Global investigation of protein-protein interactions in yeast Saccharomyces cerevisiae using re-occurring short polypeptide sequences.

Protein-protein interaction (PPI) maps provide insight into cellular biology and have received considerable attention in the post-genomic era. While large-scale experimental approaches have generated large collections of experimentally determined PPIs, technical limitations preclude certain PPIs from detection. Recently, we demonstrated that yeast PPIs can be computationally predicted using re-occurring short polypeptide sequences between known interacting protein pairs. However, the computational requirements and low specificity made this method unsuitable for large-scale investigations. Here, we report an improved approach, which exhibits a specificity of approximately 99.95% and executes 16,000 times faster. Importantly, we report the first all-to-all sequence-based computational screen of PPIs in yeast, Saccharomyces cerevisiae in which we identify 29,589 high confidence interactions of approximately 2 x 10(7) possible pairs. Of these, 14,438 PPIs have not been previously reported and may represent novel interactions. In particular, these results reveal a richer set of membrane protein interactions, not readily amenable to experimental investigations. From the novel PPIs, a novel putative protein complex comprised largely of membrane proteins was revealed. In addition, two novel gene functions were predicted and experimentally confirmed to affect the efficiency of non-homologous end-joining, providing further support for the usefulness of the identified PPIs in biological investigations.

Temporomandibular joint function in patients with longstanding rheumatoid arthritis - I. Role of periodontal status and prosthetic care - a clinical study.

PURPOSE: Temporomandibular joint (TMJ) dysfunction in rheumatoid arthritis (RA) occurs in 2 % to 86 % of RA patients. Dental factors possibly contributing to the development of TMJ dysfunction in RA patients have rarely been investigated in controlled studies. The present clinical study aimed 1) to compare patients with active, longstanding RA and healthy control subjects matched for age, sex, periodontal risk factors, dental and prosthetic status in order to obtain data on the prevalence of TMJ dysfunction in dentate RA patients and 2) to investigate a possible relationship between RA activity, general functional state and the severity of TMJ involvement. METHODS: 50 RA patients (38 F, 12 M; 54 +/- 9 years) were compared with 101 control subjects (76 F, 25 M; 54 +/- 11 years) with regard to dental, periodontal and prosthetic status and clinical TMJ findings as measured by the Helkimo indices. Clinical evaluation of RA patients included serological parameters, pain as measured by visual analog scale (VAS), a 28-joint count, a radiological destruction score, a functional status and measurement of grip strength. RESULTS: The sum of carious, missing and filled teeth was similar in both groups. RA patients had more missing teeth (p < 0.01), more gingival bleeding, deeper pockets and more attachment loss (p < 0.0001). They showed no differences with regard to the mean number of occluding pairs of teeth, tooth support, the percentage of dentures, the grade of prosthetic support. 36 % of RA patients had a unilaterally shortened dental arch compared with 11.9 % in controls (p < 0.05). 32 % of RA patients and 27.7 % of the control subjects reported TMJ or facial pain. The mean VAS was 50 +/- 19 for RA patients and 52 +/- 21 for controls. The anamnestic data and the clinical symptoms grouped according to the Helkimo index showed no significant differences between both subject groups. However, the maximal mouth opening capacity in RA patients was significantly lower (40.6 +/- 6.5 mm) than in controls (45.8 +/- 5.5 mm; p < 0.001). Analysis of the Helkimo symptom groups revealed a significantly reduced mobility index in the RA group and impaired TM-joint function in controls (p < 0.05). Grip strength was significantly correlated with mouth opening capacity, TMJ pain with tooth support. CONCLUSION: The prevalence of TMJ dysfunction in dentate patients with longstanding RA does not exceed that of healthy controls when structural risk factors predisposing to the development of temporomandibular dysfunction are taken into consideration. Maintaining adequate tooth support might help to prevent progressive TMJ impairment in the course of disease.

Risk for periodontal disease in patients with longstanding rheumatoid arthritis.

OBJECTIVE: To quantify periodontal disease in rheumatoid arthritis (RA) patients and controls, and to correlate the degree of destruction from periodontal disease and from RA. METHODS: Fifty RA patients were matched for age, sex, smoking status, and oral hygiene with 101 controls. Correlations between indices of chronic destruction in periodontal disease (gingival attachment loss) and in RA (Larsen radiographic score) were determined. RESULTS: Patients with longstanding active RA (mean +/- SD 13 +/- 8 years) who were receiving treatment with disease-modifying antirheumatic drugs (n = 46), corticosteroids (n = 38), or nonsteroidal antiinflammatory drugs (n = 43) had a higher rate of gingival bleeding (increased by 50%), greater probing depth (increased by 26%), greater attachment loss (increased by 173%), and higher number of missing teeth (increased by 29%) compared with controls. No correlation was found between the Larsen radiographic score and gingival attachment. CONCLUSION: Patients with longstanding active RA have a substantially increased frequency of periodontal disease, including loss of teeth, compared with controls. Antiinflammatory treatment interferes with periodontal disease and might have masked a possible correlation between the indices of chronic destruction in RA and periodontal disease.