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R A Watts

Publications and source records attributed to R A Watts.

At least 19 recordsLinked to original sources
PubMed1997

Two hemoglobin genes in Arabidopsis thaliana: the evolutionary origins of leghemoglobins.

We cloned two hemoglobin genes from Arabidopsis thaliana. One gene, AHB1, is related in sequence to the family of nonsymbiotic hemoglobin genes previously identified in a number of plant species (class 1). The second hemoglobin gene, AHB2, represents a class of nonsymbiotic hemoglobin (class 2) related in sequence to the symbiotic hemoglobin genes of legumes and Casuarina. The properties of these two hemoglobins suggest that the two families of nonsymbiotic hemoglobins may differ in function from each other and from the symbiotic hemoglobins. AHB1 is induced, in both roots and rosette leaves, by low oxygen levels. Recombinant AHB1 has an oxygen affinity so high as to make it unlikely to function as an oxygen transporter. AHB2 is expressed at a low level in rosette leaves and is low temperature-inducible. AHB2 protein has a lower affinity for oxygen than AHB1 but is similar to AHB1 in having an unusually low, pH-sensitive oxygen off-rate.

Amino Acid Sequence↗
PubMed1997

Classification and epidemiology of the vasculitides.

The systemic vasculitides are rare inflammatory conditions of blood vessel walls. A number of different classification schemes have been published since the first in 1952. The important developments have been the recognition of dominant blood vessel size, the distinction between primary and secondary vasculitis and the incorporation of pathogenic markers such as anti-neutrophil cytoplasmic antibodies. In 1990 the American College of Rheumatology (ACR) published criteria for the diagnosis of polyarteritis nodosa, Churg-Strauss syndrome, Wegener's granulomatosis, hypersensitivity vasculitis, Schönlein-Henoch purpura, giant cell arteritis and Takayasu arteritis. Sensitivity and specificity rates varied considerably: 71.0-95.3% for sensitivity and 78.7-99.7% for specificity. The criteria were not tested against the general population or against patients with other connective tissue diseases or rheumatic conditions. Four years later the Chapel Hill Consensus Conference (CHCC) produced definitions for the major types of vasculitis, however, these have proved controversial. Comparison in unselected patients with systemic vasculitis (in particular polyarteritis nodosa and microscopic polyangiitis) has shown that the ACR criteria and CHCC definitions identify different patients. The systemic vasculitides are somewhat more common than previously believed. The overall annual incidence approaches 40/million adults. The most common form of primary systemic vasculitis is giant cell arteritis; Wegener's granulomatosis, microscopic polyangiitis and Churg-Strauss syndrome have similar incidences. Classical polyarteritis nodosa and Takayasu arteritis are very rare in the UK.

Humans↗
PubMed1996

Effect of classification on the incidence of polyarteritis nodosa and microscopic polyangiitis.

OBJECTIVE: Polyarteritis nodosa (PAN) has been used as a generic term for systemic vasculitis. The distinction between classic PAN and microscopic polyangiitis (MPA) has not always been made. The aims of this study were to compare the American College of Rheumatology (ACR) criteria for PAN with the Chapel Hill Consensus Conference (CHCC) definitions of classic PAN and MPA, and to estimate the annual incidence of PAN and MPA. METHODS: The 1990 ACR criteria and CHCC definitions for systemic vasculitis were applied to an unselected cohort of 130 patients with systemic vasculitis attending a single district hospital in the UK between February 1, 1988 and January 31, 1994. RESULTS: Eight patients who met the ACR criteria for PAN and who also met the CHCC definition of MPA but not classic PAN were identified. A further 5 patients met the CHCC definition of MPA but not the ACR criteria for any other type of systemic vasculitis. No patient who met the CHCC definition of classic PAN was identified. The annual incidence of MPA was calculated to be 3.6/million (95% confidence interval 1.7-6.9), and the annual incidence of PAN (ACR criteria) was 2.4/million (95% confidence interval 0.9-5.3). CONCLUSION: Classic PAN as defined by the CHCC is rare, because small vessel involvement is excluded from this definition.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1996

Correlation between expression of antibodies to histone H2B and clinical activity in HIV-infected individuals.

Levels of autoantibodies specific for the histone, H2B, were measured in individuals with HIV infection. In comparison with normal (uninfected) controls, infected patients, particularly those with symptomatic disease, had significantly elevated titres of anti-H2B antibodies. Longitudinal studies confirmed that levels of these antibodies were highest in patients with lymphadenopathy and declined with the development of AIDS. In preliminary experiments designed to determine the biological significance of the anti-histone antibodies, H2B was shown to be immunologically cross-reactive with an 18-kD antigen on the surface of HIV-infected or mitogen-activated CD4+ cells. Protein sequencing of the 18-kD antigen has since shown complete homology with histone H2B. Because the titres of H2B autoantibodies were found to parallel the numbers of circulating CD4 cells, it is possible that these antibodies are involved in the destruction of the helper/inducer T lymphocyte population.

Autoantibodies↗
PubMed1996

Wegener's granulomatosis--increased incidence or increased recognition?

We aimed to calculate the annual incidence of Wegener's granulomatosis (WG) in Norfolk (UK) and to compare the clinical spectrum of disease to that seen in tertiary centres in both the UK and USA. We also aimed to examine the seasonal onset of symptoms. This was a prospective study of all patients presenting with WG to a district hospital with a well-defined stable population (515,000) during the period 1988-1993. The annual incidence for WG in the adult population is 8.5/million (95% CI 5.2-12.9). These are the first incidence figures for a well-defined population and are higher than previously published. The clinical spectrum of disease in Norfolk was similar to that seen in tertiary centres and there is supportive evidence for a seasonal variation in the onset of symptoms (highest in winter).

Adult↗
PubMed1995

Epidemiology of systemic vasculitis: changing incidence or definition?

The epidemiology of the systemic vasculitides is poorly documented. Many studies have been conducted from tertiary referral centers, with resulting problems of referral bias and uncertainty of denominator population, or have involved small populations. We have estimated the incidence of the major forms of systemic vasculitis in a stable, ethnically homogeneous population of 414,000 adults from 1988 to 1994. The overall annual incidence of systemic vasculitis (excluding giant cell arteritis) is 39/million (95% confidence intervals; ranging from 31 to 47). The annual incidence of Wegener's granulomatosis is 8.5/million (range, 5.2 to 12.9), Churg-Strauss syndrome 2.4/million (0.9 to 5.3), microscopic polyangiitis 2.4/million (0.9 to 5.3), adult Henoch-Schonlein purpura 1.2/million (0.3 to 3.5), and systemic rheumatoid vasculitis 12.5/million (8.5 to 17.7). These data suggest that the overall incidence of systemic vasculitis is greater than previously thought (10/million) with Wegener's granulomatosis and systemic rheumatoid vasculitis being the most common. Whether this represents a genuine increase in incidence or increased physician awareness is uncertain.

Churg-Strauss Syndrome↗
PubMed1995

Vasculitis.

The systemic vasculitides are a group of rare inflammatory conditions resulting in inflammation and necrosis of blood vessel walls. They are somewhat commoner than previously believed with an annual incidence approaching 40 per million. Furthermore the annual incidence of rheumatoid vasculitis is 12.5 per million and Wegener's granulomatosis is 8.5 per million. The first useful classification system for systemic vasculitis was published in 1952, since then a number of different schemes have been published. The major changes have been the recognition of the importance of dominant blood vessel size, the distinction between primary and secondary vasculitis and the incorporation of pathogenetic markers such as ANCA (see Table 6). Until relatively recently there were no widely agreed diagnostic or classification criteria. In 1990 the ACR published criteria for the diagnosis of polyarteritis nodosa, Churg-Strauss syndrome, Wegener's granulomatosis, hypersensitivity vasculitis, Henoch-Schönlein purpura, giant cell arteritis and Takayasu's arteritis. The criteria were provided in both traditional and tree format. Sensitivity and specificity rates varied considerably: 71.0-95.3% for sensitivity and 78.7-99.7% for specificity. The criteria were not tested against the general population or against patients with other connective tissue diseases or rheumatic conditions. In 1993/94 the Chapel Hill Consensus Conference developed and published definitions for the nomenclature of systemic vasculitis based on clinical features. These have not met with universal acceptance. However, they are a useful addition, since their use should result in different centres studying more homogeneous populations of patients and facilitate comparison of data between different centres. Assessment of vasculitis comprises an activity score (BVAS), damage index and quality of life/health status (SF-36). These are recent developments which are still undergoing validation.

Humans↗
PubMed1995

Isolated nail fold vasculitis in rheumatoid arthritis.

OBJECTIVES: To establish the clinical significance of isolated nail fold vasculitis in patients with rheumatoid arthritis (RA). METHODS: Patients attending hospital with established RA were assessed by a single observer using unaided vision. Isolated nail fold vasculitis (NFV) was diagnosed as small nail edge or nail fold lesions without any evidence of other extra-articular or systemic vasculitis. Patients were followed prospectively. RESULTS: Thirty patients with isolated NFV were identified and followed for a median interval of 22 months. Three patients died within three months of diagnosis and six developed complications possibly indicative of extra-articular disease: xerostomia (three), pericarditis (one), pleural effusion and empyaema (one), pulmonary fibrosis (one). No patient developed systemic vasculitis. CONCLUSION: Isolated NFV has a favourable prognosis compared with systemic vasculitis. There is a low risk of developing systemic or extra-articular disease.

Adult↗
PubMed1995

Expression of a human fetal anti-DNA antibody idiotype BEG-2 beta in the families of patients with rheumatoid arthritis.

BEG-2 is a monoclonal antibody produced by the human-human hybridoma technique from a 12 weeks old human fetus. A polyclonal antiserum was raised in an (NZW x Half-lop hybrid) rabbit against BEG-2 and the anti-BEG-2 anti-idiotype was purified and characterised. Using this rabbit reagent the expression of the BEG-2 beta idiotype was analysed in 12 patients with active rheumatoid arthritis and their close family members (n = 54). Twenty five sera from healthy controls were analysed to establish a normal range. Ten of 12 patients (83%) with rheumatoid arthritis expressed the BEG-2 idiotype as well as 11 of 54 healthy unaffected relatives (20%).

Antibodies, Antinuclear↗
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↗