Search PubMed⌕ Search

Biomedical subjects

Richard A Watts

Publications and source records attributed to Richard A Watts.

11 recordsLinked to original sources
PubMed2005

Lineage-specific differences in evolutionary mode in a salamander courtship pheromone.

Functionally equivalent genes may evolve heterogeneously across closely related taxa as a consequence of lineage-specific selective pressures. Such disparate evolutionary modes are especially prevalent in genes that encode postcopulatory reproductive proteins, presumably as a result of sexual selection. We might therefore expect genes that mediate reproduction prior to insemination to evolve in a similar manner. Plethodontid receptivity factor (PRF), a proteinaceous salamander pheromone produced by the male, increases female receptivity during courtship interactions. To test for lineage-specific differences in PRF's evolution, we intensively sampled PRF genes across the eastern Plethodon phylogeny (27 spp.; 34 populations) to compare gene diversification, rates of evolution, modes of selection, and types of amino acid substitution. Our analyses indicate that PRF evolutionary dynamics vary considerably from lineage to lineage. Underlying this heterogeneity, however, are two well-defined transitions in evolutionary mode. The first mode is representative of a typical protein profile, wherein neutral divergence and purifying selection are the dominant features. The second mode is characterized by incessant, cyclical evolution driven by positive selection. In this mode, the positively selected sites are bound by a limited assortment of acceptable amino acids that appear to evolve independently of other sites, resulting in a tremendous number of unique PRF alleles. Several of these selected sites are implicated in receptor binding. These sites are apparently involved in a molecular tango in which the male signal and female receptors coevolve within a confined molecular space. PRF's lineage-specific evolutionary dynamics, in combination with evidence of a molecular tango, highlight the molecular action of sexual selection on a chemical signal that is used during courtship.

Amino Acid Sequence↗
PubMed2005

What is known about the epidemiology of the vasculitides?

The vasculitides are conditions of unknown aetiology. Until recently, relatively little was known about their incidence and prevalence, but there are now increasing data, especially from Europe. These are conditions of the extremes of age. Kawasaki disease occurs predominately in Asian children, with a peak annual incidence of 90/100,000 children aged under 5 years. Henoch-Schonlein purpura has an incidence of 70/100,000 in those aged 4-7 years and is also more common in Asians. Primary systemic vasculitis has a peak incidence 6/100,000 in those aged 65-74 years. Giant cell arteritis is most common in Caucasians aged over 70 years, with an incidence of 53/100,000. Vasculitis has been associated with malignancy, the association being strongest between haematological malignancies and cutaneous vasculitis. There is occasionally a temporal association; failure to respond appropriately to therapy should prompt a search for malignancy. Lesions suspicious of malignancy should be biopsied even if the diagnosis of vasculitis has been histologically proven.

Age Factors↗
PubMed2004

Stabilizing selection on behavior and morphology masks positive selection on the signal in a salamander pheromone signaling complex.

Natural selection maintains the integration and coordination of sets of phenotypic characters that collectively perform a task. In functional complexes in which characters span molecular to behavioral levels of organization, we might then expect similar modes of selection to produce similar patterns in evolutionary divergence at each level. To test this expectation, we diagnosed selection at behavioral, morphological, and molecular levels for courtship pheromone signaling by plethodontid salamanders. At the levels of morphology and behavior tens of millions of years of stasis (stabilizing selection) occur on each side of a transition from vaccination to olfactory delivery modes. As a proxy for the molecular level, we used plethodontid receptivity factor (PRF), a protein that is an active component of the pheromone. We cloned PRF from 12 Plethodon spp. spanning the delivery transition and obtained multiple alleles from each individual surveyed. Analyses of 61 alleles for PRF identified elevated nonsynonymous over synonymous substitution rates along lineages in a molecular phylogeny, and at 8% of sites in the protein, indicating that positive (directional) selection has acted on this vertebrate pheromone gene. Structural models showed PRF is in a family of cytokines characterized by a four-alpha-helix bundle. Positive selection in PRF was associated with receptor binding sites that are under purifying selection in other cytokines of that family. The evolutionary dynamics of the plethodontid pheromone delivery complex consists of stabilizing selection on morphological and behavioral aspects of signal delivery but positive selection on the signal mediated by receptors. Thus, different selection modes prevail at different levels in this reproductive functional complex. Evolutionary studies of integrated sets of characters therefore require separate analyses of selective action at each level.

Amino Acid Sequence↗
PubMed2004

Epidemiology of the vasculitides.

The epidemiology of systemic vasculitis is becoming increasingly well understood. Giant cell arteritis is the commonest type of vasculitis with an incidence that is highest in populations of Scandinavian descent, where the annual incidence reaches 15 to 35/100,000 aged > 50 years. Takayasu's arteritis has a relatively uniform global incidence of one to two/million. The ANCA-associated vasculitides have an overall incidence of 20/million with a peak age of onset at 65 to 74 years. Wegener's granulomatosis appears to be more common in northern Europe compared with microscopic polyangiitis, which seems to be more common in southern Europe. Henoch-Schönlein purpura is the commonest form of childhood vasculitis in the West with an incidence of 20/100,000 aged < 17 years, but it is much rarer in adults (13/million). Kawasaki disease is commonest in the childhood population of southeast Asia; in Japan the incidence is 500/million aged < 5 years, 50% of cases occur in those aged < 2 years. Behçet's disease occurs along the Silk Road and in the Mediterranean littoral with a prevalence in Turkey of 380/100,000. The various types of vasculitis have very different geographical and ethnic distributions, which provide clues to the pathogenesis.

Journal Article↗
PubMed2003

Investigation of quality of life, mood, pain, disability, and disease status in primary systemic vasculitis.

OBJECTIVE: To assess quality of life (QOL) and psychological adjustment in primary systemic vasculitis (PSV), and to assess their relationship to disease-related measures. METHODS: Fifty-one PSV patients completed questionnaires assessing QOL (Short Form 36 [SF-36]), disability (Health Assessment Questionnaire [HAQ]), and mood (Hospital Anxiety and Depression Scale [HADS]). Illness-related measures, disease activity, and permanent damage scores (the Birmingham Vasculitis Damage Index [BVDI] modified, and the Birmingham Vasculitis Activity Scale modified) were collected. Aspects of the HAQ's psychometric properties were evaluated. RESULTS: PSV patients' SF-36 scores, except for mental health, were significantly lower than the norms, indicating poorer QOL. Using the HADS, 43.2% of patients reported increased anxiety symptoms and 25.5% increased depressive symptoms. Patients with increased pain when compared with those with little or no pain had significantly impaired scores in all SF-36 subscales, except for mental health; and they scored significantly worse on depression, fatigue, problems with sleep, and symptom severity. Patients with neuropathic symptoms and those taking high levels of steroids had significantly impaired scores on some of the relevant measures. There were no significant correlations between the modified BVDI scores with the SF-36 subscales or with the other self-report disease-related measures. The HAQ showed high internal consistency and high concurrent and discriminant validity. CONCLUSION: Many aspects of QOL are significantly impaired in PSV. Self-reported pain and disease symptoms, SF-36 scores, and depression and anxiety levels are significant indicators of the adverse impact of vasculitis on patients' lives that need to be assessed and managed.

Adaptation, Psychological↗
PubMed2003

Are environmental factors important in primary systemic vasculitis? A case-control study.

OBJECTIVE: To investigate the association between primary systemic vasculitis (PSV) and environmental risk factors. METHODS: Seventy-five PSV cases and 273 controls (220 nonvasculitis, 19 secondary vasculitis, and 34 asthma controls) were interviewed using a structured questionnaire. Factors investigated were social class, occupational and residential history, smoking, pets, allergies, vaccinations, medications, hepatitis, tuberculosis, and farm exposure in the year before symptom onset (index year). The Standard Occupational Classification 2000 and job-exposure matrices were used to assess occupational silica, solvent, and metal exposure. Stepwise multiple logistic regression was used to calculate the odds ratio (OR) and 95% confidence interval (95% CI) adjusted for potential confounders. Total PSV, subgroups (47 Wegener's granulomatosis [WG], 12 microscopic polyangiitis, 16 Churg-Strauss syndrome [CSS]), and antineutrophil cytoplasmic antibody (ANCA)-positive cases were compared with control groups. RESULTS: Farming in the index year was significantly associated with PSV (OR 2.3 [95% CI 1.2-4.6]), with WG (2.7 [1.2-5.8]), with MPA (6.3 [1.9-21.6]), and with perinuclear ANCA (pANCA) (4.3 [1.5-12.7]). Farming during working lifetime was associated with PSV (2.2 [1.2-3.8]) and with WG (2.7 [1.3-5.7]). Significant associations were found for high occupational silica exposure in the index year (with PSV 3.0 [1.0-8.4], with CSS 5.6 [1.3-23.5], and with ANCA 4.9 [1.3-18.6]), high occupational solvent exposure in the index year (with PSV 3.4 [0.9-12.5], with WG 4.8 [1.2-19.8], and with classic ANCA [cANCA] 3.9 [1.6-9.5]), high occupational solvent exposure during working lifetime (with PSV 2.7 [1.1-6.6], with WG 3.4 [1.3-8.9], and with cANCA 3.3 [1.0-10.8]), drug allergy (with PSV 3.6 [1.8-7.0], with WG 4.0 [1.8-8.7], and with cANCA 4.7 [1.9-11.7]), and allergy overall (with PSV 2.2 [1.2-3.9], with WG 2.7 [1.4-5.7]). No other significant associations were found. CONCLUSION: A significant association between farming and PSV has been identified for the first time. Results also support previously reported associations with silica, solvents, and allergy.

Adolescent↗
PubMed2003

Epidemiology of the vasculitides.

The past year has seen some notable publications in the field of vasculitis epidemiology. The appearance of reports from several different parts of the world has permitted comparisons to be made. In Europe, Wegener granulomatosis appears to be more common at high latitudes, whereas microscopic polyangiitis shows the reverse pattern. Kawasaki disease is most common in Japan. In China, the United States, and the United Kingdom, the incidence is lower, but the incidence appears to be increasing globally. Studies of infectious triggers continue to be disappointingly negative. Immunogenetic associations with cytokine polymorphisms are beginning to be reported.

Epidemiologic Studies↗
PubMed2002

New mutations of CIAS1 that are responsible for Muckle-Wells syndrome and familial cold urticaria: a novel mutation underlies both syndromes.

Mutations of CIAS1 have recently been shown to underlie familial cold urticaria (FCU) and Muckle-Wells syndrome (MWS), in three families and one family, respectively. These rare autosomal dominant diseases are both characterized by recurrent inflammatory crises that start in childhood and that are generally associated with fever, arthralgia, and urticaria. The presence of sensorineural deafness that occurs later in life is characteristic of MWS. Amyloidosis of the amyloidosis-associated type is the main complication of MWS and is sometimes associated with FCU. In FCU, cold exposure is the triggering factor of the inflammatory crisis. We identified CIAS1 mutations, all located in exon 3, in nine unrelated families with MWS and in three unrelated families with FCU, originating from France, England, and Algeria. Five mutations--namely, R260W, D303N, T348M, A439T, and G569R--were novel. The R260W mutation was identified in two families with MWS and in two families with FCU, of different ethnic origins, thereby demonstrating that a single CIAS1 mutation may cause both syndromes. This result indicates that modifier genes are involved in determining either a MWS or a FCU phenotype. The finding of the G569R mutation in an asymptomatic individual further emphasizes the importance of such modifier a gene (or genes) in determining the disease phenotype. Identification of this gene (or these genes) is likely to have significant therapeutic implications for these severe diseases.

Adolescent↗