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At least 199 records · Page 11Linked to original sources
PubMed1996

Heteroligation of a mouse monoclonal IgE antibody (La2) with small molecules, analysed by computer-aided automated docking.

A mouse monoclonal anti-TNP IgE antibody (IgE-La2) was screened by a competitive-binding ELISA with a random pool of over 2000 small molecules, mostly drugs, drug derivatives and metabolites. Thirteen of these (naproxene, beta-carboxy-chi-naphthol, oxolinic acid, hymecromone, 8-aminoquinoline, beta-naphthylamine, chi-nitrilo-cinnamic acid, 1,5-diaminonaphthaline, prolonium iodide, diaspirin, 3,4,5-trimethoxy-cinnamic acid, cycrimine, hemimellitic acid) were found to bind as strongly, or stronger, to the antibody as the immunizing hapten. We have used a Monte Carlo search technique for simulated docking of the DNP and non-DNP ligands to a model of the Fv region of IgE(La2). The validity of structural predictions made by the AutoDock program were tested on IgG(ANO2), the three-dimensional structure of which had been obtained previously by X-ray crystallography and 2D-NMR. The rms differences between the experimentally determined and auto-docked complexes in the energetically most favored binding modes were 0.31-0.44 A. Evaluation of structures of IgE(La2)-ligand complexes [including 2,4-dinitrophenol (DNP), 16 DNP amino acids, and the 13 non-DNP ligands listed above] obtained by computer-aided automated docking, suggested the existence of two subsites within an approximately 12 x 18 A2 groove extending between the H and L CDRs. Some of the ligands (DNP-Glu, 8-aminoquinoline, prolonium-I, beta-naphthylamine) were found to bind exclusively to subsite 1, others (DNP-Ala, chi-nitrilo-cinnamic acid, hemimellitic acid, beta-carboxy-chi-naphthol) to subsite 2. The majority of DNP amino acids and other ligands (oxolinic acid, 3,4,5-trimethoxy-cinnamic acid, diaspirin, [R]-cycrimine) were found to occupy an overlapping area including subsites 1 and 2, while some of the compounds (DNP-Asn, DNP-Pro, hymecromone, 1,5-naphthylenediamine) were predicted to interact with either of these subsites with comparable probabilities. When all of the docked La2-ligand complexes were taken into account, five tyrosine residues (H33, L32, L91, L92, L96) were found to provide the majority (53.4%) of all observed contact points. Thus, a multitude of interactions with aromatic residues, and a combinatorial type of interaction within the binding region, seem to be the major factors to explain the mechanism of heteroligation by IgE(La2).

Amino Acid Sequence↗
PubMed1987

Reconstruction of NOESY maps. A requirement for a reliable conformational analysis of biomolecules using 2D NMR.

The modelling of the conformation of a biomolecule in solution is based mainly on the internuclear distances deduced from measurements of nuclear Overhauser effects (nOe) in NOESY correlation maps. The distances are then used as restraints in the energy minimization procedure, which leads to one or several optimized conformations. A general and safe technique for validating these structures with respect to the experimental data is here proposed: from the internuclear distances, the relaxation matrix can be computed under the assumption of a unique rotational correlation time. By stepwise integration of these relaxation equations, the NOESY maps can be accurately reconstructed for any mixing time. Because multi-spin effects are correctly taken into account, any difference between the experimental and theoretical maps can be easily interpreted in terms of conformation, and possible inconsistencies due to conformational averaging can be pointed out. The technique is illustrated for a bacterial lipopeptide, mycosubtilin, the spectrum of which is completely assigned.

Biopolymers↗
PubMed1995

Towards eradication of measles virus: global progress and strategy evaluation.

Despite an increase in global measles vaccine coverage from under 20% in 1980 to around 80% in 1990, measles remains a major cause of morbidity and mortality world-wide. This paper addresses a number of issues relating to efforts to control measles, namely, (i) at the global level, how might we assess the impact of measles vaccination on the incidence of infection and associated disease, and, (ii), at the strategic level, how can we utilise an understanding of the transmission dynamics of childhood viral infections to aid the design of optimal immunisation programmes? Based on WHO vaccine coverage data, and organising countries according to similarities in demographic and epidemiological parameters, an age-structured model of measles transmission is used to capture the non-linear dynamics of infection and mass vaccination and to generate projections of the impact of measles immunization world-wide. The results provide a crude indication of the percentage reduction in measles cases by year 2000 (compared with no immunization) and suggest an approximately 70% reduction in cases over all ages, and 77% reduction in cases under 5 years (where there is the greatest risk of case fatality); these suggest that WHO targets for 1995 are unlikely to be achieved. In the second part of the paper, examples are given to illustrate the usefulness of a modelling approach in evaluating measles immunization policy. The introduction of MMR vaccine in the UK in 1988 has resulted in measles incidence falling to an all time low and attention has turned to the requirements of elimination. A realistic age structured model, validated using extensive serological data, is used to compare the merits of single or two dose strategies. Based upon recent estimates of vaccine efficacy (90%) and coverage (92% by end of second year of life) it is suggested that a two-dose policy with a pre-school second dose given irrespective of vaccine history is required to prevent the build up of susceptibles to epidemic proportions in the longer term. In a second example, prompted by the success of the campaign approach to polio and measles elimination in Central and South America, simple models are used to explore and quantify the process by which pulse vaccination programmes (i.e. repeated application across a wide age range) act to control transmission.

England↗
PubMed1983

An assessment of the evidence for the role of ribonucleoprotein particles in the maturation of eukaryote mRNA.

This article has sought to draw together, on the one hand, what is known of mRNA processing and its control and, on the other hand, what is known of the structure and validity of hnRNP and snRNP particles. At the same time, it has attempted to synthesize these two themes into a critical assessment of the evidence which suggests that the particles are intimately involved in processing. It cannot be said that the case is proven. The evidence is compelling but circumstantial. The last few years have seen the development of the first in vitro splicing systems (Weingartner and Keller, 1981; Goldenberg and Raskus, 1981; Kole and Weissman, 1982), the isolation of monoclonal antibodies to defined snRNP (Lerner et al., 1981a; Billings et al., 1982) and hnRNP proteins (Hugle et al., 1982), and the ability to use artificial lipid vesicles to transfer antisera (Lenk et al., 1982) and radioactive snRNA (Gross and Cetron, 1982) into cells. It is to be hoped that further refinements of these and other techniques will allow us to solve this, one of the major outstanding problems of molecular biology.

Animals↗
PubMed1988

Sensitive quantification of pseudoephedrine in human plasma and urine by high-performance liquid chromatography.

An assay for the selective quantification of pseudoephedrine in human plasma and urine was developed using high-performance liquid chromatography with UV detection at 205 nm. Analyte and internal standard were extracted from alkaline plasma or urine into a mixture of n-hexane and diethyl ether, and the organic phase was back-extracted into dilute acid. The chromatographic system comprises microparticulate cyanopropyl-silica as stationary phase and a ternary solvent mixture with ion-pair reagents as mobile phase. Using 0.25 ml plasma, the lower limit of quantification was 25 ng/ml with excellent linearity up to 1000 ng/ml. In urine, the calibration ranged from 2.5 to 100 micrograms/ml. The selectivity of the method was demonstrated for several pharmaceuticals with similar structures. The validated method was applied to a pharmacokinetic study with a single oral dose of 100 mg of pseudoephedrine in two galenic formulations. Precision and accuracy data of the assay and calculated pharmacokinetic parameters are presented.

Adolescent↗
PubMed1994

The development and validation of an age-structured model for the evaluation of disease control strategies for intestinal helminths.

Epidemiological modelling can be a useful tool for the evaluation of parasite control strategies. An age-structured epidemiological model of intestinal helminth dynamics is developed. This model includes the explicit representation of changing worm distributions between hosts as a result of treatment, and estimates the morbidity due to heavy infections. The model is used to evaluate the effectiveness of different programmes of age-targeted community chemotherapy in reducing the amount of morbidity due to helminth infection. The magnitude of age-related heterogeneities is found to be very important in determining the results of age-targeted treatment programmes. The model was verified using field data from control programmes for Ascaris lumbricoides and Trichuris trichiura, and was found to provide accurate predictions of prevalence and mean intensities of infection during and following different control regimes.

Adult↗
PubMed1997

Three-dimensional structure of the cytoplasmic face of the G protein receptor rhodopsin.

Rhodopsin is a G protein receptor from a many-membered family of membrane receptors. No high-resolution structure exists for any member of this family due to the insolubility of membrane proteins and the difficulty in crystallizing membrane proteins. Two new approaches to the structure of rhodopsin are described that circumvent these limitations: (1) individual solution structures of the four cytoplasmic domains of rhodopsin are fitted with the transmembrane domain; (2) the solution structure of a complex of the four cytoplasmic domains is determined from nuclear magnetic resonance data. The two structures are similar. To test the validity of these structures, specific site-to-site distances measured on intact membrane-bound rhodopsin are compared to the same distances on the structures reported here. Excellent agreement is obtained. Furthermore, the agreement is obtained with distances measured on the activated form of teh receptor and not with distances on the dark-adapted form of rhodopsin. This approach may prove to have general applicability for the determination of the structure for membrane proteins.

Circular Dichroism↗
PubMed1982

Sequences of three molluscan 5 S ribosomal RNAs confirm the validity of a dynamic secondary structure model.

The collection of known 5 S rRNA primary structures is enriched with the sequences from three mollusca, the snails Helix pomatia and Arion rufus, and the mussel Mytilus edulis. The three sequences can be fitted in a five-helix secondary structure model previously shown (De Wachter et al. (1982) Biochimie 64, 311-329) to apply to all 5 S RNAs regardless of their origin. One of the helices in this model can undergo a bulge-internal loop transition. Within the metazoan kingdom, the dimensions of each helix and loop are rigidly conserved, except for one helix which can comprise either 6 or 7 base pairs.

Animals↗
PubMed1997

Protein engineering tests of a homology model of Plasmodium falciparum lactate dehydrogenase.

This paper describes the testing of a homology model of Plasmodium falciparum lactate dehydrogenase (pfLDH) by protein engineering. The model had been validated in structural terms. It suggests explanations of the unusual properties of pfLDH (compared with all other LDHs). These unusual features are a lack of substrate inhibition, high activity with the synthetic coenzyme 3-acetylpyridine adenine dinucleotide (APAD+) and changes in residues at previously conserved positions. pfLDH shows several amino acid insertions and deletions in an alignment with protein sequences from all other known LDHs. The most notable is a five amino acid insertion into the active-site loop. In addition, a conserved serine at position 163 is replaced by leucine. The results showed that when the unique pfLDH structural features were engineered into Bacillus stearothermophilus lactate dehydrogenase, the thermophilic enzyme acquired the properties previously uniquely associated with the malarial enzyme. We conclude that the homology model of the malarial enzyme is adequate for the prediction of successful redesigns and, in the regions tested, is accurate.

Amino Acid Sequence↗
PubMedDate not supplied

Development and testing of the caregiver reciprocity scale.

The purpose of this study was to develop and validate the dimensions of caregiver reciprocity. Social exchange and equity theory served as a conceptual framework for examining recprocal intergenerational exchanges of assistance and support. In the first phase of the study, 12 caregivers of elderly parents, including in-laws, were interviewed to provide narrative data from which items were developed. Content validity was judged by two separate panels of experts. The revised CRS was tested with 303 adult children for reliability and validity, including internal consistency, test-retest reliability, exploratory factor analysis, and convergent and discriminant validity testing using structural equation modeling. Support for construct validity was demonstrated for four factors: Warmth and Regard, Intrinsic Rewards of Giving, Love and Affection, and Balance within Family Caregiving.

Aged↗
PubMed1995

Measuring the functional status of patients with low back pain. Assessment of the quality of four disease-specific questionnaires.

STUDY DESIGN: This study was a literature review of the quality of four disease-specific functional status questionnaires for patients with low back pain: Oswestry; Million; Roland; and Waddell disability questionnaire. OBJECTIVES: The questionnaires were evaluated in terms of general description, scale structure, reliability, validity, responsiveness, and clinical research applications. SUMMARY OF BACKGROUND DATA: Functional status is an outcome of great interest for clinical trials of low back pain. METHODS: A computer-aided search was conducted of articles published between 1981 and 1993 and references given in selected relevant publications. Articles were selected if at least one of the four functional status questionnaires was used or if the authors gave relevant information about the methodology of these questionnaires. RESULTS: There was not enough information available about the criteria of item selection used for the development of the questionnaires. The test-retest reproducibility of the questionnaires seemed satisfactory. The Oswestry and Roland disability questionnaires have been used and evaluated more frequently than the Million and Waddell. Therefore, we can be more certain about the validity and responsiveness of the former pair of questionnaires. CONCLUSION: In the absence of a gold standard, direct comparisons of evaluative functional status questionnaires in a single patient group are needed. Through direct comparisons, comparative validity and responsiveness can be assessed. Functional status measures are not currently used in many settings in which they would be valuable. It is important to encourage their wider use in clinical trials. Additional research is needed to compare and improve the existing questionnaires.

Activities of Daily Living↗
PubMed1995

The prevention of mechanical birth trauma by means of computer aided simulation of delivery by means of nuclear magnetic resonance imaging and finite element analysis.

Anatomic disproportion gains an increasing interest in obstetrics. Imaging procedures (radiologic pelvimetry, computed or magnetic resonance imaging (MRI) fail to reflect the dynamics of delivery including deformations of the birth channel as well as of fetal structures. To validate findings of imaging procedures in this respect a method has been developed to perform a dynamic, biomechanical postprocessing of the static informations obtained from MRI. Using an especially developed software MRI pixel matrices of maternal pelvis and fetal head were color-codef1p4d--according to the principle of same density--line data were created. After sectional attribution of the resulting polygones a three-dimensional mesh of so called Finite elements (FE) was created, which then can be used for deformation analysis. Fetal head was then moved through the birth channel by means of computed simulation. This allows not only ongoing deformations to be visualized but also resulting forces to be calculated for at any time of the delivery process for any point of the anatomical model. Performing these simulations assuming various anatomic and physiologic conditions an obstetrical-biomechanical data basis could be obtained, that was implemented in a PC-based expert system. This allows interpretation of pelvimetric data with regard to birth dynamics.

Biomechanical Phenomena↗
PubMed1982

The rapid disability rating scale-2.

A revised version of the Rapid Disability Rating Scale (RDRS-2) is presented. Item definitions have been sharpened and directions expanded to indicate that ratings are based upon the patient's performance in regard to behavior, and that prosthesis normally used by the patient should be included in the assessment. Three items have been added to increase the breadth of the scale. Response items have been changed from three-point to four-point ratings in order to increase group discrimination amd make the scale more sensitive to changes in treatment. The new appraisals of reliability, factor structure, and validity are reported, along with the potential uses of the scale.

Activities of Daily Living↗
PubMed1996

Alcian blue. Now you see it, now you don't.

A brief outline of the history and chemistry of the copper pthalocyanin-based Alcian blue dyes highlights the adverse effects of commercial secrecy and entrepreneurial dishonesty on the use of these valuable histochemical and biochemical reagents in the biological sciences. The acquisition of detailed and validated chemical structures required the avoidable expenditure of much time that otherwise would have been spent on new research. The combination of this chemical knowledge with experiments on isolated polyanions, using critical electrolyte concentration (CEC) techniques, established a molecular recognition paradigm of Alcian blue usage in histochemistry. New reagents (Cuprolinic and Cupromeronic blues) were synthesised to investigate and support the hypothesis that Alcian blue did not intercalate with DNA. They were made with the important additional aim of using them in electron microscopy of polynucleotides (in the case of Cuprolinic blue) and non-nucleotide polyanions, such as sulphated proteoglycans in extracellular matrices (in the case of Cupromeronic blue). The cationic groups of Alcian blue are easily removed in very mild conditions, producing insoluble blue pigment in situ (ingrain dying). This reaction underlies its unique capability to stain in repeated cycles, thus greatly amplifying sensitivity of detection of substrates present in very small amounts in tissues and on electrophoretic strips etc.

Alcian Blue↗
PubMed1991

Assessment and diagnosis of borderline personality disorder.

Borderline personality disorder is common in treatment settings and may be so in the general population. In this guide to assessment strategies for diagnosing borderline personality disorder, the authors discuss the reliability and validity of structured interviews and self-report instruments and suggest the use of a self-report questionnaire as a cost-effective screening test. Assessment problems, such as the need for longitudinal observation, are reviewed. Essential features of the recommended diagnostic approach include clarity about the diagnostic concept, consideration of the full range of diagnostic criteria, incorporation of recently developed diagnostic methodologies, care in distinguishing personality disorders from comorbid axis I syndromes, and complete assessment of the full range of axis II disorders.

Borderline Personality Disorder↗
PubMed1993

The product of the Drosophila segment polarity gene armadillo is part of a multi-protein complex resembling the vertebrate adherens junction.

Sequence similarity between the Drosophila segment polarity protein Armadillo and the vertebrate adherens junction protein beta-catenin raised the possibility that adherens junctions function in transduction of intercellular signals like that mediated by Wingless/Wnt-1. To substantiate the sequence similarity, properties of Armadillo were evaluated for consistency with a junctional role. Armadillo is part of a membrane-associated complex. This complex includes Armadillo, a glycoprotein similar in size to vertebrate cadherins, and the Drosophila homolog of alpha-catenin. Armadillo co-localizes with junctions that resemble vertebrate adherens junctions in morphology and position. These results suggest that Drosophila and vertebrate adherens junctions are structurally similar, validating use of Armadillo and its associated proteins as a model for vertebrate adherens junctions.

Animals↗
PubMed1987

Analysis of individual, intraspecific and interspecific variability in quantitative parameters of caprine tooth enamel structure.

Qualitative and quantitative features of mammalian tooth enamel structure are increasingly being used in taxonomic and phylogenetic analyses, although the variability shown by these traits has not received adequate consideration. This study evaluates the variability displayed by nine quantitative parameters in deep, intermediate, and superficial molar enamel in the closely related bovids Ovis aries and Capra hircus. These parameters are assessed in terms of the absolute and/or relative variability evinced at a given depth within a single individual, among conspecific individuals, and between species samples. The degrees of relative variability expressed at a given depth are comparable among conspecific individuals and between taxonomic samples. Nevertheless, in many instances, there are significant differences in absolute variability amongst individuals. Also, in four parameters for which individual specimen averages could be calculated, the equality of these means among conspecifics can be rejected. Variability is not equivalent at different enamel depths. The null hypothesis of equality of individual, conspecific variances can be rejected most commonly for parameters measured in deep and superficial enamel, and coefficients of variation also tend to be higher for deep and superficial enamel than for enamel of intermediate depth. The greater variability displayed by deep and especially superficial enamel may be related to the initial onset and the terminal phase of ameloblastic secretory activity. Taxonomic and phylogenetic analyses that utilize quantitative data on enamel structure are valid only if comparisons have been made at equivalent enamel depths.

Ameloblasts↗