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Results for “Enhancer”

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At least 361 records · Page 20Linked to original sources

PubMed2006

Pregnancy-enhanced store-operated Ca2+ channel function in uterine artery endothelial cells is associated with enhanced agonist-specific transient receptor potential channel 3-inositol 1,4,5-trisphosphate receptor 2 interaction.

We have previously shown that endothelial cells (EC) derived from the uterine artery (UA) of both pregnant (P-UAEC) and nonpregnant (NP-UAEC) ewes show a biphasic intracellular free Ca(2+) ([Ca(2+)](i)) response after ATP stimulation. In each case, the initial transient peak, caused by the release of Ca(2+) from the intracellular Ca(2+) stores, is mediated by purinergic receptor-Y2 and is very similar in both cell types. However, the sustained phase in particular, caused by the influx of extracellular Ca(2+), is heightened in the P-UAEC, and associates with an increased ability of the cells to demonstrate enhanced capacitative Ca(2+) entry (CCE) via store-operated channels (SOCs). Herein we demonstrated that the difference in the sustained [Ca(2+)](i) response is maintained for at least 30 min. When 2-aminoethoxydiphenyl borate (2APB) (an inhibitor of the inosital 1,4,5-trisphosphate receptor (IP3R) and possibly SOC) was used in conjunction with ATP, it was capable of completely inhibiting CCE. Since 2APB can inhibit SOC in some cell types and 2APB was capable of inhibiting CCE in the UAEC model, the role of SOC in CCE was first evaluated using the classical inhibitor La(3+). The ATP-induced sustained phase was inhibited by 10 microM La(3+), implying a role for SOC in the [Ca(2+)](i) response. Since canonical transient receptor potential channels (TRPCs) have recently been identified as putative SOCs in many cell types, including EC, the expression levels of several isoforms were evaluated in UAEC. Expression of TRPC3 and TRPC6 channels in particular was detected, but no significant difference in expression level was found between NP- and P-UAEC. Nonetheless, we were able to show that IP3R2 interacts with TRPC3 in UAEC, forming a protein complex, and that this interaction is considerably enhanced in an agonist sensitive manner by pregnancy. Thus, while IP3R and TRPC isoforms are not altered in their expression by pregnancy, enhanced functional interaction of TRPC3 with IP3R2 may underlie pregnancy-enhanced CCE in the UAEC model and so explain the prolonged [Ca(2+)](i) sustained phase seen in response to ATP.

Adenosine Triphosphate↗

PubMed1992

Culture-associated enhancement of LECAM-1 expression by lymphocytes and partial inhibition of enhancement by IL-4.

Recent studies have shown that the human leukocyte endothelial cell adhesion molecule-1 (LECAM-1) functions as a homing receptor, mediating leukocyte binding to high endothelial venules in peripheral lymph nodes. Increasing evidence has demonstrated that cytokines, such as IL-4, can modulate the expression of surface proteins such as homing receptors on a variety of cells. We thus investigated the modulatory effects of cytokines on LECAM-1 expression by lymphocytes using single- and dual-color flow cytometry. We found that the density of LECAM-1 expression increased markedly during 3 days of culture and that this culture-associated enhancement (CAE) of LECAM-1 expression was significantly inhibited by IL-4. B cells and both major T cell subsets (CD4, CD8) exhibited CAE of LECAM-1 expression, but the inhibitory effect of IL-4 on this response occurred only in the T cell populations. The inhibitory effect of IL-4 on enhanced LECAM-1 expression was reversible, and characterized all 3 LECAM-1 epitopes assessed. Natural killer cells, in contrast, did not exhibit CAE of LECAM-1 expression, and IL-4 had no modulatory effect on LECAM-1 expression by these cells. Another adhesion molecule, CD44, showed enhanced expression during culture, but this enhancement was not inhibited by IL-4. The results show that LECAM-1 expression by T and B lymphocytes is significantly increased during culture and that the inhibitory effect of IL-4 on this increase is restricted to T cells. These findings suggest that IL-4, generated during an immune response, may play a role in regulating the migration and localization of T lymphocytes to lymphoid tissues.

Antibodies, Monoclonal↗

PubMed2004

Pulmonary functional MRI: an animal model study of oxygen-enhanced ventilation combined with Gd-DTPA-enhanced perfusion.

BACKGROUND: The assessment of regional pulmonary ventilation and perfusion is essential for the evaluation of a variety of lung disorders. Pulmonary ventilation MRI using inhaled oxygen as a contrast medium can be obtained with a clinical MR scanner, without additional equipment, and has been demonstrated to be a feasible means of assessing ventilation in animal models and some clinical patients. However, few studies have reported on MR ventilation-perfusion imaging. In this study, we evaluated the usefulness of oxygen-enhanced ventilation in combination with first-pass Gd-DTPA-enhanced perfusion MRI in a canine model of pulmonary embolism and airway obstruction. METHODS: Peripheral pulmonary embolisms were produced in eight dogs by intravenous injection of gelfoam strips at the pulmonary segmental arterial level, and airway obstructions were created in five of the dogs by inserting a self-designed balloon catheter into a secondary bronchus. Oxygen-enhanced MR ventilation images were produced by subtracting images from before and after inhalation of pure oxygen. Pulmonary perfusion MR images were acquired with a dynamic three-dimensional fast gradient-echo sequence. MR ventilation and perfusion images were read and contrasted with results from general examinations of pathological anatomy, ventilation-perfusion scintigraphy, and pulmonary angiography. RESULTS: Regions identified as having airway obstructions matched using both MR ventilation and perfusion imaging, but regions of pulmonary embolisms were mismatched. The area of airway obstruction defects was smaller using MR ventilation imagery than that using ventilation scintigraphy. Abnormal perfusion regions due to pulmonary embolisms were divided into defective regions and reduced regions based on the time course of signal intensity changes. In the diagnosis of pulmonary embolisms with the technique of ventilation and perfusion MRI, sensitivity and specificity were 75.0% and 98.1%, respectively, and the diagnostic results of this MRI technique were in agreement with the results of ventilation-perfusion scintigraphy and pulmonary angiography (K: 0.899, 0.743). CONCLUSIONS: Oxygen-enhanced ventilation in combination with pulmonary perfusion MRI can be used to diagnose abnormalities of airways and blood vessels in the lungs, and can provide regional functional information with high spatial and temporal resolution. This method possesses great potential value for clinical applications.

Airway Obstruction↗

PubMed1990

Comparison of non-enhanced, bolus enhanced, and delayed scanning techniques in computed tomography of hepatic tumours.

Non-enhanced, bolus contrast medium enhanced and 4 to 6 hours delayed computed tomography of the liver was performed in a prospective study of 53 patients. Forty patients had focal lesions, in 12 of these they were hypervascular. Contrast medium was administered as an initial bolus followed by a rapid injection of meglumine metrizoate (Isopaque Cerebral). The total iodine dose varied between 56 and 63 g, which gave an average increase in attenuation of 14 HU in normal parenchyma comparing delayed with non-enhanced scanning. Presence and extent of focal lesions were evaluated in a randomized and independent analysis by two radiologists. The percentage of examinations with correct tumour description was higher with bolus scanning (observer I 73%, observer II 75%) and delayed scanning (observer I 75%, observer II 78%) than with non-enhanced scanning (observers I and II 67%). An optimal bolus technique requires an exact timing of the contrast medium administration and scanning. Delayed scanning provides an excellent supplement when the bolus examination is suboptimal or shows equivocal findings.

Adult↗

PubMed1974

Immunologic enhancement of rat renal allografts. II. Immunohistology of acutely rejecting and passively enhanced grafts.

Unmodified renal transplants from (Lewis x Brown Norway) F(1) hybrids to Lewis rats show deposition of immunoglobulin (IgG) and complement in the arteries, which cause an acute necrotizing arteritis with ischemic necrosis of the grafts. Treatment with a single dose of enhancing antiserum at the time of transplantation prevents the arterial deposition of IgG and complement, and the vascular lesions. The enhancing antibody probably acts peripherally by blocking crucial antigenic sites in the graft vasculature, since cytotoxic alloantibody is detectable in the circulation of both control and enhanced recipients. Unmodified allografts also show deposition of IgG in glomeruli accompanied by glomerular necrosis. Immunofluorescent studies indicate that these glomerular lesions are mediated by complexes of antigen and alloantibody, and at least partially also by a nonhistocompatibility antibody directed against antigens in glomerular endothelial cells. Enhancing antiserum treatment reduces glomerular IgG deposition and thus greatly mitigates the glomerular lesion as well.

Animals↗

PubMed1999

Interaction of hepatitis B viral X protein and CCAAT/ enhancer-binding protein alpha synergistically activates the hepatitis B viral enhancer II/pregenomic promoter.

The hepatitis B viral X protein (HBx) is known to exert its transactivation activity by the interaction with several cellular transcription factors. Here we report the interaction of HBx and CCAAT/enhancer-binding protein alpha (C/EBPalpha) and their effects on the enhancer/promoters of hepatitis B virus (HBV). A chloramphenicol acetyltransferase assay showed that the cotransfection of HBx and C/EBPalpha strongly activated the enhancer II/pregenomic promoter of HBV in a synergistic manner. This effect was also observed in the heterologous expression system with promoters of SV40 and herpes simplex virus thymidine kinase genes. Serial deletion analysis of the enhancer II/pregenomic promoter identified the responsible region (nucleotides 1639-1679), in which two C/EBP-binding sites are located. An in vitro interaction assay and electrophoretic mobility shift assay showed that HBx augmented the DNA binding activity of C/EBPalpha by direct interaction with it, and its basic leucine zipper domain was responsible for the interaction with HBx. Domain analysis of HBx showed that the central region (amino acids 78-103) was necessary for direct interaction with C/EBPalpha. However, the complete form of HBx was necessary for the synergistic activation of the HBV pregenomic promoter. These results suggest that the interaction of HBx and C/EBPalpha enhances the transcription of the HBV pregenomic promoter for the effective life cycle of HBV in hepatocytes.

CCAAT-Enhancer-Binding Proteins↗

PubMed1993

Facial nerve enhancement in Bell's palsy demonstrated by different gadolinium-enhanced magnetic resonance imaging techniques.

Twenty-one patients with an acute complete peripheral facial palsy, Bell's palsy, were examined by medium- and high-Tesla magnetic resonance imaging. Three contrast techniques were used: intravenous gadolinium; oral carbohydrate and intravenous gadolinium; and gadolinium, carbohydrate, and readministration of gadolinium. Three to 22 days after the onset of palsy, 12 of the 21 patients demonstrated ipsilateral facial nerve enhancement, most consistently in the meatal region, which is indicative of an inflammatory reaction. Two to 4.5 months after the onset, the enhancement had disappeared in 10 of the 12 patients. For the individual patient, contrast-enhanced magnetic resonance imaging gave little or no help in predicting the outcome of palsy. It is speculated that the intake of carbohydrate and readministration of gadolinium may improve the sensitivity of medium-high-Tesla magnetic resonance imaging in some cases.

Administration, Oral↗

PubMed1987

In vitro binding of cell-specific and ubiquitous nuclear proteins to the octamer motif of the SV40 enhancer and related motifs present in other promoters and enhancers.

We have used the gel retardation and DNase I footprinting assays to investigate the in vitro binding of nuclear proteins to the octamer motif present in domain A of the SV40 enhancer and in other enhancer and promoter elements. Three apparently cell-specific (oct-B1A, oct-B1B and oct-B2) and one ubiquitous (oct-B3) proteins were detected in various lymphoid and non-lymphoid cell extracts. We show that the previously described 'ubiquitous' NF-A1 factor may correspond in fact to two proteins, oct-B1A in HeLa cells and oct-B1B in lymphoid cells. Interestingly, the HeLa cell protein oct-B1A formed a complex with the SV40 octamer, which could be detected in gel retardation, but not in DNase I footprinting assays. This absence of protection from DNase I digestion correlates with the inactivity of the SV40 octamer in HeLa cells in vivo. We have also found that the in vitro interaction between the SV40 octamer motif and the lymphoid cell-specific protein oct-B2 was negatively modulated by a component present in the nuclear extracts from several lymphoid cell lines. The interactions between the multiple octamer-binding proteins and the related octamer motifs present in other promoter and enhancer elements were systematically compared and the possible role of these proteins in the control of transcription is discussed.

Base Sequence↗

PubMed1994

Dynamic contrast-enhanced MR imaging of the upper abdomen: enhancement properties of gadobutrol, gadolinium-DTPA-polylysine, and gadolinium-DTPA-cascade-polymer.

The enhancement properties of gadobutrol (40 and 80 mumol/kg body weight, 550 daltons), gadolinium-DTPA-polylysine (20 mumol/kg body weight, 53,000 daltons) and gadolinium-DTPA-cascade-polymer (20 mumol/kg body weight, < 30,000 Daltons) were investigated in abdominal MR imaging using a pig model (n = 24). Signal intensities before and after contrast media application were assessed using a fast single slice FLASH sequence. Measurements were made every 4 s within the first 116 s, every minute between 4 and 10 min and after 15, 20, 30, 40, 50, 60, 90, and 120 min after contrast media injection. Injection of gadobutrol resulted in typical signal intensity curves characterizing it as an extracellular agent similar to gadopentetate dimeglumine. Significant enhancement was found in all tissues except the trunk muscles when the lower dose was administered. Gadolinium-DTPA-polylysine injection resulted also in significant enhancement of the liver, the pancreas, and the renal cortex, but not of the trunk muscle, reflecting its blood pool properties known also from other macromolecular contrast agents. The signal intensity curves obtained after gadolinium-DTPA-cascade-polymer injection were similar to those obtained after polylysine injection, stressing the blood pool character of this new type of blood pool agent.

Abdomen↗

PubMed2005

Enhanced viability imaging: improved contrast in myocardial delayed enhancement using dual inversion time subtraction.

In delayed contrast-enhanced MRI for the assessment of myocardial viability, the TI time in a gated inversion-recovery segmented gradient echo sequence is usually selected to null signal from normal myocardium. Although this TI time generates good contrast between the enhancing infarcted tissue and normal myocardium, there is usually less contrast between the infarct and the blood pool. A subtractive technique utilizing two acquisitions at a long and short TI time is proposed to improve the delineation between infarct-blood and infarct-myocardium. The concept was demonstrated in six mongrel dogs with reperfused myocardial infarction. Infarct-normal myocardium contrast (signal difference) using the proposed enhanced viability imaging (ENVI) technique was 142 +/- 50% (P < 0.001) that of standard magnitude inversion recovery (IR), while at the same TI time for the primary image, infarct-blood contrast, was 247 +/- 136% (P < 0.002) that of magnitude IR. Accounting for increased noise due to the subtraction, signal difference-to-noise ratios (SDNR) did not show a significant change for infarct-myocardium but infarct-blood SDNR for ENVI was 174 +/- 105% that of magnitude-IR (P < 0.03). Thus, marked improvement in the delineation of the infarcted zone was noted over a range of TI times.

Animals↗

PubMed1999

Discrete enhancer elements mediate selective responsiveness of enhancer of split complex genes to common transcriptional activators.

In Drosophila, genes of the Enhancer of split Complex [E(spl)-C] are important components of the Notch (N) cell-cell signaling pathway, which is utilized in imaginal discs to effect a series of cell fate decisions during adult peripheral nervous system development. Seven genes in the complex encode basic helix-loop-helix (bHLH) transcriptional repressors, while 4 others encode members of the Bearded family of small proteins. A striking diversity is observed in the imaginal disc expression patterns of the various E(spl)-C genes, suggestive of a diversity of function, but the mechanistic basis of this variety has not been elucidated. Here we present strong evidence from promoter-reporter transgene experiments that regulation at the transcriptional level is primarily responsible. Certain E(spl)-C genes were known previously to be direct targets of transcriptional activation both by the N-signal-dependent activator Suppressor of Hairless [Su(H)] and by the proneural bHLH proteins achaete and scute. Our extensive sequence analysis of the promoter-proximal upstream regions of 12 transcription units in the E(spl)-C reveals that such dual transcriptional activation is likely to be the rule for at least 10 of the 12 genes. We next show that the very different wing imaginal disc expression patterns of E(spl)m4 and E(spl)mgamma are a property of small (200-300 bp), evolutionarily conserved transcriptional enhancer elements, which can confer these distinct patterns on a heterologous promoter despite their considerable structural similarity [each having three Su(H) and two proneural protein binding sites]. We also demonstrate that the characteristic inactivity of the E(spl)mgamma enhancer in the notum and margin territories of the wing disc can be overcome by elevated activity of the N receptor. We conclude that the distinctive expression patterns of E(spl)-C genes in imaginal tissues depend to a significant degree on the capacity of their transcriptional cis-regulatory apparatus to respond selectively to direct proneural- and Su(H)-mediated activation, often in only a subset of the territories and cells in which these modes of regulation are operative.

Animals↗

PubMed1994

Vascular permeability to sodium fluorescein in the rabbit cranial nerve root: possible correlation with normal cranial nerve enhancement on gadolinium-enhanced magnetic resonance imaging.

Vascular permeability in cranial nerve roots was examined after intravenous injection of sodium fluorescein in the adult rabbit. Fluorescence was observed in the distal nerves through the following portions: intracavernous portion of the oculomotor nerve, distal internal auditory canal segment of the facial nerve, and ganglionic portions of the trigeminal, glossopharyngeal and vagus nerves. In the acoustic nerve, the vestibular ganglion showed fluorescence. No fluorescence was observed in the olfactory or optic nerves. During in vivo gadolinium-enhanced magnetic resonance imaging (Gd-MRI) of two separate animals, trigeminal nerve enhancement was observed in the region showing fluorescence. Histologically, intense fluorescence was observed in ganglia and external nerve sheaths of the cranial nerves showing macroscopic fluorescence. A slight fluorescence was also seen in endoneurial connective tissue but not observed within the nerve fibers. The results of this study suggest that the physiological enhancement of human cranial nerves seen on Gd-MRI may correlate with vascular permeability.

Animals↗

PubMed2005

A Moloney murine leukemia virus driven by the Jaagsiekte sheep retrovirus enhancers shows enhanced specificity for infectivity in lung epithelial cells.

Jaagsiekte sheep retrovirus (JSRV) is the etiologic agent of ovine pulmonary adenocarcinoma (OPA), a transmissible lung cancer in sheep. One of the unique features of this virus is that in infected animals, the only tissues that show expression of the virus are the tumor cells in the lung. We previously showed that the JSRV long terminal repeat (LTR) is preferentially active in murine lung epithelial cell lines (MLE-15 and mtCC1-2). To further explore the tissue specificity, we inserted the JSRV enhancer sequences from the U3 region of the LTR into a Moloney murine leukemia virus (M-MuLV) LTR lacking its own enhancer sequences, to give the chimeric LTR DeltaMo + JS. Transient transfection assays indicated that the DeltaMo + JS LTR is > 5-fold more active in lung epithelial cell lines than in non-lung lines, compared to the wild-type M-MuLV LTR. This was due to preferential activity of the JSRV enhancers in lung epithelial cells. Moreover, M-MuLV driven by the DeltaMo + JS LTR was > 3 logs more infectious in MLE-15 cells compared to non-lung cell lines. This chimeric virus may facilitate investigations of the tissue-specificity of JSRV.

Animals↗

PubMed1989

A naturally occurring deletion in the enhancer repeats of the human papovavirus BK optimizes early enhancer function at the expense of late promoter activity.

The late promoter of the human papovavirus BK (prototype) is contained within the same region of DNA as the early promoter enhancer. This region, consisting of a 68-50-68-bp repeat and the flanking region to the late side, contains elements important for both late promoter activity and enhancer function for the early transcription unit. We have studied the importance of the naturally occurring 18-bp deletion in the middle repeat by constructing three repeats containing every possible combination of the 50- and 68-bp segments and testing their abilities to promote late transcription and activate an enhancerless SV40 early promoter. We find that the wild-type configuration of repeats gives optimal enhancer function, but is less active than other combinations for late transcription. This suggests that different interactions between the transcription elements contained within the same region of DNA are responsible for modulation of early and late transcription.

BK Virus↗

PubMed1994

Enhancer trapping by a human mid-sized neurofilament transgene reveals unexpected patterns of neuronal enhancer activity.

In ten transgenic lines, expression of a human mid-sized (M) neurofilament (NF) transgene was restricted to neurons in the central and peripheral nervous systems. However, no two lines gave identical expression patterns and none exactly matched the expression of mouse NF(M). These varied expression patterns within the neural compartment likely result from interactions of the transgene with enhancer elements located in the regions flanking the insertion site. Unexpected patterns of enhancer activity included an enhancer active in subsets of cerebellar basket cells as well as others preferentially active in subsets of motor or sensory neurons.

Amino Acid Sequence↗

PubMedDate not supplied

Relationship between an enhancer element in the human antithrombin III gene and an immunoglobulin light-chain gene enhancer.

Enhancers, cis-acting transcriptional control elements have been described in both viral and cellular genes. They influence transcription in a quantitative fashion, act over relatively large distances (several kilobases, kb) and behave independently of their position and orientation. Enhancers have been described in immunoglobulin, chymotrypsin and insulin genes. They bear little homology with each other except for an 8-base pair (bp) 'consensus' core element, GTGGAAATTTG (refs 10, 11), but even this element is sometimes non-homologous. I have searched for such elements in the human antithrombin III (AT-III) gene. AT-III is an important coagulation protein which inactivates thrombin. It is produced by the liver and, to a lesser extent, by the kidney. Here, I report that the 5' flanking region of the AT-III gene encodes a segment homologous with the enhancer containing the joining-constant kappa (J kappa-C kappa) intron of immunoglobulin kappa-chain genes. This extensive homology suggests the existence of regulatory factors that recognize common DNA sequences in lymphoid tissues and in those which express AT-III.

Acetyltransferases↗

PubMed1998

A conserved sequence block in murine and human T cell receptor (TCR) Jalpha region is a composite element that enhances TCR alpha enhancer activity and binds multiple nuclear factors.

A conserved sequence block (CSB) located in a noncoding region of the mouse and human TCR alpha/delta loci, showing six differences over 125 nucleotide positions (95% similar), was subjected to detailed analyses in this study. Transient transfection results showed that the CSB-containing element in conjunction with the TCR alpha enhancer up-regulated the alpha enhancer activity, whereas no enhancer activity was detected when CSB alone was assayed. In vitro occupancy analyses of CSB by nuclear factors reveal the existence of an unexpectedly intricate network of CSB-protein and protein-protein interactions. Lymphoid-specific as well as T-lineage-specific nuclear factors are involved to differentially form CSB-bound complexes in extracts of various tissues and cell lines. Liver was shown to contain factor(s) sequestering thymic CSB-binding factors. Furthermore, the putative binding sites for transcription factors known to be important for lymphoid-lineage development are present in CSB and are targeted by nuclear factors. On the basis of these results, we propose that the CSB element may play a role in shaping the chromatin structure by which the accessibility of TCR alpha/delta loci to the recombinase complex and/or to the transcriptional apparatus can be controlled.

Animals↗

PubMed2006

Subendocardial late gadolinium enhancement in two patients with anthracycline cardiotoxicity following treatment for Ewing's sarcoma.

Cardiotoxicity is a well-known consequence of anthracycline chemotherapy. We report CMR findings not previously described in two patients with anthracycline cardiotoxicity following treatment for Ewing's sarcoma. Subendocardial enhancement on late gadolinium contrast-enhanced CMR was present in both cases, with histological correlation in one case.

Adult↗