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Inhomogeneous enhancement of liver parenchyma secondary to passive congestion: contrast-enhanced CT.

Passive liver congestion secondary to increased hepatic venous pressure may accompany congestive heart failure. Abnormal patterns of hepatic parenchymal contrast medium enhancement in 25 patients with advanced congestive heart failure who were studied with computed tomography (CT) include a lobulated, patchy, inhomogeneous pattern in all 25 patients, an irregular perivascular enhancement in 14, and a global delay in parenchymal enhancement in nine. CT examinations showed cardiomegaly in the 20 patients with cardiac failure and pericardial effusion or thickening in the five patients with pericardial disease. Also noted were distention of the inferior vena cava (IVC) in 24 patients, hepatomegaly in 23, early reflux of contrast medium into the IVC in 21 and hepatic veins in 16, and hepatic perivascular lymph-edema in six. The abnormal patterns are thought to be due to slowing of hepatic blood flow. Confusion with Budd-Chiari syndrome and other forms of multifocal hepatic disease is avoidable with clinical and radiologic correlation.

Adult↗

Pituitary adenomas and normal pituitary tissue: enhancement patterns on gadopentetate-enhanced MR imaging.

A dynamic study of magnetic resonance (MR) imaging was used to obtain successive heavily T1-weighted coronal images (spin-echo [SE] 100/15 [repetition time msec/echo time msec]) of normal pituitary glands and pituitary adenoma immediately after patients were given an intravenous bolus injection of gadopentetate dimeglumine. The images were obtained every minute for 5-8 minutes at 1.5 T. Usual T1-weighted images (SE 600/15) were also obtained before and after the dynamic study was performed. The study group consisted of 18 patients, 10 with normal pituitary glands, and eight with pituitary adenoma. Normal pituitary glands showed maximum enhancement on the first or second image following the administration of gadopentetate dimeglumine, followed by gradual signal reduction through the later images, whereas pituitary adenomas reached a peak of enhancement later and showed slower signal reduction than normal pituitaries. The difference of enhancement patterns between the normal pituitary gland and the pituitary adenoma produced prominent image contrast on the first or second image after administration of gadopentetate dimeglumine, which improved the visualization of one microadenoma and four normal pituitary glands that had been displaced by large adenomas. Dynamic MR imaging is a useful diagnostic procedure not only for detection of microadenomas, but also for visualization of pituitary glands that have been displaced by large pituitary adenomas.

Adenoma↗

Enhancement of sensitivity and resolution of surface-enhanced laser desorption/ionization time-of-flight mass spectrometric records for serum peptides using time-series analysis techniques.

BACKGROUND: Measurement of peptide/protein concentrations in biological samples for biomarker discovery commonly uses high-sensitivity mass spectrometers with a surface-processing procedure to concentrate the important peptides. These time-of-flight (TOF) instruments typically have low mass resolution and considerable electronic noise associated with their detectors. The net result is unnecessary overlapping of peaks, apparent mass jitter, and difficulty in distinguishing mass peaks from background noise. Many of these effects can be reduced by processing the signal using standard time-series background subtraction, calibration, and filtering techniques. METHODS: Surface-enhanced laser desorption/ionization (SELDI) spectra were acquired on a PBS II instrument from blank, hydrophobic, and IMAC-Cu ProteinChip arrays (Ciphergen Biosystems, Inc.) incubated with calibration peptide mixtures or pooled serum. TOF data were recorded after single and multiple laser shots at different positions. Correlative analysis was used for time-series calibration. Target filters were used to suppress noise and enhance resolution after baseline removal and noise rescaling. RESULTS: The developed algorithms compensated for the electronic noise attributable to detector overload, removed the baseline caused by charge accumulation, detected and corrected mass peak jitter, enhanced signal amplitude at higher masses, and improved the resolution by using a deconvolution filter. CONCLUSIONS: These time-series techniques, when applied to SELDI-TOF data before any peak identification procedure, can improve the data to make the peak identification process simpler and more robust. These improvements may be applicable to most TOF instrumentation that uses analog (rather than counting) detectors.

Artifacts↗

ICOS expression by activated human Th cells is enhanced by IL-12 and IL-23: increased ICOS expression enhances the effector function of both Th1 and Th2 cells.

Previous mouse studies have shown that IL-4 increases the expression of ICOS on activated Th cells, resulting in enhanced ICOS expression on Th2 cells. In this study, we show that ICOS expression on human Th cells is not increased by IL-4, but by IL-12 and by IL-23 instead. Consequently, ICOS expression during IL-12-driven Th1 cell polarization was transiently increased compared with the levels on Th0 cells and IL-4-driven Th2 cells. Addition of IL-12 and/or IL-23 during restimulation increased ICOS expression to the same extent on pre-established Th1, Th2, and Th0 cells, indicating that ICOS levels are not stably imposed by prior polarization. In contrast to the findings in the mouse, IL-4 significantly suppressed the ICOS-enhancing effects of IL-12 and IL-23. The functional consequence of variable ICOS levels was shown in coculture experiments with cells expressing the ICOS-ligand B7-related protein 1 (either transfected Chinese hamster ovary cells or autologous dendritic cells). Ligation of ICOS on 2-day-preactivated effector cells increased their cytokine production to an extent proportional to their ICOS expression levels. As the ICOS-enhancing potentials of IL-12 and IL-23 were maintained for several days after stimulation, both on Th1 and Th2 cells, we propose the concept that local regulation of ICOS expression on activated Th cells by IL-12 and/or IL-23 may provide a powerful means to amplify effector T cell responses in peripheral tissues, independently of the polarized state of the Th cells.

Animals↗

Enhancing activity and phospholipase A2 activity: two independent activities present in the enhancing factor molecule.

Enhancing factor (EF), a molecule that increases the binding of epidermal growth factor (EGF) to A431 cells, was first isolated in our laboratory from mouse intestines, and subsequently shown to be a secretory form of phospholipase A2 (PLA2) [Mulherkar, Rao, Wagle, Patki and Deo (1993) Biochem. Biophys. Res. Commun. 195, 1254-1263]. We had proposed earlier that EF increases the binding of EGF by first binding to its own cell-surface receptor [identified as a 100 kDa molecule; Mulherkar and Deo (1986) J. Cell. Physiol. 127, 183-188], and then by creating a binding site for EGF. However, due to its PLA2 activity, there was a possibility that EF, by its phospholipase activity could be unmasking cryptic EGF receptors on the cell surface, thereby increasing the number of binding sites for EGF. To test whether enhancing activity and phospholipase activity are independent of each other, a series of mutations were created using the full-length EF cDNA as a template, expressed in 293 cells and the mutant recombinant proteins checked for EF as well as PLA2 activities. Our studies have shown that one of the mutant EF proteins, lacking PLA2 activity, retains EF activity. This demonstrates unambiguously that EF and PLA2 activities are two independent activities in the same molecule. Mutation in the Ca2+-binding loop resulted in loss of EF activity, thereby demonstrating that EF activity is Ca2+-dependent. The N-terminal region of the EF molecule appears to be crucial for the enhancing activity.

Animals↗

Immunologic enhancement of rat renal allografts. III. Immunopathologic lesions and rejection in long-surviving passively enhanced grafts.

Immunologic enhancement of renal allografts from (Lewis times Brown Norway) F1 to Lewis rats was achieved by administering a single dose of antidonor serum at the time of transplantation. A series of grafts functioning for 1 to 4 months after transplantation were examined by light and immunofluorescence microscopy to evaluate the long-term protective effects of the enhancing serum and to determine if previously unobserved lesions appeared in long survivors. Despite the absence of detectable circulating cytotoxic alloantibody, long-term allografts showed necrotizing glomerular and arterial lesions which resembled those seen in acutely rejecting grafts and were compatible with humoral rejection. Thus, in this model, there is a late decline in the ability of passive enhancement to inhibit humoral rejection. Long-term grafts also developed tubular lesions with deposition of immunoglobulin and complement on the tubular basement membranes (TBM). Anti-TBM antibodies were demonstrated in recipients' sera and found to be organ specific but not major histocompatibility antigen or species specific. This tubular lesion is therefore a unique form of allograft injury in which the immune response is directed against tissue antigen(s) which are distinct from the major histocompatibility antigens that induce rejection.

Animals↗

[Enhancement of FG020326 on sensitivity of MCF-7/ADR cells to taxotere via enhancing activation of caspase-8 and caspase-3].

BACKGROUND & OBJECTIVE: Multidrug resistance (MDR) is often characterized by over-expression of P-glycoprotein (P-gp) as drug efflux protein. Recent researches showed P-gp can inhibit caspase-dependent apoptosis, and protect MDR cells from apoptosis. This study was designed to investigate reversal effect of FG020326, a potent MDR modulator,on drug-resistance of MCF-7/ADR cells towards taxotere,and its mechanism. METHODS: Drug-resistant MCF-7/ADR cells, over-expressed P-gp, were cultured with FG020326 and taxotere. The reversal effect of FG020326 was assayed by MTT method. Apoptotic morphology of MCF-7/ADR cells was observed under fluorescent microscope after Hoechst33258 staining, cell apoptosis was measured by flow cytometry (FCM). Activation of caspase-8 and caspase-3 was measured by Western blot and colorimetric assay. RESULTS: FG020326 enhanced sensitivity of MCF-7/ADR cells to taxotere, and gave a 24-fold reversal of apoptosis-resistance with concentration of 10 micromol/L. Under effect of 10 micromol/L FG020326,chromatin condensation, apoptotic bodies, and sub-G1 peak were observed in MCF-7/ADR cells. Sensitivities of caspase-8 and caspase-3 were enhanced by demostrating cleavage of caspase-8, caspase-3,and PARP in MCF-7/ADR cells. Activities of caspase-3 and caspase-8 in MCF-7/ADR cells cultured with 10 micromol/L FG020326 and 0.1 micromol/L taxotere were increased in a time-dependent manner,and reached peak values at 48 h, which were significantly higher than those in cells cultured with taxotere alone. CONCLUSION: FG020326 may reverse drug-resistance of MCF-7/ADR cells towards taxotere through enhancing activation of caspase-8 and caspase-3 induced by taxotere.

Antineoplastic Agents, Phytogenic↗

Comparison of auto-moving table contrast-enhanced 3-D MRA and iodinated contrast-enhanced DSA for evaluating the lower-extremity arteries.

BACKGROUND: This study was conducted to compare diagnostic efficacy of contrast-enhanced 3-dimensional magnetic resonance angiography (3-D MRA) with that of the conventional x-ray iodinated digital subtraction angiography (DSA) in patients with peripheral arterial occlusive diseases (PAOD). METHODS: Twenty patients with a clinical diagnosis of PAOD participated in this study. All patients were evaluated with both contrast-enhanced 3-D MRA and conventional x-ray iodinated DSA for the arteries of their lower extremities. The DSA was performed by a selective catheterization into the bilateral common or superficial femoral arteries, whereas 3-D MRA was performed with an auto-moving table covering the vascular tree from aorta to the arteries of ankle regions with 1 bolus injection of a triple-dose (0.3 mmol/kg) contrast medium. The arteries were divided into 23 anatomic segments and graded by their appearance on a 1-4 scale (1 = normal, 4 = total occlusion or no visible vessel). Evaluators also compared the images of 3-D MRA with those of the conventional x-ray iodinated DSA (as gold standard) with respect to image quality. RESULTS: There was a high agreement (k = 0.6-1.0) between 2 observers' interpretations of the images obtained from 3-D MRA and conventional DSA. The agreement within each observer was moderate to fair (k = 0.32-0.57), and the better agreement was found with the images above knee level than those below knee level. As for the image quality of 3-D MRA, the frequencies of showing a similar image quality were 57.5%, 55%, and 37.5% at the aortofemoral, femoropopliteal, and distal leg levels, respectively. CONCLUSIONS: The main problem of the 3-D contrast enhanced MRA was the returned venous contamination of the image. It was particularly problematic for the areas below knee level. MRA can provide an initial evaluation for patients with PAOD, but cannot substitute for the conventional DSA as a precise diagnostic image modality for peripheral vascular diseases, especially for the distal legs.

Aged↗

Contrast enhancement of cystic portions in brain tumors on delayed image of gadolinium-DTPA-enhanced MR imaging.

This report describes three patients whose cystic portions were filled with intravenously injected Gadolinium-DTPA. Four cystic portions showed contrast enhancement of the whole wall on early MR images and enhancement of the content on delayed MR images. Two cystic portions showed no enhancement of content. We speculate that the difference is based upon the composition of the cyst walls.

Adolescent↗

Enhanced cloning efficiency of murine rhabdomyosarcoma cells after chlorozotocin treatment: relationship with enhanced lung metastasis.

The effect of chlorozotocin [(CZT) CAS: 54749-90-5; 2-(3-(2-chloroethyl)-3-nitrosoureido)-D-gluco-pyranose] was studied on a series of tumor cells, cultured or extracted fresh primary or transplanted tumors, by means of clonogenic assay. The ability of most rat rhabdomyosarcoma cells to form colonies in soft agar was enhanced when exposed to the water-soluble nitrosourea chloride CZT. The tumor cells tested were derived from a) several primary tumors induced in WAG rats by colloidal nickel, then cultured and exposed to CZT early during in vitro passage; b) the 9-4 tumor, also Ni-induced but maintained in long-term culture; and c) the Ni-induced 9-4/0 tumor, maintained by transplantation in syngeneic rats. No inhibition of colony formation was observed in any of the cell lines even at high concentrations of CZT. Adriamycin, chosen as a control treatment, strongly inhibited the cloning efficiency (CE) of the tumor cells. In vivo, the weekly injection of 10 mg CZT/kg body weight into syngeneic rats bearing transplanted tumors led to an enhancement of lung metastasis formation. The CZT enhancement of CE of tumor cells and its relationship to increased in vivo tumor metastasis is discussed.

Animals↗

Enhancement of the release reaction not accompanied with enhanced phosphatidylinositol turnover in the reserpinized rabbit blood platelets.

Thrombin-induced platelet release reaction examined with secretion of calcium and N-acetylglucosaminidase was significantly enhanced in the platelets from reserpine-treated rabbits as compared with the control. On the other hand, 32P-incorporation into phosphatidic acid was suppressed in the reserpinized platelets in activated state. Thrombin induced phosphatidylinositol (PI)-breakdown, which was examined by decreases in radioactivity and content of PI, and an increase in diacylglycerol, was not enhanced in the reserpinized platelets as compared with the control. The phosphorylation of the specific protein coupled to thrombin-induced platelet PI-breakdown was not stimulated in the reserpinized platelets as compared with the control. In contrast to PI, PC-degradation by thrombin was significantly stimulated in the reserpinized platelets. Possible existence of pathway(s) other than that associated with an enhancement of PI-turnover is conceivable as a mechanism involved in platelet release reaction.

Acetylglucosaminidase↗

Prediction of the time to peak hepatic enhancement to optimize contrast-enhanced spiral CT.

A technique for the prediction of the time to peak hepatic enhancement to optimize contrast-enhanced spiral CT has been developed. The procedures are (a) to inject a small amount of contrast medium rapidly via the antecubital vein and measure aortic transit time (ATT) of the bolus by single slice dynamic CT; (b) to inject contrast medium at a high rate, expecting peak hepatic enhancement to occur at ATT plus 8 seconds after the end of injection; (c) to perform spiral scanning of the liver using thin collimation and caudo-cranial table movement beginning at ATT after the end of contrast medium injection.

Aorta, Abdominal↗

[Three-dimensional gadolinium-enhanced dynamic MRI of whole liver using spectrally selected enhanced fast gradient recall sequence].

Three-dimensional gadolinium-enhanced dynamic MRI of whole liver using the spectrally selected enhanced fast gradient recall sequence (spec IR-efgre3d) was performed in five patients with HCC. Ten HCC nodules were confirmed by CTA, CTAP and Lipiodol CT, and all of them were detected with dynamic MRI. MIP images reconstructed from 3D gadolinium-enhanced dynamic MR studies clearly showed the main portal vein and its branches in all cases. Portal vein thrombosis was also demonstrated with the MIP images.

Carcinoma, Hepatocellular↗

Decreased activity and enhanced nuclear export of CCAAT-enhancer-binding protein beta during inhibition of adipogenesis by ceramide.

To identify novel molecular mechanisms by which ceramide regulates cell differentiation, we examined its effect on adipogenesis of 3T3-L1 preadipocytes. Hormonal stimulation of 3T3-L1 preadipocytes induced formation of triacylglycerol-laden adipocytes over 7 days; in part, via the co-ordinated action of CCAAT-enhancer-binding proteins alpha, beta and delta (C/EBP-alpha, -beta and -delta) and peroxisome-proliferator-activated receptor gamma (PPARgamma). The addition of exogenous N-acetylsphingosine (C2-ceramide) or increasing endogenous ceramide levels inhibited the expression of C/EBPalpha and PPARgamma, and blocked adipocyte development. C2-ceramide did not decrease the cellular expression of C/EBPbeta, which is required for expression of C/EBPalpha and PPARgamma, but significantly blocked its transcriptional activity from a promoter construct after 24 h. The ceramide-induced decrease in the transcriptional activity of C/EBPbeta correlated with a strong decrease in its phosphorylation, DNA-binding ability and nuclear localization at 24 h. However, ceramide did not change the nuclear level of C/EBPbeta after a period of 4 or 16 h, suggesting that it was not affecting nuclear import. CRM1 (more recently named 'exportin-1') is a nuclear membrane protein that regulates protein export from the nucleus by binding to a specific nuclear export sequence. Leptomycin B is an inhibitor of CRM1/exportin-1, and reversed the ceramide-induced decrease in nuclear C/EBPbeta at 24 h. Taken together, these data support the hypothesis that ceramide may inhibit adipogenesis, at least in part, by enhancing dephosphorylation and premature nuclear export of C/EBPbeta at a time when its maximal transcriptional activity is required to drive adipogenesis.

3T3 Cells↗

Clusters of nuclear factor I binding sites identify enhancers of several papillomaviruses but alone are not sufficient for enhancer function.

The long control region (LCR) of human papillomaviruses (HPV) encompasses 5-12% of the viral genome and contains an intricate network of cis responsive elements. In the LCR of seven unrelated HPV-types, namely HPV-1, 6, 8, 11, 16, 18 and 33, we have identified clusters of 4 to 7 5-TTGGC-3 motifs suggesting nuclear factor I (NFI) binding sites. We randomly selected 20 (out of a total of 38) of these motifs and showed that pure NFI from porcine liver protects virtually the same nucleotides as a factor present in crude HeLa nuclear extracts. The footprints obtained with HeLa extracts in the LCR of HPV-16 are eliminated in competition experiments by an oligonucleotide representing the palindromic adenovirus NFI binding site. Restriction fragments from the genome of HPV-11, 16 and 18, which contain this cluster of NFI binding sites associated with binding sites of unrelated transcription factors, function as transcriptional enhancers. In contrast, a fragment from HPV-8 exhibiting exclusively NFI binding sites, or polymerized NFI sites from HPV-16, are functionally inactive. NFI seems to be necessary but not sufficient for HPV enhancer activation.

Base Sequence↗

Brain metastasis of small cell lung carcinoma: comparison of Gd-DTPA enhanced magnetic resonance imaging and enhanced computerized tomography.

Small cell carcinoma of the lung (SCLC) frequently metastasizes into the brain, resulting in serious influences upon prognosis. Delayed brain damage caused by prophylactic cranial irradiation (PCI) is also problematic. Gadrinium diethylene triamine pentaacetic acid (Gd-DTPA) enhanced magnetic resonance imaging (MRI) was performed to detect early brain metastasis from SCLC, and its usefulness was compared with contrast computerized tomography (CT). Among 25 SCLC patients, brain metastasis was detected in 11 by MRI and in 10 by CT, although six of them were completely asymptomatic. In the 11 patients, 6.3 and 2.4 lesions were respectively detected on average by MRI and CT. The ability of MRI to detect metastatic lesions of > or = 15 mm diameter did not differ from that of CT, but became different as lesions became smaller (P < 0.002), and MRI had a decided advantage over CT because as many as 30 lesions of < or = 5 mm diameter were detected by MRI, whereas such lesions visualized on CT numbered only one (P < 0.0001). MRI was incomparably superior to CT (P < 0.0004) for subtentorial lesions since 18 lesions were detected on MRI, but only three, measuring > or = 25 mm in diameter, were demonstrated on CT. Gd-DTPA enhanced MRI was determined to be extremely useful in the early diagnosis of SCLC brain metastasis. MRI was thought to reduce delayed brain damage caused by PCI if performed according to an adequate schedule.

Brain Neoplasms↗

Quantifying dynamic contrast-enhanced MRI of the knee in children with juvenile rheumatoid arthritis using an arterial input function (AIF) extracted from popliteal artery enhancement, and the effect of the choice of the AIF on the kinetic parameters.

Quantification of dynamic contrast-enhanced (DCE) MRI based on pharmacokinetic modeling requires specification of the arterial input function (AIF). A full representation of the plasma concentration data, including the initial rise and decay parts, considering the delay and dispersion of the bolus contrast is important. This work deals with modeling of DCE-MRI data from the knees of children with a history of juvenile rheumatoid arthritis (JRA) by using an AIF extracted from the signal enhancement data from the nearby popliteal artery. Three models for the AIFs were considered: a triexponential (AIF1), a gamma-variate plus a biexponential (AIF2), and a biexponential (AIF3). The pharmacokinetic parameters obtained from the model were Ktrans', kep, and V'p. The results from AIF1 and AIF2 showed no statistically significant difference. However, some statistically significant differences were seen with AIF3, particularly for parameters Ktrans' and V'p in the synovium (SNVM). These results suggest the importance of obtaining an appropriate AIF representation in pharmacokinetic modeling of JRA. Specifically, the initial rising part of the AIF should be incorporated for optimal pharmacokinetic modeling results. The pharmacokinetic parameters (mean+/-SD) derived from AIF1, using the average plasma concentration data, were as follows: SNVM Ktrans'(min-1)=0.52+/-0.34, kep(min-1)=0.71+/-0.39, and V'p=0.33+/-0.16, and for the distal femoral physis (DFP) Ktrans'(min-1)=1.83+/-1.78, kep(min-1)=2.65+/-1.80, and V'p=0.46+/-0.31. The pharmacokinetic parameters in the SNVM may be useful for investigating activity and therapeutic efficacy in studies of JRA. Longitudinal studies are necessary to find or demonstrate the parameter that is more sensitive to disease activity.

Adolescent↗

Phenotypic reversion of the gypsy-induced mutation scD1 of Drosophila melanogaster by replicative transposition of a sc enhancer to the yellow gene and by mutations in the enhancer of yellow and zeste loci.

Both mutations of Drosophila melanogaster in the y2scD1 strain are caused by the insertion of gypsy, but the scD1 mutation contains, in addition, an insertion of the jockey mobile element at a distance of 1.8 kb from gypsy. The su(Hw)-binding region in the copy of gypsy in scD1 inhibits scute expression in several specific areas of the epithelium, and in particular, blocks the formation of anterior notopleural (ANP) bristles. The y2 reversions y+2MC and y2#+9 restore the formation of ANP bristles. Molecular analysis revealed that both revertants were induced by transposition into the gypsy element at the yellow locus of jockey and an adjacent 1.8-kb region of the scute gene which contains an enhancer responsible for the development of ANP bristles. The duplicated enhancer is not insulated by the su(Hw)-binding region and can interact with the scute promoter in spite of the presence of two other promoters between them. Hypomorphic mutation in the e(y)2 gene and zOp6 allele partially inhibit ANP bristle formation in flies with y+2MC and y2+9 mutations. In addition, we found that mutations in the e(y)1, e(y)3 and zeste genes may interfere with transcriptional insulation by the su(Hw)-binding region in the scD1 allele.

Alleles↗