PubMed Health⌕ Search

Biomedical subjects

W Thomson

Publications and source records attributed to W Thomson.

At least 19 recordsLinked to original sources
PubMed1992

Population genetics of rheumatoid arthritis.

A major component of genetic susceptibility to rheumatoid arthritis (RA) appears to be explained by inheritance of HLA-DRB1 alleles, which have a conserved sequence of amino acids in the third hyper-variable region of the molecule. This "shared epitope" is found on various DR4, DR1, and DR6 variants, as well as on DR10. The evidence for this "shared epitope" in RA is examined at the population level, including how it fits in with the available epidemiologic data and RA disease severity.

Alleles↗
PubMed1991

Regulation of intestinal iron absorption and mucosal iron kinetics in hereditary hemochromatosis.

In hereditary hemochromatosis (HH), increased intestinal iron absorption leads to the development of iron overload. To examine the abnormal regulation of iron absorption in this disorder, we analyzed mucosal iron kinetics in six patients with HH and in five normal subjects by using a compartmental model of intestinal iron absorption and systemic ferrokinetics. Subjects were given simultaneous oral and intravenous tracer doses of iron 59-labeled citrate and iron 55-labeled transferrin, respectively. Plasma and whole-body radioactive iron levels were then monitored serially during the next 2 weeks, and mucosal iron transport rate constants were estimated by non-linear least-squares fit of the model to these data. Iron absorption was inversely related to serum ferritin concentration in both normal subjects and patients with HH but was higher in relation to serum ferritin level among the latter (p less than 0.0002). Analysis of mucosal iron kinetics demonstrated a similar inverse relationship between the rate constant for mucosal iron uptake and serum ferritin among all subjects combined, but the mean uptake rate constant in patients with HH did not differ from that of normal subjects (p = 0.71). The mean rate constant for incorporation of iron into the mucosal storage pool in patients with HH also was comparable to that of normal subjects (p = 0.94). In contrast, the rate constant for transfer of mucosal iron to the plasma was higher in patients with HH than in normal subjects for any given serum ferritin level (p less than 0.0001), and the transfer rate constant accounted for 87% of the variability in iron absorption among all subjects. We conclude that the increased iron absorption in HH is mediated primarily by an increase in the rate constant for transfer of mucosal iron to the plasma.

Ferritins↗
PubMed1990

DNA polymorphism of the C2 and factor B gene.

C2 and factor B are encoded by very closely linked loci in the class III region of the human major histocompatibility complex on chromosome 6. The factor B gene is divided into 18 exons, and is 6 kb in length whereas the C2 gene is much larger being 18 kb in length. Sequence and Southern blot analysis has defined 5 DNA polymorphisms in the DNA encompassing the C2 and factor B loci. The most interesting of these are the SstI multi-allelic polymorphism at the 5' end and the TaqI polymorphism at the 3' end of the C2 gene. Together these allow the subdivision of haplotypes carrying the C2C and factor B F alleles. A novel combination of SstI and TaqI RFLPs is reported here.

Alleles↗
PubMed1989

Long-term follow-up of patients with echocardiographically detected mitral anular calcium and comparison with age- and sex-matched control subjects.

One hundred seven patients with echocardiographically documented mitral anular calcium (MAC) and 107 age- and sex-matched control subjects without MAC were studied and followed for a mean of 4.4 +/- 2.4 (standard deviation) years. Fourteen (7%) patients were lost to follow-up. Compared with the control group, patients with MAC had higher frequency of precordial murmurs (p less than 0.0001), cardiomegaly (p less than 0.0001), left atrial enlargement (p less than 0.0001), and rhythm and conduction disturbances (p less than 0.0001). During the follow-up, patients with MAC had higher incidence of valve replacement (p less than 0.0025), permanent pacemaker implantation (p less than 0.0025), congestive heart failure (p less than 0.0001), thromboembolic cerebrovascular event (p less than 0.01), sudden death (p less than 0.001) and total cardiac death (p less than 0.0001). However, the frequencies of myocardial infarction, coronary artery bypass surgery and angioplasty, endocarditis or noncardiac death were not significantly different between patients with MAC and the control subjects. Thus, patients with MAC have higher frequencies of precordial murmurs, cardiomegaly, left atrial and ventricular enlargement, rhythm and conduction disturbances. They more frequently undergo valve replacement and permanent pacemaker implantation, develop congestive heart failure and die of cardiac causes than age- and sex-matched control subjects.

Adult↗
PubMed1989

Comparison of five antimelanoma antibodies for identification of melanocytic cells on tissue sections in routine dermatopathology.

Five antimelanoma antibodies used on routinely processed tissue sections have been compared for their value in identifying both benign and malignant melanocytic lesions. Antibodies to S-100 protein, NKIC3, HMB45, HMB50, and FKH1 were used. S-100 protein was polyclonal, but the others were monoclonal. The tissue was fixed in neutral buffered formalin and included sections from 15 primary melanomas, 5 secondary melanomas, 10 dysplastic nevi, and 10 compound nevi. Antibodies HMB45 and NKIC3 showed the greatest degree of sensitivity.

Antibodies, Monoclonal↗
PubMed1989

Haplotypes bearing HLA-A, -B, and -DR: Bf and C4 genes in rheumatoid arthritis families.

We have compared haplotypes bearing HLA-A, -B, -DR; Bf and C4 genes in 54 rheumatoid arthritis (RA) and 24 control families. There was no statistically significant differences in C4A or C4B gene frequencies between RA and control groups, although there were trends for C4B*Q0 to be reduced and C4B2 to be increased in DR4 positive RA compared with DR4 positive controls. The lack of any strong association between C4 variants and RA overall makes it unlikely that the association between RA and genes within the MHS represents a direct effect of variants within the C4A or C4B loci themselves. On comparison of DR4-bearing haplotypes, the haplotype B15-BfS-DR4 was increased fourfold and the B44-Bfs-DR4 haplotype was less frequent in the RA group. When C4 variants were also considered, the haplotype B44-C4B*Q0-C4A3-BfS-DR4 was nine times less frequent in RA patients than in controls. The observation that different DR4 bearing haplotypes may confer either increased or decreased susceptibility to RA suggests either that it is unlikely that DR4 itself is involved in the disease process or that specific haplotypic combinations are important. Thirty-two RA patients were HLA-DR4 negative. No single DR4 negative haplotype was found to confer significantly increased susceptibility to RA.

Arthritis, Rheumatoid↗
PubMed1989

The contribution of direct immunofluorescence to the diagnosis of lupus erythematosus.

The contributions of direct immunofluorescence, light microscopy and serology to the investigation of 52 patients with possible lupus erythematosus were studied. Direct immunofluorescence was found to be most valuable in the investigation of possible systemic lupus erythematosus whilst only of supportive value in the investigation of possible chronic discoid lupus erythematosus. The importance of performing light microscopy before direct immunofluorescence in cases of possible chronic discoid lupus erythematosus is shown.

Biopsy↗
PubMed1988

Complement C4B-null alleles in Felty's syndrome.

C4A and C4B allotypes were compared in 20 patients with Felty's syndrome (FS), 52 patients with rheumatoid arthritis (RA), and 55 control subjects. Nineteen of the FS patients had HLA-DR4. A C4B-null allele was more frequent in the patients with FS (60%) than in either the RA patients (15%) or the control subjects (26%). Only the differences between patients with FS and those with RA remained statistically significant when DR4 positive subjects were compared. The C4B null allele may identify individuals within the rheumatoid population who are at risk of developing particular systemic complications.

Alleles↗
PubMed1988

Chromosome 14 markers in rheumatoid arthritis.

Phenotype frequencies for variants of the chromosome 14 markers, alpha 1 antitrypsin (protease inhibitor--Pi), and immunoglobulin heavy chain gene allotypes (Gm and Am) were examined in affected and unaffected members of multicase rheumatoid arthritis (RA) families and compared with published population data. Significantly higher frequencies of phenotypes containing Pi*Z and Pi*S were observed in unrelated index RA cases compared with UK population data. There was also a higher frequency of Pi*Z in family members without RA than in population controls but no such difference for the frequency of Pi*S. No difference in the frequency of PiM1M2 heterozygotes was seen between patients with RA and population controls. An examination of clinical data failed to show any relation between any particular feature of RA and positivity for Pi*Z or Pi*S. No significant differences in frequency of Gm phenotypes were observed between patients with RA and controls. Significant association was found, however, between Pi*Z and Gm phenotypes containing Gm(zax;g). These associations are interpreted as indicating linkage disequilibria between these alleles. No interactions between DR4 and either G1m(z), (a), or (x) allotypes were apparent in patients with RA. A significant association was seen in the index RA cases between DR4 and Pi phenotypes carrying Z or S alleles. Observations from this study provide evidence for the existence of a genetic component for RA susceptibility encoded on chromosome 14. An interactive effect of these genes with DR4 towards susceptibility appears likely.

Arthritis, Rheumatoid↗
PubMed1987

Calcific valvular aortic stenosis with and without mitral anular calcium.

Seventy-six consecutive patients, mean age 66 +/- 9 years (+/- standard deviation), with isolated aortic valve replacement for calcific valvular aortic stenosis (AS) were studied. Mitral anular calcium (MAC) was detected by echocardiography in 45 patients (59%). Patients with MAC were older (p less than 0.01), had greater peak systolic aortic valve gradients (p less than 0.025), lower cardiac indexes (p less than 0.025) and smaller valve areas (p less than 0.05) than patients without MAC. Thirty-three percent of patients (15 of 45) with MAC required permanent pacemaker implantation after aortic valve replacement, compared with only 10% of patients (3 of 31) without MAC (p less than 0.025). During the follow-up of 7 years (mean 3.8 +/- 1.6), 27% of patients (12 of 45) with MAC died from cardiac causes, compared to only 7% (2 of 31) without MAC (p less than 0.025). Thus, patients with AS and MAC are older, have more severe AS, more frequently undergo permanent pacemaker implantation after aortic valve replacement and more frequently die of cardiac causes than patients with AS and no MAC during follow-up.

Adult↗
PubMed1987

A comparison of clinical and immunogenetic features in familial and sporadic rheumatoid arthritis.

Clinical and immunogenetic factors were compared in 214 patients with sporadic rheumatoid arthritis (RA) and 117 patients from 52 multiplex families. Sex distribution, articular disease severity and seropositivity for rheumatoid and antinuclear factors were similar in familial and sporadic disease. There was a trend for Sjögren's and Felty's syndromes to be more frequent in familial RA but extraarticular disease features were otherwise similar in the 2 RA disease groups. Mean age of onset was 41.1 years in familial and 46.5 years in sporadic RA (p less than 0.0006); 67% of family probands, 74% of affected relatives and 57% of sporadic patients were HLA-DR4 positive (p less than 0.05 affected relatives vs sporadic). The similarity of clinical features found in familial and sporadic RA justifies the use of families with RA to study aspects of disease pathogenesis.

Adult↗
PubMed1986

alpha 1 Antitrypsin (PI) allotypes in rheumatoid arthritis.

alpha 1 Antitrypsin (PI) phenotypes were defined in 144 patients with rheumatoid arthritis (RA) and in 223 normal controls. The frequencies of the rare F, S, and Z variants were similar in RA and control groups. No relationships were found between PI allotypes and rheumatoid disease severity or autoantibody titre. The PI M1M2 phenotype was increased in frequency in the RA group, and phenotype frequencies in DR4 positive and negative disease were similar. These results support the suggestion that genes on the 14th chromosome which are linked to PI predispose to RA.

Arthritis, Rheumatoid↗