PMID- 10984461 OWN - NLM STAT- MEDLINE DA - 20001016 DCOM- 20001016 LR - 20041117 PUBM- Print IS - 1067-5027 VI - 7 IP - 5 DP - 2000 Sep-Oct TI - Opportunities at the intersection of bioinformatics and health informatics: a case study. PG - 431-8 AB - This paper provides a "viewpoint discussion" based on a presentation made to the 2000 Symposium of the American College of Medical Informatics. It discusses potential opportunities for researchers in health informatics to become involved in the rapidly growing field of bioinformatics, using the activities of the Yale Center for Medical Informatics as a case study. One set of opportunities occurs where bioinformatics research itself intersects with the clinical world. Examples include the correlations between individual genetic variation with clinical risk factors, disease presentation, and differential response to treatment; and the implications of including genetic test results in the patient record, which raises clinical decision support issues as well as legal and ethical issues. A second set of opportunities occurs where bioinformatics research can benefit from the technologic expertise and approaches that informaticians have used extensively in the clinical arena. Examples include database organization and knowledge representation, data mining, and modeling and simulation. Microarray technology is discussed as a specific potential area for collaboration. Related questions concern how best to establish collaborations with bioscientists so that the interests and needs of both sets of researchers can be met in a synergistic fashion, and the most appropriate home for bioinformatics in an academic medical center. AD - Yale University, New Haven, Connecticut, USA. FAU - Miller, P L AU - Miller PL LA - eng GR - G08-LM-05583/LM/NLM PT - Journal Article PL - UNITED STATES TA - J Am Med Inform Assoc JID - 9430800 SB - IM CIN - J Am Med Inform Assoc. 2000 Sep-Oct;7(5):512-6. PMID: 10984470 MH - *Computational Biology/organization & administration MH - Cooperative Behavior MH - Decision Support Systems, Clinical MH - Gene Expression MH - Genome MH - *Medical Informatics/organization & administration MH - Neurosciences MH - Research Support, U.S. Gov't, P.H.S. EDAT- 2000/09/14 11:00 MHDA- 2000/10/21 11:01 PST - ppublish SO - J Am Med Inform Assoc 2000 Sep-Oct;7(5):431-8. PMID- 10984462 OWN - NLM STAT- MEDLINE DA - 20001016 DCOM- 20001016 LR - 20041117 PUBM- Print IS - 1067-5027 VI - 7 IP - 5 DP - 2000 Sep-Oct TI - The interactions between clinical informatics and bioinformatics: a case study. PG - 439-43 AB - For the past decade, Stanford Medical Informatics has combined clinical informatics and bioinformatics research and training in an explicit way. The interest in applying informatics techniques to both clinical problems and problems in basic science can be traced to the Dendral project in the 1960s. Having bioinformatics and clinical informatics in the same academic unit is still somewhat unusual and can lead to clashes of clinical and basic science cultures. Nevertheless, the benefits of this organization have recently become clear, as the landscape of academic medicine in the next decades has begun to emerge. The author provides examples of technology transfer between clinical informatics and bioinformatics that illustrate how they complement each other. AD - Stanford University, Stanford, California 94305-5479, USA. russ.altman@stanford.edu FAU - Altman, R B AU - Altman RB LA - eng GR - GM-61374/GM/NIGMS GR - LM-05652/LM/NLM GR - LM-06422/LM/NLM PT - Journal Article PL - UNITED STATES TA - J Am Med Inform Assoc JID - 9430800 SB - IM CIN - J Am Med Inform Assoc. 2000 Sep-Oct;7(5):512-6. PMID: 10984470 MH - Academic Medical Centers/organization & administration MH - California MH - *Computational Biology/education/methods/organization & administration MH - Cooperative Behavior MH - *Medical Informatics/organization & administration MH - Research Support, Non-U.S. Gov't MH - Research Support, U.S. Gov't, Non-P.H.S. MH - Research Support, U.S. Gov't, P.H.S. MH - *Technology Transfer EDAT- 2000/09/14 11:00 MHDA- 2000/10/21 11:01 PST - ppublish SO - J Am Med Inform Assoc 2000 Sep-Oct;7(5):439-43. PMID- 10984463 OWN - NLM STAT- MEDLINE DA - 20001016 DCOM- 20001016 LR - 20001218 PUBM- Print IS - 1067-5027 VI - 7 IP - 5 DP - 2000 Sep-Oct TI - Electronic health record meets digital library: a new environment for achieving an old goal. PG - 444-52 AB - Linking the electronic health record to the digital library is a Web-era reformulation of the long-standing informatics goal of seamless integration of automated clinical data and relevant knowledge-based information to support informed decisions. The spread of the Internet, the development of the World Wide Web, and converging format standards for electronic health data and digital publications make effective linking increasingly feasible. Some existing systems link electronic health data and knowledge-based information in limited settings or limited ways. Yet many challenging informatics research problems remain to be solved before flexible and seamless linking becomes a reality and before systems become capable of delivering the specific piece of information needed at the time and place a decision must be made. Connecting the electronic health record to the digital library also requires positive resolution of important policy issues, including health data privacy, government encouragement of high-speed communications, electronic intellectual property rights, and standards for health data and for digital libraries. Both the research problems and the policy issues should be important priorities for the field of medical informatics. AD - Library of Medicine, Bethesda, Maryland 20894, USA. blh@nlm.nih.gov FAU - Humphreys, B L AU - Humphreys BL LA - eng PT - Journal Article PL - UNITED STATES TA - J Am Med Inform Assoc JID - 9430800 SB - IM MH - *Internet/standards MH - Libraries/*organization & administration/standards MH - Medical Records Systems, Computerized/*organization & administration MH - Publishing/*organization & administration/standards MH - Systems Integration EDAT- 2000/09/14 11:00 MHDA- 2000/10/21 11:01 PST - ppublish SO - J Am Med Inform Assoc 2000 Sep-Oct;7(5):444-52. PMID- 10984464 OWN - NLM STAT- MEDLINE DA - 20001016 DCOM- 20001016 LR - 20001218 PUBM- Print IS - 1067-5027 VI - 7 IP - 5 DP - 2000 Sep-Oct TI - Improving clinical communication: a view from psychology. PG - 453-61 AB - Recent research has studied the communication behaviors of clinical hospital workers and observed a tendency for these workers to use communication behaviors that were often inefficient. Workers were observed to favor synchronous forms of communication, such as telephone calls and chance face-to-face meetings with colleagues, even when these channels were not effective. Synchronous communication also contributes to a highly interruptive working environment, increasing the potential for clinical errors to be made. This paper reviews these findings from a cognitive psychological perspective, focusing on current understandings of how human memory functions and on the potential consequences of interruptions on the ability to work effectively. It concludes by discussing possible communication technology interventions that could be introduced to improve the clinical communication environment and suggests directions for future research. AD - Hewlett-Packard Research Laboratories, Bristol, England (JSP). jsp@hplb.hpl.hp.com FAU - Parker, J AU - Parker J FAU - Coiera, E AU - Coiera E LA - eng PT - Journal Article PL - UNITED STATES TA - J Am Med Inform Assoc JID - 9430800 SB - IM MH - Attitude of Health Personnel MH - Cognitive Science MH - *Communication MH - Memory MH - Personnel, Hospital/*psychology EDAT- 2000/09/14 11:00 MHDA- 2000/10/21 11:01 PST - ppublish SO - J Am Med Inform Assoc 2000 Sep-Oct;7(5):453-61. PMID- 10984465 OWN - NLM STAT- MEDLINE DA - 20001016 DCOM- 20001016 LR - 20041117 PUBM- Print IS - 1067-5027 VI - 7 IP - 5 DP - 2000 Sep-Oct TI - Comparative evaluation of three continuous speech recognition software packages in the generation of medical reports. PG - 462-8 AB - OBJECTIVE: To compare out-of-box performance of three commercially available continuous speech recognition software packages: IBM ViaVoice 98 with General Medicine Vocabulary; Dragon Systems NaturallySpeaking Medical Suite, version 3.0; and L&H Voice Xpress for Medicine, General Medicine Edition, version 1.2. DESIGN: Twelve physicians completed minimal training with each software package and then dictated a medical progress note and discharge summary drawn from actual records. MEASUREMENTS: Errors in recognition of medical vocabulary, medical abbreviations, and general English vocabulary were compared across packages using a rigorous, standardized approach to scoring. RESULTS: The IBM software was found to have the lowest mean error rate for vocabulary recognition (7.0 to 9.1 percent) followed by the L&H software (13.4 to 15.1 percent) and then Dragon software (14.1 to 15.2 percent). The IBM software was found to perform better than both the Dragon and the L&H software in the recognition of general English vocabulary and medical abbreviations. CONCLUSION: This study is one of a few attempts at a robust evaluation of the performance of continuous speech recognition software. Results of this study suggest that with minimal training, the IBM software outperforms the other products in the domain of general medicine; however, results may vary with domain. Additional training is likely to improve the out-of-box performance of all three products. Although the IBM software was found to have the lowest overall error rate, successive generations of speech recognition software are likely to surpass the accuracy rates found in this investigation. AD - Boston Veterans Administration Medical Center, Boston, Massachusetts 02130, USA. devine.eric@boston.va.gov FAU - Devine, E G AU - Devine EG FAU - Gaehde, S A AU - Gaehde SA FAU - Curtis, A C AU - Curtis AC LA - eng PT - Journal Article PL - UNITED STATES TA - J Am Med Inform Assoc JID - 9430800 SB - IM MH - Comparative Study MH - Evaluation Studies MH - Humans MH - *Medical Records Systems, Computerized MH - Research Support, U.S. Gov't, Non-P.H.S. MH - *Software MH - *Speech EDAT- 2000/09/14 11:00 MHDA- 2000/10/21 11:01 PST - ppublish SO - J Am Med Inform Assoc 2000 Sep-Oct;7(5):462-8. PMID- 10984466 OWN - NLM STAT- MEDLINE DA - 20001016 DCOM- 20001016 LR - 20041117 PUBM- Print IS - 1067-5027 VI - 7 IP - 5 DP - 2000 Sep-Oct TI - Variables that may enhance medical students' perceived preparedness for computer-based testing. PG - 469-74 AB - OBJECTIVE: To identify variables that may enhance medical student's preparedness for computer-based administration of the United States Medical Licensing Examination (USMLE). DESIGN: A cross-sectional survey of 301 medical students who completed a self-administered questionnaire. MEASUREMENTS: The questionnaire was designed to obtain information about students' computer resources, personal experience with computers, computer expertise, opinions about computers, experience with computer-based testing, perceived preparedness for the computer-based USMLE, and demographic variables. Variables related to students' perceived preparedness for the computer-based USMLE were identified by ordinal logistic regression. RESULTS: A significant regression model yielded four significant predictors: perceived preparedness for USMLE content (P: < 0.0001), opinions about computers (P: < 0.0012), gender (P: < 0.0001), and a gender by computer-based testing experience interaction (P: < 0. 0004). Computer resources, personal experience with computers, computer expertise, age, race, and year of medical school were not significant predictors. CONCLUSION: Students' perceived preparedness for computer-based administration of high-stakes examinations may be facilitated by preparing them for examination content, by enhancing their opinions about computers, and by increasing their computer-based testing experiences. AD - East Carolina University, Greenville, North Carolina, USA. dlynch@med-scape.com FAU - Lynch, D C AU - Lynch DC FAU - Whitley, T W AU - Whitley TW FAU - Emmerling, D A AU - Emmerling DA FAU - Brinn, J E AU - Brinn JE LA - eng PT - Journal Article PL - UNITED STATES TA - J Am Med Inform Assoc JID - 9430800 SB - IM MH - Attitude to Computers MH - *Computer Literacy MH - Computer User Training MH - Continental Population Groups MH - Cross-Sectional Studies MH - Educational Measurement/*methods MH - Female MH - Humans MH - Licensure, Medical MH - Logistic Models MH - Male MH - Questionnaires MH - Sex Factors MH - *Students, Medical/psychology MH - United States EDAT- 2000/09/14 11:00 MHDA- 2000/10/21 11:01 PST - ppublish SO - J Am Med Inform Assoc 2000 Sep-Oct;7(5):469-74. PMID- 10984467 OWN - NLM STAT- MEDLINE DA - 20001016 DCOM- 20001016 LR - 20041117 PUBM- Print IS - 1067-5027 VI - 7 IP - 5 DP - 2000 Sep-Oct TI - Exploring performance issues for a clinical database organized using an entity-attribute-value representation. PG - 475-87 AB - BACKGROUND: The entity-attribute-value representation with classes and relationships (EAV/CR) provides a flexible and simple database schema to store heterogeneous biomedical data. In certain circumstances, however, the EAV/CR model is known to retrieve data less efficiently than conventionally based database schemas. OBJECTIVE: To perform a pilot study that systematically quantifies performance differences for database queries directed at real-world microbiology data modeled with EAV/CR and conventional representations, and to explore the relative merits of different EAV/CR query implementation strategies. METHODS: Clinical microbiology data obtained over a ten-year period were stored using both database models. Query execution times were compared for four clinically oriented attribute-centered and entity-centered queries operating under varying conditions of database size and system memory. The performance characteristics of three different EAV/CR query strategies were also examined. RESULTS: Performance was similar for entity-centered queries in the two database models. Performance in the EAV/CR model was approximately three to five times less efficient than its conventional counterpart for attribute-centered queries. The differences in query efficiency became slightly greater as database size increased, although they were reduced with the addition of system memory. The authors found that EAV/CR queries formulated using multiple, simple SQL statements executed in batch were more efficient than single, large SQL statements. CONCLUSION: This paper describes a pilot project to explore issues in and compare query performance for EAV/CR and conventional database representations. Although attribute-centered queries were less efficient in the EAV/CR model, these inefficiencies may be addressable, at least in part, by the use of more powerful hardware or more memory, or both. AD - Yale University, New Haven, Connecticut, USA. FAU - Chen, R S AU - Chen RS FAU - Nadkarni, P AU - Nadkarni P FAU - Marenco, L AU - Marenco L FAU - Levin, F AU - Levin F FAU - Erdos, J AU - Erdos J FAU - Miller, P L AU - Miller PL LA - eng GR - G08-LM05583/LM/NLM GR - T15-LM07056/LM/NLM GR - U01-CA78266/CA/NCI PT - Journal Article PL - UNITED STATES TA - J Am Med Inform Assoc JID - 9430800 SB - IM MH - Comparative Study MH - *Database Management Systems MH - Databases/organization & administration MH - *Databases, Factual MH - Information Storage and Retrieval/*methods MH - Microbiology MH - Pilot Projects MH - Research Support, U.S. Gov't, P.H.S. EDAT- 2000/09/14 11:00 MHDA- 2000/10/21 11:01 PST - ppublish SO - J Am Med Inform Assoc 2000 Sep-Oct;7(5):475-87. PMID- 10984468 OWN - NLM STAT- MEDLINE DA - 20001016 DCOM- 20001016 LR - 20041117 PUBM- Print IS - 1067-5027 VI - 7 IP - 5 DP - 2000 Sep-Oct TI - GEM: a proposal for a more comprehensive guideline document model using XML. PG - 488-98 AB - OBJECTIVE: To develop a guideline document model that includes a sufficiently broad set of concepts to be useful throughout the guideline life cycle. DESIGN: Current guideline document models are limited in that they reflect the specific orientation of the stakeholder who created them; thus, developers and disseminators often provide few constructs for conceptualizing recommendations, while implementers de-emphasize concepts related to establishing guideline validity. The authors developed the Guideline Elements Model (GEM) using XML to better represent the heterogeneous knowledge contained in practice guidelines. Core constructs were derived from the Institute of Medicine's Guideline Appraisal Instrument, the National Guideline Clearinghouse, and the augmented decision table guideline representation. These were supplemented by additional concepts from a literature review. RESULTS: The GEM hierarchy includes more than 100 elements. Major concepts relate to a guideline's identity, developer, purpose, intended audience, method of development, target population, knowledge components, testing, and review plan. Knowledge components in guideline documents include recommendations (which in turn comprise conditionals and imperatives), definitions, and algorithms. CONCLUSION: GEM is more comprehensive than existing models and is expressively adequate to represent the heterogeneous information contained in guidelines. Use of XML contributes to a flexible, comprehensible, shareable, and reusable knowledge representation that is both readable by human beings and processible by computers. AD - Yale University, New Haven, Connecticut, USA. richard.shiffman@yale.edu FAU - Shiffman, R N AU - Shiffman RN FAU - Karras, B T AU - Karras BT FAU - Agrawal, A AU - Agrawal A FAU - Chen, R AU - Chen R FAU - Marenco, L AU - Marenco L FAU - Nath, S AU - Nath S LA - eng GR - 1-R29-LM-05552/LM/NLM GR - T15-LM07056/LM/NLM PT - Journal Article PL - UNITED STATES TA - J Am Med Inform Assoc JID - 9430800 SB - IM MH - Algorithms MH - *Hypermedia MH - Models, Theoretical MH - *Practice Guidelines MH - *Programming Languages MH - Research Support, Non-U.S. Gov't MH - Research Support, U.S. Gov't, P.H.S. EDAT- 2000/09/14 11:00 MHDA- 2000/10/21 11:01 PST - ppublish SO - J Am Med Inform Assoc 2000 Sep-Oct;7(5):488-98. PMID- 10984469 OWN - NLM STAT- MEDLINE DA - 20001016 DCOM- 20001016 LR - 20001218 PUBM- Print IS - 1067-5027 VI - 7 IP - 5 DP - 2000 Sep-Oct TI - Corpus-based statistical screening for phrase identification. PG - 499-511 AB - PURPOSE: The authors study the extraction of useful phrases from a natural language database by statistical methods. The aim is to leverage human effort by providing preprocessed phrase lists with a high percentage of useful material. METHOD: The approach is to develop six different scoring methods that are based on different aspects of phrase occurrence. The emphasis here is not on lexical information or syntactic structure but rather on the statistical properties of word pairs and triples that can be obtained from a large database. MEASUREMENTS: The Unified Medical Language System (UMLS) incorporates a large list of humanly acceptable phrases in the medical field as a part of its structure. The authors use this list of phrases as a gold standard for validating their methods. A good method is one that ranks the UMLS phrases high among all phrases studied. Measurements are 11-point average precision values and precision-recall curves based on the rankings. RESULT: The authors find of six different scoring methods that each proves effective in identifying UMLS quality phrases in a large subset of MEDLINE. These methods are applicable both to word pairs and word triples. All six methods are optimally combined to produce composite scoring methods that are more effective than any single method. The quality of the composite methods appears sufficient to support the automatic placement of hyperlinks in text at the site of highly ranked phrases. CONCLUSION: Statistical scoring methods provide a promising approach to the extraction of useful phrases from a natural language database for the purpose of indexing or providing hyperlinks in text. AD - National Library of Medicine, Bethesda, Maryland 20894, USA. wonkim@ncbi.nlm.nih.gov FAU - Kim, W AU - Kim W FAU - Wilbur, W J AU - Wilbur WJ LA - eng PT - Journal Article PL - UNITED STATES TA - J Am Med Inform Assoc JID - 9430800 SB - IM MH - *Abstracting and Indexing MH - *Hypermedia MH - Information Storage and Retrieval/*methods MH - MEDLINE MH - *Natural Language Processing MH - Statistics MH - *Unified Medical Language System MH - Vocabulary, Controlled EDAT- 2000/09/14 11:00 MHDA- 2000/10/21 11:01 PST - ppublish SO - J Am Med Inform Assoc 2000 Sep-Oct;7(5):499-511. PMID- 10984470 OWN - NLM STAT- MEDLINE DA - 20001016 DCOM- 20001016 LR - 20041117 PUBM- Print IS - 1067-5027 VI - 7 IP - 5 DP - 2000 Sep-Oct TI - Bioinformatics and clinical informatics: the imperative to collaborate. PG - 512-6 FAU - Kohane, I S AU - Kohane IS LA - eng PT - Comment PT - Editorial PL - UNITED STATES TA - J Am Med Inform Assoc JID - 9430800 SB - IM CON - J Am Med Inform Assoc. 2000 Sep-Oct;7(5):431-8. PMID: 10984461 CON - J Am Med Inform Assoc. 2000 Sep-Oct;7(5):439-43. PMID: 10984462 MH - *Computational Biology/organization & administration MH - Confidentiality MH - Cooperative Behavior MH - Costs and Cost Analysis MH - False Positive Reactions MH - Genome, Human MH - Humans MH - *Medical Informatics/organization & administration MH - Vocabulary, Controlled EDAT- 2000/09/14 11:00 MHDA- 2000/10/21 11:01 PST - ppublish SO - J Am Med Inform Assoc 2000 Sep-Oct;7(5):512-6. PMID- 11818032 OWN - NLM STAT- MEDLINE DA - 20021119 DCOM- 20021125 LR - 20041117 PUBM- Print-Electronic IS - 1471-2091 VI - 3 IP - 1 DP - 2002 TI - Kinetic comparison of tissue non-specific and placental human alkaline phosphatases expressed in baculovirus infected cells: application to screening for Down's syndrome. PG - 2 AB - BACKGROUND: In humans, there are four alkaline phosphatases, and each form exhibits a characteristic pattern of tissue distribution. The availability of an easy method to reveal their activity has resulted in large amount of data reporting correlations between variations in activity and illnesses. For example, alkaline phosphatase from neutrophils of mothers pregnant with a trisomy 21 fetus (Down's syndrome) displays significant differences both in its biochemical and immunological properties, and in its affinity for some specific inhibitors. RESULTS: To analyse these differences, the biochemical characteristics of two isozymes (non specific and placental alkaline phosphatases) were expressed in baculovirus infected cells. Comparative analysis of the two proteins allowed us to estimate the kinetic constants of denaturation and sensitivity to two inhibitors (L-p-bromotetramisole and thiophosphate), allowing better discrimination between the two enzymes. These parameters were then used to estimate the ratio of the two isoenzymes in neutrophils of pregnant mothers with or without a trisomy 21 fetus. It appeared that the placental isozyme represented 13% of the total activity of neutrophils of non pregnant women. This proportion did not significantly increase with normal pregnancy. By contrast, in pregnancies with trisomy 21 fetus, the proportion reached 60-80% of activity. CONCLUSION: Over-expression of the placental isozyme compared with the tissue-nonspecific form in neutrophils of mother with a trisomy 21 fetus may explain why the characteristics of the alkaline phosphatase in these cells is different from normal. Application of this knowledge could improve the potential of using alkaline phosphatase measurements to screen for Down's syndrome. AD - Laboratoire de Synthese et Physicochimie de Molecules d'Interet Biologique, Universite Paul Sabatier (UMR 5068), 118 route de Narbonne, 31 062, Toulouse, France. denier@cict.fr FAU - Denier, Colette C AU - Denier CC FAU - Brisson-Lougarre, Andree A AU - Brisson-Lougarre AA FAU - Biasini, Ghislaine G AU - Biasini GG FAU - Grozdea, Jean J AU - Grozdea JJ FAU - Fournier, Didier D AU - Fournier DD LA - eng PT - Journal Article DEP - 20020115 PL - England TA - BMC Biochem JID - 101084098 RN - 0 (Enzyme Inhibitors) RN - 0 (Isoenzymes) RN - 0 (Nitrophenols) RN - 0 (Organophosphorus Compounds) RN - 0 (Phosphates) RN - 0 (carcinoplacental isoenzymes) RN - 13598-51-1 (thiophosphoric acid) RN - 330-13-2 (nitrophenylphosphate) RN - 5036-02-2 (Tetramisole) RN - 6646-46-4 (4-bromotetramisole) RN - EC 3.1.3.1 (Alkaline Phosphatase) SB - IM MH - Alkaline Phosphatase/*analysis/genetics/metabolism MH - Baculoviridae/genetics MH - Comparative Study MH - Down Syndrome/diagnosis MH - Enzyme Inhibitors/chemistry/pharmacology MH - Enzyme Stability MH - Enzyme Tests MH - Female MH - Humans MH - Isoenzymes/*analysis/genetics/metabolism MH - Kinetics MH - Neutrophils/enzymology MH - Nitrophenols/chemistry/metabolism MH - Organophosphorus Compounds/chemistry/metabolism MH - Phosphates/chemistry/pharmacology MH - Placenta/*enzymology MH - Pregnancy MH - Protein Denaturation MH - Research Support, Non-U.S. Gov't MH - Tetramisole/*analogs & derivatives/chemistry/pharmacology EDAT- 2002/01/31 10:00 MHDA- 2002/11/26 04:00 PHST- 2001/08/23 [received] PHST- 2002/01/15 [accepted] PHST- 2002/01/15 [aheadofprint] PST - ppublish SO - BMC Biochem 2002;3(1):2. Epub 2002 Jan 15. PMID- 11825341 OWN - NLM STAT- MEDLINE DA - 20021119 DCOM- 20021125 LR - 20041117 PUBM- Print-Electronic IS - 1471-2091 VI - 3 IP - 1 DP - 2002 TI - Decreased insulin binding to mononuclear leucocytes and erythrocytes from dogs after S-nitroso-N-acetypenicillamine administration. PG - 1 AB - BACKGROUND: Nitric oxide (NO) and oxygen free-radicals play an important part in the destruction of beta-cells in auto- immune diabetes although the precise mechanism of interaction is still not known. This study was designed to examine any possible diabetogenic effect of NO by investigating any differences in cellular binding of insulin to its receptor on the cell membranes of erythrocytes and mononuclear leucocytes of dogs treated with the NO donor, S-nitroso-N-acetylpenicillamine (SNAP) and controls treated with captopril. RESULTS: The result obtained showed decreased binding of insulin to its receptor on the cell membranes of erythrocytes and mononuclear leucocytes. Mononuclear leucocytes from SNAP-treated dogs had decreased ability to bind insulin (16.30 +/- 1.24 %) when compared to mononuclear leucocytes from captopril-treated controls (20.30 +/- 1.93 %). Similar results were obtained for erythrocytes from dogs treated with SNAP (27.20 +/- 1.33 %) compared with dogs treated with captopril (34.70 +/- 3.58 %). Scatchard analysis demonstrated that this decrease in insulin binding was accounted for by a decrease in insulin receptor sites per cell, with mononuclear leucocytes of SNAP-treated dogs having 55 % less insulin receptor sites per cell compared with those of captopril-treated controls (P < 0.05). Average affinity and kinetic analysis revealed a 35 % decrease in the average receptor affinity, with mononuclear leucocytes from captopril-treated controls having an empty site affinity of 12.36 +/- 1.12 x 10(-8) M(-1) compared with 9.64 +/- 0.11 x 10(-8) M(-1) in SNAP-treated dogs (P < 0.05). CONCLUSION: These results suggest that acute alteration of the insulin receptor on the membranes of mononuclear leucocytes and erythrocytes occurred in dogs treated with S-nitroso-N-acetylpenicillamine. These findings suggest the first evidence of the novel role of NO as a modulator of insulin binding and the involvement of NO in the aetiology of diabetes mellitus. AD - Department of Basic Medical Sciences, University of the West Indies, Kingston, Jamaica. dmcgrowd@yahoo.com FAU - McGrowder, Donovan AU - McGrowder D FAU - Ragoobirsingh, Dalip AU - Ragoobirsingh D FAU - Dasgupta, Tara AU - Dasgupta T LA - eng PT - Journal Article DEP - 20020102 PL - England TA - BMC Biochem JID - 101084098 RN - 0 (Nitric Oxide Donors) RN - 11061-68-0 (Insulin) RN - 62571-86-2 (Captopril) RN - 79032-48-7 (S-Nitroso-N-Acetylpenicillamine) RN - EC 2.7.1.112 (Receptor, Insulin) SB - IM MH - Animals MH - Binding, Competitive MH - Captopril/pharmacology MH - Cell Membrane/metabolism MH - Dogs MH - Erythrocytes/drug effects/metabolism MH - Female MH - Insulin/*metabolism MH - Kinetics MH - Leukocytes, Mononuclear/drug effects/metabolism MH - Male MH - Nitric Oxide Donors/*pharmacology MH - Receptor, Insulin/*metabolism MH - Research Support, Non-U.S. Gov't MH - S-Nitroso-N-Acetylpenicillamine/*pharmacology EDAT- 2002/02/05 10:00 MHDA- 2002/11/26 04:00 PHST- 2001/08/06 [received] PHST- 2002/01/02 [accepted] PHST- 2002/01/02 [aheadofprint] PST - ppublish SO - BMC Biochem 2002;3(1):1. Epub 2002 Jan 2. PMID- 11825346 OWN - NLM STAT- MEDLINE DA - 20030415 DCOM- 20030424 LR - 20041117 PUBM- Print-Electronic IS - 1472-6963 VI - 2 IP - 1 DP - 2002 TI - Quality and methods of developing practice guidelines. PG - 1 AB - BACKGROUND: It is not known whether there are differences in the quality and recommendations between evidence-based (EB) and consensus-based (CB) guidelines. We used breast cancer guidelines as a case study to assess for these differences. METHODS: Five different instruments to evaluate the quality of guidelines were identified by a literature search. We also searched MEDLINE and the Internet to locate 8 breast cancer guidelines. These guidelines were classified in three categories: evidence based, consensus based and consensus based with no explicit consideration of evidence (CB-EB). Each guideline was evaluated by three of the authors using each of the instruments. For each guideline we assessed the agreement among 14 decision points which were selected from the NCCN (National Cancer Comprehensive Network) guidelines algorithm. For each decision point we recorded the level of the quality of the information used to support it. A regression analysis was performed to assess if the percentage of high quality evidence used in the guidelines development was related to the overall quality of the guidelines. RESULTS: Three guidelines were classified as EB, three as CB-EB and two as CB. The EB guidelines scored better than CB, with the CB-EB scoring in the middle among all instruments for guidelines quality assessment. No major disagreement in recommendations was detected among the guidelines regardless of the method used for development, but the EB guidelines had a better agreement with the benchmark guideline for any decision point. When the source of evidence used to support decision were of high quality, we found a higher level of full agreement among the guidelines' recommendations. Up to 94% of variation in the quality score among guidelines could be explained by the quality of evidence used for guidelines development. CONCLUSION: EB guidelines have a better quality than CB guidelines and CB-EB guidelines. Explicit use of high quality evidence can lead to a better agreement among recommendations. However, no major disagreement among guidelines was noted regardless of the method for their development. AD - H Lee Moffitt Cancer Center and Research institute, the University of South Florida, Tampa, FL, USA. crusehh@moffitt.usf.edu FAU - Cruse, Hugh AU - Cruse H FAU - Winiarek, Magdalena AU - Winiarek M FAU - Marshburn, Jan AU - Marshburn J FAU - Clark, Otavio AU - Clark O FAU - Djulbegovic, Benjamin AU - Djulbegovic B LA - eng PT - Evaluation Studies PT - Journal Article DEP - 20020111 PL - England TA - BMC Health Serv Res JID - 101088677 SB - IM MH - Algorithms MH - Benchmarking MH - Breast Neoplasms/*therapy MH - Comparative Study MH - *Consensus MH - *Evidence-Based Medicine MH - Female MH - Humans MH - Observer Variation MH - Peer Review, Research MH - Practice Guidelines/*standards MH - Quality Control MH - Regional Medical Programs/standards MH - Reproducibility of Results MH - United States EDAT- 2002/02/05 10:00 MHDA- 2003/04/25 05:00 PHST- 2001/10/20 [received] PHST- 2002/01/11 [accepted] PHST- 2002/01/11 [aheadofprint] PST - ppublish SO - BMC Health Serv Res 2002;2(1):1. Epub 2002 Jan 11. PMID- 11825347 OWN - NLM STAT- MEDLINE DA - 20030415 DCOM- 20030424 LR - 20041117 PUBM- Print-Electronic IS - 1472-6963 VI - 2 IP - 1 DP - 2002 TI - Resource use data by patient report or hospital records: do they agree? PG - 2 AB - BACKGROUND: Economic evaluations alongside clinical trials are becoming increasingly common. Cost data are often collected through the use of postal questionnaires; however, the accuracy of this method is uncertain. We compared postal questionnaires with hospital records for collecting data on physiotherapy service use. METHODS: As part of a randomised trial of orthopaedic medicine compared with orthopaedic surgery we collected physiotherapy use data on a group of patients from retrospective postal questionnaires and from hospital records. RESULTS: 315 patients were referred for physiotherapy. Hospital data on attendances was available for 30% (n = 96), compared with 48% (n = 150) of patients completing questionnaire data (95% Cl for difference = 10% to 24%); 19% (n = 59) had data available from both sources. The two methods produced an intraclass correlation coefficient of 0.54 (95% Cl 0.31 to 0.70). However, the two methods produced significantly different estimates of resource use with patient self report recalling a mean of 1.3 extra visits (95% Cl 0.4 to 2.2) compared with hospital records. CONCLUSIONS: Using questionnaires in this study produced data on a greater number of patients compared with examination of hospital records. However, the two data sources did differ in the quantity of physiotherapy used and this should be taken into account in any analysis. AD - Health Economics Research Group, Brunel University, Uxbridge, Middlesex, UK. hesradk@brunel.ac.uk FAU - Kennedy, Andrew D M AU - Kennedy AD FAU - Leigh-Brown, Anne P AU - Leigh-Brown AP FAU - Torgerson, David J AU - Torgerson DJ FAU - Campbell, James AU - Campbell J FAU - Grant, Adrian AU - Grant A LA - eng PT - Clinical Trial PT - Journal Article PT - Randomized Controlled Trial DEP - 20020117 PL - England TA - BMC Health Serv Res JID - 101088677 SB - IM MH - Adult MH - Comparative Study MH - Female MH - Great Britain MH - Health Resources/*utilization MH - *Hospital Records MH - Humans MH - Male MH - Middle Aged MH - Musculoskeletal Diseases/*therapy MH - Orthopedics/statistics & numerical data MH - Patient Compliance/*statistics & numerical data MH - Physical Therapy Department, Hospital/*utilization MH - Questionnaires MH - Referral and Consultation MH - Reproducibility of Results MH - *Self Disclosure EDAT- 2002/02/05 10:00 MHDA- 2003/04/25 05:00 PHST- 2001/11/26 [received] PHST- 2002/01/17 [accepted] PHST- 2002/01/17 [aheadofprint] PST - ppublish SO - BMC Health Serv Res 2002;2(1):2. Epub 2002 Jan 17. PMID- 11835696 OWN - NLM STAT- MEDLINE DA - 20021119 DCOM- 20021125 LR - 20041117 PUBM- Print-Electronic IS - 1471-2091 VI - 3 IP - 1 DP - 2002 TI - Characterization of a protease produced by a Trichoderma harzianum isolate which controls cocoa plant witches' broom disease. PG - 3 AB - BACKGROUND: Several Trichoderma strains have been reported to be effective in controlling plant diseases, and the action of fungal hydrolytic enzymes has been considered as the main mechanism involved in the antagonistic process. However, although Trichoderma strains were found to impair development of Crinipellis perniciosa, the causal agent of cocoa plant witches' broom disease, no fungal strain is available for effective control of this disease. We have then undertaken a program of construction of hydrolytic enzyme-overproducing Trichoderma strains aiming improvement of the fungal antagonistic capacity. The protease of an indian Trichoderma isolate showing antagonistic activity against C. perniciosa was purified to homogeneity and characterized for its kinetic properties and action on the phytopathogen cell wall. RESULTS: A protease produced by the Trichoderma harzianum isolate 1051 was purified to homogeneity by precipitation with ammonium sulfate followed by hydrophobic chromatography. The molecular mass of this protease as determined by SDS-polyacrylamide gel electrophoresis was about 18.8 kDa. Its N-terminal amino acid sequence shares no homology with any other protease. The purified enzyme substantially affected the cell wall of the phytopathogen C. perniciosa. Western-blotting analysis showed that the enzyme was present in the culture supernatant 24 h after the Trichoderma started to grow in casein-containing liquid medium. CONCLUSIONS: The capacity of the Trichoderma harzianum protease to hydrolyze the cell wall of C. perniciosa indicates that this enzyme may be actually involved in the antagonistic process between the two fungi. This fact strongly suggest that hydrolytic enzyme over-producing transgenic fungi may show superior biocontrol capacity. AD - Departamento de Biologia Celular, Universidade de Brasilia, 70910-900, Brasilia, Brazil. jdemarco@uol.com.br FAU - De Marco, Janice L AU - De Marco JL FAU - Felix, Carlos Roberto AU - Felix CR LA - eng PT - Journal Article DEP - 20020122 PL - England TA - BMC Biochem JID - 101084098 RN - 0 (Antifungal Agents) RN - EC 3.4.- (Endopeptidases) SB - IM MH - Agaricales/*drug effects/ultrastructure MH - Antifungal Agents/*analysis/isolation & purification/pharmacology MH - Cacao/microbiology MH - Cell Wall/drug effects MH - Endopeptidases/*analysis/isolation & purification/pharmacology MH - Hydrogen-Ion Concentration MH - Microscopy, Electron, Scanning MH - Pest Control, Biological MH - Plant Diseases/microbiology MH - Research Support, Non-U.S. Gov't MH - Temperature MH - Trichoderma/*enzymology/isolation & purification EDAT- 2002/02/12 10:00 MHDA- 2002/11/26 04:00 PHST- 2001/09/17 [received] PHST- 2002/01/22 [accepted] PHST- 2002/01/22 [aheadofprint] PST - ppublish SO - BMC Biochem 2002;3(1):3. Epub 2002 Jan 22. PMID- 11876827 OWN - NLM STAT- MEDLINE DA - 20021119 DCOM- 20021125 LR - 20041117 PUBM- Print-Electronic IS - 1471-2091 VI - 3 IP - 1 DP - 2002 TI - Probing substrate binding to metallo-beta-lactamase L1 from Stenotrophomonas maltophilia by using site-directed mutagenesis. PG - 4 AB - BACKGROUND: The metallo-beta-lactamases are Zn(II)-containing enzymes that hydrolyze the beta-lactam bond in penicillins, cephalosporins, and carbapenems and are involved in bacterial antibiotic resistance. There are at least 20 distinct organisms that produce a metallo-beta-lactamase, and these enzymes have been extensively studied using X-ray crystallographic, computational, kinetic, and inhibition studies; however, much is still unknown about how substrates bind and the catalytic mechanism. In an effort to probe substrate binding to metallo-beta-lactamase L1 from Stenotrophomonas maltophilia, nine site-directed mutants of L1 were prepared and characterized using metal analyses, CD spectroscopy, and pre-steady state and steady state kinetics. RESULTS: Site-directed mutations were generated of amino acids previously predicted to be important in substrate binding. Steady-state kinetic studies using the mutant enzymes and 9 different substrates demonstrated varying Km and kcat values for the different enzymes and substrates and that no direct correlation between Km and the effect of the mutation on substrate binding could be drawn. Stopped-flow fluorescence studies using nitrocefin as the substrate showed that only the S224D and Y228A mutants exhibited weaker nitrocefin binding. CONCLUSIONS: The data presented herein indicate that Ser224, Ile164, Phe158, Tyr228, and Asn233 are not essential for tight binding of substrate to metallo-beta-lactamase L1. The results in this work also show that Km values are not reliable for showing substrate binding, and there is no correlation between substrate binding and the amount of reaction intermediate formed during the reaction. This work represents the first experimental testing of one of the computational models of the metallo-beta-lactamases. AD - Department of Chemistry and Biochemistry, Miami University, Oxford, OH, USA. sutsong@yahoo.com FAU - Carenbauer, Anne L AU - Carenbauer AL FAU - Garrity, James D AU - Garrity JD FAU - Periyannan, Gopal AU - Periyannan G FAU - Yates, Robert B AU - Yates RB FAU - Crowder, Michael W AU - Crowder MW LA - eng GR - R29 AI40052/AI/NIAID PT - Journal Article DEP - 20020213 PL - England TA - BMC Biochem JID - 101084098 RN - 0 (Carbapenems) RN - 0 (Cephalosporins) RN - 0 (Metals) RN - 0 (Penicillins) RN - 41906-86-9 (nitrocefin) RN - 55520-40-6 (Tyrosine) RN - 56-45-1 (Serine) RN - 63-91-2 (Phenylalanine) RN - 7006-34-0 (Asparagine) RN - 73-32-5 (Isoleucine) RN - EC 3.5.2.- (beta-lactamase L1) RN - EC 3.5.2.6 (beta-Lactamases) SB - IM MH - Asparagine/genetics MH - Binding Sites MH - Carbapenems/metabolism MH - Cephalosporins/metabolism MH - Computational Biology MH - Isoleucine/genetics MH - Kinetics MH - Metals/analysis MH - Models, Molecular MH - Mutagenesis, Site-Directed MH - Penicillins/metabolism MH - Phenylalanine/genetics MH - Protein Binding MH - Research Support, Non-U.S. Gov't MH - Research Support, U.S. Gov't, Non-P.H.S. MH - Research Support, U.S. Gov't, P.H.S. MH - Serine/genetics MH - Stenotrophomonas maltophilia/*enzymology MH - Tyrosine/genetics MH - beta-Lactamases/chemistry/*genetics/*metabolism EDAT- 2002/03/06 10:00 MHDA- 2002/11/26 04:00 PHST- 2001/11/06 [received] PHST- 2002/02/13 [accepted] PHST- 2002/02/13 [aheadofprint] PST - ppublish SO - BMC Biochem 2002;3(1):4. Epub 2002 Feb 13. PMID- 11882257 OWN - NLM STAT- MEDLINE DA - 20030415 DCOM- 20030424 LR - 20041117 PUBM- Print-Electronic IS - 1472-6963 VI - 2 IP - 1 DP - 2002 TI - What kind of evidence is it that Evidence-Based Medicine advocates want health care providers and consumers to pay attention to? PG - 3 AB - BACKGROUND: In 1992, Evidence-Based Medicine advocates proclaimed a "new paradigm", in which evidence from health care research is the best basis for decisions for individual patients and health systems. Hailed in New York Times Magazine in 2001 as one of the most influential ideas of the year, this approach was initially and provocatively pitted against the traditional teaching of medicine, in which the key elements of knowing for clinical purposes are understanding of basic pathophysiologic mechanisms of disease coupled with clinical experience. This paper reviews the origins, aspirations, philosophical limitations, and practical challenges of evidence-based medicine. DISCUSSION: EBM has long since evolved beyond its initial (mis)conception, that EBM might replace traditional medicine. EBM is now attempting to augment rather than replace individual clinical experience and understanding of basic disease mechanisms. EBM must continue to evolve, however, to address a number of issues including scientific underpinnings, moral stance and consequences, and practical matters of dissemination and application. For example, accelerating the transfer of research findings into clinical practice is often based on incomplete evidence from selected groups of people, who experience a marginal benefit from an expensive technology, raising issues of the generalizability of the findings, and increasing problems with how many and who can afford the new innovations in care. SUMMARY: Advocates of evidence-based medicine want clinicians and consumers to pay attention to the best findings from health care research that are both valid and ready for clinical application. Much remains to be done to reach this goal. AD - Department of Clinical Epidemiology and Biostatistics Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada. bhaynes@mcmaster.ca FAU - Haynes, R Brian AU - Haynes RB LA - eng PT - Journal Article DEP - 20020306 PL - England TA - BMC Health Serv Res JID - 101088677 SB - IM MH - *Decision Making MH - Diffusion of Innovation MH - *Evidence-Based Medicine/ethics/trends MH - *Health Services Research MH - Humans MH - Knowledge MH - Patient Participation MH - Physician's Practice Patterns MH - Practice Guidelines MH - Probability MH - Randomized Controlled Trials MH - Resource Allocation/ethics MH - Uncertainty EDAT- 2002/03/08 10:00 MHDA- 2003/04/25 05:00 PHST- 2001/12/24 [received] PHST- 2002/03/06 [accepted] PHST- 2002/03/06 [aheadofprint] PST - ppublish SO - BMC Health Serv Res 2002;2(1):3. Epub 2002 Mar 6. PMID- 11884248 OWN - NLM STAT- MEDLINE DA - 20030415 DCOM- 20030424 LR - 20041117 PUBM- Print-Electronic IS - 1472-6963 VI - 2 IP - 1 DP - 2002 TI - Reporting of measures of accuracy in systematic reviews of diagnostic literature. PG - 4 AB - BACKGROUND: There are a variety of ways in which accuracy of clinical tests can be summarised in systematic reviews. Variation in reporting of summary measures has only been assessed in a small survey restricted to meta-analyses of screening studies found in a single database. Therefore, we performed this study to assess the measures of accuracy used for reporting results of primary studies as well as their meta-analysis in systematic reviews of test accuracy studies. METHODS: Relevant reviews on test accuracy were selected from the Database of Abstracts of Reviews of Effectiveness (1994-2000), which electronically searches seven bibliographic databases and manually searches key resources. The structured abstracts of these reviews were screened and information on accuracy measures was extracted from the full texts of 90 relevant reviews, 60 of which used meta-analysis. RESULTS: Sensitivity or specificity was used for reporting the results of primary studies in 65/90 (72%) reviews, predictive values in 26/90 (28%), and likelihood ratios in 20/90 (22%). For meta-analysis, pooled sensitivity or specificity was used in 35/60 (58%) reviews, pooled predictive values in 11/60 (18%), pooled likelihood ratios in 13/60 (22%), and pooled diagnostic odds ratio in 5/60 (8%). Summary ROC was used in 44/60 (73%) of the meta-analyses. There were no significant differences in measures of test accuracy among reviews published earlier (1994-97) and those published later (1998-2000). CONCLUSIONS: There is considerable variation in ways of reporting and summarising results of test accuracy studies in systematic reviews. There is a need for consensus about the best ways of reporting results of test accuracy studies in reviews. AD - Academic Dept, of Obstetrics & Gynaecology, Birmingham Women's Hospital, Birmingham B15 2TG, United Kingdom. h.honest@bham.ac.uk FAU - Honest, Honest AU - Honest H FAU - Khan, Khalid S AU - Khan KS LA - eng PT - Journal Article DEP - 20020307 PL - England TA - BMC Health Serv Res JID - 101088677 SB - IM MH - Bias (Epidemiology) MH - *Data Interpretation, Statistical MH - Databases, Bibliographic MH - Humans MH - Laboratory Techniques and Procedures/*standards MH - *Meta-Analysis MH - Pathology, Clinical/*standards MH - Quality Control MH - Reproducibility of Results MH - Research Design/*standards MH - Research Support, Non-U.S. Gov't MH - *Review Literature MH - Sensitivity and Specificity EDAT- 2002/03/09 10:00 MHDA- 2003/04/25 05:00 PHST- 2001/09/05 [received] PHST- 2002/03/07 [accepted] PHST- 2002/03/07 [aheadofprint] PST - ppublish SO - BMC Health Serv Res 2002;2(1):4. Epub 2002 Mar 7. PMID- 11914161 OWN - NLM STAT- MEDLINE DA - 20030415 DCOM- 20030422 LR - 20041117 PUBM- Electronic IS - 1472-6963 VI - 2 IP - 1 DP - 2002 Mar 21 TI - A randomised controlled trial of a patient based Diabetes Recall and Management System: the DREAM trial: a study protocol [ISRCTN32042030]. PG - 5 AB - BACKGROUND: Whilst there is broad agreement on what constitutes high quality health care for people with diabetes, there is little consensus on the most efficient way of delivering it. Structured recall systems can improve the quality of care but the systems evaluated to date have been of limited sophistication and the evaluations have been carried out in small numbers of relatively unrepresentative settings. Hartlepool, Easington and Stockton currently operate a computerised diabetes register which has to date produced improvements in the quality of care but performance has now plateaued leaving substantial scope for further improvement. This study will evaluate the effectiveness and efficiency of an area wide 'extended' system incorporating a full structured recall and management system, actively involving patients and including clinical management prompts to primary care clinicians based on locally-adapted evidence based guidelines. METHODS: The study design is a two-armed cluster randomised controlled trial of 61 practices incorporating evaluations of the effectiveness of the system, its economic impact and its impact on patient wellbeing and functioning. AD - Centre for Health Services Research, University of Newcastle, Newcastle upon Tyne, UK. martin.eccles@ncl.ac.uk FAU - Eccles, Martin AU - Eccles M FAU - Hawthorne, Gillian AU - Hawthorne G FAU - Whitty, Paula AU - Whitty P FAU - Steen, Nick AU - Steen N FAU - Vanoli, Alessandra AU - Vanoli A FAU - Grimshaw, Jeremy AU - Grimshaw J FAU - Wood, Linda AU - Wood L LA - eng PT - Clinical Trial PT - Journal Article PT - Randomized Controlled Trial DEP - 20020321 PL - England TA - BMC Health Serv Res JID - 101088677 SB - IM MH - *Database Management Systems MH - Diabetes Mellitus/diagnosis/*prevention & control MH - Efficiency, Organizational MH - England MH - *Evidence-Based Medicine MH - Family Practice/organization & administration/*standards MH - Guideline Adherence MH - Humans MH - Medical Audit MH - Patient Compliance MH - Preventive Health Services/standards/utilization MH - Primary Health Care/organization & administration/standards MH - Quality Assurance, Health Care/*organization & administration MH - Registries MH - *Reminder Systems EDAT- 2002/03/27 10:00 MHDA- 2003/04/23 05:00 PHST- 2001/12/14 [received] PHST- 2002/03/21 [accepted] PHST- 2002/03/21 [aheadofprint] PST - epublish SO - BMC Health Serv Res 2002 Mar 21;2(1):5. PMID- 11914162 OWN - NLM STAT- MEDLINE DA - 20030415 DCOM- 20030423 LR - 20041117 PUBM- Electronic IS - 1472-6963 VI - 2 IP - 1 DP - 2002 Mar 25 TI - Organization specific predictors of job satisfaction: findings from a Canadian multi-site quality of work life cross-sectional survey. PG - 6 AB - BACKGROUND: Organizational features can affect how staff view their quality of work life. Determining staff perceptions about quality of work life is an important consideration for employers interested in improving employee job satisfaction. The purpose of this study was to identify organization specific predictors of job satisfaction within a health care system that consisted of six independent health care organizations. METHODS: 5,486 full, part and causal time (non-physician) staff on active payroll within six organizations (2 community hospitals, 1 community hospital/long-term care facility, 1 long-term care facility, 1 tertiary care/community health centre, and 1 visiting nursing agency) located in five communities in Central West Ontario, Canada were asked to complete a 65-item quality of work life survey. The self-administered questionnaires collected staff perceptions of: co-worker and supervisor support; teamwork and communication; job demands and decision authority; organization characteristics; patient/resident care; compensation and benefits; staff training and development; and impressions of the organization. Socio-demographic data were also collected. RESULTS: Depending on the organization, between 15 and 30 (of the 40 potential predictor) variables were found to be statistically associated with job satisfaction (univariate analyses). Logistic regression analyses identified the best predictors of job satisfaction and these are presented for each of the six organizations and for all organizations combined. CONCLUSIONS: The findings indicate that job satisfaction is a multidimensional construct and although there appear to be some commonalities across organizations, some predictors of job satisfaction appear to be organization and context specific. AD - St, Joseph's Health System Research Network, Father Sean O'Sullivan Research Centre, Hamilton, Ontario. kruegerp@mcmaster.ca FAU - Krueger, Paul AU - Krueger P FAU - Brazil, Kevin AU - Brazil K FAU - Lohfeld, Lynne AU - Lohfeld L FAU - Edward, H Gayle AU - Edward HG FAU - Lewis, David AU - Lewis D FAU - Tjam, Erin AU - Tjam E LA - eng PT - Journal Article DEP - 20020325 PL - England TA - BMC Health Serv Res JID - 101088677 SB - IM MH - Adult MH - *Attitude of Health Personnel MH - Communication MH - Community Health Centers/organization & administration MH - Community Health Nursing/organization & administration MH - Decision Making, Organizational MH - Delivery of Health Care, Integrated/*organization & administration MH - Female MH - Forecasting MH - Hospitals, Community/organization & administration MH - Humans MH - *Job Satisfaction MH - Logistic Models MH - Male MH - Middle Aged MH - Ontario MH - Patient Care Team MH - Personnel Management/*methods MH - Questionnaires MH - Research Support, Non-U.S. Gov't MH - Residential Facilities/organization & administration EDAT- 2002/03/27 10:00 MHDA- 2003/04/24 05:00 PHST- 2001/10/01 [received] PHST- 2002/03/25 [accepted] PHST- 2002/03/25 [aheadofprint] PST - epublish SO - BMC Health Serv Res 2002 Mar 25;2(1):6. PMID- 11914163 OWN - NLM STAT- MEDLINE DA - 20030415 DCOM- 20030423 LR - 20041117 PUBM- Electronic IS - 1472-6963 VI - 2 IP - 1 DP - 2002 Mar 25 TI - Outcomes research in the development and evaluation of practice guidelines. PG - 7 AB - BACKGROUND: Practice guidelines have been developed in response to the observation that variations exist in clinical medicine that are not related to variations in the clinical presentation and severity of the disease. Despite their widespread use, however, practice guideline evaluation lacks a rigorous scientific methodology to support its development and application. DISCUSSION: Firstly, we review the major epidemiological foundations of practice guideline development. Secondly, we propose a chronic disease epidemiological model in which practice patterns are viewed as the exposure and outcomes of interest such as quality or cost are viewed as the disease. Sources of selection, information, confounding and temporal trend bias are identified and discussed. SUMMARY: The proposed methodological framework for outcomes research to evaluate practice guidelines reflects the selection, information and confounding biases inherent in its observational nature which must be accounted for in both the design and the analysis phases of any outcomes research study. AD - Division of Clinical Epidemiology, Research Institute of the McGill University Health Center, Montreal, Canada. louise.pilote@mcgill.ca FAU - Pilote, Louise AU - Pilote L FAU - Tager, Ira B AU - Tager IB LA - eng PT - Journal Article DEP - 20020325 PL - England TA - BMC Health Serv Res JID - 101088677 SB - IM MH - Biomedical Research MH - Chronic Disease/*epidemiology/therapy MH - Confounding Factors (Epidemiology) MH - Data Collection MH - Databases MH - Epidemiologic Methods MH - Evaluation Studies MH - Humans MH - Outcome Assessment (Health Care)/*methods MH - Physician's Practice Patterns/*statistics & numerical data MH - Practice Guidelines/*standards MH - Selection Bias MH - Treatment Outcome MH - Uncertainty EDAT- 2002/03/27 10:00 MHDA- 2003/04/24 05:00 PHST- 2001/10/01 [received] PHST- 2002/03/25 [accepted] PHST- 2002/03/25 [aheadofprint] PST - epublish SO - BMC Health Serv Res 2002 Mar 25;2(1):7. PMID- 11914164 OWN - NLM STAT- MEDLINE DA - 20030415 DCOM- 20030423 LR - 20041117 PUBM- Electronic IS - 1472-6963 VI - 2 IP - 1 DP - 2002 Mar 26 TI - Inter-rater agreement in the scoring of abstracts submitted to a primary care research conference. PG - 8 AB - BACKGROUND: Checklists for peer review aim to guide referees when assessing the quality of papers, but little evidence exists on the extent to which referees agree when evaluating the same paper. The aim of this study was to investigate agreement on dimensions of a checklist between two referees when evaluating abstracts submitted for a primary care conference. METHODS: Anonymised abstracts were scored using a structured assessment comprising seven categories. Between one (poor) and four (excellent) marks were awarded for each category, giving a maximum possible score of 28 marks. Every abstract was assessed independently by two referees and agreement measured using intraclass correlation coefficients. Mean total scores of abstracts accepted and rejected for the meeting were compared using an unpaired t test. RESULTS: Of 52 abstracts, agreement between reviewers was greater for three components relating to study design (adjusted intraclass correlation coefficients 0.40 to 0.45) compared to four components relating to more subjective elements such as the importance of the study and likelihood of provoking discussion (0.01 to 0.25). Mean score for accepted abstracts was significantly greater than those that were rejected (17.4 versus 14.6, 95% CI for difference 1.3 to 4.1, p = 0.0003). CONCLUSIONS: The findings suggest that inclusion of subjective components in a review checklist may result in greater disagreement between reviewers. However in terms of overall quality scores, abstracts accepted for the meeting were rated significantly higher than those that were rejected. AD - Division of Primary Health Care, University of Bristol, Cotham House, Cotham Hill, Bristol BS8 2PR, UK. alan.a.montgomery@bristol.ac.uk FAU - Montgomery, Alan A AU - Montgomery AA FAU - Graham, Anna AU - Graham A FAU - Evans, Philip H AU - Evans PH FAU - Fahey, Tom AU - Fahey T LA - eng PT - Journal Article DEP - 20020326 PL - England TA - BMC Health Serv Res JID - 101088677 SB - IM MH - Abstracting and Indexing/classification/*standards MH - Congresses MH - *Consensus MH - Data Interpretation, Statistical MH - Great Britain MH - Humans MH - Judgment MH - Manuscripts, Medical MH - Observer Variation MH - Peer Review, Research/methods/*standards MH - Primary Health Care MH - Research Support, Non-U.S. Gov't EDAT- 2002/03/27 10:00 MHDA- 2003/04/24 05:00 PHST- 2001/12/03 [received] PHST- 2002/03/26 [accepted] PHST- 2002/03/26 [aheadofprint] PST - epublish SO - BMC Health Serv Res 2002 Mar 26;2(1):8. PMID- 11943069 OWN - NLM STAT- MEDLINE DA - 20021119 DCOM- 20021122 LR - 20041117 PUBM- Electronic IS - 1471-2091 VI - 3 IP - 1 DP - 2002 Mar 27 TI - The Caenorhabditis elegans Y87G2A.14 Nudix hydrolase is a peroxisomal coenzyme A diphosphatase. PG - 5 AB - BACKGROUND: The number of Nudix hydrolase family members varies widely among different organisms. In order to understand the reasons for the particular spectrum possessed by a given organism, the substrate specificity and function of different family members must be established. RESULTS: The Y87G2A.14 Nudix hydrolase gene product of Caenorhabditis elegans has been expressed as a thioredoxin fusion protein in Escherichia coli and shown to be a CoA diphosphatase with catalytic activity towards CoA and its derivatives. The products of CoA hydrolysis were 3',5'-ADP and 4'-phosphopantetheine with Km and kcat values of 220 microM and 13.8 s(-1) respectively. CoA esters yielded 3',5'-ADP and the corresponding acyl-phosphopantetheine. Activity was optimal at pH 9.5 with 5 mM Mg2+ and fluoride was inhibitory with a Ki of 3 microM. The Y87G2A.14 gene product has a potential C-terminal tripeptide PTS1 peroxisomal targeting signal - SKI. By fusing a Y87G2A.14 cDNA to the C-terminus of yeast-enhanced green fluorescent protein, the enzyme appeared to be targeted to peroxisomes by the SKI signal when transfected into yeast cells. Deletion of SKI abolished specific targeting. CONCLUSIONS: The presence of related sequences with potential PTS1 or PTS2 peroxisomal targeting signals in other organisms suggests a conserved peroxisomal function for the CoA diphosphatase members of this group of Nudix hydrolases. AD - School of Biological Sciences, Life Sciences Building, University of Liverpool, P,O, Box 147, Liverpool L69 7ZB, UK. salamara@liv.ac.uk FAU - AbdelRaheim, Salama R AU - AbdelRaheim SR FAU - McLennan, Alexander G AU - McLennan AG LA - eng PT - Journal Article DEP - 20020327 PL - England TA - BMC Biochem JID - 101084098 RN - 85-61-0 (Coenzyme A) RN - EC 3.6.1.- (Pyrophosphatases) RN - EC 3.6.1.- (nudix hydrolase) SB - IM MH - Amino Acid Sequence MH - Animals MH - Caenorhabditis elegans/*enzymology MH - Cloning, Molecular MH - Coenzyme A/*metabolism MH - Kinetics MH - Molecular Sequence Data MH - Peroxisomes/*metabolism MH - Pyrophosphatases/genetics/isolation & purification/*metabolism MH - Research Support, Non-U.S. Gov't MH - Sequence Alignment MH - Substrate Specificity EDAT- 2002/04/12 10:00 MHDA- 2002/11/26 04:00 PHST- 2002/02/12 [received] PHST- 2002/03/27 [accepted] PHST- 2002/03/27 [aheadofprint] PST - epublish SO - BMC Biochem 2002 Mar 27;3(1):5. PMID- 11972899 OWN - NLM STAT- MEDLINE DA - 20021119 DCOM- 20021122 LR - 20041215 PUBM- Electronic IS - 1471-2091 VI - 3 IP - 1 DP - 2002 Apr 24 TI - Interconversion of Anthozoa GFP-like fluorescent and non-fluorescent proteins by mutagenesis. PG - 7 AB - BACKGROUND: Within the family of green fluorescent protein (GFP) homologs, one can mark two main groups, specifically, fluorescent proteins (FPs) and non-fluorescent or chromoproteins (CPs). Structural background of differences between FPs and CPs are poorly understood to date. RESULTS: Here, we applied site-directed and random mutagenesis in order to to transform CP into FP and vice versa. A purple chromoprotein asCP (asFP595) from Anemonia sulcata and a red fluorescent protein DsRed from Discosoma sp. were selected as representatives of CPs and FPs, respectively. For asCP, some substitutions at positions 148 and 165 (numbering in accordance to GFP) were found to dramatically increase quantum yield of red fluorescence. For DsRed, substitutions at positions 148, 165, 167, and 203 significantly decreased fluorescence intensity, so that the spectral characteristics of these mutants became more close to those of CPs. Finally, a practically non-fluorescent mutant DsRed-NF was generated. This mutant carried four amino acid substitutions, specifically, S148C, I165N, K167M, and S203A. DsRed-NF possessed a high extinction coefficient and an extremely low quantum yield (< 0.001). These spectral characteristics allow one to regard DsRed-NF as a true chromoprotein. CONCLUSIONS: We located a novel point in asCP sequence (position 165) mutations at which can result in red fluorescence appearance. Probably, this finding could be applied onto other CPs to generate red and far-red fluorescent mutants. A possibility to transform an FP into CP was demonstrated. Key role of residues adjacent to chromophore's phenolic ring in fluorescent/non-fluorescent states determination was revealed. AD - Shemiakin and Ovchinnikov Institute of Bioorganic Chemistry RAS, Miklukho-Maklaya 16/10, 117997 Moscow, Russia. biomasha@mail.ru FAU - Bulina, Maria E AU - Bulina ME FAU - Chudakov, Dmitry M AU - Chudakov DM FAU - Mudrik, Nikolay N AU - Mudrik NN FAU - Lukyanov, Konstantin A AU - Lukyanov KA LA - eng PT - Journal Article DEP - 20020424 PL - England TA - BMC Biochem JID - 101084098 RN - 0 (FP595 protein, Anemonia sulcata) RN - 0 (Luminescent Proteins) RN - 0 (fluorescent protein 583) RN - 147336-22-9 (Green Fluorescent Proteins) SB - IM MH - Amino Acid Sequence MH - *Anthozoa MH - Fluorescence MH - Green Fluorescent Proteins MH - Luminescent Proteins/*chemistry/*genetics MH - Models, Molecular MH - Molecular Sequence Data MH - Mutagenesis MH - Mutagenesis, Site-Directed MH - Research Support, Non-U.S. Gov't MH - Sequence Alignment MH - Spectrometry, Fluorescence EDAT- 2002/04/26 10:00 MHDA- 2002/11/26 04:00 PHST- 2001/12/14 [received] PHST- 2002/04/24 [accepted] PHST- 2002/04/24 [aheadofprint] PST - epublish SO - BMC Biochem 2002 Apr 24;3(1):7. PMID- 11996675 OWN - NLM STAT- MEDLINE DA - 20021119 DCOM- 20021218 LR - 20041117 PUBM- Electronic IS - 1471-2091 VI - 3 IP - 1 DP - 2002 May 7 TI - Hisactophilin is involved in osmoprotection in Dictyostelium. PG - 10 AB - BACKGROUND: Dictyostelium cells exhibit an unusual stress response as they protect themselves against hyperosmotic stress. Cytoskeletal proteins are recruited from the cytosolic pool to the cell cortex, thereby reinforcing it. In order to gain more insight into the osmoprotective mechanisms of this amoeba, we used 1-D and 2-D gel electrophoresis to identify new proteins that are translocated during osmotic shock. RESULTS: We identified hisactophilin as one of the proteins that are enriched in the cytoskeletal fraction during osmotic shock. In mutants lacking hisactophilin, viability is reduced under hyperosmotic stress conditions. In wild type cells, serine phosphorylation of hisactophilin was specifically induced by hypertonicity, but not when other stress conditions were imposed on cells. The phosphorylation kinetics reveals a slow accumulation of phosphorylated hisactophilin from 20-60 min after onset of the hyperosmotic shock condition. CONCLUSION: In the present study, we identified hisactophilin as an essential protein for the osmoprotection of Dictyostelium cells. The observed phosphorylation kinetics suggest that hisactophilin regulation is involved in long-term osmoprotection and that phosphorylation occurs in parallel with inactivation of the dynamic actin cytoskeleton. AD - Max-Planck-Institute for Biochemistry, 82152 Martinsried, Germany. pintsch@switch-biotech.com FAU - Pintsch, Tanja AU - Pintsch T FAU - Zischka, Hans AU - Zischka H FAU - Schuster, Stephan C AU - Schuster SC LA - eng PT - Journal Article DEP - 20020507 PL - England TA - BMC Biochem JID - 101084098 RN - 0 (Carrier Proteins) RN - 0 (Hypertonic Solutions) RN - 0 (Microfilament Proteins) RN - 0 (Protozoan Proteins) RN - 122962-20-3 (hisactophilin protein, Protozoan) RN - 50-70-4 (Sorbitol) RN - 56-45-1 (Serine) SB - IM MH - Animals MH - Carrier Proteins/drug effects/genetics/*metabolism MH - Cell Division/drug effects/genetics MH - Cytoskeleton/drug effects/metabolism MH - Dictyostelium/cytology/*drug effects/metabolism MH - Dose-Response Relationship, Drug MH - Electrophoresis, Gel, Two-Dimensional MH - Hypertonic Solutions/pharmacology MH - *Microfilament Proteins MH - Mutation MH - Osmotic Pressure MH - Phosphorylation/drug effects MH - Protozoan Proteins/drug effects/genetics/*metabolism MH - Research Support, Non-U.S. Gov't MH - Serine/metabolism MH - Sorbitol/*pharmacology EDAT- 2002/05/09 10:00 MHDA- 2002/12/19 04:00 PHST- 2001/12/19 [received] PHST- 2002/05/07 [accepted] PHST- 2002/05/07 [aheadofprint] PST - epublish SO - BMC Biochem 2002 May 7;3(1):10. PMID- 11997336 OWN - NLM STAT- MEDLINE DA - 20020508 DCOM- 20020605 LR - 20041117 PUBM- Print IS - 1088-9051 VI - 12 IP - 5 DP - 2002 May TI - A complete sequence of the T. tengcongensis genome. PG - 689-700 AB - Thermoanaerobacter tengcongensis is a rod-shaped, gram-negative, anaerobic eubacterium that was isolated from a freshwater hot spring in Tengchong, China. Using a whole-genome-shotgun method, we sequenced its 2,689,445-bp genome from an isolate, MB4(T) (Genbank accession no. AE008691). The genome encodes 2588 predicted coding sequences (CDS). Among them, 1764 (68.2%) are classified according to homology to other documented proteins, and the rest, 824 CDS (31.8%), are functionally unknown. One of the interesting features of the T. tengcongensis genome is that 86.7% of its genes are encoded on the leading strand of DNA replication. Based on protein sequence similarity, the T. tengcongensis genome is most similar to that of Bacillus halodurans, a mesophilic eubacterium, among all fully sequenced prokaryotic genomes up to date. Computational analysis on genes involved in basic metabolic pathways supports the experimental discovery that T. tengcongensis metabolizes sugars as principal energy and carbon source and utilizes thiosulfate and element sulfur, but not sulfate, as electron acceptors. T. tengcongensis, as a gram-negative rod by empirical definitions (such as staining), shares many genes that are characteristics of gram-positive bacteria whereas it is missing molecular components unique to gram-negative bacteria. A strong correlation between the G + C content of tDNA and rDNA genes and the optimal growth temperature is found among the sequenced thermophiles. It is concluded that thermophiles are a biologically and phylogenetically divergent group of prokaryotes that have converged to sustain extreme environmental conditions over evolutionary timescale. AD - Beijing Genomics Institute/Genomics and Bioinformatics Center, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences (CAS), Beijing 100101, China. FAU - Bao, Qiyu AU - Bao Q FAU - Tian, Yuqing AU - Tian Y FAU - Li, Wei AU - Li W FAU - Xu, Zuyuan AU - Xu Z FAU - Xuan, Zhenyu AU - Xuan Z FAU - Hu, Songnian AU - Hu S FAU - Dong, Wei AU - Dong W FAU - Yang, Jian AU - Yang J FAU - Chen, Yanjiong AU - Chen Y FAU - Xue, Yanfen AU - Xue Y FAU - Xu, Yi AU - Xu Y FAU - Lai, Xiaoqin AU - Lai X FAU - Huang, Li AU - Huang L FAU - Dong, Xiuzhu AU - Dong X FAU - Ma, Yanhe AU - Ma Y FAU - Ling, Lunjiang AU - Ling L FAU - Tan, Huarong AU - Tan H FAU - Chen, Runsheng AU - Chen R FAU - Wang, Jian AU - Wang J FAU - Yu, Jun AU - Yu J FAU - Yang, Huanming AU - Yang H LA - eng SI - GENBANK/AE008691 PT - Journal Article PL - United States TA - Genome Res JID - 9518021 RN - 0 (Codon) RN - 7704-34-9 (Sulfur) SB - IM MH - Bacillaceae/cytology/*genetics/metabolism/physiology MH - Base Composition/genetics MH - Codon/genetics MH - DNA Repair/genetics MH - DNA Replication/genetics MH - GC Rich Sequence/genetics MH - Genes, Structural, Bacterial/genetics MH - *Genome, Bacterial MH - Genomics/methods MH - Heat MH - Ion Transport/genetics MH - Molecular Sequence Data MH - Oxygen Consumption/genetics MH - Protein Biosynthesis/genetics MH - Recombination, Genetic/genetics MH - Repetitive Sequences, Nucleic Acid/genetics MH - Replication Origin/genetics MH - Research Support, Non-U.S. Gov't MH - Sequence Analysis, DNA/methods MH - Sulfur/metabolism MH - Transcription, Genetic EDAT- 2002/05/09 10:00 MHDA- 2002/06/06 10:01 AID - 10.1101/gr.219302 [doi] PST - ppublish SO - Genome Res 2002 May;12(5):689-700. PMID- 11997337 OWN - NLM STAT- MEDLINE DA - 20020508 DCOM- 20020605 LR - 20041215 PUBM- Print IS - 1088-9051 VI - 12 IP - 5 DP - 2002 May TI - Identification of a novel cis-regulatory element involved in the heat shock response in Caenorhabditis elegans using microarray gene expression and computational methods. PG - 701-12 AB - We report here the identification of a previously unknown transcription regulatory element for heat shock (HS) genes in Caenorhabditis elegans. We monitored the expression pattern of 11,917 genes from C. elegans to determine the genes that were up-regulated on HS. Twenty eight genes were observed to be consistently up-regulated in several different repetitions of the experiments. We analyzed the upstream regions of these genes using computational DNA pattern recognition methods. Two potential cis-regulatory motifs were identified in this way. One of these motifs (TTCTAGAA) was the DNA binding motif for the heat shock factor (HSF), whereas the other (GGGTGTC) was previously unreported in the literature. We determined the significance of these motifs for the HS genes using different statistical tests and parameters. Comparative sequence analysis of orthologous HS genes from C. elegans and Caenorhabditis briggsae indicated that the identified DNA regulatory motifs are conserved across related species. The role of the identified DNA sites in regulation of HS genes was tested by in vitro mutagenesis of a green fluorescent protein (GFP) reporter transgene driven by the C. elegans hsp-16-2 promoter. DNA sites corresponding to both motifs are shown to play a significant role in up-regulation of the hsp-16-2 gene on HS. This is one of the rare instances in which a novel regulatory element, identified using computational methods, is shown to be biologically active. The contributions of individual sites toward induction of transcription on HS are nonadditive, which indicates interaction and cross-talk between the sites, possibly through the transcription factors (TFs) binding to these sites. AD - Department of Genetics, Washington University School of Medicine, St. Louis, Missouri 63114, USA. FAU - GuhaThakurta, Debraj AU - GuhaThakurta D FAU - Palomar, Lisanne AU - Palomar L FAU - Stormo, Gary D AU - Stormo GD FAU - Tedesco, Pat AU - Tedesco P FAU - Johnson, Thomas E AU - Johnson TE FAU - Walker, David W AU - Walker DW FAU - Lithgow, Gordon AU - Lithgow G FAU - Kim, Stuart AU - Kim S FAU - Link, Christopher D AU - Link CD LA - eng GR - AG12423/AG/NIA GR - HG00249/HG/NHGRI GR - R25 GM62495-01/GM/NIGMS PT - Journal Article PL - United States TA - Genome Res JID - 9518021 RN - 0 (Luminescent Proteins) RN - 147336-22-9 (Green Fluorescent Proteins) RN - 9007-49-2 (DNA) SB - IM EIN - Genome Res 2002 Aug;12(8):1301 MH - Animals MH - Base Sequence MH - Binding Sites/genetics MH - Caenorhabditis elegans/*genetics MH - Comparative Study MH - Computational Biology/*methods MH - Conserved Sequence/genetics MH - DNA/metabolism MH - Gene Expression Profiling/*methods MH - Genes, Structural, Helminth/genetics MH - Green Fluorescent Proteins MH - Heat-Shock Response/*genetics MH - Luminescent Proteins/biosynthesis MH - Molecular Sequence Data MH - Mutagenesis, Site-Directed/genetics MH - Oligonucleotide Array Sequence Analysis/*methods MH - Probability MH - Promoter Regions (Genetics)/genetics MH - Regulatory Sequences, Nucleic Acid/*physiology MH - Research Support, U.S. Gov't, P.H.S. MH - Species Specificity MH - Statistics, Nonparametric MH - Up-Regulation/genetics EDAT- 2002/05/09 10:00 MHDA- 2002/06/06 10:01 AID - 10.1101/gr.228902 [doi] PST - ppublish SO - Genome Res 2002 May;12(5):701-12. PMID- 11997338 OWN - NLM STAT- MEDLINE DA - 20020508 DCOM- 20020605 LR - 20041203 PUBM- Print IS - 1088-9051 VI - 12 IP - 5 DP - 2002 May TI - Genes in a refined Smith-Magenis syndrome critical deletion interval on chromosome 17p11.2 and the syntenic region of the mouse. PG - 713-28 AB - Smith-Magenis syndrome (SMS) is a multiple congenital anomaly/mental retardation syndrome associated with behavioral abnormalities and sleep disturbance. Most patients have the same approximately 4 Mb interstitial genomic deletion within chromosome 17p11.2. To investigate the molecular bases of the SMS phenotype, we constructed BAC/PAC contigs covering the SMS common deletion interval and its syntenic region on mouse chromosome 11. Comparative genome analysis reveals the absence of all three approximately 200-kb SMS-REP low-copy repeats in the mouse and indicates that the evolution of SMS-REPs was accompanied by transposition of adjacent genes. Physical and genetic map comparisons in humans reveal reduced recombination in both sexes. Moreover, by examining the deleted regions in SMS patients with unusual-sized deletions, we refined the minimal Smith-Magenis critical region (SMCR) to an approximately 1.1-Mb genomic interval that is syntenic to an approxiamtely 1.0-Mb region in the mouse. Genes within the SMCR and its mouse syntenic region were identified by homology searches and by gene prediction programs, and their gene structures and expression profiles were characterized. In addition to 12 genes previously mapped, we identified 8 new genes and 10 predicted genes in the SMCR. In the mouse syntenic region of the human SMCR, 16 genes and 6 predicted genes were identified. The SMCR is highly conserved between humans and mice, including 19 genes with the same gene order and orientation. Our findings will facilitate both the identification of gene(s) responsible for the SMS phenotype and the engineering of an SMS mouse model. AD - Department of Molecular & Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA. FAU - Bi, Weimin AU - Bi W FAU - Yan, Jiong AU - Yan J FAU - Stankiewicz, Pawe AU - Stankiewicz P FAU - Park, Sung-Sup AU - Park SS FAU - Walz, Katherina AU - Walz K FAU - Boerkoel, Cornelius F AU - Boerkoel CF FAU - Potocki, Lorraine AU - Potocki L FAU - Shaffer, Lisa G AU - Shaffer LG FAU - Devriendt, Koen AU - Devriendt K FAU - Nowaczyk, Magorzata J M AU - Nowaczyk MJ FAU - Inoue, Ken AU - Inoue K FAU - Lupski, James R AU - Lupski JR LA - eng GR - P01 CA75719/CA/NCI GR - P01 HD38420/HD/NICHD GR - R01 NS27042/NS/NINDS PT - Journal Article PL - United States TA - Genome Res JID - 9518021 RN - 0 (Chaperonins) RN - 0 (Chromosomes, Artificial, Bacterial) RN - 0 (Chromosomes, Artificial, P1 Bacteriophage) RN - 0 (Fungal Proteins) RN - 0 (Saccharomyces cerevisiae Proteins) RN - EC 3.6.3.14 (ATPAF2 protein, human) RN - EC 3.6.3.14 (Proton-Translocating ATPases) SB - IM MH - Abnormalities, Multiple/*genetics MH - Animals MH - *Chaperonins MH - *Chromosome Deletion MH - Chromosomes, Artificial, Bacterial/genetics MH - Chromosomes, Artificial, P1 Bacteriophage/genetics MH - Chromosomes, Human, Pair 17/*genetics MH - Comparative Study MH - Contig Mapping/methods MH - Female MH - Fungal Proteins/genetics MH - Gene Order/genetics MH - Humans MH - Male MH - Mental Retardation/*genetics MH - Mice MH - Physical Chromosome Mapping/methods MH - *Proton-Translocating ATPases MH - Pseudogenes/genetics MH - Research Support, Non-U.S. Gov't MH - Research Support, U.S. Gov't, P.H.S. MH - *Saccharomyces cerevisiae Proteins MH - Syndrome MH - Synteny/*genetics EDAT- 2002/05/09 10:00 MHDA- 2002/06/06 10:01 AID - 10.1101/gr.73702 [doi] PST - ppublish SO - Genome Res 2002 May;12(5):713-28. PMID- 11997339 OWN - NLM STAT- MEDLINE DA - 20020508 DCOM- 20020605 LR - 20041117 PUBM- Print IS - 1088-9051 VI - 12 IP - 5 DP - 2002 May TI - Structure and evolution of the Smith-Magenis syndrome repeat gene clusters, SMS-REPs. PG - 729-38 AB - An approximately 4-Mb genomic segment on chromosome 17p11.2, commonly deleted in patients with the Smith-Magenis syndrome (SMS) and duplicated in patients with dup(17)(p11.2p11.2) syndrome, is flanked by large, complex low-copy repeats (LCRs), termed proximal and distal SMS-REP. A third copy, the middle SMS-REP, is located between them. SMS-REPs are believed to mediate nonallelic homologous recombination, resulting in both SMS deletions and reciprocal duplications. To delineate the genomic structure and evolutionary origin of SMS-REPs, we constructed a bacterial artificial chromosome/P1 artificial chromosome contig spanning the entire SMS region, including the SMS-REPs, determined its genomic sequence, and used fluorescence in situ hybridization to study the evolution of SMS-REP in several primate species. Our analysis shows that both the proximal SMS-REP (approximately 256 kb) and the distal copy (approximately 176 kb) are located in the same orientation and derived from a progenitor copy, whereas the middle SMS-REP (approximately 241 kb) is inverted and appears to have been derived from the proximal copy. The SMS-REP LCRs are highly homologous (>98%) and contain at least 14 genes/pseudogenes each. SMS-REPs are not present in mice and were duplicated after the divergence of New World monkeys from pre-monkeys approximately 40-65 million years ago. Our findings potentially explain why the vast majority of SMS deletions and dup(17)(p11.2p11.2) occur at proximal and distal SMS-REPs and further support previous observations that higher-order genomic architecture involving LCRs arose recently during primate speciation and may predispose the human genome to both meiotic and mitotic rearrangements. AD - Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, 77030, USA. FAU - Park, Sung-Sup AU - Park SS FAU - Stankiewicz, Pawel AU - Stankiewicz P FAU - Bi, Weimin AU - Bi W FAU - Shaw, Christine AU - Shaw C FAU - Lehoczky, Jessica AU - Lehoczky J FAU - Dewar, Ken AU - Dewar K FAU - Birren, Bruce AU - Birren B FAU - Lupski, James R AU - Lupski JR LA - eng GR - PO1 HD39420/HD/NICHD GR - R01 NS27042/NS/NINDS GR - U54 HG02045/HG/NHGRI PT - Journal Article PL - United States TA - Genome Res JID - 9518021 SB - IM MH - Abnormalities, Multiple/*genetics MH - Base Composition/genetics MH - Cell Line MH - Cell Line, Transformed MH - Chromosomes, Human, Pair 17/genetics MH - Cloning, Molecular/methods MH - Contig Mapping/methods MH - DNA Fingerprinting/methods MH - *Evolution, Molecular MH - Gene Dosage MH - Gene Duplication MH - Genome, Human MH - Humans MH - Mental Retardation/*genetics MH - Multigene Family/*genetics MH - Repetitive Sequences, Nucleic Acid/*genetics MH - Research Support, Non-U.S. Gov't MH - Research Support, U.S. Gov't, P.H.S. MH - Sequence Alignment/methods MH - Sequence Analysis, DNA/methods MH - Sequence Homology, Nucleic Acid MH - Syndrome EDAT- 2002/05/09 10:00 MHDA- 2002/06/06 10:01 AID - 10.1101/gr.82802 [doi] PST - ppublish SO - Genome Res 2002 May;12(5):729-38. PMID- 11997340 OWN - NLM STAT- MEDLINE DA - 20020508 DCOM- 20020605 LR - 20041117 PUBM- Print IS - 1088-9051 VI - 12 IP - 5 DP - 2002 May TI - Discovery of regulatory elements by a computational method for phylogenetic footprinting. PG - 739-48 AB - Phylogenetic footprinting is a method for the discovery of regulatory elements in a set of orthologous regulatory regions from multiple species. It does so by identifying the best conserved motifs in those orthologous regions. We describe a computer algorithm designed specifically for this purpose, making use of the phylogenetic relationships among the sequences under study to make more accurate predictions. The program is guaranteed to report all sets of motifs with the lowest parsimony scores, calculated with respect to the phylogenetic tree relating the input species. We report the results of this algorithm on several data sets of interest. A large number of known functional binding sites are identified by our method, but we also find several highly conserved motifs for which no function is yet known. AD - Department of Computer Science and Engineering, University of Washington, Seattle, Washington 98195-2350, USA. FAU - Blanchette, Mathieu AU - Blanchette M FAU - Tompa, Martin AU - Tompa M LA - eng PT - Letter PL - United States TA - Genome Res JID - 9518021 RN - 0 (Fish Proteins) RN - 0 (Interleukin-3) RN - 11061-68-0 (Insulin) RN - 122784-93-4 (growth hormone type I, Salmo salar) RN - 9002-72-6 (Growth Hormone) RN - 9038-94-2 (Metallothionein) SB - IM MH - Algorithms MH - Animals MH - Comparative Study MH - Computational Biology/*methods MH - DNA Footprinting/*methods MH - *Fish Proteins MH - Genes, fos/genetics MH - Genes, myc/genetics MH - Growth Hormone/genetics MH - Humans MH - Insulin/genetics MH - Interleukin-3/genetics MH - Introns/genetics MH - Metallothionein/genetics MH - Multigene Family/genetics MH - *Phylogeny MH - Promoter Regions (Genetics)/genetics MH - Regulatory Sequences, Nucleic Acid/*genetics MH - Research Support, Non-U.S. Gov't MH - Research Support, U.S. Gov't, Non-P.H.S. EDAT- 2002/05/09 10:00 MHDA- 2002/06/06 10:01 AID - 10.1101/gr.6902 [doi] PST - ppublish SO - Genome Res 2002 May;12(5):739-48. PMID- 11997341 OWN - NLM STAT- MEDLINE DA - 20020508 DCOM- 20020605 LR - 20041203 PUBM- Print IS - 1088-9051 VI - 12 IP - 5 DP - 2002 May TI - Transcriptional regulation of the stem cell leukemia gene (SCL)--comparative analysis of five vertebrate SCL loci. PG - 749-59 AB - The stem cell leukemia (SCL) gene encodes a bHLH transcription factor with a pivotal role in hematopoiesis and vasculogenesis and a pattern of expression that is highly conserved between mammals and zebrafish. Here we report the isolation and characterization of the zebrafish SCL locus together with the identification of three neighboring genes, IER5, MAP17, and MUPP1. This region spans 68 kb and comprises the longest zebrafish genomic sequence currently available for comparison with mammalian, chicken, and pufferfish sequences. Our data show conserved synteny between zebrafish and mammalian SCL and MAP17 loci, thus suggesting the likely genomic domain necessary for the conserved pattern of SCL expression. Long-range comparative sequence analysis/phylogenetic footprinting was used to identify noncoding conserved sequences representing candidate transcriptional regulatory elements. The SCL promoter/enhancer, exon 1, and the poly(A) region were highly conserved, but no homology to other known mouse SCL enhancers was detected in the zebrafish sequence. A combined homology/structure analysis of the poly(A) region predicted consistent structural features, suggesting a conserved functional role in mRNA regulation. Analysis of the SCL promoter/enhancer revealed five motifs, which were conserved from zebrafish to mammals, and each of which is essential for the appropriate pattern or level of SCL transcription. AD - Cambridge Institute for Medical Research, Cambridge University, Cambridge, CB2 2XY, United Kingdom. bg200@cam.ac.uk FAU - Gottgens, Berthold AU - Gottgens B FAU - Barton, Linda M AU - Barton LM FAU - Chapman, Michael A AU - Chapman MA FAU - Sinclair, Angus M AU - Sinclair AM FAU - Knudsen, Bjarne AU - Knudsen B FAU - Grafham, Darren AU - Grafham D FAU - Gilbert, James G R AU - Gilbert JG FAU - Rogers, Jane AU - Rogers J FAU - Bentley, David R AU - Bentley DR FAU - Green, Anthony R AU - Green AR LA - eng PT - Letter PL - United States TA - Genome Res JID - 9518021 RN - 0 (5' Untranslated Regions) RN - 0 (Chromosomes, Artificial, P1 Bacteriophage) RN - 0 (DNA-Binding Proteins) RN - 0 (Genetic Markers) RN - 0 (Proto-Oncogene Proteins) RN - 0 (Tal1 protein, mouse) RN - 0 (Transcription Factors) RN - 0 (Zebrafish Proteins) RN - 0 (tal1 protein, zebrafish) RN - 135471-20-4 (TAL1 protein, human) RN - 24937-83-5 (Poly A) SB - IM MH - 5' Untranslated Regions/genetics MH - Amino Acid Sequence MH - Animals MH - Cell Line MH - Chickens MH - Chromosomes, Artificial, P1 Bacteriophage/genetics MH - Cloning, Molecular MH - Comparative Study MH - Conserved Sequence MH - DNA-Binding Proteins/biosynthesis/*genetics/metabolism MH - Exons/genetics MH - Gene Expression Regulation, Neoplastic/*genetics MH - Genetic Markers/genetics/physiology MH - Humans MH - Leukemia, T-Cell, Acute/*genetics MH - Mice MH - Mice, Transgenic MH - Molecular Sequence Data MH - Poly A/metabolism MH - Promoter Regions (Genetics)/genetics MH - *Proto-Oncogene Proteins MH - Rats MH - Research Support, Non-U.S. Gov't MH - Sequence Homology, Nucleic Acid MH - Tetraodontiformes MH - Transcription Factors/biosynthesis/chemistry/*genetics MH - Zebrafish/genetics MH - *Zebrafish Proteins EDAT- 2002/05/09 10:00 MHDA- 2002/06/06 10:01 AID - 10.1101/gr.45502 [doi] PST - ppublish SO - Genome Res 2002 May;12(5):749-59. PMID- 11997342 OWN - NLM STAT- MEDLINE DA - 20020508 DCOM- 20020605 LR - 20041117 PUBM- Print IS - 1088-9051 VI - 12 IP - 5 DP - 2002 May TI - Determination of redundancy and systems properties of the metabolic network of Helicobacter pylori using genome-scale extreme pathway analysis. PG - 760-9 AB - The capabilities of genome-scale metabolic networks can be described through the determination of a set of systemically independent and unique flux maps called extreme pathways. The first study of genome-scale extreme pathways for the simultaneous formation of all nonessential amino acids or ribonucleotides in Helicobacter pylori is presented. Three key results were obtained. First, the extreme pathways for the production of individual amino acids in H. pylori showed far fewer internal states per external state than previously found in Haemophilus influenzae, indicating a more rigid metabolic network. Second, the degree of pathway redundancy in H. pylori was essentially the same for the production of individual amino acids and linked amino acid sets, but was approximately twice that of the production of the ribonucleotides. Third, the metabolic network of H. pylori was unable to achieve extensive conversion of amino acids consumed to the set of either nonessential amino acids or ribonucleotides and thus diverted a large portion of its nitrogen to ammonia production, a potentially important result for pH regulation in its acidic habitat. Genome-scale extreme pathways elucidate emergent system-wide properties. Extreme pathway analysis is emerging as a potentially important method to analyze the link between the metabolic genotype and its phenotypes. AD - Department of Bioengineering, University of California at San Diego, La Jolla, California 92093, USA. FAU - Price, Nathan D AU - Price ND FAU - Papin, Jason A AU - Papin JA FAU - Palsson, Bernhard O AU - Palsson BO LA - eng GR - GM57089/GM/NIGMS PT - Letter PL - United States TA - Genome Res JID - 9518021 RN - 0 (Amino Acids) RN - 0 (Nucleotides) RN - 7440-44-0 (Carbon) RN - 7727-37-9 (Nitrogen) SB - IM MH - Amino Acids/biosynthesis/metabolism MH - Biomass MH - Carbon/metabolism MH - Comparative Study MH - Escherichia coli/metabolism MH - *Genome, Bacterial MH - Genotype MH - Helicobacter pylori/*genetics/*metabolism/physiology MH - Nitrogen/metabolism MH - Nucleotides/biosynthesis MH - Phenotype MH - Research Support, Non-U.S. Gov't MH - Research Support, U.S. Gov't, Non-P.H.S. MH - Research Support, U.S. Gov't, P.H.S. EDAT- 2002/05/09 10:00 MHDA- 2002/06/06 10:01 AID - 10.1101/gr.218002. Article published online before print in April 2002 [doi] PST - ppublish SO - Genome Res 2002 May;12(5):760-9. PMID- 11997343 OWN - NLM STAT- MEDLINE DA - 20020508 DCOM- 20020605 LR - 20041117 PUBM- Print IS - 1088-9051 VI - 12 IP - 5 DP - 2002 May TI - Evidence suggesting that a fifth of annotated Caenorhabditis elegans genes may be pseudogenes. PG - 770-5 AB - Only a minority of the genes, identified in the Caenorhabditis elegans genome sequence data by computer analysis, have been characterized experimentally. We attempted to determine the expression patterns for a random sample of the annotated genes using reporter gene fusions. A low success rate was obtained for evolutionarily recently duplicated genes. Analysis of the data suggests that this is not due to conditional or low-level expression. The remaining explanation is that most of the annotated genes in the recently duplicated category are pseudogenes, a proportion corresponding to 20% of all of the annotated C. elegans genes. Further support for this surprisingly high figure was sought by comparing sequences for families of recently duplicated C. elegans genes. Although only a preliminary analysis, clear evidence for a gene having been recently inactivated by genetic drift was found for many genes in the recently duplicated category. At least 4% of the annotated C. elegans genes can be recognized as pseudogenes simply from closer inspection of the sequence data. Lessons learned in identifying pseudogenes in C. elegans could be of value in the annotation of the genomes of other species where, although there may be fewer pseudogenes, they may be harder to detect. AD - School of Biology, University of Leeds, Leeds, LS2 9JT, United Kingdom. FAU - Mounsey, Andrew AU - Mounsey A FAU - Bauer, Petra AU - Bauer P FAU - Hope, Ian A AU - Hope IA LA - eng PT - Letter PL - United States TA - Genome Res JID - 9518021 RN - 0 (Caenorhabditis elegans Proteins) SB - IM MH - Amino Acid Sequence MH - Animals MH - Caenorhabditis elegans/*genetics MH - Caenorhabditis elegans Proteins/genetics MH - Computational Biology/*methods MH - Gene Expression Regulation MH - Gene Fusion/methods MH - Genes, Reporter/genetics MH - Genes, Structural, Helminth/*genetics MH - Molecular Sequence Data MH - Pseudogenes/*genetics MH - Research Support, Non-U.S. Gov't EDAT- 2002/05/09 10:00 MHDA- 2002/06/06 10:01 AID - 10.1101/gr208802. Article published online before print in April 2002 [doi] PST - ppublish SO - Genome Res 2002 May;12(5):770-5. PMID- 11997344 OWN - NLM STAT- MEDLINE DA - 20020508 DCOM- 20020605 LR - 20041117 PUBM- Print IS - 1088-9051 VI - 12 IP - 5 DP - 2002 May TI - Analyses of the extent of shared synteny and conserved gene orders between the genome of Fugu rubripes and human 20q. PG - 776-84 AB - Cosmid and BAC contig maps have been constructed across two Fugu genomic regions containing the orthologs of human genes mapping to human chromosome 20q. Contig gene contents have been assessed by sample sequencing and comparative database analyses. Contigs are centered around two Fugu topoisomerase1 (top1) genes that were initially identified by sequence similarity to human TOP1 (20q12). Two other genes (SNAI1 and KRML) mapping to human chromosome 20 are also duplicated in Fugu. The two contigs have been mapped to separate Fugu chromosomes. Our data indicate that these linkage groups result from the duplication of an ancestral chromosome segment containing at least 40 genes that now map to the long arm of human chromosome 20. Although there is considerable conservation of synteny, gene orders are not well conserved between Fugu and human, with only very short sections of two to three adjacent genes being maintained in both organisms. Comparative analyses have allowed this duplication event to be dated before the separation of Fugu and zebrafish. Our data (which are best explained by regional duplication, followed by substantial gene loss) support the hypothesis that there have been a large number of gene and regional duplications (and corresponding gene loss) in the fish lineage, possibly resulting from a single whole genome duplication event. AD - Fugu Genomics, United Kingdom Human Genome Mapping Project Resource Centre, Wellcome Genome Campus, Hinxton Hall, Hinxton, Cambridgeshire, CB10 1SB, United Kingdom. sfsmith@hgmp.mrc.ac.uk FAU - Smith, Sarah F AU - Smith SF FAU - Snell, Philip AU - Snell P FAU - Gruetzner, Frank AU - Gruetzner F FAU - Bench, Anthony J AU - Bench AJ FAU - Haaf, Thomas AU - Haaf T FAU - Metcalfe, Judith A AU - Metcalfe JA FAU - Green, Anthony R AU - Green AR FAU - Elgar, Greg AU - Elgar G LA - eng PT - Letter PL - United States TA - Genome Res JID - 9518021 RN - 0 (Cosmids) SB - IM MH - Animals MH - Cell Line MH - Chromosomes, Human, Pair 20/*genetics MH - Comparative Study MH - Conserved Sequence/*genetics MH - Contig Mapping/methods MH - Cosmids/genetics MH - Gene Duplication MH - Gene Order/*genetics MH - *Genome MH - Genome, Human MH - Humans MH - Microscopy, Fluorescence MH - Sequence Tagged Sites MH - Synteny/*genetics MH - Takifugu/*genetics MH - Zebrafish/genetics EDAT- 2002/05/09 10:00 MHDA- 2002/06/06 10:01 AID - 10.1101/gr.221802. Article published online before print in April 2002 [doi] PST - ppublish SO - Genome Res 2002 May;12(5):776-84. PMID- 11997345 OWN - NLM STAT- MEDLINE DA - 20020508 DCOM- 20020605 LR - 20041117 PUBM- Print IS - 1088-9051 VI - 12 IP - 5 DP - 2002 May TI - Large-scale protein annotation through gene ontology. PG - 785-94 AB - Recent progress in genomic sequencing, computational biology, and ontology development has presented an opportunity to investigate biological systems from a unique perspective, that is, examining genomes and transcriptomes through the multiple and hierarchical structure of Gene Ontology (GO). We report here our development of GO Engine, a computational platform for GO annotation, and analysis of the resultant GO annotations of human proteins. Protein annotation was centered on sequence homology with GO-annotated proteins and protein domain analysis. Text information analysis and a multiparameter cellular localization predictive tool were also used to increase the annotation accuracy, and to predict novel annotations. The majority of proteins corresponding to full-length mRNA in GenBank, and the majority of proteins in the NR database (nonredundant database of proteins) were annotated with one or more GO nodes in each of the three GO categories. The annotations of GenBank and SWISS-PROT proteins are available to the public at the GO Consortium web site. AD - Compugen Inc., Jamesburg, New Jersey 08831, USA. han@cgen.com FAU - Xie, Hanqing AU - Xie H FAU - Wasserman, Alon AU - Wasserman A FAU - Levine, Zurit AU - Levine Z FAU - Novik, Amit AU - Novik A FAU - Grebinskiy, Vladimir AU - Grebinskiy V FAU - Shoshan, Avi AU - Shoshan A FAU - Mintz, Liat AU - Mintz L LA - eng PT - Letter PL - United States TA - Genome Res JID - 9518021 RN - 0 (Proteins) SB - IM MH - Animals MH - Computational Biology/*methods MH - Databases, Genetic MH - Databases, Protein MH - Genome, Human MH - Humans MH - Multigene Family MH - Proteins/*classification/*genetics/physiology MH - Sequence Analysis, Protein MH - Sequence Homology, Amino Acid EDAT- 2002/05/09 10:00 MHDA- 2002/06/06 10:01 AID - 10.1101/gr.86902 [doi] PST - ppublish SO - Genome Res 2002 May;12(5):785-94. PMID- 11997346 OWN - NLM STAT- MEDLINE DA - 20020508 DCOM- 20020605 LR - 20041117 PUBM- Print IS - 1088-9051 VI - 12 IP - 5 DP - 2002 May TI - Integration of Cot analysis, DNA cloning, and high-throughput sequencing facilitates genome characterization and gene discovery. PG - 795-807 AB - Cot-based sequence discovery represents a powerful means by which both low-copy and repetitive sequences can be selectively and efficiently fractionated, cloned, and characterized. Based upon the results of a Cot analysis, hydroxyapatite chromatography was used to fractionate sorghum (Sorghum bicolor) genomic DNA into highly repetitive (HR), moderately repetitive (MR), and single/low-copy (SL) sequence components that were consequently cloned to produce HRCot, MRCot, and SLCot genomic libraries. Filter hybridization (blotting) and sequence analysis both show that the HRCot library is enriched in sequences traditionally found in high-copy number (e.g., retroelements, rDNA, centromeric repeats), the SLCot library is enriched in low-copy sequences (e.g., genes and "nonrepetitive ESTs"), and the MRCot library contains sequences of moderate redundancy. The Cot analysis suggests that the sorghum genome is approximately 700 Mb (in agreement with previous estimates) and that HR, MR, and SL components comprise 15%, 41%, and 24% of sorghum DNA, respectively. Unlike previously described techniques to sequence the low-copy components of genomes, sequencing of Cot components is independent of expression and methylation patterns that vary widely among DNA elements, developmental stages, and taxa. High-throughput sequencing of Cot clones may be a means of "capturing" the sequence complexity of eukaryotic genomes at unprecedented efficiency. AD - Center for Applied Genetic Technologies and Department of Crop and Soil Sciences, University of Georgia, Athens, Georgia 30602, USA. dgp@arches.uga.edu FAU - Peterson, Daniel G AU - Peterson DG FAU - Schulze, Stefan R AU - Schulze SR FAU - Sciara, Erica B AU - Sciara EB FAU - Lee, Scott A AU - Lee SA FAU - Bowers, John E AU - Bowers JE FAU - Nagel, Alexander AU - Nagel A FAU - Jiang, Ning AU - Jiang N FAU - Tibbitts, Deanne C AU - Tibbitts DC FAU - Wessler, Susan R AU - Wessler SR FAU - Paterson, Andrew H AU - Paterson AH LA - eng SI - GENBANK/AZ921847 SI - GENBANK/AZ921848 SI - GENBANK/AZ921849 SI - GENBANK/AZ921850 SI - GENBANK/AZ921851 SI - GENBANK/AZ921852 SI - GENBANK/AZ921853 SI - GENBANK/AZ921854 SI - GENBANK/AZ921855 SI - GENBANK/AZ921856 SI - GENBANK/AZ921857 SI - GENBANK/AZ921858 SI - GENBANK/AZ921859 SI - GENBANK/AZ921860 SI - GENBANK/AZ921861 SI - GENBANK/AZ921862 SI - GENBANK/AZ921863 SI - GENBANK/AZ921864 SI - GENBANK/AZ921865 SI - GENBANK/AZ921866 SI - GENBANK/AZ921867 SI - 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GENBANK/AZ922834 SI - GENBANK/AZ922835 SI - GENBANK/AZ922836 SI - GENBANK/AZ922837 SI - GENBANK/AZ922838 SI - GENBANK/AZ922839 SI - GENBANK/AZ922840 SI - GENBANK/AZ922841 SI - GENBANK/AZ922842 SI - GENBANK/AZ922843 SI - GENBANK/AZ922844 SI - GENBANK/AZ922845 SI - GENBANK/AZ922846 PT - Journal Article PL - United States TA - Genome Res JID - 9518021 RN - 0 (Chromosomes, Artificial, Bacterial) RN - 0 (Genetic Markers) RN - 0 (Plant Proteins) RN - 0 (kafirin protein, Sorghum bicolor) SB - IM MH - Base Composition/genetics MH - Blotting, Southern/methods MH - Chromosomes, Artificial, Bacterial/genetics MH - Cloning, Molecular/*methods MH - Expressed Sequence Tags MH - GC Rich Sequence/genetics MH - Gene Dosage MH - *Genes, Structural, Plant MH - Genetic Markers/genetics MH - *Genome, Plant MH - Genomic Library MH - Molecular Sequence Data MH - Nucleic Acid Denaturation MH - Nucleic Acid Hybridization MH - Plant Proteins/genetics MH - Poaceae/*genetics MH - Repetitive Sequences, Nucleic Acid/genetics MH - Research Support, U.S. Gov't, Non-P.H.S. MH - Sequence Analysis, DNA/*methods MH - Temperature EDAT- 2002/05/09 10:00 MHDA- 2002/06/06 10:01 AID - 10.1101/gr.226102. Article published online before print in April 2002 [doi] PST - ppublish SO - Genome Res 2002 May;12(5):795-807. PMID- 11997347 OWN - NLM STAT- MEDLINE DA - 20020508 DCOM- 20020605 PUBM- Print IS - 1088-9051 VI - 12 IP - 5 DP - 2002 May TI - Protein coding palindromes are a unique but recurrent feature in Rickettsia. PG - 808-16 AB - Rickettsia are unique in inserting in-frame a number of palindromic sequences within protein coding regions. In this study, we extensively analyzed repeated sequences in the genome of Rickettsia conorii and examined their locations in regard to coding versus noncoding regions. We identified 656 interspersed repeated sequences classified into 10 distinct families. Of the 10 families, three palindromic sequence families showed clear cases of insertions into open reading frames (ORFs). The location of those in-frame insertions appears to be always compatible with the encoded protein three-dimensional (3-D) fold and function. We provide evidence for a progressive loss of the palindromic property over time after the insertions. This comprehensive st