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Significant Suppression (significant + suppression)
Selected AbstractsPossible mechanism of dexamethasone therapy for prostate cancer: Suppression of circulating level of interleukin-6THE PROSTATE, Issue 2 2003Koichiro Akakura Abstract BACKGROUND Glucocorticoids may have favorable effects on prostate cancer patients showing clinical and/or biochemical failure after androgen ablation. The efficacy and mechanisms of dexamethasone therapy as possible alternative endocrine therapy were investigated. METHODS Twenty five patients with prostate cancer treated by androgen ablation and showing a steady increase in serum prostate specific antigen (PSA) were treated with low-dose dexamethasone. RESULTS Of 25 patients, 11 demonstrated 50% or more decline of serum PSA and 9 showed improvement of pain on dexamethasone therapy. Of 8 patients who responded to dexamethasone thearpy, 5 had 80% or more decrease in serum interleukin-6 (IL-6). In contrast, none of 8 non-responders showed remarkable IL-6 suppression. Response of PSA was not correlated to the changes in serum dehydroepiandrosterone, dehydroepiandrosterone sulfate, or androstendione. CONCLUSIONS Significant suppression of serum IL-6, probably through inhibition of androgen-independent activation of androgen receptor, may be one of the mechanisms for the effect of dexamethasone therapy in prostate cancer patients with progressive disease. Prostate 56: 106,109, 2003. © 2003 Wiley-Liss, Inc. [source] In vivo comparison of the relative systemic bioavailability of fluticasone propionate from three anti-static spacers and a metered dose inhalerBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 2 2009Arun Nair WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT , Conventional spacers help overcome problems with co-ordination and may improve lung deposition and decrease oropharyngeal impaction. , Antistatic spacers eliminate electrostatic charge and may hence improve respirable dose delivery. , The systemic bioavailability of inhaled fluticasone propionate is primarily dependent on delivery by the pulmonary route and hence the performance of antistatic spacers can be evaluated using adrenal suppression as a sensitive surrogate for relative bioavailability to the lung after an inhalation. WHAT THIS STUDY ADDS , This study compares the relative bioavailability to the lung of inhaled fluticasone delivered via conventional pressurized metered dose inhalers (pMDI) and three antistatic spacers (plastic Zerostat-V, plastic Aerochamber Max, and metal Nebuchamber) in patients with asthma. , All three antistatic spacers when compared with pMDI significantly increased the relative bioavailability to the lungs of inhaled fluticasone in terms of relative adrenal suppression, and there were no significant differences between the plastic and metal antistatic spacers. AIMS The systemic bioavailability of inhaled fluticasone propionate (FP) depends primarily on lung absorption and can be quantified by measuring suppression of overnight and early morning urinary cortisol/creatinine (OUCC and EMUCC, respectively). The aim of the study was to determine the relative bioavailability of hydrofluoroalkane (HFA) FP to the lungs via anti-static plastic (Zerostat-V and Aerochamber Max), metal (Nebuchamber) anti-static spacers and metered dose inhaler [Flixotide Evohaler (EH) (pMDI)]. METHODS A randomized, double-blind, double-dummy, four-way crossover design was used. Eighteen mild to moderate asthmatics received single doses of placebo/HFA-FP 2 mg via the 280-ml Zerostat-V (ZS); 250-ml Nebuchamber (NC); 197-ml Aerochamber Max (AC); and pMDI (EH). Measurements of OUCC and EMUCC were made at baseline and 10 h after each dose. RESULTS Significant suppression of OUCC and EMUCC occurred from baseline with all three spacers, but not Evohaler (geometric mean fold suppression, 95% confidence interval): ZS, 2.74 (1.75, 4.30), P < 0.001; NC, 3.31 (1.81, 6.06), P < 0.001; AC, 4.98 (3.39, 7.31), P < 0.001; and for EH this was 1.42 (0.92, 2.21), P= 0.169 (equating to a 64, 70, 80 and 30% fall in OUCC via the ZS, NC, AC and EH devices, respectively). There were significant differences between all three spacers vs. EH. When compared with the Evohaler, the Zerostat V resulted in 48% greater suppression (P= 0.009); the Nebuchamber 57% greater suppression (P= 0.001); and the Aerochamber Max 71% greater suppression of OUCC (P < 0.001). CONCLUSION All three antistatic spacers significantly increased the relative systemic bioavailability of HFA-FP compared with the standard pMDI. [source] Impaired fear conditioning but enhanced seizure sensitivity in rats given repeated experience of withdrawal from alcoholEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2001D. N. Stephens Abstract Repeated experience of withdrawal from chronic alcohol treatment increases sensitivity to seizures. It has been argued by analogy that negative affective consequences of withdrawal also sensitize, but repeated experience of withdrawal from another sedative-hypnotic drug, diazepam, results in amelioration of withdrawal anxiety and aversiveness. We tested whether giving rats repeated experience of withdrawal from alcohol altered their ability to acquire a conditioned emotional response (CER). Male Hooded Lister rats were fed a nutritionally complete liquid diet as their only food source. Different groups received control diet, or diet containing 7% ethanol. Rats receiving ethanol diet were fed for either 24 days (Single withdrawal, SWD), or 30 days, with two periods of 3 days, starting at day 11, and 21, in which they received control diet (Repeated withdrawal, RWD). All rats were fed lab chow at the end of their liquid diet feeding period. Starting 12 days after the final withdrawal, groups of Control, SWD and RWD rats were given pentylenetetrazole (PTZ; 30 mg/kg, i.p.) three times a week, and scored for seizures. The occurrence of two successive Stage 5 seizures was taken as the criterion for full PTZ kindling. Other groups of control, SWD and RWD rats were trained to operate levers to obtain food, and were then exposed, in a fully counterbalanced design, to light and tone stimuli which predicted unavoidable footshock (CS+), or which had no consequences (CS,). Rats consumed approximately 17.5 g/kg/day of ethanol, resulting in blood alcohol levels of approximately 100 mg/dL. Repeated administration of PTZ resulted in increasing seizure scores. RWD rats achieved kindling criterion faster than either Control or SWD rats. No differences were seen in the groups in flinch threshold to footshock (0.3 mA). At a shock intensity of 0.35 mA, Control, but not RWD or SWD rats showed significant suppression to the CS+ CS, presentation did not affect response rates. The three groups differed in their response to pairing the CS+ with increasing shock levels, the Controls remaining more sensitive to the CS+. SWD rats showed significant suppression of lever pressing during CS+ presentations only at 0.45 and 0.5 mA, and RWD rats only at 0.5 mA. Giving rats repeated experience of withdrawal from chronic ethanol results in increased sensitivity to PTZ kindling, but reduces their ability to acquire a CER. Withdrawal kindling of sensitivity to anxiogenic events does not seem to occur under circumstances which give rise to kindling of seizure sensitivity. [source] Antibacterial activity of dental composites containing zinc oxide nanoparticles,JOURNAL OF BIOMEDICAL MATERIALS RESEARCH, Issue 1 2010Berdan Aydin Sevinē Abstract The resin-based dental composites commonly used in restorations result in more plaque accumulation than other materials. Bacterial biofilm growth contributes to secondary caries and failure of resin-based dental composites. Methods to inhibit biofilm growth on dental composites have been sought for several decades. It is demonstrated here that zinc oxide nanoparticles (ZnO-NPs) blended at 10% (w/w) fraction into dental composites display antimicrobial activity and reduce growth of bacterial biofilms by roughly 80% for a single-species model dental biofilm. Antibacterial effectiveness of ZnO-NPs was assessed against Streptococcus sobrinus ATCC 27352 grown both planktonically and as biofilms on composites. Direct contact inhibition was observed by scanning electron microscopy and confocal laser scanning microscopy while biofilm formation was quantified by viable counts. An 80% reduction in bacterial counts was observed with 10% ZnO-NP-containing composites compared with their unmodified counterpart, indicating a statistically significant suppression of biofilm growth. Although, 20% of the bacterial population survived and could form a biofilm layer again, 10% ZnO-NP-containing composites maintained at least some inhibitory activity even after the third generation of biofilm growth. Microscopy demonstrated continuous biofilm formation for unmodified composites after 1-day growth, but only sparsely distributed biofilms formed on 10% ZnO-NP-containing composites. The minimum inhibitory concentration of ZnO-NPs suspended in S. sobrinus planktonic culture was 50 ,g mL,1. ZnO-NP-containing composites (10%) qualitatively showed less biofilm after 1-day-anaerobic growth of a three-species initial colonizer biofilm after being compared with unmodified composites, but did not significantly reduce growth after 3 days. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2010. [source] Expression of Acid-Sensing Ion Channel 3 (ASIC3) in Nucleus Pulposus Cells of the Intervertebral Disc Is Regulated by p75NTR and ERK Signaling,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 12 2007Yoshiyasu Uchiyama Abstract Although a recent study has shown that skeletal tissues express ASICs, their function is unknown. We show that intervertebral disc cells express ASIC3; moreover, expression is uniquely regulated and needed for survival in a low pH and hypoeromsotic medium. These findings suggest that ASIC3 may adapt disc cells to their hydrodynamically stressed microenvironment. Introduction: The nucleus pulposus is an avascular, hydrated tissue that permits the intervertebral disc to resist compressive loads to the spine. Because the tissue is hyperosmotic and avascular, the pH of the nucleus pulposus is low. To determine the mechanisms by which the disc cells accommodate to the low pH and hypertonicity, the expression and regulation of the acid sensing ion channel (ASIC)3 was examined. Materials and Methods: Expression of ASICs in cells of the intervertebral disc was analyzed. To study its regulation, we cloned the 2.8-kb rat ASIC3 promoter and performed luciferase reporter assays. The effect of pharmacological inhibition of ASICs on disc cell survival was studied by measuring MTT and caspase-3 activities. Results: ASIC3 was expressed in discal tissues and cultured disc cells in vitro. Because studies of neuronal cells have shown that ASIC3 expression and promoter activity is induced by nerve growth factor (NGF), we examined the effect of NGF on nucleus pulposus cells. Surprisingly, ASIC3 promoter activity did not increase after NGF treatment. The absence of induction was linked to nonexpression of tropomyosin-related kinase A (TrkA), a high-affinity NGF receptor, although a modest expression of p75NTR was seen. When treated with p75NTR antibody or transfected with dominant negative-p75NTR plasmid, there was significant suppression of ASIC3 basal promoter activity. To further explore the downstream mechanism of control of ASIC3 basal promoter activity, we blocked p75NTR and measured phospho extracellular matrix regulated kinase (pERK) levels. We found that DN-p75NTR suppressed NGF mediated transient ERK activation. Moreover, inhibition of ERK activity by dominant negative-mitogen activated protein kinase kinase (DN-MEK) resulted in a dose-dependent suppression of ASIC3 basal promoter activity, whereas overexpression of constitutively active MEK1 caused an increase in ASIC3 promoter activity. Finally, to gain insight in the functional importance of ASIC3, we suppressed ASIC activity in nucleus pulposus cells. Noteworthy, under both hyperosmotic and acidic conditions, ASIC3 served to promote cell survival and lower the activity of the pro-apoptosis protein, caspase-3. Conclusions: Results of this study indicate that NGF serves to maintain the basal expression of ASIC3 through p75NTR and ERK signaling in discal cells. We suggest that ASIC3 is needed for adaptation of the nucleus pulposus and annulus fibrosus cells to the acidic and hyperosmotic microenvironment of the intervertebral disc. [source] Protective effect of rebamipide on indomethacin-induced intestinal damage in ratsJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 10 2001Hiroyuki Mizoguchi Abstract Background and Aim: We evaluated the effect of rebamipide (2-(4-chlorobenzoylamino)-3-[2(1H)-quinolinon-4-yl] propionic acid), a novel anti-ulcer drug, on indomethacin-induced small intestinal lesions in rats. Methods: The animals were administered indomethacin (10 mg/kg, s.c.), and they were killed 24 h later. Rebamipide (30,300 mg/kg) was administered p.o. twice, 30 min before, and 6 h after indomethacin. Results: Indomethacin caused hemorrhagic lesions in the rat small intestine, accompanied by an increase in enterobacterial translocation, inducible nitric oxide synthase (iNOS) and myeloperoxidase (MPO) activities, as well as thiobarbituric acid (TBA) reactants, and these changes were significantly prevented by the supplementation with 16,16-dimethyl prostaglandin E2 (dmPGE2; 10 ,g/kg, i.v.) or the pretreatment of animals with the antibiotic ampicillin. Treatment of the animals with rebamipide dose-dependently prevented the development of intestinal lesions, and this effect was mimicked by i.v. administration of superoxide dismutase (SOD: 3000 U/kg) + catalase (CAT: 5000 U/kg). The protection by rebamipide was accompanied by a significant suppression of the increase in both MPO and iNOS activities, and a complete inhibition of the increase in TBA reactants, while SOD + CAT significantly inhibited the increase of MPO activity and TBA reactants, but not iNOS activity. The bacterial translocation following indomethacin was also significantly decreased by either rebamipide or SOD + CAT. Conclusion: These results confirmed the importance of enterobacteria and iNOS/NO in the pathogenesis of indomethacin-induced small intestinal lesions, and suggested that rebamipide prevents the development of these lesions, probably by its radical scavenging action. [source] Kinetics of HBV DNA and HBsAg in acute hepatitis B patients with and without coinfection by other hepatitis virusesJOURNAL OF MEDICAL VIROLOGY, Issue 3 2003Vladimir P. Chulanov Abstract The kinetics of hepatitis B virus (HBV) and its surface antigen (HBsAg) during acute hepatitis has not yet been studied accurately in a representative number of patients. The influence of coinfecting hepatitis viruses during the acute phase of infection is not known. Three to four serum samples from 21 patients with acute HBV monoinfection and 27 with coinfection were taken at intervals of 6,10 days and analyzed for the number of HBV genome equivalents (ge) by real time polymerase chain reaction (PCR) and for HBsAg quantity using Laurell electrophoresis. Log HBV ge/ml decreased during the follow-up from 6.8,±,1.1 to 5.1,±,1.0 to 4.2,±,0.8 to 3.3,±,1.1 (mean,±,SD). The half-life times of HBV ge increased from 1.6 days at the beginning to 4 days at the end. HBsAg decreased much slower: from 38 to 23 to 12 to3.8 ,g/ml. Half-life time was around 8 days at the beginning and 5.7 days at the end, but 11 patients showed a rapid elimination of HBsAg and HBV DNA. Hepatitis C virus (HCV) coinfection did not change the kinetics of HBV ge and HBsAg significantly. A moderate but significant suppression of HBV ge levels was observed in hepatitis D virus (HDV) coinfected patients. HBsAg levels were, however, enhanced in this cohort. In conclusion, the data suggest that expression and elimination of HBV is in most patients with acute hepatitis B not altered by coinfecting hepatitis viruses. The initial decrease of HBV ge and HBsAg in serum appears to be caused by decay or non-specific removal in the absence of replacement. J. Med. Virol. 69:313,323, 2003. © 2003 Wiley-Liss, Inc. [source] Cosmic reionization constraints on the nature of cosmological perturbationsMONTHLY NOTICES OF THE ROYAL ASTRONOMICAL SOCIETY, Issue 4 2006Pedro P. Avelino ABSTRACT We study the reionization history of the Universe in cosmological models with non-Gaussian density fluctuations, taking them to have a renormalized ,2 probability distribution function parametrized by the number of degrees of freedom, ,. We compute the ionization history using a simple semi-analytical model, considering various possibilities for the astrophysics of reionization. In all our models we require that reionization is completed prior to z= 6, as required by the measurement of the Gunn,Peterson optical depth from the spectra of high-redshift quasars. We confirm previous results demonstrating that such a non-Gaussian distribution leads to a slower reionization as compared to the Gaussian case. We further show that the recent WMAP three-year measurement of the optical depth due to electron scattering, ,= 0.09 ± 0.03, weakly constrains the allowed deviations from Gaussianity on the small scales relevant to reionization if a constant spectral index is assumed. We also confirm the need for a significant suppression of star formation in minihaloes, which increases dramatically as we decrease ,. [source] Lipid solubility- and concentration-dependent attenuation of in vitro natural killer cell cytotoxicity by local anestheticsACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 7 2002J. Krog Background: Natural killer (NK) cells constitute an essential component of the innate immune system in the defence against infected and malignant cells. In this study the in vitro effect on NK cell activity of three different local anesthetics with different lipid solubility was investigated. Methods: Venous blood from seven healthy volunteers was incubated with three amide local anesthetics with three different concentrations of lipid solubility: lidocaine 0.50, 1.00 and 2.00 mg/ml, ropivacaine 0.375, 0.75 and 1.50 mg/ml, and bupivacaine 0.25, 0.50 and 1.00 mg/ml. After 1 h of incubation, mononuclear cells were isolated and cryopreserved until tested for NK cell cytotoxicity in a 4-h 51Cr-release assay against K-562 target cells. Natural killer cell cytotoxicity of mononuclear cells incubated with isotonic saline was used as the control. Results: A significant suppression in NK cell cytotoxicity was demonstrated for all three local anesthetic agents when the NK cell cytotoxicity was compared with the cytotoxicity estimated after incubation with the isotonic saline (P<0.004). Moreover a significant lipid solubility-dependent effect (P=0.0001) as well as an overall concentration-dependent effect (P<0.0001) on the NK cell cytotoxicity was found. Conclusion: The results of the present in vitro study suggest a negative association between the estimated NK cell cytotoxicity and the lipid solubility as well as the concentrations of the three local anesthetic agents tested. [source] Properties of nisin-incorporated polymer coatings as antimicrobial packaging materialsPACKAGING TECHNOLOGY AND SCIENCE, Issue 5 2002Young-Min Kim Abstract Nisin was incorporated into binder solutions of acrylic polymer and vinyl acetate-ethylene co-polymer, and then coated on to paper. Diffusive migration of incorporated nisin and the antimicrobial activity of the polymer coatings were investigated in order to understand the way of controlling nisin migration and the extent of microbial suppression by the coated paper. Vinyl acetate,ethylene co-polymer exhibited a faster rate and higher degree of migration into aqueous food simulant solutions compared to acrylic polymer, and also exhibited a higher degree of suppression against Micrococcus flavus ATCC 10240 inoculated into the microbial medium. Addition of NaCl, sugar and citric acid to water significantly reduced the rate of diffusion of nisin in the case of acrylic polymer, while only slight change was observed due to the additive for vinyl acetate-ethylene co-polymer. The simulant type slightly affected the equilibrated migration level of nisin. When the nisin-incorporated coatings were in contact with pasteurized milk and orange juice at 10°C, significant suppression of total aerobic bacteria and yeasts was observed without any noticeable difference between the two types of coatings. Copyright © 2002 John Wiley & Sons, Ltd. [source] Strong spin relaxation length dependence on electric field gradientsPHYSICA STATUS SOLIDI (C) - CURRENT TOPICS IN SOLID STATE PHYSICS, Issue 12 2006D. Csontos Abstract We discuss the influence of electrical effects on spin transport, and in particular the propagation and relaxation of spin polarized electrons in the presence of inhomogeneous electric fields. We show that the spin relaxation length strongly depends on electric field gradients, and that significant suppression of electron spin polarization can occur as a result thereof. A discussion in terms of a drift-diffusion picture, and selfconsistent numerical calculations based on a Boltzmann-Poisson approach shows that the spin relaxation length in fact can be of the order of the charge screening length. (© 2006 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] Influence of drought, salt stress and abscisic acid on the resistance of tomato to Botrytis cinerea and Oidium neolycopersiciPLANT PATHOLOGY, Issue 2 2006E. A. Achuo Abiotic stress may affect plant response to pathogen attack through induced alterations in growth regulator and gene expression. Abscisic acid (ABA) mediates several plant responses to abiotic stress. The effects of drought, salt stress and ABA on the interaction of tomato (Lycopersicon esculentum) with the biotrophic fungus Oidium neolycopersici and the necrotrophic fungus Botrytis cinerea were investigated. Drought stress resulted in a twofold increase in endogenous ABA as well as a 50% reduction in B. cinerea infection and a significant suppression of O. neolycopersici on tomato cv. Moneymaker. Salt stress did not affect B. cinerea infection, but significantly reduced infection by O. neolycopersici, with no obvious increase in endogenous ABA. Compared with the wild type, the ABA-deficient sitiens mutant was more resistant to O. neolycopersici and B. cinerea. Exogenous ABA resulted in increased susceptibility of sitiens to both pathogens, but did not increase the basal susceptibility of wild-type plants. It is concluded that, in tomato, drought and salt stress stimulate different, but possibly overlapping, pathogen-defence pathways which may not necessarily involve ABA. Meanwhile, basal endogenous ABA levels suppress the resistance of tomato to O. neolycopersici and B. cinerea, but an ABA increase above the basal level, resulting from exogenous application, does not increase susceptibility to these pathogens. [source] Interleukin-21 triggers both cellular and humoral immune responses leading to therapeutic antitumor effects against head and neck squamous cell carcinomaTHE JOURNAL OF GENE MEDICINE, Issue 1 2006Hiroshi Nakano Abstract Background Interleukin-21 (IL-21) plays important roles in the regulation of T, B, and natural killer (NK) cells. We hypothesized that the cytokine may provide a novel immunotherapy strategy for cancer by stimulating both Th1 and Th2 immune responses. In this context, antitumor immunity induced by IL-21 was examined in mice bearing subcutaneous head and neck squamous cell carcinomas (HNSCC). Methods A plasmid vector encoding murine IL-21 was injected intravenously into mice with pre-established HNSCC tumors, either alone or in combination with a vector construct expressing IL-15. Cytotoxic T lymphocyte (CTL) and NK killing activities were evaluated by chrome release assays, while HNSCC-specific antibody was examined by flow cytometry and ELISA. Results Significant antitumor effects were obtained by repeated transfection with either the IL-21 or the IL-15 gene. Co-administration of both cytokine genes resulted in increased suppression of tumor growth, significantly prolonging the survival periods of the animals. Thirty percent of the tumor-bearing mice that received the combination therapy survived for more than 300 days, completely rejecting rechallenge with the tumor at a distant site. IL-21 induced significant elevation of HNSCC-specific CTL activity, while IL-21 and IL-15 augmented NK activity in an additive manner. IL-21 gene transfer also promoted the production of tumor-specific IgG. Conclusions In vivo transduction of the IL-21 gene elicits powerful antitumor immunity, including both humoral and cellular arms of the immune response, and results in significant suppression of pre-established HNSCC. Co-transfer of the IL-15 gene further improved the therapeutic outcome, mainly by augmenting NK tumoricidal activity. The biological effects of IL-21 may be in sharp contrast to those of conventional Th1 and Th2 cytokines, suggesting intriguing implications of this cytokine for the classical concept of Th1 vs. Th2 paradigm. Copyright © 2005 John Wiley & Sons, Ltd. [source] Hypoxia-inducible factor regulation of ANK expression in nucleus pulposus cells: Possible implications in controlling dystrophic mineralization in the intervertebral discARTHRITIS & RHEUMATISM, Issue 9 2010Renata Skubutyte Objective Since nucleus pulposus cells reside under conditions of hypoxia, we determined if the expression of ANK, a pyrophosphate transporter, is regulated by the hypoxia-inducible factor (HIF) proteins. Methods Quantitative reverse transcription,polymerase chain reaction and Western blot analyses were used to measure ANK expression in nucleus pulposus cells from rats and humans. Transfections were performed to determine the effect of HIF-1/2 on ANK promoter activity. Results ANK was expressed in embryonic and mature rat discs. Oxygen-dependent changes in ANK expression in nucleus pulposus cells were minimal. However, silencing of HIF-1, and HIF-2, resulted in increased ANK expression and up-regulation of promoter activity. HIF-mediated suppression of ANK was validated by measuring promoter activity in HIF-1,,null embryonic fibroblasts. Under conditions of hypoxia, there was induction of promoter activity in the null cells as compared with the wild-type cells. Overexpression of HIF-1, and HIF-2, in nucleus pulposus cells resulted in a significant suppression of ANK promoter activity. Since the ANK promoter contains 2 hypoxia-responsive elements (HREs), we performed site-directed mutagenesis and measured promoter activity. We found that HIF-1 can bind to either of the HREs and can suppress promoter activity; in contrast, HIF-2 was required to bind to both HREs in order to suppress activity. Finally, analysis of human nucleus pulposus tissue showed that while ANK was expressed in normal tissue, there was increased expression of ANK along with alkaline phosphatase in the degenerated state. Conclusion Both HIF-1 and HIF-2 serve as negative regulators of ANK expression in the disc. We propose that baseline expression of ANK in the disc serves to prevent mineral formation under physiologic conditions. [source] Photodynamic therapy-generated tumor cell lysates with CpG-oligodeoxynucleotide enhance immunotherapy efficacy in human papillomavirus 16 (E6/E7) immortalized tumor cellsCANCER SCIENCE, Issue 5 2007Su-Mi Bae Immunotherapy with photodynamic therapy (PDT) offers great promise as a new alternative for cancer treatment; however, its use remains experimental. In this study, we examined the immunotherapeutic significance of human papillomavirus (HPV)-immortalized tumor cell lysates induced by PDT with CpG-oligodeoxynucleotide (ODN). PDT-cell lysates were generated by irradiating Radachlorin (5 µg/mL) preloaded TC-1 cells carrying HPV 16 E7. PDT-cell lysates plus ODN coinjection for protection against E7-expressing tumors as well as specific immune responses were evaluated with the following tests: heat shock protein 70 (HSP70) enzyme-linked immunosorbent assay, in vitro and in vivo tumor growth inhibition, interferon-, (IFN-,) and tumor necrosis factor-, (TNF-,) assay, cytotoxic T-lymphocyte assay, and fluorescence activated cell sorting (FACS) analysis. PDT-cell lysates plus ODN coinjection showed a significant suppression of tumor growth at both prophylactic and therapeutic levels, compared to PDT (or F/T)-cell lysates or ODN alone. In addition, we evaluated the level of the immune response with the coinjection. HSP70, an important regulator of inflammatory and immune response, was observed in abundance in the PDT-cell lysates. IFN-, production and cytotoxic T lymphocytes (CTL) responses were induced by PDT-cell lysates plus ODN injection. The coinjection resulted in PDT-cell lysate-specific antibodies (IgG1, IgG2a, IgG2b, and IgG3) and T-helper cell responses significantly higher than PDT-cell lysates alone. Moreover, IFN-, production and CTL responses were significantly induced in the PDT-cell lysate plus ODN immunized groups. These enhanced immune responses appeared to be mediated by CD8+ T cells only. These data suggest that PDT-cell lysates plus ODN injection may be an effective approach to induce CTL immune responses as a possible immunotherapeutic strategy for cancer therapy. (Cancer Sci 2007; 98: 747,752) [source] Inhibition of human allergic T-helper type 2 immune responses by induced regulatory T cells requires the combination of interleukin-10-treated dendritic cells and transforming growth factor-, for their inductionCLINICAL & EXPERIMENTAL ALLERGY, Issue 12 2006I Bellinghausen Summary Background In grass pollen-allergic individuals, T cell anergy can be induced by IL-10-treated dendritic cells (IL-10-DC) resulting in the suppression of T helper type 1 (Th1) as well as Th2 cells. This study was performed to analyse whether such IL-10-DC-treated T cells are able to act as regulatory T cells (Treg) suppressing the function of other T cells in the periphery. As transforming growth factor (TGF)-, is also a potential inducer of Treg, we additionally analysed the inhibitory capacity of TGF-,-treated T cells in this system. Materials and Methods Freshly isolated CD4+ or CD4+CD25, T cells from grass pollen-allergic donors were stimulated with autologous mature monocyte-derived allergen-pulsed DC in the presence or absence of T cells previously cultured with IL-10-DC- and/or TGF-,. Results Anergic T cells induced by allergen-pulsed IL-10-treated DC or allergen-pulsed DC and TGF-, enhanced IL-10 production and strongly inhibited IFN-, production of freshly prepared peripheral CD4+ or CD4+CD25, T cells while proliferation and Th2 cytokine production were only slightly reduced. The combination of allergen-pulsed IL-10-treated DC and TGF-, had an additional effect leading to a significant suppression also of Th2 cytokine production and proliferation. Suppression was not antigen-specific and was mainly mediated by cell-to-cell contact and by the molecule-programmed death-1 and only partially by CTLA-4, TGF-, and IL-10. Conclusion These data demonstrate that regulatory T cells that also suppress Th2 cytokine production are induced by two signals: TGF-, and IL-10-DC. This is of importance for the regulation of allergic immune responses and might be exploited for future therapeutic strategies for allergic diseases. [source] A randomized double-blind study to compare the effects of nasal fluticasone and betamethasone on the hypothalamo,pituitary,adrenal axis and bone turnover in patients with nasal polyposisCLINICAL OTOLARYNGOLOGY, Issue 6 2002P.D. Fowler Treatment of nasal polyposis with topical betamethasone is associated with suppression of the hypothalamo,pituitary,adrenal (HPA) axis and, potentially, has adverse effects on bone turnover. Fluticasone propionate is a potent corticosteroid with negligible absorption across the nasal mucosa and extensive first-pass hepatic metabolism. We performed a randomized double-blind study, in patients with nasal polyposis, comparing the effects of 8 weeks' treatment with betamethasone drops or fluticasone nasules on the HPA axis using the 1 µg tetracosactide test, and on bone turnover using two serum markers. Nine patients were allocated to each treatment. Betamethasone resulted in significant suppression in the tetracosactide test (P = 0.006), but fluticasone did not (P = 0.113). There were no differences in bone turnover or treatment efficacy between treatments. Treatment of nasal polyposis with topical betamethasone drops, but not with fluticasone nasules, suppresses the HPA axis and, given comparable efficacy, fluticasone administered via nasule should be the preferred agent. [source] | ||||||||||||||||