Biomedical subjects
Publications and source records attributed to K Bryson.
Using private hospitals over 11 weeks this winter enabled a health authority to remove more than 1,000 patients from waiting lists. Prices were comparable to, and sometimes cheaper than, the NHS. The average cost was 1,120 Pounds per treatment. Patient satisfaction seemed high. Consultant productivity was higher in the private sector.
MOTIVATION: What constitutes a baseline level of success for protein fold recognition methods? As fold recognition benchmarks are often presented without any thought to the results that might be expected from a purely random set of predictions, an analysis of fold recognition baselines is long overdue. Given varying amounts of basic information about a protein-ranging from the length of the sequence to a knowledge of its secondary structure-to what extent can the fold be determined by intelligent guesswork? Can simple methods that make use of secondary structure information assign folds more accurately than purely random methods and could these methods be used to construct viable hierarchical classifications? EXPERIMENTS PERFORMED: A number of rapid automatic methods which score similarities between protein domains were devised and tested. These methods ranged from those that incorporated no secondary structure information, such as measuring absolute differences in sequence lengths, to more complex alignments of secondary structure elements. Each method was assessed for accuracy by comparison with the Class Architecture Topology Homology (CATH) classification. Methods were rated against both a random baseline fold assignment method as a lower control and FSSP as an upper control. Similarity trees were constructed in order to evaluate the accuracy of optimum methods at producing a classification of structure. RESULTS: Using a rigorous comparison of methods with CATH, the random fold assignment method set a lower baseline of 11% true positives allowing for 3% false positives and FSSP set an upper benchmark of 47% true positives at 3% false positives. The optimum secondary structure alignment method used here achieved 27% true positives at 3% false positives. Using a less rigorous Critical Assessment of Structure Prediction (CASP)-like sensitivity measurement the random assignment achieved 6%, FSSP-59% and the optimum secondary structure alignment method-32%. Similarity trees produced by the optimum method illustrate that these methods cannot be used alone to produce a viable protein structural classification system. CONCLUSIONS: Simple methods that use perfect secondary structure information to assign folds cannot produce an accurate protein taxonomy, however they do provide useful baselines for fold recognition. In terms of a typical CASP assessment our results suggest that approximately 6% of targets with folds in the databases could be assigned correctly by randomly guessing, and as many as 32% could be recognised by trivial secondary structure comparison methods, given knowledge of their correct secondary structures.
Molecular dynamics simulations with simulated annealing are performed on polyamine-DNA systems in order to determine the binding sites of putrescine, cadaverine, spermidine and spermine on A- and B-DNA. The simulations either contain no additional counterions or sufficient Na+ ions, together with the charge on the polyamine, to provide 73% neutralisation of the charges on the DNA phosphates. The stabilisation energies of the complexes indicate that all four polyamines should stabilise A-DNA in preference to B-DNA, which is in agreement with experiment in the case of spermine and spermidine, but not in the case of putrescine or cadaverine. The major groove is the preferred binding site on A-DNA of all the polyamines. Putrescine and cadaverine tend to bind to the sugar-phosphate backbone of B-DNA, whereas spermidine and spermine occupy more varied sites, including binding along the backbone and bridging both the major and minor grooves.
SUMMARY: The PSIPRED protein structure prediction server allows users to submit a protein sequence, perform a prediction of their choice and receive the results of the prediction both textually via e-mail and graphically via the web. The user may select one of three prediction methods to apply to their sequence: PSIPRED, a highly accurate secondary structure prediction method; MEMSAT 2, a new version of a widely used transmembrane topology prediction method; or GenTHREADER, a sequence profile based fold recognition method. AVAILABILITY: Freely available to non-commercial users at http://globin.bio.warwick.ac.uk/psipred/
Analysis of our fold recognition results in the 3rd Critical Assessment in Structure Prediction (CASP3) experiment, using the programs THREADER 2 and GenTHREADER, shows an encouraging level of overall success. Of the 23 submitted predictions, 20 targets showed no clear sequence similarity to proteins of known 3D structure. These 20 targets can be divided into 22 domains, of which, 20 domains either entirely match a previously known fold, or partially match a substantial region of a known fold. Of these 20 domains, we correctly assigned the folds in 10 cases.
The results of the first Critical Assessment of Fully Automated Structure Prediction (CAFASP-1) are presented. The objective was to evaluate the success rates of fully automatic web servers for fold recognition which are available to the community. This study was based on the targets used in the third meeting on the Critical Assessment of Techniques for Protein Structure Prediction (CASP-3). However, unlike CASP-3, the study was not a blind trial, as it was held after the structures of the targets were known. The aim was to assess the performance of methods without the user intervention that several groups used in their CASP-3 submissions. Although it is clear that "human plus machine" predictions are superior to automated ones, this CAFASP-1 experiment is extremely valuable for users of our methods; it provides an indication of the performance of the methods alone, and not of the "human plus machine" performance assessed in CASP. This information may aid users in choosing which programs they wish to use and in evaluating the reliability of the programs when applied to their specific prediction targets. In addition, evaluation of fully automated methods is particularly important to assess their applicability at genomic scales. For each target, groups submitted the top-ranking folds generated from their servers. In CAFASP-1 we concentrated on fold-recognition web servers only and evaluated only recognition of the correct fold, and not, as in CASP-3, alignment accuracy. Although some performance differences appeared within each of the four target categories used here, overall, no single server has proved markedly superior to the others. The results showed that current fully automated fold recognition servers can often identify remote similarities when pairwise sequence search methods fail. Nevertheless, in only a few cases outside the family-level targets has the score of the top-ranking fold been significant enough to allow for a confident fully automated prediction. Because the goals, rules, and procedures of CAFASP-1 were different from those used at CASP-3, the results reported here are not comparable with those reported in CASP-3. Nevertheless, it is clear that current automated fold recognition methods can not yet compete with "human-expert plus machine" predictions. Finally, CAFASP-1 has been useful in identifying the requirements for a future blind trial of automated served-based protein structure prediction.
Eight cases of ovarian granuloma containing carbon pigment are described. In all cases, this distinctive lesion occurred at sites of prior laser or fulguration surgery. Three types of carbon pigment granuloma were noted, the most common being the necrobiotic granuloma. Although postoperative necrobiotic granulomas have been described in a variety of clinical sites, the carbon pigment granuloma has not been well described in the pathology literature. Recognition of this lesion seems to be of value in determining its postoperative, noninfectious nature.
7 alpha-Iodo-17 beta-hydroxy-5 alpha-androstan-3-one (7 alpha-iodo-5 alpha-dihydrotestosterone, 7 alpha-IDHT) has been synthesized as a potential radioligand for the detection and measurement of androgen receptor and for imaging of androgen-receptor-containing tissues when labeled with the gamma-emitting radionuclides 125I and 123I, respectively. In vitro binding studies show that 7 alpha-IDHT binds with high affinity to the rat and human androgen receptor (RBA = 74) compared to R1881 (RBA = 100). Further, this compound showed high specificity for the androgen receptor. 7 alpha-IDHT showed only a marginal affinity for the progestin receptor and even less affinity for the estrogen receptor. No binding was detected to the glucocorticoid receptor. These characteristics make 7 alpha-IDHT a potentially ideal agent for imaging and evaluation of androgen-receptor-containing tissues.
Since early 1987, 62 laparoscopic appendectomies have been performed without any major operative or postoperative complications. Just over half of these patients required hospitalization overnight for observation. The rest went home with activity and dietary restriction for 48 to 72 hours. Indications for the appendectomies included abdominal or pelvic pain or both, with the appendix demonstrating endometriosis, adhesions causing entrapment, or histories compatible with chronic appendicitis. Opportunities for second-look laparoscopies after laparoscopic appendectomy have been accomplished with two patients showing an encouraging lack of adhesion formation in both.
Hereditary ovalocytosis in Papua New Guinea is restricted to areas of endemic malaria and may confer increased resistance to the disease. The incidence of malaria was investigated in 1616 Melanesiams of known red cell morphology and severity of infection determined in a smaller subsample. Ovalocytics tended to be more resistant to severe malarial infections than normocytics. The ratio of parasitaemia in 112 ovalocytics compared with 741 normocytic children was 1.05 for P. falciparum; 0.90 for P. vivax; 0.54 for P. malariae, and 0.91 for infection with any species. The difficulties in conclusively demonstrating any selective advantage of the condition are discussed.