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D G Williams

Publications and source records attributed to D G Williams.

At least 37 records · Page 2Linked to original sources
PubMed1997

Clonal analysis of immunoglobulin mRNA in rheumatoid arthritis synovium: characterization of expanded IgG3 populations.

Plasma cells secreting IgG, M, and A abound in the synovium of patients with rheumatoid arthritis, yet their immunoglobulin repertoire and clonal relationship remain to be elucidated. Locally synthesized immunoglobulins probably contribute to the chronic joint inflammatory processes which are characteristic of these patients. To determine whether B lymphocyte proliferation contributes to the synovial plasma cell infiltrate, the clonality of IgG mRNA in individual synovial biopsies from an actively inflamed joint of patients with rheumatoid arthritis was investigated by a combination of cDNA length analysis and DNA sequencing. Particular sizes of immunoglobulin cDNA, detectable in subclasses 1, 3, or 4, were expressed in most synovial biopsies from one patient, suggesting their origin from expanded clones present in each biopsy. To prove a clonal relationship between recurrent cDNA lengths, immunoglobulin cDNA was cloned from three regions of synovium in three patients. The sequence of clones with a recurrent cDNA length was determined. An IgG3 clone found in most synovial biopsies of one patient was encoded by an unmutated copy of the V(H)1 gene, DP7. In contrast, IgG3 clones encoded by mutated versions of the V(H)3 gene DP49 or the V(H)4 gene DP63 were expanded in the other two patients. Different somatic mutants of these clones were isolated from different sites in these patients. The ratio of replacement/silent somatic mutations in these two families of clones suggests that the selective clonal expansion in the synovium of patients with rheumatoid arthritis is due to an antigen-driven immune response.

Adult↗
PubMed1997

C3 nephritic factor and mesangiocapillary glomerulonephritis.

The association of a C3 splitting activity, known as C3 nephritic factor (C3NeF), with mesangiocapillary glomerulonephritis (MCGN), especially MCGN type II, has long been known. Several forms of C3NeF are now recognised, the main one being an IgG which acts as an autoantibody binding to factor H, a normally occurring component of the complement system. Complement is in a continuous state of activation with inbuilt checks and controls, and factor H plays a very important part in the controlling mechanisms by preventing the overwhelming activation of complement at the stage of C3 conversion. C3NeF binds to factor H, thus preventing its inhibitory action, and allowing complement activation to proceed with, in vivo, the well-known consequences in MCGN of very low serum levels of C3. The question naturally arose whether C3NeF causes MCGN. Complex relationships between MCGN, C3NeF and partial lipodystrophy, also characterised by C3NeF and hypocomplementaemia, but preceding the development of MCGN, suggest that hypocomplementaemia predisposes to MCGN. Another possibility is that C3NeF acts directly within glomeruli to cause local complement activation and ensuing damage. Neither possibility could be resolved, but some recent observations have restimulated interest in a possible causative role for C3NeF in MCGN. First, factor H deficiency, by mechanisms other than blocking by C3NeF, in animals and man is associated with MCGN. Second, adipocytes, now known themselves to produce complement system proteins, are lysed in vitro by C3NeF, thus suggesting a mechanism for partial lipodystrophy. By analogy, the C3NeF may produce glomerular damage, as glomerular cells produce complement components.

Adolescent↗
PubMed1996

Shunt infections in children: presentation and management.

Since the earliest attempt at surgical management of hydrocephalus, infection has been a significant complication. For better assessment and care the neuroscience nurse needs to be aware of the signs and management of this condition. A retrospective review of 68 infections in 61 children was undertaken. Results showed an increased incidence of infection in the first nine months after surgery. Gram positive organisms (Staphylococcus epidermidis and Staphylococcus aureus) were most frequent; Propionobacter acnes was a significant pathogen in adolescence. Presenting symptoms included fever (26%), abdominal pain (19%), wound changes (22%) and indicators of shunt malfunction (33%). Elevated white blood cells (WBCs) in spinal fluid from shunt tap and positive cultures were most reliable laboratory data. Culturing of causative organism was sometimes difficult. A value regulated system for ventricular drainage which allows greater mobility for the patient is described.

Algorithms↗
PubMed1996

Crying, weeping or tearfulness in British and Israeli adults.

Participants (aged 20-42 years; N = 448) from Britain and Israel answered questions on their crying behaviour. They were more likely to cry alone than when with others and least likely to cry with people they did not know well. Women cried more often and for longer and with more intensity than men. Britons cried more than Israelis. Explanations in terms of differential inhibition were not supported. The sex difference was especially marked for situations involving criticism from others, anger, or problems with work, where men were particularly unlikely to cry, and least for those situations Darwin described as involving tender feelings. The pattern was related to differences documented elsewhere in which men tend to more active and confrontational styles of behaviour. British-Israeli differences were consistent with the effects of military service. Tearfulness for tender feelings increased with age in all groups. A principal component analysis distinguished crying that is intense, long lasting and difficult to stop from crying that is more diverse in appearance but more controllable. The distinction seems related to whether crying pre-empts or concurs with other ongoing activities.

Adult↗
PubMed1995

Anti-La monoclonal antibodies recognizing epitopes within the RNA-binding domain of the La protein show differential capacities to immunoprecipitate RNA-associated La protein.

The La (SS-B) autoimmune antigen is an RNA-binding protein that is present in both the nucleus and cytoplasm of eukaryotic cells, where it is found associated with RNA polymerase III transcripts. We have investigated the capacity of anti-La monoclonal antibodies SW1, SW3, and SW5 to immunoprecipitate human La ribonucleoprotein particles. Distinct differences were observed for SW3 in comparison with SW1 and SW5. While SW1 and SW5 precipitated ribonucleoproteins containing pre-tRNA, pre-5S rRNA, hY RNAs, pre-U6 snRNA or the viral EBER1 and VA RNAs, SW3 precipitated only ribonucleoproteins containing VA RNAs or (the precursor of) 7-2 RNA. Mapping of the epitopes recognized by SW1, SW3, and SW5 revealed that all three monoclonal antibodies recognize an epitope within the domain of the protein formed by the ribonucleoprotein motif. Cross-competition studies suggested that the epitope recognized by SW1 and SW5 are identical but distinct from the epitope recognized by SW3. Further analyses of the recognition of La from other species by these monoclonal antibodies revealed that they all reacted with bovine La and were not reactive with La from rodents and Xenopus laevis. Replacement of a single amino acid in the human protein by its murine counterpart abolished recognition by SW1 and SW5, but had no effect on recognition by SW3. Taken together, our results indicate that SW1 and SW5 recognize the same epitope and that SW3 recognizes a distinct epitope, both of which are located in the RNA-binding domain of La, and that the accessibility of these epitopes is differentially influenced by the association of La with various RNA polymerase III transcripts.

Amino Acid Sequence↗
PubMed1995

Antibodies to the 65 kDa mycobacterial stress protein in west Africans with rheumatoid arthritis, tuberculosis and malaria.

We have studied IgG antibodies to recombinant mycobacterial 65 kDa heat-shock protein in West African rheumatoid arthritis (RA) patients and local control groups, including those with tuberculosis or malaria. Mean levels were higher among the patients with RA than among healthy controls, but did not achieve statistical significance. Our findings may relate to the level of mycobacterial exposure in West Africa.

Africa, Western↗
PubMed1995

An analysis of HLA class II gene polymorphism in British and Greek idiopathic membranous nephropathy patients.

Fifty-two British and 29 Greek idiopathic membranous nephropathy (IMN) patients were analysed for DRB, DQA1, DQB1 and DPB1 gene polymorphism using second exon amplification and sequence-specific oligonucleotides (SSO). In addition 100 British and 92 Greek controls were analysed. A highly significant increased frequency of the DRB1*0301 allele was found in IMN patients from Britain (80%), when compared to controls (27%, OR 10.6, P = 0.000004). A lower frequency of DRB1*0301 was observed in Greek IMN patients (33%), but this was just significant before correction, when compared to Greek controls (15%, OR 3, P = 0.02). The DRB3 allele most often associated with DRB1*0301 was DRB3*0101 (OR 4.2, P = 0.00025) in British patients and DRB3*0201/2 (OR 11, P = 0.006) in Greek patients. In Greek IMN patients a decrease in DR16 was found (OR 0.08, P = 0.004), and the overall incidence of DR2 was significantly lowered when both sets of IMN patients were combined (OR 0.21, chi 2 17.6, P = 0.00013). The incidence of DQA1*0501 was raised in both Greek (96% vs. 66%, OR 9.7, chi 2 6.9, P = 0.009) and British IMN (85% vs. 45%, OR 7.4, chi 2 20, P = 0.00007) patients. This gives some support to a proposal for a major role for this allele in IMN.(ABSTRACT TRUNCATED AT 250 WORDS)

Alleles↗
PubMed1995

Sequence analysis of immunoglobulin heavy-chain variable region genes from the synovium of a rheumatoid arthritis patient shows little evidence of mutation but diverse CDR3.

To gain insight into the nature of B-lymphocyte responses in the synovium of rheumatoid arthritis (RA) patients, we amplified and sequenced immunoglobulin heavy-chain variable region genes expressed in seven IgM and three IgG-secreting synovial-derived hybridomas established from one patient. Each hybridoma V-region was encoded by unique VH-D-JH combination demonstrating that none of these hybridomas derived from clonally related B-lymphocytes in vivo. The expressed VH genes closely resembled (95.6%-100% homology) known germline VH genes in most hybridomas, including VH genes frequently used to encode autoantibodies. The antibodies produced by these hybridomas, with the exception of one IgM rheumatoid factor, did not bind to any of a large panel of autoantigens in enzyme-linked immunosorbent assay (ELISA), immunoblotting and immunofluoresence, suggesting that frequent expression of 'autoantibody-associated' VH genes does not correlate with detectable autoreactivity in this patient. Hybridoma CDR3 DNA was diverse in length and gene composition. Conserved heavy-chain cross-reactive idiotypes were expressed on 4/7 IgM- and 2/3 IgG-secreting hybridomas. The close similarity of expressed VH genes to germline counterparts of these hybridomas suggests that polyclonal activation is a prominent mechanism in B-lymphocyte activation in the synovium of this rheumatoid arthritis patient.

Arthritis, Rheumatoid↗
PubMed1995

Unusual presentations of anti-glomerular basement membrane antibody mediated disease are associated with delayed diagnosis and poor outcome.

Anti-glomerular basement membrane antibody mediated disease (anti-GBM disease) is an uncommon cause of renal failure. Presentation is usually dramatic, with renal failure and alveolar hemorrhage leading to an early diagnosis. In contrast, we here describe 3 cases which presented with atypical features, and where diagnosis was delayed due to the presence of other factors which were initially felt sufficient to explain the clinical status. No patient recovered renal function, and one died from sepsis. We also present data on 15 patients presenting to Guy's Hospital over the past 10 years with anti-GBM disease and creatinine > 500 mumol/l. The median delay from presentation to diagnosis was 7 days, range 1-81 days. Two patients died, and only one recovered renal function. We speculate that earlier referral and renal biopsy might have improved outcome in these patients, and recommend a policy of early biopsy in all cases of acute renal failure with atypical feature, delay in recovery, or where a clearcut cause is not established.

Aged↗
PubMed1994

IgA nephropathy.

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Glomerulonephritis, IGA↗
PubMed1994

Mice lacking Snrpn expression show normal regulation of neuronal alternative splicing events.

The SmN protein is closely related to the constitutively expressed RNA splicing protein SmB but is expressed only in brain and heart tissue. Mice which lack expression of SmN die shortly after birth suggesting a critical role for this protein possibly in the regulation of neuronal-specific alternative splicing events. We show here however that the neuronal-specific alternative splicing of the RNAs encoding several different classes of protein proceeds normally in mice lacking SmN expression. The potential role of SmN and the reasons for the lethal effect observed in non-expressing mice are discussed.

Alternative Splicing↗
PubMed1994

Antibodies to synthetic peptide P62 corresponding to the major epitope of rheumatoid arthritis nuclear antigen in a west African population with rheumatoid arthritis.

Using a synthetic peptide (P62) we have investigated antibodies to rheumatoid arthritis nuclear antigen (RANA) in 58 West African patients with RA, 51 with malaria, 111 with tuberculosis (TB) and 166 healthy controls by ELISA using a synthetic peptide (P62). As in Western populations the RA sera showed significantly increased levels of anti-P62 antibodies though in our study the mean titres were only elevated twofold above the controls. The levels in malaria and TB were normal. Our data extend previous work by showing that raised anti-P62 antibodies is a consistent finding in RA world-wide including indigenous West African patients.

Adult↗
PubMed1994

Binding of pentraxins to different nuclear structures: C-reactive protein binds to small nuclear ribonucleoprotein particles, serum amyloid P component binds to chromatin and nucleoli.

Binding of the human pentraxin plasma proteins, C-reactive protein (CRP) and serum amyloid P component (SAP), to the nuclei of human cells was studied using whole acute phase serum as the source of the proteins and confocal immunofluorescence microscopy. CRP and SAP clearly bound to distinct, different structures. Double staining with MoAbs to the Sm D and Sm B/B' components of small nuclear ribonucleoproteins confirmed that CRP bound exclusively to these particles. As expected, SAP bound to chromatin and, in addition, binding to the nucleolus was observed for the first time. These interactions demonstrated under relatively physiological conditions, with native pentraxins unseparated from serum and with nuclear constituents in situ, are likely to be of functional importance in vivo.

Animals↗
PubMed1994

High levels of anti-type II collagen IgG in west African patients with rheumatoid arthritis.

OBJECTIVE: To compare levels of antitype II collagen IgG in West African and British patients with rheumatoid arthritis (RA). METHODS: IgG levels to native and denatured type II collagen were measured by ELISA: RESULTS: Serum levels of antinative type II collagen IgG were raised in 17 of 58 (29%) West African patients with RA. In contrast, 14 of 89 (16%) British RA patients had raised levels of antinative type II collagen IgG. Levels of antinative type II collagen IgG were also higher in West African patients with RA than in the British patients. CONCLUSION: Our results suggest that type II collagen autoimmunity plays a more prominent role in RA in West Africa than in Britain.

Africa, Western↗