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PubMed1987

Promoter and enhancer elements from the rat elastase I gene function independently of each other and of heterologous enhancers.

An elastase-human growth hormone (hGH) fusion gene containing 205 base pairs of elastase 5' flanking region is expressed exclusively in pancreatic acinar cells of transgenic mice. This paper shows that the promoter region (-72 to +8) and the enhancer (-205 to -73) function independently of each other. The elastase enhancer can activate the heterologous mouse metallothionein gene and the hGH gene promoters; conversely, enhancers from the thymocyte-specific murine leukemia virus MCF13 and the metal regulatory elements from the metallothionein gene can activate the elastase promoter in a variety of cell types. Combinations of immunoglobulin and elastase enhancers with a heterologous promoter and the hGH gene result in expression in all of the tissues predicted by the sum of each enhancer acting alone. Thus these enhancer elements act independently of each other, suggesting that they do not have silencing activity in cells in which they are normally inactive.

Animals↗
PubMed1995

Identification of fat-cell enhancer activity in Drosophila melanogaster using P-element enhancer traps.

To identify genes important in fat-cell metabolism and development, we have screened Drosophila stocks carrying an engineered transposable element that can reveal the presence of nearby enhancer elements. We have identified those "enhancer-trap lines" that contain transposable P elements integrated near fat-cell specific enhancer elements. We anticipate that the genes associated with these enhancers will provide information concerning fat-cell function and serve as target genes for studying fat-cell specific gene expression. Furthermore, the identification of enhancer-trap lines active in the developing fat cell should provide an entry point into the molecular and genetic analysis of early fat-cell development. Analysis of two lines has revealed that the transcription factors svp, a steroid-hormone receptor, and Kr, a zinc-finger protein, are present in the fat body; these factors are likely to be involved in fat-cell gene expression. In two other lines, beta-galactosidase was detected in a subset of adepithelial cells that may be the precursors to the adult fat cell. And finally, in a single line transgene activity is present in the progenitor cells of the embryonic fat body. The genes associated with these enhancer-trap lines may be involved in fat-cell development.

Animals↗
PubMed2002

Contrast-enhanced blood-pool MR angiography with optimized iron oxides: effect of size and dose on vascular contrast enhancement in rabbits.

PURPOSE: To investigate intravascular enhancement of bolus-injectable small and ultrasmall superparamagnetic iron oxides (USPIOs) of different particle sizes and relaxivities for first-pass and blood-pool magnetic resonance (MR) angiography. MATERIALS AND METHODS: Iron oxides with different particle sizes (hydrodynamic diameters, 21, 33, 46, and 65 nm) were bolus injected intravenously at three doses (10, 20, and 40 micromol per kilogram body weight). An extracellular contrast agent (gadopentetate dimeglumine) served as a control. MR angiography was performed multiple times after intravenous injection (5-120 minutes and 24 hours later). Signal enhancement was calculated from signal intensity measurements in the abdominal aorta and renal and iliac arteries. RESULTS: Highest enhancement was seen during the first pass with all contrast agents. USPIO enhancement in the abdominal aorta increased significantly with decreasing particle size (65 nm vs 33 nm, 65 nm vs 21 nm; P <.01). CONCLUSION: The smallest iron oxide provided signal enhancement comparable with that of gadopentetate dimeglumine at 40 micromol iron per kilogram for first-pass investigations, with prolonged signal enhancement up to 25 minutes, allowing multiple measurements after injection of a single bolus.

Analysis of Variance↗
PubMed1992

Spleen: dynamic enhancement patterns on gradient-echo MR images enhanced with gadopentetate dimeglumine.

To examine the pattern of immediate enhancement with gadopentetate dimeglumine on dynamic magnetic resonance (MR) images of the spleen, this study was divided into two parts: In the first part, the authors retrospectively reviewed the dynamic MR images obtained with a fast low-angle shot (FLASH) sequence in the abdomen immediately after injection of gadopentetate dimeglumine in 137 patients. In the second part, dynamic gadolinium-enhanced FLASH images were prospectively compared with contrast material-enhanced computed tomographic (CT) scans in 17 patients with focal splenic lesions discovered on CT scans. In the first part, 108 patients (79%) had an arciform pattern of contrast enhancement; 22 patients (16%), a uniform pattern of high signal intensity; and seven patients (5%), a uniform pattern of low signal intensity. Most patients had arciform enhancement of the spleen; uniform enhancement occurred in some patients with underlying malignant or inflammatory disease. In the second part, all focal lesions seen on CT scans were seen on dynamic MR images (75 lesions), significantly more than were seen on FLASH images (15 lesions) (P < .001).

Adolescent↗
PubMed2004

Differential diagnosis of focal liver lesions in signal-enhanced ultrasound using BR 1, a second-generation ultrasound signal enhancer.

AIM: The aim was to evaluate the diagnostic value of contrast-enhanced ultrasound in the differential diagnosis of focal liver lesions, in a blinded experiment. In clinical routine the examiner can generally be influenced by the patient's history. METHOD: 62 patients with focal liver lesions, which could not be clearly differentiated and diagnosed by conventional ultrasound, were examined with contrast-enhanced (BR1, SonoVue, Bracco) ultrasound and included in a blinded prospective and randomized study. The examinations performed on a Sequoia 512 (Acuson) in a coherent contrast imaging method were recorded by an S-VHS recorder and afterwards analyzed by an examiner who did not know the patient's history. The basis of the diagnosis was the dynamic appearance and enhancement of the ultrasound contrast enhancer in different phases of liver perfusion. The conformation of the diagnoses was made by corresponding reference methods, as computer tomography, magnetic resonance imaging, biopsy and clinical follow-up. RESULTS: The following diagnoses were confirmed by reference methods: 18 patients with metastases, 4 hepatocellular carcinomas, 19 haemangiomas, 6 focal nodular hyperplasias, 13 patients with focal fatty infiltration and 2 patients with focal fatty sparing. 59 out of 62 patients with one or more liver lesions were correctly diagnosed by contrast-enhanced ultrasound. CONCLUSION: Second-generation ultrasound contrast enhancers improve the differential diagnosis of benign and malignant liver lesions considerably, especially in a blinded study.

Adult↗
PubMed1990

Leptomeningeal metastasis: a comparison of gadolinium-enhanced MR and contrast-enhanced CT of the brain.

We evaluated 14 consecutive patients with leptomeningeal metastasis prospectively, using both T1-weighted (T1W) gadolinium-DTPA-enhanced MR (Gd-MR) and contrast-enhanced CT (CE-CT). Thirteen had positive CSF cytology; the remaining patient had an atypical CSF lymphocytosis and primary CNS lymphoma. The patients (8M/6F) ranged in age from 8 to 70 years (median, 42 years). Tumor histology included 3 systemic and 2 primary CNS lymphomas, 3 breast carcinomas, 2 leukemias, 1 malignant schwannoma, 1 small cell lung cancer, 1 prostate cancer, and 1 melanoma. Both imaging methods demonstrated parenchymal volume loss equally well in all patients. Gd-MR revealed abnormal enhancement of meninges or parenchyma in 10 patients, including all 5 patients with positive CE-CT. Neither technique revealed any foci of abnormal enhancement in 4 patients. Gd-MR was superior to CE-CT in demonstrating and quantifying enhancing subarachnoid and parenchymal nodules in 6 patients and in demonstrating sulcal, dural, cisternal, tentorial, and ependymal enhancement. Our findings indicate that T1W Gd-MR is the preferred imaging modality in leptomeningeal metastasis and suggest that CE-CT is unnecessary.

Adolescent↗
PubMed2003

[Duration of enhancement and scan timing in three-dimensional contrast-enhanced MR angiography using the elliptical centric phase-encoding technique].

In the present study, we quantitatively investigated the relationship between the signal intensity in a vessel and the duration of contrast enhancement as well as scan timing in 3D contrast-enhanced MR angiography using an elliptical centric phase-encoding technique. A tube phantom filled with Gd-DTPA, acting as a vessel, was taken out from the field of view during data acquisition, by using the "pause" function of our MR scanner (GE Signa, 1.5 Tesla), thereby simulating the presence and absence of a vessel. The shortening of the duration of enhancement corresponds to the delay of scan timing from the optimal point in the phase-encoding of the centric-ordering system. The signal intensity in a vessel (1-5 mm in diameter) decreased as the duration of enhancement became shorter and the diameter of the vessel decreased. When the number of partitions was 16 or 32 in a 128-mm-thick slab, the signal intensity obtained by the elliptical centric phase-encoding technique was almost the same as that obtained by the conventional centric phase-encoding technique. However, when the number of partitions was increased (64-124), and if the duration of enhancement was short, the signal intensity obtained by the elliptical centric phase-encoding technique was higher than that obtained by the conventional centric phase-encoding technique. In conclusion, in terms of the duration of enhancement and the delay of scan timing, the elliptical centric phase-encoding technique is superior to the conventional centric phase-encoding technique when the number of partitions in a slab for 3D MR angiography is increased.

Contrast Media↗
PubMed2000

[Detectability of metastatic brain tumors using gadoteridol-enhanced MRI: usefulness of standard-dose T1-weighted spin-echo image with magnetization transfer and enhanced FLAIR].

PURPOSE: The aim of this study was to compare the detectability and image contrast of metastatic brain tumors depicted by T1-weighted MR imaging (T1WI) with the magnetization transfer (MT) technique after the administration of a standard dose(MT-SD-T1WI) or T1WI without MT after the administration of a double dose of gadoteridol(DD-T1WI). We also assessed the usefulness of enhanced fluid attenuated inversion recovery (FLAIR) for depicting very small metastatic tumors. METHODS: Forty-six MRI procedures were performed in 31 patients with metastatic brain tumors that had been diagnosed clinically and radiologically. An incremental dose technique was used with intravenous injections of 0.1 and 0.1 mmol/kg of gadoteridol. In 28 MRI procedures, enhanced FLAIR was carried out after an MT-SD-T1WI study. RESULTS: Detectability was significantly greater with both MT-SD-T1WI and DD-T1WI than with SD-T1WI. However, there was no significant difference between MT-SD- and DD-T1WI. Although an MT pulse increased the contrast between the enhanced tumor and white matter, the contrast between edema and white matter was decreased. Both MT-SD- and DD-T1WI showed small but conspicuous enhanced foci, but we could not determine whether these were vessels or small metastases on the brain surface. However, enhanced FLAIR only demonstrated foci that were thought to be small metastases. CONCLUSIONS: MT-SD- and DD-T1WI had equal ability to detect metastatic brain tumors. Enhanced FLAIR was useful for assessing very small metastases on the brain surface.

Adult↗
PubMed2004

[Evaluation of enhancement patterns using three-dimensional dynamic contrast-enhanced MR imaging in 209 cases of breast cancer].

PURPOSE: To evaluate contrast-enhanced patterns using three-dimensional (3D) dynamic MR imaging in 209 cases of breast cancer. MATERIALS AND METHODS: Three-dimensional dynamic imaging of the breast (1.5-T scanner) was performed in 755 cases. Of 227 breast carcinomas, 209 cases that were histologically confirmed were enrolled in this study. The histological diagnoses included ductal carcinoma in situ (DCIS) (n=12), invasive ductal carcinoma (n=176), mucinous carcinoma (n=10), medullary carcinoma (n=4), invasive lobular carcinoma (n=6), and other (n=1). Tumor size was a mean 24.6 mm in diameter (range, 7-110 mm), including 110 cases of small breast carcinomas (< or = 2 cm). The contrast-enhancement pattern was analyzed from the early phase of 3D-MRI and the post-contrast T1-weighted SE image acquired before the delayed phase of 3D-MRI. The type of peripheral enhancement (PE) was evaluated on the early and delayed phases of 3D-MRI. These enhancement patterns were also compared with the histological findings of small breast carcinomas. RESULTS: The sensitivity of the 209 cases of breast carcinoma was 99% (207/209) on 3D dynamic MRI. Two hundred six cases (98.6%), including all DCIS, showed strong enhancement on the early phase of 3D MRI. An increased washout pattern showing signal intensity lower than that of fat on post-contrast T1-weighted imaging was noted in 201 cases (96.1%), of which 179 cases (85.6%) showed washout patterns. PE was identified in 63 cases (30.4%) and in 35 of 110 cases of small breast carcinoma (31.8%). Delayed PE following central washout was noted in 65% of 63 cases and 71.4% of 35 cases of small breast carcinoma. Delayed PE was well correlated with marginal fibrosis. CONCLUSION: Three-dimensional dynamic MRI of the breast was highly sensitive for breast carcinoma. Delayed PE following central washout was considered a specific finding of breast carcinoma. It is important to understand the enhancement patterns of 3D dynamic MRI for excellent specificity of breast carcinomas.

Adult↗
PubMed1995

[Evaluation of AMI-25 enhanced MR imaging and enhanced helical CT for liver tumors].

To evaluate the diagnostic capability of superparamagnetic iron oxide enhanced MRI and enhanced helical CT, 17 patients with histologically or clinically diagnosed hepatocellular carcinoma or metastatic liver tumor and a total of 208 nodules were studied. The pulse sequences used were SE 500/20 (T1WI), SE 2000/20 (PDWI) and SE 2000/70 (T2WI). Contrast medium was administrated intravenously for more than 30 minutes at a dose of 10 mumoles Fe/kg. Enhanced MR images were obtained 30-90 minutes after the injection of contrast medium. With helical CT, 133 nodules were detected. With unenhanced MRI, 62 were detected on T1WI, 60 on PDWI and 77 on T2WI. On the other hand, with enhanced MRI, 165 were detected on T1WI, 190 on PDWI and 186 on T2WI. Enhanced MRI revealed the most nodules among these images (P < 0.05), and was especially effective in detecting small nodules less than 10 mm in diameter (P < 0.05). In conclusion, it was considered that superparamagnetic iron oxide enhanced MRI was useful for the detection of hepatic nodules and that the most adequate pulse sequence was PDWI.

Aged↗
PubMed1994

Homeodomain protein MHox and MADS protein myocyte enhancer-binding factor-2 converge on a common element in the muscle creatine kinase enhancer.

MHox is a mesoderm-specific homeodomain protein that binds an A/T-rich element that is essential for activity of the muscle creatine kinase (MCK) enhancer. The MHox binding site also binds the ubiquitous homeodomain protein Oct-1 as well as myocyte enhancer-binding factor-2 (MEF2), which belongs to the MADS superfamily of transactivators. To determine which of these proteins activates MCK transcription through the A/T element, we mutated this sequence such that it would selectively bind MHox, MEF2, or Oct-1 and tested the activities of the mutant enhancers in skeletal muscle cells. These mutant enhancers revealed that only MEF2 is able to activate the MCK enhancer through the A/T element. The convergence of homeodomain and MADS proteins on the A/T element in the MCK enhancer provides a mechanism through which a single DNA sequence can mediate positive and negative regulation of gene transcription and is reminiscent of the roles of these two classes of transcription factors in the control of other cell-specific genes.

Animals↗
PubMed2005

Microbubble-enhanced ultrasound exposure promotes uptake of methotrexate into synovial cells and enhanced antiinflammatory effects in the knees of rabbits with antigen-induced arthritis.

OBJECTIVE: To evaluate whether microbubble-enhanced ultrasound (US) treatment promotes the delivery of methotrexate (MTX) into synovial cells and the enhanced antiinflammatory effects of intraarticular MTX therapy in a rabbit arthritis model. METHODS: Arthritis was induced in both knees of 53 rabbits by immunization with ovalbumin. MTX including a microbubble agent was then injected into the left and right knee joints, and the right knees were exposed to US (MTX+/US+ group), while the left knees were not (MTX+/US- group). The knee joints were evaluated histologically in 7 rabbits at 5 time points up to day 56. Quantitative gene expression of interleukin-1beta (IL-1beta) in synovial tissue was measured on days 7 and 28. Eight rabbits were used for the measurement of MTX concentration in synovial tissue 12 hours after treatment. To evaluate the effect of microbubble-enhanced US treatment in the absence of MTX, only the microbubble agent was injected into the left and right knee joints of 10 rabbits with or without US exposure, and these animals were evaluated histologically on days 7 and 28. RESULTS: The MTX concentration in synovial tissue was significantly higher in the MTX+/US+ group than in the MTX+/US- group. Synovial inflammation was less prominent in the MTX+/US+ group compared with the MTX+/US- group, judging from the results of the histologic evaluation and the gene expression levels of IL-1beta in synovial tissue. It also appeared that microbubble-enhanced US exposure itself did not affect inflammation. CONCLUSION: Microbubble-enhanced US exposure promoted the uptake of MTX into synovial cells, which resulted in enhancement of the antiinflammatory effects of the intraarticular MTX injection. These results suggest that application of this technique may have clinical benefit.

Animals↗
PubMed1982

Enhanced mutagenesis parallels enhanced reactivation of herpes virus in a human cell line.

U.v. irradiation of human NB-E cells results in enhanced mutagenesis and enhanced reactivation of u.v.-irradiated H-1 virus grown in those cells ( Cornelis et al., 1982). This paper reports a similar study using herpes simplex virus (HSV) in NB-E cells. The mutation frequency of HSV (resistance of virus plaque formation to 40 micrograms/ml iododeoxycytidine ) increased approximately linearly with exposure of the virus to u.v. radiation. HSV grown in unirradiated cells gave a slope of 1.8 X 10(-5)m2/J, with 3.2 X 10(-5)m2/J for HSV grown in cells irradiated (3 J/m2) 24 h before infection. There was no evidence for mutagenesis of unirradiated virus by irradiated cells, as seen with H-1 virus. Enhanced reactivation of irradiated HSV in parallel cultures increased virus survival, manifested as a change in slope of the final component of the two-component survival curve from a D0 of 27 J/m2 in unirradiated cells to 45 J/m2 in irradiated cells. Thus, enhanced mutagenesis and enhanced reactivation occurred for irradiated HSV in NB-E cells. The difference in the enhanced mutagenesis of HSV (dependent on damaged DNA sites) and of H-1 virus (primarily independent of damaged DNA sites) is discussed in terms of differences in DNA polymerases.

Cell Line↗
PubMed1998

Enhancement of the Nipple-Areolar-Complex on Contrast-Enhanced MR Imaging of the Breast.

OBJECTIVE: To evaluate patterns of enhancement in the nipple-areolar-complex (NAC) on contrast-enhanced MRI. METHODS: We reviewed the MR images of 37 patients in which enhancement of the NAC was demonstrated on gadolinium-enhanced dynamic fast radiofrequency spoiled gradient recalled echo (fast-SPGR) images. Time intensity profiles derived from signal intensity values were constructed, and findings correlated with histological results. RESULTS: Three types of curve were observed. In the first type seen in adenoma of the nipple, rapid initial increase in signal intensity with an early peak (1 min) occurred followed by gradual washout. In the second type seen in direct invasion from carcinoma, subareolar intracystic papilloma, or Paget's disease, rapid initial increase in signal intensity followed by a more gradual increase or plateau was seen. In the third type seen in carcinoma without nipple invasion, fibrocystic disease and fibroadenoma, a gradual increase in signal intensity was observed throughout the examination period. CONCLUSION: Early and prominent enhancement of the NAC on contrast-enhanced MRImay indicate the presence of a primary lesion in the NAC or secondary involvement by a primary tumor elsewhere in the breast.

Journal Article↗
PubMed1998

Adenosine-enhanced ischemic preconditioning provides enhanced cardioprotection in the aged heart.

BACKGROUND: Recently we have reported a novel myo-protective protocol "adenosine-enhanced ischemic preconditioning" (APC), which extends and amends the protection afforded by ischemic preconditioning (IPC) by both reducing myocardial infarct size and enhancing postischemic functional recovery in the mature rabbit heart. However, the efficacy of APC in the senescent myocardium was unknown. METHODS: The efficacy of APC was investigated in senescent rabbit hearts and compared with magnesium-supplemented potassium cardioplegia (K/Mg) and IPC. Global ischemia (GI) hearts were subjected to 30 minutes of global ischemia and 120 minutes of reperfusion. Ischemic preconditioning hearts received 5 minutes of global ischemia and 5 minutes of reperfusion before global ischemia. Magnesium-supplemented potassium cardioplegia hearts received cardioplegia just before global ischemia. Adenosine-enhanced ischemic preconditioning hearts received a bolus injection of adenosine in concert with IPC. To separate the effects of adenosine from that of APC, a control group (ADO) received a bolus injection of adenosine 10 minutes before global ischemia. RESULTS: Infarct size was significantly decreased to 18.9%+/-2.7% with IPC (p<0.05 versus GI); 17.0%+/-1.0% with ADO (p<0.05 versus GI); 7.7%+/-1.3% with K/Mg (p<0.05 versus GI, IPC, and ADO); and 2.1%+/-0.6% with APC (p<0.05 versus GI, IPC, ADO, and K/Mg; not significant versus control). Only APC and K/Mg significantly enhanced postischemic functional recovery (not significant versus control). CONCLUSIONS: Adenosine-enhanced ischemic preconditioning provides similar protection to K/Mg cardioplegia, significantly enhancing postischemic functional recovery and decreasing infarct size in the senescent myocardium.

Adenosine↗
PubMed2001

Polymeric transdermal drug penetration enhancer. The enhancing effect of oligodimethylsiloxane containing a glucopyranosyl end group.

Oligodimethylsiloxanes (ODMSs) containing a beta-D-glucopyranosyl group at one chain end (Glc-ODMSs) with various molecular weights were prepared to develop a silicone-based polymeric transdermal penetration enhancer with a non-ionic polar end group. Glc-ODMSs were prepared by hydrosilylation of hydrosilyl-terminated ODMS with 1-allyl-beta-D-glucose tetraacetate in the presence of bis(benzonitrile)platinum dichloride as the catalyst, followed by hydrolysis of the acetyl groups with sodium methoxide. The enhancing effect in the drug penetration was evaluated by in vitro experiments using a two-chamber diffusion cell. Antipyrine was used as a model drug, and the amount of drug permeating through the rat abdominal skin with or without Glc-ODMS was determined by HPLC. These enhancers were effective for the penetration of antipyrine. On the other hand, the enhancing effects were influenced by the concentration of Glc-ODMS coexisted regardless of its ODMS chain length. The enhancing effect was also observed by the pretreatment of the skin with Glc-ODMS before the drug permeation, the results of which suggested that the induction periods to appear the enhancing effects were different between Glc-ODMSs with the short and the long ODMS chain lengths. Furthermore, according to the Draize test, Glc-ODMSs exhibited no irritation to the skin regardless of the ODMS chain length.

Animals↗