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Results for “Enhancer mapping”

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PubMed1995

Difference images calculated from ictal and interictal technetium-99m-HMPAO SPECT scans of epilepsy.

UNLABELLED: Image processing techniques were applied to SPECT brain images to aid in the localization of epileptic foci. METHODS: Ictal and interictal cerebral perfusion SPECT images were acquired from 12 epilepsy patients (6 temporal, 6 extratemporal) after injection of 20 mCi 99mTc-HMPAO. Each ictal scan was registered to the same patient's interictal scan. Normalization of the three-dimensional data was applied to account for global percent brain uptake and total injected activity. After registration, normalization and subtraction of the SPECT images and functional difference images were computed. Difference images were calculated, which give a quantitative measure of perfusion alterations during ictus. The resulting difference images were also registered with each patient's MRI scan which permits localization of perfusion changes onto anatomical structures. RESULTS: Areas in the brain where significant perfusion increases occur correlate with areas confirmed to be seizure foci. Four of the six patients with known temporal lobe seizure foci exhibited significant perfusion increases on the difference images. These areas demonstrate a percent increase of perfusion larger than 40%. For the extratemporal seizure patients, four of the four confirmed seizure sites were diagnosed with difference images. Results on the remaining two patients were inconclusive. CONCLUSION: When compared to side-by-side visual interpretation of the ictal and interictal SPECT images, registration of SPECT and MR images together with calculated difference maps greatly enhances the ability to localize epileptic seizure foci. This offers the potential to locate epileptic seizure foci using a noninvasive, inexpensive imaging procedure and data processing algorithm.

Adolescent↗

PubMed1996

NG-nitro-L-arginine methyl ester attenuates the maintenance and expression of methamphetamine-induced behavioral sensitization and enhancement of striatal dopamine release.

We examined the roles of nitric oxide (NO) in methamphetamine (MAP)-induced behavioral sensitization and enhancement of striatal dopamine (DA) release using both in vivo and in vitro methods. Repeated administration of MAP produced augmentation of MAP-induced locomotor activity after 3-day withdrawal of MAP and an enhancement of MAP-evoked DA release from striatal slices after 6-day withdrawal. When the NO synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester (L- NAME) was administered only during the period of MAP withdrawal, the behavioral sensitization and enhancement of DA release were attenuated significantly. In contrast, NG-nitro-D- arginine methyl ester, an inactive isomer of L-NAME, exhibited no such effect. When L-NAME was administered acutely before the challenge injection of MAP, behavioral sensitization was also attenuated only when the dose of L-NAME was high. Coadministration of L-NAME with MAP did not block the development of sensitization to MAP. We also examined whether MAP-induced behavioral sensitization and enhancement of DA release could be observed in vivo in a microdialysis experiment. Challenge injection of MAP caused marked enhancement of DA release in MAP-sensitized rats compared with saline-treated controls corresponding to robust augmentation of locomotor activity. When L-NAME was injected during the MAP withdrawal period, the enhancement of DA release and locomotor activity induced by challenge injection of MAP were attenuated. These results suggest that NO production plays a role in the maintenance (expression) of MAP-induced behavioral sensitization and enhancement of DA release but not in the development of these effects.

Animals↗

PubMed1994

A myeloid-lineage-specific enhancer upstream of the mouse myeloperoxidase (MPO) gene.

The myeloperoxidase (MPO) gene is selectively expressed during haemopoiesis in the granulocytic lineage. Compared with the erythroid (beta-globin) and B-cell (immunoglobulin) lineages, little is known of the regulatory sequences and transcription factors involved in the regulation of genes specific for granulopoiesis. We have approached this issue by identifying a strong enhancer for the murine MPO gene. A candidate enhancer region was mapped by the detection of a strong DNase I hypersensitive site, -3.4 to -3.2 kb upstream of the MPO gene. A 301 bp fragment encompassing the DNase I site was shown to have strong enhancer function in a transient assay following transfection of a reporter gene into a MPO-expressing cell (WEHI 3BD+), but was inactive in lymphoid cells. Analysis of sub-fragments revealed that the whole 301 bp fragment is required for maximal enhancer function.

Animals↗

PubMed2004

Glial tumor grading and outcome prediction using dynamic spin-echo MR susceptibility mapping compared with conventional contrast-enhanced MR: confounding effect of elevated rCBV of oligodendrogliomas [corrected].

BACKGROUND AND PURPOSE: The MR imaging characteristics of oligodendrogliomas and astrocytomas on spin-echo (SE), echo-planar relative cerebral blood volume (rCBV) maps, to our knowledge, have not previously been emphasized. We compared the specificity of SE rCBV mapping with that of conventional, contrast material-enhanced MR imaging in differentiating high- from low-grade glial tumors and in predicting survival of patients with these lesions. METHODS: Thirty consecutive adult patients with suspected gliomas underwent conventional and rCBV MR imaging. Representative maximal rCBV regions of interest were chosen from each lesion. Resultant values were normalized to those of corresponding, contralateral, uninvolved regions. These normalized CBV (nCBV) values were correlated with degree of contrast enhancement, histopathologic tumor grade, and survival. RESULTS: Twenty-two patients had astroctyomas and eight had oligodendrogliomas. With an nCBV cutoff ratio of 1.5, 13 of 13 high-grade astrocytomas were correctly categorized, three of which did not enhance. Seven of nine low-grade astrocytomas were correctly classified by their nCBV values, including one enhancing lesion. Of eight oligodendrogliomas, four of four high-grade and two of four low-grade tumors had elevated nCBV values; two low-grade oligodendrogliomas enhanced, one with nCBV greater than 1.5 and one with nCBV less than 1.5. In 19 patients with astrocytoma for whom survival data were available, correlation with survival was better for nCBV (mean survival 91 +/- 14 months for nCBV < 1.5 versus 24 +/- 27 months for nCBV > 1.5, P <.0001) than for enhancement (mean survival 61 +/- 35 months without enhancement versus 22 +/- 29 months with enhancement, P =.03). CONCLUSION: Elevated SE rCBV was a sensitive, but not specific, marker for high-grade histopathology: all high-grade tumors had nCBV foci values greater than 1.5. No tumor with nCBV region of interest less than 1.5 was high grade (100% predictive value for excluding high grade). Degree of nCBV elevation was a stronger predictor of both tumor grade and survival than was degree of enhancement. A significant proportion of low-grade glial neoplasms, most notably oligodendrogliomas, may display high rCBV foci not reflective of high-grade histopathology.

Adolescent↗

PubMed1987

Effects of methamphetamine administration on brain neurotensin-like immunoreactivity in rats.

The effects of methamphetamine (MAP) administration on neurotensin-like immunoreactivity (NTLI) were investigated in the rat brain. A single administration of MAP induced dose-dependent and reversible increases in NTLI in the caudate-putamen, limbic forebrain and midbrain. NTLI in the caudate-putamen, limbic forebrain and midbrain was also enhanced after repeated administration of MAP. It was assumed that MAP enhanced NTLI in the caudate-putamem, limbic forebrain and midbrain through its action upon the nigrostriatal and mesolimbic dopamine systems.

Animals↗

PubMed1989

Reduction of rat striatal thyrotropin-releasing hormone receptors produced by repeated methamphetamine administration.

It has been reported previously that repeated, but not continuous, administration of methamphetamine (MAP) to animals produces progressive and sustained enhancement of MAP-induced behavior (behavioral sensitization), which may be related to functional changes in central dopamine (DA) systems. To investigate the possible involvement of thyrotropin-releasing hormone (TRH), a neuromodulator of DA, both immunoreactive TRH (IR-TRH) levels and specific TRH binding were examined in rat brain regions after MAP administration either repeatedly (4 mg/kg intraperitoneally once a day for 14 consecutive days) or continuously (about 4 mg/kg/day for 13 consecutive days). Although no significant changes were observed in IR-TRH levels in any regions of the brain following repeated MAP injections, specific TRH binding in the striatum significantly decreased. Scatchard analysis revealed that the decrease was due to a reduction in the maximum number of binding sites (Bmax). Pretreatment with haloperidol prior to each MAP injection prevented this decrease. Continuous MAP administration had no effect on regional specific TRH binding. These results suggest that repeated MAP administration caused lasting dysfunction in the brain TRH system, which may be implicated in the behavioral sensitization.

Animals↗

PubMed2005

An entropy-based measure of founder informativeness.

Optimizing quantitative trait locus (QTL) mapping experiments requires a generalized measure of marker informativeness because variable information is obtained from different marker systems, marker distribution and pedigree types. Such a measure can be derived from the concept of Shannon entropy, a central concept in information theory. Here we introduce entropy-based founder informativeness (EFI), a new measure of information content generalized across pedigrees, maps, marker systems and mating configurations. We derived equations for inbred- and outbred-derived mapping populations. Mathematical properties of EFI include enhanced sensitivity to mapping population type and extension to any number of founders. To illustrate the use of EFI, we compared experimental designs for QTL mapping for three examples: (i) different marker systems for an F2 pedigree, (ii) different marker densities and sampling sizes for a BC1 pedigree and (iii) a comparison of haplotypic versus zygotic analyses of an outbred pedigree. As an a priori generalized measure of information content, EFI does not require phenotypic data for optimizing experimental designs for QTL mapping.

Alleles↗

PubMed1999

Affinity maps and relationship diagrams: two tools to enhance performance improvement.

This article describes two performance improvement tools: an affinity map and a relationship diagram. The author suggests when to use them and provides instructions on how to scan the environment of a nursing unit to discover problems, organize ideas about the problem, and find the root cause and effect of the relationship among staff's ideas about the problem. When the main cause and effect of a problem are known, management and staff can decide where to direct their process improvement efforts.

Audiovisual Aids↗

PubMed1987

Enhancement of ambulation-increasing effect produced by repeated administration of methamphetamine in rats and neurochemical changes in catecholaminergic neurons.

Male rats of the Wistar strain were repeatedly given methamphetamine (MAP) at 0.5 mg/kg, s.c., 10 times at a fixed interval of 4 days in different environmental situations. The effects of MAP administration on ambulatory activity and neurochemical parameters in the brain were investigated. MAP (0.5 mg/kg) markedly increased ambulatory activity. The ambulation-increasing effect of MAP was progressively enhanced without accompanying stereotyped behaviors when the drug was repeatedly given in the activity cage. The once enhanced effect was considered to be irreversible. In addition, the pretreatment with MAP in the activity cage produced a decrease in the maximum density of 3H-spiperone binding sites in the striatum and that of 3H-WB4101 binding sites in the cortex and hippocampus, with decreases in catecholamine and increases in its metabolites. However, the enhancement of the ambulation-increasing effect of MAP and changes in the binding sites or catecholamine metabolism were scarcely observed when the drug was repeatedly given to the rats in the narrow cage where horizontal ambulation of the animals was strongly impaired. These results suggest that the enhancing effect of MAP is closely related to the environmental situations to which the animals have been exposed to under the drug effect. Moreover, it is indicated that there is a correlation between the enhancement of the ambulation-increasing effect of MAP and changes in the neurochemical parameters. The enhancing effect of MAP is supposed to have been partially caused by changes in cerebral catecholaminergic systems, in particular an increase in catecholamine turnover.

Animals↗

PubMed2005

Enhanced FMAM based on empirical kernel map.

The existing morphological auto-associative memory models based on the morphological operations, typically including morphological auto-associative memories (auto-MAM) proposed by Ritter et al. and our fuzzy morphological auto-associative memories (auto-FMAM), have many attractive advantages such as unlimited storage capacity, one-shot recall speed and good noise-tolerance to single erosive or dilative noise. However, they suffer from the extreme vulnerability to noise of mixing erosion and dilation, resulting in great degradation on recall performance. To overcome this shortcoming, we focus on FMAM and propose an enhanced FMAM (EFMAM) based on the empirical kernel map. Although it is simple, EFMAM can significantly improve the auto-FMAM with respect to the recognition accuracy under hybrid-noise and computational effort. Experiments conducted on the thumbnail-sized faces (28 x 23 and 14 x 11) scaled from the ORL database show the average accuracies of 92%, 90%, and 88% with 40 classes under 10%, 20%, and 30% randomly generated hybrid-noises, respectively, which are far higher than the auto-FMAM (67%, 46%, 31%) under the same noise levels.

Algorithms↗

PubMed2004

Development and mapping of EST-derived simple sequence repeat markers for hexaploid wheat.

Expressed sequence tags (ESTs) are a valuable source of molecular markers. To enhance the resolution of an existing linkage map and to identify putative functional polymorphic gene loci in hexaploid wheat (Triticum aestivum L.), over 260,000 ESTs from 5 different grass species were analyzed and 5418 SSR-containing sequences were identified. Using sequence similarity analysis, 156 cross-species superclusters and 138 singletons were used to develop primer pairs, which were then tested on the genomic DNA of barley (Hordeum vulgare), maize (Zea mays), rice (Oryza sativa), and wheat. Three-hundred sixty-eight primer pairs produced PCR amplicons from at least one species and 227 primer pairs amplified DNA from two or more species. EST-SSR sequences containing dinucleotide motifs were significantly more polymorphic (74%) than those containing trinucleotides (56%), and polymorphism was similar for markers in both coding and 5' untranslated (UTR) regions. Out of 112 EST-SSR markers, 90 identified 149 loci that were integrated into a reference wheat genetic map. These loci were distributed on 19 of the 21 wheat chromosomes and were clustered in the distal chromosomal regions. Multiple-loci were detected by 39% of the primer pairs. Of the 90 mapped ESTs, putative functions for 22 were identified using BLASTX queries. In addition, 80 EST-SSR markers (104 loci) were located to chromosomes using nullisomic-tetrasomic lines. The enhanced map from this study provides a basis for comparative mapping using orthologous and PCR-based markers and for identification of expressed genes possibly affecting important traits in wheat.

Chromosome Mapping↗

PubMed1998

MAP kinase phosphatase 1 is expressed and enhanced by FK506 in surviving mamillary, but not degenerating nigral neurons following axotomy.

The MAP kinase phosphatase 1 (MKP-1), a dual serine-threonine phosphatase, inactivates the MAP kinases ERK and JNK/SAPK which are involved in neuronal survival and neuronal cell death following injury and degenerative stimuli. We have studied by immunocytochemistry whether regulation of MKP-1 is part of the cell-body response following nerve fiber transection. The expression of MKP-1 was investigated in axotomized neurons of the corpus mamillaris (CMm) and substantia nigra pars compacta (SNC) following transection of the mamillo-thalamic tract (MT) and the medial forebrain bundle (MFB), respectively. In contrast to the surviving CMm neurons, the vast majority of SNC neurons undergoes cell death following axotomy. MKP-1 immunoreactivity which is absent in untreated adult rats, appeared in CMm neurons 24 h following MT transection, reached a maximum after 2 days and persisted in a substantial proportion of CMm neurons until 20 days, the end of observation period. In contradistinction, MKP-1 could not be detected in the SNC neurons. MKP-1 immunoreactivity was virtually restricted to the nuclei of neurons. Subcutaneous injection of the immunosuppressant FK506 that protects axotomized SNC neurons against neuronal cell death, enhanced the expression of MKP-1 in CMm, but failed to do so in SNC neurons. The selective expression of MKP-1 in CMm is the first finding on a different regulation of components in the stress kinase signal pathway in surviving vs. degenerating axotomized neurons.

Animals↗

PubMed2006

Improved neuronal tract tracing using manganese enhanced magnetic resonance imaging with fast T(1) mapping.

There has been growing interest in using manganese-enhanced MRI (MEMRI) to detect neuronal activation, neural architecture, and neuronal connections. Usually Mn(2+) produces a very wide range of T(1) change. In particular, in neuronal tract tracing experiments the site of Mn(2+) injection can have very short T(1) while distant regions have small T(1) reductions, primarily due to dilution of Mn(2+). Most MEMRI studies use T(1)-weighted sequences, which can only give optimal contrast for a narrow range of T(1) changes. To improve sensitivity to the full extent of Mn(2+) concentrations and to optimize detection of low concentrations of Mn(2+), a fast T(1) mapping sequence based on the Look and Locker technique was implemented. Phantom studies demonstrated less than 6.5% error in T(1) compared to more conventional T(1) measurements. Using center-out segmented EPI, whole-brain 3D T(1) maps with 200-microm isotropic resolution were obtained in 2 h from rat brain. Mn(2+) transport from the rat olfactory bulb through appropriate brain structures could be detected to the amygdala in individual animals. The method reliably detected less than 7% reductions in T(1). With this quantitative imaging it should be possible to study more extensive pathways using MEMRI and decrease the dose of Mn(2+) used.

Animals↗

PubMed2006

Preliminary study: color map of hepatocellular carcinoma using dynamic contrast-enhanced 256-detector row CT.

To distinguish hepatocellular carcinoma (HCC) from normal liver tissue, a color map was made by dynamic contrast-enhanced 256-detector row CT developed at our institute. Dynamic enhanced CT of the liver of three patients with HCC was studied. The CT has 912 (transverse) x 256 (cranio-caudal) elements, each measuring approximately 0.5 mm x 0.5mm at the center of rotation. Scanning for 10 s (1.0 s/rotation) was started 30 s after intravenous injection of contrast medium. The reconstruction increment was 0.62 mm with a time interval of 0.1s and a matrix size of 512 x 512 x 256. Color maps were generated to show the gradient of the regression line of the time-density change. Due to volume acquisition, the 3D color map can be created using continuous 10-s scanning. The densities of the HCC and liver were decreased and increased during scanning, respectively. The HCC was detected clearly in the color map as a downward-sloping region. Dynamic enhanced 256-detector row CT could be useful for detecting malignant tumors in the liver with a short scan time.

Aged↗

PubMed1998

Role of Cx43 phosphorylation and MAP kinase activation in EGF induced enhancement of cell communication in human kidney epithelial cells.

Epidermal growth factor (EGF) has been found to induce enhanced gap junctional intercellular communication (GJIC) in the human kidney epithelial cell line K7. This is in contrast to what is reported for other cell types, which all show decreased GJIC in response to EGF. In the present study it is shown that 12-O-tetradecanoylphorbol-13-acetate (TPA) and EGF induce similar phosphorylation pattern of the gap junction protein connexin43 (Cx43) in K7 cells, although their effects on GJIC are opposite. Tyrosine phosphorylation of a 42 kD protein was observed to be induced concomitantly with phosphorylation of Cx43. EGF was however found to induce only serine phosphorylation of Cx43, indicating that the tyrosine kinase activity of the EGF receptor was not directly affecting the gap junction protein. The 42 kD protein phosphorylated on tyrosine was identified to be a mitogen activated protein (MAP) kinase. Both EGF and TPA was found to activate MAP kinase in these cells. Phosphorylation of Cx43 and enhancement of GJIC in response to EGF occurred with difference in time course. Phosphorylation of Cx43 was completed within 15 min, while the enhanced GJIC appeared 2-3 h later. It is therefore possible that regulation of synthesis or transport of Cx43 is responsible for the increase in GJIC, rather than direct involvement of Cx43 phosphorylation. This is in support of our previous finding that protein synthesis is necessary for EGF induced upregulation of GJIC in K7 cells.

Antibodies↗

PubMed2003

Using matrix peaks to map topography: increased mass resolution and enhanced sensitivity in chemical imaging.

It is well known in secondary ion mass spectrometry (SIMS) that sample topography leads to decreased mass resolution. Specifically, the ion's time of flight is dependent on where it was generated. Here, using matrix-enhanced SIMS, it is demonstrated that, in addition to increasing the yield of intact pseudomolecular ions, the matrix allows the user to semiquantitatively record the topography of a sample. Through mapping the topography-related mass shifts of the matrix (which leads to decreased mass resolution), the analogous mass shifts of higher mass ions can be deconvoluted and higher resolution and greater sensitivity obtained. Furthermore, the semiquantitative topographical map obtained can be compared with any chemical images obtained, allowing the user to quickly ascertain whether local intensity maximums are due to topological features or represent genuine features of interest.

Journal Article↗

PubMed2000

Regulation of nitric oxide production in cultured human T84 intestinal epithelial cells by nuclear factor-kappa B-dependent induction of inducible nitric oxide synthase after exposure to bacterial endotoxin.

BACKGROUND: Intestinal epithelium is consistently in contact with lipopolysaccharide (LPS) produced by intraluminal microbes. LPS induces nitric oxide production in many rodent cells, but in human cells it is very differently regulated. AIM: To test the hypothesis that exposure to LPS up-regulates nitric oxide synthesis in human intestinal epithelium. METHODS AND RESULTS: LPS induced nitric oxide synthesis in T84 cells in a time- and dose-dependent manner whereas detectable amounts of peroxynitrite were not produced. A novel selective inducible nitric oxide synthase (iNOS) inhibitor 1400 W potently inhibited LPS-induced nitric oxide synthesis in T84 cells while dexamethasone was relatively ineffective. Nitric oxide production was sensitive to cycloheximide, indicating that it was dependent on de novo protein synthesis. Nuclear factor-kappa B (NF-kappa B) inhibitor pyrrolidinedithiocarbamate abolished iNOS and nitric oxide production. Nitric oxide synthesis was also suppressed by genistein (tyrosine kinase inhibitor) and PD 98059 (p44/42 MAP kinase inhibitor) but enhanced by SB 203580 (p38 MAP kinase inhibitor). CONCLUSIONS: Intestinal epithelial cells express iNOS and produce nitric oxide in a nuclear factor-kappa B-dependent manner when exposed to LPS. The process is regulated by tyrosine kinases, and p44/42 and p38 MAP kinases. Because nitric oxide acts as an antimicrobial agent and immune modulator, these findings are implicated in the regulation of gut mucosal immunity.

Amidines↗

PubMed1995

The Wnt-1 proto-oncogene regulates MAP kinase activation by multiple growth factors in PC12 cells.

PC12/Wnt-1 cells display morphological changes in response to stimulation by select growth factors but do not respond to NGF. Furthermore, stimulation by EGF can induce neuronal differentiation in these cells but not in wild type cells. We have found that in these cells, compared to wild type PC12 cells, FGF and EGF stimulation of MAP kinase activity is enhanced, while NGF stimulation of MAP kinase in diminished. Finally, in cells expressing Wnt-1, the effect of cyclic adenosine monophosphate (cAMP) on MAP kinase activation is reversed; cAMP stimulates MAP kinase in wild type PC12 cells but inhibits MAP kinase in PC12/Wnt-1 cells. These data suggest that Wnt-1 expression alters the specificity of growth factor signaling in neuronal cells.

Animals↗