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PubMed2000

Breast masses with peripheral rim enhancement on dynamic contrast-enhanced MR images: correlation of MR findings with histologic features and expression of growth factors.

PURPOSE: To investigate the histologic bases of rim enhancement of breast masses demonstrated on dynamic contrast material-enhanced magnetic resonance (MR) images. MATERIALS AND METHODS: Dynamic MR images of breast lesions (invasive carcinoma, n = 29; other, n = 6) in 35 women were reviewed. In each patient, subtraction images of the dynamic contrast-enhanced study were obtained, and early and delayed rim enhancement and delayed internal enhancement were evaluated. The MR findings were correlated with the ratio of microvessel density of the peripheral to the central portion of the lesion, fibrosis, and other histologic features, including expression of vascular endothelial growth factor (VEGF) and transforming growth factor ss1. RESULTS: Early rim enhancement was observed in 29% and delayed rim enhancement was noted in 60% of all patients. Small cancer nests, a high ratio of peripheral-to-central microvessel density, peripheral VEGF expression, and a low ratio of peripheral-to-central fibrosis were correlated with early rim enhancement. Delayed rim enhancement was correlated with a high degree of fibrosis and inflammatory changes. Delayed internal enhancement was correlated with a high degree of fibrosis. CONCLUSION: Rim enhancement of breast lesions at MR imaging is due to a combination of angiogenesis, distribution and degree of fibrosis, expression pattern of VEGF, and various histologic features.

Adenocarcinoma, Mucinous↗

PubMed2004

Comparison of superparamagnetic iron oxide-enhanced and gadobenate dimeglumine-enhanced dynamic MRI for detection of small hepatocellular carcinomas.

OBJECTIVE: The purpose of this study was to compare superparamagnetic iron oxide (SPIO)-enhanced MRI with gadobenate dimeglumine-enhanced MRI for the detection of hepatocellular carcinoma using receiver operating characteristic (ROC) analysis. MATERIALS AND METHODS: Twenty-nine consecutive patients with 35 hepatocellular carcinomas underwent gadobenate dimeglumine-enhanced MRI (unenhanced, arterial, portal, and equilibrium phases) using 3D fat-saturated volumetric interpolated imaging and SPIO-enhanced MRI on a 1.5-T unit. SPIO-enhanced T2-weighted turbo spin-echo and T2*-weighted gradient-echo sequences were performed 48 hr after completion of the dynamic study. Three observers independently interpreted the images in random order, separately, and without patient identifiers. Diagnostic accuracy was evaluated using the alternative free response receiver operating characteristic method. Sensitivity and positive predictive value were also evaluated. RESULTS: The mean sensitivity and positive predictive value of SPIO-enhanced imaging were 81.0% and 85.0%, respectively, and those of gadobenate dimeglumine-enhanced MRI were 91.4% and 88.1%, respectively. A significant difference was seen in the sensitivity of the two MRI examinations (p < 0.05). The mean value of the area under the ROC curve (A(z)) for gadobenate dimeglumine-enhanced imaging (A(z) = 0.97 +/- 0.01) was significantly higher than that for SPIO-enhanced imaging (A(z) = 0.90 +/- 0.02) (p = 0.004). CONCLUSION: Gadobenate dimeglumine-enhanced 3D dynamic imaging showed better diagnostic performance than SPIO-enhanced imaging for the detection of hepatocellular carcinomas.

Adult↗

PubMed1986

Nuclear factors binding specific sequences within the immunoglobulin enhancer interact differentially with other enhancer elements.

The mouse immunoglobulin heavy chain (IgH) enhancer represents a cis essential control element that confers lymphoid-specific expression. Based on in vivo and in vitro competition experiments, as well as on in vivo dimethylsulfate (DMS) protection experiments, it has been inferred that cellular factors interact in trans with IgH enhancer sequences. In addition, transcription is stimulated in vitro by up to one order of magnitude in the presence of IgH enhancer sequences on an appropriate template. Thus, at least some of these factors have to be present in nuclear extracts. To examine the factors interacting with this lymphoid-specific enhancer in more detail we compared the binding pattern of nuclear factors present in B-cell, T-cell and HeLa cell extracts. We demonstrate here, using the DNase I and DMS protection methods, the specific interaction of three different nuclear factors with the central PstI--EcoRI fragment of the IgH enhancer. This fragment has previously been suggested to retain the major enhancing activity. Surprisingly, no or only minor differences were discovered when the footprints obtained with B-cell extracts were compared with those obtained with HeLa cell and T-cell extracts. Intriguingly, two factors binding specifically to different sequences of the IgH enhancer are shared by polyoma as well as Moloney sarcoma virus (MSV) and lymphotropic papova virus (LPV) enhancer, respectively. All three of these enhancer elements exhibit altered cell type specificities. This indicates the utilization of similar or identical factors for transcriptional enhancement in different cell types. A cassette model consisting of different factor binding sites will be discussed.

B-Lymphocytes↗

PubMed2005

The mechanism of ring enhancement in hepatocellular carcinoma on superparamagnetic iron oxide-enhanced T1-weighted images: an investigation into peritumoral Kupffer cells.

PURPOSE: To investigate the mechanism of ring enhancement on ferumoxides-enhanced T1-weighted (T1W) gradient echo images in malignant focal hepatic lesions. MATERIALS AND METHODS: Eighteen patients with hepatocellular carcinoma (HCC) underwent breath-hold T1-, T2-, and T2*-weighted magnetic resonance (MR) images at 1.5-Tesla after ferumoxides administration. The existence of ring enhancement on T1W, and the maximum size of the area showing decreased phagocytic activity on T2W and T2*W, and that of the area showing ring enhancement on T1W were evaluated. The Kupffer cell (KC) density of HCC itself and peritumoral liver parenchyma was assessed with KC stain sections. RESULTS: Ring enhancement was noted in 13 of 18 HCC (72%). Peritumoral KC density was increased in the ring enhancement (+) group as compared with the ring enhancement (-) group. In the ring enhancement (+) group, the tumor size measured on T2W was smaller than that measured on either T1W or T2*W, suggesting a sustained T1 relaxation effect and a decreased T2* relaxation effect in the peritumoral regions. CONCLUSION: Ring enhancement on superparamagnetic iron oxide (SPIO)-enhanced T1W may correlate with increased KC density and decreased SPIO clustering in KC in peritumoral regions.

Aged↗

PubMed2006

Low dose non-enhanced CT versus standard dose contrast-enhanced CT in combined PET/CT protocols for staging and therapy planning in non-small cell lung cancer.

PURPOSE: To evaluate low dose non-enhanced CT and standard dose contrast-enhanced CT in combined PET/CT protocols for staging and therapy planning of non-small cell lung cancer (NSCLC). METHODS: Retrospective analysis was performed of 50 consecutive patients with proven NSCLC who had been referred for primary staging (n=41) or restaging (n=9). All patients underwent a multi-phase PET/CT consisting of a low dose non-enhanced attenuation scan and an arterial and portal-venous contrast-enhanced CT scan followed by whole-body PET. Fused datasets of non-enhanced and contrast-enhanced PET/CT were compared per patient by using the TNM staging system, and per lesion regarding localisation, characterisation and delineation of tumour lesions. The staging results were validated either by histopathology or by clinical-radiological follow-up for >or=6 months. RESULTS: In 47/50 patients, the results of T staging did not differ between the two PET/CT protocols. Three patients could only be correctly classified as having T4 tumours after contrast application. Regarding N staging, both protocols yielded the same results. In M staging, there was only one patient with an improvement of the results as a result of contrast application. The lesion-based analysis of 92 sites showed no difference in the accuracy of lesion localisation and only one revision of lesion characterisation by contrast-enhanced PET/CT. The assessment of tumour delineation was altered by contrast application in 58/92 sites (p<0.0001). In 10/50 patients, contrast-enhanced PET/CT detected additional clinically important findings. CONCLUSION: In patients with advanced NSCLC, contrast-enhanced CT as part of the PET/CT protocol more accurately assessed the TNM stage in 8% of patients compared with non-contrast PET/CT. However, for planning of 3D conformal radiotherapy and non-conventional surgery, contrast-enhanced PET/CT protocols are indispensable owing to their superiority in precisely defining the tumour extent.

Adult↗

PubMed1996

"Repair' of the chorionic somatomammotropin-A "enhancer' region reveals a novel functional element in the chorionic somatomammotropin-B enhancer.

Human chorionic somatomammotropin (CS) synthesis results from the independent expression of two homologous genes, CS-A and CS-B. A transcription enhancer factor-1 (TEF-1) element and an upstream 81 bp modulatory domain, containing repressor (RF-1) and derepressor (DF-1) activities, are important for efficient CS-B enhancer function in transfected placental JEG-3 cells. The equivalent region of the CS-A gene is not active. Although the TEF-1 element is conserved between the CS-A and CS-B genes, a single base substitution is present in the DF-1 element and two more are located between the RF-1 and DF-1 sites in a region we term AF-1. Repair of the DF-1 site increased CS-A enhancer function approximately 70-fold, but repair of previously uncharacterized AF-1 sequences was also required for full (CS-B like) enhancer activity. A 5 bp disruption of AF-1 sequences in the CS-B enhancer region, resulted in a 97% loss of stimulatory activity. The AF-1 sequences showed no intrinsic enhancer activity, however, they were able to significantly repress heterologous promoter activity stimulated by a TEF-1 enhancer element. A high affinity/specificity interaction between JEG-3 nuclear protein and AF-1 sequences was confirmed by gel mobility shift assay. By comparison to "wild type' AF-1 sequences, this interaction was competed to a lesser extent by both RF-1 and DF-1 elements, but not by mutated AF-1 sequences. The major protein binding to AF-1 sequences was estimated to be 23 kDa by UV crosslinking. These data indicate that enhancer activity can be generated by modulating binding events proximal to the TEF-1 element in the CS-A "enhancer' region and that coordinated binding of AF-1 and DF-1 are required for efficient (CS-B) enhancer activity.

Base Sequence↗

PubMed2006

Myocardial enhancement pattern in patients with acute myocardial infarction on two-phase contrast-enhanced ECG-gated multidetector-row computed tomography.

AIM: To evaluate the myocardial enhancement pattern of the left ventricle on two-phase contrast-enhanced electrocardiogram (ECG)-gated multidetector computed tomography (MDCT) images in patients with acute myocardial infarction (AMI). METHODS: Two-phase contrast-enhanced ECG-gated MDCT examinations were performed in 16 patients with AMI. The presence, location and pattern of myocardial enhancement were evaluated. MDCT findings were compared with the catheter angiographic results. RESULTS: Subendocardial (n = 9) or transmural (n = 6) area of early perfusion defects of the myocardium was detected in 15 of 16 patients (94%) on early-phase CT images. Variable delayed myocardial enhancement patterns on late-phase CT images were observed in 12 patients (75%): (1) subendocardial residual perfusion defect and subepicardial late enhancement (n = 6); (2) transmural late enhancement (n = 1); (3) isolated subendocardial late enhancement (n=1); and (4) isolated subendocardial residual perfusion defect (n = 2). On catheter angiography, 14 of 15 corresponding coronary arteries showed significant stenosis. CONCLUSION: Variable abnormal myocardial enhancement pattern was seen on two-phase, contrast-enhanced ECG-gated MDCT in patients with AMI. Assessment of myocardial attenuation on CT angiography gives additional information of the location and extent of infarction.

Adult↗

PubMed1998

Chondrocyte-specific enhancer elements in the Col11a2 gene resemble the Col2a1 tissue-specific enhancer.

Type XI collagen and type II collagen are coexpressed in all cartilage, and both are essential for normal cartilage differentiation and skeletal morphogenesis. This laboratory has recently identified a 48-base pair (bp) enhancer element in the type II collagen gene Col2a1 that contains several HMG-type protein-binding sites and that can direct chondrocyte-specific expression in transient transfection and in transgenic mice. The present study has identified two short chondrocyte-specific enhancer elements within a region in the 5' portion of the type XI collagen gene Col11a2 that has previously been shown to influence chondrocyte-specific expression in transgenic mice. These Col11a2 enhancer elements, like the Col2a1 enhancer, contain several sites with homology to the high mobility group (HMG) protein-binding consensus sequence. In electrophoretic mobility shift assays, the Col11a2 elements formed a DNA-protein complex that was dependent on the presence of the HMG-like sites. It had the same mobility as the complex formed with the Col2a1 48-bp enhancer and appeared to contain the same or similar proteins, including SOX9. The Col11a2 elements directed gene expression in transient transfections of chondrocytes but not fibroblasts, and their activity was abolished by mutation of the HMG-like sites. Ectopically expressed SOX9 activated these enhancers in non-chondrocytic cells, as it also activates the Col2a1 enhancer. Finally, the Col11a2 enhancer elements both directed transgene expression to cartilage in developing mouse embryos. Overall, our results indicate that the two Col11a2 chondrocyte-specific enhancer elements share many similarities with the Col2a1 48-bp enhancer. These similarities suggest the existence of a genetic program designed to coordinately regulate the expression of these and perhaps other genes involved in the chondrocyte differentiation pathway.

Animals↗

PubMed2006

VISTA Enhancer Browser--a database of tissue-specific human enhancers.

Despite the known existence of distant-acting cis-regulatory elements in the human genome, only a small fraction of these elements has been identified and experimentally characterized in vivo. This paucity of enhancer collections with defined activities has thus hindered computational approaches for the genome-wide prediction of enhancers and their functions. To fill this void, we utilize comparative genome analysis to identify candidate enhancer elements in the human genome coupled with the experimental determination of their in vivo enhancer activity in transgenic mice [L. A. Pennacchio et al. (2006) Nature, in press]. These data are available through the VISTA Enhancer Browser (http://enhancer.lbl.gov). This growing database currently contains over 250 experimentally tested DNA fragments, of which more than 100 have been validated as tissue-specific enhancers. For each positive enhancer, we provide digital images of whole-mount embryo staining at embryonic day 11.5 and an anatomical description of the reporter gene expression pattern. Users can retrieve elements near single genes of interest, search for enhancers that target reporter gene expression to a particular tissue, or download entire collections of enhancers with a defined tissue specificity or conservation depth. These experimentally validated training sets are expected to provide a basis for a wide range of downstream computational and functional studies of enhancer function.

Animals↗

PubMedDate not supplied

Focal hepatic lesions: diagnostic value of enhancement pattern approach with contrast-enhanced 3D gradient-echo MR imaging.

Focal hepatic lesions constitute a daily challenge in the clinical setting. However, noninvasive methods can be useful in the detection and characterization of these lesions. The noninvasive diagnosis of liver lesions is usually achieved with contrast material-enhanced computed tomography and magnetic resonance (MR) imaging. Dynamic three-dimensional gradient-recalled-echo MR imaging provides dynamic contrast-enhanced thin-section images with fat saturation and a high signal-to-noise ratio and is excellent for the evaluation of various focal hepatic lesions. A comprehensive MR imaging examination in this setting includes T2-weighted and chemical shift T1-weighted imaging and demonstrates characteristic enhancement patterns that can be helpful in the diagnosis of most of these lesions. These enhancement patterns are seen during particular phases of contrast-enhanced imaging and include arterial phase enhancement, delayed phase enhancement, peripheral washout, ring enhancement, nodule-within-a-nodule enhancement, true central scar, pseudocentral scar, and pseudocapsule. Familiarity with these enhancement patterns can help in the identification of specific focal lesions of the liver.

Aged↗

PubMed1997

Distal apolipoprotein C-III regulatory elements F to J act as a general modular enhancer for proximal promoters that contain hormone response elements. Synergism between hepatic nuclear factor-4 molecules bound to the proximal promoter and distal enhancer sites.

Transient transfection assays have shown that the distal apoC-III promoter segments that contain the regulatory elements F to J enhance the strength of the tandemly linked proximal apoA-I promoter 5- to 13-fold in hepatic (HepG2) cells. Activation in intestinal (CaCo-2) cells to levels comparable to those obtained in HepG2 cells requires a larger apoA-I promoter sequence that extends to nucleotide -1500 as well as the presence of hepatic nuclear factor-4 (HNF-4). The distal apoC-III regulatory elements can also enhance 4- to 8-fold the strength of the heterologous apoB promoter in HepG2 and CaCo-2 cells. Finally, these elements in the presence of HNF-4 enhance 14.5- to 18.5-fold the strength of the minimal adenovirus major late promoter linked to two copies of the hormone response element (HRE) AID of apoA-I in both HepG2 and CaCo-2 cells. In vitro mutagenesis of the promoter/enhancer cluster established that the enhancer activity is lost by a mutation in the HRE present in the 3' end of the regulatory element I (-736 to -714) and is reduced significantly by point mutations or deletions in one or more of the regulatory elements F to J of the apoC-III enhancer. The enhancer activity also requires the HREs of the proximal apoA-I promoter. The apoC-III enhancer can also restore the activity of the proximal apoA-I and apoB promoters that have been inactivated by mutations in CCAAT/enhancers binding protein binding sites, indicating that C/EBP may not participate in the synergistic activation of the promoter/enhancer cluster. The findings suggest that the regulatory elements F to J of the apoC-III promoter act as a general modular enhancer that can potentiate the strength of proximal promoters that contain HREs. Such potentiation in the HepG2 cells can be accounted for by synergistic interactions between HNF-4 or other nuclear hormone receptors bound to the proximal and distal HREs and SP1 or other factors bound to the apoC-III enhancer. Additional factors may be required for optimal activity in CaCo-2 cells as well as for the function of this region as an intestinal enhancer.

Apolipoproteins C↗

PubMed1997

Improved contrast of enhancing brain lesions using contrast-enhanced T1-weighted fast spin-echo MR imaging.

OBJECTIVE: The purpose of this study was to evaluate the ability of T1-weighted fast spin-echo MR sequences to provide improved contrast-to-noise ratios for contrast-enhanced lesions during acquisition times shorter than those used for conventional T1-weighted spin-echo MR sequences. SUBJECTS AND METHODS: We compared contrast-to-noise ratios of 32 enhancing brain lesions in 25 patients on T1-weighted spin-echo (546/10 [TR/TE]; two excitations; acquisition time, 4 min 12 sec) and on fast spin-echo (546/10 [TR/effective TE]; echo-train length, 4; echo spacing, 10 msec; two excitations; acquisition time, 1 min 45 sec) MR images obtained at 1.5 T after i.v. administration of 0.10 mmol/kg gadopentetate dimeglumine. RESULTS: The contrast-enhanced T1-weighted fast spin-echo MR images showed approximately a 12% reduction in the signal-to-noise ratios of the background white matter without an accompanying reduction in the signal-to-noise ratios of the enhancing lesions or CSF when compared with the contrast-enhanced T1-weighted spin-echo MR images. The contrast-enhanced T1-weighted fast spin-echo MR images provided a 23% improvement in the contrast-to-noise ratios of enhancing lesions over the contrast-enhanced T1-weighted spin-echo images (p < .001). CONCLUSION: Contrast-enhanced T1-weighted fast spin-echo MR imaging showed a statistically significant improvement in contrast-to-noise ratios at much shorter scan times than those used in conventional contrast-enhanced T1-weighted spin-echo MR imaging.

Adult↗

PubMedDate not supplied

Gadobenate dimeglumine (BOPTA) enhanced MR imaging: patterns of enhancement in normal liver and cirrhosis.

To determine whether gadobenate dimeglumine (BOPTA) will adequately enhance cirrhotic liver parenchyma, and to document the enhancement patterns in cirrhosis, 14 cirrhotic and 20 non-cirrhotic patients were evaluated before and 60-120 minutes after gadolinium-BOPTA. Proof of liver cirrhosis was biopsy (6), surgical resection (3), and clinical follow-up (5). Enhancement effects were compared quantitatively by determining the liver signal-to-noise ratio (SNR) and signal enhancement in both populations. Qualitatively assessment of the liver enhancement was performed and classified as homogeneous or heterogeneous. Quantitative analysis: cirrhotic liver parenchyma presented a higher increase in SNR values, relative to non-cirrhotic liver parenchyma, on postcontrast images. Likewise the signal enhancement of cirrhotic liver parenchyma was superior to non-cirrhotic liver on T1-weighted SE images (P = .02) and in-phase GRE images (P < .001). There was no statistical difference on out-of-phase GRE images. Qualitative analysis: on T1-weighted SE postcontrast images, cirrhotic liver parenchyma showed a homogeneous enhancement in 7 patients and heterogeneous in 7. Whereas on GRE images, cirrhotic parenchyma showed heterogeneous enhancement in 9 patients and homogeneous in 5 patients. The heterogeneous enhancement was due to the presence of hypointense nodules in 7 patients and hyperintense nodules in 2 patients. In conclusion, our study has shown that the hepatobiliary contrast agent Gd-BOPTA is effective in the cirrhotic liver, demonstrating an increased liver enhancement compared with non-cirrhotic patients.

Aged↗

PubMed1991

Enhancement of propranolol hydrochloride and diazepam skin absorption in vitro: effect of enhancer lipophilicity.

The enhancement of model hydrophilic (propranolol hydrochloride) and lipophilic (diazepam) drug penetration across rat and hairless mouse skin in vitro has been studied. Preliminary experiments established that most n-alkanes having chain lengths of between 7 and 16 promote the flux of both drugs. For propranolol, enhancement varied parabolically with carbon number; for diazepam, heptane was ineffective and all others were essentially equipotent. Enhancement by n-nonane was then compared with that by n-nonanol. Propranolol flux was increased by both enhancers, whereas diazepam penetration was not affected by the less lipophilic alcohol. The enhancement of propranolol by n-nonane and n-nonanol was examined as a function of adjuvant concentration in the applied formulation. Maximum increases in maximum penetration rates of 6.5-fold (n-nonane) and 8.2-fold (n-nonanol) were determined. As expected, the enhancement was saturable, indicative of a maximally perturbed stratum corneum. Finally, the penetration enhancing abilities of six monoterpenes were assessed. The purely hydrocarbon analogues promoted both propranolol and diazepam transport to an extent similar to that of n-nonane. The terpenes with hydrogen-bonding ability, however, only enhanced propranolol flux (at a level comparable to n-nonanol). While the data reported do not directly reveal mechanistic information on percutaneous penetration enhancement, they do provide a starting point for the rational investigation of interrelationships between drug, enhancer, and skin. Such information is clearly essential for the optimization and exploitation of transdermal drug delivery.

Alkanes↗

PubMed1995

Dynamic contrast-enhanced MR imaging of the liver: parenchymal enhancement patterns.

A retrospective study of 164 patients undergoing dynamic contrast-enhanced magnetic resonance (MR) imaging was performed to assess hepatic parenchymal enhancement patterns and to correlate these patterns with hepatic function and disease. Rapid T1-weighted images were acquired before and after gadolinium administration. Hepatic enhancement patterns were analyzed blindly by two observers. Medical records were reviewed to document known liver pathology and liver function test results. A total of 72% of patients had homogeneous enhancement of the liver parenchyma; 28% had heterogeneous enhancement. Of the latter group, 61% of patients had enhancement conforming to segmental or lobar boundaries. Patients with heterogeneous enhancement patterns were more likely to have abnormal liver function test results and hepatic morphological abnormalities on their MR examinations than patients with homogeneous enhancement patterns. Heterogeneous hepatic enhancement on dynamic MR images is associated with a higher likelihood of liver disease and biochemical evidence of hepatic dysfunction than homogeneous enhancement.

Adult↗

PubMed2006

The effects of Au aggregate morphology on surface-enhanced Raman scattering enhancement.

We have identified empirically a relationship between the surface morphology of small individual aggregates (<100 Au nanoparticles) and surface-enhanced Raman scattering (SERS) enhancement. We have found that multilayer aggregates generated greater SERS enhancement than aggregates limited to two-dimensional (2D) or one-dimensional structures, independent of the number of particles. SERS intensity was measured using the 730 cm(-1) vibrational mode of the adsorbed adenine molecule on 75 nm Au particles, at an excitation wavelength of 632.8 nm. To gain insight into these relationships and its mechanism, we developed a qualitative model that considers the collections of interacting Au nanoparticles of an individual aggregate as a continuous single entity that retains its salient features. We found the dimensions of the modeled surface features to be comparable with those found in rough metal surfaces, known to sustain surface plasmon resonance and generate strong SERS enhancement. Among the aggregates that we have characterized, a three 75 nm nanoparticle system was the smallest to generate strong SERS enhancement. However, we also identified single individual Au nanoparticles as SERS active at the same wavelength, but with a diameter twice in size. For example, we observed a symmetric SERS-active particle of 180 nm in diameter. Such individual nanoparticles generated SERS enhancement on the same order of magnitude as the small monolayer Au aggregates, an intensity value significantly stronger than predicted in recent theoretical studies. We also found that an aspect of our model that relates the dimensions of its features to SERS enhancement is also applicable to single individual Au particles. We conclude that the size of the nanoparticle itself, or the size of a protrusion of an irregularly shaped single Au particle, will contribute to SERS enhancement provided that its dimensions satisfy the conditions for plasmon resonance. In addition, by considering the ratio of the generated intensities of typical 2D Au aggregates to the enhancement of individual SERS-active particles, a value of approximately 2 is determined. Its moderate value suggests that it is not the aggregation effect that is responsible for much of the observed SERS enhancement but the surface region associated with the SERS-active site.

Journal Article↗

PubMed2004

Agonist-induced internalization of leukotriene B(4) receptor 1 requires G-protein-coupled receptor kinase 2 but not arrestins.

The leukotriene B(4) (LTB(4)) receptor (BLT1) becomes desensitized upon repeated agonist stimulation. Little is known, however, about BLT1 internalization, which follows desensitization in most G-protein-coupled receptors (GPCR). In the current study, transiently expressed BLT1 readily internalized, after LTB(4) stimulation, in RBL-2H3 cells that express high levels of endogenous GPCR kinase 2 (GRK2) but did not in COS-7 or human embryonic kidney (HEK) 293 cells, which do not overexpress GRK. The internalization of BLT1 could be blocked in RBL-2H3 cells by coexpressing dominant-negative (DN) GRK2 K220R and could be promoted in HEK293 cells by coexpressing wild-type (WT) GRK2. Coexpression of WT or DN nonvisual arrestins had no effect on BLT1 internalization. Moreover, upon stimulation with LTB(4), BLT1 did not induce arrestin-green fluorescence protein redistribution in either cell type, even in the presence of overexpressed GRK2. Coimmunoprecipitation experiments confirmed that BLT1 could associate with GRK2 but not with arrestins. A C-tail-truncated mutant of BLT1 lost the capacity to internalize and associate with GRK2 upon exposure to LTB(4), suggesting that the C-tail was required for receptor internalization and association with GRK2. Taken together, our results indicate that the C terminus of BLT1 plays a pivotal role in receptor internalization and GRK2 association. Moreover, ligand-induced BLT1 internalization is dependent on GRK2 but independent of arrestins. This may allow differential, cell-type-specific signaling in response to LTB(4), depending on GRK expression levels.

Animals↗

PubMed2005

Adrenocortical carcinomas and adrenal pheochromocytomas: mass and enhancement loss evaluation at delayed contrast-enhanced CT.

PURPOSE: To retrospectively measure the adrenal gland attenuation and the percentage loss of adrenal gland enhancement at delayed contrast medium-enhanced computed tomography (CT) in patients with adrenocortical carcinomas and pheochromocytomas and to compare these data with those in patients with adenomas and metastases. MATERIALS AND METHODS: The study protocol was approved by the ethics committee, which waived informed consent. Eleven patients with proved adrenocortical carcinoma, 17 with proved pheochromocytoma, 23 with adrenal adenoma, and 16 with metastasis to the adrenal gland underwent helical CT. Nonenhanced CT was followed by contrast-enhanced CT 1 minute and 10 minutes later. Attenuation and enhancement loss values were calculated. RESULTS: The mean attenuation of adenomas (8 HU +/- 18 [standard deviation]) was significantly lower than those of adrenocortical carcinomas (39 HU +/- 14), pheochromocytomas (44 HU +/- 11), and metastases (34 HU +/- 11) on nonenhanced CT scans (P < .001). Although the mean attenuation values for nonadenomas (ie, adrenocortical carcinomas, pheochromocytomas, and metastases) were significantly higher than the value for adenomas on the 1-minute contrast-enhanced CT scans (P < .001), there was more overlap in attenuation between adenomas and nonadenomas on contrast-enhanced scans than on nonenhanced scans. On the 10-minute delayed contrast-enhanced scans, the mean attenuation of adenomas (32 HU +/- 17) was significantly lower than the mean attenuations of carcinomas (72 HU +/- 15), pheochromocytomas (83 HU +/- 14), and metastases (66 HU +/- 13) (P < .001). At optimal threshold values of 50% for absolute percentage of enhancement loss and 40% for relative percentage of enhancement loss at 10 minutes, both the sensitivity and the specificity for the diagnosis of adenoma were 100% when adenomas were compared with carcinomas, pheochromocytomas, and metastases. CONCLUSION: The enhancement loss in adrenocortical carcinomas and pheochromocytomas is similar to that in adrenal metastases but significantly less than that in adrenal adenomas. The percentage change in contrast material washout is a useful adjunct to absolute CT attenuation values in differentiating adrenal adenomas from adrenocortical carcinomas and pheochromocytomas.

Adenoma↗