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PubMed1990

Purification of TCF-1 alpha, a T-cell-specific transcription factor that activates the T-cell receptor C alpha gene enhancer in a context-dependent manner.

The differentiation of T cells into functionally diverse subpopulations is controlled in part, by transcriptional activation and silencing; however, little is known in detail about the proteins that influence this developmental process. We have purified a new T-cell-specific factor, TCF-1 alpha, that is implicated in the activation of genes encoding a major component of the human T-cell receptor (TCR). TCF-1 alpha, originally identified and purified through its binding sites on the HIV-1 promoter, was found to bind to the TCR alpha enhancer and to promoters for several genes expressed at significantly earlier stages of T-cell development than the TCR alpha gene (e.g., p56lck and CD3 delta). Sequences related to the TCF-1 alpha binding motif (5'-GGCACCCTTTGA-3') are also found in the human TCR delta (and possibly TCR beta) enhancers. Southwestern and gel renaturation experiments with the use of purified protein fractions revealed that TCF-1 alpha activity is derived from a family of 57- to 53-kD proteins that are abundantly expressed in mature and immature T-cell lines (Jurkat, CCRF-CEM) and not in mature B cells (JY, Namalwa) or nonlymphoid (HeLa) cell lines. A small 95-bp fragment of the TCR alpha control region that contains the TCF-1 alpha binding site juxtaposed between a cAMP-response element (the CRE or T alpha 1 motif) and the binding site for a distinct lymphoid-specific protein (TCF-2 alpha) behaved as a potent T-cell-specific enhancer in vivo. Tandem copies of this enhancer functioned synergistically in mature (Jurkat) T-cell lines as well as resting and activated immature (CCRF-CEM) T-cell lines. Mutation of the TCF-1 alpha binding site diminished enhancer activity and disrupted the synergism observed in vivo between tandem enhancer repeats. The TCF-1 alpha binding site was also required for TCR alpha enhancer activity in transcriptionally active extracts from Jurkat but not HeLa cells, confirming that TCF-1 alpha is a T-cell-specific transcription factor. Curiously, the TCF-1 alpha binding element was inactive in vivo when removed from its neighboring elements on the TCR alpha enhancer and positioned in one or more copies upstream of a heterologous promoter. Thus, the transcriptional activity of TCF-1 alpha appears to depend on the TCF-2 alpha and T alpha 1 (CREB) transcription factors and the context of its binding site within the TCR alpha enhancer.

Base Sequence↗

PubMed1990

Multiple doses of diacylglycerol and calcium ionophore are necessary to activate AP-1 enhancer activity and induce markers of macrophage differentiation.

In contrast to phorbol esters, multiple doses of diacylgycerols are needed to differentiate U937 human monoblastic leukemic cells to a macrophage-like phenotype. Although both of these agents similarly activate protein kinase C in vitro, it is not known why these agents appear to have differing biologic effects. One possibility is that they regulate gene transcription in slightly different ways. Regulation of gene transcription by phorbol esters is complex and involves the stimulation of the transactivating proteins Jun and Fos which form dimers and bind to the AP-1 enhancer elements (5'-TGAGTCA-3'). To understand whether diacylglycerols regulate gene transcription similarly to phorbol esters and to examine whether activation of AP-1 enhancer activity is correlated with differentiation, we have treated U937 human monoblastic leukemic cells with these agents and examined activation of transcription from AP-1 enhancer elements. We find that, although a single dose of diacylglycerol, like phorbol esters, is sufficient to elevate mRNA levels of both the c-jun and c-fos protooncogenes, in contrast to phorbol esters there is no increase in either Jun protein or activation of AP-1 enhancer activity. However, multiple doses of this agent given over 24 h stimulate repeated elevations in c-jun and c-fos mRNA, increases in Jun protein, and enhancer activation. Treatment of U937 cells with ionomycin, a calcium ionophore, also stimulates an increase in c-jun mRNA, but neither activates AP-1 enhancer activity nor stimulates differentiation of these cells. However ionomycin functions to enhance the effects of diacylglycerols both on transcriptional activation and U937 differentiation. These results suggest a complex regulation of AP-1 enhancer activity in U937 cells by diacylglycerols involving both transcriptional and post-transcriptional regulatory mechanisms. Maximal activation of AP-1 enhancer elements, and not changes in jun and fos mRNA, is correlated with increases in markers of U937 differentiation. These changes may be important in the early events leading to differentiation of hematopoietic cells.

Blotting, Northern↗

PubMed1994

Activation of keratin 19 gene expression by a 3' enhancer containing an AP1 site.

We previously reported that the human keratin 19 (K19) gene was expressed in nonkeratinizing oral epithelial subtypes, and that the steady state K19 mRNA levels in different normal epithelial subtypes correlated with the levels of the retinoic acid receptor (RAR) beta-mRNA (Hu, L., Crowe, D. L., Rheinwald, J. G., Chambon, P., and Gudas, L. J. (1991) Cancer Res. 51, 3972-3981). To elucidate the mechanisms by which the K19 gene is differentially expressed in various epithelial subtypes, we isolated phage containing human K19 genomic DNA from a human placental library. Through transient transfection assays with various K19/CAT constructs that contain different portions of K19 genomic DNA, an enhancer sequence has been identified in the K19 3'-flanking region. In normal human epithelial cell strains, the activity of this enhancer correlates with K19 mRNA abundance. This enhancer activates both the K19 and TK basal promoters in HeLa cells. A high level of K19/CAT fusion mRNA was detected when this K19 3' enhancer sequence was present at the 3' end of the fusion gene whereas no K19/CAT fusion transcript was detected if this 3' K19 enhancer sequence was absent, suggesting that the 3' K19 enhancer is crucial for the positive regulation of K19 expression. Deletion analysis has permitted the localization of the enhancer to a 19-base pair sequence which contains an AP1 binding site (AGTCATCT). Point mutations within this AP1 site completely abolished K19 enhancer activity in HeLa cells. Co-transfections of a c-jun expression vector with K19/CAT reporter constructs demonstrated that c-jun was able to activate the K19 promoter via the 3' K19 enhancer. Collectively, these data indicate that a cis-acting AP1 element and its associated trans-acting effector proteins regulate expression of lineage-specific genes in epithelial cells.

Base Sequence↗

PubMed1994

Type I procollagen COOH-terminal proteinase enhancer protein: identification, primary structure, and chromosomal localization of the cognate human gene (PCOLCE).

Type I procollagen COOH-terminal proteinase (C-proteinase) enhancer, a glycoprotein that binds to the COOH-terminal propeptide of type I procollagen and enhances procollagen C-proteinase activity, was purified from mouse fibroblast culture media. Partial amino acid sequences obtained from proteolytic fragments were found to have identity with the deduced amino acid sequence of a cDNA clone of unknown function, previously isolated from a mouse astrocyte library. Sequences of mouse enhancer cDNA, obtained in the present study, predict a approximately 50-kDa, 468-amino acid protein that differs from the 43-kDa, 402-amino acid protein predicted by the previously reported astrocyte-derived clone. Human cDNAs encode an enhancer of 449 amino acids. Previous biochemical studies have found the mouse enhancer as a 55-kDa form, which is readily processed to 36- and 34-kDa forms, retaining full C-proteinase enhancing activity and the ability to bind the COOH-terminal propeptide. Data presented here show the 36-kDa form to correspond to the amino-terminal portion of the 55-kDa protein. This is the most conserved region between mouse and human enhancers, comprising two domains with homology to domains found in a number of proteases and proteins with developmental functions. Such domains are thought to mediate interactions between proteins. Mouse enhancer RNA is shown to be at highest levels in collagen-rich tissues, especially tendon. The human enhancer gene, PCOLCE, is localized to 7q21.3-->q22, the same chromosomal region containing the type I collagen alpha 2 chain gene, COL1A2.

Amino Acid Sequence↗

PubMed1994

A quantitative measurement of the dependence of short-term synaptic enhancement on presynaptic residual calcium.

We simultaneously measured presynaptic free calcium ion concentration ([Ca2+]i) and synaptic strength at the crayfish claw opener neuromuscular junction (nmj) under a variety of experimental conditions. Our experiments were designed both to test the hypothesis that elevated [Ca2+]i is necessary and sufficient for the induction of a form of synaptic enhancement that persists for several seconds after tetanic stimulation--augmentation--and to determine the quantitative relationship between elevated [Ca2+]i and this enhancement. Action potential trains increased [Ca2+]i and enhanced transmission. During the decay phase of synaptic enhancement known as augmentation (time constant of decay approximately 7 sec at 20 degrees C with < 200 microM fura-2 in terminals), [Ca2+]i was elevated 700 nM or less above rest and an essentially linear relationship between [Ca2+]i and enhancement was observed. Introduction of exogenous Ca2+ buffers into the presynaptic terminal slowed the buildup and recovery kinetics of both [Ca2+]i and the component of synaptic enhancement corresponding to augmentation. The slope of the relationship relating delta [Ca2+]i to augmentation was not changed. The time course of augmentation and recovery of [Ca2+]i remained correlated as the temperature of the preparation was changed from about 10 degrees C to 20 degrees C, but the quantitative relationship of enhancement to [Ca2+]i was increased more than two- to threefold. During moderate frequency trains of action potentials, a slowly developing component of the total synaptic enhancement was approximately linearly related to residual [Ca2+]i measured with fura-2. The quantitative relationship between [Ca2+]i and this component of synaptic enhancement during trains was the same as that during synaptic augmentation after trains.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗

PubMed1994

An Ig heavy chain enhancer of the channel catfish Ictalurus punctatus: evolutionary conservation of function but not structure.

The teleost fishes are among the earliest evolutionary lineages to have an Ig heavy chain (IgH) locus whose organization approximates that of mammals. To understand transcriptional control of the IgH locus in a teleost fish and to gain insight into the evolution of the control elements, the enhancer activity in the IgH locus of the channel catfish, Ictalurus punctatus, was investigated. Segments of the locus extending from upstream of the proximal JH gene to 2.5 kb downstream of the second transmembrane (TM2) exon of the mu gene were tested in transient transfection expression assays in murine myeloma and T cell lines, and in catfish B lymphoblastoid, monocyte-like, and putative T cell lines. In marked contrast to mammals, no enhancer activity was observed in the catfish JH to C mu intron, but strong enhancer activity (approaching that of the murine IgH intronic enhancer) was identified in a 1.8-kb segment that included the TM2 exon. This catfish enhancer was active in a B lineage-specific manner in both catfish and murine cells. It was not localized in a small core region, but appeared to contain multiple, dispersed cooperative elements rich in octamer- and mu E5-related motifs. Although the catfish IgH enhancer shares functional characteristics with the mammalian IgH intronic and 3' enhancers, its unusual organization does not permit any obvious inferences concerning evolutionary relationships between the catfish enhancer and any one of the murine IgH enhancers.

Animals↗

PubMed1994

Evaluation of fat suppression in contrast-enhanced MR of neoplastic and inflammatory spine disease.

PURPOSE: To determine the benefit of fat suppression in conjunction with gadolinium enhancement for evaluating neoplastic and inflammatory diseases of the spine. METHODS: Contrast-enhanced T1-weighted images were compared with the corresponding contrast-enhanced T1-weighted images with fat suppression in 14 patients with various neoplastic and inflammatory spine diseases. RESULTS: Contrast-enhanced T1-weighted images with fat suppression showed enhancing lesions in all cases of vertebral disease (five cases), but in one case some metastases did not enhance. Paravertebral (nine lesions), epidural (seven lesions), and intradural-extramedullary (six lesions) were delineated better with contrast-enhanced fat suppression. In the 14 cases (29 lesions), nine lesions were seen only on contrast-enhanced images with fat suppression. Integrity of the vertebral end plates was assessed more accurately on fat-suppressed images. CONCLUSION: Although noncontrast T1-weighted images are sufficient to screen for vertebral disease, contrast-enhanced images with fat suppression may detect additional lesions. Fat suppression should be used in conjunction with gadolinium for evaluating epidural, paravertebral, and intradural-extramedullary spinal lesions.

Adipose Tissue↗

PubMed1996

Identification of a novel dexamethasone responsive enhancer in the human CYP3A5 gene and its activation in human and rat liver cells.

The human liver cytochromes P450 3A (CYP3As), orthologous to the rat glucocorticoid inducible forms, are composed of at least four differentially expressed members. To begin the study of the molecular events in the glucocorticoid regulation of CYP3A5, we fused 5' sequences of CYP3A5 to the chloramphenicol acetyltransferase gene in a vector that contains the herpes simplex virus thymidine kinase promoter. In HepG2 cells, the largest 5' CYP3A5 gene fragment (1.4 kb) suppressed the TK promoter. However, suppression was overcome by addition of 10 microM dexamethasone. A series of unidirectional deletions revealed a unique 219-bp fragment (-891 to -1109 bp upstream from the transcriptional start site) that conferred dexamethasone responsiveness on the TK promoter regardless of either the distance or orientation from the promoter and thus appears to be an enhancer. Nucleotide sequence analysis of this CYP3A5 enhancer revealed no consensus 15-bp glucocorticoid responsive element (GRE) (GGTACANNNTGTTCT); however, two GRE "half-sites" (TGTTCT) were found separated by 160 bp. Although dexamethasone stimulated the CYP3A5 enhancer only 3-4-fold in HepG2 cells, the CYP3A5 enhancer was stimulated 7- and 12-fold in immortalized primary human hepatocytes and primary rat hepatocyte cultures, respectively. The glucocorticoid receptor (GCR) seems to be indispensable to this process because 1) dexamethasone induction can be blocked by the antiglucocorticoid RU-486, 2) dexamethasone-dependent transcriptional activation of the CYP3A5 enhancer in HepG2 cells required cotransfection of an expression vector containing the intact GCR, yet 3) cotransfection with a plasmid that contains a mutation in the ligand binding domain of the GCR does not activate the CYP3A5 enhancer in the presence of dexamethasone. To further localize the dexamethasone responsive region of the 219-bp CYP3A5 enhancer, it was subdivided and fused to the TKCAT expression vector. Transfection analysis in HepG2 cells demonstrated that neither GRE half-site can independently confer dexamethasone responsiveness on the TK promoter. Block mutations of either of the two GRE half-sites or point mutations at specific GCR binding sites eliminates dexamethasone inducibility, demonstrating the half-sites need to interact. Electromobility shift assays indicate that the CYP3A5 5'-GRE half-site 1) specifically binds purified GCR, 2) can displace binding of the GCR to a consensus GRE, and 3) shifts a protein in HepG2 nuclear extracts that is supershifted by GCR antibody, demonstrating that this enhancer is an authentic GRE. This is the first study to demonstrate that a member of the human CYP3A gene family contains an enhancer that binds the GCR and that this binding is critical to transcriptional activation by dexamethasone.

Animals↗

PubMed1996

Intensity of MR contrast enhancement does not correspond to clinical and electroneurographic findings in acute inflammatory facial nerve palsy.

PURPOSE: To determine the value of MR contrast enhancement in predicting the course of acute inflammatory facial nerve palsy and in selecting patients for surgical decompression. METHODS: Six patients with an acute inflammatory incomplete or complete peripheral facial nerve palsy (five idiopathic and one herpetic in origin) had repeated MR imaging studies with and without contrast enhancement, electroneurography, and clinical examinations to establish a connection between the intensity of contrast enhancement on MR images, the clinical condition, and the electrophysiological data. The examinations were performed every second day starting on the first day of admission until clinical recovery was proved by clinical deblockage (spontaneous clinical improvement). The last examination was performed 3 months after the onset of the facial nerve palsy. RESULTS: An abnormal, very intense contrast enhancement of the facial nerve was always present in the distal intrameatal and proximal tympanic segments and in the geniculate ganglion. The labyrinthine segment exhibited a mild to moderate enhancement, and the distal tympanic and mastoid segments showed a moderate to intense enhancement. The intensity of contrast enhancement did not correspond to the severity, duration, or course of the facial nerve palsy, and the electroneurographic data had no predictive value in indicating the severity of the inflammatory process. Three months after clinical recovery, a persistent and more or less unchanged or even slightly more intense contrast enhancement was observed. CONCLUSION: The long-lasting intense contrast enhancement seen in the facial nerve segments of patients who have acute peripheral inflammatory facial nerve palsy is explained by a two-phase breakdown of the blood-nerve barrier.

Adult↗

PubMed1998

[Enhanced MR imaging with a nonionic contrast gadolinium complex, Gadoteridol, for lumbar disc herniation].

The aim of this study was to evaluate the usefulness for lumbar disc herniation of enhanced imaging with a nonionic contrast gadolinium complex (Gadoteridol). Among 130 discs in 26 patients, 27 herniated discs were shown on MR sagittal imaging. They were classified into 4 types according to the enhancement pattern of the disc on MR sagittal imaging (Type Ia: nonenhancement, Type Ib: globular enhancement, Type II: strong enhancement, Type III: ring enhancement). The results were as follows: Type Ia: 3, Type Ib: 15, Type II: 7, Type III: 2. A total of herniated discs were enhanced with Gadoteridol. Surgery was performed in 5 patients (Type Ib: 1, Type II: 4). The herniated disc of Type Ib extruded but did not rupture the posterior ligament, whereas the herniated discs of Type II extruded and ruptured the posterior ligament. Thus, the herniated discs were enhanced with the nonionic contrast agent Gadoteridol. If the disc herniates over the posterior ligament, it might be strongly enhanced. Therefore, enhanced MR imaging is thought to be useful to establish the diagnosis of lumbar disc herniation.

Adult↗

PubMedDate not supplied

Sensitivity of enhanced MR in multiple sclerosis: effects of contrast dose and magnetization transfer contrast.

BACKGROUND AND PURPOSES: New strategies have been developed to improve the sensitivity of contrast-enhanced MR imaging in quantifying disease activity in patients with multiple sclerosis (MS). The goal of the present study was to evaluate the sensitivity of T1-weighted images after injection of a triple dose of contrast material and application of a magnetization transfer (MT) pulse in the detection of enhancing lesions as compared with the conventional approach. METHODS: Monthly MR images were obtained in 13 patients with relapsing-remitting MS for a period of 3 months. The MR studies were performed on two separate occasions with single- and triple-dose contrast material. In each session, T1- and T2-weighted spin-echo images with and without the MT pulse were obtained before and after contrast administration. All images were evaluated in a blinded fashion and scored in random order and consensually by two readers. The number of total and new enhancing lesions and active images was counted. RESULTS: Eighty-six percent more enhancing lesions and 54% more new enhancing lesions were detected with triple-dose as compared with single-dose non-MT sequences, whereas single-dose MT images depicted 33% more enhancing lesions and 18% more new enhancing lesions than the single-dose non-MT images. Twenty-nine percent more lesions were detected on triple-dose non-MT images than on single-dose MT images. The combination of a triple dose of contrast material and MT did not produce any significant change in detection of enhancing lesions as compared with a triple dose of contrast without MT. CONCLUSION: The use of a triple dose of contrast material is the best approach to maximize the sensitivity of enhanced MR imaging.

Adult↗

PubMed1997

Opposite effects of astrocyte-derived soluble factor(s) on the functional expression of fetal peptidergic neurons in aggregate cultures: enhancement of neuropeptide Y and suppression of somatostatin.

Previous studies established that fetal rat and human neuropeptide Y (NPY) cortical neurons in aggregate cultures are differentially regulated. Whereas brain-derived neurotrophic factor (BDNF) or phorbol 12-myristate-13-acetate (PMA) induces NPY production in rat cultures, only PMA does so in human cultures. We addressed these questions: 1) Do soluble products of rat or human astrocytes (conditioned medium; rCM and hCM, respectively) enhance the functional expression of cultured NPY neurons and if so, do they enhance the expression of somatostatin (SRIF) neurons as well? 2) Is the NPY-enhancing activity (EA) in the CM species specific? rCM enhanced (approximately 2-fold) both basal and BDNF-stimulated production of NPY and coculture of rat aggregates and astrocytes did not prevent this NPY-EA. Likewise, the hCM enhanced (approximately 2.5-fold) basal and PMA-stimulated production of NPY by human aggregates. Moreover, the hCM enhanced NPY production by rat aggregates and rCM enhanced NPY production by human aggregates. In addition, rCM and hCM each enhanced BDNF-, forskolin-, or PMA-stimulated NPY production by rat aggregates. Under each of the above conditions, the rCM/hCM suppressed (approximately 50%) production of SRIF by rat aggregates. In summary, secretory products of rat and human astrocytes exert opposite effects on the functional expression of NPY and SRIF neurons in culture: enhancement of NPY and suppression of SRIF. By the criteria evaluated in this study, these astrocyte-derived activities do not exhibit species specificity.

Animals↗

PubMed1999

Biliary hamartomas: solitary and multiple lesions shown on current MR techniques including gadolinium enhancement.

The purpose of this study was to describe the magnetic resonance (MR) imaging features of biliary hamartomas on T1- and T2-weighted and gadolinium-enhanced sequences, and to correlate these findings with histopathology. MR imaging findings in four patients with pathologically proved biliary hamartomas are described. In all patients, MR imaging sequences, including T1- and T2-weighted and early and late gadolinium-enhanced images, were retrospectively evaluated for the size, morphology, signal intensity, and enhancement pattern of the lesions. Correlation was made between the MR imaging findings and histopathology. Biliary hamartomas ranged in diameter from 0.5 to 1.5 cm. Lesions were solitary in one patient and numerous in three patients. In all patients, the lesions were low signal on T1-weighted images and high signal and well-defined on T2-weighted images and demonstrated thin rim enhancement on early post-gadolinium images that persisted on late post-gadolinium images. No appreciable central enhancement of the lesions was observed. At histopathology, the lesions were composed of cystic spaces and fibrous stroma. Lesions showed compressed liver parenchyma surrounding the lesions (three cases) and inflammatory cell infiltrate (one case), which correlated with the rim enhancement on the gadolinium-enhanced MR images. Most of the biliary hamartomas in our small series were less than 1 cm in diameter and of high signal intensity on T2-weighted images, and had a thin rim of enhancement on early and late post-gadolinium images. The imaging features were explainable by the underlying histopathology. In patients with known malignancy, caution should be exercised not to misinterpret these lesions as metastases due to the presence of thin rim enhancement. J. Magn. Reson Imaging 1999;10:196-201, 1999.

Adult↗

PubMed1985

Postoperative contrast enhancement in patients with brain tumor.

Contrast enhancement resulting from surgical trauma may mimic residual enhancing tumor, thereby complicating the interpretation of postoperative computed tomographic scans. We assessed the natural history of postoperative enhancement in 10 patients with brain tumor. Contrast enhancement distinguishable from residual enhancing tumor appeared along the operative margin following tumor resections but not lobectomies. Enhancement appeared as early as the fifth postoperative day, was most intense at two weeks, and persisted for several months. Prior to the fifth postoperative day, enhancement reflected residual tumor. Edema and artifacts were more prominent on the first and second postoperative days than on the third and fourth. We recommend that postoperative computed tomographic scans to assess residual enhancing tumor be performed on the third or fourth postoperative day. This timing avoids postoperative enhancement and minimizes interpretative difficulties caused by artifacts.

Adult↗

PubMed1986

Chemical enhancement of SA7 virus transformation of hamster embryo cells: evaluation by interlaboratory testing of diverse chemicals.

Twelve chemicals from diverse structural classes were tested under code for their capacity to enhance the transformation of Syrian hamster embryo cells by simian adenovirus SA7 in two independent laboratories. Pretreatment of hamster cells with eight of those chemicals (reserpine, dichlorvos, methapyrilene hydrochloride, benzidine dihydrochloride, diphenylhydantoin, cinnamyl anthranilate, 11-aminoundecanoic acid, and 4,4'-oxydianiline) produced repeatable enhancement of SA7 transformation at two or more consecutive dose levels, which constitutes clear evidence of enhancing activity in this assay. Both toxic and nontoxic doses of each of these chemicals caused enhancement of virus transformation. Two chemicals (2,6-dichloro-p-phenylenediamine and cinnamaldehyde) produced some evidence of enhancing activity (repeatable transformation enhancement at one dose). Dose ranges for cytotoxicity and enhancement of SA7 transformation were similar in both laboratories for all chemicals producing activity. The final two chemicals, chloramphenicol sodium succinate and ethylene thiourea, failed to reproducibly demonstrate either significant cytotoxicity or enhancement of SA7 transformation at concentrations up to 10-20 mM. The test results for these 12 chemicals were combined with the test results for 9 known carcinogens and noncarcinogens in order to evaluate relationships between activity, dose response, and lowest effective enhancing concentration for these compounds, as well as to correlate them with rodent carcinogenesis classifications. The Syrian hamster embryo cell-SA7 system demonstrated reproducible test responses in both intra- and interlaboratory studies and detected 13 out of 15 known rodent carcinogens.

Adenoviridae↗

PubMed1993

TPA-enhanced invasion of Matrigel associated with augmentation of cell motility but not metalloproteinase activity in a highly metastatic variant (L-10) of human rectal adenocarcinoma cell line RCM-1.

We previously found that the enhanced activity to invade Matrigel upon stimulation with 12-O-tetradecanoylphorbol-13-acetate (TPA) was one of the major properties of a highly metastatic variant (L-10) of a human rectal adenocarcinoma cell line RCM-1. To clarify the mechanism of this enhancement, we examined the effect of TPA on 2 major biological factors involved in tumor cell invasion: cell motility and matrix-degrading metalloproteinase activity. The enhanced invasiveness was inhibited by protein-kinase-C inhibitors. TPA markedly enhanced both haptotactic response to type-IV collagen and motility on tissue-culture glass substrate of L-10 cells in a dose-response manner quite similar to that of TPA-enhanced invasion of Matrigel. On the other hand, TPA showed little enhancement of metalloproteinase production, which was assessed by gelatin- and casein-zymography, and of type-IV collagenolytic activity. Addition of TIMP (tissue inhibitors of metalloproteinase)-I inhibited TPA-enhanced invasion of Matrigel by only up to 13%. Thus, TPA treatment of L-10 cells enhanced invasion of Matrigel in association with augmentation of cell motility but did not enhance metalloproteinase activity.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMedDate not supplied

Contrast-enhanced power Doppler sonography and helical computed tomography for assessment of vascularity of small hepatocellular carcinomas before and after percutaneous ablation.

PURPOSE: We compared the usefulness of Levovist-enhanced power Doppler imaging (PDI) and helical CT in the depiction of tumor vascularity before and after percutaneous ablation of small hepatocellular carcinomas (HCCs). METHODS: Thirty-one cirrhotic patients with solitary unresectable HCCs smaller than 5 cm (mean size, 2.7 +/- 0.8 cm; range, 1.5-5.0 cm) recruited over a 15-month period were treated with percutaneous ethanol injection (n = 9) or radiofrequency ablation (n = 22). PDI, contrast-enhanced PDI (using Levovist), and multiphase contrast-enhanced helical CT were performed before and after percutaneous ablation, and vascularity findings were compared. RESULTS: Levovist significantly increased baseline intratumoral Doppler signals on PDI compared to non-contrast PDI. The most frequent tumor vascularity pattern was heterogeneous (45%). Vascularity was identified in all tumors by both contrast-enhanced PDI and helical CT before ablation. After percutaneous ablation, intratumoral vascularity was detected in 11 tumors by contrast-enhanced PDI and in 15 tumors by CT. The sensitivity, specificity, and diagnostic accuracy of contrast-enhanced PDI in demonstrating intratumoral vascularity, with CT being the gold standard, were 66%, 93%, and 81%, respectively. There was significant agreement between the 2 modalities in the depiction of tumor vascularity after ablation (kappa = 0.6, p = 0.001). However, there were 5 false negatives and 1 false positive with contrast-enhanced PDI. Complete tumor necrosis was achieved in 21 patients (68%). CONCLUSIONS: There was a good concordance between contrast-enhanced PDI and helical CT in the depiction of HCC vascularity before and after percutaneous ablation. However, although contrast-enhanced PDI may be useful for real-time guidance of treatment, its low sensitivity makes it inadequate to accurately assess the completeness of ablation.

Aged↗

PubMed2004

Synovitis and soft tissue impingement of the ankle: assessment with enhanced three-dimensional FSPGR MR imaging.

PURPOSE: To assess soft tissue impingement as well as synovitis of the ankle associated with trauma by using contrast-enhanced (CE), fat-suppressed, three-dimensional, fast gradient-recalled acquisition in the steady state with radiofrequency spoiling (FSPGR) magnetic resonance (MR) imaging. MATERIALS AND METHODS: A total of 36 patients who had had chronic ankle pain associated with a traumatic injury undertook fat-suppressed CE three-dimensional FSPGR MR imaging and then arthroscopy of the ankle. The ankle joint was divided into four compartments by anatomic details: the anterolateral gutter, anteromedial gutter, anterior recess, and posterior recess. Synovial enhancement was graded as follows: grade I, no enhancement; grade II, linear enhancement; grade III, focal nodular enhancement; and grade IV, irregular nodular enhancement. MR grading of the synovial enhancement (synovitis, grade III or IV; soft tissue impingement, grade III or IV with its intrusion from the capsular reflection) was compared with arthroscopic findings. A control study of twenty asymptomatic ankles was done for determining enhancement. Arthroscopy confirmed synovitis in 47 compartments of 27 patients. Of the 27 patients, 15 revealed soft tissue impingement in 17 compartments. RESULTS: For the assessment of synovitis, fat-suppressed CE three-dimensional FSPGR MR imaging had an accuracy of 72.9%, sensitivity of 91.5%, and specificity of 63.9%; whereas for that of soft tissue impingement it had an accuracy of 94.4%, sensitivity of 76.5%, and specificity of 96.9%. All of the asymptomatic subjects showed grade I (81%) or II (19%) synovial enhancement. CONCLUSION: Fat-suppressed CE three-dimensional FSPGR MR imaging was sensitive for the evaluation of synovitis of the ankle associated with trauma, whereas it was specific for soft tissue impingement evaluation.

Adolescent↗