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At least 1,225 records · Page 68Linked to original sources
PubMed1996

Efficacy of agonist-stimulated MEK activation determines the susceptibility of mitogen-activated protein (MAP) kinase to inhibition in rat aortic smooth muscle cells.

In rat aortic smooth muscle cells, platelet-derived growth factor (PDGF) stimulated a sustained activation of mitogen-activated protein kinase (MAP kinase) while the response to angiotensin II (AII) was transient. This was due to a relatively greater initial activation of MAP kinase kinase (MEK) and a correspondingly greater residual MEK activity at later time points. Pretreatment of cells with the novel MEK inhibitor PD 098059 reduced MEK activation at 5 min in response to each agonist by a similar proportion (70%); however, at this time point MAP kinase activation in response to PDGF was only marginally affected while the response to AII was substantially reduced. PD 098059 did, however, reduce PDGF-stimulated MEK activity after 30 min and this correlated with a loss in MAP kinase activity and DNA synthesis. Pretreatment with forskolin also caused a similar pattern of inhibition of agonist-stimulated MEK and MAP kinase activity. Only following protein kinase C down-regulation were both AII- and PDGF-stimulated MAP kinase activation substantially reduced and this correlated with the virtual loss of both MEK and c-Raf-1 activity in response to both agents. The differential inhibition of MAP kinase activation by forskolin was not due to specific activation of A-Raf by PDGF; both PDGF and AII stimulated A-Raf kinase and this activity was strongly inhibited by forskolin. These results suggest that the efficacy of MEK activation determines the duration of MAP kinase activation and the susceptibility of MAP kinase activation to inhibition by different agents. The results also argue against the selective activation of A-Raf by PDGF as a mechanism to explain the differences in the kinetics of MAP kinase activity stimulated by AII and PDGF.

Angiotensin II↗
PubMed1992

Finding locations in the environment: the map as mediator.

When an observer (O) uses a map (M) whose orientation does not correspond to the orientation of the environment (E) in which performance occurs, substantial errors occur: these are called map alignment effects. Much of the prior research on map/environment (M/E) alignment has involved maps of simple paths, although alignment effects have also been demonstrated for you-are-here (YAH) maps. A study is reported in which simple YAH maps were used to test the hypothesis that errors with misaligned maps would fall into categories predictable from the application of inappropriate cognitive operations to the misaligned maps, as demonstrated earlier by Rossano and Warren. Further, performance under conditions of M/E misalignment was compared with performance under map/observer (M/O) misalignment, the situation in which the map is sideways or upside-down with respect to the observer. The major hypothesis was supported: predictable errors occurred under conditions of M/E misalignment. Errors under conditions of M/O misalignment were significantly smaller. Furthermore, when given the choice of using M/E or M/O alignment, each at the expense of the other, the overwhelming choice was to retain M/E rather than M/O alignment. This pattern of results occurred even when environmental features were represented by words rather than by lines and shapes on the map. The results underscore the robustness of map alignment effects.

Adult↗
PubMed1993

Identification and molecular characterization of E-MAP-115, a novel microtubule-associated protein predominantly expressed in epithelial cells.

A novel microtubule-associated protein (MAP) of M(r) 115,000 has been identified by screening of a HeLa cell cDNA expression library with an anti-serum raised against microtubule-binding proteins from HeLa cells. Monoclonal and affinity-purified polyclonal antibodies were generated for the further characterization of this MAP. It is different from the microtubule-binding proteins of similar molecular weights, characterized so far, by its nucleotide-insensitive binding to microtubules and different sedimentation behavior. Since it is predominantly expressed in cells of epithelial origin (Caco-2, HeLa, MDCK), and rare (human skin, A72) or not detectable (Vero) in fibroblastic cells, we name it E-MAP-115 (epithelial MAP of 115 kD). In HeLa cells, E-MAP-115 is preferentially associated with subdomains or subsets of perinuclear microtubules. In Caco-2 cells, labeling for E-MAP-115 increases when they polarize and form blisters. The molecular characterization of E-MAP-115 reveals that it is a novel protein with no significant homologies to other known proteins. The secondary structure predicted from its sequence indicates two domains connected by a putative hinge region rich in proline and alanine (PAPA region). E-MAP-115 has two highly charged regions with predicted alpha-helical structure, one basic with a pI of 10.9 in the NH2-terminal domain and one neutral with a pI of 7.6 immediately following the PAPA region in the acidic COOH-terminal half of the molecule. A novel microtubule-binding site has been localized to the basic alpha-helical region in the NH2-terminal domain using in vitro microtubule-binding assays and expression of mutant polypeptides in vivo. Overexpression of this domain of E-MAP-115 by transfection of fibroblasts lacking significant levels of this protein with its cDNA renders microtubules stable to nocodazole. We conclude that E-MAP-115 is a microtubule-stabilizing protein that may play an important role during reorganization of microtubules during polarization and differentiation of epithelial cells.

Alanine↗
PubMed1998

Active MAP kinase in mitosis: localization at kinetochores and association with the motor protein CENP-E.

To investigate possible involvement of the mitogen-activated protein (MAP) kinases ERK1 and ERK2 (extracellular signal-regulated kinases) in somatic cell mitosis, we have used indirect immunofluorescence with a highly specific phospho-MAP kinase antibody and found that a portion of the active MAP kinase is localized at kinetochores, asters, and the midbody during mitosis. Although the aster labeling was constant from the time of nuclear envelope breakdown, the kinetochore labeling first appeared at early prometaphase, started to fade during chromosome congression, and then disappeared at midanaphase. At telophase, active MAP kinase localized at the midbody. Based on colocalization and the presence of a MAP kinase consensus phosphorylation site, we identified the kinetochore motor protein CENP-E as a candidate mitotic substrate for MAP kinase. CENP-E was phosphorylated in vitro by MAP kinase on sites that are known to regulate its interactions with microtubules and was found to associate in vivo preferentially with the active MAP kinase during mitosis. Therefore, the presence of active MAP kinase at specific mitotic structures and its interaction with CENP-E suggest that MAP kinase could play a role in mitosis at least in part by altering the ability of CENP-E to mediate interactions between chromosomes and microtubules.

3T3 Cells↗
PubMed1999

Comparison of the diagnostic information in relative cerebral blood volume, maximum concentration, and subtraction signal intensity maps based on magnetic resonance imaging of gliomas.

RATIONALE AND OBJECTIVES: The authors investigate the validity of regional relative cerebral blood volume (rCBV) versus maximum concentration and subtraction signal intensity (SI) maps using simple reconstruction modes in patients with gliomas. METHODS: Twenty-five patients were studied using a 1.5 T magnetic resonance imaging scanner. To calculate the rCBV map, the magnetic resonance susceptibility effect SI/time curves were first transformed into concentration/time curves; then a gamma-variate function was fitted and the area under the curve was integrated. From the concentration/time data, the maximum concentration (MAX) maps were calculated pixel per pixel as the maximum peak amplitude of the concentration/time curve. Subtraction (SUB) maps are a result of simple image subtraction of pixelwise baseline SI minus the highest peak of susceptibility change pixel per pixel. Region of interest means SI measurement of the different maps was compared using statistical t test correlation. RESULTS: Normal gray to white matter contrast did not show a significant difference among the rCBV, MAX, and SUB maps. Based on statistical evaluation, the low-grade lesions did not differ significantly in the rCBV, MAX, and SUB maps. The group with high-grade lesions (12 patients) showed no significant difference in standardized rCBV, MAX, and SUB maps. CONCLUSION: Compared to rCBV maps, the simple MAX and SUB maps demonstrated good correlation in both high-grade and low-grade gliomas. This simpler approach could establish first-pass reconstruction in clinical settings because it reduces the need for time-consuming postprocessing.

Adult↗
PubMed2006

Combining central and peripheral videokeratoscope maps to investigate total corneal topography.

PURPOSE: To extend the area of standard corneal topography maps, one central map is combined with six peripheral maps after correlating them in a custom written computer program. METHODS: The point corresponding to the vertex normal of the central map is found in each of the peripheral maps. Data from the peripheral maps can then be added on to the edges of the central map to create a topography map that extends from limbus to limbus horizontally and vertically. RESULTS: The average size of the combined maps from 15 subjects was 11.3 +/- 0.3 mm horizontally and 10.3 +/- 0.3 mm vertically, compared to 9.2 +/- 0.4 mm horizontally and 7.5 +/- 0.7 mm vertically for the standard single maps. These values represent an increase in surface area of approximately 70%. CONCLUSIONS: The topography of the entire cornea can be represented by combining multiple measurements from a Placido videokeratoscope. Conic fits based on central topography data are a poor representation of the total corneal shape.

Adult↗
PubMed2004

A comprehensive genetic map of the cattle genome based on 3802 microsatellites.

A microsatellite-based high-density genetic map facilitates for fine mapping of hereditary traits of interest, characterization of meiosis, and providing a foundation for physical map construction. Here, we developed a comprehensive genetic map on the basis of >880,000 genotypes across the USDA MARC cattle reference families with a potential genetic resolution of 0.8 cM at the 95% confidence level ( approximately 800 kb in the bovine genome). We incorporated 2325 microsatellites into the second-generation genetic map by linkage analysis based on sex-averaged two-point LOD scores (>3.0), of which 2293 were fine-mapped by multipoint linkage analysis. The new 3160-cM map comprised of 29 sex-averaged autosomal linkage groups and a sex-specific X-chromosome linkage group includes 3960 markers with 2389 positions, resulting in an average interval size of 1.4 cM. More than half (51%) of the total length of the map is covered with intervals of 2.0 cM or less, and the largest gap is a 10.2-cM interval on the X-linkage group. The new map should accelerate fine mapping and positional cloning of genes for genetic diseases and economically important traits in cattle, as well as related livestock species, such as sheep and goat.

Animals↗
PubMed2006

Dynamical behavior of hydrodynamic Lyapunov modes in coupled map lattices.

In our previous study of hydrodynamic Lyapunov modes (HLMs) in coupled map lattices, we found that there are two classes of systems with different lambda-k dispersion relations. For coupled circle maps we found the quadratic dispersion relations lambda approximately k2 and lambda approximately k for coupled standard maps. Here, we carry out further numerical experiments to investigate the dynamic Lyapunov vector (LV) structure factor which can provide additional information on the Lyapunov vector dynamics. The dynamic LV structure factor of coupled circle maps is found to have a single peak at omega=0 and can be well approximated by a single Lorentzian curve. This implies that the hydrodynamic Lyapunov modes in coupled circle maps are nonpropagating and show only diffusive motion. In contrast, the dynamic LV structure factor of coupled standard maps possesses two visible sharp peaks located symmetrically at +/- omega. The spectrum can be well approximated by the superposition of three Lorentzian curves centered at omega=0 and +/-omegau, respectively. In addition, the omega-k dispersion relation takes the form omegau=cuk for k --> 2pi/L. These facts suggest that the hydrodynamic Lyapunov modes in coupled standard maps are propagating. The HLMs in the two classes of systems are shown to have different dynamical behavior besides their difference in spatial structure. Moreover, our simulations demonstrate that adding damping to coupled standard maps turns the propagating modes into diffusive ones alongside a change of the lambda-k dispersion relation from lambda approximately k to lambda approximately k2. In cases of weak damping, there is a crossover in the dynamic LV structure factors; i.e., the spectra with smaller k are akin to those of coupled circle maps while the spectra with larger k are similar to those of coupled standard maps.

Journal Article↗
PubMed2006

Gabor-based kernel PCA with doubly nonlinear mapping for face recognition with a single face image.

In this paper, a novel Gabor-based kernel principal component analysis (PCA) with doubly nonlinear mapping is proposed for human face recognition. In our approach, the Gabor wavelets are used to extract facial features, then a doubly nonlinear mapping kernel PCA (DKPCA) is proposed to perform feature transformation and face recognition. The conventional kernel PCA nonlinearly maps an input image into a high-dimensional feature space in order to make the mapped features linearly separable. However, this method does not consider the structural characteristics of the face images, and it is difficult to determine which nonlinear mapping is more effective for face recognition. In this paper, a new method of nonlinear mapping, which is performed in the original feature space, is defined. The proposed nonlinear mapping not only considers the statistical property of the input features, but also adopts an eigenmask to emphasize those important facial feature points. Therefore, after this mapping, the transformed features have a higher discriminating power, and the relative importance of the features adapts to the spatial importance of the face images. This new nonlinear mapping is combined with the conventional kernel PCA to be called "doubly" nonlinear mapping kernel PCA. The proposed algorithm is evaluated based on the Yale database, the AR database, the ORL database and the YaleB database by using different face recognition methods such as PCA, Gabor wavelets plus PCA, and Gabor wavelets plus kernel PCA with fractional power polynomial models. Experiments show that consistent and promising results are obtained.

Algorithms↗
PubMed1998

MAP kinases and vascular smooth muscle function.

The mitogen-activated protein (MAP) kinase family members are ubiquitously expressed protein kinases activated in response to a variety of extracellular stimuli and shown to be involved in cell growth, transformation, differentiation and apoptosis. MAP kinases have been implicated in both growth and apoptosis of vascular smooth muscle cells (VSMC) which suggests that they play important roles in cardiovascular diseases such as essential hypertension, atherosclerosis, and restenosis followed angioplasty. The MAP kinases are themselves components of specific kinase cascades characterized by activation by specific stimuli, families of related serine and threonine kinases and downstream substrates that include other kinases, transcription factors, membrane receptors and other cell mediators. Cross-talk among the different MAP kinases results in direct modulation of signal transduction. In addition, increased expression and activation of MAP kinase phosphatases plays an important role in MAP kinase inactivation. Our laboratory has used angiotensin II (AngII), a potent activator of all MAP kinases in VSMC, to study mechanisms by which MAP kinases are regulated by vasoactive peptides. In this review, we describe the mechanisms by which AngII activates MAP kinases, and potential roles for MAP kinases in AngII-dependent effects on VSMC function.

Animals↗
PubMed2005

Using concept maps to optimize the composition of collaborative student groups: a pilot study.

AIM: The aim of this paper is to stimulate interest in the practical classroom application of concept mapping strategies as an approach that teachers can easily use to enhance collaborative learning. BACKGROUND: Concept mapping has been developed as a tool to support meaningful learning. However, much of the research literature fails to explain how concept maps might be most gainfully employed within the classroom. As a result, concept mapping is a tool that is under-used. METHODS: Students on a postgraduate teacher preparation programme for nurses were arranged in triads on the basis of the morphology of individually-produced concept maps for the topics of 'genetics' and 'pathogenic microbes'. They were arranged in heterogeneous triads to produce a consensus map for 'pathogenic microbes', and then in homogeneous triads to produce a consensus map for 'genetics'. The number of acceptable propositions found in their individual maps was compared with the number found in the consensus group maps, and gain scores were calculated for each participant. FINDINGS: Participants arranged in triads of individuals having very different knowledge structures were found to make a greater improvement than those arranged in triads composed of individuals with qualitatively similar knowledge structures. CONCLUSIONS: The study was undertaken with a very small sample and only looked at two topic areas. However, the findings support the idea that collaborative groups work most effectively when individuals within the group bring different perspectives to a problem, and that this perspective can be usefully identified within the classroom environment as variations in concept map morphology.

Concept Formation↗
PubMed2006

The enteropathogenic Escherichia coli (EPEC) Map effector is imported into the mitochondrial matrix by the TOM/Hsp70 system and alters organelle morphology.

Enteropathogenic Escherichia coli (EPEC) is a human intestinal pathogen and a major cause of diarrhoea, particularly among infants in developing countries. EPEC target the Map and EspF multifunctional effector proteins to host mitochondria - organelles that play crucial roles in regulating cellular processes such as programmed cell death (apoptosis). While both molecules interfere with the organelles ability to maintain a membrane potential, EspF plays the predominant role and is responsible for triggering cell death. To learn more about the Map-mitochondria interaction, we studied Map localization to mitochondria with purified mitochondria (from mammalian and yeast cells) and within intact yeast. This revealed that (i) Map targeting is dependent on the predicted N-terminal mitochondrial targeting sequence, (ii) the N-terminal 44 residues are sufficient to target proteins to mitochondria and (iii) Map import involves the mitochondrial outer membrane translocase (Tom22 and Tom40), the mitochondrial membrane potential, and the matrix chaperone, mtHsp70. These results are consistent with Map import into the mitochondria matrix via the classical import mechanism. As all known, Map-associated phenotypes in mammalian cells are independent of mitochondrial targeting, this may indicate that import serves as a mechanism to remove Map from the cytoplasm thereby regulating cytoplasmic function. Intriguingly, Map, but not EspF, alters mitochondrial morphology with deletion analysis revealing important roles for residues 101-152. Changes in mitochondrial morphology have been linked to alterations in the ability of these organelles to regulate cellular processes providing a possible additional role for Map import into mitochondria.

Amino Acid Motifs↗
PubMed1998

Involvement of tyrosine kinases, Ca2+ and PKC in activation of mitogen-activated protein (MAP) kinase in human polymorphonuclear neutrophils.

1. Activation of mitogen-activated protein (MAP) kinase is an early response to a wide variety of stimuli and plays an important role in the regulation of cellular functions. In the present study we investigated the activation of MAP kinase in human polymorphonuclear neutrophils (PMNs). 2. Activity of MAP kinase and protein kinase C (PKC) was measured radiometrically from the rate of phosphorylation of specific peptide substrates. Protein phosphorylation was measured by immunoprecipitation and Western blot analysis. 3. N-Formyl-Met-Leu-Phe (fMLP), phorbol 12-myristate, 13-acetate (PMA) and the Ca2+-ATPase inhibitors thapsigargin (Tg) and cyclopiazonic acid (CPA) increased MAP kinase activity significantly. The tyrosine kinase inhibitors erbstatin and herbimycin A partially inhibited the effects of fMLP and PMA, and completely abolished the effects of both Tg and CPA. The specific PKC inhibitor calphostin C suppressed activation of MAP kinase produced by fMLP and PMA, but had no effect on that produced by Tg and CPA. Tg and CPA were without effect on PKC activity. 4. Immunoprecipitation and Western blot analysis indicated that the 42 and 44 kDa tyrosine-phosphorylated proteins found after stimulation of PMNs were both members of the MAP kinase family. Pretreatment of PMNs with staurosporine, EGTA or erbstatin significantly reduced the tyrosine phosphorylation of MAP kinase(s). 5. These results suggest that in human PMNs, MAP kinase can be stimulated in both a PKC-dependent and a PKC-independent manner. The Ca2+ signal leads to activation of tyrosine kinases, which contribute to the activation of MAP kinase. However, a PMA-sensitive Ca2+-independent pathway also exists. Mobilization of Ca2+ and activation of PKC synergistically induce maximal MAP kinase activation and tyrosine phosphorylation.

Calcium↗
PubMed1987

Simultaneous multichannel cardiac mapping systems.

There is much current interest in simultaneous multichannel cardiac mapping. In this paper we give recommendations for the construction of a cardiac mapping system. Because the field of cardiac mapping is relatively young, optimum mapping techniques and all possible applications have not yet been developed. Therefore, the mapping system should be flexible and it should have many capabilities. The system should be digital; if variable gains are used, the amplifiers should be programmable and controlled by a microprocessor. It should be possible to analyze previous recordings and acquire additional recordings simultaneously. The mapping system should be able to record continuously for at least tens of minutes and preferably for hours. The recorded data stream should be a self-contained unit, holding all important electrophysiologic information as well as the recorded electrode signals. The programs should be written in C under a UNIX operating system. A minimum of 64 channels should be used for epicardial or endocardial mapping and a minimum of 128 channels for three-dimensional intramural mapping. The leakage current requirements for multichannel mapping systems are too stringent and should be re-evaluated. The major limitation to progress in cardiac mapping is neither the hardware nor the software; it is the electrode: its construction, its placement, its fixation, and the interpretation of its recordings.

Cardiac Pacing, Artificial↗
PubMed1996

Activation of MAP kinases and phosphorylation of caldesmon in canine colonic smooth muscle.

1. Phosphorylation of caldesmon was assayed in canine colonic circular smooth muscle strips labelled with 32P and stimulated with 10 microM acetylcholine. Caldesmon was isolated by two-dimensional non-equilibrium pH gel electrophoresis. Stimulation with acetylcholine increased caldesmon phosphorylation significantly from a basal level of 0.6 +/- 0.07 to 1.1 +/- 0.15 mol P1 (mol caldesmon)-1 after 2 min. 2. MAP kinase activities were measured in SDS extracts of muscle by a gel reconstitution method using myelin basic protein. Myelin basic protein kinase activities were observed at 38, 44, 50 and 57 kDa by the gel reconstitution method. Endogenous caldesmon kinase activities were also identified by the gel reconstitution method at 38, 44 and 50 kDa. The 38 and 44 kDa kinases comigrated with proteins labelled by anti-ERK1 MAP kinase antibodies on Western blots. Both 38 and 44 kDa MBP kinase activities increased significantly during contractions induced by 10 microM acetylcholine, 0.1 microM neurokinin A and 70 mM potassium. 3. Phorbol dibutyrate (0.1 microM) potentiated activation of MAP kinases and contraction of depolarized muscles while producing a decrease in fura-2 fluorescence ratio. This suggests that protein kinase C activation is coupled to MAP kinase activity in colonic smooth muscle. 4. MAP kinases isolated form muscle homogenates by Mono Q chromatography were assayed using the specific MAP kinase substrate peptide APRTPGGRR. Stimulation of muscles for 2 min with 10 microM acetylcholine activated both ERK1 and ERK2 MAP kinase activities 2-fold. 5. To determine the effects of caldesmon phosphorylation by MAP kinase on the cross-bridge cycle, actin sliding velocity was measured with an in vitro motility assay. Unphosphorylated turkey gizzard caldesmon (3 microM) significantly reduced mean sliding velocity. Phosphorylation of caldesmon with sea star ERK1 MAP kinase reversed the inhibitory effect of caldesmon on sliding velocity. The results are consistent with a protein kinase cascade being activated by contractile agonists in gastrointestinal smooth muscle which activates ERK MAP kinases leading to phosphorylation of caldesmon. Phosphorylation of caldesmon in vivo may reverse inhibitory influences of caldesmon on cross-bridge cycling.

Acetylcholine↗
PubMed1979

Electron microscopic mapping of RNA transcribed from the late region of polyoma virus DNA.

The polyoma virus (Py) RNA species transcribed from the L DNA strand of the "late" region of the Py genome in Py-infected mouse cells have been mapped by hybridization with specific fragments of Py DNA followed by electron microscopic visualization of the hybrids. Total cellular polyadenylated Py-specific RNA molecules having an S value in the range of 16S to 20S were purified by oligodeoxythymidylic acidcellulose column chromatography, preparative hybridization with Py DNA, and sucrose gradient centrifugation. Cytoplasmic Py-specific RNA was similarily purified, except that it was not fractionated by sucrose gradient centrifugation. Hybrids of these RNA molecules and Py DNA fragments were spread for electron microscopy by either the cytochrome c technique or the bacteriophage T4 gene 32 protein method. The polyadenylic acid at the 3'-end of the RNA in the hybrids was identified by labeling with simian virus 40 DNA circles to which polybromodeoxyuridylic acid tails had been covalently attached. These experiments revealed the presence of three L DNA strand transcripts in both RNA preparations. Two of these RNA molecules were found to be spliced from chains transcribed from two noncontiguous parts of the late region. The third molecule either is a continuous transcript of the entire late region or contains a splicing feature which is too small to be reliably observed by the electron microscope methods used. The 5'-ends of the three RNA species map within a region extending from 68 to 70 map units on the Py restriction endonuclease map. Each of the two spliced molecules contains a 5'-terminal leader sequence transcribed from a DNA segment with an estimated length of 60 to 110 nuvleotides. The 3'-ends of the leaders map at 66.7 +/- 1.0 and 66.4 +/- 0.50 map units. In these molecules the 5'-ends of the other part (the main body) map at 59.4 +/- 0.90 and 49.4 +/- 2.0 map units, respectively. The 3'-termini of all three RNA species map at 24 to 25 map units.

DNA, Viral↗
PubMedDate not supplied

Portability issues for a structured clinical vocabulary: mapping from Yale to the Columbia medical entities dictionary.

OBJECTIVE: To examine the issues involved in mapping an existing structured controlled vocabulary, the Medical Entities Dictionary (MED) developed at Columbia University, to an institutional vocabulary, the laboratory and pharmacy vocabularies of the Yale New Haven Medical Center. DESIGN: 200 Yale pharmacy terms and 200 Yale laboratory terms were randomly selected from database files containing all of the Yale laboratory and pharmacy terms. These 400 terms were then mapped to the MED in three phases: mapping terms, mapping relationships between terms, and mapping attributes that modify terms. RESULTS: 73% of the Yale pharmacy terms mapped to MED terms. 49% of the Yale laboratory terms mapped to MED terms. After certain obsolete and otherwise inappropriate laboratory terms were eliminated, the latter rate improved to 59%. 23% of the unmatched Yale laboratory terms failed to match because of differences in granularity with MED terms. The Yale and MED pharmacy terms share 12 of 30 distinct attributes. The Yale and MED laboratory terms share 14 of 23 distinct attributes. CONCLUSION: The mapping of an institutional vocabulary to a structured controlled vocabulary requires that the mapping be performed at the level of terms, relationships, and attributes. The mapping process revealed the importance of standardization of local vocabulary subsets, standardization of attribute representation, and term granularity.

Clinical Laboratory Information Systems↗
PubMed2003

p38 MAP kinase regulates BMP-4-stimulated VEGF synthesis via p70 S6 kinase in osteoblasts.

We previously reported that p70 S6 kinase takes part in bone morphogenetic protein-4 (BMP-4)-stimulated vascular endothelial growth factor (VEGF) synthesis in osteoblast-like MC3T3-E1 cells. Recently, we showed that BMP-4-induced osteocalcin synthesis is regulated by p44/p42 MAP kinase and p38 MAP kinase in these cells. In the present study, we investigated whether the MAP kinases are involved in the BMP-4-stimulated synthesis of VEGF in MC3T3-E1 cells. PD-98059 and U-0126, inhibitors of the upstream kinase of p44/p42 MAP kinase, failed to affect BMP-4-stimulated VEGF synthesis. SB-203580 and PD-169316, inhibitors of p38 MAP kinase, significantly reduced VEGF synthesis, whereas SB-202474, a negative control for p38 MAP kinase inhibitor, had little effect on VEGF synthesis. The BMP-4-stimulated phosphorylation of p38 MAP kinase was not affected by rapamycin, an inhibitor of p70 S6 kinase. On the contrary, SB-203580 and PD-169316 reduced the BMP-4-stimulated phosphorylation of p70 S6 kinase. In addition, anisomycin, an activator of p38 MAP kinase, phosphorylates p70 S6 kinase, and the phosphorylation was suppressed by SB-203580. LY-294002, an inhibitor of phosphatidylinositol 3-kinase, failed to suppress the phosphorylation of p38 MAP kinase induced by BMP-4. Not BMP-4 but anisomycin weakly induced the phosphorylation of phosphoinositide-dependent kinase-1. However, anisomycin had little effect on phosphorylation of either Akt or the mammalian target of rapamycin. Taken together, our results suggest that p38 MAP kinase functions in BMP-4-stimulated VEGF synthesis as a positive regulator at a point upstream from p70 S6 kinase in osteoblasts.

Animals↗