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PubMed2002

Synergistic activity of the ninth and tenth FIII domains of human fibronectin depends upon structural stability.

The ninth and tenth FIII domains (FIII9-10) of human fibronectin act in synergy to promote cell adhesion via the interaction with integrin receptors. Here we describe the functional and structural properties of a set of recombinant FIII9-10 mutants containing various alanine substitutions within the key synergistic site, DRVPHSRN in FIII9, either alone or in combination with another substitution (Leu(1408) to Pro), on the opposite face of FIII9, that increases stability and the functional capacity of FIII9-10. We show that the introduction of mutations into the synergistic sequence of FIII9-10 has a negative effect on the adhesion of baby hamster kidney fibroblasts and results in reduced ability of these ligands to recognize integrin alpha(5)beta(1). Conformational stability of the FIII9 domain in the synergy site mutants is likewise reduced in comparison with native FIII9. The Leu(1408) to Pro substitution in mutant FIII9-10 proteins carrying substitutions in the synergy site results in a substantial recovery of the adhesive activity of the mutants and affinity to alpha(5)beta(1). In keeping with the enhancement of functional activity, the Leu(1408) to Pro substitution in the FIII9-10 synergy site mutants also causes a significant increase in conformational stability of FIII9. These observations imply a strong positive correlation between the biological activity and conformational stability of the assessed FIII9-10 mutants and suggest that a Leu(1408) to Pro substitution restores the biological activity of the mutants via their ability to restore their conformational stability. We conclude that domain stability may be a major determinant of the synergistic potential of FIII9. Our data underscore the value of using more than one approach in such structure-function studies and the requirement for validating the global structural integrity of protein ligands in which sequences that disrupt function have been perturbed.

Animals↗
PubMed2003

Exon-intron structure and evolution of the Lipocalin gene family.

The Lipocalins are an ancient protein family whose expression is currently confirmed in bacteria, protoctists, plants, arthropods, and chordates. The evolution of this protein family has been assessed previously using amino acid sequence phylogenies. In this report we use an independent set of characters derived from the gene structure (exon-intron arrangement) to infer a new lipocalin phylogeny. We also present the novel gene structure of three insect lipocalins. The position and phase of introns are well preserved among lipocalin clades when mapped onto a protein sequence alignment, suggesting the homologous nature of these introns. Because of this homology, we use the intron position and phase of 23 lipocalin genes to reconstruct a phylogeny by maximum parsimony and distance methods. These phylogenies are very similar to the phylogenies derived from protein sequence. This result is confirmed by congruence analysis, and a consensus tree shows the commonalities between the two source trees. Interestingly, the intron arrangement phylogeny shows that metazoan lipocalins have more introns than other eukaryotic lipocalins, and that intron gains have occurred in the C-termini of chordate lipocalins. We also analyze the relationship of intron arrangement and protein tertiary structure, as well as the relationship of lipocalins with members of the proposed structural superfamily of calycins. Our congruence analysis validates the gene structure data as a source of phylogenetic information and helps to further refine our hypothesis on the evolutionary history of lipocalins.

Amino Acid Sequence↗
PubMed1997

Analysis of the in vitro secondary structure of cucumber mosaic virus satellite RNA.

The solution conformation of two variants of cucumber mosaic virus satellite RNA (CMV satRNA) was analyzed using several enzymatic and chemical probes. Ribonuclease T1 and nuclease S1 were used to map unpaired nucleotides, and nuclease V1 was used to detect double-stranded, or stacked, bases. Chemical probing with dimethylsulphate and diethylpyrocarbonate also identified unpaired and unstacked nucleotides, respectively. Modified or cleaved positions were identified by direct gel electrophoresis of radioactively labeled RNA, or by analysis of DNA sequence patterns generated by primer-extension with reverse transcriptase. Additional information was obtained by a gel-fractionation method under nondenaturing conditions for the identification of base paired fragments. On these data, a model for the in vitro secondary structure of CMV satRNA is proposed. Results support the existence of a complex structure with 51% of nucleotides involved in base pairs (40 G:C, 28 G:U, and 18 A:U pairs). Several structural elements, numbered I-VI, were defined, and interactions between separate domains are suggested. Comparisons of experimental data and a formerly reported secondary structure model for CMV satRNA support the validity of the structure we propose.

Base Composition↗
PubMed1997

Psychometric analysis of the Functional Assessment of Cancer Therapy-General (FACT-G) scale in a rural sample.

BACKGROUND: Quality of life for persons with cancer has been studied extensively in urban populations. The Functional Assessment of Cancer Therapy-General (FACT-G) scale was developed for use in clinical trials. The authors tested the psychometric properties of the FACT-G scale in a sample of rural cancer patients. METHODS: A systematic replication of the 1993 study by Cella et al., in which FACT-G was developed, was employed to assess the reliability, validity, and factor structure of the scale. RESULTS: The reliability and validity of the FACT-G scale for evaluating rural cancer patients was determined to be sufficient for research purposes. The factor structure was the same as that reported by Cella et al. CONCLUSIONS: The FACT-G scale is appropriate for use in studies of the quality of life of rural cancer patients.

Aged↗
PubMed2002

Prediction of structure and function of G protein-coupled receptors.

G protein-coupled receptors (GPCRs) mediate our sense of vision, smell, taste, and pain. They are also involved in cell recognition and communication processes, and hence have emerged as a prominent superfamily for drug targets. Unfortunately, the atomic-level structure is available for only one GPCR (bovine rhodopsin), making it difficult to use structure-based methods to design drugs and mutation experiments. We have recently developed first principles methods (MembStruk and HierDock) for predicting structure of GPCRs, and for predicting the ligand binding sites and relative binding affinities. Comparing to the one case with structural data, bovine rhodopsin, we find good accuracy in both the structure of the protein and of the bound ligand. We report here the application of MembStruk and HierDock to beta1-adrenergic receptor, endothelial differential gene 6, mouse and rat I7 olfactory receptors, and human sweet receptor. We find that the predicted structure of beta1-adrenergic receptor leads to a binding site for epinephrine that agrees well with the mutation experiments. Similarly the predicted binding sites and affinities for endothelial differential gene 6, mouse and rat I7 olfactory receptors, and human sweet receptor are consistent with the available experimental data. These predicted structures and binding sites allow the design of mutation experiments to validate and improve the structure and function prediction methods. As these structures are validated they can be used as targets for the design of new receptor-selective antagonists or agonists for GPCRs.

Algorithms↗
PubMed1997

Validation of the Bech-Rafaelsen Mania Scale using latent structure analysis.

The essential criteria of internal validity have not been sufficiently evaluated for any mania rating scale, although the fulfillment of such criteria is a prerequisite for summing the item scores to give a total score reflecting the severity of mania, and for comparing total scores across patient groups that differ with regard to variables such as age and sex. This study investigated the internal validity of the Bech-Rafaelsen Mania Scale (MAS), based on the ratings of 100 consecutively admitted drug-free DSM-III-R manic patients. Application of logistic latent structure models did not statistically confirm the additivity of the MAS. However, a modified MAS (the MAS-M) arising from the analyses fulfilled the measurement model. Transferability of the MAS-M across age and sex was also confirmed. The MAS-M showed an acceptable concurrent validity and an adequate sensitivity in discriminating between responders and non-responders among patients participating in a drug trial. The MAS-M presented here is the first mania rating scale that has been shown to fulfil statistical criteria for internal validity.

Adult↗
PubMed2006

Work design and management in the manufacturing sector: development and validation of the Work Organisation Assessment Questionnaire.

OBJECTIVES: To examine the factor structure, reliability, and validity of a new context-specific questionnaire for the assessment of work and organisational factors. The Work Organisation Assessment Questionnaire (WOAQ) was developed as part of a risk assessment and risk reduction methodology for hazards inherent in the design and management of work in the manufacturing sector. METHOD: Two studies were conducted. Data were collected from 524 white- and blue-collar employees from a range of manufacturing companies. Exploratory factor analysis was carried out on 28 items that described the most commonly reported failures of work design and management in companies in the manufacturing sector. Concurrent validity data were also collected. A reliability study was conducted with a further 156 employees. RESULTS: Principal component analysis, with varimax rotation, revealed a strong 28-item, five factor structure. The factors were named: quality of relationships with management, reward and recognition, workload, quality of relationships with colleagues, and quality of physical environment. Analyses also revealed a more general summative factor. Results indicated that the questionnaire has good internal consistency and test-retest reliability and validity. Being associated with poor employee health and changes in health related behaviour, the WOAQ factors are possible hazards. It is argued that the strength of those associations offers some estimation of risk. Feedback from the organisations involved indicated that the WOAQ was easy to use and meaningful for them as part of their risk assessment procedures. CONCLUSIONS: The studies reported here describe a model of the hazards to employee health and health related behaviour inherent in the design and management of work in the manufacturing sector. It offers an instrument for their assessment. The scales derived which form the WOAQ were shown to be reliable, valid, and meaningful to the user population.

Adolescent↗
PubMed1986

Simultaneous-successive factor structure of the WISC-R: a validation study.

It has been suggested that the Wechsler Intelligence Scale for Children--Revised (WISC--R) may usefully be interpreted in terms of a Simultaneous-Successive factor structure. A previous attempt to validate this hypothesis via factor analysis of 8 of the 12 WISC--R subtests was later shown to be an unreliable test of this model. The present study, performed upon 36 children, aged 6 1/2 to 12 1/2 yr., 45% female, 83% black, tested the validity of the two-factor model vis-á-vis the Kaufman Assessment Battery for Children (K-ABC), which is reported to have an unambiguous Simultaneous-Sequential (Successive) factor structure. Present results do not support a salient Simultaneous-Successive structure for the WISC--R, and clinicians should be wary of using the proposed two-factor model of the WISC--R for diagnostic or remedial purposes.

Child↗
PubMed1996

The Adolescent Relapse Coping Questionnaire: psychometric validation.

OBJECTIVE: The present study was undertaken to assess the factor structure and psychometric validity of the Adolescent Relapse Coping Questionnaire (ARCQ). The ARCQ is designed to assess alcohol and other drug abusing adolescents coping with situations providing temptations for alcohol and other drug use. METHOD: This was a prospective longitudinal study of 136 (79 male) alcohol and other drug abusing adolescents who were an average of 16.9 years old. Consecutive admissions were recruited from two adolescent, inpatient alcohol and drug abuse treatment facilities. Subjects completed the ARCQ as part of a 1-year-posttreatment interview and were subsequently interviewed 2 years posttreatment. RESULTS: Analyses yielded three coping factors which were evaluated for construct and criterion validity. Factor 1 contained generic cognitive and behavioral problem-solving strategies, Factor 2 represented self-critical cognitions and Factor 3 included abstinence-focused coping strategies. The factors had good internal consistency (alpha = .78 to .82) and collectively accounted for 40% of the variance in the principle components analysis. The abstinence-oriented coping factor was significantly correlated with current alcohol and drug use and measures of situation appraisal, and significantly predicted alcohol and drug use during the year following assessment. CONCLUSIONS: The findings provide evidence for the psychometric validity of the ARCQ, provide convergent validation for the utility of the temptation-coping construct and further highlight differences between adult and teen addictive relapse.

Adaptation, Psychological↗
PubMed1989

The Psychosomatic Symptom Checklist revisited: reliability and validity in a chronic pain population.

A psychometric evaluation of the SUNYA Revision of the Psychosomatic Symptom Checklist (PSC) was conducted with 405 chronic pain patients who completed the PSC as part of a diagnostic battery. Several properties of the measure were examined, including its reliability, internal consistency, discriminant validity, and factor structure. Contrary to a previous study, the measure demonstrated a modest reliability, a poor discriminant validity, and a multifactor structure that accounted for only a small proportion of the variance in the measure. Thus, the PSC did not appear to be an adequate measure of general psychosomatic distress when used with chronic pain patients. For these patients, the PSC may measure symptom clusters rather than general psychosomatic symptomatology. Since the PSC is used in various clinical populations, the results underscore the importance of investigating the properties of the measure in these populations.

Adult↗
PubMed1980

Mental retardation as a Facade Self phenomenon: construct validation.

Predictions from Wagner's Structural Analysis theory were tested to validate a theoretical explanation of the personality of mentally retarded adults. The Rorschach and Hand Test were administered to 44 medical students and 60 institutionalized mentally retarded adults. Results coincided with predictions based on Structural Analysis. Implications of these results for the diagnosis of mental retardation were discussed. The potential of a special Rorschach Facade Self Index for differential diagnosis of other forms of psychopathology was noted.

Adult↗
PubMed2006

Reliability and validity of the Icelandic version of the Problem Area in Diabetes (PAID) Scale.

BACKGROUND: Diabetes is a burdensome disease that increases distress among people with diabetes. OBJECTIVES: To test the validity and reliability of an Icelandic version of the problem area in diabetes scale (PAID) and to assess the hitherto unknown distress level of Icelandic people with insulin requiring diabetes. DESIGN: Methodological research design. SETTING: Diabetes clinics. PARTICIPANTS: People with insulin-dependent diabetes, between 18 and 61 years. METHODS: All instruments were translated using a back-translation technique. Participants answered three consecutive questionnaires in succession, the PAID scale, the diabetes empowerment scale (DES) and the diabetes knowledge test (DKT). Principical component analysis with varimax rotation was conducted on the PAID scale to identify latent factors. RESULTS: Factor analysis revealed two factors: (a) distress in relation to life with diabetes, with Cronbach alpha coefficient of 0.93 and (b) distress in relation to management of diabetes, with Cronbach alpha coefficient of 0.88, for PAID overall Cronbach alpha coefficient was 0.94. PAID showed neither floor nor ceilings effects. Propositions set to indicate validity were generally met. However, PAID's factor structure and predictive validity needs to be tested further. CONCLUSIONS: The Icelandic version of PAID is sufficiently psychometrically robust. PAID is simple to administer and by using the scale clinicians can identify people at risk for developing diabetes-related distress. The results are comparable to results from studies in other countries using the PAID scale.

Adaptation, Psychological↗
PubMed2004

Psychometric properties of the Dutch version of the Washington Psychosocial Seizure Inventory.

PURPOSE: The psychometric properties of the Dutch version of the Washington Psychosocial Seizure Inventory (WPSI) were investigated. METHODS: The dimensional structure, reliability, and validity of the WPSI scales were assessed in 218 patients with epilepsy. The association with relevant patient and epilepsy characteristics also was studied. RESULTS: An exploratory seven-factor principal components analysis was compared with a confirmatory factor analysis, and a loss of 3.36% of total variance was found. To increase the homogeneity of the scales, 30 items with low factor loadings or highest factor loading on the wrong clinical scale were excluded. This resulted in a higher amount of explained variance and improvement of the factor loadings of the remaining items. The reliability and validity of the WPSI scales was satisfactory to good. No clinically relevant associations were found between the WPSI scales and patient and epilepsy characteristics. CONCLUSIONS: The factor structure, reliability, and validity of the Dutch translation of the WPSI are good and comparable to the original English version of Dodrill. The results demonstrate that shortening the WPSI makes the inventory more reliable and the clinical scales less dependent on each other.

Adaptation, Psychological↗
PubMedDate not supplied

[The pilot program in Mexican clinical laboratories. I. The characterization of structure and productivity].

OBJECTIVE: To validate a questionnaire which evaluates the structure of clinical laboratories and to obtain information on its productivity. PARTICIPANTS: A group of 18 laboratories belonging to hospitals of second (N = 15) and third (N = 3) levels of health care. Fifteen participants belong to the public sector and three are first rate private institutions. They are located in the metropolitan area of Mexico City comprising the Federal District (N = 12) and the State of Mexico (N = 6). METHODS: The questionnaire has 12 items which received a 0, 1/2 or 1 score. The maximum possible score for a perfect laboratory as well as for any question is 100. The questionnaire was filled during a visit to the participating hospitals by auditors of the agency of the Ministry of Health in charge of licensing laboratories at a national level. Information covering six months of work was obtained to calculate productivity using number of tests per worker per month. RESULTS: The global score of the 18 participants was 49. The private ones had the highest scores (79 to 96) which was to be expected as they were selected for their high technical and human resources. The five State laboratories had a score above the global mean, but only one of the Federal ones was in this situation. A high interlaboratory variability was observed, i.e. productivity in the highest rated was nine times larger than in the lowest rated. This finding suggests the presence of interlaboratory differences in the criteria used in the collection of productivity information. CONCLUSIONS: This short questionnaire can be used as a first approximation to identify structure deficiencies of the Mexican clinical laboratories.

Efficiency, Organizational↗
PubMed2006

Development and validation of a consistency based multiple structure alignment algorithm.

SUMMARY: We introduce an algorithm that uses the information gained from simultaneous consideration of an entire group of related proteins to create multiple structure alignments (MSTAs). Consistency-based alignment (CBA) first harnesses the information contained within regions that are consistently aligned among a set of pairwise superpositions in order to realign pairs of proteins through both global and local refinement methods. It then constructs a multiple alignment that is maximally consistent with the improved pairwise alignments. We validate CBA's alignments by assessing their accuracy in regions where at least two of the aligned structures contain the same conserved sequence motif. RESULTS: CBA correctly aligns well over 90% of motif residues in superpositions of proteins belonging to the same family or superfamily, and it outperforms a number of previously reported MSTA algorithms.

Algorithms↗
PubMed2004

Preliminary validity and reliability testing of a structured clinical interview for pathological gambling.

The psychometric properties of a clinician-administered, DSM-IV-based, structured clinical interview for pathological gambling (SCI-PG) were examined. Seventy-two consecutive subjects requesting treatment for gambling problems were administered the SCI-PG. Reliability and validity were determined. Classification accuracy was examined using longitudinal course of illness. The SCI-PG demonstrated excellent inter-rater and test-retest reliability. Concurrent validity was observed with the South Oaks Gambling Screen (SOGS). Discriminant validity was observed with measures of anxiety and depression. The SCI-PG demonstrated both high sensitivity and specificity based on longitudinal assessment. The SCI-PG demonstrated excellent reliability and validity in diagnosing PG in subjects presenting with gambling problems. These findings require replication in other groups to examine their generalizability.

Demography↗
PubMed2000

Structure-based sequence alignment for the beta-trefoil subdomain of the clostridial neurotoxin family provides residue level information about the putative ganglioside binding site.

Clostridial neurotoxins embrace a family of extremely potent toxins comprised of tetanus toxin (TeNT) and seven different serotypes of botulinum toxin (BoNT/A-G). The beta-trefoil subdomain of the C-terminal part of the heavy chain (H(C)), responsible for ganglioside binding, is the most divergent region in clostridial neurotoxins with sequence identity as low as 15%. We re-examined the alignment between family sequences within this subdomain, since in this region all alignments published to date show obvious inconsistencies with the beta-trefoil fold. The final alignment was obtained by considering the general constraints imposed by this fold, and homology modeling studies based on the TeNT structure. Recently solved structures of BoNT/A confirm the validity of this structure-based approach. Taking into account biochemical data and crystal structures of TeNT and BoNT/A, we also re-examined the location of the putative ganglioside binding site and, using the new alignment, characterized this site in other BoNT serotypes.

Amino Acid Sequence↗
PubMed1992

Validity of exposure data derived from a structured questionnaire.

It is often convenient to obtain occupational exposure information directly from employees. However, there is little published evidence on the validity of such data. Information from a short, pre-coded, structured questionnaire, administered by non-expert interviewers, was compared with information derived from management in five factories in the printing and plastics industries in England in 1986. Values of sensitivity ranged from 24% to 85% for eight different exposures, and specificity was at least 67% for seven of the eight agents. Those exposures which were described in chemically specific terms tended to have relatively higher specificities but lower sensitivities. Male workers' reports tended to have higher sensitivity but lower specificity compared with those of female workers. Workers who had been employed in the company for more than 10 years were no more accurate than their colleagues. Subjects who reported a phase of subfertility or at least one miscarriage did not have a higher proportion of false positives than the population as a whole, indicating an absence of reporting bias. Major improvements are highly desirable, especially to reduce underreporting of exposures. The use of workers' own names for agents may improve reporting.

Age Factors↗