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 1,513 records · Page 84Linked to original sources

PubMed1991

CT of acute pancreatitis: correlation between lack of contrast enhancement and pancreatic necrosis.

This study was performed to determine if a correlation exists between pancreatic parenchymal enhancement or lack thereof on contrast-enhanced CT and surgical evidence of pancreatic necrosis. Accurate CT assessment of pancreatic vascular perfusion would be helpful in preoperative planning before pancreatic debridement and necrosectomy. The CT scans and medical records were blindly and retrospectively reviewed in 13 patients with the operative diagnosis of pancreatic necrosis. In all cases, CT examinations preceded surgery within 72 hr. Surgical and pathologic findings served as the gold standards for the diagnosis of pancreatic necrosis. Seven (54%) of 13 patients had a region or regions of parenchymal necrosis within the head, body, and/or tail of the pancreas seen during surgery. All seven of these patients had no pancreatic enhancement on CT in at least one region of the pancreas (CT sensitivity = 100%). In four of the seven, two regions were found to be necrotic at surgery, but only one of the two segments did not enhance on CT scans. In three of the seven patients, lack of contrast enhancement on CT (no enhancement of the pancreatic head and body in two patients and throughout the gland in another) correlated with necrosis in the same regions at surgery. The remaining six (46%) patients, who had peripancreatic or small, focal, and/or superficial areas of pancreatic necrosis at surgery, had normal pancreatic enhancement on CT. Our results show that regions of pancreatic necrosis found surgically correlate with lack of enhancement of pancreatic parenchyma on CT. Peripancreatic necrosis and minor areas of focal or superficial parenchymal necrosis were not detected on CT.

Acute Disease↗

PubMed1992

Gadopentetate dimeglumine-enhanced MR imaging of the postoperative lumbar spine: comparison of fat-suppressed and conventional T1-weighted images.

OBJECTIVE: Gadopentetate dimeglumine-enhanced T1-weighted MR imaging has been used to distinguish epidural fibrosis from recurrent disk herniation in the postoperative lumbar spine. Potential interpretative difficulties relate to detection of subtle contrast enhancement and distinction of enhanced tissue from surrounding epidural fat. The objective of this study was to evaluate the utility of fat-suppressed T1-weighted imaging in improving the depiction of postoperative abnormalities. SUBJECTS AND METHODS: Forty-one patients with recurrent signs and symptoms after previous laminectomy and diskectomy were examined with conventional and fat-suppressed T1-weighted imaging before and after IV administration of gadopentetate dimeglumine. MR images were analyzed for the presence or absence of an epidural soft-tissue mass located anterior and/or lateral to the thecal sac. When such masses were identified, their contrast enhancement behavior was characterized according to the volume, intensity, and pattern of enhancement. Epidural fibrosis was diagnosed by using established MR imaging criteria. In patients with evidence of recurrent disk herniation, diagnosis was based on surgery in six patients and on MR imaging findings in the remainder. RESULTS: Soft-tissue masses were present at 32 of the 43 levels operated on, representing epidural fibrosis (n = 21) or disk herniation (n = 11). Fat suppression improved depiction of contrast enhancement associated with sites of epidural fibrosis. The extent, intensity, and homogeneity of enhancement was greater with fat suppression than with conventional imaging, although the ability to distinguish epidural fibrosis from recurrent disk herniation was not improved. CONCLUSION: Use of the fat-suppression technique results in increased relative intensity and homogeneity of contrast enhancement associated with sites of epidural fibrosis. However, it does not result in significant improvement in the ability to differentiate fibrotic tissue from recurrent disk herniation. Fat suppression does not appear to be indicated for routine use in imaging of the postoperative lumbar spine, but may be useful as a problem-solving tool in selected patients.

Adult↗

PubMed2000

Small renal masses: assessment of lesion characterization and vascularity on dynamic contrast-enhanced MR imaging with fat suppression.

OBJECTIVE: The aim of our study was to characterize renal lesions equal to or smaller than 3.0 cm using dynamic contrast-enhanced MR imaging with fat suppression by means of quantitative analysis of signal intensity. MATERIALS AND METHODS: We retrospectively reviewed the MR imaging examinations of 35 patients (20 with renal cell carcinoma, eight with angiomyolipoma, and seven with complicated cysts) who were studied with spin-echo and dynamic fat-suppressed gradient-recalled echo MR sequences, before and after the administration of gadopentetate dimeglumine. Every 30 sec after contrast injection, we measured the lesion percentage of enhancement and the ratio of contrast (lesion-renal cortex signal intensity difference) to noise. RESULTS: Ten renal cell carcinomas were classified as hypervascular (enhancement greater than that of renal cortex) and 10 as hypovascular. The percentage of enhancement of hypervascular carcinomas was similar to that of renal cortex until 150 sec and greater in the late sequences (180-210 sec, p < 0.01). Hypovascular carcinomas had a lower percentage of enhancement than hypervascular carcinomas (60-210 sec, p < 0.005). Angiomyolipomas, after an early enhancement peak, showed values similar to those of hypovascular carcinomas. Complicated cysts had very low enhancement (p < 0.001). The baseline contrast-to-noise ratio was negative for all lesions (hypointensity with respect to renal cortex). After gadolinium injection, the contrast-to-noise ratio of hypervascular carcinomas rose, becoming positive after 150 sec. Until 60 sec, the contrast-to-noise ratio of hypovascular carcinomas declined slightly, whereas that of angiomyolipomas and cysts fell sharply; then the three curves remained stable (60-210 sec, p < 0.05 for all matches except angiomyolipomas versus cysts). CONCLUSION: Quantitative analysis of signal intensity variations during dynamic contrast-enhanced MR imaging with fat suppression can be useful in the characterization of small renal lesions.

Adult↗

PubMed1998

A novel type of regulatory element is required for promoter-specific activity of the PDGF-B intronic enhancer region.

We have previously described a non-classical, promoter-specific enhancer for the human Platelet-Derived Growth Factor B (PDGF-B) gene. In JEG-3 choriocarcinoma cells the activity of the enhancer depends upon co-operation with a sequence (the Enhancer-Dependent cis Co-activator "EDC" element) within the promoter. The PDGF-B enhancer fails to activate heterologous promoters, indicating that promoter-specificity depends on an element within the enhancer that can recognise a target sequence within the promoter. Here we identify a sequence within the enhancer of the PDGF-B gene which directs activation of the PDGF-B promoter by distal cis-acting elements. This specifies the wild-type PDGF-B promoter as the target for the enhancer and has been designated the EDC specificity element (EDCse). The cell-type specific nature of this interaction is extended by the observation that the EDCse is also dispensable for enhancer activity in breast-cancer cells (ZR-75). Concomitant to this observation, JEG-3 and ZR-75 cells differ in the binding of nuclear factors to the EDCse. We discuss the relevance of the EDC/EDCse system in regulation of gene expression.

5' Untranslated Regions↗

PubMedDate not supplied

The use of contrast-enhanced color Doppler ultrasound in the differentiation of retinal detachment from vitreous membrane.

OBJECTIVE: To compare the clinical utility of contrast-enhanced color Doppler US in the differentiation of retinal detachment (RD) from vitreous membrane (VM) with that of various conventional US modalities, and to analyze the enhancement patterns in cases showing an enhancement effect. MATERIALS AND METHODS: In 32 eyes examined over a recent two-year period, RD (n=14) and VM (n=18) were confirmed by surgery (n=28) or clinical follow-up (n=4). In all cases, gray-scale, color Doppler, and power Doppler US were performed prior to contrast injection, and after the intravenous injection of Levovist (Schering, Berlin) by hand for 30 seconds at a dose of 2.5 g and a concentration of 300 mg/mL via an antecubital vein, contrast-enhanced color Doppler US was performed. At Doppler US, the diagnostic criterion for RD and VM was whether or not color signals were visualized in membranous structures. RESULTS: Diagnostic accuracy was 78% at gray-scale US, 81% at color Doppler US, 59% at power Doppler US, and 97% at contrast-enhanced color Doppler US. The sensitivity of color Doppler US to color signals in RD increased from 57% to 93% after contrast enhancement. The enhancement patterns observed were signal accentuation (n=3), signal extension (n=2), signal addition (n=3), and new signal visualization (n=5). CONCLUSION: Contrast-enhanced color Doppler US was the most accurate US modality for differentiating RD from VM, showing a significantly increased signal detection rate in RD.

Adolescent↗

PubMed2000

Test-bolus injection for optimization of arterial phase imaging during contrast-enhanced hepatic MR imaging.

Contrast enhancement during the dynamic MR imaging is important for the detection and characterization of focal liver lesions. The purpose of this study was to determine whether or not a timing examination with a injection of a 1.0-mL bolus of gadopentetate dimeglumine into the antecubital vein followed by rapid dynamic scanning and measurement of signal intensity of the aorta could help to obtain proper arterial-dominant phase images for the characterization of focal hepatic lesions during subsequent multiphase dynamic MR imaging. The imaging delay to acquisition of the first gadolinium-enhanced image for multiphase dynamic MR imaging was set to equal the time to peak aortic enhancement during the test examination. The first contrast-enhanced images of 80 patients with 160 focal liver lesions (hepatocellular carcinoma, n = 79; cavernous hemangioma, n = 51; metastatic tumor, n = 30) were then retrospectively reviewed. Peak aortic enhancement occurred between 10 and 28 seconds (mean, 16.5 seconds +/- 3.1) after starting the infusion of contrast material in 80 patients during the test-examination. Depending on the findings of intrahepatic vascular enhancement on the full-scale dynamic images, hepatic arterial phase (n = 11, 14%) or sinusoid phase (n = 65, 81%) imaging was obtained during the first gadolinium-enhanced acquisition in 76 (95%) of 80 patients. Three different lesions were well characterized and easily distinguished from each other (p < .0001) on the first-phase images depending on their enhancement pattern. In the majority of patients, timing examination with test-bolus injection was helpful in obtaining qualified images for the characterization of various focal lesions.

Adult↗

PubMed2000

Regulation of germline promoters by the two human Ig heavy chain 3' alpha enhancers.

The human IgH 3' enhancers, located downstream of each of the two Calpha genes, modulate germline (GL) transcription of the IgH genes by influencing the activity of promoter-enhancer complexes upstream of the switch and intervening (I) regions. The regulation of GL alpha1 and alpha2 promoters by different human 3' enhancer fragments was investigated in cell lines representing various developmental stages. Both alpha1HS1,2 and alpha2HS1,2 fragments show equally strong enhancer activity on the GL alpha1 and alpha2 promoters in both orientations when transiently transfected into a number of mature B cell line (DG75, CL-01, and HS Sultan). However, there is no activity in a human pre-B cell line (NALM-6) nor a human T cell line (Jurkat). HS3 shows no enhancer activity by itself in any of the cell lines, whereas a modest effect is noted using HS4 in the three mature B cell lines. However, the combination of the alpha2HS3-HS1,2-HS4 fragments, which together form a potential locus control region, displays a markedly stronger enhancer activity than the individual fragments with a differential effect on the alpha1 and alpha2 promoters as compared with the gamma3 promoter. Our results suggest that the human GL alpha promoter may be regulated by two independent pathways. One pathway is induced by TGF-beta1 which directs IgA isotype switch through activation of the GL alpha promoter and no TGF-beta1-responsive elements are present in the different 3' enhancer fragments. The other route is through the human 3' enhancer regions that cis-up-regulate the GL alpha promoter activity in mature B cells.

3' Untranslated Regions↗

PubMed2000

A single 3' alpha hs1,2 enhancer in the rabbit IgH locus.

Multiple cis-acting elements including the intronic enhancer and the 3'alpha enhancer (3'alphaE) regulate expression of the Ig heavy chain genes during B cell development. A 3'alphaE is composed of DNase I-hypersensitive sites, hs1,2, hs3a,b, and hs4, found 3' of the murine Calpha gene as well as 3' of both human Calpha genes, Calpha1 and Calpha2. Rabbits have 13 Calpha genes, and we tested whether a 3'alphaE is associated with each of these genes. To identify 3'alphaE regions we developed a rabbit hs1,2 probe and used this to search for enhancer homologues of human hs1,2 in a genomic fosmid library. We identified a single hs1,2 fragment 8-kb downstream of Calpha13, the presumed 3'-most Calpha gene. We also identified and partially sequenced a new Calpha gene, Calpha14, located 6 kb upstream of Calpha13. Genomic Southern blot analysis confirmed that the rabbit genome contains only one hs1,2 enhancer region. We tested the enhancer activity of the hs1,2 with the SV40, V(H), and Ialpha promoters using the luciferase reporter gene in transient transfection assays and found that it significantly enhanced the activity of SV40 and V(H) promoters and slightly enhanced an Ialpha promoter. We conclude that the rabbit has a single hs1,2 enhancer that resides at the 3' end of the IgH gene cluster and may constitute one of the cis-elements regulating the expression of IgH genes.

3' Untranslated Regions↗

PubMed2002

Characterization of chromatin structure and enhancer elements for murine recombination activating gene-2.

Recombination-activating genes (RAGs) play a critical role in V(D)J recombination machinery and their expression is specifically regulated during lymphocyte ontogeny. To elucidate the molecular mechanisms regulating murine RAG-2 expression, we examined a chromatin structure of 25-kb DNA segment adjacent to murine RAG-2 by analyzing DNase I hypersensitive (HS) sites. In a RAG-2-expressing murine pre-B cell line, three lymphoid cell-specific HS sites (HS1, HS2, and HS3) were identified. Among these HS sites, one HS site (HS3) that locates in the RAG-2 promoter was associated only with RAG-2-expressing cell lines. Using the transient enhanced green fluorescence protein reporter gene assays, we identified two enhancer elements in the 5'-upstream region of RAG-2 that corresponded to HS1 and HS2. One of the enhancer elements (D3) exhibited enhancer activity only in the lymphoid cell lines. Analysis of the transgenic mice carrying the enhanced green fluorescence protein-reporter gene linked with D3 revealed that D3 activated the reporter gene-expression in the primary lymphoid tissues, but not in the secondary lymphoid tissues or nonlymphoid tissues. D3 was active in CD4(-)CD8(-), but not in CD4(+)CD8(+) or CD4(+)CD8(-) thymocytes in the thymus, and also active in B220(+)IgM(-), but not in B220(+)IgM(+), cells in the bone marrow. Finally, our data suggested that C/EBP may bind to the D3 enhancer and function as one of the transcription factor(s) responsible for the enhancer activity. These results show that the tissue- and stage-specific expression of murine RAG-2 is regulated by alteration of the chromatin structure as well as cis-regulatory enhancer elements.

3T3 Cells↗

PubMed2002

The human IL-3 locus is regulated cooperatively by two NFAT-dependent enhancers that have distinct tissue-specific activities.

The human IL-3 gene is expressed by activated T cells, mast cells, and eosinophils. We previously identified an enhancer 14 kb upstream of the IL-3 gene, but this element only functioned in a subset of T cells and not in mast cells. To identify additional mechanisms governing IL-3 gene expression, we mapped DNase I hypersensitive (DH) sites and evolutionarily conserved DNA sequences in the IL-3 locus. The most conserved sequence lies 4.5 kb upstream of the IL-3 gene and it encompassed an inducible cyclosporin A-sensitive DH site. A 245-bp fragment spanning this DH site functioned as a cyclosporin A-sensitive enhancer, and was induced by calcium and kinase signaling pathways in both T cells and mast cells via an array of three NFAT sites. The enhancer also encompassed AML1, AP-1, and Sp1 binding sites that potentially mediate function in both T and myeloid lineage cells, but these sites were not required for in vitro enhancer function in T cells. In stably transfected T cells, the -4.5-kb enhancer cooperated with the -14-kb enhancer to activate the IL-3 promoter. Hence, the IL-3 gene is regulated by two enhancers that have distinct but overlapping tissue specificities. We also identified a prominent constitutive DH site at -4.1 kb in T cells, mast cells, and CD34(+) myeloid cells. This element lacked in vitro enhancer function, but may have a developmental role because it appears to be the first DH site to exist upstream of the IL-3 gene during hemopoietic development before IL-3 expression.

Animals↗

PubMed2002

[Evaluation of transrectal power-Doppler ultrasonography and effect of contrast-enhancement for detecting prostate cancer].

PURPOSE: There are many reports about the usefulness of transrectal power-Doppler ultrasonography (PDUS) for detecting prostate cancer because of the high microvessel density in cancerous tissue in the prostate. The purpose of this study was to assess the role of PDUS and contrast-enhanced transrectal power-Doppler ultrasonography (enhanced PDUS) in the identification of prostate cancer. MATERIALS AND METHODS: One hundred forty-two cases (90 cases without enhancement, 52 cases with enhancement) of suspected prostate cancer found with digital rectal examination (DRE), transrectal ultrasound (TRUS) abnormal or prostate specific antigen (PSA) elevation were evaluated by PDUS and enhanced PDUS. RESULTS: Forty-three (30.3%) cases of cancer were detected, and there was a significant difference (p < 0.05) between PDUS group (22 cases, 24.4%) and enhanced PDUS (21 cases, 40.0%). However, there were no significant statistical results about the usefulness of enhancement to detect prostate cancer although imaging was clear with contrast agent. The results of statistical analysis of PDUS use were almost the same as for PSA of more than 10.1 ng/ml. Combination with PDUS was very helpful to detect prostate cancers. The positive predictive value of the combination with DRE, TRUS and PSA improved from 68.0% to 81.0% with the addition of PDUS. In particular, cancer was revealed frequently (65.8%) in peripheral hypoechoic lesions on gray-scale TRUS with hypervascular areas on PDUS. CONCLUSIONS: We conclude that enhancement with contrast agent is not especially useful in the identification of prostate cancer although imaging was clear with contrast agent. However, PDUS is useful especially for hypoechoic peripheral areas. It is suggested that we should add PDUS to DRE, TRUS and PSA examinations.

Aged↗

PubMed2002

Contrast-enhanced Doppler perfusion index: clinical and experimental evaluation.

OBJECTIVE: To assess the potential of the power Doppler signal intensity rate of enhancement due to contrast agent wash-in for assessment of hepatic hemodynamics. METHODS: With the use of standardized settings, power Doppler sonography was performed before and after administration of a contrast agent. Video-recorded examinations were digitized for offline analysis on a personal computer. The temporal changes of the power Doppler signal intensity were quantified to provide contrast agent wash-in curves. The contrast-enhanced Doppler perfusion index was defined by the ratio of the wash-in gradient of the hepatic artery and portal vein as contrast-enhanced Doppler perfusion index = hepatic artery gradient/(hepatic artery gradient + portal vein gradient). The contrast-enhanced Doppler perfusion index was evaluated at 4 contrast agent doses in each of 14 patients with liver metastases and 3 patients with hemangiomas. An in vitro flow model was used to determine the relationships between the power Doppler rate of enhancement and flow in vessels of 4, 8, and 12 mm in diameter. RESULTS: In vivo, there was a significantly higher (P < .0001) mean contrast enhanced Doppler perfusion index in patients with liver metastases (mean, 0.59; 95% confidence interval, 0.54-0.63), compared with patients with hemangiomas (mean, 0.33; 95% confidence interval, 0.24-0.41). The corresponding coefficients of variations were 25% for patients with liver metastases and 31% for patients with hemangiomas. In vitro, the power Doppler rate of enhancement was proportional to flow speed and independent of vessel diameter. CONCLUSIONS: Measurement of the contrast-enhanced Doppler perfusion index may have potential in assessment of hepatic hemodynamics and focal liver disease.

Blood Flow Velocity↗

PubMed2002

Contrast-enhanced sonography of small pancreatic mass lesions.

OBJECTIVE: To evaluate the usefulness of contrast-enhanced wideband harmonic gray scale sonography in assessing the vascularity of small pancreatic mass lesions. METHODS: Twenty-five patients with 25 pancreatic mass lesions (20 pancreatic carcinomas, 1 islet cell tumor, 1 malignant lymphoma, and 3 focal inflammatory pancreatic masses due to chronic pancreatitis) were examined. All patients held their breath for 20 to 50 seconds after injection of a contrast agent while the vascularity of the tumor was observed on contrast-enhanced wideband harmonic gray scale sonography (early phase). We then monitored the tumor enhancement 60 to 120 seconds after the injection while the patients held their breath for a few seconds (delayed phase). RESULTS: All 20 (100%) of the pancreatic carcinomas showed no contrast enhancement in the early phase. Fifteen (75%) of the 20 pancreatic carcinomas also showed no contrast enhancement in the delayed phase. The remaining 5 (25%) pancreatic carcinomas showed mild enhancement in the peripheral regions of the tumor in the delayed phase. The other pancreatic masses showed mild or pronounced enhancement throughout the entire lesions in both the early and delayed phases. CONCLUSIONS: Contrast-enhanced wideband harmonic gray scale sonography is a useful tool for differentiating pancreatic carcinomas from focal inflammatory pancreatic masses or hypervascular pancreatic tumors.

Aged↗

PubMed1999

Contrast enhancement of intracranial lesions: conventional T1-weighted spin-echo versus fast spin-echo MR imaging techniques.

BACKGROUND AND PURPOSE: The T1-weighted fast spin-echo (T1-FSE) MR imaging sequence is not used routinely, since the speed advantage is not as dramatic as it is in T2-weighted imaging. We evaluated the T1-FSE sequence to determine whether this technique can replace the conventional T1-weighted spin-echo (T1-SE) sequence for routine contrast-enhanced imaging. METHODS: Sixty-nine patients with intracranial enhancing lesions underwent both T1-SE and T1-FSE sequences in a random order after administration of contrast agent. Acquisition time was 55 seconds for the T1-FSE sequence and 2 minutes 38 seconds for the SE sequence. The conspicuity of enhancing lesions, peritumoral edema, and gray-to-white matter contrast as well as motion and flow artifacts were analyzed. Signal-to-noise ratios of enhancing lesions, gray matter, and white matter as well as contrast-to-noise ratios (CNRs) of enhancing lesions, with gray matter with white matter as the standard, were calculated. RESULTS: The conspicuity of enhancing lesions was better on T1-FSE sequences than on T1-SE sequences, although the difference in the CNRs of enhancing lesions did not reach significance. Images obtained with the T1-FSE sequence showed less flow and motion artifacts than did those obtained with the T1-SE sequence. The conspicuity of peritumoral edema and gray-to-white matter contrast was lower on the T1-FSE images than on the T1-SE images. CONCLUSION: The T1-FSE sequence reduces imaging time and has the potential to replace the conventional T1-SE sequence for the evaluation of enhancing lesions in the brain when time is a consideration.

Adolescent↗

PubMed2003

Assessment of metastatic cervical adenopathy using dynamic contrast-enhanced MR imaging.

BACKGROUND AND PURPOSE: Morphologic assessment by conventional imaging methods of lymph node metastases in patients with squamous cell carcinoma of the head and neck is, at best, insensitive. Doppler sonography has shown that lymph node metastases exhibit alterations in the number of vessels and blood flow. We assessed the ability of dynamic contrast-enhanced MR imaging to differentiate normal from diseased nodes in this patient population. METHODS: Twenty-one patients with newly diagnosed squamous cell carcinoma and no previous treatment were studied with the use of a head and neck phased array surface coil. Anatomic imaging included high resolution T1-weighted, fat-saturated fast spin-echo T2-weighted, and contrast-enhanced T1-weighted imaging (0.99-1.32 mm(3) voxels). The dynamic contrast-enhanced MR imaging was performed by using a 2D fast spoiled gradient recalled sequence with single dose bolus injection of contrast agent. Calculated values included time to peak, peak enhancement, maximum slope, and washout slope for the enhancement. All patients underwent neck dissection as part of their indicated treatment, and imaging results were correlated with pathologic findings. RESULTS: Dynamic contrast-enhanced MR imaging and pathology comparisons were obtained for 68 nodes. There was significantly longer time to peak (P <.001), lower peak enhancement (P <.05), lower maximum slope (P <.01), and slower washout slope (P <.05) in the tumor-involved nodes compared with the normal nodes. CONCLUSION: Analysis of dynamic contrast-enhanced MR imaging can differentiate normal from diseased lymph nodes in patients with squamous cell carcinoma of the head and neck.

Adult↗

PubMed1992

Immunoglobulin kappa gene enhancers synergistically activate gene expression but independently determine chromatin structure.

Previous studies have located transcriptional enhancer elements within both the intron and 3'-region of the mouse kappa immunoglobulin gene. Here we address the role of these two enhancers in specifying gene activity and specific chromatin structures. MOPC41 kappa gene constructs, either intact or containing deletions of one or both enhancers, were introduced into S194 mouse plasmacytoma cells for transient and stable expression studies. Transient expression assays revealed that the basal level expression exhibited by enhancerless constructs was activated 100-200-fold by the two enhancers together in a synergistic fashion. A similar trend was observed when both enhancers were present in stably integrated constructs, although the synergy was less pronounced. Analysis of DNase I hypersensitive sites in the chromatin revealed that stably integrated constructs established hypersensitive sites about the enhancer sequences. These sites demonstrated the same nuclease susceptibility as those associated with the endogenous gene(s), and their establishment was independent of the presence of the other enhancer. Thus, although both enhancers are required for maximal gene expression, the elements act independently in determining specific chromatin structures.

Animals↗

PubMed2004

[Visualization of brain perfusion by contrast-enhanced ultrasonography: preliminary study in rabbits].

PURPOSE: We evaluated the usefulness of an agent for contrast-enhanced ultrasonography (galactose parmitine acid: Levovist) in visualizing brain perfusion in rabbits. MATERIALS AND METHODS: Six rabbits were involved in this study. A hole in the skull bone was made under anesthesia and used as an acoustic window. An ischemic model (3 of 6 rabbits) was made by surgically occluding the M1 portion of the middle cerebral artery. Power Doppler images (PDI) and B-mode Harmonic images (HI) before and after intravenous injections of the contrast medium (150 mg/body) were obtained using the HDI5000 (ATL) equipped with a linear-type 5-12 Mhz probe. RESULTS: Smaller arteries were clearly visualized by contrast-enhanced PDI. However, enhancement of brain parenchyma was not clear on PDI. Enhancement of brain parenchyma was observed clearly on contrast-enhanced HI. Enhancement was strong during the first pass and then diminished quickly. In ischemic models, hypoperfusion in the right cerebral hemisphere (the occluded side) were clearly observed on contrast-enhanced HI. CONCLUSION: Brain perfusion in rabbits can be observed on contrast-enhanced Harmonic ultrasonographic imaging. It is suggested to be useful for human clinical cases, including hypoxic ischemic brain injury in infants.

Animals↗

PubMed2005

[Melatonin inhibits the proliferation of pituitary prolactin-secreting tumor by suppressing the enhancer elements mutation of PRL gene in the rat].

In order to investigate the molecular mechanisms of the inhibition of the proliferation of 17-beta-estradiol (E(2))-induced pituitary prolactin-secreting tumor (prolactinoma) by melatonin (MLT) in the rat, we examined the inhibitory effects of MLT on the proliferation of E(2)-induced prolactinoma of the rat and the suppressing effects of MLT on the enhancer elements mutation of PRL gene in vivo and in vitro. The results showed that the weights of prolactinomas in MLT groups, in which 0.25 mg or 0.50 mg per day per rat of MLT was administered subcutaneously at 18:00, were decreased significantly. Out of the dosage of MLT, such as 0.05, 1.00 mg and 2.00 mg per day per rat, the antitumor action of MLT is less or disappointing. Polymerase chain reaction (PCR) and DNA sequencing showed five mutations in the enhancer elements of PRL gene in prolactinoma, such as -1885 point mutation (C --> G), -1857 - -1855 substitution (ACA --> G), -1792 - -1791 insertion G, -1383 - -1382 insertion (GGTGTGTG), -1265 - -1250 deletion (GTGTGTGTGTGTGTGT). Excluding of -1885 point mutation (C --> G), the mutation in the prolactinoma treated with 0.25 mg per day per rat MLT was decreased, such as -1792 - -1791 without insertion of G, -1856 - -1855 deletion AC, -1385 - -1384 deletion TG, -1250 - -1253 deletion GTGT. Firefly luciferase reporter gene systems showed that the luminosity of enhancer elements-luciferase reporter fusion gene in normal pituitary, prolactinoma treated without or with 0.25 mg per day per rat MLT were (13448.17+/-3012.74), (161831.67+/-60996.01), and (10212.17+/-634.71) OD units. Compared with the normal pituitary, the activity of PRL gene enhancer elements in prolactinoma was increased by 11 times (P<0.001). Compared with the prolactinoma, the activity of PRL gene enhancer elements in prolactinoma treated with MLT was decreased by 93.69% (P<0.001). Analysis of the space structure of PRL gene enhancer elements showed that the bending index in prolactinoma was higher than that in prolactinoma treated with MLT, which was higher than that in the normal pituitary. These results demonstrate that one of the important molecular mechanisms of MLT inhibiting the proliferation of prolactinoma is related to the reduction of enhancer elements mutation of PRL gene. These data also suggest that MLT-induced attenuation of enhancer elements mutation of PRL gene is involved in decreasing the bending index and attenuating the higher expression of PRL gene.

Animals↗