Showing papers by "David Eisenberg published in 2004"

The HUPO PSI's molecular interaction format--a community standard for the representation of protein interaction data.

Abstract: A major goal of proteomics is the complete description of the protein interaction network underlying cell physiology. A large number of small scale and, more recently, large-scale experiments have contributed to expanding our understanding of the nature of the interaction network. However, the necessary data integration across experiments is currently hampered by the fragmentation of publicly available protein interaction data, which exists in different formats in databases, on authors' websites or sometimes only in print publications. Here, we propose a community standard data model for the representation and exchange of protein interaction data. This data model has been jointly developed by members of the Proteomics Standards Initiative (PSI), a work group of the Human Proteome Organization (HUPO), and is supported by major protein interaction data providers, in particular the Biomolecular Interaction Network Database (BIND), Cellzome (Heidelberg, Germany), the Database of Interacting Proteins (DIP), Dana Farber Cancer Institute (Boston, MA, USA), the Human Protein Reference Database (HPRD), Hybrigenics (Paris, France), the European Bioinformatics Institute's (EMBL-EBI, Hinxton, UK) IntAct, the Molecular Interactions (MINT, Rome, Italy) database, the Protein-Protein Interaction Database (PPID, Edinburgh, UK) and the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING, EMBL, Heidelberg, Germany).

Heavy Metal Content of Ayurvedic Herbal Medicine Products

Abstract: ContextLead, mercury, and arsenic intoxication have been associated with the use of Ayurvedic herbal medicine product (HMPs).ObjectivesTo determine the prevalence and concentration of heavy metals in Ayurvedic HMPs manufactured in South Asia and sold in Boston-area stores and to compare estimated daily metal ingestion with regulatory standards.Design and SettingSystematic search strategy to identify all stores 20 miles or less from Boston City Hall that sold Ayurvedic HMPs from South Asia by searching online Yellow Pages using the categories markets, supermarkets, and convenience stores, and business names containing the word India, Indian cities, and Indian words. An online national directory of Indian grocery stores, a South Asian community business directory, and a newspaper were also searched. We visited each store and purchased all unique Ayurvedic HMPs between April 25 and October 24, 2003.Main Outcome MeasuresConcentrations (μg/g) of lead, mercury, and arsenic in each HMP as measured by x-ray fluorescence spectroscopy. Estimates of daily metal ingestion for adults and children estimated using manufacturers’ dosage recommendations with comparisons to US Pharmacopeia and US Environmental Protection Agency regulatory standards.ResultsA total of 14 (20%) of 70 HMPs (95% confidence interval, 11%-31%) contained heavy metals: lead (n = 13; median concentration, 40 μg/g; range, 5-37 000), mercury (n = 6; median concentration, 20 225 μg/g; range, 28-104 000), and/or arsenic (n = 6; median concentration, 430 μg/g; range, 37-8130). If taken as recommended by the manufacturers, each of these 14 could result in heavy metal intakes above published regulatory standards.ConclusionsOne of 5 Ayurvedic HMPs produced in South Asia and available in Boston South Asian grocery stores contains potentially harmful levels of lead, mercury, and/or arsenic. Users of Ayurvedic medicine may be at risk for heavy metal toxicity, and testing of Ayurvedic HMPs for toxic heavy metals should be mandatory.

Prolinks: a database of protein functional linkages derived from coevolution

Abstract: The advent of whole-genome sequencing has led to methods that infer protein function and linkages. We have combined four such algorithms (phylogenetic profile, Rosetta Stone, gene neighbor and gene cluster) in a single database - Prolinks - that spans 83 organisms and includes 10 million high-confidence links. The Proteome Navigator tool allows users to browse predicted linkage networks interactively, providing accompanying annotation from public databases. The Prolinks database and the Proteome Navigator tool are available for use online at http://dip.doe-mbi.ucla.edu/pronav.

Prevalence and patterns of adult yoga use in the United States: results of a national survey.

Abstract: Background Although yoga appears to be popular in the United States, there are no published studies on yoga's prevalence or patterns of use. Methods In 1998 we surveyed by telephone a nationally representative sample of 2055 English-speaking U.S. adults (60% weighted response rate) regarding yoga use. Results Of the respondents, 7.5% used yoga at least once in their lifetime and 3.8% used yoga in the previous 12 months. Respondents who used yoga at least once were more likely than non-users to be female (68% vs. 51%), college educated (68% vs. 45%), and urban dwellers (93% vs. 74%). Factors independently associated with yoga use at least once included female gender (OR 2.5 [95% CI 1.7-3.8]), baby boomer age group (ages 34-53) compared to pre-baby boomers (> or = 54 (2.3 [1.4-4.0]), education beyond high school (2.2 [1.4-3.5]), residing in large and small metropolitan areas compared to non-metropolitan areas (3.8 [1.8-7.8] and 2.7 [1.3-5.8], respectively), and use of other CAM therapies (5.3 [2.7-10.5]). Of respondents using yoga in the previous 12 months, 64% reported using yoga for wellness, 48% for health conditions, and 21% specifically for back or neck pain. Ninety percent felt yoga was very or somewhat helpful and 76% did not report spending money related to their yoga. Conclusions In 1998 an estimated 15.0 million American adults had used yoga at least once in their lifetime and 7.4 million during the previous year. Yoga was used for both wellness and specific health conditions often with perceived helpfulness and without expenditure.

Use of mind-body medical therapies.

Abstract: OBJECT: Research demonstrating connections between the mind and body has increased interest in the potential of mind-body therapies. Our aim was to examine the use of mind-body therapies, using data available from a national survey. DESIGN: Analysis of a large nationally representative dataset that comprehensively evaluated the use of mind-body therapies in the last year. SETTING: United States households. PATIENTS/PARTICIPANTS: A total of 2,055 American adults in 1997–1998. INTERVENTIONS: Random national telephone survey. MEASURES AND MAIN RESULTS: We obtained a 60% weighted overall response rate among eligible respondents. We found that 18.9% of adults had used at least 1 mind-body therapy in the last year, with 20.5% of these therapies involving visits to a mind-body professional. Meditation, imagery, and yoga were the most commonly used techniques. Factors independently and positively associated with the use of mind-body therapies in the last year were being 40 to 49 years old (adjusted odds ratio [AOR], 2.03; 95% confidence interval [CI], 1.33 to 3.10), being not married (AOR, 1.78; 95% CI, 1.34 to 2.36), having an educational level of college or greater (AOR, 2.21; 95% CI, 1.57 to 3.09), having used self-prayer for a medical concern (AOR, 2.53; 95% CI, 1.87 to 3.42), and having used another complementary medicine therapy in the last year (AOR, 3.77; 95% CI, 2.74 to 5.20). While used for the full array of medical conditions, they were used infrequently for chronic pain (used by 20% of those with chronic pain) and insomnia (used by 13% of those with insomnia), conditions for which consensus panels have concluded that mind-body therapies are effective. They were also used by less than 20% of those with heart disease, headaches, back or neck pain, and cancer, conditions for which there is strong research support. Mind-body therapies were generally used concomitantly with conventional care: 90% of those using a mind-body therapy in the last year had seen a physician and 80% of mind-body therapies used were discussed with a physician. CONCLUSIONS: Although mind-body therapies were commonly used, much opportunity exists to increase use of mind-body therapies for indications with demonstrated efficacy.

An amyloid-forming segment of β2-microglobulin suggests a molecular model for the fibril

Abstract: In humans suffering from dialysis-related amyloidosis, the protein β2-microglobulin (β2M) is deposited as an amyloid; however, an amyloid of β2M is unknown in mice. β2M sequences from human and mouse are 70% identical, but there is a seven-residue peptide in which six residues differ. This peptide from human β2M forms amyloid in vitro, whereas the mouse peptide does not. Substitution of the human peptide for its counterpart in the mouse sequence results in the formation of amyloid in vitro. These results show that a seven-residue segment of human β2M is sufficient to convert β2M to the amyloid state, and that specific residue interactions are crucial to the conversion. These observations are consistent with a proposed Zipper-spine model for β2M amyloid, in which the spine of the fibril consists of an anhydrous β-sheet.

Common dietary supplements for weight loss.

Abstract: Over-the-counter dietary supplements to treat obesity appeal to many patients who desire a "magic bullet" for weight loss. Asking overweight patients about their use of weight-loss supplements and understanding the evidence for the efficacy, safety, and quality of these supplements are critical when counseling patients regarding weight loss. A schema for whether physicians should recommend, caution, or discourage use of a particular weight-loss supplement is presented in this article. More than 50 individual dietary supplements and more than 125 commercial combination products are available for weight loss. Currently, no weight-loss supplements meet criteria for recommended use. Although evidence of modest weight loss secondary to ephedra-caffeine ingestion exists, potentially serious adverse effects have led the U.S. Food and Drug Administration to ban the sale of these products. Chromium is a popular weight-loss supplement, but its efficacy and long-term safety are uncertain. Guar gum and chitosan appear to be ineffective; therefore, use of these products should be discouraged. Because of insufficient or conflicting evidence regarding the efficacy of conjugated linoleic acid, ginseng, glucomannan, green tea, hydroxycitric acid, L-carnitine, psyllium, pyruvate, and St. John's wort in weight loss, physicians should caution patients about the use of these supplements and closely monitor those who choose to use these products.

Prayer for health concerns: results of a national survey on prevalence and patterns of use.

Abstract: very helpful. Factors independently associated with increased use of prayer (P.05) included age older than 33years(age34-53years:oddsratio[OR],1.6[95%confidence interval (CI), 1.3-2.1]; age 54 years: OR, 1.5 [95% CI, 1.1-2.0]); female sex (OR, 1.4 [95% CI, 1.11.7]); education beyond high school (OR, 1.5 [95% CI, 1.2-1.8]);andhavingdepression,chronicheadaches,back and/or neck pain, digestive problems, or allergies. Only 11% of respondents using prayer discussed it with their physicians.

Use of Logic Relationships to Decipher Protein Network Organization

Abstract: A major focus of genome research is to decipher the networks of molecular interactions that underlie cellular function. We describe a computational approach for identifying detailed relationships between proteins on the basis of genomic data. Logic analysis of phylogenetic profiles identifies triplets of proteins whose presence or absence obey certain logic relationships. For example, protein C may be present in a genome only if proteins A and B are both present. The method reveals many previously unidentified higher order relationships. These relationships illustrate the complexities that arise in cellular networks because of branching and alternate pathways, and they also facilitate assignment of cellular functions to uncharacterized proteins.

Complementary and alternative medical therapies for chronic low back pain: What treatments are patients willing to try?

Abstract: Although back pain is the most common reason patients use complementary and alternative medical (CAM) therapies, little is known about the willingness of primary care back pain patients to try these therapies. As part of an effort to refine recruitment strategies for clinical trials, we sought to determine if back pain patients are willing to try acupuncture, chiropractic, massage, meditation, and t'ai chi and to learn about their knowledge of, experience with, and perceptions about each of these therapies. We identified English-speaking patients with diagnoses consistent with chronic low back pain using automated visit data from one health care organization in Boston and another in Seattle. We were able to confirm the eligibility status (i.e., current low back pain that had lasted at least 3 months) of 70% of the patients with such diagnoses and all eligible respondents were interviewed. Except for chiropractic, knowledge about these therapies was low. Chiropractic and massage had been used by the largest fractions of respondents (54% and 38%, respectively), mostly for back pain (45% and 24%, respectively). Among prior users of specific CAM therapies for back pain, massage was rated most helpful. Users of chiropractic reported treatment-related "significant discomfort, pain or harm" more often (23%) than users of other therapies (5–16%). Respondents expected massage would be most helpful (median of 7 on a 0 to 10 scale) and meditation least helpful (median of 3) in relieving their current pain. Most respondents indicated they would be "very likely" to try acupuncture, massage, or chiropractic for their back pain if they did not have to pay out of pocket and their physician thought it was a reasonable treatment option. Most patients with chronic back pain in our sample were interested in trying therapeutic options that lie outside the conventional medical spectrum. This highlights the need for additional studies evaluating their effectiveness and suggests that researchers conducting clinical trials of these therapies may not have difficulties recruiting patients.

Double-blind placebo-controlled trial of static magnets for the treatment of osteoarthritis of the knee: results of a pilot study.

Abstract: CONTEXT Outpatient clinical studies of magnet therapy, a complementary therapy commonly used to treat osteoarthritis (OA), have been limited by the absence of a credible placebo control. OBJECTIVE Our objective was to assess the feasibility and promise of studying static magnetic therapy for knee OA and determine the ability of a new placebo-magnet device to provide concealment of group assignment. DESIGN Randomized, double-blind, placebo-controlled clinical trial. SETTING Academic teaching hospital in Boston. PARTICIPANTS We enrolled 29 subjects with idiopathic or post-traumatic OA of the knee. INTERVENTIONS Subjects received either high-strength magnetic (active) or placebo-magnetic (placebo) knee sleeve treatment for 4 hours in a monitored setting and self-treatment 6 hours daily for 6 weeks. MAIN OUTCOME MEASURES Primary outcomes were change in knee pain as measured by the WOMAC Osteoarthritis Index Pain Subscale at 6 weeks and extent of group concealment at study end. RESULTS At 4 hours, VAS pain scores (+/- SE) on a 5-item scale (0-500, 500 worst) decreased 79 +/- 18 mm in the active group and 10 +/- 21 mm in the placebo group (P 0.2) believed that they had been assigned to the active treatment group. CONCLUSION Despite our small sample size, magnets showed statistically significant efficacy compared to placebo after 4 hours under rigorously controlled conditions. The sustained efficacy of magnetic therapy for knee osteoarthritis could be assessed in an adequately powered trial utilizing an appropriate control such our new placebo-magnet device.

In silico simulation of biological network dynamics

Abstract: Realistic simulation of biological networks requires stochastic simulation approaches because of the small numbers of molecules per cell. The high computational cost of stochastic simulation on conventional microprocessor-based computers arises from the intrinsic disparity between the sequential steps executed by a microprocessor program and the highly parallel nature of information flow within biochemical networks. This disparity is reduced with the Field Programmable Gate Array (FPGA)-based approach presented here. The parallel architecture of FPGAs, which can simulate the basic reaction steps of biological networks, attains simulation rates at least an order of magnitude greater than currently available microprocessors.

Practice patterns of naturopathic physicians: Results from a random survey of licensed practitioners in two US States

Abstract: Background Despite the growing use of complementary and alternative medicine (CAM) by consumers in the U.S., little is known about the practice of CAM providers. The objective of this study was to describe and compare the practice patterns of naturopathic physicians in Washington State and Connecticut.

DPANN: Improved sequence to structure alignments following fold recognition

Abstract: In fold recognition (FR) a protein sequence of unknown structure is assigned to the closest known three-dimensional (3D) fold. Although FR programs can often identify among all possible folds the one a sequence adopts, they frequently fail to align the sequence to the equivalent residue positions in that fold. Such failures frustrate the next step in structure prediction, protein model building. Hence it is desirable to improve the quality of the alignments between the sequence and the identified structure. We have used artificial neural networks (ANN) to derive a substitution matrix to create alignments between a protein sequence and a protein structure through dynamic programming (DPANN: Dynamic Programming meets Artificial Neural Networks). The matrix is based on the amino acid type and the secondary structure state of each residue. In a database of protein pairs that have the same fold but lack sequences-similarity, DPANN aligns over 30% of all sequences to the paired structure, resembling closely the structural superposition of the pair. In over half of these cases the DPANN alignment is close to the structural superposition, although the initial alignment from the step of fold recognition is not close. Conversely, the alignment created during fold recognition outperforms DPANN in only 10% of all cases. Thus application of DPANN after fold recognition leads to substantial improvements in alignment accuracy, which in turn provides more useful templates for the modeling of protein structures. In the artificial case of using actual instead of predicted secondary structures for the probe protein, over 50% of the alignments are successful.

PFIT and PFRIT: bioinformatic algorithms for detecting glycosidase function from structure and sequence

Abstract: The identification of the enzymes involved in the metabolism of simple and complex carbohydrates presents one bioinformatic challenge in the post-genomic era. Here, we present the PFIT and PFRIT algorithms for identifying those proteins adopting the α/β barrel fold that function as glycosidases. These algorithms are based on the observation that proteins adopting the α/β barrel fold share positions in their tertiary structures having equivalent sets of atomic interactions. These are conserved tertiary interaction positions, which have been implicated in both structure and function. Glycosidases adopting the α/β barrel fold share more conserved tertiary interactions than α/β barrel proteins having other functions. The enrichment pattern of conserved tertiary interactions in the glycosidases is the information that PFIT and PFRIT use to predict whether any given α/β barrel will function as a glycosidase or not. Using as a test set a database of 19 glycosidase and 45 nonglycosidase α/β barrel proteins with low sequence similarity, PFIT and PFRIT can correctly predict glycosidase function for 84% of the proteins known to function as glycosidases. PFIT and PFRIT incorrectly predict glycosidase function for 25% of the nonglycosidases. The program PSI-BLAST can also correctly identify 84% of the 19 glycosidases, however, it incorrectly predicts glycosidase function for 50% of the nonglycosidases (twofold greater than PFIT and PFRIT). Overall, we demonstrate that the structure-based PFIT and PFRIT algorithms are both more selective and sensitive for predicting glycosidase function than the sequence-based PSI-BLAST algorithm.

A web-based comparative genomics tutorial for investigating microbial genomes.

Abstract: As the number of completely sequenced microbial genomes continues to rise at an impressive rate, it is important to prepare students with the skills necessary to investigate microorganisms at the genomic level. As a part of the core curriculum for first-year graduate students in the biological sciences, we have implemented a web-based tutorial to introduce students to the fields of comparative and functional genomics. The tutorial focuses on recent computational methods for identifying functionally linked genes and proteins on a genome-wide scale and was used to introduce students to the Rosetta Stone, Phylogenetic Profile, conserved Gene Neighbor, and Operon computational methods. Students learned to use a number of publicly available web servers and databases to identify functionally linked genes in the Escherichia coli genome, with emphasis on genome organization and operon structure. The overall effectiveness of the tutorial was assessed based on student evaluations and homework assignments. The tutorial is available to other educators at http://www.doe-mbi.ucla.edu/~strong/m253.php.