CONCEPTS IN MAGNETIC RESONANCE, Issue 5 2007
Gang Zheng
Abstract Artifacts arising from background gradients are very common in NMR diffusion (i.e., PGSE) experiments involving B0 gradients because of the unavoidable magnetic susceptibility differences and B0 inhomogeneity within and around the sample. This article presents the general methodology to develop PGSE sequences with background gradient suppression. Most of the available methods which can be used for the suppression of the effects of background gradients are discussed. And two newly developed methods are presented in detail: frequency analysis of spin-dephasing, which assumes the artifacts due to background gradients come from the resonance between the spin-dephasing caused by applied gradients and background gradients, and asymmetric bipolar stimulated-echo-based PGSE, which can suppress the effects of nonconstant background gradients. © 2007 Wiley Periodicals, Inc.Concepts Magn Reson Part A 30A: 261,277, 2007. [source]

Inflammatory cytokines augments TGF-,1-induced epithelial-mesenchymal transition in A549 cells by up-regulating T,R-I

CYTOSKELETON, Issue 12 2008
Xiangde Liu
Abstract Epithelial-mesenchymal transition (EMT) is believed to play an important role in fibrosis and tumor invasion. EMT can be induced in vitro cell culture by various stimuli including growth factors and matrix metalloproteinases. In this study, we report that cytomix (a mixture of IL-1,, TNF-, and IFN-,) significantly enhances TGF-,1-induced EMT in A549 cells as evidenced by acquisition of fibroblast-like cell shape, loss of E-cadherin, and reorganization of F-actin. IL-1, or TNF-, alone can also augment TGF-,1-induced EMT. However, a combination of IL-1, and TNF-, or the cytomix is more potent to induce EMT. Cytomix, but not individual cytokine of IL-1,, TNF-, or IFN-,, significantly up-regulates expression of TGF-, receptor type I (T,R-I). Suppression of T,R-I, Smad2 or Smad3 by siRNA partially blocks EMT induction by cytomix plus TGF-,1, indicating cytomix augments TGF-,1-induced EMT through enhancing T,R-I and Smad signaling. These results indicate that inflammatory cytokines together with TGF-,1 may play an important role in the development of fibrosis and tumor progress via the mechanism of epithelial-mesenchymal transition. Cell Motil. Cytoskeleton 2008. © 2008 Wiley-Liss, Inc. [source]

Treatment of diabetic hypertension

DIABETES OBESITY & METABOLISM, Issue 5 2009
David S. H. Bell
Insulin resistance and hyperglycaemia combine to make hypertension more prevalent in the type 2 diabetic patient. Blood pressure goals below those for the non-diabetic subject have been shown to be more effective in lowering mortality and cardiovascular events in the diabetic patient. To achieve these goals in most cases, three to five antihypertensives from different therapeutic groups need to be utilized. Suppression of the renin,angiotensin system (RAS) with angiotensin-converting enzyme inhibitors, angiotensin 2 receptor blockers or a renin inhibitor should be the primary therapy. A second goal should be suppression of the sympathetic nervous system utilizing a beta-blocker that does not increase insulin resistance. The addition of a diuretic, calcium channel blocker or a vasodilator to suppressors of the RAS and sympathetic nervous system aid in achieving hypertensive goals in the diabetic patient. Achieving hypertensive goals with suppression of the RAS and sympathetic nervous system should result in a decrease in mortality and cardiovascular events in the diabetic hypertensive patient. In this review article, the benefits and disadvantages of the different antihypertensive therapies in the diabetic patient are discussed. [source]

Suppression of post-prandial hyperglycaemia by pioglitazone improved islet fibrosis and macrophage migration in the Goto,Kakizaki rat

DIABETES OBESITY & METABOLISM, Issue 9 2008
H. Mizukami
First page of article [source]

Suppression of electromagnetic radiation noise from wireless modules in the millimeter-wave band by means of alumina containing carbon black

ELECTRONICS & COMMUNICATIONS IN JAPAN, Issue 10 2010
Yasuharu Takase
Abstract Unwanted electromagnetic (EM) radiation generated from wireless modules in the millimeter-wave band used for car radar creates errors and results in performance degradation of electronic equipment. In this paper, to reduce these unwanted EM waves, an optimal design to add the function of EM wave absorption to the lid for the module is examined. Alumina-containing carbon black is used as a wave absorption material for the lid. Absorption of 20 dB or more is obtained as a measured result with the cover added for EM wave absorption at 60 GHz. The wireless module was also analyzed in the millimeter-wave band with the designed material used for the lid. The radiation and the reflection of electric power were greatly reduced by the loss electric power from the lid. Therefore, effective data for suppressing unwanted EM radiation noise from wireless modules in the millimeter-wave band can be provided. © 2010 Wiley Periodicals, Inc. Electron Comm Jpn, 93(10): 25,33, 2010; Published online in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/ecj.10216 3 [source]

Suppression of the mouse double minute 4 gene causes changes in cell cycle control in a human mesothelial cell line responsive to ultraviolet radiation exposure

ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 9 2009
Melisa Bunderson-Schelvan
Abstract The TP53 tumor suppressor gene is the most frequently inactivated gene in human cancer identified to date. However, TP53 mutations are rare in human mesotheliomas, as well as in many other types of cancer, suggesting that aberrant TP53 function may be due to alterations in its regulatory pathways. Mouse double minute 4 (MDM4) has been shown to be a key regulator of TP53 activity, both independently as well as in concert with its structural homolog, Mouse Double Minute 2 (MDM2). The purpose of this study was to characterize the effects of MDM4 suppression on TP53 and other proteins involved in cell cycle control before and after ultraviolet (UV) exposure in MeT5a cells, a nonmalignant human mesothelial line. Short hairpin RNA (shRNA) was used to investigate the impact of MDM4 on TP53 function and cellular transcription. Suppression of MDM4 was confirmed by Western blot. MDM4 suppressed cells were analyzed for cell cycle changes with and without exposure to UV. Changes in cell growth as well as differences in the regulation of direct transcriptional targets of TP53, CDKN1A (cyclin-dependent kinase 1,, p21) and BAX, suggest a shift from cell cycle arrest to apoptosis upon increasing UV exposure. These results demonstrate the importance of MDM4in cell cycle regulation as well as a possible role inthe pathogenesis of mesothelioma-type cancers. Environ. Mol. Mutagen. 2009. © 2009 Wiley-Liss, Inc. [source]

Seizure Suppression by Adenosine A1 Receptor Activation in a Mouse Model of Pharmacoresistant Epilepsy

EPILEPSIA, Issue 7 2003
Nicolette Gouder
Summary: Purpose: Because of the high incidence of pharmacoresistance in the treatment of epilepsy (20,30%), alternative treatment strategies are needed. Recently a proof-of-principle for a new therapeutic approach was established by the intraventricular delivery of adenosine released from implants of engineered cells. Adenosine-releasing implants were found to be effective in seizure suppression in a rat model of temporal lobe epilepsy. In the present study, activation of the adenosine system was applied as a possible treatment for pharmacoresistant epilepsy. Methods: A mouse model for drug-resistant mesial temporal lobe epilepsy was used, in which recurrent spontaneous seizure activity was induced by a single intrahippocampal injection of kainic acid (KA; 200 ng in 50 nl). Results: After injection of the selective adenosine A1 -receptor agonist, 2-chloro- N6 -cyclopentyladenosine (CCPA; either 1.5 or 3 mg/kg, i.p.), epileptic discharges determined in EEG recordings were completely suppressed for a period of ,3.5 h after the injections. Seizure suppression was maintained when 8-sulfophenyltheophylline (8-SPT), a non,brain-permeable adenosine-receptor antagonist, was coinjected systemically with CCPA. In contrast, systemic injection of carbamazepine or vehicle alone did not alter the seizure pattern. Conclusions: This study demonstrates that activation of central adenosine A1 receptors leads to the suppression of seizure activity in a mouse model of drug-resistant epilepsy. We conclude that the local delivery of adenosine into the brain is likely to be effective in the control of intractable seizures. [source]

Seizure Suppression by Adenosine-releasing Cells Is Independent of Seizure Frequency

EPILEPSIA, Issue 8 2002
Detlev Boison
Summary: ,Purpose: Intraventricular cellular delivery of adenosine was recently shown to be transiently efficient in the suppression of seizure activity in the rat kindling model of epilepsy. We tested whether the suppression of seizures by adenosine-releasing grafts was independent of seizure frequency. Methods: Adenosine-releasing cells were encapsulated and grafted into the lateral brain ventricle of rats kindled in the hippocampus. During 4 weeks after grafting, electric test stimulations were delivered at a frequency of either once a week or 3 times per week. Seizure activity was evaluated by visual scoring of seizure severity and by the recording of EEGs. Results: Adenosine released from encapsulated cells exerted potent antiepileptic activity for ,2 weeks. One week after grafting, treated rats displayed a complete protection from clonic seizures, and a protection from focal seizures was observed in the majority of animals. Seizure suppression was accompanied by a reduction of afterdischarges in EEG recordings. The protective efficacy of the grafted cells was the same irrespective of whether electrical test stimulations were delivered 1 or 3 times per week. Rats receiving control grafts continued to display full clonic convulsions. Conclusions: This study demonstrated that the frequency of test stimulations did not influence the seizure-suppressive potential of adenosine-releasing grafts. Thus the local delivery of adenosine is likely to be effective in seizure control over a threefold range of seizure-discharge frequency. [source]

Suppression of inflammatory responses by celastrol, a quinone methide triterpenoid isolated from Celastrus regelii

EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 9 2009
D. H. Kim
Abstract Background, Celastrol, a quinone methide triterpenoid isolated from the Celastraceae family, exhibits various biological properties, including chemopreventive, antioxidant and neuroprotective effects. In this study, we showed that celastrol inhibits inflammatory reactions in macrophages and protects mice from skin inflammation. Materials and methods, Anti-inflammatory effects of celastrol (0,1 ,M) were examined in lipopolysaccharide (LPS)-stimulated RAW 264·7 macrophages. To investigate the effects of celastrol (0,50 ,g per mice) in vivo, activation of myeloperoxidase (MPO) and histological assessment were examined in the 12- O -tetradecanoyl-phorbol-13-acetate (TPA)-induced mouse ear oedema model. Results, Our in vitro experiments showed that celastrol suppressed not only LPS-stimulated generation of nitric oxide and prostaglandin E2, but also expression of inducible nitric oxide synthase and cyclooxygenase-2 in RAW264·7 cells. Similarly, celastrol inhibited LPS-induced production of inflammatory cytokines, including tumour necrosis factor-, and interleukin-6. In an animal model, celastrol protected mice from TPA-induced ear oedema, possibly by inhibiting MPO activity and production of inflammatory cytokines. Conclusions, Our data suggest that celastrol inhibits the production of inflammatory mediators and is a potential target for the treatment of various inflammatory diseases. [source]

Suppression of viral replication with highly active antiretroviral therapy has no impact on the functional profile of HIV-specific CD8+ T cells

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 6 2008
Mariola López
Abstract A better control of viral replication in long-term non-progressors has been associated with polyfunctional CD8+ T cell responses. However, low levels of HIV replication could be the cause rather than the consequence of enhanced immune responses in long-term non-progressors. The functional profile and the expansion ability of HIV-Gag- and HIV-Nef-specific CD8 responses were analysed measuring the production of MIP-1,, IL-2, TNF-, and expression of CD107, using polychromatic flow cytometry, in 36,HIV-infected patients at baseline and after 12,months of highly active antiretroviral therapy (HAART) and complete viral suppression. Most patients presented detectable Gag and Nef responses both at baseline and after 1,year of HAART, with a significant decline after achieving viral suppression. At baseline, the majority of CD8+ response was due to cells producing only MIP-1, or simultaneously MIP-1, and CD107. The functional profile did not significantly change after achieving complete viral suppression with HAART. Therefore, control of HIV-1 replication after 1,year of HAART had no significant impact on the quality of HIV-1-specific CD8 response, but the effects of treatment in long-term, or of early HAART are not known. Thus, it is still uncertain whether multifunctional CD8 responses are the cause or consequence of low plasma viremia. [source]

CLINICAL STUDY: Suppression of cue-induced heroin craving and cue-reactivity by single-trial transcutaneous electrical nerve stimulation at 2 Hz

ADDICTION BIOLOGY, Issue 2 2006
Fei Zhong
ABSTRACT The purpose of the present study was to investigate the efficacy of 2 Hz transcutaneous electrical nerve stimulation (TENS) to reduce cue-induced heroin craving and the corresponding cardiovascular responses. Seventy heroin addicts with at least 1 month of abstinence were enrolled and randomly divided into two groups of 35, to receive single-trial 2 Hz TENS (TENS group) or mock TENS (mock group) during experimental procedure, respectively. They were required to express their degree of craving by visual analog scale before and after the presentation of a video-cue, and after TENS treatment, which lasted for 30 minutes. Heart rate and arterial blood pressure were simultaneously monitored in 56 cases, with 28 in each group. Results show that in mock group, video-cue induced a dramatic increase of craving score, which did not return to baseline in 150 minutes, whereas in the TENS group, 2 Hz TENS treatment produced a significant decrease of craving, reaching baseline in 90 minutes. Video-cue induced a significant increase of heart rate and systolic and diastolic blood pressure, which remained elevated for at least 60 minutes in the mock group; whereas in the TENS group, they returned to baseline immediately after the termination of TENS. These results indicate that the craving induced by a heroin-related cue can be immediately and significantly suppressed, and the cardiovascular activation totally abolished by a single-trial 2 Hz TENS for 30 minutes [source]

Suppression of Ni4Ti3 Precipitation by Grain Size Refinement in Ni-Rich NiTi Shape Memory Alloys,

ADVANCED ENGINEERING MATERIALS, Issue 8 2010
Egor A. Prokofiev
Severe plastic deformation (SPD) processes, such as equal channel angular pressing (ECAP) and high pressure torsion (HPT), are successfully employed to produce ultra fine grain (UFG) and nanocrystalline (NC) microstructures in a Ti,50.7,at% Ni shape memory alloy. The effect of grain size on subsequent Ni-rich particle precipitation during annealing is investigated by transmission electron microscopy (TEM), selected area electron diffraction (SAD, SAED), and X-ray diffraction (XRD). It is observed that Ni4Ti3 precipitation is suppressed in grains of cross-sectional equivalent diameter below approximately 150,nm, and that particle coarsening is inhibited by very fine grain sizes. The results suggest that fine grain sizes impede precipitation processes by disrupting the formation of self-accommodating particle arrays and that the arrays locally compensate for coherency strains during nucleation and growth. [source]

Suppression of excitatory cholinergic synaptic transmission by Drosophila dopamine D1-like receptors

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 9 2007
Ning Yuan
Abstract The physiological function of dopamine is mediated through its G-protein-coupled receptor family. In Drosophila, four dopamine receptors have been molecularly characterized so far. However, due largely to the absence of a suitable preparation, the role of Drosophila dopamine receptors in modulating central synaptic transmission has not been examined. The present study investigated mechanisms by which dopamine modulates excitatory cholinergic synaptic transmission in Drosophila using primary neuronal cultures. Whole-cell recordings demonstrated that cholinergic excitatory postsynaptic currents (EPSCs) were down-regulated by focally applied dopamine (10,500 µm). The vertebrate D1 specific agonists SKF38393 and 6-chloro-APB (10 µm) mimicked dopamine-mediated suppression of cholinergic synaptic transmission with higher potency. In contrast, the D2 agonists quinpirole and bromocriptine did not alter cholinergic EPSCs, demonstrating that dopamine-mediated suppression of cholinergic synaptic transmission is specifically through activation of Drosophila D1-like receptors. Biophysical analysis of miniature EPSCs indicated that cholinergic suppression by activation of D1-like receptors is presynaptic in origin. Dopamine modulation of cholinergic transmission is not mediated through the cAMP/protein kinase A signaling pathway as cholinergic suppression by dopamine occurred in the presence of the protein kinase A inhibitor H-89. In addition, an adenylate cyclase activator, forskolin, led to an increase, not a decrease, of cholinergic EPSC frequency. Finally, we showed that activation of D1-like receptors decreased the frequency of action potentials in cultured Drosophila neurons by inhibiting excitatory cholinergic transmission. All our data demonstrated that activation of D1-like receptors in Drosophila neurons negatively modulates excitatory cholinergic synaptic transmission and thus inhibits neuronal excitability. [source]

Silencing dopamine D3 -receptors in the nucleus accumbens shell in vivo induces changes in cocaine-induced hyperlocomotion

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2005
Amine Bahi
Abstract The dopamine D3 receptor (D3R) is an important pharmacotherapeutic target for its potential role in psychiatric disorders and drug dependence. To further explore its function in rats, a regulatable lentivirus, Lenti-D3, holding the rat D3R cDNA, has been constructed as well as three nonregulatable lentiviruses, Lenti-D3-siRNA1, Lenti-D3-siRNA2 and Lenti-D3-siRNA3, expressing small hairpin RNAs, aimed at silencing D3R expression and specifically targeted against different regions of the D3R mRNA. In vitro, Lenti-D3 expressed D3R and could efficiently be blocked with Lenti-D3-Sils. These viruses were stereotaxically injected into the shell part of the nucleus accumbens (NAcc) and effects of passive cocaine delivery on locomotor activity were assessed. Manipulations of D3R levels induced changes in the locomotor stimulant effects of cocaine as compared to control treatment. Suppression of dopamine (DA) D3R in the NAcc by means of local knockdown (with Lenti-D3-Sils) increased locomotor stimulant effects, whereas its overexpression with Lenti-D3 drastically reduced them. The latter effects could be reversed when animals were fed doxycycline, which prevented lentiviral-mediated DA D3R overexpression in the NAcc. Gene expression assessed by quantitative RT-PCR confirmed very efficient gene knockdown in vivo in animals treated with Lenti-D3-Sils (> 93% silencing of D3R gene). Thus D3R expression significantly contributes to behavioural changes associated with chronic cocaine delivery. [source]

Suppression of c-fos induction in the nucleus accumbens prevents acquisition but not expression of morphine-conditioned place preference

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 9 2000
Bryan K. Tolliver
Abstract The c-fos immediate-early gene is induced by morphine and other drugs of abuse in the nucleus accumbens (NAc), a mesolimbic region implicated in drug abuse and reward. This study examined the role of c-fos in the acquisition and expression of the conditioned place paradigm (CPP) in the rat by suppressing Fos protein expression with c-fos antisense oligodeoxynucleotides (ODNs). CPP was completely prevented by c-fos antisense ODN infused bilaterally into the NAc prior to each systemic morphine injection, whereas sense and missense NAc injections had no effect on CPP. NAc administration of c-fos antisense ODN after the last systemic morphine conditioning session did not affect the expression of morphine-CPP. These results suggest that c-fos expression in NAc is necessary for the acquisition but not expression of morphine-CPP, and they have important implications for understanding conditioned behaviours and drug craving and addiction. [source]

Specific Ca2+ Fluorescent Sensor: Signaling by Conformationally Induced PET Suppression in a Bichromophoric Acridinedione

EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 34 2009
Pichandi Ashokkumar
Abstract A series of acridinedione-based bichromophoric podand systems 1a,c were synthesized and characterized. Among these, bichromophore 1c shows specific binding of Ca2+ in the presence of other biologically important metal ions like Na+, K+, Mg2+, and Zn2+. The selective complexation was proved by steady-state emission, time-resolved emission, and 1H NMR titration. Signaling of the binding event was achieved by Ca2+ -induced folding of the bichromophore, resulting in PET suppression in the acridinedione chromophore. Involvement of a PET process in the optical signaling was confirmed by comparing bichromophores 1a,c with non-PET compound 2 and monochromophore model compound 3. Non-PET compound 2 failed to give optical response upon Ca2+ binding as a result of the absence of a PET process in the Ca2+ -bound complex. Monochromophore 3 shows a similar optical response, which is the same as that in 1c. Titration of the metal-ion-bound complex of 1c with EDTA released the metal ion from the complex, thereby regaining the original photophysical properties of the bichromophore.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009) [source]

Decomposing the construct of ambivalence over emotional expression in a Chinese cultural context

EUROPEAN JOURNAL OF PERSONALITY, Issue 3 2005
Sylvia Xiaohua Chen
The present study examined the construct of ambivalence over emotional expression proposed by King and Emmons (1990) in the Chinese context, and identified a factor structure different from those proposed in previous Western studies. The results of this study provided discriminant validity for this newly extracted two-factor structure of ambivalence, viz., Emotional Rumination and Emotional Suppression. Emotional Rumination was significantly predicted by the personality scales of introversion and inferiority, and the belief dimension of fate control, whereas Emotional Suppression was predicted by the personality scales of diversity, face, and harmony, and the belief dimension of social complexity. The different effects of Emotional Rumination and Emotional Suppression in predicting life satisfaction showed that emotional experience has its own specific characteristics in Chinese culture, and that responding to its emic characteristics will yield a more culturally responsive understanding of emotional experience and expression. Copyright © 2004 John Wiley & Sons, Ltd. [source]

Suppression of Premature Fracture of Silicon under Three-Point Bending: Role of Nanoscale Localized Deformation of Metallic Multilayered Coating,

ADVANCED ENGINEERING MATERIALS, Issue 1-2 2009
Yuan-Ping Li
Brittle single crystal Si with and without Au/Cu multilayer coating was investigated via three-point bending test. Load-bearing capacity of the Si coated with the Au/Cu multilayer is improved evidently compared with the bare Si. Especially the nanoscale plastic deformation of the multilayer was observed to be effective in delaying instable crack propagation within the Si. That would shed significant light in toughening methods of brittle materials. [source]

Suppression of sidelobes in OFDM systems by multiple-choice sequences,

EUROPEAN TRANSACTIONS ON TELECOMMUNICATIONS, Issue 6 2006
Ivan Cosovic
In this paper, we consider the problem of out-of-band radiation in orthogonal frequency-division multiplexing (OFDM) systems caused by high sidelobes of the OFDM transmission signal. Suppression of high sidelobes in OFDM systems enables higher spectral efficiency and/or co-existence with legacy systems in the case of OFDM spectrum sharing systems. To reduce sidelobes, we propose a method termed multiple-choice sequences (MCS). It is based on the idea that transforming the original transmit sequence into a set of sequences and choosing that sequence out of the set with the lowest power in the sidelobes allows to reduce the out-of-band radiation. We describe the general principle of MCS and out of it we derive and compare several practical MCS algorithms. In addition, we shortly consider the combination of MCS sidelobe suppression method with existing sidelobe suppression methods. Numerical results show that with MCS approach OFDM sidelobes can be reduced significantly while requiring only a small amount of signalling information to be sent from transmitter to receiver. For example, in an OFDM overlay scenario sidelobes power is reduced by around 10,dB with a signalling overhead of only 14%. Copyright © 2006 AEIT. [source]

Suppression of urokinase receptor expression by bikunin is associated with inhibition of upstream targets of extracellular signal-regulated kinase-dependent cascade

FEBS JOURNAL, Issue 16 2002
Hiroshi Kobayashi
Our laboratory showed that bikunin, a Kunitz-type protease inhibitor, suppresses 4,-phorbol 12-myristate 13-acetate (PMA)- or tumor necrosis factor-alpha (TNF,)-induced urokinase-type plasminogen activator (uPA) expression in different cell types. In addition to its effects on protease inhibition, bikunin could be modulating other cellular events associated with the metastatic cascade. To test this hypothesis, we examined whether bikunin was able to suppress the expression of uPA receptor (uPAR) mRNA and protein in a human chondrosarcoma cell line, HCS-2/8, and two human ovarian cancer cell lines, HOC-I and HRA. The present study showed that (a) bikunin suppresses the expression of constitutive and PMA-induced uPAR mRNA and protein in a variety of cell types; (b) an extracellular signal-regulated kinase (ERK) activation system is necessary for the PMA-induced increase in uPAR expression, as PD098059 and U0126, which prevent the activation of MEK1, reduce the uPAR expression; (c) bikunin markedly suppresses PMA-induced phosphorylation of ERK1/2 at the concentration that prevents uPAR expression, but does not reduce total ERK1/2 antigen level; (d) bikunin has no ability to inhibit overexpression of uPAR in cells treated with sodium vanadate; and (e) we further studied the inhibition of uPAR expression by stable transfection of HRA cells with bikunin gene, demonstrating that bikunin secretion is necessary for inhibition of uPAR expression. We conclude that bikunin downregulates constitutive and PMA-stimulated uPAR mRNA and protein possibly through suppression of upstream targets of the ERK-dependent cascade, independent of whether cells were treated with exogenous bikunin or transfected with bikunin gene. [source]

Suppression of splenic macrophage Candida albicans phagocytosis following in vivo depletion of natural killer cells in immunocompetent BALB/c mice and T-cell-deficient nude mice

FEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 3 2002
I Algarra
Abstract The resistance of mice to systemic infections caused by Candida albicans is associated with activated splenic macrophages. In addition, there is a correlation between natural killer (NK) cell activation and the resistance to systemic candidiasis. The present study was designed to clarify the role of NK cells in the control of splenic macrophage C. albicans phagocytosis by either depleting NK cells (anti-asialo GM1 treatment) or maintaining them in an activated state (tilorone treatment) in both immunocompetent BALB/c mice and T-cell-deficient nude mice. The results of the in vitro phagocytosis assays were analyzed by flow cytometry and demonstrate the pivotal role of NK cells in controlling the capacity of splenic macrophages to phagocytose C. albicans. In summary, these data provide evidence that the NK cells are the main inducers of phagocytic activity of splenic macrophages and that they mediate the protection against C. albicans systemic infection. [source]

Suppression of ectomycorrhizal development in young Pinus thunbergii trees inoculated with Bursaphelenchus xylophilus

FOREST PATHOLOGY, Issue 3 2001
Ichihara
In order to study the changes in ectomycorrhizal development during symptom expression of pine wilt disease, root window observations were conducted concurrent with measurements of leaf water potential as well as photosynthetic and transpiration rates of 5-year-old Pinus thunbergii trees that were inoculated with the pinewood nematode (PWN) Bursaphelenchus xylophilus. Infected trees were compared with girdled and uninfected control trees. Ectomycorrhizas developed constantly during the experimental period in control trees but did not develop in the girdled trees. Ectomycorrhizal development ceased within 2 weeks in those trees that finally died after PWN infection. In the trees that survived PWN infection, ectomycorrhizal development ceased within 1,4 weeks of inoculation but was resumed thereafter within 3,6 weeks. Ectomycorrhizal development ceased prior to a decrease in both photosynthetic rate and leaf water potential in the inoculated trees. Restriction du développement ectomycorhizien chez de jeunes Pinus thunbergii inoculés par Bursaphelenchus xylophilus Pour étudier les modifications du développement ectomycorhizien durant l'évolution des symptômes de flétrissement des pins, un suivi des racines a été réalisé en parallèle avec des mesures du potentiel hydrique foliaire, de la photosynthèse et de la transpiration chez des Pinus thunbergiiâgés de 5 ans inoculés avec le nématode des pins (PWN), Bursaphelenchus xylophilus. Des arbres infectés ont été comparés à des arbres cernés et des témoins non infectés. Les ectomycorhizes se sont développées de façon constante durant la période d'observation chez les arbres témoins mais non pas chez les arbres cernés. Le développement ectomycorhizien s'était arrêté en 2 semaines chez les arbres qui sont morts de l'infection du PWN. Chez les arbres qui ont survécu à l'infection du PWN, le développement ectomycorhizien avait cessé 1 à 4 semaines après l'inoculation mais avait repris ensuite entre la 3ème et la 6ème semaine. Le développement ectomycorhizien cessait avant la diminution de la photosynthèse et du potentiel hydrique foliaire chez les arbres inoculés. Unterdrückung der Ektomykorrhizabildung in jungen Pinus thunbergii nach Inokulation mit Bursaphelenchus xylophilus Um Veränderungen der Ektomykorrhizabildung während der Symptomausprägung der Kiefernwelke zu untersuchen, wurde diese mit Hilfe von ,Wurzelfenstern' beobachtet. Gleichzeitig wurde das Wasserpotential der Blätter sowie die Photosynthese- und Transpirationsraten fünfjähriger Pinus thunbergii gemessen, die mit dem Erreger der Kiefernwelke (PWN) Bursaphelenchus xylophilus inokuliert worden waren. Die infizierten Bäume wurden mit geringelten Bäumen und mit nicht infizierten Kontrollen verglichen. In den Kontrollbäumen entwickelten sich während des gesamten Beobachtungszeitraumes kontinuierlich Ektomykorrhizen, es bildeten sich jedoch keine bei den geringelten Bäumen. Die Ektomykorrhizabildung hörte bei den Bäumen, die nach der PWN-Infektion schliesslich abstarben, innerhalb von zwei Wochen auf. Bei Bäumen, welche die PWN-Infektion überlebten, war die Ektomykorrhizabildung ein bis vier Wochen nach der Inokulation unterbrochen, sie wurde aber nach drei bis sechs Wochen wieder fortgesetzt. Die Bildung der Ektomykorrhiza hörte in den inokulierten Bäumen auf, bevor die Photosyntheserate und das Wasserpotential in den Blättern abnahmen. [source]

Suppression of NF-,B-dependent gene expression by a hexamethylene bisacetamide-inducible protein HEXIM1 in human vascular smooth muscle cells

GENES TO CELLS, Issue 2 2003
Rika Ouchida
Background: Neointima formation is a characteristic feature of atherosclerosis and post-angioplasty restenosis, in which various soluble factors and mechanical injury stimulate signalling pathways in vascular smooth muscle cells (VSMC), promoting their migration and proliferation, and the eventual formation of the neointima. The transcription factor NF-,B has been shown to play a pivotal role in this process. Hexamethylene bisacetamide, an inhibitor of VSMC proliferation, induces the mRNA expression of HEXIM1 (hexamethylene bisacetamide-inducible protein 1). However, the protein expression and function of HEXIM1 remain unknown. Results: In the present study, we demonstrated that HEXIM1 localizes in the cytoplasm and nucleus, and its nuclear expression is restricted to discrete speckled areas. Treatment of VSMC with hexamethylene bisacetamide up-regulated HEXIM1 expression, not only in mRNA but also protein levels. Moreover, HEXIM1 is shown to suppress the transcriptional activity of NF-,B via its C-terminal leucine-rich domain. A glutathione-S-transferase pull down assay indicated that HEXIM1 interacts with the p65 subunit of NF-,B. In VSMC, treatment with hexamethylene bisacetamide resulted in a down-modulation of the transcription of NF-,B target genes. Conclusion: We may therefore conclude that HEXIM1 plays an inhibitory role in NF-,B-dependent gene expression in VSMC and is the candidate of a novel therapeutic target for inhibition of VSMC proliferation. [source]

Carbon dioxide exchange of a Russian boreal forest after disturbance by wind throw

GLOBAL CHANGE BIOLOGY, Issue 3 2002
Alexander Knohl
Abstract The exchange of carbon dioxide (CO2) between the atmosphere and a forest after disturbance by wind throw in the western Russian taiga was investigated between July and October 1998 using the eddy covariance technique. The research area was a regenerating forest (400 m × 1000 m), in which all trees of the preceding generation were uplifted during a storm in 1996. All deadwood had remained on site after the storm and had not been extracted for commercial purposes. Because of the heterogeneity of the terrain, several micrometeorological quality tests were applied. In addition to the eddy covariance measurements, carbon pools of decaying wood in a chronosequence of three different wind throw areas were analysed and the decay rate of coarse woody debris was derived. During daytime, the average CO2 uptake flux was ,3 µmol m,2s,1, whereas during night-time characterised by a well-mixed atmosphere the rates of release were typically about 6 µmol m,2s,1. Suppression of turbulent fluxes was only observed under conditions with very low friction velocity (u* , 0.08 ms,1). On average, 164 mmol CO2 m,2d,1 was released from the wind throw to the atmosphere, giving a total of 14.9 mol CO2 m,2 (180 g CO2 m,2) released during the 3-month study period. The chronosequence of dead woody debris on three different wind throw areas suggested exponential decay with a decay coefficient of ,0.04 yr,1. From the magnitude of the carbon pools and the decay rate, it is estimated that the decomposition of coarse woody debris accounted for about a third of the total ecosystem respiration at the measurement site. Hence, coarse woody debris had a long-term influence on the net ecosystem exchange of this wind throw area. From the analysis performed in this work, a conclusion is drawn that it is necessary to include into flux networks the ecosystems that are subject to natural disturbances and that have been widely omitted into considerations of the global carbon budget. The half-life time of about 17 years for deadwood in the wind throw suggests a fairly long storage of carbon in the ecosystem, and indicates a very different long-term carbon budget for naturally disturbed vs. commercially managed forests. [source]

Suboccipital Nerve Blocks for Suppression of Chronic Migraine: Safety, Efficacy, and Predictors of Outcome

HEADACHE, Issue 6 2010
Silvia Weibelt RN
(Headache 2010;50:1041-1044) Background., Approximately 1 in 50 Americans is afflicted by chronic migraine (CM). Many patients with CM describe cervicogenic headache. Options for treating CM effectively are at present quite limited. Objective., To determine the safety and efficacy of occipital nerve blocks (ONBs) used to treat cervicogenic chronic migraine (CCM) and to identify variables predictive of a positive treatment response. Methods., Using a uniform dose and injection paradigm, we performed ONBs consecutively on a series of patients presenting with CCM. Patients were stratified according to specific findings found to be present or absent on physical examination. A positive treatment outcome was defined as a 50% or greater reduction in headache days per month over the 30 days following treatment relative to the 30-day pre-treatment baseline. We used a 5-point Likert scale as one of the secondary outcome variables. Results., We treated 150 consecutive patients with unilateral (37) or bilateral (113) ONBs. At the 1-month follow-up visit 78 (52%) exhibited evidence of a positive treatment response according to the primary outcome variable, and 90 (60%) reported their headache disorder to be "better" (44; 29%) or "much better" (46; 30%). A total of 8 (5%) patients reported adverse events within the ensuing 72 hours, and 3 (2%) experienced adverse events that reversed spontaneously but required emergent evaluation and management. Conclusion., For suppression of CCM, ONBs may offer an attractive alternative to orally administered prophylactic therapy. [source]

Suppression of liver regeneration and hepatocyte proliferation in hepatocyte-targeted glypican 3 transgenic mice,

HEPATOLOGY, Issue 3 2010
Bowen Liu
Glypican 3 (GPC3) belongs to a family of glycosylphosphatidylinositol-anchored, cell-surface heparan sulfate proteoglycans. GPC3 is overexpressed in hepatocellular carcinoma. Loss-of-function mutations of GPC3 result in Simpson-Golabi-Behmel syndrome, an X-linked disorder characterized by overgrowth of multiple organs, including the liver. Our previous study showed that GPC3 plays a negative regulatory role in hepatocyte proliferation, and this effect may involve CD81, a cell membrane tetraspanin. To further investigate GPC3 in vivo, we engineered transgenic (TG) mice overexpressing GPC3 in the liver under the control of the albumin promoter. GPC3 TG mice with hepatocyte-targeted, overexpressed GPC3 developed normally in comparison with their nontransgenic littermates but had a suppressed rate of hepatocyte proliferation and liver regeneration after partial hepatectomy. Moreover, gene array analysis revealed a series of changes in the gene expression profiles in TG mice (both in normal mice and during liver regeneration). In unoperated GPC3 TG mice, there was overexpression of runt related transcription factor 3 (7.6-fold), CCAAT/enhancer binding protein alpha (2.5-fold), GABA A receptor (2.9-fold), and wingless-related MMTV integration site 7B (2.8-fold). There was down-regulation of insulin-like growth factor binding protein 1 (8.4-fold), Rab2 (5.6-fold), beta-catenin (1.7-fold), transforming growth factor beta type I (3.1-fold), nodal (1.8-fold), and yes-associated protein (1.4-fold). Changes after hepatectomy included decreased expression in several cell cycle,related genes. Conclusion: Our results indicate that in GPC3 TG mice, hepatocyte overexpression of GPC3 suppresses hepatocyte proliferation and liver regeneration and alters gene expression profiles, and potential cell cycle,related proteins and multiple other pathways are involved and affected. (HEPATOLOGY 2010;52:1060,1067) [source]

Endpoints of therapy in chronic hepatitis B,

HEPATOLOGY, Issue S5 2009
Jordan J. Feld
Because clearance of hepatitis B virus (HBV) infection is rarely, if ever, achievable, the goals of therapy necessarily focus on prevention of bad clinical outcomes. Ideally, therapies would be shown to prevent tangible clinical endpoints like development of cirrhosis, end-stage liver disease and hepatocellular carcinoma. However, these endpoints typically take years or decades to occur and are therefore impractical targets for clinical trials which last only 1-2 years. As a result, surrogate biomarkers that are believed to correlate with long-term outcome are used to evaluate therapy. Of the clinical, biochemical, serological, virological, and histological endpoints that have been evaluated, none has been shown to be ideal on its own. Symptoms are uncommon and aminotransferase levels fluctuate spontaneously. Loss of hepatitis B e antigen (HBeAg) has been the traditional therapeutic endpoint; however, the indefinite durability off treatment and the emergence of HBeAg-negative disease have made it inadequate as the sole goal of therapy. Loss of hepatitis B surface antigen is associated with improved clinical outcomes, but it is rarely achieved with current therapies. Suppression of viral replication, as measured by serum HBV DNA levels, has become the major goal of therapy, particularly if maintained off therapy. Although useful, the significance of viral levels depends on the stage of disease, degree of liver damage, and the type of therapy. Finally, liver biopsy, often considered the gold standard, is invasive, prone to sampling error, and may take years to change significantly. At present, there is no ideal biomarker for evaluation of therapies for hepatitis B. Future research should be directed at development and validation of surrogate markers that accurately predict or reflect clinically relevant outcomes of chronic hepatitis B. (HEPATOLOGY 2009;49:S96,S102.) [source]

Suppression of HCV-specific T cells without differential hierarchy demonstrated ex vivo in persistent HCV infection

HEPATOLOGY, Issue 6 2003
Kazushi Sugimoto
Hepatitis C virus (HCV) has a high propensity for persistence. To better define the immunologic determinants of HCV clearance and persistence, we examined the circulating HCV-specific T-cell frequency, repertoire, and cytokine phenotype ex vivo in 24 HCV seropositive subjects (12 chronic, 12 recovered), using 361 overlapping peptides in 36 antigenic pools that span the entire HCV core, NS3-NS5. Consistent with T-cell-mediated control of HCV, the overall HCV-specific type-1 T-cell response was significantly greater in average frequency (0.24% vs. 0.04% circulating lymphocytes, P = .001) and scope (14/36 vs. 4/36 pools, P = .002) among the recovered than the chronic subjects, and the T-cell response correlated inversely with HCV titer among the chronic subjects (R = ,0.51, P = .049). Although highly antigenic regions were identified throughout the HCV genome, there was no apparent difference in the overall HCV-specific T-cell repertoire or type-1/type-2 cytokine profile relative to outcome. Notably, HCV persistence was associated with a reversible CD4-mediated suppression of HCV-specific CD8 T cells and with higher frequency of CD4+CD25+ regulatory T cells (7.3% chronic vs. 2.5% recovered, P = .002) that could directly suppress HCV-specific type-1 CD8 T cells ex vivo. In conclusion, we found that HCV persistence is associated with a global quantitative and functional suppression of HCV-specific T cells but not differential antigenic hierarchy or cytokine phenotype relative to HCV clearance. The high frequency of CD4+CD25+ regulatory T cells and their suppression of HCV-specific CD8 T cells ex vivo suggests a novel role for regulatory T cells in HCV persistence. [source]

Preemptive lamivudine therapy based on HBV DNA level in HBsAg-positive kidney allograft recipients

HEPATOLOGY, Issue 5 2002
Tak Mao Chan
Hepatitis B surface antigen (HBsAg)-positive kidney transplant recipients have increased liver-related mortality. The impact of lamivudine treatment on patient survival, the optimal time to start treatment, and the feasibility of discontinuing treatment have not been determined. This study examined these issues with a novel management protocol. Serum hepatitis B virus (HBV) DNA levels were measured serially in HBsAg-positive kidney transplant recipients, and lamivudine was administered preemptively to patients with increasing HBV DNA levels with or without elevation of aminotransferase levels. Outcomes of patients who underwent transplantation before or after institution of this preemptive management strategy (in January 1996) were compared. Eleven de novo patients (91.7%) who underwent transplantation between 1996 and 2000 and 15 existing patients (39.5%) who underwent transplantation between 1983 and 1995 received preemptive lamivudine therapy for 32.6 ± 13.3 months. The treatment criteria were met by de novo patients at 8.4 ± 6.2 months (range, 1-18 months) after transplantation. Suppression of HBV DNA and normalization of aminotransferase levels were achieved in all treated patients, and 21.4% had hepatitis B e antigen (HBeAg) seroconversion. The survival of preemptively managed de novo transplant patients was similar to that of HBsAg-negative controls, whereas HBsAg-positive patients who underwent transplantation before January 1996 had inferior survival (relative risk of death, 9.7 [P < .001]; relative risk of liver-related mortality, 68.0 [P < .0001]). Eleven patients (40.7%) developed lamivudine resistance. Discontinuation of lamivudine was attempted in 12 low-risk patients after stabilization and was successful in 5 (41.7%). In conclusion, preemptive lamivudine therapy based on serial HBV DNA levels and clinical monitoring improved the survival of HBsAg-positive renal allograft recipients. Treatment can be discontinued safely in selected patients after stabilization to minimize the selection of drug-resistant HBV mutants. [source]

Real-Time Observation and Control of Pentacene Film Growth on an Artificially Structured Substrate

ADVANCED MATERIALS, Issue 48 2009
Yuki Tsuruma
Suppression of nucleation around a gold electrode during pentacene growth on a SiO2 channel is found by photoemission electron microscopy. Mass flow is driven by the difference between the molecular orientations on SiO2 and gold. The poor connectivity at the channel/electrode boundary causes degradation in the performance of a field-effect transistor, which is found to be improved by self-assembled monolayer treatment on the electrode (see figure; thickness in monolayers (ML)). [source]