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Biomedical subjects

D Middleton

Publications and source records attributed to D Middleton.

At least 109 records · Page 6Linked to original sources
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↗
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↗
PubMed1995

Genetic diversity in the non-structural gene of parvovirus B19 detected by single-stranded conformational polymorphism assay (SSCP) and partial nucleotide sequencing.

A homologous region in the parvovirus B19 non-structural gene (B19 nt 1399-1682) was examined in 50 samples from patients with a wide variety of B19-related disease from various countries by PCR amplification, single-stranded conformational polymorphism (SSCP) assay and nucleotide sequencing. Five SSCP types were confirmed by nucleotide sequence analysis. Of a total of 6 mutations, all were silent. Types 3 and 4 accounted for 92% of strains. There was no correlation between genome type and either clinical illness or patient age. However, there was a correlation between SSCP type and country of origin. Type 3 strains predominated in Japan (18/26) and the UK (6/8), whereas type 4 predominated in the USA (9/12). Notably, type 3 strains also predominated among females (14/18), whereas there were approximately equal numbers of strain types 3 (7/17) and 4 (8/17) among males; an observation which remains unexplained. Within the Japanese group, although type 3 strains predominated overall, strains isolated from 1981 to 1987 consisted of types 1 (2/15), 2 (1/15), 3 (8/15), and 4 (4/15), whereas strains isolated from 1990 to 1994 consisted almost entirely of type 3 (10/11).

Adolescent↗
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↗
PubMed1994

Transfusion of one HLA-DR antigen-matched blood to potential recipients of a renal allograft.

Patients awaiting a renal transplant were given 1 HLA-DR antigen-matched blood in order to compare the sensitization and graft outcome of these patients with those of control patients, who had been given random blood before transplantation. No differences in sensitization, measured by the formation of HLA antibodies, or in graft survival were found between the 2 groups. However, the incidence of rejection episodes was significantly reduced in the patients who received blood matched for 1 HLA-DR antigen compared with the patients who received random blood.

Blood Grouping and Crossmatching↗
PubMed1994

TAP1 and TAP2 polymorphism in multiple sclerosis patients.

The frequency of TAP1 and TAP2 gene polymorphisms in MS patients was compared with that of a normal population. A significant increase in TAP2-379-VAL homozygosity and TAP2-565-ALA homozygosity was found in HLA-DRB1*1501-DQB1*0602-negative patients.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

Identification of MHC--molecular biology.

Many of the molecular methods currently in use in the histocompatibility laboratory have been described. The use of a specific technique will depend on the laboratory's requirements. Obviously those laboratories involved in cadaver transplantation will use techniques suitable for single sample analysis which give results within six hours. Other laboratories dealing with large numbers of samples will use techniques which favour batch analysis. Some laboratories, depending on their needs, may use a combination of methods. All techniques are being continually updated to allow for the detection of newly discovered alleles.

HLA Antigens↗
PubMed1994

Increased renal allograft thrombosis in CAPD patients.

In a retrospective analysis of 202 renal transplant procedures in the years 1989-1992 we identified an excess of grafts lost from primary renovascular thrombosis in patients receiving continuous ambulatory peritoneal dialysis (CAPD) compared to haemodialysis (HD) patients (9 CAPD versus 0 HD, Chi-squared = 9.63; P < 0.01). All graft losses from thrombosis occurred within 16 days of surgery. Possible predisposing causes were identified in three patients. Donor age was greater in CAPD patients losing their kidneys from thrombosis compared to the overall CAPD group [mean (SD) years, 43.0(12.9) versus 29.1(15.8); P = 0.01] whereas no significant difference in haematocrit, platelet count, antibody status, cyclosporin use, peroperative hypotension, primary diagnosis, smoking, or diabetes mellitus was found. Data from the EDTA registry for 1990-91 show that graft loss from primary renovascular thrombosis in UK-treated patients was reported in 7.1% of CAPD recipients compared with 1.8% in haemodialysis. We suggest that CAPD patients are at greater risk of graft loss from renovascular thrombosis than HD patients and may require more intensive fluid and anticoagulant treatment in the perioperative period.

Adolescent↗
PubMed1994

Comparison of serological and DNA HLA-DR typing results for transplantation in Western Europe, Eastern Europe, North America and South America.

In a previous study, DNA typing revealed that 25% of serological HLA-DR typings of kidney transplants were incorrect. In the current study, we analyzed whether this error rate had improved in recent years, and whether there were differences according to geographical region. From 1988 to 1991 the error rate of serological typing improved slightly in Western Europe from 19% to 16%, and in North America, from 21% to 16%. In Eastern Europe, the error rate decreased from 49% to 33% in 1991, whereas the rate remained high in South America at 60% in 1988 and 72% in 1991. The high error rates in South America and Eastern Europe reflected a lack of good quality serological typing reagents. The 16% typing errors in Western Europe and North America demonstrated the current limit of serological techniques for cadaver donor typing and underlined the need for prospective DNA typing.

DNA↗
PubMed1994

Is the phenotypic combination A1B8Cw7DR3 a marker for male longevity?

OBJECTIVE: To study whether individual Human Leucocyte Antigens (HLA) at the HLA 1 or 11 loci or the phenotypic combination A1B8Cw7DR3 were associated with longevity. DESIGN: Direct comparison of the > 90-year-old subjects with a control group. SETTING: Northern Ireland population with little migratory mobility. SUBJECTS: The > 90-year-old group (79 females, 38 males) was compared with a control group consisting of 150 unrelated blood donors (81 females, 69 males). MEASUREMENTS: Human Leucocyte Antigen (HLA) Class 1 typing was carried out on 117 nonagenarians (mean age 93.7 years) and 150 younger controls (mean age 33.7 years) using conventional serological methods; HLA DR typing was carried out on 102 of the 117 > 90-year-old subjects, together with the 150 control subjects, and performed using restriction fragment length polymorphisms. The frequency of the phenotypic combination A1B8Cw7DR3 was measured in both groups. RESULTS: There were no significant differences in the HLA antigen frequencies between the very elderly groups and the younger subjects at the A, B, C, and DR loci. The phenotypic combination A1B8Cw7DR3 was significantly increased (X3) in nonagenarian men compared with young men but not between elderly women and young women. There was a trend for increased representation of this phenotype in elderly men compared with women of the same age. CONCLUSIONS: The frequency of the supratype A1B8Cw7DR3 was significantly increased in very elderly men but not in elderly women. Since this phenotypic combination has been associated with immune surveillance and/or hyperactivity in Caucasians, there is the suggestion that it could influence longevity through immune mechanisms but that sex differences may exist in its influence and expression.

Aged↗