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At least 415 records · Page 23Linked to original sources

PubMed2000

Enhanced phospholipase C activity in the cultured skin fibroblast obtained from patients with coronary spastic angina: possible role for enhanced vasoconstrictor response.

OBJECTIVES: We measured phospholipase C (PLC) activity in the cultured skin fibroblasts obtained from patients with and without coronary spasm and examined its correlation with coronary artery vasomotility. BACKGROUND: Coronary artery vasomotility is enhanced in coronary spastic angina (CSA), but no information is available for the intracellular signaling. In spontaneously hypertensive rats, PLC activity in the skin fibroblasts has been shown to be enhanced. METHODS: Skin fibroblasts obtained from 24 patients with CSA-14 with organic coronary artery disease (CAD) and 12 control subjects--were cultured by the explant method. Activity of PLC was determined by incubating the membrane fraction with 3H-phosphatidyl inositol bisphosphate and by quantifying 3H-inositol trisphosphate. In patients with CSA and control subjects, the relations between PLC activity and coronary artery basal tone and constrictor response to intracoronary acetylcholine (ACh) were examined. RESULTS: Activity of PLC (pmol/protein [mg] per min) was 1.74+/-0.19 in patients with CSA; 0.90+/-0.12 in patients with CAD; and 0.65+/-0.07 in control subjects (p<0.001, patients with CSA vs. patients with CAD and control subjects; p = NS, patients with CAD vs. control subjects). According to the Lineweaver-Burk plot, Michaelis constant (micromol/liter) of PLC was 28+/-4 in patients with CSA; 49+/-14 in patients with CAD; and 56+/-10 in control subjects (p<0.05, patients with CSA vs. control subjects), whereas the maximal velocity was not different between the three groups. There were significant positive correlations between PLC activity and both basal tone (p = 0.0108) and response to ACh (p = 0.0053). Western blot analysis using membrane fraction demonstrated that 89% of PLC isoenzymes detected was of the delta1 isoform. CONCLUSIONS: Because the PLC activity measured was genetically defined and was positively correlated with coronary artery vasomotility, enhanced PLC activity may be involved in the pathogenesis of coronary spasm.

Angina Pectoris, Variant↗

PubMed1996

Aluminosilicates enhance the infectivity of cytomegalovirus in urine using centrifugation-enhanced antigen detection technology.

Due to the inherent lability of CMV, necessary laboratory identification of this infectious agent is often compromised by a delay in specimen transport. Previous studies have addressed the phenomenon of infectivity enhancement/reduction in the rate of infectivity loss by the incorporation into various viral assay systems of trace concentrations of the adsorbents montmorillonite (bentonite [M]) or kaolinite (kaolin [K]). We extended these studies to the clinical setting to identify whether such aluminosilicates would effect an enhanced level of CMV infectivity. The shell vial assay-indirect immunofluorescent assay (SVA-IFA) was utilized in comparative testing throughout this study. The addition of trace concentrations of M or K to the SVA-IFA was found to enhance the infectivity of CMV in urine by 115 and 126%, respectively. The total CMV detection rate by SVA-IFA was 29% (30/105). Three of the 30 (10%) CMV positive specimens were detected only in shell vials which had been supplemented with K or M. Two specimens were isolation positive alone. The addition of K or M to shell vials immediately prior to the start of the SVA-IFA has the potential of (a), enhancing assay readability by increasing the number of fluorescent focus units per vial monolayer and (b), of detecting positive urine specimens with low viral titers which might otherwise not be identified using the conventional SVA-IFA procedure.

Antigens, Viral↗

PubMed1997

Enhanced nephrotoxicity of acetaminophen in fructose-induced hypertriglyceridemic rats: contribution of oxidation and deacetylation of acetaminophen to an enhancement of nephrotoxicity.

Fructose-induced hypertriglyceridemic Sprague-Dawley (SD) rats become resistant to hepatotoxicity and susceptible to nephrotoxicity of acetaminophen (APAP) as compared with normal SD rats. Fischer-344 rats, which are susceptible to APAP nephrotoxicity, have two toxic metabolic pathways involving cytochrome P450-dependent oxidation of APAP to N-acetyl-p-benzoquinone imine (NAPQI) and P450-independent deacetylation of APAP to p-aminophenol (PAP). SD rats, however, have only the former pathway. This study was undertaken to investigate whether alterations in the metabolic pathways of APAP and in the intrinsic susceptibility to toxic metabolites are responsible for an enhancement of APAP nephrotoxicity in the fructose-pretreated SD-rats. In the non-pretreated rats, the inhibition of APAP oxidation by the MFO inhibitor, piperonyl butoxide, and deacetylation by carboxyesterase inhibitor, bis(p-nitrophenyl)phosphate, did not alter APAP-induced renal lesions. In contrast, these inhibitors protected the fructose-pretreated rats from APAP-induced renal lesions. Since there were no differences in the severity of gentamicin-, chloroform, and 45 min-ischemia/reperfusion-induced renal lesions between the non-pretreated and the fructose-pretreated rats, it is unlikely that the increased intrinsic susceptibility to chemicals and their metabolites in the fructose-pretreated rats is a major factor in the enhancement of APAP nephrotoxicity. These results indicate that the enhancement of APAP nephrotoxicity in the fructose-pretreated rats is due, at least in part, to an alteration in metabolic pathways of APAP.

Acetaminophen↗

PubMed2003

The E box motif CAGGTG enhances somatic hypermutation without enhancing transcription.

The frequency of somatic hypermutations of an Ig kappa transgene with an artificial test insert, RS, is at least 4-fold higher than that of three related transgenes. The four transgenes differ only in the sequence of a 96 bp insert within the variable region. RS is hypermutable over the total 625 nucleotides of the variable/joining region. The RS insert contains two CAGGTG sequences, potential binding sites for basic helix-loop-helix proteins. Changing CAGGTG to AAGGTG reduces the mutability to that of the non-RS transgenes without altering the mutation pattern. The CAGGTG motif enhances somatic hypermutation without enhancing transcription. A DNA probe containing the two CAGGTG sites, but not AAGGTG, binds E47 and gives rise to two specific EMSA bands with nuclear extracts from mutating cells. Possible actions of this enhancer of somatic hypermutation are discussed.

Animals↗

PubMed2003

Single-molecule surface enhanced resonance Raman spectroscopy of the enhanced green fluorescent protein.

In the present contribution, we demonstrated that surface-enhanced resonance Raman scattering spectra from single green fluorescent proteins (GFPs) were obtained. The most important findings are the direct detection of the conversion between a deprotonated and a protonated form of the chromophore at the single-molecule level via the corresponding vibrational fingerprints, and the fact that the enhanced green fluorescent protein (EGFP) also shows a high surface enhanced resonance Raman scattering (SERRS) signal. Our findings show the potential of the technique to study structural dynamics of protein molecules at a single-molecule level.

Green Fluorescent Proteins↗

PubMed1990

Enhancement of the in vitro skin permeability of azidothymidine (AZT) via iontophoresis and chemical enhancer.

Azidothymidine (AZT) was used as a model drug to study the effect of iontophoresis on the skin permeation of a neutral compound. The rate of in vitro permeation across hairless rat skin was low and highly variable. With iontophoresis treatment the permeation rate was two- to threefold greater than by passive diffusion. The addition of varying amounts of sodium chloride to the donor enhanced the iontophoretic permeation rate an additional two- to threefold possibly due to convective forces. The addition of N-decylmethyl sulfoxide (C10MSO) to the donor increased the permeation rate by several hundred-fold over passive diffusion for hairless rat skin and approximately 75-fold for human skin. No additional enhancement was observed with the combination of C10MSO and iontophoresis treatment at constant current or constant voltage. It may be that the presence of C10MSO lowers the zeta potential of the skin, thus enhancement due to convective flow is minimized.

Animals↗

PubMed1992

Enhanced bioavailability of cefoxitin using palmitoyl L-carnitine. I. Enhancer activity in different intestinal regions.

The conditions under which the absorption enhancer palmitoyl L-carnitine chloride (PCC) improved the bioavailability of the poorly absorbed antibiotic cefoxitin throughout the rat intestine has been studied. Cefoxitin alone was appreciably absorbed only in the duodenum (31% vs less than 7% elsewhere). PCC solutions (3 mg/rat, pH 4.0) enhanced cefoxitin bioavailability (F) by 0-, 22-, 16-, and greater than 32-fold in the duodenum, jejunum, ileum, and colon regions, respectively. The inability of PCC to improve F in the duodenum could not likely be attributed to enzymatic degradation of the enhancer, since coadministration with protease and esterase inhibitors produced similar results (F = 30%). Coadministration of PCC solution with cefoxitin in the unligated or ligated colon, increased F to 33 and 76%, respectively. Qualitatively similar results were seen with PCC suspensions (3 mg/rat, pH 6.0). Maintaining a high concentration of cefoxitin and PCC in a restricted region (i.e., by ligating a 2- to 3-cm section of the colon) afforded a two- to threefold advantage over an unligated colon section. The difference in cefoxitin bioavailability between ligated and unligated colon was probably due to sample spreading and subsequent/simultaneous dilution.

Adjuvants, Pharmaceutic↗

PubMed2003

Immunoassay using probe-labelling immunogold nanoparticles with silver staining enhancement via surface-enhanced Raman scattering.

This paper reports a novel immunoassay based on surface-enhanced Raman scattering (SERS) and immunogold labelling with silver staining enhancement. Immunoreactions between immunogold colloids modified by a Raman-active probe molecule (e.g., 4-mercaptobenzoic acid) and antigens, which were captured by antibody-assembled chips such as silicon or quartz, were detected via SERS signals of Raman-active probe molecule. All the self-assembled steps were subjected to the measurements of ultraviolet-visible (UV-vis) spectra to monitor the formation of a sandwich structure onto a substrate. The immunoassay was performed by a sandwich structure consisting of three layers. The first layer was composed of immobilized antibody molecules of mouse polyclonal antibody against Hepatitis B virus surface antigen (PAb) on a silicon or quartz substrate. The second layer was the complementary Hepatitis B virus surface antigen (Antigen) molecules captured by PAb on the substrate. The third layer was composed of the probe-labelling immunogold nanoparticles, which were modified by mouse monoclonal antibody against Hepatitis B virus surface antigen (MAb) and 4-mercaptobenzoic acid (MBA) as the Raman-active probe on the surface of gold colloids. After silver staining enhancement, the antigen is identified by a SERS spectrum of MBA. A working curve of the intensity of a SERS signal at 1585 cm(-1) due to the [small nu](8a) aromatic ring vibration of MBA versus the concentration of analyte (Antigen) was obtained and the non-optimized detection limit for the Hepatitis B virus surface antigen was found to be as low as 0.5 [micro sign]g mL(-1).

Animals↗

PubMed2000

Retrovirally mediated transfer of a G protein-coupled receptor kinase (GRK) dominant-negative mutant enhances endogenous calcitonin receptor signaling in Chinese hamster ovary cells. GRK inhibition enhances expression of receptors and receptor mRNA.

G protein-coupled receptor kinases (GRKs) initiate pathways leading to agonist-dependent phosphorylation and desensitization of G protein-coupled receptors. However, the role of GRKs in modulation of signaling properties of native receptors has not been clearly defined. Here we addressed this question by generating Chinese hamster ovary (CHO) cells stably expressing a dominant-negative mutant of GRK2 (DN-GRK2), K220R, using retrovirally mediated gene transfer, and we assessed function of the endogenously expressed calcitonin (CT) receptors. We found that CT-mediated responses were prominently enhanced in CHO cells expressing DN-GRK2 compared with mock-infected control CHO cells with approximately 3-fold increases in CT-promoted cAMP production in whole cells and adenylyl cyclase activity in membrane fractions. CT-promoted phosphoinositide hydrolysis was also enhanced in DN-GRK2 cells. The number of CT receptors was increased approximately 3-fold in DN-GRK2 cells, as assessed by (125)I-salmon CT-specific binding, and this was associated with increased CT receptor mRNA levels. These results indicate that DN-GRK2 has multiple consequences for CT receptor signaling, but a primary effect is an increase in CT receptor mRNA and receptor number and, in turn, enhanced CT receptor signaling. As such, our findings provide a mechanistic basis for previous observations regarding agonist-promoted down-regulation of CT receptors and for resistance and escape from response to CT in vitro and in vivo. Moreover, the data suggest that blunting of receptor desensitization by DN-GRK2 blocks a GRK-mediated tonic inhibition of CT receptor expression and response. We speculate that GRKs play a similar role for other G protein-coupled receptors as well.

Animals↗

PubMed2002

Intravenous contrast-enhanced Doppler sonography and intra-arterial carbon dioxide-enhanced sonography in the assessment of hepatocellular carcinoma vascularity before and after treatment.

PURPOSE: To compare i.v. contrast-enhanced sonography (CEUS), power Doppler sonography (PDUS) and i.a. carbon dioxide-enhanced sonography (CO2US) in assessing hepatocellular carcinoma (HCC) vascularities before and after treatment. Differences between PDUS and CEUS with the aid of CO2US were also observed. MATERIAL AND METHODS: In all, 43 patients with 67 histologically proved HCCs were examined with PDUS, CEUS, and CO2US. Among these tumors, 36 were HCCs before treatment and 31 were HCCs treated by transcatheter arterial chemoembolization or percutaneous ethanol injection or a combination of these two treatments. CO2US was used as the gold standard when comparing the PDUS and CEUS. RESULTS: Of the 36 untreated HCC tumors, 20 (55.6%) were hypervascular compared with the liver parenchyma at PDUS, 28 (77.8%) at CEUS, 31 (86.1%) at the early phase of CO2US and 32 (88.9%) at the late phase of CO2US. Of the 31 post-treatment HCCs, 11 (35.5%) showed hypervascularity at PDUS, 25 (80.6%) at CEUS, 25 (80.6%) at the early phase of CO2US and 26 (83.9%) at the late phase of CO2US. CONCLUSION: CO2US was superior to CEUS and CEUS was superior to PDUS for the detection of tumor vascularity in both untreated and treated HCCs. The duration of enhancement at CEUS was shorter than at CO2US. The ability of CO2US to detect additional small tumors was not possible with PDUS and CEUS.

Carbon Dioxide↗

PubMed1972

Specific heterologous enhancement of immune responses. IV. Specific generation of a thymus-derived enhancing factor.

In short-term cultures of thymocytes from tetanus toxoid-immunized mice, the addition of 1 ng of toxoid generated the release of a soluble factor which was capable of enhancing the immune response to a heterologous immunogen. The addition of supernatants from such cultures to assay cultures of sheep erythrocyte-stimulated normal spleen cells produced a significant augmentation of the hemolytic plaque response. Culture fluid from similar cultures of normal thymocytes or primed thymocytes cultured without the priming antigen were inactive. The enhancing factor was nondialyzable, heat stable (56 degrees C, 30 min), resistant to DNAse and RNAse, but was inactivated by protease. A factor produced by specifically stimulated primed spleen cells had similar characteristics. In toxoid-stimulated, mixed cell cultures containing primed thymocytes or spleen cells and normal spleen cells, tenfold fewer thymocytes than spleen cells were needed to produce a comparable degree of enhancement of the anti-sheep erythrocyte plaque-forming cell response.

Animals↗

PubMed2001

Deletion of calcineurin and myocyte enhancer factor 2 (MEF2) binding domain of Cabin1 results in enhanced cytokine gene expression in T cells.

Cabin1 binds calcineurin and myocyte enhancer factor 2 (MEF2) through its COOH-terminal region. In cell lines, these interactions were shown to inhibit calcineurin activity after T cell receptor (TCR) signaling and transcriptional activation of Nur77 by MEF2. The role of these interactions under physiological conditions was investigated using a mutant mouse strain that expresses a truncated Cabin1 lacking the COOH-terminal calcineurin and MEF2 binding domains. T and B cell development and thymocyte apoptosis were normal in mutant mice. In response to anti-CD3 stimulation, however, mutant T cells expressed significantly higher levels of interleukin (IL)-2, IL-4, IL-9, IL-13, and interferon gamma than wild-type T cells. The enhanced cytokine gene expression was not associated with change in nuclear factor of activated T cells (NF-AT)c or NF-ATp nuclear translocation but was preceded by the induction of a phosphorylated form of MEF2D in mutant T cells. Consistent with the enhanced cytokine expression, mutant mice had elevated levels of serum immunoglobulin (Ig)G1, IgG2b, and IgE and produced more IgG1 in response to a T cell-dependent antigen. These findings suggest that the calcineurin and MEF2 binding domain of Cabin1 is dispensable for thymocyte development and apoptosis, but is required for proper regulation of T cell cytokine expression probably through modulation of MEF2 activity.

Adaptor Proteins, Signal Transducing↗

PubMed1992

Calculation of radiation dose enhancement factors for dose enhancement therapy of brain tumours.

When brain tumours are loaded with iodinated contrast media (CM) and exposed to x-rays, the photoelectrons, Auger electrons and fluorescent x-rays from the iodine enhance the radiation dose absorbed by the tumour. A modified CT scanner, the CTX, can be used to localize the tumour and to deliver the dose enhancement therapy. Monte Carlo calculations are presented here of the central-axis radiation depth dose in a brain containing a tumour loaded with an iodine concentration of 5 mg ml-1 and irradiated with the CTX operated at various kV settings. The dose enhancement factor (DEF) is also calculated for various field sizes and for 5 mg ml-1 of gadolinium in the tumour when the CTX is operated at 140 kV. The calculated values of the DEF are close to published experimental results.

Animals↗

PubMed2000

Enhanced GABA(A) inhibition enhances synchrony coding in human perception.

The benzodiazepine, lorazepam enhances the efficiency of local, inhibitory GABA(A) synapses in the cortex, which stabilize postsynaptic, excitatory activity by synchronizing their own discharges at around 40 Hz. Treatment with lorazepam has also been shown to adversely influence detection performance in perceptual tasks, suggesting a role for GABA(A)-mediated synchronization during visuo-perceptual organization. Consistent with these findings we report that reaction times to target stimuli were slower following lorazepam treatment. However, when targets followed presentation of a synchronized prime, presented within a flickering 40-Hz display matrix, the effects of priming were amplified relative to baseline and control conditions. We conclude that enhanced GABA(A)-induced inhibition enhances stimulus-evoked synchronization with differential effects upon mechanisms of perceptual segmentation and grouping.

Adult↗

PubMed2006

Hepatic metastases of hemangiopericytoma: contrast-enhanced MRI, contrast-enhanced ultrasonography and angiography findings.

Hemangiopericytoma is a rare and characteristically hypervascular tumour. We report a case of hepatic metastases of hemangiopericytoma for which there was correlative imaging by ultrasonography, ultrasonography with second-generation contrast agent (BR1), computed tomography, gadolinium-enhanced, Gd-BOPTA-enhanced and ferumoxides-enhanced magnetic resonance, and angiography. To our knowledge, this is the first reported case in which all these modalities were used in the diagnostic evaluation.

Abdominal Pain↗

PubMed2003

Screening of stress enhancer based on analysis of gene expression profiles: enhancement of hyperthermia-induced tumor necrosis by an MMP-3 inhibitor.

To improve the therapeutic benefit of hyperthermia, we examined changes of global gene expression after heat shock using DNA microarrays consisting of 12 814 clones. HeLa cells were treated for 1 h at 44 degrees C and RNA was extracted from the cells 0, 3, 6, and 12 h after heat shock. The 664 genes that were up or down-regulated after heat shock were classified into 7 clusters using fuzzy adaptive resonance theory (fuzzy ART). There were 41 genes in two clusters that were induced in the early phase after heat shock. In addition to shock response genes, such as hsp70 and hsp40, the stress response genes c-jun, c-fos and egr-1 were expressed in the early phase after heat shock. We also found that expression of matrix metalloproteinase 3 (MMP-3) was enhanced during the early response. We therefore investigated the role of MMP-3 in the heat shock response by examining HeLa cell survival after heat treatment in the presence and absence of an MMP-3 inhibitor, N-isobutyl-N-(4-methoxyphenylsulfonyl)glycylhydroxamic acid (NNGH) or N-hydroxy-2(R)-[[4- methoxysulfonyl](3-picolyl)amino]-3-methylbutaneamide hydrochloride (MMI270). The number of surviving cells 3 days after heat treatment significantly decreased, reaching 3.5% for NNGH and 0.2% for MMI270. These results indicate that the MMP-3 inhibitors enhanced heat shock-induced cell death and behaved as stress enhancers in cancer cells. This valuable conclusion was reached as a direct result of the gene expression profiling that was performed in these studies.

Cell Survival↗

PubMed1994

Absorption enhancement of intrapulmonary administered insulin by various absorption enhancers and protease inhibitors in rats.

The effects of absorption enhancers and protease inhibitors on the pulmonary absorption of insulin were examined by means of an in-situ pulmonary absorption experiment. Absorption enhancers used in this study were sodium glycocholate, linoleic acid-surfactant mixed micelles and N-lauryl-beta-D-maltopyranoside whereas aprotinin, bacitracin and soybean trypsin inhibitor were used as protease inhibitors. The absorption of insulin from the lung was evaluated by its hypoglycaemic effect. In the absence of these additives, a slight hypoglycaemic effect was obtained following intrapulmonary administration of insulin. However, we found significant and continuous hypoglycaemic effects after the insulin administration with these additives. N-Lauryl-beta-D-maltopyranoside and bacitracin appeared to be more effective for enhancing the pulmonary absorption of insulin than the other adjuvants. These findings suggest that the use of these two adjuvants would be a useful approach for improving the pulmonary absorption of insulin.

Absorption↗

PubMed2001

A self-coherence enhancement algorithm and its application to enhancing three-dimensional source estimation from EEGs.

In this paper a new algorithm is proposed to enhance the spatial resolution of solutions of the underdetermined EEG inverse problem. Termed the self-coherence enhancement algorithm (SCEA), the present algorithm provides a self-coherence solution, which is a function of the high order self-coherence estimate of an unbiased smooth estimate of the underdetermined EEG inverse solution. The order of the high order self-coherence function is determined by the blurring level of the actual source distribution as represented by a normalized blurring index. The proposed SCEA algorithm may be used to enhance the spatial resolution of an inverse solution obtained by any inverse reconstruction algorithm. Computer simulation studies have been conducted to evaluate the performance of the SCEA and to compare its performance to that of the LORETA and the FOCUSS algorithms.

Algorithms↗