SEARCH · PubMed Health

Results for “Enhancer”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 703 records · Page 39Linked to original sources

PubMed2003

Real-time contrast-enhanced ultrasound of the spleen: examination technique and preliminary clinical experience.

PURPOSE: To report our preliminary experience in the evaluation of the spleen using a real-time contrast-specific ultrasound module in combination with a second-generation contrast agent. MATERIALS AND METHODS: In a 7-month period, 55 patients (34 males and 21 females, aged 5-77 years) with spleen disorders were evaluated by means of contrast-enhanced ultrasound. Two patients were studied because of baseline evidence of an accessory spleen and both underwent ultrasound follow-up. Twenty-five patients were studied for abdominal trauma and results were correlated with those of helical CT. Three patients were examined for suspected splenic infarction and for all CT correlation was obtained. Finally, twenty-five subjects were examined for focal diseases, such as lymphomas (17 cases) and focal lesions (8 cases); contrast-enhanced US results were correlated with those of CT (8 cases), MRI (2 cases), ultrasound follow-up (8 cases), biopsy (2 cases) or splenectomy (1 case). After an initial baseline study, the contrast-enhanced examinations were carried out using a dedicated unit equipped with a continuous contrast-specific module at low acoustic pressure. The examination started immediately after rapid contrast injection and lasted approximately 4 minutes. In the comparison between baseline and contrast-enhanced ultrasound, the following aspects were considered: detection rate of parenchymal changes, lesion extent (equal to CT, under- or overestimated), and lesion conspicuity (lesion-to-parenchyma gradient, from 0 = absent to 3 = high). RESULTS: In the 2 patients with accessory spleen, an enhancement very similar to that of the adjacent parenchyma was present and a small vascular pedicle was noted. Among the trauma patients, 18 had a direct splenic injury and one showed splenic contraction and hypoperfusion due to shock. In 74% of cases, a peritoneal effusion was demonstrated both with baseline and contrast-enhanced ultrasound; perisplenic blood collections (58% of cases) were identified in 42% of patients by both baseline and contrast-enhanced ultrasound; post-traumatic infarction was always revealed by contrast-enhanced ultrasound (11% of cases) but never by baseline ultrasound; parenchymal injuries were detected with a sensitivity of 63% by baseline ultrasound and a sensitivity of 89% by contrast-enhanced ultrasound. Moreover, contrast-enhanced ultrasound revealed findings undetectable on conventional ultrasound: global splenic hypoperfusion in 2 cases (due to shock in one and pedicle avulsion in the other), intraparenchymal contrast collections in 21% of positive cases (as confirmed by CT), extrasplenic contrast leakage in 1 of 2 cases demonstrated by CT. Of the 3 cases of splenic infarction, baseline sonography only only identified two, whereas the contrast-enhanced examination clearly identified three. Contrast-enhanced ultrasound revealed 35 of 39 focal lesions in patients studied for Hodgkin's disease and splenic focal lesions. Baseline ultrasound had a lower sensitivity (23 lesions). Lesion extension shown by contrast-enhanced sonography was equivalent to that provided by standard methods in 88% of cases (underestimated in 9% and overestimated in 3%); baseline US correctly estimated lesion size in 52% of cases, under- and overestimating them in 35% and 13% of cases, respectively. Lesion conspicuity was graded as 1 (low) in 16%, 2 (moderate) in 67%, and 3 (high) in 17% of the cases identified by enhanced sonography. Baseline ultrasound was less effective: conspicuity was graded as 1 in 42%, 2 in 39%, and 3 in 19% of cases. CONCLUSIONS: The spleen is the ideal organ to be studied with second-generation contrast media due to its superficial location, high vascularity, small size and homogeneous texture. Contrast-enhanced ultrasound is a simple, poorly-invasive and accurate tool for the evaluation of splenic disorders. If our data are confirmed, it will be possible to reduce the use of more complex technologies such as CT and MRI.

Adolescent↗

PubMed1988

Redundancy of information in enhancers as a principle of mammalian transcription control.

In contrast to prokaryotes, in which strong transcriptional signals can be located within very short DNA segments, typical mammalian enhancers are about 200 base-pairs long. We reasoned that a minimal length of enhancer-active DNA is required for a high transcription rate in higher eukaryotes, and that segments from a single enhancer or from different enhancers might be multimerized or combined to satisfy such a requirement. To test this, enhancer fragments from different viruses were joined in a recombinant simian virus 40 (SV40) and screened for efficiency of viral growth. The 48 combinations tested show that the hypothesis is basically correct. For example, two subfunctional heterologous enhancer fragments can together form a functional enhancer. No enhancer shorter than 84 base-pairs could promote SV40 growth, i.e. in no case did we find a short "superstrong" enhancer segment. To test whether multimerization of a short fragment would result in a strong enhancer, we have synthesized a 50 base-pair enhancer segment derived from Herpesvirus saimiri. One to six copies of this oligonucleotide gave an incremental increase in enhancer activity. We propose, therefore, that mammalian gene regulation is based on a redundancy of information that can be provided either by a combination of different DNA sequence elements, or by multiple copies of the same element. Also, the finding of strong and weak enhancers suggests that in most cases an enhancer is permanently required for transcription of a gene, rather than acting in an all-or-none fashion to establish a transcription complex, after which it becomes dispensable.

Animals↗

PubMed2006

Pulmonary nodule characterization: a comparison of conventional with quantitative and visual semi-quantitative analyses using contrast enhancement maps.

PURPOSE: To determine whether conventional nodule densitometry or analysis based on contrast enhancement maps of indeterminate lung nodules imaged with contrast-enhanced CT can distinguish benign from malignant lung nodules. MATERIALS AND METHOD: Thin section, contrast-enhanced CT (baseline, and post-contrast series acquired at 45, 90,180, and 360 s) was performed on 29 patients with indeterminate lung nodules (14 benign, 15 malignant). A thoracic radiologist identified the boundary of each nodule using semi-automated contouring to form a 3D region-of-interest (ROI) on each image series. The post-contrast series having the maximum mean enhancement was then volumetrically registered to the baseline series. The two series were subtracted volumetrically and the subtracted voxels were quantized into seven color-coded bins, forming a contrast enhancement map (CEM). Conventional nodule densitometry was performed to obtain the maximum difference in mean enhancement values for each nodule from a circular ROI. Three thoracic radiologists performed visual semi-quantitative analysis of each nodule, scoring each map for: (a) magnitude and (b) heterogeneity of enhancement throughout the entire volume of the nodule on a five-point scale. Receiver operator characteristic (ROC) analysis was conducted on these features to evaluate their diagnostic efficacy. Finally, 14 quantitative texture features were calculated for each map. A statistical analysis was performed to combine the 14 texture features to a single factor. ROC analysis of the derived aggregate factor was done as an indicator of malignancy. All features were analyzed for differences between benign and malignant nodules. RESULTS: Using 15 HU as a threshold, 93% (14/15) of malignant and 79% (11/14) of benign nodules demonstrated enhancement. The ROC curve when higher values of enhancement indicate malignancy was generated and area under the curve (AUC) was 0.76. The visually scored magnitude of enhancement was found to be less effective in distinguishing malignant from benign lesions, with an average AUC of 0.62. The visually scored pattern of enhancement was found to be more effective with an average AUC of 0.79. From the statistical analysis performed to combine the texture features to a single factor, the area under the ROC curve was 0.84. CONCLUSION: The present study suggests that visual semi-quantitative and quantitative characterization of contrast enhancement patterns may potentially enhance the discrimination between benign and malignant nodules. Further studies and correlation with pathologic material will be important to better understand the potential interplay between CT enhancement features, host stromal elements, and neovascularity that may contribute to these patterns.

Adult↗

PubMed2005

The HS2 enhancer of the beta-globin locus control region initiates synthesis of non-coding, polyadenylated RNAs independent of a cis-linked globin promoter.

The HS2 enhancer in the beta-globin locus control region (LCR) regulates transcription of the globin genes 10-50 kb away. Earlier studies show that a transcription mechanism initiated by the HS2 enhancer through the intervening DNA in the direction of the cis-linked promoter and gene mediates long-range enhancer function. Here, we further analyzed the enhancer-initiated RNAs and their mode of transcription from the HS2 enhancer in the endogenous genome of erythroid K562 cells, in plasmids integrated into K562 cells and in purified DNA used as template in in vitro transcription reactions. We found that the HS2 enhancer was able to initiate transcription autonomously in the absence of a cis-linked globin promoter. The enhancer-initiated, intergenic RNAs were different from the mRNA synthesized at the promoter in several aspects. The enhancer RNAs were synthesized not from a defined site but from multiple sites both within and as far as 1 kb downstream of the enhancer. The enhancer RNAs did not appear to contain a normal cap structure at the 5' ends. They were polyadenylated at multiple sites within 3 kb downstream of their initiation sites and were therefore shorter than 3 kb in lengths. The enhancer RNAs remained in discrete spots within the nucleus and were not processed into mRNA or translated into proteins. These particular features of enhancer-initiated transcription indicate that the transcriptional complex assembled by the enhancer was different from the basal transcription complex assembled at the promoter. The results suggest that in synthesizing non-coding, intergenic RNAs, the enhancer-assembled transcription complex could track through the intervening DNA to reach the basal promoter complex and activate efficient mRNA synthesis from the promoter.

DNA, Intergenic↗

PubMedDate not supplied

Cell-type specific protein binding to the enhancer of simian virus 40 in nuclear extracts.

Enhancers are cis-acting activators of transcription from homologous or heterologous promoter elements of viral and cellular genes (see refs 1-6 for reviews). The activity of the simian virus 40 (SV40) (refs 7-9) and immunoglobulin heavy-chain gene (IgH) (refs 10, 11) enhancers has been reproduced to some extent in vitro and appears to be mediated by trans-acting factors both in vitro and in vivo. The SV40 enhancer consists of multiple sequence motifs in two domains, A and B (Fig. 1, see ref. 14): domain B contains GT-I and -II and two TC motifs, of which only TC-II is important for enhancer activity in HeLa cells; and domain A contains the P and the two Sph motifs, the repetition of which generates the sequence 5'-ATGCAAAG-3', similar to the 'octameric' sequence of the IgH enhancer, (Fig. 4i; refs 14, 16), where it is important for enhancing activity. Each SV40 enhancer motif is a binding site for a protein or proteins present in HeLa cell nuclear extracts. Unlike the SV40 enhancer, which is active in HeLa and lymphoid B cells, the IgH enhancer is preferentially active in B cells, suggesting that not all the trans-acting factors necessary for its activity are present in HeLa cells. However, the IgH enhancer can compete with the SV40 enhancer in vitro in HeLa or lymphoid cell extracts and in vivo in B cells. Here we show that both human HeLa and BJA-B lymphoid B-cell nuclear extracts contain proteins that bind to specific, sometimes overlapping, motifs of the SV40 enhancer. Some binding is cell-specific, suggesting that it is not the same set of sequence motifs and proteins that is responsible for the enhancer activity in the two cell types. This is confirmed by our results obtained in vivo with mutated SV40 enhancers.

B-Lymphocytes↗

PubMed2002

The co-activator p300 associates physically with and can mediate the action of the distal enhancer of the FGF-4 gene.

Distal enhancers commonly regulate gene expression. However, the mechanisms of transcriptional mediation by distal enhancers remain largely unknown. To better understand distal enhancer-mediated transcription, we examined the regulation of the FGF-4 gene. The FGF-4 gene is regulated during early development by a powerful distal enhancer located downstream of the promoter in exon 3. Sox-2 and Oct-3 bind to the enhancer and are required for the activation of the FGF-4 gene. Previously, we implicated the co-activator p300 as a mediator of Sox-2/Oct-3 synergistic activation of a heterologous promoter, suggesting that p300 may play a role in mediating enhancer activation of the FGF-4 gene. In this study, we provide both functional and physical evidence that p300 plays an important role in the action of the FGF-4 enhancer. Specifically, we show that E1a, but not a mutant form of E1a that is unable to bind p300, inhibits enhancer activation of the FGF-4 promoter. We also demonstrate that Gal4/p300 fusion proteins can stimulate the FGF-4 promoter when bound to the FGF-4 enhancer. Additionally, we present evidence that p300 mediation of the FGF-4 enhancer requires acetyltransferase activity. Importantly, we also show that Sox-2 and p300 are physically associated with the endogenous FGF-4 enhancer but weakly associated with the endogenous FGF-4 promoter. These results are consistent with a model of transitory interaction between the distal enhancer and the FGF-4 promoter. Our results also suggest that intragenic distal enhancers may use mechanisms that differ from extragenic distal enhancers.

Animals↗

PubMed2025

dbscATAC: a resource of single-cell super-enhancers/enhancers and gene markers derived from scATAC-seq data.

MOTIVATION: scATAC-seq enables high-resolution mapping of cis-regulatory elements. It has been widely applied to uncover cell-type-specific regulatory networks and complement scRNA-seq analysis in numerous studies. However, a large number of datasets generated by scATAC-seq remain underutilized due to limited exploration of super-enhancers/typical enhancers and gene markers. A comprehensive resource enabling cell-type-specific annotation of cis-regulatory elements and their dynamic enhancer-gene linkages remains an urgent unmet need for scATAC-seq. RESULTS: We present dbscATAC, a specialized single-cell database for annotating super-enhancers, gene markers, and enhancer-gene interactions derived from scATAC-seq data. Using improved machine learning algorithms, we identified 213 835 super-enhancers across 520 tissue/cell types from three species, as well as 347 484 gene markers, 13 470 526 enhancers, and 10 402 346 enhancer-gene interactions derived from 1 668 076 single cells spanning 1028 tissue/cell types in 13 species. An easy-to-use online platform with multiple analytic modules and hierarchical query options was developed for searching, browsing and visualizing single-cell super-enhancers, enhancers, and gene markers. dbscATAC provides a comprehensive resource to facilitate the exploration of enhancer landscapes, gene regulation, and cell-type-specific characteristics in single-cell epigenomics. AVAILABILITY AND IMPLEMENTATION: The database with all the super-enhancer/enhancer annotation data is available at http://singlecelldb.com/dbscATAC/index.php. And the source code of dbscATAC for prediction of SEs, enhancers, and gene markers are available at https://github.com/EvansGao/dbscATAC. The source code, tissue/cell type description, and data summary can be downloaded at DOI: 10.6084/m9.figshare.28706414.scATAC-seq, Database, Super-enhancers/enhancers, Gene markers.

Enhancer Elements, Genetic↗

PubMed1992

Repression of the hepatitis B virus enhancer by a cellular factor.

The enhancer element of hepatitis B virus (HBV) regulates the transcription of all HBV mRNA, including the pregenomic mRNA used during replication. This pregenomic mRNA is transcribed from the core gene promoter which is located 500 bp downstream from the HBV enhancer element. To examine the effect of the HBV enhancer on the activity of the core gene promoter, we constructed various plasmids containing different combinations of HBV enhancer and core gene promoter sequences regulating the expression of the chloramphenicol acetyltransferase gene. When the HBV enhancer was positioned immediately adjacent to the core gene promoter, the enhancer increased the activity of the core gene promoter nearly 30-fold. In contrast, the HBV enhancer only modestly stimulated the core gene promoter (less than threefold) at its native position in the HBV genome. This weak HBV enhancer activity was due to a DNA sequence located between the enhancer and the core gene promoter and not due to the increased distance between the enhancer and the core gene promoter. Competition experiments demonstrated that a trans-acting factor(s) bound this sequence and repressed the enhancer. This DNA sequence contains the C/EBP, AP-1 and NF-1 regulatory sites. No inhibition of enhancer activity was observed when only the AP-1 and C/EBP sites were present. Repression of the HBV enhancer was not detected when the NF-1 site was disrupted, indicating that the NF-1 site was involved in the suppression of the HBV enhancer.

Base Sequence↗

PubMed1991

The enhancer of human papillomavirus type 16: binding sites for the ubiquitous transcription factors oct-1, NFA, TEF-2, NF1, and AP-1 participate in epithelial cell-specific transcription.

The enhancer of human papillomavirus type 16 (HPV-16) is considered to be specific for epithelial cells, in particular for cervical carcinoma-derived cell lines. We reexamined this hypothesis with the complete enhancer as well as nonoverlapping subclones and found all clones to be active in epithelial cell lines derived from the epidermis and from carcinomas of the cervix, mammary gland, and colon, but inactive in fibroblast, lymphoma, and embryonal carcinoma cells. Although the virus infects only human mucosal epithelia, enhancer activity was independent of the exact type or of the species of origin of the transfected epithelial cell. In spite of epithelial cell specificity, we found that the activity of the HPV-16 enhancer varied strongly from a cytomegalovirus enhancer and the simian virus 40 enhancer in a cell line-dependent manner. This suggests varying quantitative contributions of enhancer elements rather than regulation by an all-or-none switch. Cell type specificity was maintained by a 91-bp subclone of the 400-bp enhancer. Most of the enhancer activity of this fragment was eliminated by alternative mutations in binding sites for the ubiquitous factors AP-1, nuclear factor 1 (NF1), or TEF-2. These three types of factors bind this 91-bp enhancer without cooperation, although activation appears to be synergistic. Outside the 91-bp fragment, a motif typical for papillomavirus enhancers, namely an octamerlike sequence flanked by an NF1-binding site, contributes to enhancer function, as the activity was strongly reduced upon its deletion. In HPV-16, this motif is bound by the oct-1 factor as well as by a probably novel factor, NFA, whereas a related motif of HPV-11 is recognized only by NFA. On examination, none of the five types of transcription factors involved in HPV enhancer activation was restricted to epithelial cells, but NF1, AP-1, and oct-1 were present in higher concentration in HeLa cells than in fibroblasts. Only NF1 showed some qualitative cell type-specific differences. We propose that the epithelial specificity of the HPV-16 enhancer is brought about via binding sites for supposed ubiquitous transcription factors. The mechanism of this activation apparently involves synergism between factors that vary in concentration and may include cell-specific functional differences residing outside the DNA-binding domain of these factors.

3T3 Cells↗

PubMed1999

Sequence-specific and/or stereospecific constraints of the U3 enhancer elements of MCF 247-W are important for pathogenicity.

The oncogenic potential of many nonacute retroviruses is dependent on the duplication of the enhancer sequences present in the unique 3' (U3) region of the long terminal repeat (LTR). In a molecular clone (MCF 247-W) of the murine leukemia virus MCF 247, a leukemogenic mink cell focus-inducing (MCF) virus, the U3 enhancer sequences are tandemly repeated in the LTR. We mutated the enhancer region of MCF 247-W to test the hypothesis that the duplicated enhancer sequences of this virus have a sequence-specific and/or a stereospecific role in enhancer function required for transformation. In one virus, we inserted 14 nucleotide bp into the novel sequence generated at the junction of the two enhancers to generate an MCF virus with an interrupted enhancer region. In the second virus, only one copy of the enhancer sequences was present. This second virus also lacked the junction sequence present between the two enhancers of MCF 247-W. Both viruses were less leukemogenic and had a longer mean latency period than MCF 247-W. These data indicate that the sequence generated at the junction of the two enhancers and/or the stereospecific arrangement of the two enhancer elements are required for the full oncogenic potential of MCF 247-W. We analyzed proviral LTRs within the c-myc locus in tumor DNAs from mice injected with the MCF virus with the interrupted enhancer region. Some of the proviral LTRs integrated upstream of c-myc contain enhancer regions that are larger than those of the injected virus. These results are consistent with the suggestion that the virus with an interrupted enhancer changes in vivo to perform its role in the transformation of T cells.

Animals↗

PubMed2003

The human cytomegalovirus major immediate-early enhancer determines the efficiency of immediate-early gene transcription and viral replication in permissive cells at low multiplicity of infection.

To determine the effect of the human cytomegalovirus (CMV) major immediate-early (MIE) enhancer or promoter on the efficiency of viral replication in permissive human cells, we constructed recombinant viruses with their human MIE promoter, enhancer, and promoter plus enhancer replaced with the murine CMV components. After a low multiplicity of infection (MOI) (0.01 PFU/cell), recombinant human CMV with the murine CMV promoter replicated like the wild type but recombinant virus with the murine enhancer replicated less efficiently. Immediate-early (IE) viral protein pIE72 (UL123), early viral protein (UL44), and viral DNA synthesis were significantly decreased. The effect of the human CMV enhancer substitution with the murine CMV enhancer was also demonstrated in different cell types by using recombinant virus with the UL127 promoter, driving the expression of green fluorescent protein (GFP). After an MOI of 1, GFP expression was high with the human CMV enhancer and significantly lower with the murine CMV enhancer. Even though at a high MOI (10 PFU/cell), the murine CMV enhancer was as efficient as the human CMV enhancer for the transcription of IE genes in human foreskin fibroblast cells, at lower MOIs, the murine CMV enhancer was less efficient. Proximal and distal chimeras of the human and murine enhancers also replicated less efficiently at a low MOI and expressed lower levels of GFP from the UL127 promoter. These experiments demonstrate that the entire human CMV enhancer has evolved for the efficient expression of the viral IE and early genes in human cells. Possible functions of the human CMV enhancer and promoter at a low MOI are discussed.

Animals↗

PubMed1999

Species-specific differences in positive and negative regulatory elements in the renin gene enhancer.

A distal transcriptional enhancer has been previously reported upstream of the mouse renin gene. A homologous sequence is also present upstream of the human renin gene, but the mouse and human renin enhancers differ markedly in their ability to activate transcription of a renin promoter. Although the 2 enhancers share high homology in their 202-bp promoter distal portions, their 40-bp proximal portions are heterogeneous. Chimeric enhancers were used to test the role of the 40-bp segment (m40) of the enhancer by using transient transfection analysis in mouse kidney renin-expressing As4. 1 cells. Deletion of m40 from the mouse renin enhancer or its addition to the human renin enhancer did not significantly change transcriptional activity when placed close to a mouse or human renin promoter. However, when placed further upstream of a renin promoter, the same deletion and substitution markedly altered enhancer activity. Electrophoretic gel mobility shift analysis identified 2 elements, a and b, in m40 that specifically bound nuclear proteins from As4.1 cells. Mutagenesis and transient transfection analysis revealed that element b accounts for the function of m40 and that element a antagonizes the positive influence of element b. Gel competition and supershift analysis revealed that nuclear factor-Y, a ubiquitous CAAT-box binding protein, binds to element a. Sequence analysis revealed that the human renin enhancer has a natural loss-of-function mutation in element b that affects its ability to transactivate when placed far upstream of a promoter. Reversion of the human renin element b to match the mouse sequence restored transactivation of the enhancer in mouse As4.1 cells. These data suggest that element b cooperates with the rest of the enhancer to maintain full enhancer activity, whereas element a may regulate enhancer activity. Sequence differences in these elements may explain the functional differences in the mouse and human renin enhancer sequences.

Animals↗

PubMed1998

Gamma-globin gene promoter elements required for interaction with globin enhancers.

Normal expression of the human beta-globin domain genes is dependent on at least three types of regulatory elements located within the beta-globin domain: the locus control region (LCR), globin enhancer elements (3'beta and 3'Agamma), and the individual globin gene promoter and upstream regions. It has been postulated that regulation occurs through physical interactions between factors bound to these elements, which are located at considerable distances from each other. To identify the elements required for promoter-enhancer interactions from a distance, we have investigated the expression of the wild-type, truncated, and mutated gamma-globin promoters linked to the 5'HS2 enhancer. We show that in K562 cells, 5'HS2 increases activity approximately 20-fold from both a wild-type and truncated (-135 --> +25) gamma promoter and that truncation or site-directed mutagenesis of the tandem CCAAT boxes eliminated the enhancement by 5'HS2. Mutation of the gamma-globin gene promoter GATA-1 binding sites did not decrease either promoter strength or enhancement of activity by 5'HS2. To determine if enhanced expression of gamma-globin gene promoters carrying mutations associated with hereditary persistence of fetal hemoglobin (HPFH) was due to greater interactions with enhancers, we linked these HPFH gamma-globin gene promoters to 5'HS2 and demonstrated a twofold to threefold higher expression than the corresponding wild-type promoter plus enhancer in MEL cells. Addition of the Agamma-globin gene 3' enhancer to a plasmid containing the gamma-globin gene promoter and 5'HS2 did not further enhance promoter strength. Furthermore, we have demonstrated that the previously identified core 5'HS2 enhancer (46-bp tandem AP-1/NF-E2 sites) increased expression only when located 5', but not 3', to the gamma-globin-luciferase reporter gene, suggesting that its enhancer effect is not by DNA looping. Our results suggest that CCAAT boxes, but not GATA or CACCC binding sites, are required for interaction between the gamma-globin promoter and the LCR/5'HS2 and that regulatory elements in addition to the core enhancer may be required for the enhancer to act from a distance.

Animals↗

PubMed1999

Dynamic T1-weighted spin-echo MR imaging: the role of digital subtraction in the demonstration of enhancing brain lesions.

We compared subtracted and non-subtracted images obtained from a contrast-enhanced dynamic T1-weighted spin echo (SE) magnetic resonance (MR) technique for the demonstration of enhancing brain lesions with and without associated hemorrhage. Thirty-four patients with enhancing brain lesions or subacute parenchymal hematomas were imaged using a contrast-enhanced dynamic T1-weighted SE MR technique modified by a keyhole scheme. On-line digital subtraction was performed. Non-subtracted and subtracted dynamic scans were compared for conspicuity and contrast-to-noise ratios (CNRs) of enhancing brain lesions. The presence and pattern of enhancement in the subacute parenchymal hematomas were evaluated on the subtracted images. In all, 47 enhancing brain lesions were detected on both the non-subtracted and the subtracted images. The enhancing brain lesions were more conspicuous on the subtracted images (P < 0.05). There was an increase in CNRs of the enhancing lesions on the subtracted images compared with the non-subtracted ones (P < 0.001). Seventeen subacute parenchymal hematomas were detected on the non-subtracted images. The subtracted images demonstrated enhancement in 15 hematomas (8 rim enhancement only/7 both nodular and rim enhancement). Digital subtraction in contrast-enhanced dynamic T1-weighted SE MR imaging is helpful in demonstrating enhancing brain lesions with and without associated hemorrhage.

Aged↗

PubMed2004

Contrast-enhanced power Doppler sonography of ductal pancreatic adenocarcinomas: correlation with digital subtraction angiography findings.

PURPOSE: The purpose of this prospective study was to utilize contrast-enhanced power Doppler sonography to evaluate the enhancement characteristics of ductal pancreatic adenocarcinomas and correlate them with the tumor vascularity observed on digital subtraction angiography (DSA). METHODS: Twenty consecutive patients with ductal pancreatic adenocarcinoma underwent power Doppler sonography and DSA. Tumor vascularity was assessed using unenhanced and contrast-enhanced power Doppler sonography. The contrast agent Levovist was administered intravenously by bolus injection of a dose of 2.5 g at a concentration of 350 mg/mL; saline was administered immediately thereafter. The patients were asked to hold their breath for 30 seconds (for the period 15-45 seconds after saline injection) while the early phase of enhancement was studied; the delayed phase of enhancement was observed between 60 and 120 seconds after saline administration, while patients breathed gently. RESULTS: None of the 20 pancreatic carcinomas showed any color signals on power Doppler sonography before administration of the contrast medium. Seventeen (85%) of the 20 pancreatic carcinomas also showed no enhancement in the early and delayed phases of contrast-enhanced power Doppler sonography. However, in the early phase of contrast-enhanced power Doppler sonography; 1 lesion showed pronounced enhancement and 2 showed mild enhancement. On DSA, the 17 carcinomas showing no enhancement on power Doppler sonography were found to be hypovascular, whereas the remaining 3 carcinomas with contrast enhancement on power Doppler sonography were found to be hypervascular. CONCLUSIONS: The enhancement characteristics of the ductal pancreatic adenocarcinomas correlated well with the tumor vascularity observed on DSA. However, further study is needed to determine the accuracy of contrast-enhanced sonography in the diagnosis of pancreatic masses.

Adult↗

PubMed1995

Evaluation of solitary pulmonary nodules with dynamic contrast-enhanced MR imaging--a promising technique.

The evaluation of a solitary pulmonary nodule (SPN) is one of the most frequently encountered challenges in thoracic radiology. In addition to a "state-of-the-art" evaluation of SPNs with CT and biopsy techniques, recently the assessment of the enhancement characteristics with iodinized contrast agents has shown its potential to improve the characterization of SPNs. We investigated whether dynamic contrast-enhanced MRI is suitable to assess the degree and kinetics of MR contrast enhancement and whether this technique could help in the noninvasive specification of SPNs. We studied prospectively 21 patients with SPNs. T1-weighted and proton density-weighted spoiled gradient-echo breath-hold images (2D-FLASH) were obtained before and after the administration of Gd-DTPA in a standard dosage of 0.1 mmol/kg body weight. The maximum enhancement and the initial velocity of contrast uptake were assessed and correlated with pathohistological findings. To quantify contrast enhancement, we used the relative signal intensity increase (S(rel)) and the recently introduced enhancement factor (EF) and contrast uptake equivalent (CE). Dynamic contrast-enhanced MRI proved to be well suited for the assessment of the contrast enhancement characteristics of SPNs. Significant differences were found in the degree and kinetics of contrast enhancement for specific types of nodules. Malignant neoplastic SPNs enhanced stronger and faster than benign neoplastic SPNs. The strongest and fastest enhancement, however, was found in a benign type of nodules where histology revealed inflammatory/fibrous lesions. These differences in contrast enhancement between the different pathohistological groups were more significant when EF and CE rather than S(rel) was used for the quantification of contrast enhancement. The results of this study indicate a potential role for dynamic contrast-enhanced MRI in the preoperative noninvasive evaluation of SPNs using EF and CE as contrast uptake assessment parameters.

Contrast Media↗

PubMed1990

Percutaneous penetration of acyclovir through excised hairless mouse and rat skin: effect of vehicle and percutaneous penetration enhancer.

The effects of vehicle and percutaneous penetration enhancer on the penetration of acyclovir through excised hairless mouse and rat skin were investigated. Four solvents, propylene glycol (PG), ethanol (ET), isopropanol (IPA), and isopropyl myristate (IPM), were employed as vehicles, in combination with four enhancers, 1-farnesylazacycloheptan-2-one (7FU), 1-geranylazacycloheptan-2-one (7GU), 1-geranylazacyclopentan-2-one (5GU), and 1-dodecylazacycloheptan-2-one (Azone). Acyclovir was suspended in vehicles to avoid the effect of the thermodynamic activity of acyclovir in the vehicle. The penetration of acyclovir through hairless mouse skin from IPA was enhanced by 7GU, whereas that from IPM was not affected. All combinations of vehicle and penetration enhancer were examined using rat skin. No effect of the enhancers was observed in the IPM vehicle. The estimated solubility parameters of vehicles and enhancers indicated that the polarities of IPM and the enhancers are similar, which prevents effective penetration of the enhancers from IPM. However, the penetration of acyclovir from the other vehicles was increased by the enhancers. The combination of hydrophilic vehicle and hydrophobic enhancer resulted in a large enhancing effect. The disappearance of the enhancers from the vehicle correlated with their enhancing activity, but other factors also seemed to affect the penetration enhancement of acyclovir.

Acyclovir↗

PubMed1995

Increased adhesion as a mechanism of antibody-dependent and antibody-independent complement-mediated enhancement of human immunodeficiency virus infection.

Enhancement of human immunodeficiency virus (HIV) infection by complement alone or in conjunction with antibodies was studied experimentally and theoretically. Experimental studies showed that while HIV-positive sera neutralize HIV infection, the addition of fresh complement abrogated neutralization and could even cause enhancement. Enhancement was blocked by anti-complement receptor 2 antibodies, and infection under enhancing conditions could be blocked by soluble CD4. Antibody-dependent complement-mediated enhancement (C'ADE) was dependent on the alternative complement activation pathway, as factor B-deficient serum could enhance only after the addition of factor B. The observed enhancement was also antibody dependent, since the addition of antibodies increased the level of enhancement. Under C'ADE conditions, infection reached a plateau within 5 min and was not caused by activation of cells by factors in the human serum. On the contrary, preincubation of cells with complement decreased the level of enhancement. A theoretical model of HIV infection in vitro which exhibited similar enhancement in an antibody- and complement concentration-dependent way was developed. Model studies indicated that the enhanced infection process could be explained by the fact that virions, because of complement deposition on the surface, bind more efficiently to cells. The model also indicated that the saturation of the enhanced infection process seen after a few minutes could be caused by saturation of the complement receptors. The effect of neutralizing antibodies can thus be overcome by the enhancing effect of complement that facilitates the contact between gp120 and CD4. These studies demonstrate that the main features of the complement-dependent enhancement phenomenon can be understood in terms of a simple mathematical model.

CD4 Antigens↗