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Biomedical subjects

C Friedman

Publications and source records attributed to C Friedman.

At least 19 recordsLinked to original sources
PubMed2004

Biological nomenclatures: a source of lexical knowledge and ambiguity.

There has been increased work in developing automated systems that involve natural language processing (NLP) to recognize and extract genomic information from the literature. Recognition and identification of biological entities is a critical step in this process. NLP systems generally rely on nomenclatures and ontological specifications as resources for determining the names of the entities, assigning semantic categories that are consistent with the corresponding ontology, and assignment of identifiers that map to well-defined entities within a particular nomenclature. Although nomenclatures and ontologies are valuable for text processing systems, they were developed to aid researchers and are heterogeneous in structure and semantics. A uniform resource that is automatically generated from diverse resources, and that is designed for NLP purposes would be a useful tool for the field, and would further database interoperability. This paper presents work towards this goal. We have automatically created lexical resources from four model organism nomenclature systems (mouse, fly, worm, and yeast), and have studied performance of the resources within an existing NLP system, GENIES. Using nomenclatures is not straightforward because issues concerning ambiguity, synonymy, and name variations are quite challenging. In this paper we focus mainly on ambiguity. We determined that the number of ambiguous gene names within the individual nomenclatures, across the four nomenclatures, and with general English ranged from 0%-10.18%, 1.187%-20.30%, and 0%-2.49% respectively. When actually processing text, we found the rate of ambiguous occurrences (not counting ambiguities stemming from English words) to range from 2.4%-32.9% depending on the organisms considered.

Artificial Intelligence↗
PubMed2002

Hormonal regulation of interleukin-6 production in human adipocytes.

OBJECTIVE: To elucidate the hormonal regulation of interleukin-6 (IL-6) production by human adipose tissue and its relation to leptin. DESIGN: In vitro study. Human adipocytes were incubated with dexamethasone (with or without RU486), norepinephrine and epinephrine (with or without propranolol), or insulin. MEASUREMENTS: IL-6 and leptin secretion by human adipocytes. RESULTS: A gradual increase in IL-6 secretion by adipocytes during differentiation was observed. A positive correlation was found between basal IL-6 release and both glycerol 3-phosphate dehydrogenase activity--a marker of adipocyte differentiation-and leptin release. Dexamethasone decreased IL-6 secretion and increased leptin secretion in a dose-dependent manner. Both catecholamines increased IL-6 and leptin secretion. The effects of dexamethasone and catecholamines on IL-6 and leptin were abrogated by RU486 and propranolol, respectively. Incubation with insulin resulted in a dose-dependent stimulation of IL-6 and leptin secretion. CONCLUSIONS: IL-6 is produced by human adipocytes and is a potential marker of adipocyte differentiation. Furthermore it is a hormonally regulated cytokine, suppressed by glucocorticoids, and stimulated by catecholamines and insulin in physiological concentrations.

Adipocytes↗
PubMed2001

Transcriptional activity of multiple copies of a subtelomerically located olfactory receptor gene that is polymorphic in number and location.

We report here on the transcriptional activity of multiple copies of a subtelomerically located olfactory receptor (OR) gene, OR-A. Due to recent duplication events, both the copy number and chromosomal location of OR-A vary among humans. Sequence analyses of 180 copies of this gene, derived from 12 chromosome ends in 22 individuals, show that the main coding exon of all but one copy is an intact open reading frame with 0-5 predicted amino acid differences. We detected transcription of OR-A in both olfactory epithelium and testis tissue using RT-PCR amplification with primers designed on the basis of a computationally predicted gene structure. Two alternatively spliced forms of transcripts, one encoding an isoform with an extended N-terminus, were found in both tissues. A third transcript, derived from a second promoter, was also observed in testes. The start methionine is predicted in all transcripts to lie in an upstream exon rather than the main coding exon, as is typical for most other OR genes. By examining sequence variants among transcripts, we show that transcription of this gene occurs at multiple chromosomal locations. Our results lend credence to the idea that OR diversity could be generated in rearrangement-prone subtelomeric regions and show that polymorphism in subtelomeric regions could lead to individual-to-individual variation in the expressed repertoire of OR genes.

Alternative Splicing↗
PubMed2001

Genomic analysis of orthologous mouse and human olfactory receptor loci.

Olfactory receptor (OR) genes represent approximately 1% of genomic coding sequence in mammals, and these genes are clustered on multiple chromosomes in both the mouse and human genomes. We have taken a comparative genomics approach to identify features that may be involved in the dynamic evolution of this gene family and in the transcriptional control that results in a single OR gene expressed per olfactory neuron. We sequenced approximately 350 kb of the murine P2 OR cluster and used synteny, gene linkage, and phylogenetic analysis to identify and sequence approximately 111 kb of an orthologous cluster in the human genome. In total, 18 mouse and 8 human OR genes were identified, including 7 orthologs that appear to be functional in both species. Noncoding homology is evident between orthologs and generally is confined within the transcriptional unit. We find no evidence for common regulatory features shared among paralogs, and promoter regions generally do not contain strong promoter motifs. We discuss these observations, as well as OR clustering, in the context of evolutionary expansion and transcriptional regulation of OR repertoires.

5' Untranslated Regions↗
PubMed2001

A homogeneous fluorometric assay for measuring cell adhesion to immobilized ligand using V-well microtiter plates.

We have developed a homogeneous high-capacity assay format for measuring integrin- and selectin-dependent cell binding to immobilized ligand using V-well microtiter plates. 2',7'-Bis(2-carboxyethyl)-5-(and-6)-carboxylfluorescence, acetoxymethylester-labeled cells are added to ligand-coated V-shaped microtiter wells. Bound cells are separated from free cells using centrifugal force to produce shear stress. Nonadherent cells accumulate in the nadir of the well and are measured using a fluorescence plate reader. Antibody or low-molecular-weight inhibitors of either the ligand or the cell surface receptor result in less cell binding, more cells in the pellet, and increased signal. The optimization and validation of the very late antigen-4/vascular cell adhesion molecule-1 assay is described in detail. We demonstrate that this assay can be rapidly adapted to measure other integrin- and selectin-mediated interactions. This assay format has several advantages over conventional assays. The centrifugal process is biologically relevant and eliminates the washing steps to remove nonadherent cells that can cause well-to-well and plate-to-plate variation. Because the assay is robust with a high signal-to-noise ratio and low variability, it is ideally suited for studying multiple parameters of cell adhesion and for high capacity screening.

Anti-Allergic Agents↗
PubMed2001

A physical map of the human genome.

The human genome is by far the largest genome to be sequenced, and its size and complexity present many challenges for sequence assembly. The International Human Genome Sequencing Consortium constructed a map of the whole genome to enable the selection of clones for sequencing and for the accurate assembly of the genome sequence. Here we report the construction of the whole-genome bacterial artificial chromosome (BAC) map and its integration with previous landmark maps and information from mapping efforts focused on specific chromosomal regions. We also describe the integration of sequence data with the map.

Chromosomes, Artificial, Bacterial↗
PubMed2001

Integration of cytogenetic landmarks into the draft sequence of the human genome.

We have placed 7,600 cytogenetically defined landmarks on the draft sequence of the human genome to help with the characterization of genes altered by gross chromosomal aberrations that cause human disease. The landmarks are large-insert clones mapped to chromosome bands by fluorescence in situ hybridization. Each clone contains a sequence tag that is positioned on the genomic sequence. This genome-wide set of sequence-anchored clones allows structural and functional analyses of the genome. This resource represents the first comprehensive integration of cytogenetic, radiation hybrid, linkage and sequence maps of the human genome; provides an independent validation of the sequence map and framework for contig order and orientation; surveys the genome for large-scale duplications, which are likely to require special attention during sequence assembly; and allows a stringent assessment of sequence differences between the dark and light bands of chromosomes. It also provides insight into large-scale chromatin structure and the evolution of chromosomes and gene families and will accelerate our understanding of the molecular bases of human disease and cancer.

Chromosome Aberrations↗
PubMed2001

Randomized trial of supplemental beta-carotene to prevent second head and neck cancer.

Beta-carotene has established efficacy in animal models of oral carcinogenesis and has been shown to regress oral precancerous lesions in humans. The purpose of this study was to see whether these effects extended to the prevention of oral/pharyngeal/laryngeal (head and neck) cancer in humans. The subject population for this randomized, placebo-controlled, double-blinded clinical trial included 264 patients who had been curatively treated for a recent early-stage squamous cell carcinoma of the oral cavity, pharynx, or larynx. Patients were assigned randomly to receive 50 mg of beta-carotene per day or placebo and were followed for up to 90 months for the development of second primary tumors and local recurrences. After a median follow-up of 51 months, there was no difference between the two groups in the time to failure [second primary tumors plus local recurrences: relative risk (RR), 0.90; 95% confidence interval (CI), 0.56-1.45]. In site-specific analyses, supplemental beta-carotene had no significant effect on second head and neck cancer (RR, 0.69; 95% CI, 0.39-1.25) or lung cancer (RR, 1.44; 95% CI, 0.62-3.39). Total mortality was not significantly affected by this intervention (RR, 0.86; 95% CI, 0.52-1.42). Whereas none of the effects were statistically significant, the point estimates suggested a possible decrease in second head and neck cancer risk but a possible increase in lung cancer risk. These effects are consistent with the effects observed in trials using intermediate end point biological markers in humans, in which beta-carotene has established efficacy in oral precancerous lesions but has no effect or slightly worsens sputum cytology, and in animal carcinogenicity studies, in which beta-carotene has established efficacy in buccal pouch carcinogenesis in hamsters but not in animal models of respiratory tract/lung carcinogenesis, with some suggestions of tumor-promoting effects in respiratory tract/lung. If our results are replicated by other ongoing/completed trials, this suggests a critical need for mechanistic studies addressing differential responses in one epithelial site (head and neck) versus another (lung).

Adult↗
PubMed2001

Disambiguating ambiguous biomedical terms in biomedical narrative text: an unsupervised method.

With the growing use of Natural Language Processing (NLP) techniques for information extraction and concept indexing in the biomedical domain, a method that quickly and efficiently assigns the correct sense of an ambiguous biomedical term in a given context is needed concurrently. The current status of word sense disambiguation (WSD) in the biomedical domain is that handcrafted rules are used based on contextual material. The disadvantages of this approach are (i) generating WSD rules manually is a time-consuming and tedious task, (ii) maintenance of rule sets becomes increasingly difficult over time, and (iii) handcrafted rules are often incomplete and perform poorly in new domains comprised of specialized vocabularies and different genres of text. This paper presents a two-phase unsupervised method to build a WSD classifier for an ambiguous biomedical term W. The first phase automatically creates a sense-tagged corpus for W, and the second phase derives a classifier for W using the derived sense-tagged corpus as a training set. A formative experiment was performed, which demonstrated that classifiers trained on the derived sense-tagged corpora achieved an overall accuracy of about 97%, with greater than 90% accuracy for each individual ambiguous term.

Algorithms↗
PubMed2001

Electronic chart review as an aid to postdischarge surgical site surveillance: increased case finding.

BACKGROUND: At the University of Michigan Hospitals and Health Centers, there is increasing use of an electronic medical record. Because orthopedic surgeons dictate all outpatient visits to the patient's electronic record, total knee arthroplasties were chosen to determine whether the use of electronic medical records increased case finding. METHODS: All patients who underwent a total knee arthroplasty during the study period (1996-1999) were followed prospectively with the use of the National Nosocomial Infection Surveillance System definitions. Traditional surveillance methods were used to ascertain infections. In addition, each patient's postdischarge outpatient clinic chart was reviewed electronically for 1 year after operation. RESULTS: From 1996 to 1999, 555 procedures were performed. Overall, 25 infections were identified after operation. Seven infections were identified through traditional surveillance methods, which resulted in an average surgical site infection rate of 1.3%. The use of electronic chart review surveillance after discharge revealed a rate of 4.5%, which was significantly higher than traditional surveillance (P <.01). Eighteen of 25 infections (72%) would not have been identified with the use of traditional surveillance methods. CONCLUSION: Postdischarge electronic chart review enhanced case finding significantly, which resulted in a more accurate infection rate. Awareness should be given to the institutions' surveillance methods and intensity when comparing to published rates.

Arthroplasty, Replacement, Knee↗
PubMed2001

The efficacy and safety of once-daily Kytril (granisetron hydrochloride) tablets in the prophylaxis of nausea and emesis following fractionated upper abdominal radiotherapy.

This multicenter, randomized, double-blind study compared the efficacy and safety of once-daily oral granisetron 2 mg (n = 134) and placebo (n = 126) as prophylaxis for nausea and emesis in patients receiving upper abdominal fractionated radiotherapy. Patients were scheduled to receive 10-30 fractions of radiotherapy; granisetron (two 1-mg tablets) or placebo was administered 1 hr before radiotherapy on each scheduled treatment day. Treatment comparisons were made at 24 hr and at 10 and 20 fractions. Patients treated with granisetron experienced greater emetic control than those treated with placebo as evidenced by median times to first emesis (35 vs. 9 days, p < 0.001) and first nausea (11 vs. 1 day, p < 0.001). Overall endpoint analysis showed that proportionally more granisetron than placebo patients were emesis free (57.5% vs. 42.1%, p = 0.0047) and nausea free (30.6% vs. 16.7%, p = 0.0042). Furthermore, 25% more granisetron-treated than placebo-treated patients were emesis free and 20% more were nausea free on at least 80% of study treatment days. The most commonly reported adverse experiences in granisetron-treated patients were diarrhea, asthenia, and constipation. These findings demonstrate that a once-daily, 2-mg dose of oral granisetron is well tolerated and significantly more effective than placebo in preventing nausea and emesis induced by fractionated radiotherapy to the upper abdomen.

Abdomen↗
PubMed2001

GENIES: a natural-language processing system for the extraction of molecular pathways from journal articles.

Systems that extract structured information from natural language passages have been highly successful in specialized domains. The time is opportune for developing analogous applications for molecular biology and genomics. We present a system, GENIES, that extracts and structures information about cellular pathways from the biological literature in accordance with a knowledge model that we developed earlier. We implemented GENIES by modifying an existing medical natural language processing system, MedLEE, and performed a preliminary evaluation study. Our results demonstrate the value of the underlying techniques for the purpose of acquiring valuable knowledge from biological journals.

Artificial Intelligence↗
PubMed2001

Identification of non-functional human VNO receptor genes provides evidence for vestigiality of the human VNO.

In mammals, the vomeronasal organ (VNO) contains chemosensory receptor cells that bind to pheromones and induce a variety of social and reproductive behaviors. It has been traditionally assumed that the human VNO (Jacobson's organ) is a vestigial structure, although recent studies have shown minor evidence for a structurally intact and possibly functional VNO. The presence and function of the human VNO remains controversial, however, as pheromones and VNO receptors have not been well characterized. In this study we screened a human Bacterial Artificial Chromosome (BAC) library with multiple primer sets designed from human cDNA sequences homologous to mouse VNO receptor genes. Utilizing these BAC sequences in addition to mouse VNO receptor sequences, we screened the High Throughput Genome Sequence (HTGS) database to find additional human putative VNO receptor genes. We report the identification of 56 BACs carrying 34 distinct putative VNO receptor gene sequences, all of which appear to be pseudogenes. Sequence analysis indicates substantial homology to mouse V1R and V2R VNO receptor families. Furthermore, chromosomal localization via FISH analysis and RH mapping reveal that the majority of the BACs are localized to telomeric and centromeric chromosomal localizations and may have arisen through duplication events. These data yield insight into the present state of pheromonal olfaction in humans and into the evolutionary history of human VNO receptors.

Amino Acid Sequence↗
PubMed2001

Are clinicians correct when they believe they are correct? Implications for medical decision support.

The process of clinical decision support is linked to the validity of clinicians' confidence in their judgments. Clinicians who are appropriately confident-highly confident when they are correct and less confident when they are incorrect-will access computer-based and other information resources only when they are needed. Clinicians who are consistently underconfident will rely on external resources when they are not needed. Those who are overconfident, who believe they are correct when in fact they are not, will be prone to medical errors. An extensive literature indicates a general tendency toward overconfidence in human judgment. This study explores the relationship between confidence and "correctness", across three levels of clinical experience, in the task domain of diagnosis in internal medicine. We created detailed synopses of 36 diagnostically challenging cases and divided them into four equivalent sets of nine cases each. We asked 216 subjects at three experience levels (72 senior medical students, 72 senior medical residents, and 72 faculty attendings) to generate a differential diagnosis for each of the nine cases in one randomly-assigned set, and simultaneously to indicate their level of confidence in each of their diagnoses. We then examined the relationship between the correctness of these diagnoses (the appearance of the correct diagnosis anywhere in the hypothesis list) and these confidence judgments, for all subjects and separately for subjects at each experience level. Results indicate a small but statistically significant relationship associating correctness with higher confidence for all subjects (Kendall's tau b =.-106;p <.0001). This statistical relationship is strongest for the students ( tau b =.-121;p <.001), somewhat lesser but still significant for the faculty-level attendings ( tau b =.-103;p <.005), and non-significant ( tau b =.-041 ) for the residents. (The negative correlations are a coding artifact.) Subjects in this study showed a tendency toward underconfidence: they had low confidence in correct diagnoses more often than they had high confidence when wrong. Nonetheless, they were overconfident and thus "error prone" for 17% of cases overall. The medical students were possibly overmatched by the difficulty of the cases, so their concordance between confidence and correctness may have resulted from an awareness that they were often guessing. The relatively low concordance seen in the residents and attendings makes a strong argument that decision support systems to reduce medical errors should include both "push" and "pull" models. In sum, these results indicate that medical decision support systems cannot rely exclusively on clinicians' perceptions of their information needs, as such perceptions will frequently be incorrect.

Clinical Medicine↗
PubMed2001

Evaluating the UMLS as a source of lexical knowledge for medical language processing.

Medical language processing (MLP) systems rely on specialized lexicons in order to recognize, classify, and normalize medical terminology, and the performance of an MLP system is dependent on the coverage and quality of such lexicons. However, the acquisition of lexical knowledge is expensive and time-consuming. The UMLS is a comprehensive resource that can be used to acquire lexical knowledge needed for medical language processing. This paper describes methods that use these resources to automatically create lexical entries and generate two lexicons. The first lexicon was created primarily using the UMLS, whereas the second was created by supplementing the lexicon of an existing MLP system called MedLEE with entries based on the UMLS. We subsequently carried out a study, which is the primary focus of this paper, using MedLEE with each of the two lexicons and also the current MedLEE lexicon to measure performance. Overall accuracy, sensitivity, and specificity using the lexicon primarily based on the UMLS were.86,.60, and.96 respectively. Those measures using the MedLEE lexicon alone were.93,.81, and.93, which was significantly better except for specificity; performance using the supplemental lexicon was exactly the same as performance using solely the MedLEE lexicon.

Natural Language Processing↗
PubMed2001

A study of abbreviations in the UMLS.

Abbreviations are widely used in medicine. The understanding of abbreviations is important for medical language processing and information retrieval systems. The Unified Medical Language System (UMLS) contains a large number of abbreviations. We hypothesized that extracting and studying the UMLS abbreviations can be helpful for understanding the characteristics of abbreviations in medicine. In this paper, we describe a method for extracting abbreviations from the UMLS. We evaluated the method and studied the ambiguous nature of the abbreviations. In addition, the coverage of the UMLS abbreviations in medical reports was studied. Using our method, we extracted 163,666 unique (abbreviation, full form) pairs from the UMLS with a precision of 97.5%, and a recall of 96%. The UMLS abbreviations were highly ambiguous: 33.1% of abbreviations with six characters or less had multiple meanings; the average number of different full forms for all abbreviations with six characters or less was 2.28. The coverage of the UMLS abbreviations in medical reports was over 66%.

Abbreviations as Topic↗
PubMed2001

Automating SNOMED coding using medical language understanding: a feasibility study.

This paper evaluates qualitatively the use of the MedLEE natural language processing system to code medical narratives directly into the SNOMED nomenclature, while retaining the MedLEE information model data structure. A gold standard is produced from narrative text manually coded in SNOMED. An automated parsing and SNOMED-coding of the narrative text is then automatically generated by MedLEE. By comparing MedLEE s output to that of the Gold Standard, the capacities of SNOMED and MedLEE to represent the clinical information are subsequently evaluated leading to qualitative observations on their respective strengths and constraints. In this study, MedLEE did code to SNOMED and captures the codes in a sub-structure amenable to interoperability with the description logic of SNOMED RT, showing an approach that augments and formalizes SNOMED s compositional representation methods to accurately capture information from clinical narratives.

Feasibility Studies↗