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I J Simpson

Publications and source records attributed to I J Simpson.

At least 19 recordsLinked to original sources
PubMed1998

Visualisation of extensive water ribbons and networks in a DNA minor-groove drug complex.

The crystal structure is reported of a complex between an ethyl derivative of the minor-groove drug furamidine and the dodecanucleotide duplex d(CGCGAATTCGCG)2, which has been refined to 1.85 A resolution and an R factor of 16.6% for data collected at -173 degreesC. An exceptionally large number (220) of water molecules have been located. The majority of these occur in the first coordination shell of solvation. There are extensive networks of connected waters, both in the major and minor grooves. In particular, there are 21 water molecules associated with the minor-groove drug, via hydrogen bonds from the four charged nitrogen atoms. One cluster of four waters is situated in the groove itself; the majority are on the outer edge of the groove, and serve to bridge between the outward-directed drug nitrogen atoms and backbone phosphate oxygen atoms. These bridges are both intra- and inter-strand, with the net effect that the outer edge of the drug molecule is covered by ribbons of water molecules.

Antifungal Agents↗
PubMed1998

TCRBV14S1 and rheumatoid arthritis revisited: abnormalities in the percentage of transcribed TCRBV14S1 family genes in PBMC from rheumatoid arthritis patients.

The purpose of this study was to identify Vbeta gene families that are associated with rheumatoid arthritis (RA). A PCR-based assay was used to compare the Vbeta repertoire of unstimulated PBMC from 18 RA patients and 18 matched controls. The influence of an HLA-DRB1-binding peptide (HA307-319) on the Vbeta repertoire of PBMC in culture was compared in 11 RA patients and 10 controls. There was a larger variance in the percentage of BV14S1 transcripts in unstimulated PBMC from RA patients than from controls (p = 0.0003). The mean percentage of BV14S1 transcripts was higher in RA patients when prednisone-treated RA patients were excluded from the analysis (p = 0.0006). In vitro stimulation with the HA307-319 peptide increased the percentage of BV14S1 transcripts in PBMC from RA patients (+ 1.5 +/- 0.4%, p < 0.005) but not controls (+ 0.3 +/- 0.2%, ns), and the difference between RA patients and controls was significant (p = 0.03). In conclusion, there is an association between RA and the BV14S1 gene family in New Zealand patients.

Arthritis, Rheumatoid↗
PubMed1996

Repertoire of transcribed peripheral blood T-cell receptor beta chain variable-region genes in acute rheumatic fever.

Patients with severe group A streptococcal infections have abnormalities in the Vbeta repertoire of peripheral blood T cells that are consistent with superantigen stimulation by cytoplasmic membrane proteins. The purpose of this study was to determine whether similar changes in Vbeta repertoire could be found for patients with acute rheumatic fever (ARF). The mean Vbeta repertoire of peripheral blood T cells in nine hospitalized ARF patients was similar to that of 34 controls and did not change during 6 months of follow-up in 6 of the ARF subjects. We were unable to detect changes in the Vbeta repertoire of peripheral blood T cells from patients with ARF that could be attributed to the influence of a superantigen.

Acute Disease↗
PubMed1995

Search for linkage disequilibrium between alleles in the T cell receptor alpha and beta chain loci and susceptibility to rheumatic fever.

A population-based linkage disequilibrium study was conducted to search for associations between alleles in T cell receptor alpha and beta chain polymorphic loci and susceptibility to rheumatic fever. The allele frequencies of four T cell receptor locus restriction fragment length polymorphisms were measured in 47 European and 51 Maori subjects with a history of rheumatic fever. These allele frequencies were compared to the allele frequencies in three or four independently recruited, race-matched control groups totalling 125 Europeans and 117 Maoris with no history of rheumatic fever. The polymorphisms studied were (locus/enzyme/probe) C alpha/Taq1/Y14, V alpha/Taq1/Y14, V beta 7/BAMHI/V beta 7.4 and V beta 8/BAMHI/V beta 8.1. There was no evidence for linkage disequilibrium between rheumatic fever and these Tcr alleles in either the Maori or European subjects.

Adult↗
PubMed1995

Peripheral blood T lymphocytes in systemic vasculitis: increased T cell receptor V beta 2 gene usage in microscopic polyarteritis.

Antigen recognition by T lymphocytes is mediated by cell surface receptors T cell specificity depends on the variable, diversity and junctional (VDJ) regions of the alpha and beta polypeptide chains of the T cell receptor (TCR). The expression of the variable region genes of the beta chain (V beta) has been analysed to study the involvement of peripheral blood T cells in systemic vasculitis. RNA was extracted from peripheral blood lymphocytes of 12 patients with microscopic polyarteritis, 10 with Wegener's granulomatosis, six with unclassified vasculitis, and 28 healthy age- and sex-matched individuals. Complementary DNA was made from RNA and amplified by the anchored polymerase chain reaction (PCR) using redundant oligonucleotide primers for the TCR V beta genes. To determine if the dominant usage of a V beta gene family reflected the presence of particular T cell clones, cDNA was amplified with primers for the specific V beta gene family. The product was screened for sequence homogeneity by single-stranded conformational polymorphism (SSCP) and cloned to sequence the adjoining TCR (D beta) J beta region. A significant increase in the mean percentage expression of the V beta 2.1 gene was seen in vasculitis patients (11.4 + 1.0% (mean + s.e.m.)) compared with controls (6.6 + 0.6%; P < 0.003). The most marked increase was seen in microscopic polyarteritis (13.9 + 1.7%; P < 0.0001). There were also increases in the expression of V beta 3, 13 and 14 in peripheral blood of vasculitis patients compared with controls. SSCP analysis of V beta 2.1 amplified products indicated the presence of oligoclonal bands in a smaller proportion of patients (8/27) than controls (12/28). There was no strong evidence for the conservation of the TCR V beta 2.1 junctional region sequence data from a sample group of three patients with oligoclonal bands. Thus, a subset of patients with systemic vasculitis, particularly those with microscopic polyarteritis, have increased TCR V beta 2.1 gene expression in their peripheral blood T cell repertoire. As superantigens binding V beta 2.1 are postulated to activate T cells with diverse CDR3 sequences, it is proposed that a superantigen is involved in the immunopathogenesis of vasculitis.

Adult↗
PubMed1993

Population study of T cell receptor V beta gene usage in peripheral blood lymphocytes: differences in ethnic groups.

The T cell receptor (TCR) V beta repertoire in peripheral blood lymphocytes (PBL) of a large number of healthy individuals was analysed by quantifying V beta-specific mRNA using the method of anchored multiprimer DNA amplification and a reverse dot blot assay. Among 16 V beta gene families examined, particular V beta genes were noted to be unequally expressed in the PBL of 70 healthy donors. The frequently used genes belong to the V beta 4, 5, 6, 8 and 13 (12) families, while V beta 1, 9 and 15 were the least frequently used gene families. This bias in gene usage was observed in all individuals. Marked deviation from the mean percentage usage was noted for some V beta genes in individuals when their PBL were examined serially, but the common pattern of biased usage was not grossly distorted. When the TCR repertoire of different ethnic groups was examined, a lower mean frequency of V beta 3.2 was seen in the repertoire of 19 Caucasians compared with 25 age-matched Samoans (P < 0.003). Conversely, the expression of V beta 5.1 and V beta 5.3 was higher in Caucasians than in 51 age-matched Polynesians (Maoris and Samoans, P < 0.003). Considering the 20% co-efficient of variation in the estimate of V beta gene usage, our data from 70 unrelated individuals suggest that in PBL, individual variations in the TCR repertoire were superimposed upon a common biased usage of V beta genes in the general population.

Base Sequence↗
PubMed1991

Cure of Salmonella hadar endovascular infection with medical therapy.

Endovascular infection due to salmonellae is an uncommon condition with an extremely poor prognosis. We describe a patient with endovascular infection due to Salmonella hadar who was cured by prolonged medical treatment with third generation cephalosporin and fluoroquinolone antibiotics.

Cephalosporins↗
PubMed1986

Surreptitious diuretic ingestion mimicking Bartter's syndrome.

Surreptitious diuretic use was found in a patient with longstanding hypokalaemia thought to be due to Bartter's syndrome. Measurement of urinary chloride excretion and repeated qualitative testing for diuretics in the urine were necessary to make a diagnosis.

Bartter Syndrome↗
PubMed1985

Factors affecting outcome after chest injury.

From 1978 to 1983 a total of 328 patients was admitted to Royal Newcastle Hospital Intensive Care Unit with chest injuries; 255 had other injuries as well. Of the 328, 171 developed acute respiratory failure, 174 received mechanical ventilation (159 for acute respiratory failure) and 46 died. The commonest causes of death were head injury (19), sepsis (10) and uncontrollable haemorrhage (10). Associated head (131) and/or abdominal (89) injuries tripled mortality. Those without respiratory, cardiac, renal or hepatic failure (155) had a mortality rate of 5.8% while the remainder had mortality rates of 21.6%, 12.5%, 37.5% and 100%, for respiratory (171), cardiac (8), renal (8) and hepatic (5) failures, respectively. Shock was present on admission in 55, of whom 19 died. Sepsis developed in 59 and 14 with this complication died. Sepsis remains a potentially avoidable late cause of death and attention needs to be directed towards limiting invasive techniques of management to those which are necessary, and towards early diagnosis of abdominal injuries with early exploratory surgery. The best chance of survival in the initial phase of injury may lie in the establishment of an integrated regional trauma centre system together with improved pre-hospital and retrieval systems.

Abdominal Injuries↗
PubMed1984

C1q binding and C1q deviation assays using enzyme labelled C1q.

Methods for the enzyme labelling of C1q are described. The C1q conjugates have been incorporated into suitably modified C1q deviation and C1q binding assays for circulating immune complexes. These assays show the expected high positivity rate in sera from patients with systemic lupus erythematosus. The assays using enzyme labelled C1q confer considerable advantages over their counterparts using 125I.

Alkaline Phosphatase↗
PubMed1983

Lupus nephritis: clinicopathological correlations.

We have reviewed our experience of lupus nephropathy in Auckland over a 15 year period during which time 70 biopsies were obtained from 56 patients with systemic lupus erythematosus. Based on appearances by light microscopy, the biopsies were categorised as mesangial, focal, diffuse or membranous lupus nephritis. Immunofluorescence, where performed, was positive in all instances, including those biopsies showing only mesangial disease by light microscopy. By electronmicroscopy, biopsies with mesangial disease by light microscopy usually had deposits confined to the mesangium, while more severe forms of disease usually had deposits present both around the loops and in the mesangium. Clinical renal abnormalities were uncommon in the mesangial group, usual in the focal group and ubiquitous in the diffuse group. Notably, four of the 18 patients who had no clinical renal or urinary abnormalities, had focal or diffuse disease, indicating a small but definite risk of missing significant renal disease if a biopsy is not performed.

Adult↗
PubMed1983

Immune complexes in normal subjects.

Immune complex (IC) levels were measured in normal subjects using the C1q solid phase, C1q deviation, C1q binding and polyethylene glycol precipitation assays. Significant changes in IC levels were seen in normals with each of the assays but the pattern of variation was not consistent between assays or subjects or in the same subject from day-to-day. There were no consistent changes with meals, time of day, exercise or the prior administration of prednisone. Low levels of IC appear to be normal in plasma but the variation in IC levels is not explained. Normal IC may well comprise mixtures of non-specific immunoglobulin aggregates, rheumatoid factor-immunoglobulin complexes, idiotype-anti-idiotype complexes as well as specific antibody complexes with antigens from food, infective agents and other sources.

Adult↗