol consumption is a major cause of liver disease. The modification of hepatic proteins by acetaldehyde (AcH), the primary metabolite of ethanol, has for some time been suggested as one of the major events initiating alcoholic liver disease. 2. These alterations in protein structure are believed to affect liver cell function, and may serve to activate the immune system. 3. This review considers the interaction between AcH and macromolecules and its functional implications.

Acetaldehyde↗
PubMed1987

Heterogeneity and origins of the alpha-thalassemias.

The alpha-globin gene cluster is far from static. It shows remarkable diversity within and among populations, both in gene number and in the pattern of polymorphisms involving the hypervariable regions. The deletions that have given rise to alpha(0)-thalassemia appear to have resulted from rare genetic events, and the affected chromosomes have been distributed among localized populations by selection. On the other hand, the deletions that have given rise to at least one of the alpha(+)-thalassemias seem to have occurred on multiple occasions in different populations. The genesis of this condition, the most common single gene disorder, may reflect the concerted evolution of the alpha-globin genes, and the alpha(+)-thalassemias may have arisen as a by-product of this evolutionary process. The existence of such a polymorphic gene family and the fact that its mutations are the most common single gene disorders in man provide us with a remarkable, natural model for studying population genetics at the molecular level. Further analysis of this cluster may provide valuable information about the timing of racial diversions, population movements, and the molecular events that have helped to maintain such high gene frequencies for some of the mutations of these loci.

Biological Evolution↗
PubMed1986

The relationship between the common mutations of the alpha gene cluster and its evolutionary history.

The alpha globin gene cluster is far from static. It shows remarkable diversity within and among populations, both in gene number and the pattern of polymorphisms involving the HVRs. The deletions which have given rise to alpha o thalassemia appear to have resulted from rare genetic events and the affected chromosomes have been distributed among localized populations by selection. On the other hand, the deletions which have given rise to at least one of the alpha+ thalassemias seem to have occurred on multiple occasions in different populations. The genesis of this condition, the commonest single gene disorder, may reflect the concerted evolution of the alpha globin genes, and the alpha+ thalassemias may have arisen as a by-product of this evolutionary process. The existence of such a polymorphic gene family and the fact that its mutations are the commonest single gene disorders in man, provide us with a remarkable, natural model for studying population genetics at the molecular level. Further analysis of this cluster, and of the beta globin genes, may provide valuable information about the timing of racial diversions, population movements, and the molecular events which have helped to maintain such high gene frequencies for some of the mutations of these loci.

Biological Evolution↗
PubMedDate not supplied

Experimental production of new zymodemes of Entamoeba histolytica supports the hypothesis of genetic exchange.

By mixing in culture zymodemes of Entamoeba histolytica, clones showing a different pattern from the 2 parents have been obtained on 3 occasions. Two new zymodemes (XI alpha- and XXI) have thus been produced, which belong to the third generation of a family of E. histolytica zymodemes apparently obtained by genetic exchange. A hypothesis for the molecular basis of those exchanges is discussed. We report also the observation of probable mutation.

Animals↗
PubMedDate not supplied

Acetaldehyde/protein interactions: are they involved in the pathogenesis of alcoholic liver disease?

Alcohol abuse is a major cause of liver disease. While ethanol itself has been shown to be hepatotoxic, its primary metabolite acetaldehyde has also been implicated in the pathogenesis of alcoholic liver disease. The majority of ethanol metabolism occurs in the liver and high concentrations of acetaldehyde accumulate during chronic ethanol abuse. Acetaldehyde has been shown to react with many proteins in vitro, forming stable covalent adducts. These modifications can act as neoantigens and may also alter biological function. Acetaldehyde-modified proteins have been detected in the livers of ethanol-fed rats and human alcoholics. Circulating antibodies reactive with modified proteins have also been detected. A direct linkage between acetaldehyde-modified proteins, antibodies and liver damage has yet to be established, but current research should clarify the picture in the next few years.

Acetaldehyde↗