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Biomedical subjects

W R Taylor

Publications and source records attributed to W R Taylor.

At least 145 records · Page 8Linked to original sources
PubMed1993

Identification and classification of protein fold families.

We have developed a method for identifying fold families in the protein structure data bank. Pairwise sequence alignments are first performed to extract families of homologous proteins having 35% or more sequence identity. Representatives are selected with the best resolution and R-factor to give a nonhomologous data set. Subsequent structure comparisons between all members of this set detect homologous folds with low sequence identity but highly conserved structures. By softening the requirement on structural similarity, families of analogous proteins are obtained that have related folds but more diverse structures. Representatives are selected to give a non-analogous data set. Starting with 1410 chains from the Brookhaven Data Bank, we generate a set of 150 nonhomologous folds and a set of 112 non-analogous folds. Analysis of sequence and structure conservation within the larger families shows the globins to be the most highly conserved family and the TIM barrels the most weakly conserved.

Classification↗
PubMed1993

Protein fold refinement: building models from idealized folds using motif constraints and multiple sequence data.

A general solution to the problem of directly incorporating data from multiple sequence alignments into the construction of molecular models was approached through the calculation of an estimated pairwise distance based on conserved hydrophobicity. A scaling method was developed that allowed the required bulk geometric properties of the estimated pair-wise distances (mean and mean squared) to mimic those expected in a globular protein. These properties were maintained independently of the composition, length, number or degree of conservation of the original sequences. Despite being a poor estimate for individual distances were found to be compatible with the native structure and could be weighted highly. While the estimated distances provided a general drive towards hydrophobic packing, more specific structure (including secondary structures and motifs) were induced by regularization towards an ideal form. These constraints were used to refine an outline starting structure (derived only from secondary structure axes) towards a compact form that was sufficiently protein-like for side chains to be added with almost no further adjustment of the alpha-carbon positions. This process allows rough folds based on abstract representations of protein architecture to be rapidly converted to a form where they can be analysed by the growing number of methods designed to assess molecular models.

Chemical Phenomena↗
PubMed1993

Hemodynamics and vascular endothelial biology.

The vascular endothelium, as the interface between flowing blood and the underlying vessel wall, not only resides in a hemodynamic environment, but also is a mediator of flow-related influences. In recent years, particularly with the advent of cell culture studies, much has been learned about the effects of this mechanical environment. This brief review focuses on these more recent cell culture studies, emphasizing the effects of flow and the associated shear stress on vascular endothelial biology. Included are endothelial cell shape and orientation, cytoskeletal components, endocytosis, proliferation, and signal recognition/transduction mechanisms. Of particular interest are mechanical effects on the release of vasoactive substances, and recent studies of prostacyclin, endothelin, and nitric oxide are discussed. Through this review it will be demonstrated that flow has a major influence on the synthesis and release of such substances.

Animals↗
PubMed1993

Health care CBA/CEA: an update on the growth and composition of the literature.

Cost-benefit (CBA) and cost-effectiveness analyses (CEA) are methods that enumerate the costs and consequences associated with health-related technologies, services, and programs. This article examines the trends in published CBA and CEA of personal health services from 1979 through 1990. It is based on a bibliography that was compiled to help address the immense need for information on the variation and effectiveness of medical practices, particularly as researchers expand their analysis to a study of the cost effectiveness of medical and surgical interventions, health care technologies, preventive practices, and other health programs. A systematic search was conducted for all articles under the heading "cost-benefit analysis" (which includes cost-effectiveness analysis) and "costs and cost analysis." Data sources included the MEDLARS (National Library of Medicine) database, other bibliographies in specialized areas, reference lists in key articles, and contacts with researchers in the field. All titles and abstracts were scanned to determine if the articles pertained to personal health services and if both costs and consequences were assessed. If both criteria were met, the article was included in the bibliography. This search resulted in 3,206 eligible CBA/CEA publications from 1979 through 1990. The publications were subdivided into two major categories: reports of studies and "other" publications, including reviews, descriptions of methodology, letters, and editorials. Reports of studies and "other" publications were classified into approximately 250 different topic areas. The studies were further classified by parameters, such as study type, publication vehicle, and medical function. This article describes the results of this classification and describes trends during 1979 to 1990 compared with 1966 to 1978. The classification of study reports and "other" publications into 250 topic areas is presented in Appendix A. The entire bibliography is reproduced in Appendix B. Detailed tables of findings are presented in Appendix C, and the results are illustrated graphically in Appendix D. Appendix E provides the coding scheme used in the bibliography's data base.

Cost-Benefit Analysis↗
PubMed1993

On-line access to a cost-benefit/cost-effectiveness analysis bibliography via CDC WONDER.

The Centers for Disease Control and Prevention (CDC) is undertaking an assessment of prevention effectiveness; using information from cost-benefit and cost-effectiveness analysis (CBA/CEA) studies will be integral to this effort. To facilitate this work, a bibliography of articles that discusses both the costs and consequences of personal health services has been created. For 1979 to 1990, 3,206 articles were identified and classified into more than 250 topics. To provide simplified, readily available access to this resource in a system in which searches would not be key-word dependent, the authors created an on-line version of the bibliography and incorporated it into CDC WONDER, the CDC's on-line public health information system. Users can limit their queries by traditional bibliographic criteria (author, journal, publication type, year of publication, and country of origin); the full text of the abstract; or criteria particular to the CBA/CEA bibliography (topic, study type, and medical function). Having the CBA/CEA bibliography in CDC WONDER allows it to be searched and updated easily and also permits researchers to create personalized subsets of references. This on-line bibliography should help researchers in their efforts to identify gaps in knowledge of the relationship between costs and outcomes and the role of prevention in controlling health care expenditures.

Centers for Disease Control and Prevention, U.S.↗
PubMed1993

Autocrine control of wound repair by insulin-like growth factor I in cultured endothelial cells.

The repair process of the vascular endothelium is modulated by growth factors from both endogenous (within the vessel wall) and exogenous (blood borne) sources. We utilized a tissue culture model of endothelial wounding to gain further insight into the potential autocrine control of proliferation during wound repair. Cultured porcine aortic endothelial monolayers were mechanically wounded by passing a 7-mm sterile glass rod over the surface of the culture. Proliferation at the wound edge was quantified using [3H]thymidine autoradiography. In wounded cultures incubated in media supplemented with 10% fetal calf serum, 81 +/- 2% of the nuclei at the wound edge were labeled. When the cultures were incubated in serum-free media, proliferation at the wound edge was only slightly diminished with 65 +/- 3% (P < 0.05) of the cells labeled. These findings raise the possibility that there is a significant contribution from autocrine growth factors to endothelial wound repair. To evaluate the potential role of insulin-like growth factor I (IGF-I) in the wound repair process, we used a radioimmunoassay to measure IGF-I secretion. Wounded cultures exhibited a 187 +/- 58% increase in IGF-I production when compared with nonwounded cultures (P < 0.05). To determine the extent to which endogenous IGF-I mediates the proliferative response of endothelial cell monolayers to wounding, wounded cultures were incubated with inactivating concentrations of IGF-I antibody. When IGF-I antibody was present in the culture media, only 26 +/- 3% of the nuclei at the wound edge were labeled with [3H]thymidine (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

A new approach to protein fold recognition.

The prediction of protein tertiary structure from sequence using molecular energy calculations has not yet been successful; an alternative strategy of recognizing known motifs or folds in sequences looks more promising. We present here a new approach to fold recognition, whereby sequences are fitted directly onto the backbone coordinates of known protein structures. Our method for protein fold recognition involves automatic modelling of protein structures using a given sequence, and is based on the frameworks of known protein folds. The plausibility of each model, and hence the degree of compatibility between the sequence and the proposed structure, is evaluated by means of a set of empirical potentials derived from proteins of known structure. The novel aspect of our approach is that the matching of sequences to backbone coordinates is performed in full three-dimensional space, incorporating specific pair interactions explicitly.

Algorithms↗
PubMed1992

Fast structure alignment for protein databank searching.

A fast method is described for searching and analyzing the protein structure databank. It uses secondary structure followed by residue matching to compare protein structures and is developed from a previous structural alignment method based on dynamic programming. Linear representations of secondary structures are derived and their features compared to identify equivalent elements in two proteins. The secondary structure alignment then constrains the residue alignment, which compares only residues within aligned secondary structures and with similar buried areas and torsional angles. The initial secondary structure alignment improves accuracy and provides a means of filtering out unrelated proteins before the slower residue alignment stage. It is possible to search or sort the protein structure databank very quickly using just secondary structure comparisons. A search through 720 structures with a probe protein of 10 secondary structures required 1.7 CPU hours on a Sun 4/280. Alternatively, combined secondary structure and residue alignments, with a cutoff on the secondary structure score to remove pairs of unrelated proteins from further analysis, took 10.1 CPU hours. The method was applied in searches on different classes of proteins and to cluster a subset of the databank into structurally related groups. Relationships were consistent with known families of protein structure.

Amino Acid Sequence↗
PubMed1992

The rapid generation of mutation data matrices from protein sequences.

An efficient means for generating mutation data matrices from large numbers of protein sequences is presented here. By means of an approximate peptide-based sequence comparison algorithm, the set sequences are clustered at the 85% identity level. The closest relating pairs of sequences are aligned, and observed amino acid exchanges tallied in a matrix. The raw mutation frequency matrix is processed in a similar way to that described by Dayhoff et al. (1978), and so the resulting matrices may be easily used in current sequence analysis applications, in place of the standard mutation data matrices, which have not been updated for 13 years. The method is fast enough to process the entire SWISS-PROT databank in 20 h on a Sun SPARCstation 1, and is fast enough to generate a matrix from a specific family or class of proteins in minutes. Differences observed between our 250 PAM mutation data matrix and the matrix calculated by Dayhoff et al. are briefly discussed.

Algorithms↗
PubMed1992

Childhood chronic illness: prevalence, severity, and impact.

BACKGROUND: Using data from the 1988 National Health Interview Survey, this article presents national estimates of the prevalence and impact of childhood chronic conditions. METHODS: Proxy responses to a checklist of child health conditions administered for 17,110 children under 18 years of age were used. Conditions were classified as chronic if they were first noticed more than 3 months prior to the interview or if they were the type that would ordinarily be of extended duration, such as arthritis. RESULTS: An estimated 31% of children were affected by chronic conditions. Among these children, highly prevalent conditions included respiratory allergies 9.7 per 100, repeated ear infections 8.3 per 100 and asthma 4.3 per 100. These children can be divided into three groups: 66% with mild conditions that result in little or no bother or activity limitation; 29% with conditions of moderate severity that result in some bother or limitation of activity, but not both; and 5% with severe conditions that cause frequent bother and limitation of activity. The 5% with severe conditions accounted for 19% of physician contacts and 33% of hospital days related to chronic illness. CONCLUSIONS: Childhood chronic conditions have highly variable impacts on children's activities and use of health care.

Activities of Daily Living↗
PubMed1992

Impact of childhood asthma on health.

In 1988, the National Health Interview Survey contained a supplemental questionnaire on childhood conditions that included asthma. The authors used these data from 17,110 households to determine the disease burden resulting from asthma and to determine the functional status of children with and without asthma by linking information from the core and supplemental questionnaires. The prevalence of asthma in children younger than 18 years of age in the United States as reported by an adult in the household was 4.3% in 1988 and was 3.2% in 1981, the last time a comparable questionnaire was used in the National Health Interview Survey. The difference between the prevalences of asthma was statistically significant (95% confidence interval for the difference was 0.7% to 1.5%). An estimated 2.7 million children younger than 18 years were reported by an adult in the household to have had asthma in the past year. The added burden of illness experienced by children with asthma compared with children without asthma was an additional 10.1 million days missed from school, 12.9 million contacts with medical doctors, and 200,000 hospitalizations. Almost 30% of children with asthma had some limitation in activity, compared with only 5% of children without asthma. A greater proportion of black children experienced more severe functional disability and had more frequent hospitalizations than white children with asthma. Ten percent of children with asthma had severe disease as measured by frequency of bother and limitations in function; these children accounted for 35% of hospitalizations for asthma and 77% of the days in the hospital.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

The treatment of adult hyperglycaemia in an African rural hospital.

This paper describes the treatment of adult diabetic ketoacidosis in an African rural hospital in which there were only rudimentary diagnostic facilities. It is intended to be a practical guide to doctors working under similar conditions. It also deals with some of the pathophysiological mechanisms underlying diabetic ketoacidosis but emphasises the use of clinical skills in patient assessment and management.

Blood Glucose↗
PubMed1992

Evidence for synergistic interactions between ras, myc and a mutant form of p53 in cellular transformation and tumor dissemination.

Mouse 10T1/2 cells were transfected with combinations of T24 H-ras, human c-myc and the proline 193 mutant form of p53. The three-gene ras/myc/p53 combination was significantly more efficient than single genes or double gene combinations in inducing transformed foci in vitro. An analysis of cell lines isolated after transfections with ras, ras/myc, ras/p53 and ras/myc/p53 indicated that the last combination contained significantly higher levels of ras protein than the other combinations, produced tumors in syngeneic mice with a shorter latency period, and exhibited an increased ability to form lung tumors in an in vivo experimental metastasis assay. Synergistic interactions between ras, myc and mutant p53 genes were observed in focus formation and metastasis assays, suggesting that the action of the three oncogenes in malignant transformation occurs along separate but interactive pathways. These results support a working model of oncogene cooperativity in which alterations in myc and p53 permit elevated expression of ras, which is important in a mechanism affecting both cellular transformation in vitro and tumor dissemination in vivo.

Animals↗
PubMed1991

An extension of secondary structure prediction towards the prediction of tertiary structure.

Secondary structure prediction parameters and optimised decision constants for use with the method of Garnier et al. [(1978) J. Mol. Biol. 120, 97-120] have been derived for two new and distinct substates of beta-structure. These we term internal and external on the basis of their hydrogen bonding patterns. The profiles of the amino acids for several of the parameters are considerably different in the two substates. Predictions using the new parameters attempt to distinguish the strands at the core of the beta-sheet from those at its edges and so restrict the possible topologies in tertiary structure prediction. The potential application of these parameters is illustrated for the class of beta/alpha proteins.

Adenylate Kinase↗
PubMed1991

A hypothetical model for the peptide binding domain of hsp70 based on the peptide binding domain of HLA.

The sequences of the peptide binding domains of 33 70 kd heat shock proteins (hsp70) have been aligned and a consensus secondary structure has been deduced. Individual members showed no significant deviation from the consensus, which showed a beta 4 alpha motif repeated twice, followed by two further helices and a terminus rich in Pro and Gly. The repeated motif could be aligned with the secondary structure of the functionally equivalent peptide binding domain of human leucocyte antigen (HLA) class I maintaining equivalent residues in structurally important positions in the two families and a model was built based on this alignment. The interaction of this domain with the ATP domain is considered. The overall model is shown to be consistent with the properties of products of chymotryptic cleavage.

Adenosine Triphosphate↗
PubMed1991

Visualization of structural similarity in proteins.

Two new methods for the visualization of structural similarity in proteins with known three-dimensional structures are presented. They are based on the degree of equivalence of alpha-carbon pairs in two proteins. The quantitative measure for residue equivalence is the comparison score generated using the sequence and structure alignment method of Taylor and Orengo, which is based on the comparison of interatomic distances (and other properties that can be defined on a residue basis). The first method uses information on corresponding alpha-carbon positions to display vectors joining these structurally equivalent residues. These vectors can be defined as target constraints, and their minimization "bends" the two proteins toward a common average structure. In the average structure the corresponding residues virtually superpose, while insertions and deletions become clearly visible. The second method uses the comparison scores to perform a weighted least-squares fit of the two structures. It is further used to color code the two structures according to the score value, i.e., their similarity, on a continuous scale from red to blue. Examples of the methods for the comparison of flavodoxin, chemotaxis Y protein and L-arabinose-binding protein are given.

Amino Acid Sequence↗
PubMed1991

Towards protein tertiary fold prediction using distance and motif constraints.

Based on a simplified model of the all-alpha class of protein, all packing arrangements of alpha-helices were generated and assessed by both general and specific structural rules. The method was applied to myoglobin and parvalbumin, which were both ranked in the top 4% of folds under the general packing constraints. Incorporation of the restrictions implied by the EF-hand motifs of parvalbumin were sufficient to select the correct fold as one of two (equal scoring) possibilities. Myoglobin scored well under the general packing constraints and the addition of a single distance constraint, implied by haem binding, was sufficient to select the correct fold as one of several candidates. Incorporation of a score for complementary hydrophobic packing between helices further selected myoglobin as a unique fold but did not improve the ranking of parvalbumin. For both proteins, the alpha-helices were predicted from multiply aligned sequences using pattern-matching methods and no specific aspect of the known X-ray structures influenced this or the prediction of the correct folds. Although the method is currently of limited generality, its further applications and extension to a more detailed structural level are discussed.

Amino Acid Sequence↗