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Biomedical subjects

R A Watts

Publications and source records attributed to R A Watts.

At least 55 records · Page 3Linked to original sources
PubMed1994

Sequence analysis and fine specificity of two human monoclonal antibodies to histone H1.

Two human IgM lambda monoclonal antibodies (MAb) derived from the splenic lymphocytes of patients with idiopathic thrombocytopenia (Ben) and systemic lupus erythematosus (Wri) were studied. BEN-27 and WRI-170 hybridoma supernatants were screened for binding to ssDNA, dsDNA, poly (ADP-ribose), cardiolipin, histone subclasses and Klebsiella K30 cell wall antigen. Of this panel of antigens, BEN-27 and WRI-170 antibodies reacted only with histone H1. Their fine specificity was defined by direct and inhibition ELISA with synthetic peptides of the major human H1b variant. Antibody WRI-170 was shown to bind to both the N- and C-terminal peptides encompassing residues 1-16 and 204-218 of H1b whereas BEN-27 reacted only with peptide 204-218. To analyse the genetic origin of these autoantibodies, we determined the nucleotide sequence of the heavy (H) and light (L) chain variable regions of these two hybridomas. BEN-27 and WRI-170 MAbs were found to use VH1-DN1-JH4/V lambda 3-J lambda 2 and VH3-DIR2-D21/9-JH1/V lambda 2-J lambda 2 gene segment combinations respectively. Between 70 and 95% homology was demonstrated when the mRNA sequences for BEN-27 and WRI-170 were compared with published VH and V lambda germline sequences. This finding suggests that BEN-27 heavy and light chains and WRI-170 light chain use unidentified VH and V lambda germline gene segments whereas WRI-170 heavy chain derives from a VH gene segment recently identified. It is noteworthy that the CDRs of the two MAbs contain several negatively charged amino acids which are assumed to be of critical importance in antigen binding. Moreover, striking similarities are observed between BEN-27 heavy chain CDR2 and a previously described murine anti-H1 Ab heavy chain CDR2.

Amino Acid Sequence↗
PubMed1994

Familial eosinophilic fasciitis and breast cancer.

Eosinophilic fasciitis (EF) is an uncommon condition which unlike systemic sclerosis has only rarely been associated with solid malignancies. We report the occurrence of EF in two sisters, both of whom developed contemporaneous breast cancer.

Breast Neoplasms↗
PubMed1994

The arthropathy of the Muckle-Wells syndrome.

Muckle-Wells syndrome (MWS) is a rare condition characterized by urticaria, arthralgias, deafness and amyloid nephropathy. The arthropathy is poorly documented. We describe the arthropathy occurring in four cases of MWS and discuss the management. Each patient developed recurrent bouts of transient synovitis. One patient developed a persistent sterile pyoarthrosis.

Adult↗
PubMed1994

The incidence of rheumatoid vasculitis in the Norwich Health Authority.

Systemic rheumatoid vasculitis (SRV) is an uncommon but potentially serious complication of RA. The incidence of SRV is unknown. The aim of this study was to estimate the incidence of SRV in the UK. Over a 6-yr period vigorous attempts were made to identify all patients with newly diagnosed SRV living within the Norwich Health Authority (NHA). The overall annual incidence of SRV is 12.5/million (95% CI: 8.5-17.7). The annual incidence rate for men was 15.8/million (95% CI: 9.5-24.7) and 9.4/million (95% CI: 4.8-16.4) for women. The incidence of SRV in this study is higher than previous estimates.

Adult↗
PubMed1993

Arthro-osteitis--a clinical spectrum.

Arthro-osteitis is an uncommon condition which can be associated with palmoplantar pustulosis. It forms part of a group of conditions which include the synovitis, acne, pustulosis, hyperostosis, osteitis syndrome (SAPHO) and sternocostoclavicular hyperostosis. We report four cases illustrating the clinical spectrum of this condition which occurred in the absence of concomitant skin lesions. One patient had extensive aortic calcification a feature not previously reported in this condition, which may represent a low grade inflammatory aortitis.

Adult↗
PubMed1993

Expression of public idiotypes in patients with Lyme arthritis.

OBJECTIVE: Joints are often affected in Lyme disease and in some instances this may be due to immune autoreactivity. To characterise further the immune response in this disease investigations were carried out to determine the expression of three public idiotypes on serum immunoglobulins in patients with Lyme disease during the development of varying degrees of arthritis. METHODS: The expression of idiotypes (Ids) 16/6, BEG2, and PR4, first identified on monoclonal antibodies to DNA, was determined by an enzyme linked immunosorbent assay (ELISA) in serial blood samples from 12 patients with Lyme disease over a mean period of six years during the development of a variety of arthritic symptoms, and in serum samples from healthy control subjects and control subjects with systemic lupus erythematosus. RESULTS: Expression of serum IgM or IgG public Ids 16/6 and BEG2 was significantly increased in patients with Lyme disease. IgA Id 16/6 expression, in contrast, was significantly increased only during episodes of arthritis and was also related to its severity. IgM and IgG Id 16/6 expression was related to their respective total immunoglobulin concentration and, in the case of IgM, to the level of IgM antibodies to Borrelia burgdorferi, whereas similar findings were not apparent with IgA antibodies. This may indicate that the IgA response is related to the pathogenesis of arthritis, especially as total IgA and IgA Id 16/6 levels were found to increase over the duration of disease. Sequential analysis of antibodies also showed restriction in the expression of Id 16/6 as it was never found on all immunoglobulin isotypes at the same time, and Id PR4 was never expressed. Ids 16/6 and BEG2 expression, however, may be associated as seven patients expressed these idiotypes simultaneously. CONCLUSIONS: These data indicate the use of public idiotypes in the immune response against B burgdorferi, which may be restricted in terms of idiotype class and isotype expression, and a possible association between IgA antibodies bearing Id 16/6 with arthritis.

Adult↗
PubMed1993

Treatment of Paget's disease of bone with single dose intravenous pamidronate.

OBJECTIVES: To assess the efficacy of a single intravenous infusion of pamidronate in Paget's disease of bone. METHODS: Fourteen patients with active Paget's disease (raised serum alkaline phosphatase, bone pain or neurological involvement) were treated with a single intravenous infusion of 105 mg pamidronate. Patients were assessed for biochemical and clinical improvement for up to two years following treatment. A further infusion was given following symptomatic relapse (pain at a known site of pagetic involvement). RESULTS: Serum alkaline phosphatase fell following treatment, with a nadir 5.9 months after treatment. Bone pain was improved in nine of 12 patients after six months. Retreatment of four patients resulted in a similar response. CONCLUSION: Single dose intravenous pamidronate (105 mg) is a convenient and effective treatment for Paget's disease.

Aged↗
PubMed1993

Fat necrosis. An unusual cause of polyarthritis.

Metastatic fat necrosis is a form of lobular panniculitis which together with synovitis is an unusual complication of pancreatic disease. It can precede an attack of pancreatitis. Pancreatic disease should therefore be remembered as a cause of panniculitis. Serum amylase and abdominal ultrasonography should be considered to exclude pancreatic disease in cases of panniculitis of uncertain etiology. We describe a case of metastatic fat necrosis and discuss the appearance on magnetic resonance imaging.

Arthritis↗
PubMed1992

Humanised monoclonal antibody therapy for rheumatoid arthritis.

Monoclonal antibodies that target T cells have shown some benefit in rheumatoid arthritis although responses have not been long lasting. This is partly due to insufficient therapy consequent upon antibody immunogenicity. Use of humanised antibodies, which are expected to be less foreign to man than conventional rodent antibodies, might overcome this problem. We therefore assessed in a phase 1 open study the potential of a "lymphocyte depleting" regimen of the humanised monoclonal antibody CAMPATH-1H in 8 patients with refractory rheumatoid arthritis. Apart from symptoms associated with first infusions of antibody, adverse effects were negligible. Significant clinical benefit was seen in 7 patients, lasting for eight months in 1. After one course of therapy, there was no measurable antiglobulin response, although 3 out of 4 patients have become sensitised on retreatment. Humanisation reduces the immunogenicity of rodent antibodies but anti-idiotype responses may still be seen on repeated therapy, even in patients sharing immunoglobulin allotype with the humanised antibody.

Adult↗
PubMed1991

Detection of human and murine common idiotypes of DNA antibodies in tissues and sera of patients with autoimmune diseases.

The expression in tissue and serum of a panel of murine and human common DNA antibody idiotypes (Ids) (BEG 2, PR 4, F-423, I-402, II-28, IV-228, V-88) has been investigated. The murine V-88 Id was detected in eight out of 10 and the human BEG 2 Id in five out of 10 labial biopsies from patients with Sjögren's syndrome. The murine F-423, I-402 and IV-228 Ids were identified in one out of 10 biopsies. In each case the pattern of staining was similar with staining of the acinar basement membrane and a cell population. Using double-labelling immunohistochemistry this cell population were identified as plasma cells. No staining was seen in four normal labial biopsies. The V-88 Id was detected on the epithelial aspect of the thickened basement membrane in three out of nine renal biopsies from patients with systemic lupus erythematosus (SLE). None of the other Ids (BEG 2, PR4, IV-228, F-423 or I-402) could be detected in renal tissue. None of the Ids were found in skin biopsies from SLE patients. Id V-88 may, like the 16/6 Id to which it is phenotypically related, play a role in the pathogenesis of renal lesions in SLE. The BEG 2 Id could be detected in the serum of patients with rheumatoid arthritis (RA) and active untreated tuberculosis. Ids II-28, V-88 and I-402 were elevated in serum from patients with Sjögren's syndrome and II-28 Id in serum from patients with myositis and RA. None of the Ids were elevated in serum from patients with SLE. Apart from the BEG 2 Id, none of the Ids were elevated in serum from patients with tuberculosis or Gram-negative infections. The presence of murine Ids in human tissue and serum suggests that they are cross-species idiotypes and have been conserved through evolution.

Animals↗
PubMed1991

Sequence analysis and idiotypic relationships of BEG-2, a human fetal antibody reactive with DNA.

Monoclonal antibody (mAb) BEG-2 is a dsDNA binding IgM lambda derived from a 12-week human fetus. Two binding site idiotypes (BEG-2 Id alpha and BEG-2 Id beta) have been defined with the use of polyclonal rabbit anti-idiotypic anti-serum. BEG-2 Id alpha is located on the lambda light chain and has been described previously. The BEG-2 Id beta is present on the mu heavy chain. By means of a direct binding ELISA, BEG-2 Id beta has been identified on EBV-derived mAbs from human fetal liver or spleen (5%), human cord blood (2.7%) and adult peripheral blood (1%). In addition, the Id is present on 8.5% of adult spleen-derived hybridoma antibodies and 6% of RA synovium-derived hybridoma antibodies. In all populations the presence of the Id is strongly associated with binding to DNA and other polyanions. Competition assays indicated that the Id was located at or near the antigen-binding site on these molecules. To explore the structural basis of this binding, a major part of the BEG-2 heavy chain was sequenced and found to be encoded by a member of the VH4 family joined to a variant of JH5 by a very short Diversity or N region. Of the BEG-2 Id beta positive mAbs for which the VH family has been determined, five are encoded by VH4 and two are encoded by VH6, but none is encoded by other families. Thus, the BEG-2 Id beta identifies a set of polyreactive antibodies that are common in fetal life, persist into adulthood and are encoded by VH6 and, a subset of VH4 genes.

Amino Acid Sequence↗