PubMed Health⌕ Search

Biomedical subjects

L R Moore

Publications and source records attributed to L R Moore.

At least 19 recordsLinked to original sources
PubMed2026

Assessment of the impact of manual curation in BioCyc.

INTRODUCTION: BioCyc is an extensive collection of databases of genomic and pathway information for microorganisms and model eukaryotes. These organismal databases integrate diverse biological data by combining computationally inferred information, data imported from other databases, and, for selected organisms, literature-based manual curation. This study investigates the magnitude and significance of annotation changes performed during the curation of 10 prokaryotic genomes to better understand the rate of erroneous annotations and the value of BioCyc curation. METHODS: We identified curation changes by finding cases where the annotation of the protein at the start of the curation process differed from its annotation at the end of the process. RESULTS: We found that across a sample of curated databases (n = 10), the annotation of 6,753, or 25.6% of the proteins in the pooled protein dataset (n = 26,126) were modified. Assessment of considerable sampling fractions of these proteins found that a median of 62% (mean of 52.9%) represented functionally informative name changes, rather than stylistic annotation changes. These results were then extrapolated to total proteins with name changes with uncertainty quantified via finite population correction, indicating that most Tier 2 Biocyc PGDBs received hundreds of functionally informative name changes during manual curation. On average 363, or13% (±5.4% SD) of the proteins encoded in each genome received functionally informative annotation changes, ranging from 5.3% (Streptococcus pneumoniae D39V) to 22.7% (Staphylococcus aureus NCTC 8325). DISCUSSION: These findings demonstrate a substantial improvement in the accuracy of manually curated BioCyc databases compared with automated annotation pipelines. This result is particularly impactful as the rate of downstream propagation of erroneous annotations across biological databases can significantly compromise scientific discovery.

annotation errors↗
PubMed2003

Genetic polymorphisms and personality in healthy adults: a systematic review and meta-analysis.

A meta-analysis was conducted on studies reporting data on associations between candidate genes and human personality. Studies reporting data for psychiatric populations (including organic disease and substance abuse) were excluded. A total of 46 studies contributed to the analysis. Pooled data using a fixed-effects model suggested significant associations between the 5HTT LPR, DRD4 c>t, DRD4 length, DRD2 A1/A2, DRD3 A1/A2 polymorphisms and personality traits. A multivariate analysis using a mixed-effects model and including age, sex and predominant ethnicity as covariates was applied to the analyses of 5HTT LPR and DRD4 length polymorphism data. Only the association between the 5HTT LPR polymorphism and avoidance traits remained significant (P=0.038). However, sensitivity analyses excluding data from studies reporting allele frequencies not in Hardy-Weinberg equilibrium and unpublished data resulted in this association no longer being significant. Implications for the design of future association studies of human personality are discussed, including the likely sample sizes that will be required to achieve sufficient power and the potential role of moderating variables such as sex.

Adult↗
PubMed2000

The use of magnetite-doped polymeric microspheres in calibrating cell tracking velocimetry.

Continuous magnetic separation, in which there is no accumulation of mass in the system, is an inherently dynamic process, requiring advanced knowledge of the separable species for optimal instrument operation. By determining cell magnetization in a well-defined field, we may predict the cell trajectory behavior in the well-characterized field environments of our continuous separators. Magnetization is determined by tracking the migration of particles with a technique known as cell tracking velocimetry (CTV). The validation of CTV requires calibration against an external standard. Furthermore, such a standard, devoid of the variations and instabilities of biological systems, is needed to reference the method against day-to-day shifts or trends. To this end, a method of synthesizing monodisperse, magnetite-doped polymeric microspheres has been developed. Five sets of microspheres differing in their content of magnetite, and each of approximately 2.7 microm diameter, are investigated. An average gradient of 0.18 T/mm induces magnetic microsphere velocities ranging from 0.45 to 420 microns/s in the CTV device. The velocities enable calculation of the microsphere magnetization. Magnetometer measurements permit the determination of magnetization at a flux density comparable to that of the CTV magnet's analysis region, 1.57 T. A comparison of the results of the CTV and magnetometer measurements shows good agreement.

Cells, Cultured↗
PubMed2000

Study of magnetic particles pulse-injected into an annular SPLITT-like channel inside a quadrupole magnetic field.

Advantages of the continuous magnetic flow sorting for biomedical applications over current, batch-wise magnetic separations include high throughput and a potential for scale-up operations. A continuous magnetic sorting process has been developed based on the quadrupole magnetic field centered on an annular flow channel. The performance of the sorter has been described using the conceptual framework of split-flow thin (SPLITT) fractionation, a derivative of field-flow fractionation (FFF). To eliminate the variability inherent in working with a heterogenous cell population, we developed a set of monodisperse magnetic microspheres of a characteristic magnetization, and a magnetophoretic mobility, similar to those of the cells labeled with a magnetic colloid. The theory of the magnetic sorting process has been tested by injecting a suspension of the magnetic beads into the carrier fluid flowing through the sorter and by comparing the theoretical and experimental recovery versus total flow-rate profiles. The position of the recovery maxima along the total flow-rate axis was a function of the average bead magnetophoretic mobility and the magnetic field intensity. The theory has correctly predicted the position of the peak maxima on the total flow-rate axis and the dependence on the bead mobility and the field intensity, but has not correctly predicted the peak heights. The differences between the calculated and the measured peak heights were a function of the total flow-rate through the system, indicating a fluid-mechanical origin of the deviations from the theory (such as expected of the lift force effects in the system). The well-controlled elution studies using the monodisperse magnetic beads, and the SPLITT theory, provided us with a firm basis for the future sorter evaluation using cell mixtures.

Magnetics↗
PubMed1999

Detection of rare MCF-7 breast carcinoma cells from mixtures of human peripheral leukocytes by magnetic deposition analysis.

BACKGROUND: The presence of malignant breast cancer cells in bone marrow or peripheral blood is a prognostic factor. We tested the capacity of a novel magnetic cell analyzer to detect rare cancer cells in mixtures with human peripheral leukocytes. METHODS: Human peripheral leukocytes were spiked with cells of the MCF-7 line, and the cell mixture was labeled with anti-epithelial membrane antigen antibody and a magnetic colloid. The MCF-7 cells were selectively captured on a magnetic deposition substrate from the flowing leukocyte and MCF-7 cell mixture. RESULTS: The recovery of the MCF-7 cells from the original mixture ranged from 20% to 60%. The limit of detection of the MCF-7 cells was 10(-6) (n = 9). The morphology of the captured cancer cells was well preserved and comparable to that observed in cytospin smears. All deposited cells were located in a small area of 1.4 mm x 6 mm and could be quickly identified with an optical microscope following Wright's staining. CONCLUSIONS: This is a proof-of-principle study using a simplified model of rare cancer cells in a leukocyte mixture. The clinical relevance of the method will be tested in the future by extension to patient bone marrow samples and using antibody cocktails to increase specificity against the breast carcinoma cells.

Antibodies, Monoclonal↗
PubMed1998

Continuous, flow-through immunomagnetic cell sorting in a quadrupole field.

A flow-through quadrupole magnetic cell separator has been designed, built, and evaluated by using a cell model system of human peripheral T lymphocytes (CD4+, CD8+, and CD45+ cells). The immunomagnetic labeling was accomplished by using a sandwich of mouse anti-human monoclonal antibody conjugated to fluorescein isothiocyanate and rat anti-mouse polyclonal antibody conjugated to a colloidal magnetic nanoparticle. The feed and sorted fractions were analyzed by FACScan flow cytometry. The magnetically labeled cells were separated from nonlabeled ones in a flow-through cylindrical column within a quadrupole field, which exerted a radial, outward force on the magnetic cells. The flow rate of the cell samples was 0.1-0.75 ml/min, and the flow rate of sheath fluid was 1.5-33.3 times that of the sample flow rate. The maximum shear stress exerted on the cell was less than 1 dyne/cm2, which was well below the level that would threaten cell integrity and membrane disruption. The maximum magnetic field was 0.765 T at the channel wall, and the gradient was 0.174 T/mm. The highest purity of selected cells was 99.6% (CD8 cells, initial purity of 26%), and the highest recovery of selected cells was 79% (CD4 cells, initial purity of 20%). The maximum throughput of the quadrupole magnetic cell separator was 7,040 cells/s (CD45 cells, initial purity of 5%). Theoretical calculations showed that the throughput can be increased to 10(6) cells/s by a scale-up of the current prototype.

Animals↗
PubMed1998

Lymphocyte fractionation using immunomagnetic colloid and a dipole magnet flow cell sorter.

The relationship between cell function and surface marker expression is a subject of active investigation in biology and medicine. These investigations require separating cells of a homogeneous subset into multiple fractions of varying marker expression. We have developed a novel cell sorter, the dipole magnet flow sorter (DMFS), which separates selected T lymphocyte subpopulations, targeted by immunomagnetic colloid, into multiple fractions according to cell surface marker expression, as determined by flow cytometry. A narrow stream of cells is introduced into a sheath of carrier fluid in a rectangular channel while subjected to a perpendicular magnetic force. The special design of the pole pieces ensures a constant magnetic force acting on the magnetically labeled cells in the separation area. Cells are spread across the flow in relation to their magnetophoretic mobility. Separation is achieved by control of the positions of the effluent stream boundaries, which separate fluid volumes with cells of different magnetophoretic mobility. CD4 and CD8 T lymphocytes labeled with primary antibody-fluorescein isothiocyanate (FITC) conjugate and anti-FITC-magnetic colloid are the chosen cell systems. Flow cytometry analysis shows that, for CD4 cells, a three-fold increase in total marker number per cell is observed when comparing the highest to the lowest fluorescence fractions. Similarly, a four-fold increase in total marker number is observed for CD8 cells. We also observed the separation of two dissimilar cell types that differed in expression of the CD4 marker, monocytes and T helper lymphocytes. We believe that this type of separation is applicable to any cells in suspension for which a suitable antibody exists and, due to the comparatively gentle nature of the process, is particularly suitable for the sorting of fragile cells.

Biomedical Engineering↗
PubMed1998

Physiology and molecular phylogeny of coexisting Prochlorococcus ecotypes.

The cyanobacterium Prochlorococcus is the dominant oxygenic phototroph in the tropical and subtropical regions of the world's oceans. It can grow at a range of depths over which light intensities can vary by up to 4 orders of magnitude. This broad depth distribution has been hypothesized to stem from the coexistence of genetically different populations adapted for growth at high- and low-light intensities. Here we report direct evidence supporting this hypothesis, which has been generated by isolating and analysing distinct co-occurring populations of Prochlorococcus at two locations in the North Atlantic. Co-isolates from the same water sample have very different light-dependent physiologies, one growing maximally at light intensities at which the other is completely photoinhibited. Despite this ecotypic differentiation, the co-isolates have 97% similarity in their 16S ribosomal RNA sequences, demonstrating that molecular microdiversity, commonly observed in microbial systems, can be due to the coexistence of closely related, physiologically distinct populations. The coexistence and distribution of multiple ecotypes permits the survival of the population as a whole over a broader range of environmental conditions than would be possible for a homogeneous population.

Cyanobacteria↗
PubMed1992

Central venous catheterization in patients with coagulopathy.

To explore the risk of bleeding complications during percutaneous central venous catheterization in patients with coagulopathy, 40 liver transplant recipients underwent 259 percutaneous central venous catheterizations. Two hundred two catheterizations were performed in patients with coagulopathy, as evidenced by their prothrombin times, activated partial thromboplastin times, and/or platelet counts. Furthermore, no attempt was made to correct these episodes of coagulopathy with medications or infusion of blood products. No serious bleeding complications occurred during the 259 catheterizations, which suggests that experienced clinicians using appropriate techniques may safely perform central venous catheterization in patients with abnormal prothrombin times, activated partial thromboplastin times, and platelet counts.

Blood Coagulation Disorders↗
PubMed1990

Co-culture of primary pulmonary cells to model alveolar injury and translocation of proteins.

Primary rat alveolar type II cells and early passage rat lung fibroblasts were co-cultured on opposite sides of a collagen-coated polycarbonate filter. This is an approach to "model", in part, an alveolar wall to study mechanisms of cytotoxicity and translocation of bioactive materials from the alveolar space to the lung interstitium. Type II cells were recovered from adult rat (Fischer 344) lungs by enzyme digestion and "panning". Lung fibroblasts were separated from the same species, cultured initially in 10% fetal bovine serum and used in the co-culture system at early passage. The type II cells formed a monolayer of dedifferentiated epithelium which provided a barrier on the upper side of the collagen (human type IV)-coated filter. The fibroblasts on the bottom of the filter replicated logarithmically in the presence of serum, could be rendered quiescent in defined medium and then returned to rapid growth phase with the reintroduction of serum. The intact epithelial monolayer excluded trypan blue, albumin, platelet-derived growth factor, and alpha2-macroglobulin from the lower compartment of the culture chamber. Altering the integrity of the monolayer by a variety of means allowed translocation of these materials through the collagen-coated filters. Particularly interesting was the effect of taurine chloramine which caused subtle changes in the alveolar epithelium and allowed subsequent translocation of albumin. In addition, we showed that rat alveolar macrophages remain viable with some spreading on the surface of the epithelial monolayer. This co-culture system will have future application in the study of how reactive oxygen species might affect the epithelial barrier, and whether macrophage-derived growth factors can influence fibroblast proliferation if the monolayer is intact or injured.

Animals↗
PubMed1989

Personal safety. It is a matter of awareness.

The safety and security points discussed in this article are only a few of the awareness tips that can add to your personal safety. When reporting to work, especially during odd hours, be suspicious of all activities. Ask yourself, "What if?" Becoming a victim or not becoming a victim is easy.

Crime↗
PubMed1988

Development of the rabbit model for studying the effects of propranolol on cardiac contractility: relationship of intravenous pharmacodynamics and pharmacokinetics.

The New Zealand white rabbit (3-4 kg) was chosen as an experimental model to determine the effects of propranolol, by intravenous bolus administration, on cardiac contractility. The cardiovascular effects were measured by systolic time interval recordings for up to 8 h. The study was performed on two groups of animals with 5 rabbits receiving active drug and another 5 rabbits receiving saline placebo. All animals were anesthetized by parenteral administration of urethane/acepromazine. The results indicated that at 15 min after intravenous administration, propranolol caused a maximum decrease in heart rate (p less than 0.01), as well as a maximum increase in QS2 (p less than 0.01), LVET (p less than 0.01), PEP (p less than 0.01) and PEP/LVET (p less than 0.05). Approximately 90 min after drug administration, a significant (p less than 0.01) "rebound phenomenon" was observed in the active group which continued throughout the 8-h observation period. This preliminary study suggests that the rabbit is a useful animal model to study the effects of propranolol on cardiac contractility.

Animals↗
PubMed1987

Urethane-acepromazine: a novel method of administering parenteral anesthesia in the rabbit.

Stable long-term anesthesia in the rabbit (greater than 8 hr) has been achieved by the administration of urethane and acepromazine. Twenty-five healthy male New Zealand white rabbits weighing 2 to 4 kg were used for this study. Two groups of animals were studied. The first group of 11 rabbits received urethane (1.0 g/kg) and acepromazine (1 mg/0.46 kg). This resulted in stable light plane anesthesia for 13.5 +/- 4.5 hr (mean + S.D.). The second group of 14 rabbits received urethane (1.3 g/kg) and acepromazine (1 mg/0.46 kg) which resulted in deep plane anesthesia for 23.0 +/- 4 hr. Heart rate and respiratory rate remained stable throughout the entire period and all animals were alert and without any observable side effects by 48 +/- 3 hr. This study indicates that the combination of urethane-acepromazine is a safe and reproducible parenteral anesthetic that may be used in studies of long duration in rabbits.

Acepromazine↗
PubMed1986

Forensic psychology: an empirical review of experimental research.

The present paper evaluated the first 11 years of experimental research (1973-1983) publications, with a focus on forensic psychology, that were cited in Psychological Abstracts. Articles were reviewed for type of methodology and statistical analyses employed as well as the relationship between the number of empirical and nonempirical articles. Trends in publications are presented, and the type of empirical research is evaluated. Results indicate: a paucity of experimental research; a significant difference between empirical and nonempirical publications; and a transition--albeit based on a limited number of research publications--from descriptive to correlational and experimental research over time.

Forensic Psychiatry↗
PubMedDate not supplied

Magnetic flow sorting using a model system of human lymphocytes and a colloidal magnetic label.

Cells of identical physical properties that differ in the expression of surface proteins can be sorted conveniently using immunospecific stains conjugated to fluorescent, or magnetic, labels. Immunomagnetic cell sorting using commercial batch sorters offers advantages of high sorting capacity, high viability of sorted fractions, and high depletion rates; its disadvantages are low enrichment rate and batch processing. The authors developed and tested a continuous, flow-through magnetic cell sorter for small volume, experimental cell enrichment. Freshly isolated human peripheral lymphocytes were labeled using an immunofluoromagnetic sandwich consisting of mouse anti human CD8 monoclonal antibody-fluorescein conjugate and rat anti mouse polyclonal antibody-colloidal iron-dextran conjugate. A total of 2-3 min lymphocytes were sorted per hour using a saturation magnetic field of 1.334 T and a five channel sorter. The fluorescent cells were distributed among the channels in relation to their fluorescence intensity and magnetic susceptibility. The purity (68-85%) and enrichment rates (16-34x) were comparable to those of commercial batch magnetic separators; sorting capacity and recovery of the enriched fractions (up to 32%) were limited by the small scale of the sorter. Future direction is focused on increasing the resolution, recovery, and sorting capacity of the enriched fractions, and testing the sorter on other cell systems.

Animals↗
PubMedDate not supplied

Rapid cell isolation by magnetic flow sorting for applications in tissue engineering.

Rapid and efficient cell sorting methods are important for tissue progenitor cell isolation. We built and evaluated a laboratory prototype of a continuous flow, quadrupole magnetic cell sorter. The sorter was tested on a model cell system of human peripheral lymphocytes. The helper T cell subpopulation was targeted by primary, mouse anti-CD4 monoclonal antibody conjugated to a fluorochrome (FITC), and magnetized by secondary, anti-FITC antibody magnetic colloid. The purities and recoveries of the cell fractions were measured by flow cytometry and an automated cell counter. Cells were spread across the flow according to their magnetophoretic mobilities. The purity of the CD4 cell enriched fraction was 99.6%, and the purity of the CD4 cell depleted fraction was 2% for an initial CD4 cell purity of 36%; the corresponding recovery of the enriched CD4 cell fraction was 59% at a sorting speed of 4,200 cells/s (four experiments). The recovery could be increased to 90% with a concomitant decrease in the purity of CD4 cell enriched fraction to 66%. This type of sorting should be applicable to any cells in suspension for which a suitable antibody exists, in particular, to large, fragile cells.

Antibodies, Monoclonal↗