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Biomedical subjects

K I Welsh

Publications and source records attributed to K I Welsh.

At least 199 records · Page 11Linked to original sources
PubMed1988

Arthritis in patients with psoriasis is associated with an immunoglobulin gene polymorphism.

Using a DNA probe for the switch region of immunoglobulin heavy chain genes, together with the restriction endonuclease Sst I, we detected a particular polymorphic DNA pattern in 17 of 28 patients (60.7%) with psoriatic arthropathy but in only 5 of 41 patients (12.2%) with psoriasis alone. Our findings suggest that genes in the immunoglobulin region confer susceptibility to the development of arthropathy in patients with psoriasis.

Adult↗
PubMed1988

Family studies in scleroderma (systemic sclerosis) demonstrating an HLA-linked increased chromosomal breakage rate in cultured lymphocytes.

An increased chromosomal breakage rate (ICBR) was found in 27 of 28 patients with scleroderma (systemic sclerosis, SS) - 5 with the syndrome including calcinosis cutis, Raynaud phenomenon, esophagus hypomotility, sclerodactyly and telangiectasia (CREST), 4 incomplete CREST, 1 overlapping syndrome, 18 progressive systemic sclerosis (PSS). Not only the patients, but also about half of their first-degree relatives showed an increased chromosomal breakage rate (more than 5 breaks per 100 metaphases). This character segregated as a dominant marker in nine families of scleroderma patients. In the six informative of the nine families, the ICBR trait showed close linkage with the HLA region on chromosome 6 (total lod score 5.5 at theta = 0). In these families, ICBR was predominantly observed in linkage with HLA haplotype A1, Cw7, B8, C4AQ0B1, DR3 which is frequently observed in autoimmune diseases. The nature of the agent inducing chromosomal breakage in cultured lymphocytes of some, but not all family members of scleroderma patients remains to be clarified.

Cells, Cultured↗
PubMed1988

MHC class II sequences of an HLA-DR2 narcoleptic.

Narcolepsy has a 98% association with the DR2-Dw2/DQw1 haplotype. To establish if a disease-specific allele is present in narcolepsy, a cDNA library was made from a B-cell line from a DR2,4/DQw1,3 narcoleptic. Clones encoding the two expressed DR2 beta chains, along with DQw1 alpha and beta chains, were isolated and completely sequenced. The coding regions of these four genes were similar to published nucleotide and protein sequences from corresponding healthy controls, with some minor exceptions. The 3' untranslated region of one of the DR2 beta genes in the narcoleptic was extended by 42 bp. Complete sequences were not available for DQw1.2 alpha or beta from healthy individuals, but first domain nucleotide sequences showed only a single nonproductive difference in DQ alpha. Partial protein sequences of both DQ alpha and beta from published data were identical. Although the effects of minor differences cannot be ruled out completely, it is concluded that there are probably no narcolepsy-specific DR beta or DQ alpha/beta sequences, and that the alleles found in narcolepsy are representative of those found in the healthy population.

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↗
PubMed1988

Successful transplantation of kidneys bearing previously mismatched HLA A and B locus antigens.

Transplantation of kidneys bearing HLA antigens to which recipients have previously been exposed is generally avoided, and such prudence is a well-documented means of preventing early graft loss. Prior exposure and subsequent reactions can, however, take a wide variety of forms, and blanket avoidance may prevent many deserving patients from being transplanted. In our region, operating through a single tissue-typing laboratory, we follow a consistent policy of allowing retransplantation with kidneys bearing previous mismatches, provided no relevant antibody response has been detected. Twenty-one of 34 such transplants remain functioning at time periods ranging from 7 months to 7 years. Four were lost due to rejection within the 1st month, and the remaining 9 functioned for periods ranging from 2 months to 8 years. Three were lost for reasons other than rejection. Our antibody screening policy and our criteria for a negative crossmatch results in the exclusion of two-thirds of all repeat mismatch transplantations. The results indicate that in the remaining third, transplantation can be performed across a repeat mismatch with excellent long-term results, provided our defined crossmatch policy is adhered to strictly.

Antilymphocyte Serum↗
PubMed1988

Immunoglobulin heavy chain switch region polymorphisms are not associated with type 1 diabetes.

In order to ascertain whether the immunoglobulin heavy chain genes are important in the aetiology of Type 1 diabetes, we have used restriction fragment length polymorphism (RFLP) analysis of genomic DNA to study 148 Caucasoid subjects with Type 1 diabetes and 146 normal Caucasoid subjects. A DNA probe homologous to the switch regions for the IgM (S mu) and IgA1 (S alpha 1) genes when used in conjunction with the restriction endonuclease Sst I detects RFLPs at both these loci. There were no significant differences in phenotype or gene frequencies for the alleles of S mu or S alpha 1 in the patients when compared with control subjects; nor were there significant associations of S mu or S alpha 1 with HLA-DR type or gender.

Adolescent↗
PubMed1988

Relation of mesangial IgA glomerulonephritis to polymorphism of immunoglobulin heavy chain switch region.

We have investigated the switch regions of Ig heavy chain genes of patients with IgA glomerulonephritis (IgA-GN) using restriction fragment length polymorphism (RFLP) analysis. Genomic DNA from patients and controls was digested with the restriction endonuclease Sst I and transferred to nylon membranes using the Southern blot procedure and hybridized with a probe homologous to the switch region of the Ig C mu gene (S mu) which detects RFLPs in both S mu and the switch region of the Ig C alpha 1 gene (S alpha 1). A significant decrease in the frequency of the 2.6;2.1 kb heterozygous S mu phenotype was found in patients with IgA-GN (P = 0.003). With respect to the S alpha 1 region, there was a significant increase in the frequency of the 7.4 kb S alpha 1 phenotype (P = 0.002). In addition, a significant increase in the frequency of the 7.4 kb S alpha 1 allele was found (P = 0.0002). These results suggest that gene(s) within the Ig heavy chain loci may be important in the pathogenesis of IgA-GN.

Genes, Regulator↗
PubMed1987

Seronegative and seropositive rheumatoid arthritis: similar diseases.

A case control study of 50 rheumatoid factor positive (RA+) and 50 rheumatoid factor negative (RA-) patients with rheumatoid arthritis has been carried out. As expected, the RA+ group has significantly more nodules and vasculitis. In terms of clinical joint involvement, the RA- had large-joint involvement. Radiologically, seropositive disease was characterized by more severe involvement of the metacarpophalangeal joints of the thumb and index fingers and in all the metatarsophalangeal joints of the feet. There was no difference either clinically or radiologically between the two groups in terms of symmetry of joint disease or wrist involvement. Of special interest was the finding that the prevalence of HLA-DR4 was elevated to the same degree in both groups but that genetic markers for ankylosing spondylitis and for psoriasis (HLA-B27 and Cw6 respectively) were similar in both groups and not increased above control population levels. It is concluded that the entity defined as RA includes patients with and without rheumatoid factor (RF) in their serum and that this determines differences in disease expression. Whether these differences are the consequences or the cause of RF cannot be concluded on the basis of this study.

Arthritis, Rheumatoid↗
PubMed1987

A major histocompatibility complex class III allotype (C4B 2) associated with primary biliary cirrhosis (PBC).

Primary Biliary Cirrhosis (PBC) is a female associated disease of unknown aetiology, although there is evidence of immunological abnormalities. There is no known cure; liver damage is progressive and eventually fatal, although transplantation can prevent patient death. Data presented here show, for the first time, a strong association in Caucasoids between PBC and the major histocompatibility complex (MHC). 45% of patients studied, compared with only 17% in a control group, expressed an MHC Class III allotype C4B 2 (pc = 0.014). Polymorphisms of MHC Class I, Class II, and other Class III gene products which flank the C4 genes were not found to be associated with the disease. Although we cannot rule out the involvement of other loci linked to the C4B 2 complement gene, the data provide strong evidence that this genetic area is implicated in the pathogenesis of this disease.

Complement C3↗
PubMed1987

Factors influencing circulating OKT8 cell phenotypes in patients with multiple sclerosis.

Peripheral blood OKT8 cell phenotypes were correlated with measurements of plasma cortisol and serological evidence for exposure to 15 infectious agents, in longitudinal studies involving 13 patients with multiple sclerosis, 13 of their siblings, nine spouses and 13 unrelated controls; 44/48 individuals were HLA typed. Neither circadian rhythms, nor exposure to any one infectious agent accounted for the serial changes in OKT8 cells but there was an association between the presence of HLA-DR2 and periodic reductions in OKT8 cells irrespective of clinical status. Taken with previously reported serial observations in patients and cohabiting relatives, this finding provides indirect evidence for an interplay between environmental and genetic factors in determining OKT8 cell phenotypes in multiple sclerosis.

Antibodies↗
PubMed1987

Polymorphism of the T cell receptor beta-chain in Graves' disease.

We investigated the T cell antigen receptor constant (TCR beta) beta-chain genes of patients with Graves' disease using restriction fragment length polymorphism analysis. Genomic DNA from patients and normal subjects was digested with the restriction endonuclease Bg1 II, transferred to nylon membranes using the Southern blot technique, and hybridized with a TCR beta probe. A significant increase in the frequency of the 10.0; 9.2-kilobase heterozygous phenotype was found in GD (68.6%) vs. 42.1% in normal subjects (P = 0.003). Using the complex phenotype TCR homozygote (hetero) DR3 as a reference (odds ratio = 1.00), we found that the risk for Graves' disease was restricted to TCR beta heterozygote/DR3+ individuals (odds ratio = 8.31; chi 2 = 11.82; P = 0.0009); in the absence of TCR beta heterozygosity, DR3 was not significantly associated with the disease. These results suggest that TCR beta chain genes also are associated with susceptibility to GD and that the association is most pronounced in (or restricted to) those individuals who are HLA DR3 positive.

Chromosomes, Human, Pair 7↗
PubMed1987

T cell receptor beta chain polymorphisms are associated with insulin-dependent diabetes.

We investigated the T cell receptor constant beta chain (TCR C beta) genes of patients with insulin dependent diabetes mellitus (IDDM) using DNA restriction fragment length polymorphism (RFLP) analysis. Genomic DNA from patients and controls was digested with the restriction endonuclease Bg1 II and transferred to nylon filters using the Southern blot procedure. This enzyme identifies a polymorphic site between the two TCR C beta chain genes. We have found a highly significant increase in the frequency of the 10.0; 9.2 kilobase heterozygous phenotype in patients with IDDM (62.7% versus 42.0% in normal controls; P = 0.0006). In identical twin pairs, this association was most striking in those concordant for IDDM (79.2% versus 42.0% in controls; P = 0.0006).

Adolescent↗
PubMed1986

Antinuclear antibodies in the relatives and spouses of patients with systemic sclerosis.

The families of 65 patients with systemic sclerosis were examined clinically and serum samples from each subject were tested for antinuclear antibodies (ANA) by immunofluorescence on HEp2 cells and for precipitating antibodies to soluble cellular antigens including Scl-70. Of 217 blood relatives, 58 (27%) had ANA (42 speckled, 13 nucleolar, one centromere, two homogeneous); 22 (10%) had precipitins, one anti-Scl-70, one anti-PM-Scl, one anti-nRNP, two anti-Ro(SSA), the remainder unidentified). Family members tended to share ANA patterns. Of 38 spouses, nine (24%) had ANA (all speckled) and two showed unidentified precipitins. This compares with an incidence of ANA and precipitins in a control population of 8% and 1% respectively. Antibodies were more common in female than male relatives (particularly in mothers and sisters of probands). Twenty one of the 58 family members with ANA had clinical features of connective tissue disease; the remainder were asymptomatic. The presence of genetic factors influencing autoimmunity is suggested by the incidence of autoantibodies in first degree relatives. Similar observations in spouses, however, indicate that environmental factors may also have a role in these immune abnormalities.

Antibodies, Antinuclear↗
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↗