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Results for “Enhancer mapping”

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At least 811 records · Page 45Linked to original sources

PubMed2006

Pituitary macroadenomas: preoperative evaluation of consistency with diffusion-weighted MR imaging--initial experience.

PURPOSE: To prospectively evaluate use of diffusion-weighted (DW) magnetic resonance (MR) images and apparent diffusion coefficient (ADC) maps for determination of the consistency of macroadenomas. MATERIALS AND METHODS: The study protocol was approved by the institutional ethics committee, and informed consent was obtained from all patients. Twenty-two patients with pituitary macroadenoma (10 men, 12 women; mean age, 54 years +/- 17.09 [standard deviation]; range, 21-75 years) were examined. All patients underwent MR examination, which included T1-weighted spin-echo and T2-weighted turbo spin-echo DW imaging with ADC mapping and contrast material-enhanced T1-weighted spin-echo imaging. Regions of interest (ROIs) were drawn in the macroadenomas and in normal white matter on DW images, ADC maps, and conventional MR images. Consistency of macroadenomas was evaluated at surgery and was classified as soft, intermediate, or hard. Histologic examination was performed on surgical specimens of macroadenomas. Mean ADC values, signal intensity (SI) ratios of tumor to white matter within ROIs on conventional and DW MR images, and degree of enhancement were compared with tumor consistency and with percentage of collagen content at histologic examination by using analysis of variance for linear trend. RESULTS: The mean value of ADC in the soft group was (0.663 +/- 0.109) x 10(-3) mm(2)/sec; in the intermediate group, (0.842 +/- 0.081) x 10(-3) mm(2)/sec; and in the hard group, (1.363 +/- 0.259) x 10(-3) mm(2)/sec. Statistical analysis revealed a significant correlation between tumor consistency and ADC values, DW image SI ratios, T2-weighted image SI ratios, and percentage of collagen content (P < .001, analysis of variance). No other statistically significant correlations were found. CONCLUSION: Findings in this study suggest that DW MR images with ADC maps can provide information about the consistency of macroadenomas.

Adenoma↗

PubMed1990

Identification and characterization of an enhancer in the coding region of the genome of human immunodeficiency virus type 1.

Transcription of human immunodeficiency virus type 1 (HIV-1) is regulated by cis-acting DNA elements located in the viral long terminal repeats, by viral transregulatory proteins, and by cellular transcription factors acting in concert to modulate the degree of viral expression. We demonstrate that a DNA fragment corresponding to the central portion of the HIV-1 genome exhibits enhancer activity when cloned upstream of the thymidine kinase promoter of herpes simplex virus. This enhancer is inducible by phorbol 12-myristate 13-acetate in HeLa cells and is independent of its position and orientation with respect to the promoter. We have mapped the activity of the enhancer to two independent domains encompassing nucleotides 4079-4342 (end of the pol gene) and nucleotides 4781-6026 (vif gene and first coding exon of tat). This intragenic enhancer and its subdomains demonstrate cellular specificity because they are only active in specific cell lines. The presence of similar intragenic enhancer elements in other retroviruses suggests that they might be a conserved feature of this family of viruses.

Base Sequence↗

PubMed2005

Clinical management of hepatic malignancies: ferucarbotran-enhanced magnetic resonance imaging versus contrast-enhanced spiral computed tomography.

This study compares ferucarbotran-enhanced magnetic resonance (MR) imaging with spiral computed tomography (CT) in the clinical management of patients with suspected hepatic malignancy. One hundred fifty-nine patients with suspected liver malignancy were included in a prospective, multicenter, phase IIIB clinical trial. Patients were examined with baseline plus contrast-enhanced spiral CT and with baseline plus ferucarbotran-enhanced MR imaging. For each patient, four maps of liver lesions were constructed by a trusted blind party on the basis of (a) baseline plus contrast-enhanced spiral CT, (b) baseline MR imaging, (c) baseline plus ferucarbotran-enhanced MR imaging, and (d) final diagnosis. Three blinded experts evaluated the treatment options for each map. The concordance of the treatment choice based on imaging with the treatment choice based on final diagnosis was verified. The final therapeutic decision was radical therapy for 85 patients, palliative therapy for 49 patients, and no treatment for 25 patients who had a final diagnosis of benign lesion. Proper treatment allocation was achieved in 121 (76%) of 159 patients when the evaluation was based on liver maps obtained from spiral CT, in 97 (61%) of 159 patients when the evaluation was based on liver maps obtained from baseline MR imaging, and in 136 (85%) of 159 patients when the evaluation was based on liver maps obtained from baseline plus ferucarbotran-enhanced MR imaging. MR imaging with ferucabotran was significantly superior to spiral CT for correct treatment allocation (P = 0.0167). Ferucarbotran-enhanced MR imaging is superior to spiral CT in clinical management of patients with suspected hepatic malignancy.

Adult↗

PubMed1997

Transactivation of an intronic hematopoietic-specific enhancer of the human Wilms' tumor 1 gene by GATA-1 and c-Myb.

The Wilms' tumor 1 gene (WT1) encodes a zinc-finger transcription factor which is expressed in a tissue-specific manner. Our studies indicate that in addition to the promoter, other regulatory elements are required for tissue-specific expression of this gene. A 258-base pair hematopoietic specific enhancer in intron 3 of the WT1 gene increased the transcriptional activity of the WT1 promoter by 8-10-fold in K562 and HL60 cells. Sequence analysis revealed both a GATA and a c-Myb motif in the enhancer fragment. Mutation of the GATA motif decreased the enhancer activity by 60% in K562 cells. Electrophoretic mobility shift assays showed that the GATA-1 protein in K562 nuclear extracts binds to this motif. Cotransfection of the enhancer containing reporter construct with a GATA-1 expression vector showed that GATA-1 transactivated this enhancer, increasing the CAT reporter activity 10-15-fold. Similar analysis of the c-Myb motif by cotransfection with the enhancer CAT reporter construct and a c-Myb expression vector showed that c-Myb transactivated the enhancer by 5-fold. A DNase I-hypersensitive site has also been mapped in the 258-base pair enhancer region. These data suggest that GATA-1 and c-Myb are responsible for the activity of this enhancer in hematopoietic cells and may bind to the enhancer in vivo.

Base Sequence↗

PubMed1996

Linkage map integration.

The algorithms that drive the map+ program for locus-oriented linkage mapping are presented. They depend on the enhanced location database program ldb+ to specify an initial comprehensive map that includes all loci in the summary lod file. Subsequently the map may be edited or order constrained and is automatically improved by estimating the location of each locus conditional on the remainder, beginning with the most discrepant loci. Operating characteristics permit rapid and accurate construction of linkage maps with several hundred loci. The map+ program also performs nondisjunction mapping with tests of nonstandard recombination. We have released map+ on Internet as a source program in the C language together with the location database that now includes the LODSOURCE database. The anonymous ftp is cedar.genetics.soton.ac.uk and the World Wide Web address is http://cedar.genetics.soton.ac.uk/public_html.

Algorithms↗

PubMed1997

Mitogen-activated protein kinase translocates to the nucleus during ischaemia and is activated during reperfusion.

Growth factors and various cellular stresses are known to activate mitogen-activated protein (MAP) kinase, which plays a role in conveying signals from the cytosol to the nucleus. The phosphorylation of MAP kinase is thought to be a prerequisite for translocation. Here, we investigate the translocation and activation of MAP kinase during ischaemia and reperfusion in perfused rat heart. Ischaemia (0-40 min) induces the translocation of MAP kinase from the cytosol fraction to the nuclear fraction. Immunohistochemical observation shows that MAP kinase staining in the nucleus is enhanced after ischaemia for 40 min. Unexpectedly, tyrosine phosphorylation of MAP kinase is unchanged in the nuclear fraction during ischaemia, indicating that unphosphorylated MAP kinase translocates from the cytosol to the nucleus. During reperfusion (0-30 min), after ischaemia for 20 min, tyrosine phosphorylation of MAP kinase in the nuclear fraction is increased with a peak at 10 min of reperfusion. The activation is confirmed by MAP kinase activity with similar kinetics to the tyrosine phosphorylation. However, the amount of MAP kinase in the fraction is almost constant during reperfusion for 10 min. Although an upstream kinase for MAP kinase, MAP kinase/extracellular signal-regulated kinase kinase (MEK)-1, remains in the cytosol throughout ischaemia and reperfusion, MEK-2, another upstream kinase for MAP kinase, is constantly present in the nucleus as well as in the cytoplasm, based on analyses by fractionation and immunohistochemistry. Furthermore, MEK-2 activity in the nuclear fraction is rapidly increased during post-ischaemic reperfusion. These findings demonstrate that nuclear MAP kinase is activated by tyrosine phosphorylation during reperfusion, probably by MEK-2.

Animals↗

PubMed2004

Dynamic cerebral autoregulation is impaired in glaucoma.

OBJECTIVES: Autonomic and endothelial dysfunction is likely to contribute to the pathophysiology of normal pressure glaucoma (NPG) and primary open angle glaucoma (POAG). Although there is evidence of vasomotor dysregulation with decreased peripheral and ocular blood flow, cerebral autoregulation (CA) has not yet been evaluated. The aim of our study was to assess dynamic CA in patients with NPG and POAG. MATERIALS AND METHODS: In 10 NPG patients, 11 POAG patients and 11 controls, we assessed the response of cerebral blood flow velocity (CBFV) to oscillations in mean arterial pressure (MAP) induced by deep breathing at 0.1 Hz. CA was assessed from the autoregressive cross-spectral gain between 0.1 Hz oscillations in MAP and CBFV. RESULTS: 0.1 Hz spectral powers of MAP did not differ between NPG, POAG and controls; 0.1 Hz CBFV power was higher in patients with NPG (5.68+/-1.2 cm(2) s(-2)) and POAG (6.79+/-2.1 cm(2) s(-2)) than in controls (2.40+/-0.4 cm(2) s(-2)). Furthermore, the MAP-CBFV gain was higher in NPG (2.44+/-0.5 arbitrary units [a.u.]) and POAG (1.99+/-0.2 a.u.) than in controls (1.21+/-0.1 a.u.). CONCLUSION: Enhanced transmission of oscillations in MAP onto CBFV in NPG and POAG indicates impaired cerebral autoregulation and might contribute to an increased risk of cerebrovascular disorders in these diseases.

Adult↗

PubMed1998

Further characterization of the murine collagenase (type IVB) gene promoter and analysis of mRNA expression in murine tissues.

The collagenase B type IV (Col4B) gene is highly expressed in the osteoclast, the primary bone-resorbing cell. However, factors that regulate expression of the Col4B gene are not well characterized. A murine P1 genomic clone containing a 94 kb sequence insert which contains the Col4B gene was isolated. A 4 kb EcoR1 DNA fragment containing the 5' flanking sequence of the gene was further subcloned and restriction mapped. Putative transcription factors such as SRY, Lyf-1, and GATA1 and 2, binding motifs were identified by sequence analysis in this promoter region. Enhancer and suppressor regions were mapped by transient expression of Col4B gene promoter deletion mutant-luciferase reporter gene constructs in HepG2 cells. Col4B mRNA expression in different murine tissues was analyzed by reverse transcription-polymerase chain reaction and demonstrated high levels of expression in bone, clavaria, spleen and thymus. This promoter provides a valuable tool for targeting gene expression to the osteoclast.

Animals↗

PubMed2003

Activation of the knirps locus links patterning to morphogenesis of the second wing vein in Drosophila.

The adjacent knirps (kni) and knirps-related (knrl) genes encode functionally related zinc finger transcription factors that collaborate to initiate development of the second longitudinal wing vein (L2). kni and knrl are expressed in the third instar larval wing disc in a narrow stripe of cells just anterior to the broad central zone of cells expressing high levels of the related spalt genes. Here, we identify a 1.4 kb cis-acting enhancer element from the kni locus that faithfully directs gene expression in the L2 primordium. We find that three independent ri alleles have alterations mapping within the L2-enhancer element and show that two of these observed lesions eliminate the ability of the enhancer element to direct gene expression in the L2 primordium. The L2 enhancer can be subdivided into distinct activation and repression domains. The activation domain mediates the combined action of the general wing activator Scalloped and a putative locally provided factor, the activity of which is abrogated by a single nucleotide alteration in the ri(53j) mutant. We also find that misexpression of genes in L2 that are normally expressed in veins other than L2 results in abnormal L2 development. These experiments provide a mechanistic basis for understanding how kni and knrl link AP patterning to morphogenesis of the L2 vein by orchestrating the expression of a selective subset of vein-promoting genes in the L2 primordium.

Alleles↗

PubMed2004

Benign prostate hyperplasia: evaluation of treatment response with DCE MRI.

Benign prostate hyperplasia (BPH) is a major disease and its non-surgical therapy a major area of interest. The purpose of this study was to establish perfusion parameters in beagles with BPH using dynamic contrast-enhanced (DCE) MRI and to investigate changes due to the effects of finasteride treatment. Twelve male beagles (mean age 4.4 +/- 0.9,years) were divided into a control and treatment group that received a daily dose of 1 mg/kg finasteride. DCE MRI was carried out in a clinical scanner using a 3D spoiled gradient echo sequence prior to and during treatment. 0.2 mmol/kg contrast agent (gadoteridol) was administered with an injection rate of 0.2 ml/s followed by a 15 ml flush of saline. Contrast enhancement was evaluated by pharmacokinetic mapping of a two-compartment model with colour overlay images in addition to regional ROI analysis. Quantitative parameters were defined by the amplitude of contrast enhancement A, the exchange rate k(ep) and the time to maximum signal enhancement. Dynamic contrast-enhanced MRI investigations of the prostate revealed two distinct zones, an inner, periurethral zone and an outer, parenchymal zone. The periurethral zone is highly vascularized, whereas the parenchymal zone is moderately vascularized when compared to other parenchymal organs. During treatment, in the parenchymal zone the intensity of enhancement (amplitude A) and the time to maximum signal enhancement increased, while the exchange rate k(ep) decreased. Dynamic contrast-enhanced MRI of BPH reveals distinct differences between individual zones within the prostate. Moreover, changes during successful treatment suggest increased blood volume per volume of tissue and decreased vessel leakiness.

Animals↗

PubMed1996

Discrimination between different E-box-binding proteins at an endogenous target gene of c-myc.

c-myc plans a key role in regulating mammalian cell proliferation and apoptosis. The gene codes for a transcription factor, Myc, that belongs to the helix-loop-helix/leucine zipper (HLH/LZ) family of proteins. Myc heterodimerizes with a partner protein termed Max; the heterodimeric complex binds to CAC(G/A)TG (E-box) sequences and activates transcription from these sites. However, several other HLH/LZ proteins, including USF and TFE-3, bind to and trans-activate from the same element, yet have no documented effect on cell proliferation or apoptosis. Therefore, it is likely that mechanisms exist that discriminate between these proteins for activation of natural target genes of Myc. We now show that trans-activation from the E-box in the rat prothymosin-alpha intron enhancer is indeed specific for Myc, and identify both the distance from the start site of transcription and a second E-box element adjacent to that recognized by Myc as critical determinants of specificity. Surprisingly, transcription activation domains required for Myc to activate from this distal enhancer position differ from previously mapped domains and closely correlate with those domains essential for transformation. As observed in transformation assays, Myc and Max strongly synergize in activation from a distal enhancer position. Our data suggest that trans-activation from the prothymosin intron enhancer is a faithful reflection of the transforming properties of the Myc protein.

Animals↗

PubMed1999

Effect of diaspirin cross-linked hemoglobin on normal and postischemic microcirculation of the rat pancreas.

Microcirculatory alterations with reduced nutritive supply to the pancreas could be the cause of hyperamylasemia, which occurs in some patients receiving the vasoactive oxygen carrier diaspirin cross-linked hemoglobin (DCLHb) in clinical studies. Therefore, the effects of DCLHb on rat pancreas microcirculation were evaluated. Anesthetized Sprague-Dawley rats received one of the following treatments during baseline conditions (n = 7 rats/group): 10% hydroxyethyl starch (HAES) (0.4 ml/kg), DCLHb (400 mg/kg), or DCLHb (1,400 mg/kg). After 1 h of complete, reversible pancreatic ischemia, other animals received 10% HAES (0.4 ml/kg) or DCLHb (400 mg/kg) during the onset of reperfusion. The number of red blood cell-perfused capillaries (functional capillary density, FCD) and the level of leukocyte adherence in postcapillary venules in the pancreas were assessed by means of intravital microscopy during 2 h after treatment. In the nonischemic groups, FCD was 18% greater after DCLHb (1,400 mg/kg) than after 10% HAES treatment without any increase in leukocyte adherence. In the inschemia-reperfusion (I/R) 10% HAES group, FCD was significantly (P < 0.05) lowered, leukocyte adherence enhanced, and mean arterial pressure (MAP) reduced by 31% compared with nonischemic animals. DCLHb treatment in the I/R group resulted in a slight increase in FCD, a significant (P < 0.05) reduction of leukocyte adherence, and a complete restoration of MAP compared with the animals of the I/R control group. Thus our data provide no evidence for a detrimental effect on the pancreatic microcirculation or an enhanced risk of postischemic pancreatitis by DCLHb.

Animals↗

PubMed2000

Lactoferrin upregulates the expression of CD4 antigen through the stimulation of the mitogen-activated protein kinase in the human lymphoblastic T Jurkat cell line.

The main biological properties of lactoferrin are thought to concern inflammation and immunomodulation processes, including maturation of immature B and T cells. Lactoferrin accelerates T-cell maturation by inducing the expression of the CD4 surface marker. In this report, using the Jurkat T-cell line, we have shown that lactoferrin upregulates the expression of CD4 antigen through the activation of a transduction pathway. Using an anti-phosphotyrosine antibody, lactoferrin was demonstrated to induce a cascade of phosphorylation of numerous proteins on their tyrosine residues. This tyrosine-phosphorylation was transient, reaching maxima between 5 and 10 min. We also identified the mitogen-activated protein kinase (MAP kinase) which presented an enhanced catalytic activity, reaching a maximum at 10 min of incubation with lactoferrin. Moreover, the use of inhibitors such as genistein and PD98059, tyrosine kinases and MAP kinase kinase (or MEK) inhibitors respectively, allowed us to correlate the activation of MAP kinase with the upregulation of CD4 expression. Finally, using Lck-defective Jurkat cells, our results showed that the p56(lck) (Lck) kinase is necessary for MAP kinase activity and CD4 expression. This paper demonstrates that lactoferrin activates transduction pathway(s) in lymphoblastic T-cells, and that Lck and the Erk2 isoform of MAP kinase are implicated in the upregulation of CD4, induced by lactoferrin in these cells.

CD4 Antigens↗

PubMed1988

Mapping of event-related desynchronization and type of derivation.

Event-related desynchronization (ERD) is a term describing alpha band amplitude changes in response to an event (stimulus presentation, self-paced movement, etc.). ERD mapping is a brain-imaging technique used to display the topographical pattern and time course of alpha power changes. Multi-lead EEG data referred to one ear were recorded during voluntary finger movements. From these data, transverse bipolar, source and common average reference derivations and the laplacian operator were calculated, and ERD maps are computed. The ERD is enhanced and best localized with the laplacian operator method, or with source derivations. ERD maps with ear reference required cautious interpretation.

Alpha Rhythm↗

PubMed1991

Characterization of the hepatitis B virus EnhI enhancer and X promoter complex.

The hepatitis B virus EnhI enhancer element overlaps the promoter of the X gene. By performing methylation interference experiments, four protein factor binding sites clustered in a 120-bp region were found to control the EnhI enhancer and X promoter activities. Deletion mapping experiments indicated that the two upstream protein factor binding sites constituted a basal enhancer module. This module, likely bound by a liver-specific factor and a ubiquitous factor, could activate the herpes simplex virus thymidine kinase gene promoter by 5- or 10-fold, depending on the orientation, in Huh7 cells, a liver-derived cell line, but not in other cell types tested. The two downstream protein factor binding sites interact with the upstream basal enhancer module in an orientation- and distance-dependent manner to increase the enhancer activity by another 10-fold. In addition, at least one of the two downstream protein factor binding sites is also essential for the X promoter activity.

Base Sequence↗

PubMed1996

Angiotensinogen gene activation by angiotensin II is mediated by the rel A (nuclear factor-kappaB p65) transcription factor: one mechanism for the renin angiotensin system positive feedback loop in hepatocytes.

The renin-angiotensin system controls blood pressure through the enzymatic production of the vasopressor angiotensin II (AII) from the angiotensinogen (AGT) precursor. Intravascular AII production stimulates de novo synthesis of its precursor in a positive feedback loop through increased gene expression. In this study, we investigate the effects of AII on AGT gene expression. At nanomolar concentrations, All activates transcription of the native AGT gene; this region is mapped to the AGT gene multihormone-inducible enhancer (-615 to -470). Within the multihormone-inducible enhancer, site-directed mutations of the acute-phase response element (APRE) that interfere with nuclear factor-kappa B (NF-kappa B) transcription factor binding also abolish All responsiveness. The APRE functions as a rapidly inducible All-inducible enhancer with peak reporter activity detected after a 4-h stimulation; this effect occurs only when the type 1 AII receptor is expressed. All induces sequence-specific NF-KB binding to the APRE in HepG2 nuclear extracts. Moreover, AII infusions of primary rat hepatocyte cultures produces a rapid 4-fold increase in sequence-specific NF-kappa B binding to the APRE. Antibodies against the transcriptional activator subunit, Rel A, quantitatively supershift the nucleoprotein complex, whereas antibodies to other NF-kappa B members do not, demonstrating that Rel A APRE-binding activity is AII-inducible. Transient overexpression of Rel A(1-551) activates the AGT multihormone-inducible enhancer. AII-inducible domains of Rel A were mapped by cotransfecting a chimeric GAL4-Rel A fusion protein with a reporter gene containing GAL4-binding sites. GAL4-Rel A(1-551) was an AII-inducible transactivator. Deletion of the NH(2)-terminal 254 amino acids of Rel A produces a constitutive transactivator, indicating that Rel A is activated by AII in a manner dependent on its NH(2) terminus. These studies define one mechanism for the renin-angiotensin system positive feedback loop in hepatocyctes.

Angiotensin II↗

PubMed2006

First-pass contrast-enhanced myocardial perfusion MRI using a maximum up-slope parametric map.

Magnetic resonance first-pass perfusion imaging offers a noninvasive method for the rapid, accurate, and reproducible assessment of cardiac function without ionizing radiation. Quantitative or semiquantitative analysis of changes in signal intensity (SI) over the whole image sequence yields a more efficient analysis than direct visual inspection. In this paper, a method to generate maximum up-slope myocardial perfusion maps is presented. The maximum up-slope is defined by comparison of the SI variations using frame-to-frame analysis. A map of first-pass transit of the contrast agent is constructed pixel by pixel using a linear curve fitting model. The proposed method was evaluated using data from eight subjects. The data from the parametric maps agreed well with those obtained from traditional, manually derived region-of-interest methods as shown through ANOVA. The straightforward implementation and increase in image analysis efficiency resulting from this method suggests that it may be useful for clinical practice.

Adult↗

PubMed2005

Cancer metastasis-suppressing peptide metastin upregulates excitatory synaptic transmission in hippocampal dentate granule cells.

Metastin is an antimetastatic peptide encoded by the KiSS-1 gene in cancer cells. Recent studies found that metastin is a ligand for the orphan G-protein-coupled receptor GPR54, which is highly expressed in specific brain regions such as the hypothalamus and parts of the hippocampus. This study shows that activation of GPR54 by submicromolar concentrations of metastin reversibly enhances excitatory synaptic transmission in hippocampal dentate granule cells in a mitogen-activated protein (MAP) kinase-dependent manner. Synaptic enhancement by metastin was suppressed by intracellular application of the G-protein inhibitor GDP-beta-S and the calcium chelator BAPTA. Analysis of miniature excitatory postsynaptic currents (mEPSCs) revealed an increase in the mean amplitude but no change in event frequency. This indicates that GPR54 and the mechanism responsible for the increase in EPSCs are postsynaptic. Metastin-induced synaptic potentiation was abolished by 50 microM PD98059 and 20 microM U0126, two inhibitors of the MAP kinases ERK1 and ERK2. The effect was also blocked by inhibitors of calcium/calmodulin-dependent kinases and tyrosine kinases. RT-PCR experiments showed that both KiSS-1 and GPR54 are expressed in the hippocampal dentate gyrus. Metastin is thus a novel endogenous factor that modulates synaptic excitability in the dentate gyrus through mechanisms involving MAP kinases, which in turn may be controlled upstream by calcium-activated kinases and tyrosine kinases.

Action Potentials↗