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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

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

Histologic basis for increased extraocular muscle enhancement in gadolinium-enhanced MR imaging.

Minimal to mild enhancement of skeletal muscles is normally seen on gadolinium-enhanced magnetic resonance images. The enhancement of the extraocular muscles is much more intense than that of other skeletal muscles. The authors investigated the structural features of extraocular muscles that contribute to this increased enhancement. After comparing samples of extraocular muscle and quadriceps muscle, the authors concluded that the rich vascularity and the prominence of extravascular space most probably cause extraocular muscles to demonstrate intense enhancement on gadolinium-enhanced images.

Gadolinium DTPA

Transformation by human papillomavirus type 16 (HPV16) DNA but not HPV6b DNA is enhanced by addition of the human cytomegalovirus enhancer.

Primary human cervical epithelial cells immortalized by human papillomavirus type 16 (HPV16) DNA exhibit altered morphology and differentiation characteristic of transformation, but show a lack of transformed phenotype relative to HPV18 DNA immortalized cells in terms of anchorage-independent growth (Pecoraro, Lee, Morgan, and Defendi, 1991, Am. J. Pathol. 138, 1-8). This is completely corrected by inserting a strong heterologous enhancer derived from human cytomegalovirus DNA upstream from the HPV16 long control region. The cells immortalized by this DNA form colonies in agar comparable to those formed by HPV18 DNA immortalized cells. The enhanced transformation capability correlates with increased levels of HPV16 E6-E7 and E5 transcripts. The HPV16 DNA containing this strong enhancer also transforms C127 mouse cells with increased efficiency and strength relative to the natural HPV16 DNA, as measured by the numbers and size of the colonies in agar. The positive effects of this strong enhancer appear specific for HPVs associated with genital malignancies such as HPV16, since HPV6b DNA (primarily in benign tumors) with or without the strong cytomegalovirus enhancer is incapable of immortalizing primary human cervical epithelial cells or allowing efficient growth of C127 mouse cells in agar. These results suggest that the diminished oncogenic properties of HPV16 versus HPV18 DNA in cultured cells and in human malignancies may reside in the long control regions of these viruses and, additionally, may define another difference in the oncogenic properties of HPVs associated with benign or malignant genital neoplasia.

Animals

Thin-rim enhancement in Gd-DTPA-enhanced magnetic resonance images of tuberculoma: a new finding of potential differential diagnostic importance.

The article describes rim enhancement seen on Gd-DTPA-enhanced magnetic resonance (MR) images of two patients with tuberculoma. Pathologic examination of the surgical specimens disclosed that the peripheral portion of the tuberculoma, which showed contrast enhancement, was composed mainly of a fibrous capsule and epithelioid granulomas and that the central zone, which showed no contrast enhancement, was composed of caseous necrotic material. In a retrospective study of MR images from 20 consecutive cases of surgically proven bronchogenic carcinoma, none showed a thin enhancing rim on postcontrast MR images. Although confirmation of these findings must await further experience, the postcontrast MR findings described here may prove to be of value in distinguishing tuberculoma and possibly other granulomatous lesions from bronchogenic carcinoma.

Adult

Ovarian follicle cell enhancers from the Drosophila yolk protein genes: different segments of one enhancer have different cell-type specificities that interact to give normal expression.

This paper examines ovarian transcription of the divergently oriented yolk protein genes 1 and 2 (yp1 and yp2) of Drosophila melanogaster. We report germ line transformation results demonstrating that yp1 and yp2 are transcribed in the same subpopulations of ovarian follicle cells. Our results show that this expression pattern is directed by two enhancers: ovarian enhancer 1, located between the genes, and ovarian enhancer 2, located within the first exon of yp2. Analysis of the expression pattern resulting from alterations in ovarian enhancer 1 demonstrates that different segments of this enhancer have different positive or negative effects on the cell-type specificity of transcription.

Animals

[Enhancement of cellular transforming activities of truncated EJ c-H-ras-1 with viral enhancers or with c-myc].

The 2.9kb Sac I fragment (EJ2.9), which lacks the previously reported promoter/enhancers of the activated human c-H-ras-1, was used to study the interaction with the tumor virus promoter/enhancers or with the activated c-myc. When EJ2.9 constructs linked to the viral promoter/enhancers or to a viral enhancer even in the antisense orientation was transfected to the mouse cells, 16-39% of the foci induced with those linked in the sense orientation were formed. Further, the transforming activity decreased dramatically when the deletion was introduced from the upstream Sac I site to the 61 bases (-61) upstream of translational initiation codon, but the deletions to -144 did not significantly change the activity. Cotransfections with the activated c-myc were found also to enhance the transforming activity of EJ2.9 constructs either with or without the LTR linked in the antisense orientation. The transfected ras and myc were expressed as 1.2 and 2.5kb mRNAs, respectively, in each transformant. The in vitro mutagenesis suggested that the c-myc protein was involved in the enhancement. These results raise the possibility that the viral enhancers activate a cryptic promoter (s) within the region between -1 and -144 of p21 initiation codon by interacting with the region between -61 and -144 and that the c-myc protein also activates the same or different cryptic promoter(s) within the intron 0 or noncoding region of exon I, thus leading to the enhancement of the EJ2.9 transforming activity.

Animals

Prominent dural enhancement adjacent to nonmeningiomatous malignant lesions on contrast-enhanced MR images.

Prominent dural enhancement was noted in 10 (16%) of 61 superficial malignant intracranial tumors studied with contrast-enhanced MR imaging during a 2-year period. Included were six glioblastomas, three parenchymal metastases, and one case of dural metastasis. Seven patients had surgery. In four, there was extensive leptomeningeal invasion in the center of the lesion. In two of these lesions there was firm attachment of the center of the tumor to the dura, but without dural invasion despite extensive external carotid artery supply to the tumor in one case. In two cases the overlying dura was normal, and there was no leptomeningeal tumoral invasion. In the case of dural metastasis, huge nodular lesions were present along the inner aspect of the dura. In none of the cases did prominent dural enhancement adjacent to the tumor correspond with tumoral invasion or extension to the dura. Prominent dural enhancement on contrast-enhanced MR images appears to be much less frequent in malignant tumor than in meningioma, where it is seen in up to 60% of the cases. We believe this finding is more likely to represent reactive changes of the dura than tumoral invasion.

Brain Neoplasms

Contrast-enhanced MR images in patients with meningioma: importance of enhancement of the dura adjacent to the tumor.

Linear enhancement (flare sign) along the dura mater that was continuous with or emanated from the dural margin of meningiomas was frequently observed on contrast-enhanced MR images obtained in 18 patients with intracranial meningiomas (surgically proved). Preoperative MR studies obtained at 1.5 T after administration of gadopentetate dimeglumine were reviewed retrospectively to determine the clinical significance of this sign. Thirteen (72%) of the 18 meningiomas exhibited the finding adjacent to the dural attachments. Four meningiomas of the cerebellopontine angle showed enhancement along the internal auditory canals. Three specimens of the dura adjacent to the tumor in different patients with this finding revealed proliferation of connective tissues abounding with vessels along the dura without definite tumor invasion. The flare sign is thought to be a common finding of meningiomas on contrast-enhanced MR images obtained with high-resolution sequences, and it is observable without tumor invasion. This sign in the cerebellopontine angle should not be misinterpreted as enhancement of acoustic schwannomas.

Adult

A tumor promoting phorbol ester, TPA, enhances polyomavirus DNA replication by activating the function of the viral enhancer.

The effect of tumor promoter, 12-O-tetradecanoylphorbol 13-acetate (TPA) on enhancer dependent polyomavirus (Py) DNA replication was examined in cells expressing Py large T antigen. The results showed that TPA enhanced Py DNA replication by stimulating the activity of the A element, one of the two cores of Py enhancer. Of the three subdomains of the A element, the biding sites of PEBP1 (PEA1), a member of AP1 family, and of PEBP5 were by themselves able to activate Py DNA replication. Furthermore, each binding site of PEBP1 and PEBP5 responded to TPA to enhance Py DNA replication. The results suggest that growth promoting signals could activate DNA replication directly via enhancer binding proteins.

Antigens, Polyomavirus Transforming

Enhancement studies on algae and isolated chloroplasts. Part II. Enhancement of oxygen evolution in intact chloroplasts.

Intact isolated chloroplasts were shown to exhibit a characteristic three-phase pattern of development of oxygen evolution activity. The first phase, Phase I, appeared to be an equilibration phase in which the isolated chloroplasts adapted to the conditions on the electrode surface. It was characterised by a rapidly increasing rate of oxygen evolution accompanied by decreasing enhancement signals. The second phase, Phase II, was an intermediate phase in which the rate of oxygen evolution was maximal and no enhancement was observed. In the last phase, Phase III, the rate of oxygen fell again, normal enhancement was still missing, but the samples appeared to undergo slow adaptive changes closely related to the State I-State II changes previously reported for whole cell systems. The concentrations of Mg2+ within the chloroplast were shown to play an important role in the control of the development of both the oxygen evolution and enhancement signals. It was shown how these signals could be explained in terms of a model that was consistent with that developed in Part I of this investigation to account for the variability of enhancement of the alga Chlorella pyrenoidosa.

Chlorella

Regulation of human monocyte/macrophage function by extracellular matrix. Adherence of monocytes to collagen matrices enhances phagocytosis of opsonized bacteria by activation of complement receptors and enhancement of Fc receptor function.

In inflammation monocytes emigrate from the peripheral circulation into an extravascular area rich in extracellular matrix proteins. In this milieu, phagocytes ingest and kill invading pathogens. In the present studies, we found that monocytes adhered to type I collagen gels phagocytized 2.5-12-fold more opsonized Escherichia coli, Staphylococcus aureus, Streptococcus pyogenes, and Streptococcus pneumoniae than plastic-adherent monocytes. The rate of phagocytosis and the number of bacteria ingested by collagen-adherent monocytes was equal to, or greater than, the number of bacteria ingested by 7-d cultured macrophages (M phi). Although both collagen- and plastic-adherent monocytes were bactericidal for E. coli and S. aureus, more bacteria were killed by collagen-adherent monocytes by virtue of their enhanced phagocytic capacity. Cultured M phi only were bacteriostatic. Adherence of monocytes to collagen gels activated C receptors (CR) types 1 and 3 for phagocytosis, and enhanced Fc receptor (FcR)-mediated phagocytosis. Collagen- and plastic-adherent monocytes produced equivalent amounts of superoxide anion in response to phorbol myristate acetate and opsonized zymosan. Thus, the enhanced phagocytosis and killing of opsonized bacteria by collagen-adherent monocytes appear to be by regulation of the function of membrane CR and FcR, without apparent enhancement of the respiratory burst. These data suggest that adherence of monocytes to the extracellular matrix during inflammation may rapidly activate these cells for enhanced phagocytic bactericidal activity.

Blood Bactericidal Activity

Prokaryotic transcriptional enhancers and enhancer-binding proteins.

A number of prokaryotic enhancer-binding proteins activate transcription by specialized forms of RNA polymerase. The enhancer-binding proteins catalyse isomerization of the initial complex formed between RNA polymerase and a promoter from the closed to the open state. To do so, one class of enhancer-binding proteins contacts its cognate polymerase by DNA loop formation but the other, which is represented by a single member, does not. Despite this difference, both classes of enhancer-binding proteins must hydrolyse ATP to catalyse open complex formation.

Amino Acid Sequence

Structural and functional analysis of a replication enhancer: separation of the enhancer activity from origin function by mutational dissection of the replication origin gamma of plasmid R6K.

The plasmid R6K possesses three distinct origins of replication: alpha, beta, and gamma. The replication origin gamma of plasmid R6K performs a dual function: (i) as an origin itself and (ii) as an enhancer element required in cis for the activation at a distance of the other two replication origins alpha and beta. We have dissected the gamma origin/enhancer by site-directed mutagenesis and have reached the following conclusions. The origin function can be specifically inactivated without impairing the enhancer function by insertion and/or deletion mutations near the opposite ends of the origin gamma sequence. One such mutation deleted sequences that included the left DnaA site I. The second mutation involved insertion of linker sequences that resulted in a spatial alteration between the right DnaA site II and the VIIth pi binding iteron (tandemly repeated binding sites). Other mutations that either partly or completely deleted the A+T-rich sequence adjacent to, but not including, the pi binding iterons also abrogated enhancer and origin function and suggested that pi binding sites were necessary but not sufficient for enhancer activity. Finally, the functional analysis of a set of mutants of the gamma origin/enhancer suggested that a continuous stretch of 300 base pairs is necessary for origin gamma function and that the sequences that included the binding sites for pi, DnaA, and integration host factor proteins are required in the correct stereochemical alignment to impart origin activity.

Bacterial Proteins

Binding of SL3-3 enhancer factor 1 transcriptional activators to viral and chromosomal enhancer sequences.

Interactions between SL3-3 enhancer factor 1 (SEF1) proteins and the enhancer of the murine leukemia virus SL3-3 were analyzed. SEF1 proteins were found to interact with two different DNA sequences within the DNA repeat region of the enhancer; these two motifs cooperated in enhancing initiation of transcription in T lymphocytes. Using an electrophoretic mobility shift assay, we identified nucleotides that are important for the SEF1 binding, and we deduced a sequence, 5'-TTTGCGGTTA/T-3' with highly improved binding of SEF1 proteins. We show that many different SEF1 binding sequences exist in the transcription control regions of different viral and cellular genes. The results indicate a general role of SEF1 proteins in T-cell gene expression.

Animals

An extravascular component of contrast enhancement in cranial computed tomography. Part II. Contrast enhancement and the blood-tissue barrier.

The authors provide evidence of significant extravasation of contrast media responsible for the contrast enhancement of pathological tissue on computed tomography. The tissue-blood ratio of enhancement was calculated by the EMI scanner in 2 patients after injection of contrast material and prior to surgery; tumor-blood ratios for red blood cell and plasma tracers were calculated after surgery. The ratios of enhancement demonstrated the analogy between contrast enhancement and the leaking of radionuclide across the blood-brain barrier. This phenomenon may cause error if this technique is used for the measurement of cerebral blood volume. The area for complementary roles of CT and radionuclide brain imaging seems to be narrower than expected.

Animals

Focal liver disease: comparison of dynamic contrast-enhanced CT and T2-weighted fat-suppressed, FLASH, and dynamic gadolinium-enhanced MR imaging at 1.5 T.

Dynamic contrast medium-enhanced computed tomography (CT), T2-weighted fat-suppressed spin-echo (T2FS) magnetic resonance (MR) imaging, and breath-hold T1-weighted fast low-angle shot (FLASH) MR imaging before and after dynamic gadopentetate dimeglumine injection were compared in 73 patients with clinically suspected liver disease. Observer confidence for presence of focal lesions was determined by using receiver operating characteristic analysis. For all MR images, hepatic lesion-liver signal-to-noise ratios were evaluated qualitatively. and resolution and presence of artifacts were evaluated qualitatively. Lesion detection was greatest with T2FS (n = 272) and enhanced FLASH (n = 244) and was statistically greater with both of these than with CT (n = 220) and FLASH (n = 219) (P less than .03). Correct lesion characterization was greatest with enhanced FLASH (n = 236) (P less than .01), followed by CT (n = 199), FLASH (n = 164), and T2FS (n = 144). Enhanced FLASH was particularly successful in characterization of 5-mm- to 1.5-cm-diameter lesions as cystic or solid.

Adenoma

Specific DNA binding to a major histocompatibility complex enhancer sequence by a synthetic 57-residue double zinc finger peptide from a human enhancer binding protein.

Two 57-residue peptides containing one pair of "zinc fingers" from a human enhancer binding protein were prepared by solid-phase peptide synthesis. One peptide (MBP-DF) contained the native sequence, while the second peptide ([Abu11]MBP-DF) has an alpha-aminobutyric acid residue substituted for a nonconserved cysteine residue at position 11. The peptides were characterized by several chemical and physical methods, and their DNA binding properties were evaluated using gel retardation experiments. Spectroscopic studies demonstrated that addition of metal ions such as zinc and cobalt resulted in specific conformational changes in both peptides, indicating that cysteine-11 does not appear to be involved in metal chelation. One-dimensional 1H NMR studies indicate that a stable folded structure is formed upon addition of zinc, and the chemical shift pattern is consistent with that previously observed for one constituent single finger (Omichinski, J., Clore, G. M., Appella, E., Sakaguchi, K., and Gronenborn, A. M. (1990) Biochemistry 29, 9324-9334). Gel retardation experiments demonstrate that the peptides are capable of interacting with a 15-mer oligonucleotide comprising a portion of the major histocompatibility complex enhancer sequence and that the interaction is zinc-dependent. The dissociation constant for the [Abu11]MBP-DF peptide is 1.4 x 10(-7) M with maximal binding occurring at a zinc-to-peptide ratio of 2 to 1. The binding specificity observed with respect to related enhancer sequences exhibits the same relative order as noted previously for the whole protein. Studies with point mutants of the major histocompatibility complex enhancer binding sequence indicate that the last GC base pair in a four-guanine stretch plays a pivotal role in the interaction between the peptide and DNA.

Amino Acid Sequence