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Biomedical subjects

B Robson

Publications and source records attributed to B Robson.

At least 37 records · Page 2Linked to original sources
PubMed1993

Trial of an asthma action plan in the Maori community of the Wairarapa.

AIMS: An asthma action plan has been tested in a study conducted by Wairarapa Maori community health workers and the Wellington asthma research group. There were several distinctive features of the project, including the programme of marae-based asthma clinics, and the partnership between the researchers and the Maori community groups. This paper describes the process by which the study was conducted since this experience may be relevant to future Maori health research projects. METHODS: The programme was launched with a series of hui at marae in the Wairarapa, and marae-based clinics were set up. These were followed up by further support from the Maori community health workers who helped people to keep diaries to monitor their asthma, and generally maintained contact. The severity of asthma in the participants was compared for a two-month period before the action plan was introduced, and for a four-month period after the plan was introduced. RESULTS: There was a high participation rate, with 91% (63/69) of participants finishing the programme, 75% of whom adequately completed their daily asthma diaries. Asthma control improved significantly in the participants. They commented positively on the programme, and particularly on the marae-based clinics. CONCLUSIONS: The study was successful in terms of participation in the marae-based clinics, acceptance and use of the plan, and improvement in asthma control of the participants. The findings indicate what can be achieved when researchers and Maori community groups work in partnership.

Asthma↗
PubMed1993

Prevalence of asthma symptoms among adolescents in the Wellington region, by area and ethnicity.

AIMS: To compare the self-reported prevalence of asthma symptoms, among 12 to 15 year olds in three districts in the greater Wellington region, and to compare prevalence among three ethnic groups--Maori, Pacific Island and others. METHODS: Third form students from 13 secondary schools in the Wellington region, were surveyed using a video questionnaire and a standardised written questionnaire, during July 1991. RESULTS: Using the video questionnaire, the prevalence of wheeze during the previous 12 months was similar in Wellington city (32%), Lower Hutt (38%), and Porirua (37%); the corresponding findings using the written questionnaire were 28%, 27% and 30% respectively. The reported prevalence was also similar among Maori (38% using the video and 29% using the written questionnaire) and other children (36% and 30% respectively), but lower among Pacific Island children (31% and 20% respectively). The prevalence and frequency of severe attack of wheezing was similar in all three districts and all three ethnic groups. CONCLUSIONS: These findings contradict previous speculations of possible differences in asthma prevalence or severity within the greater Wellington region. They are consistent with other evidence that there are at most minor differences in asthma prevalence between Maori and nonMaori children in New Zealand; however, asthma prevalence may be lower among Pacific Island children. Thus ethnic differences in asthma morbidity and mortality are not likely to be due to differences in prevalence, but more likely relate to differences in access to and delivery of asthma care.

Adolescent↗
PubMed1992

Natural sequence code representations for compression and rapid searching of human-genome style databases.

Numeric descriptions ('bio-informatic descriptions') of amino acid residues have been developed which will be of value whenever the quality and quantity of information in very large (i.e. 'human genome style') gene and protein sequences is to be compared or manipulated. These codes are as natural as possible by our criteria (the same principles could be used in revision of the criteria). In particular, in storing and searching large amounts of sequence data, natural codes--which relate to the properties of amino acids--can be combined with existing fast-search algorithms but introduce several advantages. The code can be assigned such that sub-selection of bits leads to compressed databases with residues defined less specifically, by classes of properties. The most compressed representation leads to the specification of a residue as polar or non-polar, while the most extended representation used at present also allows specification of, for example, glyco-asparagine and phosphoserine. Preliminary studies on both a supercomputer and smaller machines suggest a 'worst-case' speeding of approximately 4.5-fold. For more intelligent searching, coding extensions mixed with the basic sequence data give the sequence data some of the character of a computer program.

Amino Acid Sequence↗
PubMed1992

Markers of risk of asthma death or readmission in the 12 months following a hospital admission for asthma.

A case-control study has previously been reported of asthma deaths in people aged 5-45 years who had a hospital admission for asthma (the index admission) in New Zealand during 1981-1987. The study has been re-analysed to examine the association between markers of asthma severity and risk of asthma death or hospital admission; patients prescribed fenoterol were excluded from this re-analysis because of the previously reported interaction between fenoterol, asthma severity, and asthma deaths. The re-analysis included 39 patients who died of asthma during the 12 months after their index admission, 226 patients who had a readmission for asthma during the 12 months after their index admission, and 263 controls chosen from all index admissions. An admission in the previous 12 months was the strongest marker of subsequent risk of death (odds ratio (OR) = 3.5, 95% confidence interval (CI): 1.8-6.9, P less than 0.01), and was also a strong marker of subsequent risk of readmission (OR = 3.0, 95% CI: 2.1-4.2, P less than 0.01); the risk increased with the number of previous admissions. Three or more categories of prescribed asthma drugs was also associated with subsequent death (OR = 1.7, 95% CI: 0.9-3.3, P = 0.13) or readmission (OR = 1.9, 95% CI: 1.3-2.7, P less than 0.01); prescribed oral corticosteroids was only weakly associated with subsequent death (OR = 1.3, 95% CI: 0.6-2.8, P = 0.59), but was more strongly associated with subsequent readmission (OR = 1.9, 95% CI: 1.2-2.8, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

The prognosis of adenosquamous carcinomas of the uterine cervix.

OBJECTIVES: Firstly, to identify a cohort of women with invasive adenosquamous carcinomas of the uterine cervix, including mucin-producing squamous cell carcinomas. Secondly, to compare the biological characteristics and behaviour of a cohort of adenosquamous carcinomas with a cohort of non-mucin-producing squamous cell carcinomas. DESIGN: Histological review, retrospective survival analysis. SETTING: Regional multidisciplinary gynaecological oncology service. SUBJECTS: 161 cases of stage 1B and above invasive cervical carcinoma presenting between 1 January 1980 and 31 July 1987. Thirty nine women with adenosquamous carcinomas were compared with 103 women with non-mucin-producing squamous cell tumours. RESULTS: Inclusion of routine stains for mucin in the assessment of histological material resulted in the reclassification of 38 (24%) of the cases, including the identification of 31 mucin-producing squamous cell carcinomas. The survival with adenosquamous tumours was significantly worse than with squamous cell cancers (P = 0.006), 5-year survival rates being 52% and 75% respectively. Multivariate analysis showed that this effect was explained by differences in clinical stage, pelvic lymph node metastasis and vascular invasion by tumour. CONCLUSIONS: The application of routine mucin stains to cervical tumours identifies a group of previously unrecognized adenosquamous cancers. Tumours so identified are likely to pursue a more aggressive clinical course associated with a poorer survival when compared to non-mucin-producing squamous carcinomas.

Adenocarcinoma↗
PubMed1991

Influence of the local amino acid sequence upon the zones of the torsional angles phi and psi adopted by residues in proteins.

A set of parameters is derived to express the influence of the local amino acid sequence on the torsional angles phi and psi adopted by each residue in a protein. The formalism used, which is based on information theory, evaluates the probability for a given residue to be in a particular zone of the Ramachandran map. Comparisons with crystallographic structures suggest that the method can extract almost all of the available information from the local sequence and show that the local sequence carries only, on average, about 65% of the information necessary for specifying the conformation of a given residue in a protein. The rest is specified by long-range interactions that are specific for each protein fold. The parameters derived here provide a more detailed description of the prediction than other methods in allowing the allocation of the torsional angles for residues having an aperiodic structure and are intended to be used for directing the conformational search in a subsequent simulation of the three-dimensional structure. This method should also predict segments of the polypeptide chain that are the most stable and thus less sensitive to long-range interactions.

Amino Acid Sequence↗
PubMed1991

Development and testing of protocols for computer-aided design of peptide drugs, using oxytocin.

Considerable clinical interest in neuropeptides and peptide hormones has stimulated recent research and development of peptide-based drugs. This process differs from most classical drug discovery procedures because peptide molecules have considerable inherent flexibility. In the present paper, to identify lowest energy and metastable conformers for drug design, and to develop protocols for such studies, conformational search algorithms, incorporating empirical energy calculations, have been applied in the analysis of the peptide oxytocin. Energy minimization in torsion angle space was carried out from a variety of starting conformations, including published structures, in all-atom mode and all with distance constraints for disulphide bond formation. The energy-minimized conformations have been further optimized by a mapping method. Complementary simulations have been performed in united-atom mode and a model representing the effects of water using dummy sites has been developed and tested for this representation. Several of the preferred conformers together with de novo conformations have been used as starting points in molecular dynamics simulations; 28 low potential energy conformations were located at a temperature of 4 K. Conformations are analysed to identify hydrogen bonds, phi-psi angle distributions and the RMS values relative to the X-ray structure of deamino-oxytocin. The modelled structure of lowest energy in the molecular mechanics calculations was also that of least RMS deviation from the crystal structure; whilst structures of lower energy but larger deviation were identified by molecular dynamics techniques. A metastable structure has been identified which satisfies existing criteria for the "active form", and this model is tested by a theoretical residue-substitution technique, to provide clues on the agonist/antagonist relationship at the atomic level.

Computers↗
PubMed1990

Comparison of the X-ray structure of baboon alpha-lactalbumin and the tertiary predicted computer models of human alpha-lactalbumin.

The previously predicted structures of human alpha-lactalbumin by homology with hen egg white lysozyme by an automatic method, after the alignment stage, are compared to the X-ray determined structure of baboon alpha-lactalbumin. The root mean square by rotation method (RMSR) deviations for 122 C-alpha atoms between the two models and the X-ray structure are 2.0 A and 2.3 A. The RMSR deviations for all atoms, except for differences in human and baboon sequences, are 2.8 A and 3.1 A. If the flexible C-terminus (residues 112-122) are removed then these RMSR deviations are reduced to 2.4 A and 2.3 A respectively. These results are consistent with the fact that the RMSR deviation between the human and baboon X-ray structures increases from residue 112 onwards and is conformationally flexible.

Amino Acid Sequence↗
PubMed1990

The expert system approach to predicting protein structure.

Prediction of protein structure is an open-ended problem. Since an approach from first principles cannot be taken in reasonable computer time, short-cuts using further data are necessary. Such data include information about the specific protein in question, and information in databases which are about proteins in general. Is it possible to write a general, flexible 'superalgorithm' which would suit most circumstances? If so, it would seem likely to overcome one of the most understated but nonetheless greatest difficulties associated with molecular modelling and computer-aided drug design--reproducibility. To this end, a 'polymorphic programming environment' has been developed which represents both an expert system and a high-level language for theoretical chemists and molecular biologists. This language is GLOBAL (Ball et al., 1990). In a series of earlier studies, and more recently by means of GLOBAL itself, the nature of reproducibility and its rather surprising limits have been explored, and in general the current status and future potential of protein modelling have been examined.

Expert Systems↗
PubMed1988

Secondary structure prediction: combination of three different methods.

A combination of three complementary secondary structure prediction methods is presented. The methods used are the GOR III method, the Homologue method and a new method, the bit pattern method, which is based on hydrophilic/hydrophobic residue patterns. For this purpose a hydropathy scale was developed and is presented here. The combination algorithm (Combine method) was designed to take the best results of each method and use their differences in order to improve the prediction. The combination yields 65.5% correctly predicted residues in three states: alpha-helix (H), beta-strand (E) and aperiodic structure (C) which is an improvement ranging from 2.5 to 6.5% compared with the individual methods when tested with a 67-polypeptide chain database. Seventy-five per cent of the regular secondary structure (H and E) runs are correctly located and beta-sheet runs are much better located by the Combine method in comparison to the other methods.

Predictive Value of Tests↗
PubMed1987

Further developments of protein secondary structure prediction using information theory. New parameters and consideration of residue pairs.

We have re-evaluated the information used in the Garnier-Osguthorpe-Robson (GOR) method of secondary structure prediction with the currently available database. The framework of information theory provides a means to formulate the influence of local sequence upon the conformation of a given residue, in a rigorous manner. However, the existing database does not allow the evaluation of parameters required for an exact treatment of the problem. The validity of the approximations drawn from the theory is examined. It is shown that the first-level approximation, involving single-residue parameters, is only marginally improved by an increase in the database. The second-level approximation, involving pairs of residues, provides a better model. However, in this case the database is not big enough and this method might lead to parameters with deficiencies. Attention is therefore given to overcoming this lack of data. We have determined the significant pairs and the number of dummy observations necessary to obtain the best result for the prediction. This new version of the GOR method increases the accuracy of prediction by 7%, bringing the amount of residues correctly predicted to 63% for three states and 68 proteins, each protein to be predicted being removed from the database and the parameters derived from the other proteins. If the protein to be predicted is kept in the database the accuracy goes up to 69.7%.

Amino Acid Sequence↗
PubMed1987

Studies on rationales for an expert system approach to the interpretation of protein sequence data. Preliminary analysis of the human epidermal growth factor receptor.

The molecular modelling of larger proteins benefits from a preliminary analysis of the sequence to identify regions of potential structural and functional importance. In this study the sequence of the epidermal growth factor receptor has been analysed using a variety of established methods and novel procedures developed for the study of weak internal and external homologies and for the use of homologous sequences in the prediction of secondary and super-secondary structures. The procedures explored here are potentially suitable for incorporation into an expert system for the initial investigation of protein sequence data.

Amino Acid Sequence↗
PubMed1987

Computer-aided design and physiological testing of a luteinising hormone-releasing hormone analogue for 'adjuvant-free' immunocastration.

An analogue of LHRH containing an extension of Gly-Cys at the carboxyl-terminus has been designed to permit reproducible coupling to a suitably modified carrier via a thioether bond. Potential energy calculations indicated that this analogue adopted a conformation in solution virtually identical to the type II' turn around Gly-6-Leu-7 predicted for native LHRH. Intradermal administration of a conjugate of this analogue with purified protein derivative of tuberculin to male rats previously primed with BCG vaccine rapidly led to complete testicular regression. This adjuvant-free immunisation protocol may represent an alternative to castration for the veterinary control of reproductive function.

Animals↗
PubMed1987

Modelling of alpha-lactalbumin from the known structure of hen egg white lysozyme using molecular dynamics.

The prediction of protein conformation by homology is being widely pursued using interactive computer graphics. However, there have been a limited number of energy minimization and/or molecular dynamics studies for such predictions. This paper reports one such study on alpha-lactalbumin, a system that can be tested as the X-ray crystal structure has recently been determined. The differences in structure of the Ca2+ binding loop reported for the holo-protein (Stuart et al., Nature, 324 [1986] 84-87) and that predicted for the apoprotein could be attributed to the presence or absence of the Ca2+ ion.

Animals↗