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Biomedical subjects

J D Moore

Publications and source records attributed to J D Moore.

At least 19 recordsLinked to original sources
PubMed1995

An intelligent interactive system for delivering individualized information to patients.

This paper is a report on the first phase of a long-term, interdisciplinary project whose goal is to increase the overall effectiveness of physicians' time, and thus the quality of health care, by improving the information exchange between physicians and patients in clinical settings. We are focusing on patients with long-term and chronic conditions, initially on migraine patients, who require periodic interaction with their physicians for effective management of their condition. We are using medical informatics to focus on the information needs of patients, as well as of physicians, and to address problems of information exchange. This requires understanding patients' concerns to design an appropriate system, and using state-of-the-art artificial intelligence techniques to build an interactive explanation system. In contrast to many other knowledge-based systems, our system's design is based on empirical data on actual information needs. We used ethnographic techniques to observe explanations actually given in clinic settings, and to conduct interviews with migraine sufferers and physicians. Our system has an extensive knowledge base that contains both general medical terminology and specific knowledge about migraine, such as common trigger factors and symptoms of migraine, the common therapies, and the most common effects and side effects of those therapies. The system consists of two main components: (a) an interactive history-taking module that collects information from patients prior to each visit, builds a patient model, and summarizes the patients' status for their physicians; and (b) an intelligent explanation module that produces an interactive information sheet containing explanations in everyday language that are tailored to individual patients, and responds intelligently to follow-up questions about topics covered in the information sheet.

Anthropology, Cultural↗
PubMed1995

Superior nitrogen balance after laparoscopic-assisted colectomy.

BACKGROUND: Although early resumption of enteral feeding after gastrointestinal surgery results in improved nitrogen balance and lower infectious complications, no postoperative nutritional data after laparoscopic-assisted colectomy exists. OBJECTIVE: The authors prospectively compared nitrogen balance after laparoscopic-assisted colectomy versus open colectomy. METHODS: This is a series of colon resections (open, N = 10; laparoscopic-assisted, N = 9) at the Ferguson-Blodgett Hospital, Grand Rapids, Michigan, between January and March 1993. Nitrogen intake and 24-hour urine collections were performed on postoperative days 1, 3, and 7 for the analysis of total urinary nitrogen and urinary 3 methylhistidine-(3mH). RESULTS: The time to passage of flatus (4.7 +/- 0.6; 2.0 +/- 0.2), resumption of oral intake (6.1 +/- 0.7; 1.4 +/- 0.2; p < 0.05, Student's test), first bowel movement (5.2 +/- 1.0; 3.0 +/- 0.3; p < 0.05, Student;s t test), and discharge (10.3 +/- 1.3; 4.1 +/- 1.8; p < 0.05, Student's t test) occurred significantly earlier in the laparoscopic-assisted colectomy group. Overall hospital charges were lower in the laparoscopic-assisted colectomy group ($11,572 +/- $823 vs. $13,961 +/- $1050). The operative time was higher in the laparoscopic-assisted colectomy group (176 +/- 12 hours vs. 105 +/- 17 hours, p < 0.05,Student's test). Blood loss was higher in the open group (805 +/- 264 mL vs 217 +/- 32 mL, p < 0.05, Student's test). Urinary nitrogen losses were similar between the two groups; however, significantly more patients in the laparoscopic-assisted colectomy group achieved net positive nitrogen on day 3 (6/9; 0/10; p < 0.05, Fisher's exact test), and day 7 (9/9; 4/10; p < 0.05, Fisher's exact test). Infectious complications occurred less frequently in the laparoscopic-assisted colectomy group (0/9 vs. 4/10; p < 0.05, Fisher's exact test). CONCLUSIONS: Patients undergoing laparoscopic-assisted colectomy can achieve early resumption of enteral nutrition with earlier return to positive nitrogen balance compared with open colectomy. This may offer benefits of fewer infectious complications and lower cost of care.

Colectomy↗
PubMed1994

Evolution of transcription-regulating proteins by enzyme recruitment: molecular models for nitrogen metabolite repression and ethanol utilisation in eukaryotes.

Studies on the quinic acid utilisation gene (qut) cluster in Aspergillus nidulans showed that the genes encoding transcriptional activator and repressor proteins evolved by co-opting duplicated copies of genes encoding metabolic enzymes. In order to test the hypothesis that this was a general route for the genesis of regulatory proteins, the origins of the major control protein mediating nitrogen metabolite repression (an example of inter-pathway regulation) and ethanol utilisation (an example of intra-pathway regulation) in filamentous fungi were sought. The regulatory proteins mediating nitrogen metabolite repression were deduced to have originated in a duplication of genes encoding the anthranilate synthase complex which is active in the shikimate pathway. The major protein regulating ethanol utilisation was deduced to have its origin in the fusion of duplicated genes encoding the aldehyde and alcohol dehydrogenases (ALDA and ALCA). These data strongly support the view that transcriptional regulatory proteins evolve by the recruitment of functional domains provided by metabolic enzymes.

Aspergillus nidulans↗
PubMed1994

Crystallization of a type II dehydroquinase from Mycobacterium tuberculosis.

A type II 3-dehydroquinase from Mycobacterium tuberculosis has been crystallized in the presence of 6% polyethyleneglycol 6000. Data from these crystals have been collected to a resolution of 2.2 A on a rotating anode X-ray source. The space group has been determined as F23 with unit cell dimensions of a = b = c = 127.8 A. There is one molecule in the asymmetric unit.

Crystallization↗
PubMed1994

Efficient independent activity of a monomeric, monofunctional dehydroquinate synthase derived from the N-terminus of the pentafunctional AROM protein of Aspergillus nidulans.

The dehydroquinate synthase (DHQ synthase) functional domain from the pentafunctional AROM protein of Aspergillus nidulans has previously been overproduced in Escherichia coli [van den Hombergh, Moore, Charles and Hawkins (1992) Biochem J. 284, 861-867]. We now report the purification of this domain to homogeneity and subsequent characterization. The monofunctional DHQ synthase was found to retain efficient catalytic activity when compared with the intact pentafunctional AROM protein of Neurospora crassa [Lambert, Boocock and Coggins (1985) Biochem J. 226, 817-829]. The apparent kcat. was estimated to be 8 s-1, and the apparent Km values for NAD+ and 3-deoxy-D-arabino-heptulosonate phosphate (DAHP) were 3 microM and 2.2 microM respectively. These values are similar to those reported for the intact N. crassa enzyme, except that the apparent Km for NAD+ reported here is 15-fold higher. The monofunctional DHQ synthase domain is inactivated by treatment with chelating agents in the absence of substrates and is re-activated by the addition of metal ions; among those tested, Zn2+ gave the highest kcat./Km value. The enzyme is inactivated by diethyl pyrocarbonate; both the substrate, DAHP, and the product phosphate protected against inactivation. Size-exclusion chromatography suggested an M(r) of 43,000 for the monofunctional domain, indicating that it is monomeric and compactly folded. The c.d. spectrum confirmed that the domain has a compact globular conformation; the near-u.v. c.d. of zinc- and cobalt-reactivated domains were superimposable.

Alcohol Oxidoreductases↗
PubMed1994

A retrospective study of circovirus infection in pigeons: nine cases (1986-1993).

Circovirus infections were diagnosed in 12 pigeons from the United States 4 pigeons from Australia, and 1 pigeon from Canada (1986-1993). Circovirus was identified by electron microscopic examination of basophilic botryoid cytoplasmic inclusions that had a histologic appearance similar to that of psittacine beak and feather disease virus inclusions. Inclusions were seen in splenic, bursal, gut-associated, and bronchus-associated lymphoid tissue macrophages and in bursal epithelial cells. Inclusions were composed of paracrystalline arrays of tightly packed, nonenveloped icosahedral virions 14-17 nm in diameter. Histologic changes in the spleens ranged from lymphofollicular hyperplasia with mild discrete lymphocellular necrosis to lymphoid depletion and diffuse histiocytosis. Lesions in the bursa of Fabricius ranged from mild lymphocellular necrosis to severe cystic bursal atrophy. Remaining histologic findings coincided with concurrent bacterial, viral, fungal, and parasitic infections. Immunoperoxidase staining and DNA in situ hybridization demonstrated that pigeon circovirus is distinct from psittacine beak and feather disease virus; however both viruses apparently share some homologous DNA sequences. Clinical and diagnostic findings indicate that pigeon circovirus may be similar to psittacine beak and feather disease virus with respect to acquired immunodeficiency and subsequent multiple secondary infections.

Animals↗
PubMed1994

Generating patient-specific interactive natural language explanations.

Patient compliance is a significant problem and is strongly correlated with the patients' understanding of their condition and prescribed treatment. Since doctors typically do not have large amounts of time to educate patients, and impersonal, voluminous patient handouts are largely ineffective, we propose the use of a sophisticated computer-based information system to generate tailored, interactive handouts to communicate with patients. Our system uses text planning and user modeling techniques to generate natural language descriptions of migraine, its symptoms, triggering factors and prescriptions. The system is capable of handling follow-up questions requesting further information, and generating responses in the context of previously supplied information--a capability unavailable in previous patient information systems. The system tailors its interaction to: (i) the class of migraine patients, (ii) the individual patient, and (iii) the previous dialogue. Preliminary evaluation of the system indicates that patients find it useful and informative. More extensive evaluation is in progress.

Computer-Assisted Instruction↗
PubMed1994

Disseminated neoplastic cells in Mytilus trossulus: verification of host species origin by (16S-like) rRNA sequence comparison.

Disseminated neoplasia is a leukemia-like disease that occurs in many species of bivalve molluscs worldwide, including the bay mussel (Mytilus trossulus). The etiology of the disease is undetermined, but an early report proposed that the anomalous bivalve cells were actually an invasive parasite rather than cancerous cells of host origin. Comparison of partial sequences of small subunit rRNA from normal and putative cancer cells was performed to resolve this issue. These studies showed a close phylogenetic relationship of the different forms of cancer cells to each other (similarity coefficient, 0.982), to the normal hemocytes (similarity coefficient, 0.990, 0.992), and to the oyster, Crassostrea virginica (similarity coefficient, 0.895-0.927). A large phylogenetic distance separates all 3 mussel hemocyte types from several representative protists (similarity coefficient, 0.702-0.761). These results indicate that the disseminated neoplastic cells in mussels are indeed proliferative host cells and not unicellular parasites.

Animals↗
PubMed1993

Using the UMLS Semantic Network as a basis for constructing a terminological knowledge base: a preliminary report.

Sharing and reuse of knowledge bases is recognized in Artificial Intelligence and Medical Informatics as beneficial, but difficult. Reusing an existing knowledge base can save considerable time and effort during the knowledge engineering phase, and facilitates integration of systems. However, the degree to which knowledge can be shared among different applications is still mainly an empirical question. In this paper, we describe the preliminary results of our attempt to reuse the UMLS Semantic Network as an ontology for the knowledge base of a patient education system.

Algorithms↗
PubMed1992

Inducible overproduction of the Aspergillus nidulans pentafunctional AROM protein and the type-I and -II 3-dehydroquinases from Salmonella typhi and Mycobacterium tuberculosis.

The aroQ gene of Mycobacterium tuberculosis, encoding a type-II 3-dehydroquinase, and the aroD gene of Salmonella typhi, encoding a type-I 3-dehydroquinase, have been highly overexpressed in Escherichia coli using the powerful trc promoter contained within the expression vector pKK233-2. The M. tuberculosis type-II 3-dehydroquinase has been purified in bulk from overproducing strains of E. coli to greater than 95% homogeneity. The protein is extremely heat-stable, is active as a homododecamer and has the lowest reported Km value of any type-II 3-dehydroquinase. The pentafunctional aromA gene of Aspergillus nidulans has been overexpressed more than 120-fold in an A. nidulans aromA- qutB- double mutant from a truncated quinate-inducible qutE promoter, such that the AROM protein is visible as a significant fraction (approx. 6%) in cell-free crude extracts. The M. tuberculosis aroQ gene has been fused to the same truncated qutE promoter and shown to encode quinate-inducible 3-dehydroquinase activity that allows a qutE- mutant strain of A. nidulans to utilize quinate as sole carbon source.

Alcohol Oxidoreductases↗
PubMed1992

Crystallization of a type I 3-dehydroquinase from Salmonella typhi.

Crystals have been grown of a type I 3-dehydroquinase from both Escherichia coli and Salmonella typhi. However, only those from S. typhi diffract to a resolution of 2.3 A on a conventional X-ray source and are suitable for structure determination. The space group has been determined as P2(1)2(1)2 with unit cell dimensions a = 48.01 A, b = 114.29 A, c = 42.87 A. There is one subunit in the asymmetric unit.

Bacterial Proteins↗
PubMed1992

Overproduction in Escherichia coli of the dehydroquinate synthase domain of the Aspergillus nidulans pentafunctional AROM protein.

The pentafunctional AROM protein of Aspergillus nidulans is encoded by the complex aromA locus and catalyses steps 2-6 in the synthesis of chorismate, the common precursor for the aromatic amino acids and p-aminobenzoic acid. DNA sequences encoding the 3-dehydroquinate synthase (DHQ synthase) and 3-dehydroquinase domains of the AROM protein have been amplified with the inclusion of a translational stop codon at the C-terminus by PCR technology. These amplified fragments of DNA have been subcloned into the prokaryotic expression vector pKK233-2 and expressed in Escherichia coli. As a result, the DHQ synthase domain is overproduced in E. coli, forming 30% of total cell protein, and can be purified to greater than 80% homogeneity by a simple two-step protocol. The 3-dehydroquinase domain is produced at a specific activity 8-fold greater than the corresponding activity encoded by the aromA gene in A. nidulans. The qutB gene of A. nidulans encoding quinate dehydrogenase has similarly been subjected to PCR amplification and expression in E. coli. The quinate dehydrogenase is not overproduced, but is active in E. coli as a shikimate dehydrogenase, as the presence of the qutB gene allows the growth of an E. coli mutant strain lacking shikimate dehydrogenase on minimal medium lacking aromatic-amino-acid supplementation.

Alcohol Oxidoreductases↗
PubMed1992

Differential flux through the quinate and shikimate pathways. Implications for the channelling hypothesis.

The qutC gene encoding dehydroshikimate dehydratase has been constitutively overexpressed in Aspergillus nidulans from a range of 1-30-fold over the normal wild-type level. This overexpression leads to impaired growth in minimal medium which can be alleviated by the addition of aromatic amino acids to the medium. Overexpression of the qutC gene in mutant strains lacking protocatechuic acid (PCA) oxygenase leads to the build up of PCA in the medium, which can be measured by a simple assay. Measuring the rate of production of PCA in strains overproducing dehydroshikimate dehydratase and correlating this with the level of overproduction and impaired ability to grow in minimal medium lacking aromatic amino acids leads to the conclusion that (a) the metabolites 3-dehydroquinate and dehydroshikimate leak from the AROM protein at a rate comparable with the extent of flux catalysed by the AROM protein, (b) the AROM protein has a low-level channelling function probably as a result of the close juxtaposition of five active sites and (c) this channelling function is only physiologically significant under non-optimal conditions of nutrient supply and oxygenation, when the organism is in situ in its natural environment.

Alcohol Oxidoreductases↗
PubMed1992

Expression of the mouse c-abl type IV proto-oncogene product in the insect cell baculovirus system.

The cellular gene c-abl is the normal homologue of the transforming gene (v-abl) within the genome of the Abelson leukaemia virus. The cDNA sequence coding for the cellular form of the murine abl gene (c-abl type IV) has been inserted into the baculovirus transfer vector, pAc36C, so that the c-abl gene is under the control of the polyhedrin promoter of Autographa californica nuclear polyhedrosis virus (AcNPV). Spodoptera frugiperda cells infected with the recombinant transfer vector in the presence of wild type AcNPV DNA yielded recombinant, polyhedrin negative virus that expressed moderate levels of the c-Abl protein (representing approx. 0.5-1% of the stained cellular proteins as determined by densitometric scanning). The insect derived c-Abl protein was compared to the P210-BCR/ABL protein from K562 cells, a cell line derived from a patient with chronic myelogenous leukaemia. Antibodies raised against synthetic peptides based on c-abl encoded peptides react with the insect derived c-Abl. In addition, the baculovirus derived c-Abl protein has a tyrosine kinase activity as demonstrated by phosphorylation of a synthetic polypeptide and also by autophosphorylation. Phosphoamino acid analysis of immunoprecipitated, autophosphorylated baculovirus derived c-Abl protein indicates that the majority of label incorporated is on the tyrosine residues. Immunofluorescence microscopy has been used to show that the majority of the c-Abl protein expressed in cells infected with recombinant virus is located in the nuclear and plasma membranes.

Animals↗
PubMed1991

Alternate pathogenesis of systemic neoplasia in the bivalve mollusc Mytilus.

The proliferative disease systemic neoplasia, also termed hemic neoplasia or disseminated sarcoma, was studied in four Puget Sound, Washington populations of the bay mussel (Mytilus sp.). Using flow cytometric measurement of DAPI-stained cells withdrawn from the hemolymph, DNA content frequency histograms were generated for 73 individuals affected by the disease. The cells manifesting systemic neoplasia were found to exist as either of two separate types, characterized by G0G1 phase nuclear DNA contents of either approximately 4.9 x haploid (pentaploid form) or approximately 3.8 x haploid (tetraploid form). The two disease forms were found to coexist in all four mussel populations sampled, with overall relative prevalences of 66% pentaploid form, 29% tetraploid form, and 5% exhibiting both disease forms simultaneously. These findings represent the first unequivocal demonstration of multiple cell types in a bivalve neoplasia. The two forms appear to represent separate pathogenetic processes rather than sequential stages of a single pathogenesis. Two cell cycling parameters associated with proliferative activity were employed to compare the alternate forms: (i) the percentage of cells assigned to the DNA Synthesis (S) phase of the neoplastic cell cycle, and (ii) the proportion of neoplastic cell mitotic figures in hemocytological preparations. Mean values for both parameters were significantly higher for mussels with the tetraploid form of the disease, suggesting a higher rate of proliferation relative to the pentaploid form. Qualitatively, cells of the tetraploid form contained slightly lower nuclear and cytoplasmic volumes compared to those of the pentaploid form. An observed wide variation in neoplastic cell nuclear size within either disease form may reflect the distribution of cells in the G0G1, S, and G2M phases of the cell cycle. Potential etiologic relationships between the two forms are discussed.

Animals↗