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Biomedical subjects

L B Ellis

Publications and source records attributed to L B Ellis.

At least 19 recordsLinked to original sources

The University of Minnesota Biocatalysis/Biodegradation Database: emphasizing enzymes.

The University of Minnesota Biocatalysis/Biodegradation Database (UM-BBD, http://umbbd.ahc.umn.edu/) provides curated information on microbial catabolic enzymes and their organization into metabolic pathways. Currently, it contains information on over 400 enzymes. In the last year the enzyme page was enhanced to contain more internal and external links; it also displays the different metabolic pathways in which each enzyme participates. In collaboration with the Nomenclature Commission of the International Union of Biochemistry and Molecular Biology, 35 UM-BBD enzymes were assigned complete EC codes during 2000. Bacterial oxygenases are heavily represented in the UM-BBD; they are known to have broad substrate specificity. A compilation of known reactions of naphthalene and toluene dioxygenases were recently added to the UM-BBD; 73 and 108 were listed respectively. In 2000 the UM-BBD is mirrored by two prestigious groups: the European Bioinformatics Institute and KEGG (the Kyoto Encyclopedia of Genes and Genomes). Collaborations with other groups are being developed. The increased emphasis on UM-BBD enzymes is important for predicting novel metabolic pathways that might exist in nature or could be engineered. It also is important for current efforts in microbial genome annotation.

Bacteria↗

The University of Minnesota Biocatalysis/Biodegradation database: microorganisms, genomics and prediction.

The University of Minnesota Biocatalysis/Biodegradation Database (http://www.labmed.umn.edu/umbbd/ ) begins its fifth year having met its initial goals. It contains approximately 100 pathways for microbial catabolic metabolism of primarily xenobiotic organic compounds, including information on approximately 650 reactions, 600 compounds and 400 enzymes, and containing approximately 250 microorganism entries. It includes information on most known microbial catabolic reaction types and the organic functional groups they transform. Having reached its first goals, it is ready to move beyond them. It is poised to grow in many different ways, including mirror sites; fold prediction for its sequenced enzymes; closer ties to genome and microbial strain databases; and the prediction of biodegradation pathways for compounds it does not contain.

Biodegradation, Environmental↗

Environmental biotechnology informatics.

Environmental biotechnology informatics is in its infancy and is growing fast. Computer and information science can assist environmental biotechnology by developing biological databases and building mathematical models of biological systems. Funding and training limitations in this field may, however, hinder its future growth.

Biodegradation, Environmental↗

Continuing professional education and the selection of candidates: the case for a tripartite model.

This paper argues the case for a tripartite model involving the manager educator and practitioner in the selection of candidates to programmes of continuing professional education (CPE). Nurse educators are said to play a key link in the education practice chain (Pendleton & Myles 1991), yet with the introduction of a market philosophy for education, the educator appears to have little, if any, influence over the selection of CPE candidates. Empirical studies on the value of an effective system for identifying the educational needs of the individual and the locality are unequivocal in specifying the benefits of a collaborative selection process (Larcombe & Maggs 1991). However, there are few studies that offer a model of collaboration and fewer still on how to operationalize such a model. This paper presents the policy and legislative context of CPE leading to the development of a market philosophy. The tension between educational reforms such as life-long learning and diminishing and finite resources are highlighted. These strategic issues provide the backdrop and rationale for considering the process for identifying CPE needs, and the characteristics of an effective system as suggested in the literature. Finally, this paper outlines recommendations for a partnership between the manager practitioner and educationalist in the selection of CPE candidates.

Education, Nursing, Continuing↗

The University of Minnesota Biocatalysis/Biodegradation Database: specialized metabolism for functional genomics.

The University of Minnesota Biocatalysis/Biodegradation Database (UM-BBD, http://www.labmed.umn.edu/umbbd/i nde x.html) first became available on the web in 1995 to provide information on microbial biocatalytic reactions of, and biodegradation pathways for, organic chemical compounds, especially those produced by man. Its goal is to become a representative database of biodegradation, spanning the diversity of known microbial metabolic routes, organic functional groups, and environmental conditions under which biodegradation occurs. The database can be used to enhance understanding of basic biochemistry, biocatalysis leading to speciality chemical manufacture, and biodegradation of environmental pollutants. It is also a resource for functional genomics, since it contains information on enzymes and genes involved in specialized metabolism not found in intermediary metabolism databases, and thus can assist in assigning functions to genes homologous to such less common genes. With information on >400 reactions and compounds, it is poised to become a resource for prediction of microbial biodegradation pathways for compounds it does not contain, a process complementary to predicting the functions of new classes of microbial genes.

Bacteria↗

Financing a future for public biological data.

MOTIVATION: The public web-based biological database infrastructure is a source of both wonder and worry. Users delight in the ever increasing amounts of information available; database administrators and curators worry about long-term financial support. An earlier study of 153 biological databases (Ellis and Kalumbi, Nature Biotechnol., 16, 1323-1324, 1998) determined that near future (1-5 year) funding for over two-thirds of them was uncertain. More detailed data are required to determine the magnitude of the problem and offer possible solutions. METHODS: This study examines the finances and use statistics of a few of these organizations in more depth, and reviews several economic models that may help sustain them. RESULTS: Six organizations were studied. Their administrative overhead is fairly low; non-administrative personnel and computer-related costs account for 77% of expenses. One smaller, more specialized US database, in 1997, had 60% of total access from US domains; a majority (56%) of its US accesses came from commercial domains, although only 2% of the 153 databases originally studied received any industrial support. The most popular model used to gain industrial support is asymmetric pricing: preferentially charging the commercial users of a database. At least five biological databases have recently begun using this model. Advertising is another model which may be useful for the more general, more heavily used sites. Microcommerce has promise, especially for databases that do not attract advertisers, but needs further testing. The least income reported for any of the databases studied was $50,000/year; applying this rate to 400 biological databases (a lower limit of the number of such databases, many of which require far larger resources) would mean annual support need of at least $20 million. To obtain this level of support is challenging, yet failure to accept the challenge could be catastrophic. CONTACT: lynda@tc.umn. edu

Computational Biology↗

Predicting biodegradation.

Biodegradation is important for natural and industrial cycling of environmental chemicals. Industries and government regulators increasingly seek to know the fate of chemicals in the environment and thus prevent potential negative impacts on human or ecosystem health. However, millions of organic compounds are known, and most will remain unstudied with respect to biodegradation. This necessitates the development of organized biodegradation information coupled with predictive methods. Biodegradation prediction methods are being developed using the information contained in the University of Minnesota Biocatalysis/ Biodegradation database. Heuristic rules are derived from compiled biodegradation information. Additional rules are generated by deconstructing compounds into a set of the 40 most common organic functional groups. The rules consist of deriving biochemically plausible catabolic reactions for each of the functional groups. More complex compounds, containing multiple functional groups, are analysed using higher order rules requiring prioritizing enzymatic attack and reactions cleaving functional groups. While biodegradation prediction, like weather prediction, will never be perfect, it can be an important tool for guiding industry, regulators and experimentalists.

Bacteria↗

Representing metabolic pathway information: an object-oriented approach.

MOTIVATION: The University of Minnesota Biocatalysis/Biodegradation Database (UM-BBD) is a website providing information and dynamic links for microbial metabolic pathways, enzyme reactions, and their substrates and products. The Compound, Organism, Reaction and Enzyme (CORE) object-oriented database management system was developed to contain and serve this information. RESULTS: CORE was developed using Java, an object-oriented programming language, and PSE persistent object classes from Object Design, Inc. CORE dynamically generates descriptive web pages for reactions, compounds and enzymes, and reconstructs ad hoc pathway maps starting from any UM-BBD reaction. AVAILABILITY: CORE code is available from the authors upon request. CORE is accessible through the UM-BBD at: http://www. labmed.umn.edu/umbbd/index.html.

Databases, Factual↗

In pursuit of optimal rejuvenation of the forehead: endoscopic brow lift with simultaneous carbon dioxide laser resurfacing.

Coronal foreheadplasty has long been the traditional method of improving the aesthetic appearance of the forehead, permitting not only repositioning of ptotic tissues but also direct access for modification of the "frown" muscles. However, it was only moderately successful in eliminating vertical corrugator lines or deeply etched transverse wrinkles. The recent advent of the endoscopic brow lift has permitted us to minimize the dysesthesias associated with the coronal approach by making the incisions shorter and radially oriented and by being more precise in the muscle resection. Nonetheless, endoscopic brow lift gives no further improvement in persistent deep vertical and transverse wrinkles. Carbon dioxide laser resurfacing can improve the existing wrinkles but does not eliminate the muscular cause of forehead wrinkles. It seemed reasonable that combining these techniques might yield better results than either procedure alone. To evaluate this possibility, 30 patients with simultaneous endoscopic brow lift and carbon dioxide resurfacing were compared with 24 patients having laser resurfacing only and with 26 patients who had traditional coronal foreheadplasty. Both foreheadplasty groups had corrugator resection. All patients were evaluated at least 4 to 6 months postoperatively. Ratings were based on the percent of wrinkles removed, both vertical and transverse. The ratings were performed with predetermined criteria by a surgeon not involved with the operative procedures nor after care. A rating of "excellent" (> or = 95 percent reduction in wrinkles) was obtained in 50 percent of coronal foreheadplasties; 41.7 percent of carbon dioxide resurfacing alone and 80 percent of endobrow lifts with carbon dioxide laser resurfacing. There was no vascular compromise from this latter combination of procedures, no hypertrophic scars, and no impairment of healing. We conclude that endoscopic brow lift with carbon dioxide laser resurfacing is a safe and perhaps more effective means of aesthetic rejuvenation of the forehead.

Adult↗

A manganese-dependent dioxygenase from Arthrobacter globiformis CM-2 belongs to the major extradiol dioxygenase family.

Almost all bacterial ring cleavage dioxygenases contain iron as the catalytic metal center. We report here the first available sequence for a manganese-dependent 3,4-dihydroxyphenylacetate (3,4-DHPA) 2,3-dioxygenase and its further characterization. This manganese-dependent extradiol dioxygenase from Arthrobacter globiformis CM-2, unlike iron-dependent extradiol dioxygenases, is not inactivated by hydrogen peroxide. Also, ferrous ions, which activate iron extradiol dioxygenases, inhibit 3,4-DHPA 2,3-dioxygenase. The gene encoding 3,4-DHPA 2,3-dioxygenase, mndD, was identified from an A. globiformis CM-2 cosmid library. mndD was subcloned as a 2.0-kb SmaI fragment in pUC18, from which manganese-dependent extradiol dioxygenase activity was expressed at high levels in Escherichia coli. The mndD open reading frame was identified by comparison with the known N-terminal amino acid sequence of purified manganese-dependent 3,4-DHPA 2,3-dioxygenase. Fourteen of 18 amino acids conserved in members of the iron-dependent extradiol dioxygenase family are also conserved in the manganese-dependent 3,4-DHPA 2,3-dioxygenase (MndD). Thus, MndD belongs to the extradiol family of dioxygenases and may share a common ancestry with the iron-dependent extradiol dioxygenases. We propose the revised consensus primary sequence (G,T,N,R)X(H,A)XXXXXXX(L,I,V,M,F)YXX(D,E,T,N,A)PX(G,P) X(2,3)E for this family. (Numbers in brackets indicate a gap of two or three residues at this point in the sequence.) The suggested common ancestry is also supported by sequence obtained from genes flanking mndD, which share significant sequence identity with xylJ and xylG from Pseudomonas putida.

3,4-Dihydroxyphenylacetic Acid↗

Valid and invalid implementations of GOR secondary structure predictions.

GOR algorithms have long been a standard methodology for predicting protein secondary structure from primary sequence. We have developed two short validation sequences for the GOR I and GOR II algorithms. Use of these sequences with seven commercial and non-commercial implementations of these algorithms demonstrated that several were incorrect implementations, including two of the three commercial modules implementing the GOR I algorithm. This may be due to an easy misinterpretation of the GOR I algorithm and related data tables. We present the validation sequences and discuss implications of this widely propagated error on secondary and tertiary structure prediction, using several proteins of known structure in three different structural classes as examples. A valid GOR I implementation predicts secondary structure increases the accuracy of predictions by from 1-13 percentage points over an invalid implementation based on the easy misinterpretation. A valid implementation of the GOR I and GOR II algorithms is available from the authors.

Algorithms↗

MIF protein are theta-class glutathione S-transferase homologs.

MIF proteins are mammalian polypeptides of approximately 13,000 molecular weight. This class includes human macrophage migration inhibitory factor (MIF), a rat liver protein that has glutathione S-transferase (GST) activity (TRANSMIF), and the mouse delayed early response gene 6 (DER6) protein. MIF proteins were previously linked to GSTs by demonstrating transferase activity and observing N-terminal sequence homology with a mu-class GST (Blocki, F.A., Schlievert, P.M., & Wackett, L.P., 1992, Nature 360, 269-270). In this study, MIF proteins are shown to be structurally related to the theta class of GSTs. This is established in three ways. First, unique primary sequence patterns are developed for each of the GST gene classes. The patterns identify the three MIF proteins as theta-like transferase homologs. Second, pattern analysis indicates that GST members of the theta class contain a serine residue in place of the N-terminal tyrosine that is implicated in glutathione deprotonation and activation in GSTs of known structure (Liu, S., et al., 1992, J. Biol. Chem. 267, 4296-4299). The MIF proteins contain a threonine at this position. Third, polyclonal antibodies raised against recombinant human MIF cross-react on Western blots with rat theta GST but not with alpha and mu GSTs. That MIF proteins have glutathione-binding ability may provide a common structural key toward understanding the varied functions of this widely distributed emerging gene family. Because theta is thought to be the most ancient evolutionary GST class, MIF proteins may have diverged early in evolution but retained a glutathione-binding domain.

Amino Acid Sequence↗

Computer-based patient education revisited.

Good patient education teaches ideas and skills that help patients cope with immediate medical problems, maintain health and avoid disease. Patient education is increasingly important as hospital stays are shortened, patients become more active health consumers, and there is more need to document informed consent for treatment. It is difficult to provide consistent high quality patient education and reimbursement is problematic. Computers have unique attributes for individualized, effective instruction, including variable lesson pacing controlled by the patient and the ability to accurately track the level of patient understanding to document informed consent and for third party reimbursement purposes. The ability of the computer to persuade as well as inform helps motivate behavior change. The unrealized potential of computer-based patient education makes clear the need for further research on how to effectively use this unique tool for patient education.

Health Behavior↗

Using claims data for epidemiologic research. The concordance of claims-based criteria with the medical record and patient survey for identifying a hypertensive population.

In this study, a method was developed to identify health plan members with hypertension from insurance claims, using medical records and a patient survey for validation. A sample of 2,079 patients from two study sites with medical service or pharmacy claims indicating a diagnosis of essential hypertension were surveyed, and the medical records of 182 of the 1,275 survey respondents were reviewed. Where the criteria to identify hypertensive patients used both the medical and pharmacy claims, there was 96% agreement with either the medical record or the patient survey. Where the criteria relied on medical claims alone, the agreement rate decreased to 74% with the medical record and 64% with the patient survey. Where the criteria relied on the pharmacy claims alone, the agreement rate was 67% with the medical record and 75% with the patient survey. Combined evidence from medical service and pharmacy claims yielded a high level of agreement with alternative, more costly sources of data in identifying patients with essential hypertension. As it is more thoroughly investigated, claims data should become a more widely accepted resource for epidemiologic research.

Adolescent↗