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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↗
PubMedDate not supplied

Chemical markup, XML, and the World Wide Web. 4. CML schema.

A revision to Chemical Markup Language (CML) is presented as a XML Schema compliant form, modularized into nonchemical and chemical components. STMML contains generic concepts for numeric data and scientific units, while CMLCore retains most of the chemical functionality of the original CML 1.0 and extends it by adding handlers for chemical substances, extended bonding models and names. We propose extension via new namespaced components for chemical queries, reactions, spectra, and computational chemistry. The conformance with XML schemas allows much greater control over datatyping, document validation, and structure.

Journal Article↗
PubMed2001

JSEM: a framework for identifying and evaluating indicators.

There are two issues in indicator development that have not been adequately addressed: (1) how to select an optimal combination of potentially redundant indicators that together best represent an endpoint, given cost constraints; (2) how to identify and evaluate indicators when the endpoint is unmeasured. This paper presents an approach to identifying and evaluating combinations of indicators when the mathematical relationships between the indicators and an endpoint may not be quantified, a limitation common to many ecological assessments. The approach uses the framework of Structural Equation Modeling (SEM), which combines path analysis with measurement models, to formalize available information about potential indicators and to evaluate their potential adequacy for representing an endpoint. Unlike traditional applications of SEM which require data on all variables, our approach---judgement-based SEM (JSEM)--can utilize expert judgement regarding the strengths and shapes of indicator-endpoint relationships. JSEM is applied in two stages. First, a conceptual model that relates variables in a network of direct and indirect linkages is developed, and is used to identify indicators relevant to an endpoint. Second, an index of indicator strength--i.e., the strength of the relationship between the endpoint and a set of indicators--is calculated from estimates of correlation between the modeled variables, and is used to compare alternative sets of indicators. The second stage is most appropriate for large, long-term assessments. Although JSEM is not a statistical technique, basing JSEM on SEM provides a structure for validating the conceptual model and for relining the index of indicator strength as data become available. Our main objective is to contribute to a rigorous and consistent selection of indicators even when knowledge about the ability of indicators to represent an endpoint is limited to expert judgement.

Ecosystem↗
PubMed1997

Do authors of review articles use systematic methods to identify, assess and synthesize information?

PURPOSE: Review articles are an important source of summary information for practising clinicians to assist them in remaining current with the rapidly expanding medical literature. Consequently it is essential that these be of the highest quality. In this study we evaluate, according to published criteria, the methodological quality of review articles (R) including meta-analysis (MA) appearing in a major cancer journal, Journal of Clinical Oncology (JCO), 1983-1995. METHODS: A hand-search of JCO was performed, from the first issue January 1983 through December 1995, to identify R, defined as publications that describe and comment on studies relevant to a specific topic or clinical intervention. Only those dealing with aspects of treatment of human cancer were considered further. Methodological quality was first assessed using 8 criteria proposed by Mulrow, rated independently by two medical oncologists as: specified, unclear or not specified. MA, including studies of dose intensity, were further analyzed according to 23 more detailed criteria proposed by Sacks et al. and rated as adequate, partial or no/unknown compliance. RESULTS: Of 176 review articles, 122 dealt with aspects of treatment of cancer. Compliance with four of Mulrow's eight criteria was generally good, in that 99% clearly stated a purpose, all attempted qualitative synthesis of data. 95% presented a summary and 76% considered future directions. However, in the 106 qualitative reviews (QR), authors rarely gave information on methods of data identification (11.3%), data selection (10.4%) and assessment of validity (8.4%). Structured abstracts seemed to improve the focus and clarity of QR and there was a minor improvement in deficient areas in the later time cohort (1990-1995). Based on 'adequate' compliance with each of the 23 criteria identified by Sacks et al., six dose intensity studies scored 7-12, seven literature data MA scored 10-15 and three individual patient data MA scored 16-18. The highest scores were in the sections relating to prospective design, combinability and statistical analysis. Factors relating to control of bias, sensitivity analysis and application of results were addressed less consistently. CONCLUSIONS: With the exception of MA, the majority of authors contributing reviews to a major cancer journal, JCO, did not use systematic methods to identify, assess and synthesize information. Initiatives such as the Cochrane Collaboration Cancer Network can support and educate clinicians who wish to perform systematic reviews, but quality of reviews would also improve if author, editors and readers systematically applied any of the sets of criteria now available in the literature.

Humans↗
PubMed2000

Progress Testing for Postgraduate Medical Education: a Four-Year Experiment of American College of Osteopathic Surgeons Resident Examinations.

An experiment of progress testing for postgraduate medical education was evaluated for the psychometric properties and evaluation utilities of its outcome. Psychometric analysis emphasized reliability, construct validity, exam structure, and equating quality, while analysis of evaluation value focused on growth trajectories of several cohorts of residents. The analyses concluded that progress testing for postgraduate education was feasible. The value of progress testing for postgraduate medical education assessment was unique and promising.

Journal Article↗
PubMed1999

Linguistic styles: language use as an individual difference.

Can language use reflect personality style? Studies examined the reliability, factor structure, and validity of written language using a word-based, computerized text analysis program. Daily diaries from 15 substance abuse inpatients, daily writing assignments from 35 students, and journal abstracts from 40 social psychologists demonstrated good internal consistency for over 36 language dimensions. Analyses of the best 15 language dimensions from essays by 838 students yielded 4 factors that replicated across written samples from another 381 students. Finally, linguistic profiles from writing samples were compared with Thematic Apperception Test coding, self-reports, and behavioral measures from 79 students and with self-reports of a 5-factor measure and health markers from more than 1,200 students. Despite modest effect sizes, the data suggest that linguistic style is an independent and meaningful way of exploring personality.

Adolescent↗
PubMed2001

Methodological issues in interviewing and using self-report questionnaires with people with mental retardation.

In this article the authors review methodological issues that arise when interviews and self-report questionnaires are used with people with mental retardation and offer suggestions for overcoming some of the difficulties described. Examples are drawn from studies that use qualitative methodology, quantitative studies assessing different question types, and studies reporting on the development of instruments measuring psychiatric symptoms, self-concept, and quality of life. Specific problems that arise with respect to item content (e.g., quantitative judgments, generalizations), question phrasing (e.g., modifiers), response format (e.g., acquiescence, multiple-choice questions), and psychometric properties (factor structure and validity) are discussed. It is argued that because many self-report questionnaires include questions that have been found to be problematic in this population, more attention needs to be paid to establishing the validity of such measures and to clearly defining the population for which the instrument is designed.

Adult↗
PubMed2000

Wine drinking and diet in Italy.

OBJECTIVE: To investigate the relation between wine drinking and intake of selected indicator foods, which may vary in various populations. DESIGN: Cross-sectional analysis of the comparison group of a case- control study. SETTING: A network of teaching and general hospitals from six Italian areas. SUBJECTS: 5642 control subjects (3261 females and 2381 males) aged 20-74 y (median age 58 y), admitted for acute, non-neoplastic conditions unrelated to alcohol consumption. Participation rate was over 95%. INTERVENTION: Trained interviewers collected information using a structured and validated questionnaire. The average intakes of selected food items were computed, together with the multivariate odds ratios (OR) of eating above the median of each food. RESULTS: No appreciable difference in either sex for any food indicator considered (fruit, raw vegetables, cooked vegetables, salad and fish) was observed between abstainers, wine, and other alcoholic beverage drinkers. If anything, female wine drinkers reported less frequently high consumption of salad (OR=0.8) and raw vegetables (OR=0.8), both estimates being of borderline significance. CONCLUSIONS: In no instance did wine drinkers or mixed drinkers (who include a large proportion of wine drinkers, too) show an association with indicators of healthy diet. SPONSORSHIP: Italian Association for Cancer Research, Milan, Italy. European Journal of Clinical Nutrition (2000) 54, 177-179

Adult↗
PubMed2000

Refined and whole grain cereals and the risk of oral, oesophageal and laryngeal cancer.

OBJECTIVE: To investigate the possible differential role of refined and whole grain cereals on the risk of upper digestive and respiratory tract neoplasms. DESIGN: Hospital-based case-control study. SETTING: University Hospital of Lausanne, Switzerland. SUBJECTS: A total of 156 incident cases of cancers of the oral cavity and pharynx, 101 of the oesophagus, 40 of the larynx, and 349 control subjects admitted for a wide spectrum of acute non-neoplastic conditions. INTERVENTION: Trained interviewers collected information using a structured and validated questionnaire. Odds ratios (OR) of various cancers for a tertile increment of intake of refined and whole grains were estimated using unconditional multiple logistic regression. RESULTS: Refined grains were directly related to the risk of cancer of the oral cavity and pharynx (OR=1.9 for the highest tertile), oesophagus (OR=3.7) and larynx (OR=4.0). In contrast, whole grain cereals were protective, with OR of 0.6 for oral cavity and pharynx, 0.3 for oesophagus, and 0.7 for larynx. For the three sites combined, the OR for the highest tertile was 5.7 for refined grains and 0.5 for wholegrains. The trends in risk for refined grains were significant for all sites and their combination, and for wholegrain for oesophageal cancer and all sites. CONCLUSIONS: Even if inference on causality and the biological interpretation remain open to discussion, the present data indicate and further quantify that refined cereals are an unfavourable, but whole grain ones a favourable indicator of the risk of upper aerodigestive and respiratory tract neoplasms.

Adult↗
PubMed2000

Assessment of psychiatric patients' competency to give informed consent: legal safeguard of civil right to autonomous decision-making.

Amendment of the Mental Health and Welfare Law in Japan will limit admission for medical care and protection only for those individuals who are incapable of giving consent to admission. This is a first in the history of the Japanese mental health legislation. By reviewing the law and psychiatric literature, it is argued that: (i) informed consent is a legal transaction that embodies the idea of an individual's right to autonomous decision-making in medical settings; (ii) health professionals have a duty to protect those individuals who cannot decide medical matters because of lack of capacity to do so; (iii) some patients are marginally incompetent so assessment of their competency is essential in protecting patients' civil rights; (iv) in order for a competency assessment to be reliable (and hence fair) the method should be psychometrically sound; (v) at the same time, in order for a competency assessment to be valid, the structure of a competency assessment should match the patient's psychological, cultural, and social background; and (vi) because informed consent is a process rather than a cross-sectional event, a competency assessment should be performed in everyday practice. The use of a brief and semistructured interview to assess patients' competency to give informed consent may meet all of the requirements described.

Decision Making↗
PubMed2001

Lymph nodes in the human female breast: a review of their detection and significance.

Our experience led us to test the hypothesis that lymph nodes are not uncommon within the substance of the human female breast mound. The following specimen types and sources were used to survey the presence of intramammary lymph nodes in the human female breast mound: (1) cadaver breasts; (2) community hospital breast specimens; and (3) university and VA hospital specimens. We found true lymph nodes within and associated with breast specific tissue (ie, tissue that includes duct and gland structures), thereby validating the hypothesis posed. We discuss the significance of these findings in terms of our dominant patient care paradigm (the Triple Test-physical examination, imaging, and fine-needle aspiration [FNA]) and the choice of patient care management options. We conclude the following: lymph nodes occur in any quadrant of the breast mound; recognizing the possibility of intramammary lymph nodes is important when choosing between patient management options; intramammary lymph nodes can be sampled by FNA; intramammary lymph nodes can contain various disease processes; and in the Oregon Health Sciences University Multidisciplinary Breast Clinic, these intramammary lymph nodes are commonly identified by imaging methods and are more likely to be sampled by FNA than either by core or excisional biopsy.

Adult↗
PubMed2001

Clinical outcomes that fetal surgery for myelomeningocele needs to achieve.

INTRODUCTION: The development of techniques to close open neural tube malformations prior to birth has generated great interest and hope for fetal interventions and their outcomes. To plan a randomized trial, as is being discussed at three centres in the United States, the determination of what constitutes a clinically significant improvement in outcome is critical. To date, preliminary observations from two centres suggest that improvements may occur, not in spinal cord function as originally postulated, but in the extent of the hindbrain hernia and the frequency that shunting is required to control hydrocephalus. PURPOSE: The determination of what outcome would constitute an important and clinically significant difference in outcome to be achieved by fetal intervention for myelomeningocele. METHOD: Parents of patients and patients treated in our myelomeningocele clinic were surveyed using a structured and validated tool. From the perspective of a recommendation to a close friend or family member, the interviewees were asked to quantify on a scale from 0 to 100 the chance of specific outcomes (need for a shunt, need for a wheelchair, change of urinary incontinence) that a fetal operation would need to predictably achieve. RESULTS: Responses were obtained from 77 patients/families. The fifty percentile response in each study dimension was as follows: the chance of needing a shunt was 12 % (range 0 - 50 %), the chance of needing a wheelchair was 8 % and the chance of being incontinent was 5 % (range 0 - 25 %). CONCLUSIONS: Fetal interventions will have to achieve significant improvements in the control of hydrocephalus, mobilization and continence over postnatal treatment to be justified.

Adult↗
PubMed2003

[Intraoperative histological sections in obstetric brachial plexus lesions--comparison of macroscopic appearance, HE staining and toluidine blue staining].

In brachial plexus lesions and their revision, evaluation of nerve stumps is very important for the reconstructive strategy. We intraoperatively perform cryostat sections, Haematoxilin-Eosin (HE) stained, and compare the clinical appearance of the nerves to the microscopic results. Toluidine blue staining is later used to validate the structural details. Intraneural fibrosis can be traced safely with both staining methods, in root avulsions a histology is helpful, too. For more proximal, intraforaminal lesions semithin section stained with toluidine-blue are less informative than are HE-stained cryostat sections. In these lesions the clinical control by electrical stimulation and evoked potentials is superior.

Adult↗
PubMed2001

A membrane-distal segment of the integrin alpha IIb cytoplasmic domain regulates integrin activation.

Previous evidence suggests that interactions between integrin cytoplasmic domains regulate integrin activation. We have constructed and validated recombinant structural mimics of the heterodimeric alpha(IIb)beta(3) cytoplasmic domain. The mimics elicited polyclonal antibodies that recognize a combinatorial epitope(s) formed in mixtures of the alpha(IIb) and beta(3) cytoplasmic domains but not present in either isolated tail. This epitope(s) is present within intact alpha(IIb)beta(3), indicating that interaction between the tails can occur in the native integrin. Furthermore, the combinatorial epitope(s) is also formed by introducing the activation-blocking beta(3)(Y747A) mutation into the beta(3) tail. A membrane-distal heptapeptide sequence in the alpha(IIb) tail ((997)RPPLEED) is responsible for this effect on beta(3). Membrane-permeant palmitoylated peptides, containing this alpha(IIb) sequence, specifically blocked alpha(IIb)beta(3) activation in platelets. Thus, this region of the alpha(IIb) tail causes the beta(3) tail to resemble that of beta(3)(Y747A) and suppresses activation of the integrin.

Amino Acid Sequence↗
PubMed2000

Structure of an 11-mer DNA duplex containing the carbocyclic nucleotide analog: 2'-deoxyaristeromycin.

2'-deoxyaristeromycin (dAr) is a nucleoside analogue that is resistant to the action of DNA glycosylases. High-resolution NMR spectroscopy and molecular dynamics simulations were used to determine the three-dimensional structure of an 11-mer DNA containing a single dAr.T base pair at its center. Analysis of the spectra revealed the existence of a right-handed duplex in solution, stabilized by Watson-Crick hydrogen bonding and base-stacking interactions. The carbocyclic sugar adopted a C1'-exo conformation and sugars of the 3'-flanking base pair had puckers in the O4'-endo range. The dAr.T base pair was mildly propeller twisted, and the dAr analogue showed a positive roll with the 3'-flanking base. Our findings indicate that the observed resistance of dAr-containing oligodeoxynucleotides to the catalytic action of DNA glycosylases relates to its electronic properties rather than structure, and validate the use of dAr and related carbocyclic nucleoside analogues for biological and structure/function relationship studies.

Computer Simulation↗
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↗