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R W Vaughan

Publications and source records attributed to R W Vaughan.

At least 73 records · Page 4Linked to original sources
PubMed1992

Amino acid substitutions at position 38 of the DR beta polypeptide confer susceptibility to and protection from primary sclerosing cholangitis.

Previous studies based on serological HLA phenotyping have implicated genes in the HLA class II region in susceptibility to and protection from primary sclerosing cholangitis. In a recent report, the HLA DRw52a antigen was present in all 29 patients who had been referred for liver transplantation. In this study, HLA DRB, DQA and DQB genotypes were studied using gene amplification and sequence-specific oligonucleotide probing in 71 patients with primary sclerosing cholangitis and 68 healthy controls to determine the frequency among the patients of the DRB3*0101 allele that encodes DRw52a and whether other class II alleles are involved in susceptibility or protection. DRB3*0101 was the most strongly associated allele, being present in 55% of the patients and 22% of the controls. Survival among the DRB3*0101-positive patients was reduced compared with the DRB3*0101-negative patients. Both DRB3*0101 and DRB5*0101, a possible second DRB susceptibility allele, encode a leucine residue at position 38 of the DR beta molecule. The DRB4*0101 allele, which encodes DRw53 and may be protective, encodes an alanine residue at this position. Susceptibility to and protection from primary sclerosing cholangitis may result from amino acid substitutions at position 38 of the DR beta molecule because maximum relative risk was conferred by two leucine-38-containing DR beta molecules, whereas minimum relative risk was conferred by two alanine-38-containing molecules.

Alleles↗
PubMed1992

HLA DQA, DQB, and DRB genotyping by oligonucleotide analysis: distribution of alleles and haplotypes in British caucasoids.

A precise method for comprehensive HLA DQA and DQB genotyping using gene amplification and hybridization with sequence-specific oligonucleotide (SSO) probes is described. Twenty-four SSO probes were used to detect all DQ allotypes defined by nucleotide sequence variation in the second exons of the DQ genes, using a standard set of conditions for all probes at each locus. Five hundred individuals were genotyped for 8 DQA1 and 16 DQB1 alleles by using this method and for 33 alleles of the DRB1, DRB3, DRB4, and DRB5 genes by using previously described SSO probes. The 4-locus DQB1-DQA1-DRB1-DRB3/4/5 haplotypes present were characterized on the basis of known linkage disequilibrium between class II alleles. Fifty-two different haplotypes that have previously been described were further characterized at the nucleotide sequence level and two novel haplotypes were identified. The distributions of these alleles and haplotypes in 177 randomly selected healthy Caucasoid controls from the United Kingdom are reported. These results identify further haplotypic diversity in the HLA class II region, even though strong linkage disequilibrium exists between the DR and DQ gene loci.

Adult↗
PubMed1991

Immunogenetic prediction of pulmonary fibrosis in systemic sclerosis.

75 systemic sclerosis patients were independently tested for pulmonary fibrosis, autoantibodies, and MHC class II genes. 24 of 42 (57%) patients with pulmonary fibrosis had either HLA DR3/DRw52a or anti-Scl-70 vs 2 of 33 (6%) patients without pulmonary fibrosis. The presence of DR3/DRw52a or anti-Scl-70 gives a relative risk of 16.7 for the development of pulmonary fibrosis in a patient with scleroderma--a risk substantial enough to require careful monitoring of these patients and treatment at an early stage of disease.

Autoantibodies↗
PubMed1991

A family study confirms that the HLA-DP associations with celiac disease are the result of an extended HLA-DR3 haplotype.

Genotyping for HLA-DR, -DQ, and -DP antigens by restriction fragment length polymorphism (RFLP) analysis along with identification of restriction fragments associated with celiac disease (CD) were undertaken in 13 families in which more than one member had CD. Major histocompatibility complex class II haplotypes for the family members were constructed which included both genotypes and RFLP markers. In 12 of the families all the affected members shared an HLA haplotype which included HLA-DR3a, DQw2 and a BglII 4.0-kb DQA fragment. Eight of these 12 haplotypes also included HLA-DPw1 and both a RsaI 4.0-kb DPB fragment and an XbaI 16.0-kb DPA fragment. In one family, the two affected members shared an HLA-DR7, DQw2 haplotype, although both their second haplotypes included HLA-DR3a and -DQw2. The results suggest that HLA-DP genes do not play an independent predisposing role in the etiology of CD but do mark a disease-associated extended haplotype. This haplotype contains genes coding for specific HLA products which may be necessary for the disease to develop. The findings support the hypothesis that the presence of a specific DQ alpha/DQ beta heterodimer, encoded in a cis arrangement on HLA-DR3a haplotypes, predisposes to celiac disease.

Adolescent↗
PubMed1991

Ambulatory surgery and the hospital.

Ambulatory surgery can be a win-win proposition for patients, physicians, payers, and even for hospitals. The main elements at risk are high costs and the traditional models of hospital-based surgical care. If hospitals delay their responses to the challenges of the free-standing surgicenter, the latter will become as common as the multispecialty group practice. Health care institutions need to address some questions in responding to this trend: how hospitals should act to transform their bureaucratic, inefficient systems; who should assume the leadership role; and how much autonomy and pluralism will be appropriate.

Ambulatory Surgical Procedures↗
PubMed1991

Application of polymerase chain reaction (PCR) to HLA-C locus typing.

Polymerase chain reaction/oligonucleotide typing was used to identify HLA-Cw*0601 (Cw6) in patients with psoriasis and psoriatic arthritis. The assignment of HLA-Cw*0601 was established by the concordant presence of codons for alanine (position 73), lysine (position 80) and tryptophan (position 97). The frequencies of all three codons were increased in the patient groups.

Arthritis, Psoriatic↗
PubMed1990

Genes encoding the beta-chains of HLA-DR7 and HLA-DQw2 define major susceptibility determinants for idiopathic nephrotic syndrome.

1. We have investigated the frequencies of the major histocompatibility complex class II alleles by restriction fragment length polymorphism analysis, using DR, DQ and DP complementary DNA probes, in 40 Caucasoid steroid-sensitive nephrotic children. 2. A significant association with HLA-DR7 was demonstrated (P = 2 x 10(-5); aetiological fraction 0.6). The DQB1 gene of HLA-DQw2 was present in 83% of our patients (P = 2 x 10(-4); aetiological fraction 0.7). We present evidence that it contributes a second susceptibility allele. 3. A weak association between the uncommon HLA-DP-Cp63 allele and the disease was also observed. 4. Our data suggest that the immune events in steroid-sensitive nephrotic syndrome are defined by a particular immunogenetic background involving the beta-chain genes of HLA-DR7 and HLA-DQw2.

Adolescent↗
PubMed1990

The application of oligonucleotide probes to HLA class II typing of the DRB sub-region.

A plan for DRB typing at the sequence level is detailed. Only one polymerase chain amplification reaction is needed and the application of a limited number of short oligonucleotide probes allows an almost complete definition of DRB alleles. The scheme was tested on 40 homozygous cell-lines selected to cover a wide range of specificities, and 40 RFLP-typed controls. The results are presented and discussed. The simplicity and accuracy of this scheme are emphasized.

Alleles↗
PubMed1990

HLA class II and T cell receptor gene polymorphisms in psoriatic arthritis and psoriasis.

HLA-DRB, DQA and DQB genes as well as the T cell receptor (TcR) alpha, beta, and gamma genes were studied by Southern blot analysis of genomic DNA from patients with psoriatic arthritis (PsA) and psoriasis alone (Ps). A subtype of DR7, DR7a, was found in 38.8% of patients with PsA, 41.5% of patients with Ps, and in 8% of healthy individuals (N) (PsA vs N: pc = 0.0002, RR = 7.1; Ps vs N: pc = 0.0002, RR = 7.9). No association with TcR genes was found. Our findings suggest either that the DR7a allele may be in linkage disequilibrium with HLA-Cw6 or that it may be an important susceptibility factor for PsA and Ps.

Adult↗
PubMed1989

Southern blot analysis of HLA-DP gene polymorphisms in Caucasoid rheumatoid arthritis (RA) patients and controls.

Despite extensive analysis of the incidence of HLA-DR and HLA-DQ allele frequencies in defined autoimmune disease groups, there is very little information available on HLA-DP allele frequencies. This is largely because HLA-DP typing has until recently been restricted to primed lymphocyte typing (PLT). However, allelic polymorphism of the HLA-DP subregion can now be studied by Southern blot analysis or genotyping with DPA1 and DPB1 probes. By direct counting of allele-specific DNA fragments, we have analyzed the frequencies of five major DP genotypes (DPw1, DPw2, DPw3/6, DPw4, and DPw5), in a large number of Caucasoid rheumatoid arthritis (RA) patients (n = 74), and controls (n = 91). The predicted frequency of DP alleles in both patient and control groups was comparable to PLT-determined DP allele frequencies in normal Caucasoids. However, the gene frequency of DPw4 was increased in the RA patients, with 51% of the patients studied scoring as DPw4, 4 homozygotes. With the exception of one possible combination (DPw5 and DRw6) in the controls, no significant linkage disequilibrium was detected between DP and DR alleles in either patient or control groups. Thus the prevalence of DPw4 in the RA patients is independent of any disease association with the DR loci, and may represent a new class II association with RA.

Arthritis, Rheumatoid↗
PubMed1989

Anesthesiologists in North Carolina: a survey reflecting emerging subspecialization.

This North Carolina case study addresses the migration of anesthesiologists into subspecialty, clinical areas of anesthesiology over a 4-year period (1984 to 1987). Three hundred fourteen members of the North Carolina Society of Anesthesiologists (NCSA) were surveyed using a one-page questionnaire. The response rate was 93.6%. The questionnaire elicited data to characterize the magnitude of change in anesthesiologist manpower, to assess emerging subspecialization, to describe the flux of anesthesiologists entering and leaving practice, and to detail evolving modes of practice. Results indicated a net increase in manpower averaging 8.8% per year in academic programs, whereas clinical community practitioners increased physician positions at a rate three times the former (27% increase per year). Of 184 anesthesiologists recruited to North Carolina over 4 years, 75 different residency programs were represented; 48% of new anesthesiologists were from southern educational programs and 44% entered practice with fellowships (i.e., postgraduate year 4 to 5). The principal fellowship was cardiac (33%). Subspecialty areas were represented in all 53 reporting clinical practices. The principal practice mode emerging was hospital-based, same day surgery (85%) followed by pediatric anesthesia (81%), perioperative pain management (68%), obstetric anesthesia (63%), and an anesthesia "clinic" (54%). Respondents expected additional practice options over the next 3 years with anesthesia for ambulatory diagnostic and therapeutic modalities projected to emerge at the fastest rate. In conclusion, anesthesiologists in North Carolina seem to be filling unmet needs in obstetric and cardiac anesthesia, critical care, ambulatory surgery, and pain therapy units. These observations may represent a vignette of the national scene.

Anesthesiology↗
PubMed1989

A DQA1 allele is strongly associated with idiopathic membranous nephropathy.

The high molecular weight genomic DNA from 31 patients with idiopathic membranous nephropathy (IMN) has been digested with a restriction endonuclease Taq I, electrophoresed, blotted and hybridised with probes to the HLA-DRB, -DQA, -DQB, -DPA and -DPB genes. The restriction endonuclease Msp I was also used with the HLA-DPA and -DPB probes. The resulting restriction fragment length polymorphism (RFLP) has been analysed and compared with 55 controls treated in the same way. There was a significant increase in the DRB restriction fragments associated with HLA-DR3 (Fisher's p = 0.011), in particular with a sub-division of DR3 (Fisher's p = 0.0038). These results confirm at the DNA level serological correlations observed for IMN. A 4.5 Kb DQA RFLP was significantly raised in IMN patients (Fisher's p = 0.002) and is proposed as a major disease susceptibility factor.

Alleles↗
PubMed1988

Association of membranous nephropathy with T-cell receptor constant beta chain and immunoglobulin heavy chain switch region polymorphisms.

We have investigated T-cell antigen receptor constant beta chain genes (Tcr C beta) and immunoglobulin (Ig) heavy chain switch region genes of HLA-DR-typed patients with membranous nephropathy (MN) employing DNA restriction fragment length polymorphism (RFLP) analysis. When a Tcr C beta probe in conjunction with the restriction endonuclease Bgl II was used, a significant increase in the frequency of a 10.0; 9.2 kb heterozygous RFLP phenotype was found in MN (75.0% versus 42.1% in controls; P = 0.002). When Sst I-restricted DNA from MN patients was hybridized with a DNA probe homologous to the switch region flanking the Ig C mu heavy chain gene (S mu), there was a significant decrease in the frequency of the 2.1; 2.6 kb heterozygous RFLP phenotype in MN (24.0% versus 54.6% in controls; P = 0.004). These results suggest that Tcr beta and Ig heavy chain loci, as well as HLA antigens, may be important in the pathogenesis of MN.

Genes↗
PubMed1986

Immunoglobulin heavy chain switch region restriction fragment length polymorphisms are associated with renal disease.

We describe here, to our knowledge for the first time, associations between polymorphisms at the genomic DNA level in the immunoglobulin gene region and renal diseases which lead to chronic renal failure. Recent studies have shown that protein polymorphisms, present in immunoglobulin (Ig) heavy chains (Gm allotypes) are associated with certain forms of renal disease and with end stage renal failure per se. To investigate this association at the DNA level we have used probes which recognize Ig heavy chain genes and this report describes results obtained with one of these, the S mu switch region probe. With the restriction endonuclease Sst 1 (or the isoschizomer; Sac I) a number of restriction fragment length polymorphisms (RFLP) can be obtained which are recognized by this probe and there is a highly significant association between certain of these and renal disease. This is the first report of Ig switch region polymorphisms being associated with disease, yet our results suggest that S mu RFLP are more closely linked to renal disease than Ig protein polymorphisms.

Humans↗
PubMed1985

Immunoglobulin C mu gene restriction fragment length polymorphisms associated with chronic renal failure.

The DNA's of 41 patients with various forms of renal disease and of 52 controls were investigated for restriction fragment length polymorphisms (RFLP), using a probe recognising the immunoglobulin Cmu heavy chain gene. With the restriction endonuclease Sst 1, 50 of the controls and 12 of the patients had the expected single 4.3 kilobase (kb) fragment. The remaining 29 patients and 2 controls displayed two patterns of banding, 8 patients and 1 control had a 6.8 kb band in addition to the 4.3 kb, and 21 patients and 1 control had a single band of 5.1 kb. In addition, a significant association between high creatinine levels (greater than 150 mumol/l) and abnormal bands was found (21/25 patients with high levels had abnormal bands compared with only 5/16 patients with normal levels). These results are evidence for an association between the human immunoglobulin heavy chain region and renal disease and they apparently confirm an association already reported at the protein level. However, the new RFLP bands, although reproducible and restricted to renal patients, occur in an area where few polymorphisms would be expected. Further, the association with high creatinine suggests some subtle interaction between the creatinine pathway and this area of the human chromosome.

Creatinine↗