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Biomedical subjects

F Williams

Publications and source records attributed to F Williams.

At least 55 records · Page 3Linked to original sources
PubMed1997

Natural inactivation of a common HLA allele (A*2402) has occurred on at least three separate occasions.

HLA-A*2402 is common and widely distributed in human populations. Several individuals were identified who type genotypically for A*2402, but are serologically null for the HLA-A24 Ag. Sequencing and transfection of genomic DNA fragments containing null and wild-type A*2402 alleles, and the related A*2301 allele, revealed three different null alleles (A*2409N, A*2411N, and A*2402(low)), each of which differs from A*2402 by a single nucleotide change within the 6.7-kb sequence. The A*2301 and A*2402 sequences differ by no substitutions additional to those previously determined for the 1.1-kb cDNA. In exon 4, A*2409N has an in-frame stop codon, while A*2411N has a nucleotide insertion that alters the reading frame, causing premature termination. A*2402(low) has a nucleotide substitution near the splice acceptor site for intron 2 that impairs the production of correctly spliced mRNA. For A*2409N and A*2411N, mRNA is undetectable by Northern analysis, whereas A*2402(low) produces a low level of mRNA and a concomitant amount of normal A*2402 protein at the cell surface. The protein expressed from the A*2402(low) allele is sufficient to stimulate an alloreactive T cell response. On a background of unexpected sequence homogeneity, the single nucleotide changes in the A*2409N, A*2411, and A*2402(low) alleles have dramatic effects upon gene expression and are of likely importance for HLA matching in clinical transplantation. Segregation of at least three independently inactivated A*2402 alleles in human populations raises the possibility that loss of A*2402 may be the result of natural selection.

Alleles↗
PubMed1997

Application of an HLA-B PCR-SSOP typing method to a bone marrow donor registry.

A previously reported HLA-B PCR-SSOP typing method has been applied to those individuals, from the local bone marrow registry, with only one detectable HLA-B antigen by serology. The PCR-SSOP method detected the serologically defined HLA-B antigen in all cases. In addition, PCR-SSOP detected the presence of a second HLA-B allele in 19.9% of these individuals. The method was also applied to all individuals where serology could only determine the HLA-B antigen as a broad specificity. All antigens were split by the PCR-SSOP method, indicating that the method is more specific than serology. Using a combination of PCR-SSOP and serologically determined types for 5000 individuals on the local bone marrow registry, HLA-B frequencies for the Northern Ireland population have been calculated.

Alleles↗
PubMed1997

Development of PCR-SSOP for HLA-A typing of bone marrow registry donors.

A medium resolution PCR-SSOP typing method, using 26 digoxigenin labelled probes, has been established for the identification of HLA-A alleles. The system is capable of discriminating all of the serologically defined specificities except for eight heterozygous combinations which are however rare in Caucasians. The method has been applied to 1,838 individuals on the local bone marrow registry who either had only one detectable HLA-A antigen, or a HLA-A antigen whose presence had been queried using the serological technique or a broad HLA-A specificity assigned by the serological technique. In all but one case the serologically assigned antigens were detected with the PCR-SSOP method. In addition, PCR-SSOP detected the presence of a second HLA-A allele in over 10% of individuals who had been previously homozygous. Frequency information, based on a population of 5,000 individuals, has been established using a combination of molecular and serological typing data.

Bone Marrow↗
PubMed1997

Development of PCR-SSOP for the identification of HLA-A*02 subtypes and determination of HLA-A*02 frequencies within different ethnic populations.

A PCR-SSOP typing method, involving a single PCR amplification in conjunction with 19 digoxigenin labelled oligonucleotide probes, has been developed for the identification of 17 known HLA-A*02 alleles. The method has been applied to four populations (Northern Ireland, Singapore Chinese, Shetland Island and Mexican) and percentages of HLA-A*02 alleles determined within each population.

Alleles↗
PubMed1997

HLA class I DNA typing of 215 "HLA-A, -B, -DR zero mismatched" kidney transplants.

DNA typing for HLA class II improves the typing quality and this was shown previously to be relevant for kidney graft survival. In this project we addressed the question whether molecular typing for HLA class I also increases the efficacy of HLA matching in kidney transplantation. 215 HLA-A,-B,-DR zero-mismatched donor/recipient pairs as defined by serological typing were selected. Retrospective HLA-A and HLA-B typing was performed both by the PCR-SSP and the PCR-SSOP method. DNA typing for HLA-A revealed discrepant results to serology in 5.7% of the donors and 2.8% of the recipients. HLA-B typing discrepancies were found in 6.6% of the donors and 5.6% of the recipients. 10.4% of the donors and 6.5% of the recipients showed either an HLA-A or an HLA-B discrepancy Nearly one-third of the HLA-A discrepancies affected A19 splits. The most common reason for HLA-A discrepancies was the erroneous assignment of serological blanks, whereas HLA-B errors were caused mainly by the assignment of incorrect specificities. DNA typing allowed the definition of HLA-A and -B split specificities in all 118 "splitable" cases for which only broad specificities were reported based on serological typing. A total of 183 DNA class I compatible transplants had a 15% higher one-year graft survival rate than 32 transplants for which DNA typing revealed a class I incompatibility

DNA Probes, HLA↗
PubMed1997

Molecular typing of HLA class I and class II antigens in Indian kala-azar patients.

HLA has been shown to be associated with many diseases. To find out whether host genetic factors like the HLA are involved in susceptibility to kala-azar (visceral leishmaniasis) in India, we formulated an association study with genetically related controls. All samples were typed by PCR SSOP (sequence specific oligonucleotide probes) for HLA class I (A and B) and class II (DR) antigens. The test of association we used was the transmission disequilibrium test (TDT). No significant evidence for association with any of the three HLA loci was obtained.

Disease Susceptibility↗
PubMed1997

Defendants are clueless--the 30-day psychiatric observation.

OBJECTIVE: To investigate the understanding and expectations of defendants referred to Valkenberg Hospital for 30-day observation. DESIGN: Defendants referred for 30 days of psychiatric assessment were surveyed by means of a semi-structured interview within 3 days of admission. PARTICIPANTS: One hundred consecutive referrals from the Western, Northern and Eastern Cape were considered; 88 were eventually entered into the study. RESULTS: All defendants were generally ignorant of the reasons for referral, but had a good understanding of court procedure and wrongfulness. Mentally ill subjects differed only in their not being able to distinguish between a guilty/not guilty plea. Most did not have legal representation, did not personally request the assessment and denied guilt of the alleged offence. CONCLUSIONS: Mental illness affects triability but not necessarily criminal responsibility. Disturbingly, most defendants were without legal representation and were unaware of the purpose, implications and possible outcomes of psychiatric observation. It is imperative that the legislation governing these aspects be reviewed.

Adolescent↗
PubMed1996

Long-range PCR amplification as an alternative strategy for characterizing novel HLA-B alleles.

We have developed a simple, rapid and reliable method for specifically amplifying and cloning full-length HLA-B genes from genomic DNA. Using this methodology we characterized three alleles of interest at the molecular level. Two of the alleles appeared in our routine class I PCR-SSOP typing system, a variant of B*5801 found in the Daudi cell line and RCE 56 and a variant of B*4101 found in a number of volunteer donors on our Bone Marrow Donor Registry. The third, a variant B35 allele found in RCE 80, was first identified as unusual by serology. Our sequencing analysis of exon 2 and exon 3 identified two of these alleles as the recently reported novel HLA-B*5802 and HLA-B*4102 alleles, while the third represents a new B35 allele officially designated B*3513.

Alleles↗
PubMed1996

The diffuse infiltrative lymphocytosis syndrome. Clinical and immunogenetic features in 35 patients.

OBJECTIVE: To study the epidemiological, clinical, serological and immunogenetic features of the diffuse infiltrative lymphocytosis syndrome (DILS). DESIGN: Consecutive series of 35 patients with DILS diagnosed from 1992 to 1995 in a cohort of 4100 outpatients infected with HIV-1. METHODS: Thirty-five individuals with DILS were ascertained from this cohort and followed for 720 patient-months. Clinical, serological and immunogenetic features of these patients were studied and their demographics were compared with the rest of the outpatient population. RESULTS: DILS was found to be more prevalent in African Americans (60%) than in Caucasians (26%) or Mexican Americans (14%) [odds ratio (OR), 2.32; 95% confidence interval (CI), 1-12-4.81; P = 0.02] and in persons with male-to-male transmission of HIV-1 (71%) (OR, 2.82; 95% CI, 1.29-6.29; P = 0.007). All patients had bilateral parotid gland enlargement. The majority had sicca symptoms. The most common extraglandular sites of disease were lung (31%), muscle (26%), and liver (23%). Four patients had biopsy-proven polymyositis. Thirteen patients met the 1993 Centers for Disease Control and Prevention case definition of AIDS. Sixteen (52%) patients expressed human leukocyte antigen (HLA)-DRS (DRB1*1102), DR6 (DRB1*1301, *1302), or DR7, and 11 (36%) expressed HLA-DR2. CONCLUSIONS: DILS is more common in African Americans and in persons with male-to-male transmission of HIV-1. HIV-associated polymyositis appears to occur in the setting of DILS.

Adult↗
PubMed1995

Modification of an HLA-B PCR-SSOP typing system leading to improved allele determination.

Modifications have been introduced to a previously reported HLA-B PCR-SSOP typing system. This has enabled further definition of alleles, determination of the probe pattern of some alleles not previously examined and identification of patterns of possible new alleles. However there are still some alleles that cannot be differentiated and there are several alleles which when present as a homozygote have the same pattern as in combination with another allele. When the method was applied to the typing of 66 consecutive cadaveric donors there were three donors whose type differed from the serological type.

Alleles↗
PubMed1995

Cardiovascular risk reduction: a randomized trial of two health promotion strategies for lowering risk in a community with low socioeconomic status.

AIM: To compare the effects of information pamphlets with those of group counselling on cardiovascular risk among individuals from a community with low socioeconomic status. METHODS: Risk factors for coronary heart disease were assessed in 1131 men and women from a community with low socioeconomic status in suburban Melbourne. Individuals deemed to be at moderate risk, on the basis of an integrated risk score greater than 65, were asked to participate in a randomized trial comparing two simple interventions designed to reduce cardiovascular risk. One hundred and sixty-four individuals were randomly assigned to group A (n = 85) and participated in a single group counselling session lasting between 1.5 and 2.0 h. Group B (n = 79) received a specially prepared pamphlet that provided brief written information concerning risk-factor modification. Both groups were asked to attend a follow-up assessment of risk factors 3 and 6 months after entry. RESULTS: There were no significant difference in the change in risk-factor levels between those receiving information pamphlets and those attending the group counselling session after 3 or 6 months of follow-up. Small but significant decreases (P<0.05) were seen in systolic and diastolic blood pressures (-5/4 mmHg for group A, -5/3 mmHg for group B), total plasma cholesterol level (-0.30 mmol/l for groups A and B) and overall coronary risk score (-14.4 and -13.9 for groups A and B, respectively). Body weight remained unchanged during the study period in both groups. CONCLUSION: Screening together with 1.5-2h group counselling had no more influence on cardiovascular risk factors than screening together with provision of information pamphlets in a population with low socioeconomic status.

Adolescent↗