SEARCH · PubMed Health

Results for “Enhancer”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,045 records · Page 58Linked to original sources

PubMed1990

Measurement of antibody-dependent infection enhancement of four dengue virus serotypes by monoclonal and polyclonal antibodies.

Although its underlying mechanisms are poorly understood, data comparing each of the four dengue virus serotypes suggest that in vitro antibody-dependent infection enhancement is a reproducible and measurable phenomenon related to other serological measures of antibody-virus binding. Information characterizing infection enhancement may provide clues to disease pathogenesis for dengue and other viruses that exhibit antibody-enhanced infection. We propose criteria for the detection and quantification of in vitro antibody-dependent enhancement of flavivirus infection based on observations using all four dengue virus serotypes, macrophage-like cell lines and human peripheral blood monocytes, and various immune sera and monoclonal antibodies. It is proposed that antibody-dependent infection enhancement is defined by the following findings: (i) significantly increased virus production is measured in quantitative assays at different points on the growth curve; (ii) assays of the virus output of cells infected with mixtures of constant amounts of virus and serial dilutions of the pre-existing antibody source produce characteristic 'enhancement profiles' of rising and falling virus output over at least a 10(-3)-fold dilution range; (iii) for each enhancing antibody source the dilution producing maximal infection enhancement is related to other serological measures of binding to the envelope, or another virus component; (iv) infection enhancement is detected with different antibody sources and virus strains (when available) tested over a range of m.o.i.; (v) other causes of enhanced virus production are ruled out.

Animals↗

PubMed1995

Enhancement of cyclic AMP accumulation mediated by 5-HT after chronic amitriptyline treatment in NG 108-15 cells.

1. The effects of chronic in vitro administration of amitriptyline, a tricyclic antidepressant, on 5-hydroxytryptamine (5-HT) receptor-mediated adenylyl cyclase activity was studied in the neuroblastoma x glioma hybrid cell line, NG 108-15. 2. Treatment of NG 108-15 cells with 8 microM amitriptyline for 3 days increased forskolin-stimulated (0.1 microM) adenosine 3':5'-cyclic monophosphate (cyclic AMP) accumulation. Addition of 5-HT (0.1-100 microM) increased forskolin-stimulated cyclic AMP accumulation in amitriptyline-treated cells in a concentration-dependent manner. However, 5-HT did not affect forskolin-stimulated cyclic AMP accumulation in untreated cells. 3. The 5-HT4 receptor agonist, 5-methoxytryptamine, significantly enhanced forskolin-stimulated cyclic AMP accumulation in amitriptyline-treated cells. In contrast, amitriptyline treatment failed to modify 8-hydroxy-2-(di-n-propylamine) tetralin-induced inhibition of forskolin-stimulated cyclic AMP accumulation. 4. Pretreatment of cells with pertussis toxin did not affect the 5-HT-induced enhancement of cyclic AMP accumulation. 5. The 5-HT-induced enhancement of cyclic AMP accumulation in amitriptyline-treated cells was attenuated by the 5-HT4 receptor antagonists, GR 113808 and ICS 205-930, with relatively low potency. However, spiperone, SCH 23390, and pindolol were completely ineffective against this 5-HT-induced enhancement. 6. Chronic treatment with amitriptyline did not modify the cyclic AMP production stimulated by prostaglandin E1 or cholera toxin. This treatment also had no effect on GTP gamma S-, NaF-, and Mn(2+)-stimulated cyclic AMP accumulation in isolated cell membranes. 7. Chronic treatment with the 5-HT receptor antagonists, pindolol or ICS 205-930, did not inhibit the 5-HT-induced enhancement of cyclic AMP accumulation.8. Chronic treatment with other antidepressant drugs, imipramine, mianserin or paroxetine, elicited the 5-HT-induced enhancement of cyclic AMP accumulation.9. Taken together, these results suggest that chronic amitriptyline treatment of NG 108-15 cells causes 5-HT to enhance forskolin-stimulated cyclic AMP accumulation by enhancing 5-HT receptor-mediated stimulation of adenylyl cyclase and not by reducing 5-HT-mediated inhibition of adenylyl cyclase. The 5-HT-induced enhancement of cyclic AMP accumulation in amitriptyline-treated cells may result from changes at the level of the 5-HT receptor rather than at the level of G, proteins or adenylyl cyclase. It is unlikely that this enhancement of cyclic AMP accumulation is caused by long-term antagonism of the 5-HT receptor by amitriptyline.

Adenylyl Cyclases↗

PubMed1999

Contrast-Enhanced Transcranial and Extracranial Duplex Sonography: Preliminary Results of a Multicenter Phase II/III Study with SonoVuetrade mark.

Transcranial sonography is an ultrasonographic application with real problems of insufficient signal to noise ratio, which make it a primary candidate for applying ultrasonographic contrast enhancing agents. Within an international randomized multicenter phase II/III study, we investigated ten patients with insufficient Doppler signal retrieval using transcranial and extracranial color-coded duplex sonography to define safety, toxicity, optimal dosing, and the potential of the new ultrasound contrast agent SonoVue(trade mark). Patients were studied with standard color duplex systems. SonoVue(trade mark) was administered by IV bolus injection at four different doses. Efficacy parameters included the assessment of global quality of Doppler investigations, color Doppler (CD), and spectral Doppler (SD) evaluated by semiquantitative analysis using a four-point scale from 0 to 3 (very poor to excellent) and the duration of clinically useful signal enhancement. In addition, CD enhancement, evaluated at best signal enhancement, was assessed using a five-point scale, from no enhancement, slight, moderate, optimal to excessive (0-4). All examinations were compared to "gold" standard imaging (magnetic resonance imaging, digital subtraction angiography) to evaluate diagnostic confidence at optimum dosage. No serious adverse events were observed. Mean signal increase over baseline in CD or SD was 2 out of 4 points. Mean time to appearance of contrast enhancement was 22.8 seconds (9-52 sec) at the optimal dosage. The mean duration of enhancement was 281 seconds(20-593 sec) at the optimal dosage, which was of 2.4 ml of SonoVuetrade mark in nine patients. CD and SD signal enhancement (n = 20, CD + SD) was considered optimal in 12 of 20, excessive in 1 of 20, and moderate or insufficient in 5 of 20 and 2 of 20 cases, respectively. There was a tendency for superior improvement in CD signal enhancement. Diagnostic confidence was improved in 8 of 10 cases without false diagnostic conclusions. SonoVuetrade mark has been demonstrated to be a powerful and safe echo signal enhancing agent, which significantly improves transcranial and extracranial ultrasound investigations and increases the confidence in diagnosis.

Journal Article↗

PubMed1986

Computerized enhancement of retinal nerve fiber layer.

We investigated a number of image processing techniques for enhancing the retinal nerve fiber layer (NFL) in fundus photographs taken with red-free light. Wedge-type defects within the NFL were enhanced best by contrast enhancement algorithms such as histogram modification and extremum sharpening. Narrow, slitlike NFL defects can be enhanced by directional enhancement techniques. Normal NFL features were enhanced best by high-pass filtering techniques such as homomorphic filtering and adaptive enhancement. The enhanced normal NFL may be useful in the analysis of diffuse NFL loss. All of these successful enhancements of normal and defective features indicate that enhancing fundus photographs with digital image processing techniques should facilitate early detection of optic nerve damage from glaucoma and other diseases.

Computers↗

PubMed1993

Mechanisms underlying enhanced responses of J receptors of cats to excitants in pulmonary oedema.

1. The responses of J receptors to certain excitants were recorded during pulmonary oedema produced by phosgene gas (320-1080 p.p.m.) or alloxan, 150 mg kg-1 i.v., in cats anaesthetized with sodium pentobarbitone, 35 mg kg-1 I.P. 2. The responses of fourteen (out of fifteen) J receptors to phenyl diguanide (PDG) were greatly enhanced after phosgene, the enhancement being highly significant (P = < 0.01) in twenty-one out of twenty-six responses. The enhancements were also highly significant after alloxan in the case of another twelve receptors. Similar enhancements were observed in the case of responses to nicotine and capsaicin. This suggests that the enhancement of the responses of J receptors to excitants occurs in a non-specific manner after phosgene and alloxan. 3. The enhanced responses occurred in the absence of any significant increase in the estimated concentration of the excitants in pulmonary artery blood. 4. The enhanced responses to PDG were not closely related to the oedema-induced activity; several occurred during periods of silence of the receptors and in thirteen receptors the enhanced responses occurred before the increase in the oedema-induced activity had begun. 5. A possible role of histamine, 5-HT, prostaglandins and bradykinin in enhancing the responses to PDG after phosgene was excluded. 6. The results therefore suggest that the non-specific enhancement of the responses of the J receptors to excitants must be due to the increased permeability of the capillaries produced by phosgene and alloxan leading to greater movement of the excitants to the J receptors. However, certain unidentified factors may also be involved.

Alloxan↗

PubMed1991

Interaction of nuclear factor EF-1A with the polyomavirus enhancer region.

Enhancer factor 1A (EF-1A) is a mammalian nuclear protein that previously was shown to bind cooperatively to the repeated core enhancer element I sequence in the adenovirus E1A enhancer region. We now have characterized three binding sites for EF-1A in the polyomavirus A2 (Py) enhancer region. Site 1 resides in the Py A enhancer domain, and sites 2 and 3 reside in the Py B enhancer domain. EF-1A binding to Py site 1 is independent of cooperation with other EF-1A sites or the adjacent binding sites for PEA-1 and PEA-2, two murine nuclear factors that bind in the Py A enhancer domain. EF-1A binding to Py sites 2 and 3, in contrast, is cooperative, similar to the situation previously observed with binding sites in the adenovirus E1A enhancer region. In a transient replication assay, EF-1A site 1 functions synergistically with the PEA-1 and PEA-2 sites in the A enhancer domain to enhance Py replication. The functional cooperativity observed with the EF-1A, PEA-1, and PEA-2 sites in vivo does not reflect cooperative DNA binding interactions, as detected in vitro. Py EF-1A site 1 alone is capable of weakly stimulating Py replication. EF-1A site 1 overlaps with the binding sites for the murine nuclear protein PEA-3 and the ets family of oncoproteins.

Adenoviridae↗

PubMed2002

Focal hepatic masses: enhancement patterns with SH U 508A and pulse-inversion US.

PURPOSE: To evaluate the role of SH U 508A-enhanced ultrasonography (US) in the differentiation of focal hepatic masses. MATERIALS AND METHODS: Contrast material-enhanced pulse inversion US was performed on 58 unknown hepatic lesions: 23 hepatocellular carcinomas, 10 focal nodular hyperplasias, 16 hemangiomas, and nine metastases. Selected images were sequentially reviewed by readers blinded to the final diagnosis. On a baseline image, they determined lesion echogenicity, and on a vascular image, the presence or absence of distinct vascularity. On an arterial phase interval-delay flash image and a postvascular image, they assessed enhancement of the lesion and liver. Responses were compared with confirmed diagnoses. RESULTS: Focal nodular hyperplasia was characterized by detectable vascularity and positive enhancement on interval-delay and postvascular scans (sensitivity, 83% [eight of 10 lesions]; specificity, 98% [40 of 41 lesions]). Hepatocellular carcinoma also showed detectable vascularity and positive enhancement on interval-delay images but no postvascular enhancement (sensitivity, 68% [14 of 20 lesions]; specificity, 74% [23 of 31 lesions]). Vascular imaging with SH U 508A did not contribute to the diagnosis of metastasis or hemangioma. However, no or weak enhancement during the arterial phase flash without postvascular enhancement produced a sensitivity of 83% (seven of eight lesions) and sensitivity of 77% (33 of 43 lesions) for metastasis. Peripheral nodular enhancement on arterial phase flash images was highly specific (98% [37 of 38 lesions]) but not sensitive (44% [six of 13 lesions]) for hemangioma. CONCLUSION: SH U 508A-enhanced pulse-inversion interval-delay flash and postvascular phase imaging are helpful in differential diagnosis of focal hepatic lesions.

Adult↗

PubMed2003

Contrast-enhanced MR imaging of postoperative scars and VX2 carcinoma in rabbits: comparison of macromolecular contrast agent and gadopentetate dimeglumine.

PURPOSE: To compare the magnetic resonance (MR) imaging enhancement patterns of a blood pool contrast agent, SH L 643A, with those of gadopentetate dimeglumine in postoperative scars and VX2 carcinomas in rabbits and to compare these enhancement patterns with microvessel density in pathologic specimens. MATERIALS AND METHODS: Eighteen rabbits with experimentally induced postoperative scars (n = 12) or VX2 carcinoma (n = 6) in the thighs underwent sequential MR imaging first with gadopentetate dimeglumine and then, 24 hours later, with SH L 643A. The enhancement ratios (ie, the ratios of postcontrast to precontrast signal intensity) and the microvessel densities of postoperative scars and VX2 carcinomas were assessed. Differences were tested for by using the Mann-Whitney U and Wilcoxon signed rank tests. RESULTS: In postoperative scars, enhancement ratios were consistently lower with injection of SH L 643A than with injection of gadopentetate dimeglumine for up to 30 minutes (P <.05). In postoperative scars, mean peak enhancement ratios were 1.29 +/- 0.15 (SD) with injection of SH L 643A and 1.61 +/- 0.31 with injection of gadopentetate dimeglumine (P <.01). In VX2 carcinomas, the enhancement ratios were not significantly different with injection of SH L 643A than with injection of gadopentetate dimeglumine at all time points. The mean difference between the enhancement ratios of the VX2 carcinomas and postoperative scars was 0.64 +/- 0.10 (range, 0.50-0.77) with SH L 643A and 0.36 +/- 0.16 (range, 0.17-0.66) with gadopentetate dimeglumine (P <.01). The mean microvessel density (in terms of vessels per field of view) was 10.7 +/- 5.5 for postoperative scars and 30.0 +/- 7.7 for VX2 carcinoma (P <.001). CONCLUSION: The difference between the enhancement ratios of postoperative scars and VX2 carcinomas with SH L 643A was greater than that with gadopentetate dimeglumine. Enhancement ratios at SH L 643A-enhanced MR imaging corresponded well with microvessel density in postoperative scars and VX2 carcinomas.

Animals↗

PubMed2004

Abdominal aortic aneurysm: contrast-enhanced US for missed endoleaks after endoluminal repair.

PURPOSE: To evaluate contrast material-enhanced ultrasonography (US) for depiction of endoleaks after endovascular abdominal aortic aneurysm repair (or endovascular aneurysm repair [EVAR]) in patients with aneurysm enlargement and no evidence of endoleak. MATERIALS AND METHODS: From November 1998 to February 2003, 112 patients underwent EVAR. At follow-up, duplex US and biphasic multi-detector row computed tomographic (CT) angiography were performed. In 10 patients (group A), evident aneurysm enlargement was observed, with no evidence of complications, at both CT angiography and duplex US. Group A patients, 10 men (mean age, 69.6 years +/- 10 [standard deviation]), underwent US after intravenous bolus injection of a second-generation contrast agent, with continuous low-mechanical index (0.01-0.04) real-time tissue harmonic imaging. Group B patients, 10 men (mean age, 71.3 years +/- 8.2) with aneurysm shrinkage and no evidence of complications, and group C patients, 10 men (mean age, 73.2 years +/- 6) with CT angiographic evidence of endoleak, underwent contrast-enhanced US. Digital subtraction angiography (DSA) was performed in groups A and C. Endoleak detection and characterization were assessed with imaging modalities used in groups A-C; at contrast-enhanced US, time of detection of endoleak, persistence of sac enhancement, and morphology of enhancement were evaluated. RESULTS: In group A, contrast-enhanced US depicted one type I, six type II, one type III, and two undefined endoleaks that were not detected at CT angiography. All leakages were characterized by slow and delayed echo enhancement detected at longer than 150 seconds after contrast agent administration. DSA results confirmed findings in all patients; percutaneous treatment was performed. In group B, contrast-enhanced US did not show echo enhancement; in group C, results with this modality confirmed findings at CT angiography and DSA. CONCLUSION: Contrast-enhanced US depicts endoleaks after EVAR, particularly when depiction fails with other imaging modalities.

Aged↗

PubMed2006

Liver fibrosis: noninvasive diagnosis with double contrast material-enhanced MR imaging.

PURPOSE: To retrospectively evaluate the accuracy of double contrast material-enhanced (hereafter double-enhanced) magnetic resonance (MR) imaging depiction of hepatic fibrosis, with histopathologic analysis findings as the reference standard. MATERIALS AND METHODS: The institutional review board approved this HIPAA-compliant study and waived the requirement for informed consent. One hundred one patients (58 men, 43 women; mean age +/- standard deviation, 52 years +/- 10) who underwent double-enhanced MR imaging with superparamagnetic iron oxide (SPIO)-enhanced and double-enhanced spoiled gradient-echo (SPGR) sequences between 2001 and 2004 and had a reliable reference standard for the diagnosis of liver fibrosis were included. Two blinded MR radiologists retrospectively scored qualitative (reticulation, nodularity, and total scores) and quantitative (contrast-to-noise ratio between hyperintense and hypointense liver regions, coefficient of variation, and noise-corrected coefficient of variation) liver texture features on MR images in consensus. The image scores for patients with advanced (METAVIR fibrosis score >/= 3) versus those for patients with mild (METAVIR score </= 2) fibrosis were compared, and receiver operating characteristic curves were determined. Diagnostic performance values were calculated at the optimal operating point. Mann-Whitney U and unpaired Student t tests were performed. RESULTS: Qualitative and quantitative image scores were significantly higher for patients with METAVIR fibrosis scores of 3 or higher than for those with scores of 2 or lower (P < .001); on SPIO-enhanced SPGR images, differences increased with increasing echo time. Diagnostic performance for detection of grade 3 or more severe fibrosis was better with the double-enhanced sequence than with the SPIO-enhanced sequences, and qualitative scores had higher diagnostic performance than quantitative scores. The sensitivity, specificity, and accuracy of qualitative scores on double-enhanced SPGR images were higher than 90%. CONCLUSION: Advanced hepatic fibrosis can be detected by using double-enhanced MR imaging. Although diagnostic performance depended on the sequence and scoring system used, sensitivity, specificity, and accuracy values higher than 90% were achievable.

Contrast Media↗

PubMed1990

Cranial postoperative site: assessment with contrast-enhanced MR imaging.

To define duration and patterns of postoperative contrast material enhancement, the authors evaluated magnetic resonance (MR) images obtained with gadolinium diethylenetriaminepentaacetic acid (DTPA) in 46 patients who had undergone major intracranial surgery. Intervals between surgery and MR imaging ranged from 1 day to 40 years (median, 1.3 years). Moderate or marked brain and dural enhancement was noted in nearly every patient imaged within 3 months of surgery, but all brain enhancement was gone by 1 year. Abnormal dural enhancement was noted in every patient imaged within 1 year of surgery and in approximately 50% at 1-2 years afterward. One patient had persistent mild enhancement of the dura 40 years after surgery. MR images revealed enhancement in several sites not frequently recognized on computed tomographic (CT) scans. Brain and meningeal enhancement with Gd-DTPA at cranial operative sites was more extensive and persisted much longer than is commonly seen on contrast-enhanced CT scans. Enhancement of the brain or pia mater does not normally last beyond 1 year, but dural enhancement may persist for decades.

Adult↗

PubMed1990

Early cerebral infarction: gadopentetate dimeglumine enhancement.

Gadopentetate dimeglumine was administered prospectively to 50 patients who presented for magnetic resonance (MR) imaging within 2 weeks after a cortical cerebral infarction. Twenty-two patients (44%) were imaged within 3 days after clinical ictus. Abnormalities detected with gadopentetate dimeglumine enhancement were observed in 46 (92%) of 50 patients. Classic parenchymal enhancement was a late finding, observed in all patients (17 of 17) imaged at 7-14 days after infarction. Before this time, three additional phases of contrast material-related abnormalities were observed. Enhancement of vessels supplying the infarct ("intravascular enhancement sign") was the earliest finding, seen in 17 (77%) of 22 infarcts aged 1-3 days. From day 2 to day 6, abnormal enhancement of meninges adjacent to the infarct was frequently noted ("meningeal enhancement sign"). Finally, a transition phase that combined intravascular or meningeal enhancement with early parenchymal enhancement was seen from day 3 to day 6. Gadopentetate dimeglumine-enhanced MR imaging in early stroke reveals evidence of vascular engorgement and sluggish flow, which precede the development of classic parenchymal enhancement.

Brain↗

PubMed1994

Carpal tunnel syndrome: evaluation of median nerve circulation with dynamic contrast-enhanced MR imaging.

PURPOSE: To identify mechanism(s) responsible for carpal tunnel syndrome (CTS). MATERIALS AND METHODS: At dynamic gadolinium-enhanced magnetic resonance (MR) imaging, the enhancement pattern of the sagittal section of the median nerve in 10 wrists of nine patients with CTS (two men and seven women, aged 43-60 years [mean, 52 years 10 months]) was studied while each wrist was in a neutral, flexed, and/or extended position. Five asymptomatic volunteers (four men and one woman, aged 23-54 years [mean, 31 years 5 months]) also underwent MR imaging to establish the normal enhancement patterns. RESULTS: Two distinctly abnormal patterns of median-nerve enhancement were revealed: marked or no enhancement. Marked enhancement was attributed to nerve edema, and the lack of enhancement was attributed to ischemia. Marked enhancement changed to no enhancement changed to no enhancement when the wrists were in a flexed or extended position. This change was associated with an aggravation of the symptoms of CTS. CONCLUSIONS: CTS may result from a circulatory disturbance rather than from deformation or compression of the nerve.

Adult↗

PubMed1997

Menstrual cycle and age: influence on parenchymal contrast medium enhancement in MR imaging of the breast.

PURPOSE: To evaluate the influence of menstrual cycle and age on parenchymal contrast medium enhancement in magnetic resonance (MR) imaging of the breast. MATERIALS AND METHODS: Dynamic gadolinium-enhanced fast low-angle shot, three-dimensional breast MR imaging was performed with high temporal and spatial resolution (eight measurements in 10 minutes). Menstrual cycle evaluations and age-influence studies were performed in 44 patients aged 27-55 years with a regular cycle (mean age, 41.5 years) and in 103 patients aged 15-79 years (mean age, 49.3 years), respectively. A region of interest was placed in each quadrant of the breast for evaluation of parenchymal enhancement. Quadrants with complete involution or lesions and patients who received hormonal therapy were excluded [corrected]. Analysis of variance was performed. RESULTS: Parenchymal contrast medium enhancement in cycle days 7-20 (geometric mean enhancement at minutes 1-10 = 0.12-0.47) was significantly lower than that in cycle days 21-6 (geometric mean, 0.17-0.98; P < or = .001). Contrast medium enhancement in patients aged 35-50 years (mean enhancement, 0.17-0.75) was significantly higher than that in patients aged younger than 35 years or older than 50 years (mean enhancement, 0.12-0.40; P < .01). CONCLUSION: Patients showed statistically significantly lower parenchymal enhancement in menstrual cycle days 7-20 than in days 21-6. Patients aged 35-50 years yielded higher parenchymal enhancement than did younger patients and older patients.

Adolescent↗

PubMed1998

Aortic and hepatic contrast medium enhancement at CT. Part I. Prediction with a computer model.

PURPOSE: To develop a physiologic model of contrast medium enhancement by incorporating available physiologic data and contrast medium pharmacokinetics and to predict organ-specific contrast medium enhancement at computed tomography (CT) with various contrast medium injection protocols in patients of variable height and weight. MATERIALS AND METHODS: A computer-based, compartmental model of the cardiovascular system was generated by using human physiologic parameters and more than 100 differential equations to describe the transport of contrast medium. Blood volume, extracellular fluid volume, and regional blood flow were estimated from available data. Local structures were modeled mathematically to describe the distribution and dispersion of intravascularly administered iodinated contrast medium. A global model was formed by integrating regional circulation parameters with the models of local structures. Aortic and hepatic CT contrast-enhancement curves were simulated for three protocols and were compared with mean enhancement curves in three groups of 25-28 patients (80 patients total; 28 in one group, 25 in one group, and 27 in one group) receiving the same protocols. The percent difference in maximum enhancement between the simulated and empiric curves and the enhancement difference index (sum of the area difference between the simulated and empiric curves divided by the total area under the empiric curve) were computed. RESULTS: The simulated and empiric enhancement curves closely agreed in maximum enhancement (the mean percent difference in the aorta was 7.4%; liver, 4.8%) and in variation over time (mean enhancement difference index in the aorta was 11.6%; liver, 12.7%). CONCLUSION: A computer-based, physiologic model that may help predict organ-specific CT contrast medium enhancement for different injection protocols was developed. Such a physiologic model may have many clinical applications.

Adult↗

PubMed2005

Radiosensitivity enhancement by celecoxib, a cyclooxygenase (COX)-2 selective inhibitor, via COX-2-dependent cell cycle regulation on human cancer cells expressing differential COX-2 levels.

To characterize the radiation-enhancing effects on human cancer cells and underlying mechanisms of celecoxib, a cyclooxygenase (COX)-2 selective inhibitor, and to ascertain whether its effects are COX-2 dependent. Clonogenic cytotoxicity assays and radiation survival assays after treatment with celecoxib +/- radiation were done on four human cancer cell lines that expressed differential COX-2 levels. Stably COX-2 knocked down or overexpressed cell lines were developed, and clonogenic assays, apoptosis assays, or cell cycle change measurements were conducted after treatment with celecoxib +/- radiation. Prostaglandin E(2) (PGE2) was applied to medium after treatment with celecoxib +/- radiation to determine whether the radiation-enhancing effect associated with celecoxib results from reduced generation of prostaglandin. Celecoxib's radiation-enhancing effect was observed in COX-2-expressing A549 and NCI-H460 cells but was not observed in the COX-2 nonexpressing MCF-7 and HCT-116 cells. Celecoxib's radiation-enhancing effects in A549 cells were shown to disappear after the administration of COX-2 knocked down. In contrast, the HCT-116 cells were radiosensitized by celecoxib after being transfected with COX-2 expression vector. The addition of PGE2 after treatment with celecoxib +/- radiation had no significant effects on celecoxib's radiation-enhancing effects in A549 and COX-2 transfected HCT-116 cells. Radiation-induced G2-M arrest was enhanced and sustained in the COX-2-overexpressing cells compared with that seen in COX-2 low-expressing cells. Celecoxib or NS-398 effected no changes or attenuated radiation-induced G(2)-M arrest in the COX-2-overexpressing cells but further enhanced the radiation-induced G(2)-M arrest in the COX-2 low-expressing cells. Celecoxib's radiation-enhancing effects seem to occur in a COX-2 expression-dependent manner in the cancer cells. This effect does not seem to be the result of reduced PGE2 generation. Celecoxib may exert an inhibitory effect on enhanced radiation-induced G2-M arrest in the COX-2-overexpressing cells, which may allow the arrested cells to enter mitosis and die after radiation, but may also further enhance radiation-induced G2-M arrest in the COX-2 low-expressing cells, by virtue of another mechanism.

Apoptosis↗

PubMed2005

Cognitive enhancement mediated through postsynaptic actions of norepinephrine on ongoing cortical activity.

We propose two distinct types of norepinephrine (NE)-neuromodulatory systems: an enhanced-excitatory and enhanced-inhibitory (E-E/E-I) system and a depressed-excitatory and enhanced-inhibitory (D-E/E-I) system. In both systems, inhibitory synaptic efficacies are enhanced, but excitatory ones are modified in a contradictory manner: the E-E/E-I system enhances excitatory synaptic efficacies, whereas the D-E/E-I system depresses them. The E-E/E-I and D-E/E-I systems altered the dynamic property of ongoing (background) neuronal activity and greatly influenced the cognitive performance (S/N ratio) of a cortical neural network. The E-E/E-I system effectively enhanced S/N ratio for weaker stimuli with lower doses of NE, whereas the D-E/E-I system enhanced stronger stimuli with higher doses of NE. The neural network effectively responded to weaker stimuli if brief gamma-bursts were involved in ongoing neuronal activity that is controlled under the E-E/E-I neuromodulatory system. If the E-E/E-I and the D-E/E-I systems interact within the neural network, depressed neurons whose activity is depressed by NE application have bimodal property. That is, S/N ratio can be enhanced not only for stronger stimuli as its original property but also for weaker stimuli, for which coincidental neuronal firings among enhanced neurons whose activity is enhanced by NE application are essential. We suggest that the recruitment of the depressed neurons for the detection of weaker (subthreshold) stimuli might be advantageous for the brain to cope with a variety of sensory stimuli.

Action Potentials↗

PubMed2003

Contrast-enhanced ultrasound imaging for aortic stent-graft surveillance.

PURPOSE: To compare unenhanced and enhanced ultrasound imaging to computed tomographic angiography (CTA) or magnetic resonance angiography (MRA) for surveillance of aortic endografts. METHODS: Thirty consecutive patients (29 men; mean age 69 years, range 50-82) who underwent endovascular aortic aneurysm repair agreed to participate in a follow-up program. Patients underwent CTA (26/30) or MRA (4/30), plain abdominal radiography, and unenhanced and enhanced ultrasound examinations at 3, 12, and 24 months to evaluate aneurysm diameter, endoleaks, and graft patency. The accuracy of ultrasound was compared with CTA or MRA as the reference standards. RESULTS: Twenty-six patients reached the 24-month assessment (mean follow-up 30 months, range 6-60). All endoleaks detected by CTA or MRA were confirmed by enhanced ultrasound; the aneurysm diameter in these patients remained unchanged or increased. In patients without endoleaks on any imaging method, the sac diameter remained unchanged or decreased. Endoleaks disclosed by enhanced ultrasound alone, all type II, numbered 16 at 3 months, 6 at 12 months, and 3 at 24 months. In this group, the aneurysm diameter remained unchanged or increased. Enhanced ultrasound yielded 100% sensitivity in detecting endoleaks, but compared with CTA and MRA, all endoleaks detected by enhanced ultrasound alone were false positives (mean specificity 65%). Nevertheless, because changes in the postoperative aneurysm diameter were similar in patients with endoleaks detectable on CTA/MRA and on enhanced ultrasound ("true positives") and in those with endoleaks detectable only on enhanced ultrasound ("false positives"), some endoleaks were possibly "true positive" results. CONCLUSIONS: Enhanced ultrasound is a useful method in the long-term surveillance of endovascular aortic aneurysm repairs, possibly in association with CTA or MRA. Enhanced ultrasound also seems able to identify endoleaks missed by other imaging techniques, but this conclusion awaits further investigation.

Aged↗