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Results for “Enhancer”

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PubMed1996

The postoperative lumbar spine: enhanced MR evaluation of the intervertebral disk.

PURPOSE: To document the pattern of enhancement and morphologic changes on MR images that occur in the intervertebral disk and adjacent vertebral bodies after diskectomy and to correlate the presence of intervertebral disk enhancement with the preoperative and postoperative clinical findings. METHODS: Preoperatively, and at 3 months and 6 months after surgery, 94 adults who had first-time surgery for a herniated lumbar intervertebral disk that was associated with radiculopathy, expressed as leg symptoms or signs (with or without lower back pain), were asked to respond to a questionnaire regarding pain, were given serial physical examinations, and were examined with contrast-enhanced MR imaging. The measures of clinical outcome that were evaluated included the straight leg raise sign, radicular pain, and lower back pain. Type of disk herniation, intervertebral disk enhancement, disk space height, and degenerative end-plate changes were also assessed. RESULTS: Of the 94 patients evaluated, 19 (20%) had postoperative intervertebral disk enhancement that was not present on the preoperative study. The pattern of enhancement was remarkably consistent, with 18 of the cases showing linear enhancement within the intervertebral disk, manifested as two thin bands paralleling the end plates. End-plate enhancement was present in 7 (37%) of the 19 patients with disk enhancement. There were no significant associations between disk enhancement and specific clinical symptoms before or after surgery. CONCLUSION: Our group of asymptomatic postoperative patients had anular enhancement (curette site), disk enhancement, and vertebral end-plate enhancement on MR images without evidence of disk space infection. This finding points out the need to understand asymptomatic postoperative changes that are sequelae of surgery and not necessarily indicators of infection.

Adolescent↗

PubMed2004

Detection and characterization of focal hepatic lesions: mangafodipir vs. superparamagnetic iron oxide-enhanced magnetic resonance imaging.

PURPOSE: To compare the mangafodipir-enhanced magnetic resonance (MR) and superparamagnetic iron oxide (SPIO)-enhanced images for their ability to detect and characterize focal hepatic lesions. MATERIALS AND METHODS: Unenhanced, mangafodipir-enhanced, and SPIO-enhanced hepatic MR images obtained from 64 patients were analyzed. A total of 121 hepatic lesions were included: 66 hepatocellular carcinomas (HCCs), 26 metastases, 14 hemangiomas, 5 cysts, 3 cholangiocarcinomas, 4 focal nodular hyperplasias (FNHs), 2 abscesses, and 1 adenoma. Two radiologists independently reviewed the two sets of images in a random order: 1) the unenhanced and mangafodipir-enhanced images (the mangafodipir set) and 2) the unenhanced and SPIO-enhanced images (the SPIO set). This study compared the accuracy of lesion detection, the ability to distinguish between a benign and malignant lesion, and the ability to distinguish between the hepatocellular and nonhepatocellular origins of the lesions using the areas (Az) under the receiver operating characteristic (ROC) curve. RESULTS: The overall accuracy for detecting focal lesions was significantly higher (P < 0.05) with the SPIO set (Az = 0.846 and 0.871 for readers 1 and 2, respectively) than with the mangafodipir set (Az = 0.716 and 0.766). Most of the lesions detected only with the SPIO-enhanced MR images by the readers were small HCCs. For lesions larger than 15 mm, the sensitivities of the two contrast enhancement techniques were similar for both readers. The accuracy of the mangafodipir and SPIO sets in distinguishing between benign and malignant lesions was comparable. The accuracy for distinguishing between the hepatocellular and nonhepatocellular origins of the lesions was significantly higher (P < 0.05) using the mangafodipir set (Az = 0.897 and 0.946) than using the SPIO set (Az = 0.741 and 0.833). CONCLUSION: SPIO- and mangafodipir-enhanced images were comparable for detection of focal hepatic lesions other than small HCCs, which were better detected on the SPIO-enhanced images. Mangafodipir-enhanced images are likely better than the SPIO-enhanced images for distinguishing between focal liver lesions with a hepatocellular or nonhepatocellular origin.

Adult↗

PubMedDate not supplied

Dynamic enhancement of upper abdominal organs in normal volunteers with MRI and effects of contrast dose reduction.

BACKGROUND: To quantify enhancement parameters of the upper abdominal organs over time during magnetic resonance (MR) examinations and to evaluate the effect of a dose reduction of contrast medium on these parameters. METHODS: Ten volunteers underwent two separate dynamic enhanced MR examinations with 0.1 and 0.075 mmol/kg of contrast medium, respectively. Breath-hold gradient-echo T1-weighted images were acquired every second for 118 s followed by delayed images. The percentages of enhancement, the time to maximum enhancement, and the area under the time-versus-enhancement curve were calculated for each organ. RESULTS: The mean times to maximum percentage of enhancement were less than 25 s for the pancreas, kidneys, and spleen and 50 s for the liver. The mean values of maximum percentage of enhancement for the standard/reduced doses were 72%/62% (pancreas), 165%/155% (kidneys), 114%/87% (spleen), and 67%/53% (liver). This difference was significant when liver enhancement was considered (p = 0.02). In addition, when the areas under the time-versus-enhancement curves were compared, the difference between the standard dose and reduced dose was significant for all organs tested (p < 0.05). CONCLUSIONS: Dynamic scanning of the upper abdomen should start early after contrast injection. Injection parameters should be standardized to capture arterial and venous enhancements in liver examinations. A 25% dose reduction did not significantly affect peak enhancement (except for the liver) but did significantly reduce overall enhancement.

Adult↗

PubMed2001

Contrast-enhanced MR imaging of the endolymphatic sac in patients with sudden hearing loss.

Our objective was to evaluate the frequency of contrast enhancement of the endolymphatic sac in patients with sudden hearing loss. Forty consecutive patients with sudden sensorineural hearing loss (20 males and 20 females; age range 11-82 years), 40 age-matched control subjects, and 5 patients with Meniere's disease were examined using the same imaging protocol on a 1.5-T MR system. Pre- and post-contrast-enhanced T1-weighted 3D spoiled gradient-echo sequence (3D SPGR; TR/TE=23/10 ms, no. of excitations=1, flip angle=30 degrees) images were obtained using a voxel size of 0.6 x 0.7 x 0.8 mm(3). Contrast enhancement in the area of the endolymphatic sac was assessed by two radiologists, and the frequency of contrast enhancement was compared between the three study groups. Enhancement of the ipsilateral endolymphatic sac was observed in 30 of the 40 patients with sudden hearing loss (75%). Twenty of these 30 patients also showed enhancement on the contralateral side, and 1 patient showed enhancement only on the contralateral side. Only 1 of the 5 patients with Meniere's disease showed enhancement. Nine of the 40 control subjects (22.5%) showed enhancement (bilateral enhancement in 5 subjects, unilateral in 4). The frequency of enhancement in patients with sudden hearing loss was significantly higher than that in control subjects ( P<0.0001) or patients with Meniere's disease ( P<0.05). The frequency of contrast enhancement of the endolymphatic sac is significantly increased in patients with sudden hearing loss, but further study is necessary to clarify the relationship between this finding and the pathophysiology of sudden hearing loss.

Adolescent↗

PubMed2005

Diagnostic usefulness of segmental and linear enhancement in dynamic breast MRI.

The aim of this study was the evaluation of the diagnostic usefulness of ductal or segmental enhancement in dynamic breast MRI. Segmental and ductal enhancement have been established as the breast MRI hallmarks of intraductal breast cancer (DCIS); however, the positive predictive value of this imaging finding is still unknown. In our study, we analysed the overall prevalence of a segmental or a linear enhancement pattern on breast MRI for an unselected cohort of patients. The aim was to evaluate the diagnostic usefulness of segmental or linear enhancement. Second, we asked whether biopsy was necessary also in the absence of mammographic findings suggestive of DCIS. Prospective, consecutive evaluation of 1,003 patients undergoing bilateral dynamic breast MRI. Studies were interpreted by two experienced breast radiologists. A diagnostic or screening two-view mammogram was available for all patients. Biopsy or short-term breast MRI follow-up was recommended for patients showing a segmental or a linear enhancement pattern on breast MRI. The patients' final diagnoses were established by imaging guided excisional or core biopsy or by clinical plus conventional imaging follow-up for a period of 2 years. The prevalence of segmental or linear enhancement was determined for patients with a final diagnosis of benign breast disease compared with those with a diagnosis of breast cancer. One hundred twenty patients had invasive breast cancer, 24 patients had DCIS and 859 patients had unsuspicious breast MRI or benign breast disease. A segmental or a linear enhancement pattern was found for 50/1,003 (5%) patients (17 DCIS, 33 benign breast diseases). Accordingly, the positive predictive value of segmental and linear enhancement is 34% (17/50); the specificity of this criterion is 96% (826/859). For 4/24 (17%) patients, DCIS was visible as segmental or linear enhancement on dynamic breast MRI, whereas no abnormalities were visible on the corresponding mammogram. The overall prevalence of a ductal or a segmental enhancement pattern on breast MRI is low. But this finding has a high specificity and a moderate positive predictive value for intraductal neoplastic changes. We conclude that if segmental or linear enhancement is identified on breast MRI further work-up is necessary. We recommend either direct MR-guided vacuum-assisted core biopsy or short-term follow-up breast MRI within 3 months. If ductal enhancement then persists, MR-guided biopsy should be recommended even in the absence of mammographically visible signs of DCIS.

Biopsy↗

PubMed2006

Contrast-enhanced flair imaging in the evaluation of infectious leptomeningeal diseases.

PURPOSE: The purpose of our study was to compare contrast-enhanced fluid-attenuated inversion recovery (FLAIR) images with contrast-enhanced T1 weighted images for infectious leptomeningitis. MATERIALS AND METHODS: We studied twenty-four patients with a clinical suspicion of infectious meningitis with unenhanced FLAIR, contrast-enhanced T1 weighted and contrast-enhanced FLAIR MR sequences. Twelve patients had cytologic and biochemical diagnosis of meningitis on cerebrospinal fluid (CSF) examination obtained 48 h before or after the MR study. Sequences were considered positive if abnormal signal was seen in the subarachnoid space (cistern or sulci) or along pial surface. RESULTS: Twenty-seven examinations in 24 patients were performed. Of the 12 patients (thirteen studies) in whom cytology was positive, unenhanced FLAIR images were positive in six cases (sensitivity 46%), contrast-enhanced FLAIR images were positive in 11 (sensitivity 85%), and contrast-enhanced T1 weighted MR images were positive in 11 patients (sensitivity 85%). Of the 12 patients (14 studies) in whom cerebrospinal fluid study was negative, unenhanced FLAIR images were negative in 13, contrast-enhanced FLAIR images were negative in 11, and contrast-enhanced T1 weighted MR images were negative in eight. Thus, the specificity of unenhanced FLAIR, contrast-enhanced FLAIR and contrast-enhanced T1 weighted images was 93, 79 and 57%, respectively. CONCLUSION: Our results suggest that post-contrast FLAIR images have similar sensitivity but a higher specificity compared to contrast-enhanced T1 weighted images for detection of leptomeningeal enhancement. It can be a useful adjunct to post-contrast T1 weighted images in evaluation of infectious leptomeningitis.

Adolescent↗

PubMed2006

Contrast-enhanced ultrasonography depicts small tumor vessels for the evaluation of pancreatic tumors.

OBJECTIVE: The aim of this study is to evaluate the efficacy of contrast-enhanced ultrasonography for the diagnosis of pancreatic tumors. MATERIALS AND METHODS: Contrast-enhanced ultrasonography with Levovist was performed on 62 consecutive patients (53 with pancreatic cancer, 4 with islet cell tumor, 3 with inflammatory pancreatic tumor, and 2 with metastatic tumor). The vascular and perfusion image phases of the tumors were evaluated and compared with the findings of contrast-enhanced computed tomography. RESULTS: Contrast-enhanced ultrasonography showed tumor vessels around and/or in the tumor at the vascular image phase in 79% of pancreatic cancer patients (42/53). At the perfusion image phase, 96% of pancreatic cancers (51/53) were classified as hypo-enhancement type. However, tiny spotty or irregular heterogeneous enhanced lesions were found in 84% of hypo-enhanced pancreatic cancer patients (43/51). The presence of small vessels at the vascular image phase was closely correlated with the presence of these intratumor regional enhanced lesions at the perfusion image phase (kappa coefficient=0.42). The sensitivity of contrast-enhanced ultrasonography (100%) for pancreatic cancer was superior to that of contrast-enhanced computed tomography (91%), but no significant difference was observed between the two (McNemar test: p=0.063). CONCLUSION: Contrast-enhanced ultrasonography with Levovist successfully visualizes fine vessels and enhancement in pancreatic tumors, and is useful for evaluating pancreatic tumors.

Adult↗

PubMed2004

Relationship between lesion size and signal enhancement on subtraction fat-suppressed MR imaging of the breast.

OBJECTIVE: To investigate the relationship between size and whole lesion enhancement of breast neoplasms. MATERIALS AND METHODS: Fat-suppressed subtraction MRI was performed in 94 breast lesions (44 malignant, 50 benign) with pathologically confirmed diagnoses. Of these, all malignant lesions and 31 of the 50 benign lesions showed enhancement. The degree of enhancement was quantified by using an ROI tracing around the whole lesion and calculated as the percentage increase in signal intensity between the corresponding precontrast and postcontrast images. RESULTS: The 44 malignant lesions showed enhancement percentage of 38.3% to 186.4% (mean 109.9%), and the 31 benign lesions showed enhancement percentage of 12.8% to 180.2% (mean 79.5%). The difference is statistically significant (P = .002). In 54 small lesions (28 malignant, 26 benign) with enhancing pixel areas of <300 mm(2) corresponding to a diameter of approximately 19.5 mm, an enhancement exceeding 75% of baseline separated malignant lesions (mean enhancement 116.7%) from benign ones (mean enhancement 72.8%) (P = .0001). This gave a sensitivity of 100% and a specificity of 69%, a positive predictive value of 78%, negative predictive value of 100% and an accuracy of 85% in using >75% enhancement increase in detecting malignancy in small (<300 mm(2)) enhancing lesions. CONCLUSION: The high sensitivity in the detection of small malignant lesions suggests a potential for the method to be used in assessment of small enhancing breast lesions.

Adult↗

PubMed2004

The comparative study of tumor angiogenesis and CT enhancement in pancreatic carcinoma.

PURPOSE: The purpose of this work was to study the correlation of pancreatic phase Computed tomography (CT) enhancement, intratumoral microvessel density (MVD) and pathologic grades in pancreatic carcinoma and to evaluate the relationship between CT enhancement degree and the malignancy degree of pancreatic carcinoma. METHODS: 34 patients with pancreatic carcinoma underwent CT scanning before resection. The enhancement degrees and forms of tumor were observed in pancreatic phase. The operational sample was stained with HE and CD34 marked by immunohistochemistry. MVD and histopathological grades of pancreatic carcinoma were examined. CT enhancement of the tumor, MVD counting in hot spot areas of neoplastic parenchymal cells and pathological grades of pancreatic carcinoma were comparatively analyzed. RESULT: Highly differentiated pancreatic adenocarcinoma was identified in 16 patients, moderately differentiated tumor in seven and poorly differentiated tumor in 11. Isodensity CT enhancement was demonstrated in 13 cases, slight low density enhancement in nine, slight low density enhancement along with small cyst lesion in nine and slight low density enhancement along with large cyst lesion in three. The counting of MVD with CD34 marked by immunohistochemistry in hot spot areas of neoplastic parenchyma cells were small in ten cases, medium in 16 and large in eight. The pathological grades correlated with CT enhancement of tumor (r=0.7857, P<0.001). The pathological grade correlated with MVD counting of tumor (r=0.3613, P<0.05). The CT enhancement of tumor correlated with MVD (r=0.6768, P<0.001). CONCLUSION: There was obvious and significant correlation between CT enhancement, pathological grades and MVD numbers in the hot spot areas of tumor. The extent of CT enhancement was inversely proportional to the malignancy degree of pancreatic carcinoma, and inversely proportional to MVD numbers in the hot spot areas of neoplastic parenchyma. The MVD in the hot spot areas of neoplastic parenchyma cells could also reflect the prognosis of the patients, and was directly proportional to malignancy degree of pancreatic carcinoma.

Adenocarcinoma↗

PubMed1997

Characterization of focal hepatic masses by dynamic contrast-enhanced MR imaging: findings in 311 lesions.

This study aimed to determine the overall accuracy of known enhancement patterns for the characterization of a large series of focal hepatic masses on dynamic contrast-enhanced magnetic resonance (MR) images. Breath-hold T1-weighted images of the liver acquired before intravenous gadolinium administration and serially over 6-10 min after contrast injection were acquired in < 25 a using FLASH or rapid spin-echo pulse sequences. A total of 311 proven focal hepatic masses in 128 patients were analyzed, including 192 malignant lesions (166 metastases and 26 hepatomas) and 119 benign lesions (48 cavernous hemangiomas, 45 hepatic cysts, and 26 other abnormalities). The lesions were evaluated for a variety of characteristics independently by two reviewers who were blinded to results. Cavernous hemangiomas showed early peripheral nodular enhancement (80% sensitivity and 99% specificity) and hepatic cysts showed no enhancement (100% sensitivity and 95% specificity). Hepatic metastases showed variable, moderate enhancement (47% by one reviewer and 74% by the other). Metastatic lesions from hypervascular primary neoplasms displayed peak enhancement during the hepatic artery dominant (bolus) phase, while other malignant neoplasms showed later peak enhancement (72% sensitivity and 77% specificity). Five metastatic foci with early homogeneous enhancement showed a delayed peripheral washout of contrast (rim sign), while no nonmetastatic foci displayed this finding (3% sensitivity and 100% specificity). Characteristic enhancement patterns of focal hepatic lesions were described in a large series of patients. This study confirms results of previous investigators who have shown that early nodular peripheral enhancement was highly specific for hemangiomas and lack of enhancement was highly specific for hepatic cysts. Hypervascular metastatic foci show earlier peak enhancement than other malignant lesions. Some (2-3%) metastatic lesions display a peripheral washout of contrast on serial images, with 100% specificity.

Adolescent↗

PubMed2002

Prognostic significance of tumor-enhancement and angiogenesis in oligodendroglioma.

OBJECTIVE: To study the prognostic significance of angiogenesis and enhancement on contrast-enhanced computerized tomography (CT) in oligodendrogliomas. MATERIAL AND METHODS: CD34 immunostaining was employed in samples of 26 low-grade oligodendrogliomas from patients treated by extensive resection and radiotherapy to determine the tumor angiogenesis index (TAI), calculated by measuring the immunostained endothelial surface area, in microm(2), per 1000 tumor cells. Preoperative CT scan was evaluated in each case, and the absence or presence of tumor enhancement after contrast administration was recorded. Survival was analyzed and statistically compared for subgroups of patients with lesions in which the TAI was less than or greater than 15, and for subgroups of patients having tumors showing presence or absence of enhancement on contrast-enhanced CT. RESULTS: Survival of patients with tumors showing a TAI of less than 15 was 100% and 71% at 5 and 10 years, respectively, vs a survival of 50% and 0% for patients showing a TAI of more than 15 (P < 0.05). The 14 patients whose tumors showed enhancement in preoperative contrast-enhanced CT had 5- and 10-year survival rates of 57% and 14%, respectively, vs 100% and 83% for the 12 patients whose tumors presented no enhancement (P < 0.05). Moreover, 79% of the tumors showing contrast enhancement had a TAI greater than 15, while 92% of those exhibiting no enhancement had a TAI of less than 15. CONCLUSION: These findings indicate a relationship between enhancement on preoperative CT scan and endothelial surface area in oligodendrogliomas, and suggest that this enhancement and the TAI may be considered angiogenesis-related factors with similar prognostic significance in terms of survival.

Antigens, CD34↗

PubMedDate not supplied

A mutated polyoma virus enhancer which is active in undifferentiated embryonal carcinoma cells is not repressed by adenovirus-2 E1A products.

Enhancers stimulate transcription of several eukaryotic genes (for review see ref. 1). While some enhancers, like that of simian virus 40 (SV40), are active in a wide range of cell types, others are more cell-specific. For example, the polyoma virus (Py) enhancer is not active in undifferentiated embryonal carcinoma (EC) cells, such as F9 cells, while it is active in differentiated cells. In contrast, the SV40 enhancer is active in both undifferentiated and differentiated EC cells. One possible explanation for this difference is that the two viral enhancers interact with different positively or negatively acting transcription factors, a notion supported by in vitro experiments showing that the Py enhancer interacts with proteins that do not bind to the SV40 enhancer. Some viral and cellular enhancers, including the Py and SV40 enhancers, can be negatively regulated by the products of the E1A transcription unit of adenovirus-2. As it has been postulated that undifferentiated F9 cells contain an E1A-like activity, it is possible that the latter is responsible for the lack of activity of the Py enhancer in these cells. We show here that the E1A products do not repress a point mutant of the Py enhancer (Py ECF9.1; ref. 11 and references therein) that is active in undifferentiated F9 cells. This result is consistent with the idea that undifferentiated F9 cells contain a cellular repressor that blocks the Py enhancer and that this repressor has the same target sequence as the E1A proteins.

Adenovirus Early Proteins↗

PubMed2026

An encyclopedia of human enhancer-gene regulatory interactions.

Identifying transcriptional enhancers and their target genes is essential for understanding gene regulation and the effect of human genetic variation on disease1-6. Here we create and evaluate a resource of more than 92 million enhancer-gene regulatory interactions across 1,458 biosamples covering 369 cell types and tissues, by integrating predictive models, chromatin states, three-dimensional contacts and large-scale genetic perturbations generated by the ENCODE Consortium7. We first create a systematic benchmarking pipeline to compare predictive models, assembling a dataset of 10,356 element-gene pairs measured in CRISPR perturbation experiments, more than 30,000 fine-mapped expression quantitative trait loci and 569 fine-mapped genome-wide association study (GWAS) variants linked to a probable causal gene. Using this framework, we develop ENCODE-rE2G, a predictive model achieving state-of-the-art performance across several prediction tasks, demonstrating that iterative perturbations and supervised machine learning can build increasingly accurate predictive models of enhancer regulation. Using ENCODE-rE2G, we build an encyclopedia of enhancer-gene regulatory interactions in the human genome, revealing global properties of enhancer networks, identifying differences in regulatory complexity across genes and improving analyses linking noncoding variants to target genes and cell types for common complex diseases. By interpreting the model, we find that beyond enhancer activity and three-dimensional enhancer-promoter contacts, additional features that guide enhancer-promoter communication include promoter class and enhancer-enhancer synergy. These genome-wide maps of enhancer-gene regulatory interactions, benchmarking software, predictive models and insights about enhancer function provide a valuable resource for future studies of gene regulation and human genetics.

Humans↗

PubMed2002

[Analysis of vascularity in breast tumors--comparison of high frequency ultrasound and contrast-enhanced color harmonic imaging].

PURPOSE: To compare the ability of standard power Doppler and color harmonic imaging for visualising breast tumor vascularity using ultrasound probes of various frequencies, and to evaluate the influence on diagnostic accuracy using ultrasound contrast agent. MATERIALS AND METHODS: Twenty patients (x = 43.6 +/- 11.7 years) with suspected malignancy of the breast underwent power Doppler to evaluate vascularity and to offer a differential diagnosis of the lesion. Two criteria were used for differential diagnosis: The quantitative extent of vascularity ("percentage vessel area", PVA) and the qualitative assessment of vascular architecture. The following power Doppler modes were compared in every patient: Plain and enhanced (Levovist(R)) 9 MHz and 12 MHz standard power mode and enhanced 9 MHz color harmonic imaging-(CHI). RESULTS: The PVA increased from a mean of 2.2 +/- 2.9 % (9 MHz standard plain) via 4.8 +/- 4.1 % (12 MHz standard plain), 9.7 +/- 15.3 % (9 MHz standard enhanced), 17.4 +/- 20.0 % (9 MHz CHI enhanced) up to 19.4 +/- 14.8 % (12 MHz standard enhanced). The perceptibility of the vascular structure was best using the enhanced 12 MHz standard power mode, immediately followed by the enhanced 9 MHz CHI mode. The improved detection of vascular signal did not translate into improved diagnostic accuracy. The highest diagnostic accuracy (95 %) was obtained using the enhanced 9 MHz CHI mode (criterion "PVA") and the enhanced 9 MHz standard power mode (criterion "vascular structure"), whereas the 12 MHz probes delivered insufficient diagnostic accuracy and very low specificity. CONCLUSION: Best quantitative and qualitative visualisation of the tumor vascularity was achieved using the enhanced 12 MHz standard power mode. Nevertheless, the highest diagnostic accuracy was obtained using enhanced 9 MHz standard power Doppler and enhanced 9 MHz color harmonic imaging. The visualisation of tumor vascularity and, partially, the diagnostic accuracy are improved significantly by color harmonic imaging without changing the probe frequently.

Adult↗

PubMed1995

Sequences located 3' to the breakpoint of the hereditary persistence of fetal hemoglobin-3 deletion exhibit enhancer activity and can modify the developmental expression of the human fetal A gamma-globin gene in transgenic mice.

Expression of fetal gamma-globin genes in individuals with the deletion forms of hereditary persistence of fetal hemoglobin (HPFH) has been attributed either to enhancement by 3' regulatory elements juxtaposed to gamma-globin genes or to deletion of gamma-gene silencers normally residing within the beta-globin gene cluster. In the present study, we tested the hypothesis of imported enhancers downstream of beta-globin gene using the HPFH-3 deletion as a model. The abnormal bridging fragment of 13.6 kilobases (kb) containing the A gamma-gene with its flanking sequences and 6.2 kb of the juxtaposed region was microinjected into fertilized mouse eggs. Twelve transgenic mice positive for the fragment were generated. Samples from 11.5-day yolk sacs, 16-day fetal liver, and adult blood were analyzed for A gamma-mRNA using RNase protection assays. Three mice lacked A gamma expression in the yolk sac indicating non-optimal integration site. Four expressed A gamma-mRNA at the embryonic stage only, while two expressed A gamma-mRNA in both embryonic and fetal liver erythroid cells. Since the A gamma-gene with its normal flanking sequences and in the absence of the locus control region is expressed only in embryonic cells of transgenic mice, these data suggest that the juxtaposed sequences have altered the developmental specificity of the fetal gamma-globin gene. These sequences were further tested for the presence of an enhancer element, by their ability to activate a fusion reporter gene consisting of the CAT gene linked to the gamma-globin gene promoter, in erythroid (K562) and non-erythroid (HeLa) cells. A 0.7-kb region located immediately 3' to the breakpoint, enhanced chloramphenicol acetyltransferase activity by 3-fold in erythroid cells. The enhancer also activated the embryonic epsilon-globin gene promoter by 2-fold but not the adult beta- or delta-globin gene promoters. The enhancer represents a region of previously known complex tandem repeats; in this study we have completed the sequencing of the region encompassing the 0.7-kb enhancer element. Multiple areas of the enhancer region exhibit homology to the core element of the simian virus 40 enhancer and to the sequences of the human 3' A gamma- and the chicken 3' beta-globin enhancers. A consensus binding site for the erythroid specific GATA-1 transcription factor and seven consensus sites for the ubiquitous CP1 transcription factor are also included within the enhancer. These data suggest that these sequences located immediately 3' to the breakpoint of the HPFH-3 deletion, exhibit both the structure and the function of an enhancer, and can modify the developmental specificity of the fetal gamma-globin genes, resulting in their continued expression during adult life.

Animals↗

PubMed1996

Metazoan rDNA enhancer acts by making more genes transcriptionally active.

Enhancers could, in principle, function by increasing the rate of reinitiation on individual adjacent active promoters or by increasing the probability that an adjacent promoter is activated for transcription. We have addressed this issue for the repetitive metazoan rDNA enhancer by microinjecting Xenopus oocytes with enhancer-less and enhancer-bearing genes and determining by EM the frequency that each gene type forms active transcription units and their transcript density. We use conditions where transcription requires the normal rDNA promoter and is stimulated 30-50-fold by the enhancer. (In contrast, at saturating template conditions as used in previous EM studies, an aberrant mode of transcription is activated that is not affected by the rDNA enhancer or by the generally recognized rDNA promoter). The active transcription units on enhancer-less genes are found to be as densely packed with nascent transcripts and polymerases as those on enhancer-bearing genes and on the endogenous rRNA genes. Significantly, the enhancer-bearing genes are approximately 30-50-fold more likely to form such active transcription units than enhancer-less genes, consistent with their amounts of transcript. Complementary studies confirm that the enhancer does not affect elongation rate, the stability of the transcription complex, or transcript half-life. These data demonstrate that the repetitive metazoan rDNA enhancer causes more genes to be actively transcribed and does not alter the reinitiation rate on individual active genes.

Animals↗

PubMed1988

Do transcriptional enhancers also augment DNA replication?

Enhancers are DNA elements that augment transcription in cis, independent of distance and orientation. Evidence such as hormone dependent neoplastic cell growth and the stimulation of viral replication by sequences present in enhancers suggests that enhancers may also directly affect DNA replication. We tested this hypothesis in recombinant plasmids by asking whether sequences that stimulated DNA replication shared the properties of transcriptional enhancers. The homologous simian virus 40 (SV40) core enhancer was ligated either adjacent to or 2.6 kb distant from the SV40 minimal origin of replication (ori) in both orientations. Plasmids were transfected into T antigen producing COS cells, and episomal DNA was harvested for quantitation of replication. Replication could be assessed either as accumulation of fmol of MboI sensitive progeny DNA, or as a transition in % DNA in replicated (MboI sensitive) versus unreplicated (DpnI sensitive) form. The two measures were related exponentially (r = 0.86). The SV40 enhancer augmented replication 1.5-10 fold. The effect was time dependent, distance dependent (only the adjacent enhancer locus stimulated replication), partially orientation dependent, and enhancer copy number independent. Phorbol ester did not affect replication. The heterologous glucocorticoid enhancer had no effect on replication. We conclude that the SV40 enhancer's cis-effect on replication seems to be dependent on the close proximity to the replication origin of specific homologous sequences within the enhancer, rather than a typical enhancer-like effect.

Animals↗

PubMed2002

Gadolinium diethylenetriaminepentaacetic acid enhancement in magnetic resonance imaging in relation to symptoms and signs among sciatic patients: a cross-sectional study.

STUDY DESIGN: A cross-sectional descriptive study. OBJECTIVES: Gadolinium enhancement in lumbar magnetic resonance imaging is not used routinely. The current study explored the possible intercorrelations of enhancement patterns with clinical symptoms and signs. SUMMARY OF BACKGROUND DATA: Rim enhancement has been reported to occur in the periphery of disc herniations, and it is thought to represent neovascularization. To the authors' knowledge, the significance of the enhancement in relation to clinical symptoms has not been studied. METHODS: Magnetic resonance imaging of the lumbar spine with intravenous gadolinium diethylenetriaminepentaacetic acid was performed in each patient. Various contrast enhancement parameters and volume of herniation were evaluated, and their correlations with clinical signs and symptoms (straight leg raising, motor defect, Achilles reflex, leg and back pain, disability) were analyzed. RESULTS: The extent of rim enhancement correlated highly significantly with the degree of disc displacement, being most pronounced in the case of sequesters. The duration of sciatic symptoms correlated negatively with enhancement. The clinical symptoms did not correlate significantly with the different enhancement parameters or disc herniation volume. Straight leg raising correlated only slightly with the extent of rim enhancement (P = 0.04) when bulges were excluded. Achilles reflex abnormality correlated significantly with all enhancement parameters for lesions at L5-S1. In the final stepwise logistic regression model, contrast enhancement extent correlated most significantly with abnormal Achilles reflex (P = 0.0002). CONCLUSIONS: Although rim enhancement of disc herniation is thought to represent a beneficial phagocytotic phenomenon, it may also have a harmful effect on the adjacent nerve root.

Achilles Tendon↗