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Kinds of DC Terms modified by DC Selected AbstractsDendritic cells: biology of the skinCONTACT DERMATITIS, Issue 1 2009Mascha J. Toebak Allergic contact dermatitis results from a T-cell-mediated, delayed-type hypersensitivity immune response induced by allergens. Skin dendritic cells (DCs) play a central role in the initiation of allergic skin responses. Following encounter with an allergen, DCs become activated and undergo maturation and differentiate into immunostimulatory DCs and are able to present antigens effectively to T cells. The frequency of allergic skin disorders has increased in the past decades. Therefore, the identification of potential sensitizing chemicals is important for skin safety. Traditionally, predictive testing for allergenicity has been conducted in animal models. For regulatory reasons, animal use for sensitization testing of compounds for cosmetic purposes is shortly to be prohibited in Europe. Therefore, new non-animal-based test methods need to be developed. Several DC-based assays have been described to discriminate allergens from irritants. Unfortunately, current in vitro methods are not sufficiently resilient to identify allergens and therefore need refinement. Here, we review the immunobiology of skin DCs (Langerhans' cells and dermal dendritic cells) and their role in allergic and irritant contact dermatitis and then explore the possible use of DC-based models for discriminating between allergens and irritants. [source] Studies on multiphased mixed crystals of NaCl, KCl and KICRYSTAL RESEARCH AND TECHNOLOGY, Issue 1 2009M. Priya Abstract Multiphased mixed crystals of NaCl, KCl and KI were grown by the melt method, for the first time. Densities and refractive indices of all the grown crystals were determined and used for the estimation of the composition in the crystal. Atomic absorption spectroscopic measurements were done to estimate the metal atom contents in the crystal. Lattice parameters and thermal parameters (Debye-Waller factor, mean square amplitude of vibration, Debye temperature and Debye frequency) were determined from the X-ray powder diffraction data. DC and AC electrical measurements were done at various temperatures ranging from 40 to 150°C. Activation energies were also estimated. The observed lattice parameters showed that the system exhibits three phases each nearly corresponds to NaCl, KCl and KI. The thermal and electrical parameters show a highly nonlinear bulk composition dependence. Results are reported. (© 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] Characterization of reactive DC magnetron sputtered TiAlN thin filmsCRYSTAL RESEARCH AND TECHNOLOGY, Issue 10 2008B. Subramanian Abstract Thin films of about 1,m Titanium Aluminum Nitride (TiAlN) were deposited onto mild steel substrates by reactive direct current (DC) magnetron sputtering using a target consisting of equal segments of titanium and aluminum. X-ray diffraction (XRD) analysis showed that the TiAlN phase had preferred orientations along 111 and 200 with the face-centered cubic structure. Scanning Electron Microscope (SEM) and Atomic Force Microscope (AFM) analyses indicated that the films were uniform and compact. Photoluminescence (PL) spectra reveal that TiAlN thin films are of good optical quality. Laser Raman studies revealed the presence of characteristic peaks of TiAlN at 312.5, 675, and 1187.5 cm,1. (© 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] Wine, Ethnography, and French HistoryCULTURE, AGRICULTURE, FOOD & ENVIRONMENT, Issue 1-2 2004Associate Professor Kolleen M. Guy Vintages and Traditions: An Ethnohistory of Southwest French Wine Cooperatives. Robert C. Ulin. Washington, DC: Smithsonian Institution Press, 1996. Cultivating Dissent: Work, Identity, and Praxis in Rural Languedoc. Winnie Lem. Albany: State University of New York Press, 1999. [source] Embryonic dermal condensation and adult dermal papilla induce hair follicles in adult glabrous epidermis through different mechanismsDEVELOPMENT GROWTH & DIFFERENTIATION, Issue 2 2006Mutsumi Inamatsu Hair induction in the adult glabrous epidermis by the embryonic dermis was compared with that by the adult dermis. Recombinant skin, composed of the adult sole epidermis and the embryonic dermis containing dermal condensations (DC), was transplanted onto the back of nude mice. The epidermis of transplants formed hairs. Histology on the induction process demonstrated the formation of placode-like tissues, indicating that the transplant produces hair follicles through a mechanism similar to that underlying hair follicle development in the embryonic skin. An isolated adult rat sole skin piece, inserted with either an aggregate of cultured dermal papilla (DP) cells or an intact DP between its epidermis and dermis, was similarly transplanted. The transplant produced hair follicles. Histology showed that the epidermis in both cases surrounded the aggregates of DP cells. The epidermis never formed placode-like tissues. Thus, it was concluded that the adult epidermal cells recapitulate the embryonic process of hair follicle development when exposed to DC, whereas they get directly into the anagen of the hair cycle when exposed to DP. The expression pattern of Edar and Shh genes, and P-cadherin protein during the hair follicle development in the two types of transplants supported the above conclusion. [source] A role for innate immunity in type 1 diabetes?DIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 2 2003H. Beyan Abstract Two arms of the immune system, innate and adaptive immunity, differ in their mode of immune recognition. The innate immune system recognizes a few highly conserved structures on a broad range of microorganisms. On the other hand, recognition of self or autoreactivity is generally confined to the adaptive immune response. Whilst autoimmune features are relatively common, they should be distinguished from autoimmune disease that is infrequent. Type 1 diabetes is an immune-mediated disease due to the destruction of insulin secreting cells mediated by aggressive immune responses, including activation of the adaptive immune system following genetic and environmental interaction. Hypotheses for the cause of the immune dysfunction leading to type 1 diabetes include self-reactive T-cell clones that (1) escape deletion in the thymus, (2) escape from peripheral tolerance or (3) escape from homeostatic control with an alteration in the immune balance leading to autoimmunity. Evidence, outlined in this review, raises the possibility that changes in the innate immune system could lead to autoimmunity, by either priming or promoting aggressive adaptive immune responses. Hostile microorganisms are identified by genetically determined surface receptors on innate effector cells, thereby promoting clearance of these invaders. These innate effectors include a few relatively inflexible cell populations such as monocytes/macrophages, dendritic cells (DC), natural killer (NK) cells, natural killer T (NKT) cells and ,, T cells. Recent studies have identified abnormalities in some of these cells both in patients with type 1 diabetes and in those at risk of the disease. However, it remains unclear whether these abnormalities in innate effector cells predispose to autoimmune disease. If they were to do so, then modulation of the innate immune system could be of therapeutic value in preventing immune-mediated diseases such as type 1 diabetes. Copyright © 2002 John Wiley & Sons, Ltd. [source] REFRACTORY DIVERTICULAR COLITIS WITH PROGRESSIVE ULCERATIVE COLITIS-LIKE CHANGES EXTENDING TO THE RECTUMDIGESTIVE ENDOSCOPY, Issue 3 2009Tateki Yamane A 68-year-old man visited our department because of diarrhea and bloody stools. Colonoscopy revealed diverticula scattered in the sigmoid colon with localized mucosal edema and reddening. The mucosa became somewhat rough 9 months later, and had an erosive, ulcerative colitis (UC)-like appearance after a further 6 months, with these changes extending to the rectum. These findings led to a diagnosis of diverticular colitis (DC) with UC-like changes. The condition was refractory to treatment including drug therapy and was thus surgically treated. No cases of DC have been reported in Japan, and a refractory case of DC with progressive UC-like changes extending to the rectum is rare even in Europe and the USA. [source] Grading Functional Mitral Regurgitation by Tissue Doppler,Derived Isovolumic Acceleration Parameters in Patients with Nonischemic Dilated CardiomyopathyECHOCARDIOGRAPHY, Issue 7 2010Tansu Karaahmet M.D. Functional mitral regurgitation (FMR) is relatively common in heart failure and it is associated with adverse prognosis. The severity of FMR is usually assessed by echocardiography. Tissue Doppler echocardiography is used to acquire signals to determine the myocardial systolic functional parameters, including systolic ejection velocity and the systolic isovolumic acceleration (IVAs) rate. We investigated the utility of isovolumic acceleration parameters to grade the severity of FMR in nonischemic dilated cardiomyopathy (DC) patients. We analyzed the left ventricular systolic IVA rate, systolic isovolumic contraction (IVCs) velocity, and IVA duration (IVAd) values in 73 patients with DC. Patients were subgrouped according to FMR grade (Group I = mitral regurgitation mild and moderate; Group II = mitral regurgitation severe). IVAs was similar between two groups; however IVCs and IVAd were significantly higher in Group II than Group I. The IVCs cutoff value to predict severe FMR was 1.2 cm/sec (sensitivity 75% and specificity 70%). The IVAd cutoff value to predict severe FMR was 33 ms (sensitivity 77% and specificity 77%). Patients with IVCs , 1.2 cm/sec and IVAd , 33 ms had significantly higher FMR volume than the other subgroups. IVCs and IVAd values are useful to determine FMR severity in patients with DC. (Echocardiography 2010;27:815-822) [source] C-Reactive Protein and Aortic Stiffness in Patients with Idiopathic Dilated CardiomyopathyECHOCARDIOGRAPHY, Issue 1 2007Feridun Kosar M.D. Background: Previous studies have shown an association between C-reactive protein (CRP)and arterial stiffness in most cardiovascular diseases. Increased CRP levels and arterial stiffness have been considered independent predictors of cardiovascular mortality in cardiovascular disease and even in the general population. Objective: The aim of this study was to investigate the relationship between CRP, a marker of systemic inflammation and aortic stiffness in patients with idiopathic dilated cardiomyopathy (DCMP). Methods: Serum CRP levels and aortic stiffness parameters were measured in DCMP patients (n= 37) and age- and gender-matched control subjects (n= 30). High-sensitivity CRP levels were determined by an immunonephelometry assay. Aortic strain (AS) and aortic distensibility (AD) were calculated from the aortic diameters measured using M-mode echocardiography and blood pressure obtained by sphygmomanometry. Results: Serum levels of CRP in DCMP patients were higher than in the control subjects (5.47 ± 2.06 mg/L and 2.35 ± 0.47 mg/L, P < 0.001, respectively). AS and AD were significantly decreased in DCMP patients compared to the controls (P < 0.001 and P < 0.001, respectively). There were positive correlations between CRP, and (r = 0.3.64, P = 0.027) smoking (r = 0.3.56, P = 0.024), and increasing age (r = 0.587, P < 0.001), and negative correlations between CRP, and DBP (r =,0.485, P < 0.001), diameter change (DC; r =,0.493, P < 0.001), AS (r =,0.526, P < 0.001), and AD (r =,0.626, P < 0.001). Conclusion: We have shown that there is a significant relation between high serum CRP levels and impaired aortic stiffness in patients with idiopathic DCMP. These findings may indicate an important role of CRP in the pathogenesis of impaired aortic stiffness in idiopathic DCMP. [source] Fourier Transformed Large Amplitude Square-Wave Voltammetry as an Alternative to Impedance Spectroscopy: Evaluation of Resistance, Capacitance and Electrode Kinetic Effects via an Heuristic ApproachELECTROANALYSIS, Issue 15-16 2005Abstract A detailed simulation of Fourier transformed large amplitude square-wave voltammetry is presented in the frequency domain for the process Red,Ox+e,. The simulation takes into account the influence of the electrode kinetics (Butler,Volmer model), uncompensated resistance (Ru) and double layer capacitance (Cdl). Of particular significance is the prediction that the even harmonic responses are only detected in the presence of quasi-reversibility or uncompensated resistance, and also are essentially devoid of charging current. In contrast, the DC and odd harmonic AC components exhibit much larger faradaic currents and also contain charging current. Conveniently, detailed analysis of the simulated DC and AC harmonic components reveals the presence of readily recognised patterns of behaviour with unique levels of sensitivity to electrode kinetics, Ru and Cdl, that facilitate quantitative analysis of these terms. These electrochemical parameters are generally calculated by small amplitude impedance spectroscopy and utilisation of linear analysis of equivalent circuits. Experimental studies on the one electron oxidation of ferrocene in dichloromethane (0.1,M Bu4NPF6) and the one electron reduction of [Fe(CN)6]3, in aqueous 0.5,M KCl electrolyte analysed via heuristic forms of data analysis based on recognition of patterns of behaviour, are presented as examples of a reversible process with significant uncompensated resistance and a quasi-reversible process with minimal ohmic drop, respectively. Results demonstrate the advantages of a more intuitively implemented form of data analysis than presently available with conventional forms of impedance spectroscopy. [source] Electroconductive Hydrogels: Electrical and Electrochemical Properties of Polypyrrole-Poly(HEMA) CompositesELECTROANALYSIS, Issue 7 2005Sean Brahim Abstract Composites of inherently conductive polypyrrole (PPy) within highly hydrophilic poly(2-hydroxyethyl methacrylate)-based hydrogels (p(HEMA)) have been fabricated and their electrochemical properties investigated. The electrochemical characteristics observed by cyclic voltammetry suggest less facile reduction of PPy within the composite hydrogel compared to electropolymerized PPy, as shown by the shift in the reduction peak potential from ,472,mV for electropolymerized polypyrrole to ,636,mV for the electroconductive composite gel. The network impedance magnitude for the electroconductive hydrogel remains quite low, ca. 100,,, even upon approach to DC, over all frequencies and at all offset potentials suggesting retained electronic (bipolaronic) conductivity within the composite. In contrast, sustained application of +0.7 V (vs. Ag/AgCl, 3,M Cl,) for typically 100,min. (conditioning) to reduce the background amperometric current to <1.0,,A, resulted in complete loss of electroactivity. Nyquist plots suggest that sustained application of such a modest potential to the composite hydrogel results in impedance characteristics that resembles p(HEMA) without evidence of the conducting polymer component. PPy composite gels supported a larger ferrocene monocarboxylate diffusivity (Dappt=7.97×10,5,cm2,s,1) compared to electropolymerized PPy (Dappt=5.56×10,5,cm2,s,1), however a marked reduction in diffusivity (Dappt=1.01×10,5,cm2,s,1) was observed with the conditioned hydrogel composite. Cyclic voltammograms in buffer containing H2O2 showed an absence of redox peaks for electrodes coated with PPy-containing membranes, suggesting possible chemical oxidation of polypyrrole by the oxidant [source] Voltammetry as a Virtual Potentiometric Sensor in Modeling of a Metal-Ligand System and Refinement of Stability Constants.ELECTROANALYSIS, Issue 8 2004Part 1. Abstract A mathematical conversion of data coming from nonequilibrium and dynamic voltammetric techniques (a direct current sampled (DC) and differential pulse (DP) polarography) into potentiometric sensor type of data is described and tested on a dynamic metal-ligand system. A combined experiment involving DCP, DPP and glass electrode potentiometry (GEP) was performed on a single solution sample containing a fixed [LT],:,[MT] ratio (acid-base titration). Dedicated potentiometric software ESTA was successfully employed in the refinement operations performed on virtual potentiometric (VP) data obtained from DC and DP polarography. It was possible to refine stability constants either separately, from VP-DC or VP-DP, or simultaneously from any combination of VP-DC, VP-DP and GEP. The concept of VP-DC or VP-DP is reported for the first time and numerous documented and possible advantages are discussed. The proposed procedure can be easily utilized also by nonelectrochemists who are interested in, e.g., the ligand design strategies. [source] A 3-D dielectrophoretic filter chipELECTROPHORESIS, Issue 7 2007Ciprian Iliescu Dr. Abstract The paper presents a 3-D filter chip employing both mechanical and dielectrophoretic (DEP) filtration, and its corresponding microfabrication techniques. The device structure is similar to a classical capacitor: two planar electrodes, made from a stainless steel mesh, and bonded on both sides of a glass frame filled with round silica beads. The solution with the suspension of particles flows through both the mesh-electrodes and silica beads filter. The top stainless steel mesh (with openings of 60,,m and wires of 30,,m-thickness) provides the first stage of filtration based on mechanical trapping. A second level of filtration is based on DEP by using the nonuniformities of the electric field generated in the capacitor due to the nonuniformities of the dielectric medium. The filter can work also with DC and AC electric fields. The device was tested with yeast cells (Saccharomyces cerevisae) and achieved a maximal trapping efficiency of 75% at an applied AC voltage of 200,V and a flow rate of 0.1,mL/min, from an initial concentration of cells of 5×105 cells/mL. When the applied frequency was varieted in the range between 20 and 200,kHz, a minimal value of capture efficiency (3%) was notticed at 50,kHz, when yeast cells exhibit negative DEP and the cells are repelled in the space between the beads. [source] Cyclical electrical field flow fractionationELECTROPHORESIS, Issue 9 2005Bruce K. Gale Abstract Cyclical electrical field flow fractionation (Cy/ElFFF) is demonstrated in a standard electrical field flow fractionation (ElFFF) channel for the first time. Motivation for the use of alternating current (AC) fields in a traditionally direct current (DC) technique are discussed. The function of the system over a wide range of operating conditions is explored and challenges associated with various operating conditions reported. Retention of polystyrene nanoparticle standards is accomplished and the effect of varying parameters of the applied field, such as voltage and frequency, are explored. The first separations using this technique are demonstrated. The experimental results are compared to analytical models previously reported in the literature. The general trend of the experimental results is similar to those predicted in theoretical models and possible reasons for discrepancies are elucidated. Suggestions are made for improving the separation and analysis method, and possible applications explored. [source] Analysis by DC,EPG of the resistance to Bemisia tabaci on an Mi -tomato lineENTOMOLOGIA EXPERIMENTALIS ET APPLICATA, Issue 3 2001Y.X. Jiang Abstract The tomato Mi gene confers resistance to nematodes, Meloidogyne spp., and to the potato aphid, Macrosiphum euphorbiae (Thomas). Previous greenhouse choice assays with Bemisia tabaci (Gennadius) showed that tomato commercial varieties carrying this gene had significantly lower values of host suitability and whitefly reproduction than varieties lacking Mi. This indicated that Mi, or another gene in its region, could regulate partial resistance. In order to characterise this resistance, probing and feeding behaviour of Bemisia tabaci B-biotype was studied with DC Electrical Penetration Graph (EPG) technique on the near-isogenic tomato lines Moneymaker (without Mi) and Motelle (carrying Mi). Significant differences (P < 0.05) between tomato lines were found in EPG parameters related to epidermis and/or mesophyll tissues. On Motelle, a lower percentage of whiteflies achieved phloem phase and they made more probes before attaining first phloem phase, had a higher ratio (number of probes before first phloem phase)/(total number of probes), had a longer total duration of non-probing time, and a longer time before making the first intracellular puncture and before making the first phloem phase. In contrast, most of the parameters related to phloem phase were found not to differ significantly between these near-isogenic lines. The behavioural data strongly suggest that the partial resistance in the variety Motelle is due to factors in the epidermis and/or mesophyll that inhibit the whiteflies from reaching phloem sieve elements. However, once the stylets reach a sieve element, whitefly behaviour did not differ between the two varieties. Thus, phloem sap of the two varieties appears to be equally acceptable to the whiteflies. Further studies are necessary to provide a better understanding of these mechanisms of resistance to whiteflies in tomatoes. [source] Tumor prevalence and biomarkers of exposure and response in brown bullhead (Ameiurus nebulosus) from the Anacostia River, Washington, DC and Tuckahoe River, Maryland, USAENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 3 2004Alfred E. Pinkney Abstract We valuated liver and skin tumor prevalence and biomarkers of exposure and response in brown bullhead (Ameiurus nebulosus) from three locations in the Anacostia River (Washington, DC, USA), a Chesapeake Bay region of concern. The Tuckahoe River (Maryland, USA) served as a reference. Each river was sampled in fall 2000 and spring 2001. In the Anacostia, prevalence of liver tumors was 50 to 68%, and prevalence of skin tumors was 13 to 23% in large (,260 mm, age ,3 years) bullheads. Liver and skin tumor prevalence was 10 to 17% and 0%, respectively, in small (150,225 mm, age 1,2 years) bullheads. Tuckahoe bullhead liver tumor prevalence was 0 to 3% (large) and 0% (small); none had skin tumors. Biliary polynuclear aromatic hydrocarbon (PAH)-like fluorescent metabolites and liver DNA adduct concentrations were elevated in large and small Anacostia bullheads. Mean adduct concentrations were 16 to 28 times higher than those in Tuckahoe fish. Chromatograms revealed a diagonal radioactive zone, indicating polycyclic aromatic compound (PAC)-DNA adducts. The biomarker data and the 10 to 17% liver tumor prevalence at ages 1 to 2 suggest that these year classes are likely to have a high prevalence as they reach age 3 and older. This study provides the strongest evidence to date of the role of PAHs in tumor development in Anacostia bullheads. [source] Effect of Dipotassium Clorazepate on Ainygdaloid-Kiiidling and Comparison Between Amygdaloid- and Hippocampal-Kindled Seizures in RatsEPILEPSIA, Issue 2000Kouichiro Amano Purpose: We reportcd previously that dipotassium clorazcpate (potassium 7-chloro-2, 3-dihydro-2-oxo-S-phcnyI- l H- l, 4-bcnzodiazepinc-3-carboxylate potassium hydroxide: DC), an antianxiety drug, suppressed hippocampel kindled scizures in rats i n a dose-dependent manner (Amano et al. Psychiatry Clin Neuroscienccs 1998; 52: 459,462). Its effect on kindling, howcver, has not been evaluated. Moreover, differcnces in the anticonvulsive effccts of conventional anticonvulsants bctween amygdaloid-and hippocampal-kindlcd seizures have becn reportcd (Kamci et al. Arch. Int. Pharmacodyn I98 1; 249: 164,176). To clarify the anticonvulsive propcrties of DC, we examined its effects on amygdaloid kindling and compared it for 7 succcssive days against amygdaloid- and hippocampal-kindled seizures using thc rat kindling model of epilcpsy. Methods: Adult inale Wistar rata weighing 220,330 g werc used. Electrodes were implanted stereotaxically into thc left basoiatcfiil amygdala or the left dorsal hippocampus under pcntobarhital ancsthesia. Expcriment 1: Anticonvulsive effect on amygdaloid-kindled seizurcs. Rats having >5 consecutive stage-5 seimrcs were htimulated at the generalizcd seizure-triggering threshold (GST) intensity 30 minutes after i.p. administration or DC or saline. Experiment 2: Effect on amygdala kindling. In other groups of Tiits, the amygdala was stimulated once daily following 30 minutes i.p. administration or DC at 5 mg/kg or saline until the first stage-5 seizure was attained. Experimcnt 3: Comparison of anticonvulsive effect bctween amygdaloid- and hippocampal-kindled scizures. In other groups of rats having 5 consecutive stage-5 seizures, the GST was determined. Furthermorc, rats having >I0 stage-5 scizures induced at thc GST intensity were testcd once a day for 7 consecutive days. Thc stimulation was delivercd 30 minutes aftcr i.p. administration of DC or saline. Results: Expcriment I: DC suppresscd amygdaloid-kindled scizures in a dose-depcndent manner. Significant reduction of aftcr-discharge duration compared with the control group was observed at dosagcs of 2 mg/kg or more, hut complete suppression of after-discharges was observed in only I of 7 sessions at the highcst dose. Expcriment 2: Thc number of stimulations rcquired for the first stage-5 seiiurc in the 5 mg/kg dosage group was 14.1+1.4 stimulations, which was significantly greater than the 10.2+1.7 stimulations in the control group (P4.01). The contralateral cortical afterdischarge duration i n the DC treated group was signilicantly shortcr than thc afterdischarge duration in the amygdala at the first 7 stimulations, whereas it was significantly shorter only the first 3 stimulations i n the control group. Experiment 3: DC suppressed amygdaloid-kindled seizures at 2 and 5 mg/kg, whcreas I mg/kg or morc suppresscd hippocampal-kindlcd seizures. Conclusions: Thc result of the present study suggcst that thc principal anticonvulsive cffect of DC is likely to be relatcd mainly to attenuation of propagation of scizure activity rather than to an elevatcd seizure threshold, which may support our previously findings that increased stimulus intensity could not complctcly reverse thc anticonvulsive effects of DC. Thus, differences in effective dosages in both amygdaloid- and hippocampal-kindled seizures may suggcst a difference in the neuronal mechanisms that arc cvolved in this kindling. The present study dcmonstratcd that DC has a modest anticonvulsive effect without serious adverse effccts, which indicates thc clinical uscfulness of DC for treatment intractable epilepsy. [source] Analysis of a radiographic technique for measurement of equine metacarpal bone shapeEQUINE VETERINARY JOURNAL, Issue S33 2001L. J. WALTER Summary Accuracy and limitations of a radiographic technique were established for measurement of metacarpal bone shape in horses. A radiographic index (RI) has been used to measure changes in third metacarpal (Mc3) bone shape in response to training in young racehorses. The aim of these experiments was to determine the effects of positioning of the radiographic equipment on RI measurements from lateromedial radiographs of a left ex vivo metacarpus. Repeatability of the RI measurement in left lateromedial and right mediolateral view Mc3s were evaluated. The width of the dorsal cortex (DC), palmar cortex (PC) and medulla (M) were measured at a position 25 mm distal to the nutrient foramen and the RI calculated where RI = [(DC+PC)/M] x [DC/PC]. The reference RI values were obtained from 12 standard lateromedial radiographs. Factors analysed included the optimum focus-object distance, the angle at which the x-ray machine was positioned, the distance of the cassette from the limb, and the horizontal angle and vertical tilt of the cassette. The RI values included within the confidence interval (mean ° 1.96 x s.d.) were considered sufficiently accurate. The optimum focus-object distance was 1 m. Accurate measurements were obtained when the cassette was held as close to the limb as possible with the horizontal angle not exceeding 5°. The x-ray machine needed to be orientated within 6° of the lateromedial plane. These findings suggest that the radiographic index can be used to measure Mc3 bone shape, providing there is accurate alignment of the x-ray machine, cassette, and limb, with respect to one another. [source] Tumour cell,dendritic cell fusion for cancer immunotherapy: comparison of therapeutic efficiency of polyethylen-glycol versus electro-fusion protocolsEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 3 2002M. Lindner Abstract Background ,Fusion of tumour cells with dendritic cells (DC) is a powerful new technology to increase tumour vaccine immunogenicity. The aim of this study was to compare fusion protocols with syngenic DCs with respect to the efficiency of polyethylen-glycol-(PEG) and electric pulse-mediated fusions for induction of protective anti-tumour immune responses. As a model we chose a low immunogenic and metastatic murine mammary carcinoma cell line, which mimics clinically relevant tumour features. Methods FACS-staining, chromium release assay, therapeutic immunization, adoptive transfer. Results ,We show that the parental line with low cell surface expression of MHC molecules as well as a lacZ transfectant becomes highly immunogenic upon fusion with DCs. This was true for PEG- as well as for electro-fused cells. Immunization with products of DCs and tumour cells cocultivated for 16 h without the fusing agent PEG also caused induction of profound anti-tumour immunity, while this was not the case when using parental tumour cells or their lacZ transfectants as vaccines. Immune protection against the parental tumour cells after vaccination with fused cells was long-lasting and could be transferred via immune spleen cells into immuno-incompetent nude (nu/nu) mice. Conclusion ,Fusion products of DA3hi mammary carcinoma cells and DCs produced by an electric pulse were similar to those produced by PEG fusion with regard to vaccine potency in prophylactic antitumour immunization assays in vivo. Therefore, both techniques seem to be promising for clinical application. [source] Targeting of LcrV virulence protein from Yersinia pestis to dendritic cells protects mice against pneumonic plagueEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 10 2010Yoonkyung Do Abstract To help design needed new vaccines for pneumonic plague, we targeted the Yersinia pestis LcrV protein directly to CD8,+ DEC-205+ or CD8,, DCIR2+ DC along with a clinically feasible adjuvant, poly IC. By studying Y. pestis in mice, we could evaluate the capacity of this targeting approach to protect against a human pathogen. The DEC-targeted LcrV induced polarized Th1 immunity, whereas DCIR2-targeted LcrV induced fewer CD4+ T cells secreting IFN-,, but higher IL-4, IL-5, IL-10, and IL-13 production. DCIR-2 targeting elicited higher anti-LcrV Ab titers than DEC targeting, which were comparable to a protein vaccine given in alhydrogel adjuvant, but the latter did not induce detectable T-cell immunity. When DEC- and DCIR2-targeted and F1-V+ alhydrogel-vaccinated mice were challenged 6,wk after vaccination with the virulent CO92 Y. pestis, the protection level and Ab titers induced by DCIR2 targeting were similar to those induced by F1-V protein with alhydrogel vaccination. Therefore, LcrV targeting to DC elicits combined humoral and cellular immunity, and for the first time with this approach, also induces protection in a mouse model for a human pathogen. [source] The interferon-inducible gene IFI16 secretome of endothelial cells drives the early steps of the inflammatory responseEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 8 2010Rossella Baggetta Abstract The IFN-inducible human IFI16 gene is highly expressed in endothelial cells as well as epithelial and hematopoietic tissues. Previous gene array analysis of human umbilical vein endothelial cells overexpressing IFI16 has revealed an increased expression of genes involved in inflammation and apoptosis. In this study, protein array analysis of the IFI16 secretome showed an increased production of chemokines, cytokines and adhesion molecules responsible for leukocyte chemotaxis. Functional analysis of the promoter for CCL20, the chemokine responsible for leukocyte recruitment in the early steps of inflammation, by site-specific mutation demonstrated that NF-,B is the main mediator of CCL20 induction at the transcriptional level. Finally, both Langerhans DC and B-lymphocyte migration triggered by supernatants from IFI16-overexpressing endothelial cells was partially inhibited by Ab inactivating CCL4, CCL5 and CCL20 chemokines. Altogether, these results demonstrate that the IFI16 gene, through its secretome, regulates proinflammatory activity of endothelial cells, thus corroborating its role in the early steps of inflammation. [source] HIV-1 impairs in vitro priming of naïve T cells and gives rise to contact-dependent suppressor T cellsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 8 2010Karlhans F. Che Abstract Priming of T cells in lymphoid tissues of HIV-infected individuals occurs in the presence of HIV-1. DC in this milieu activate T cells and disseminate HIV-1 to newly activated T cells, the outcome of which may have serious implications in the development of optimal antiviral responses. We investigated the effects of HIV-1 on DC,naïve T-cell interactions using an allogeneic in vitro system. Our data demonstrate a dramatic decrease in the primary expansion of naïve T cells when cultured with HIV-1-exposed DC. CD4+ and CD8+ T cells showed enhanced expression of PD-1 and TRAIL, whereas CTLA-4 expression was observed on CD4+ T cells. It is worth noting that T cells primed in the presence of HIV-1 suppressed priming of other naïve T cells in a contact-dependent manner. We identified PD-1, CTLA-4, and TRAIL pathways as responsible for this suppresion, as blocking these negative molecules restored T-cell proliferation to a higher degree. In conclusion, the presence of HIV-1 during DC priming produced cells with inhibitory effects on T-cell activation and proliferation, i.e. suppressor T cells, a mechanism that could contribute to the enhancement of HIV-1 pathogenesis. [source] Stress for maintaining memory: HSP70 as a mobile messenger for innate and adaptive immunityEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 6 2010Taoyong Chen Abstract HSP are abundant and conserved proteins present in all cells. Upon temperature shock or other stress stimuli, HSP are synthesized intracellularly, which may protect cells from protein denaturation or from death. Although HSP are synthesized intracellularly, HSP can also be mobilized to the plasma membrane or even be released under stress conditions. Elucidating the roles of cell surface and extracellular HSP in immune regulation has attracted much attention in recent years. Extracellularly, HSP can serve a cytokine function to initiate both innate and adaptive immunity through activation of APC. HSP serves also a chaperone function and facilitates presentation of antigen peptide to T cells. Similarly, cell surface HSP may activate APC and promote antigen presentation through cell,cell contact. A study in this issue of the European Journal of Immunology demonstrates that cell surface HSP70 on DC induced by stress can upregulate membrane-associated IL-15, which in turn promotes the proliferation of CD4+CD45RA memory T cells. Moreover, a DC-CD4+ T-cell interacting circuit formed by CD40L on T cells and CD40 on DC is proposed to play a role in the maintenance of memory homeostasis. This study has widened our view of HSP in adaptive immunity as well as their classical functions such as APC activator and antigen carrier. [source] CD8,+ DC are not the sole subset cross-presenting cell-associated tumor antigens from a solid tumorEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 6 2010Alison M. McDonnell Abstract One of the clear paradoxes in tumor immunology is the fact that cross-presentation of cell-associated tumor antigens to CD8+ T cells is efficient, yet CTL generation is weak, and tumors continue to grow. We examined, for the first time whether this may be due to alterations in the phenotype or function of cross-presenting DC using a solid tumor model expressing a membrane bound neo-antigen (hemagglutinin, HA). Tumor antigen was constitutively cross-presented in the tumor-draining LN throughout tumor progression by CD11c+ DC. Further analysis revealed that both CD8,+ and CD8,, DC subsets, but not plasmacytoid DC, were effective at cross-presenting HA tumor antigen. The proportions of DC subsets in the tumor-draining LN were equivalent to those seen in the LN of naïve mice; however, a significant increase in the expression of the potential inhibitory B7 molecule, B7-DC, was noted and appeared to be restricted to the CD8,, DC subset. Therefore LN resident CD8,+ DC are not the sole DC subset capable of cross-presenting cell-associated tumor antigens. Migratory tumor DC subsets with altered co-stimulatory receptor expression may contribute to induction and regulation of tumor-specific responses. [source] Stress-activated dendritic cells interact with CD4+ T cells to elicit homeostatic memoryEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 6 2010Yufei Wang Abstract Evidence is presented that thermal or oxidizing stress-activated DC interact with CD4+ T cells to induce and maintain a TCR-independent homeostatic memory circuit. Stress-activated DC expressed endogenous intra-cellular and cell surface HSP70. The NF-,B signalling pathway was activated and led to the expression of membrane-associated IL-15 molecules. These interacted with the IL-15 receptor complex on CD4+ T cells, thus activating the Jak3 and STAT5 phosphorylation signalling pathway to induce CD40 ligand expression, T-cell proliferation and IFN-, production. CD40 ligand on CD4+ T cells in turn re-activated CD40 molecules on DC, inducing DC maturation and IL-15 expression thereby maintaining the feedback circuit. The proliferating CD4+ T cells were characterized as CD45RA, CD62L+ central memory cells, which underwent homeostatic proliferation. The circuit is independent of antigen and MHC-class-II-TCR interaction as demonstrated by resistance to TCR inhibition by ZAP70 inhibitor or MHC-class II antibodies. These findings suggest that stress can activate a DC-CD4+ T-cell interacting circuit, which may be responsible for maintaining a homeostatic antigen-independent memory. [source] MAPK3 deficiency drives autoimmunity via DC armingEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 5 2010Ivo Bendix Abstract DC are professional APC that instruct T cells during the inflammatory course of EAE. We have previously shown that MAPK3 (Erk1) is important for the induction of T-cell anergy. Our goal was to determine the influence of MAPK3 on the capacity of DC to arm T-cell responses in autoimmunity. We report that DC from Mapk3,/, mice have a significantly higher membrane expression of CD86 and MHC-II and , when loaded with the myelin oligodendrocyte glycoprotein , show a superior capacity to prime naïve T cells towards an inflammatory phenotype than Mapk3+/+ DC. Nonetheless and as previously described, Mapk3,/, mice were only slightly but not significantly more susceptible to myelin oligodendrocyte glycoprotein-induced EAE than WT littermate mice. However, Mapk3+/+ mice engrafted with Mapk3,/, BM (KO,WT) developed a severe form of EAE, in direct contrast to WT,KO mice, which were even less sick than control WT,WT mice. An infiltration of DC and accumulation of Th17 cells was also observed in the CNS of KO,WT mice. Therefore, triggering of MAPK3 in the periphery might be a therapeutic option for the treatment of neuroinflammation since absence of this kinase in the immune system leads to severe EAE. [source] Complement C5a regulates IL-17 by affecting the crosstalk between DC and ,, T cells in CLP-induced sepsisEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 4 2010Ruonan Xu Abstract Complement 5a (C5a) and Interleukin-17 (IL-17) are two important inflammatory mediators in sepsis. Here we studied the mechanisms underlying regulation of IL-17 by anaphylatoxin C5a. We found that C5a blockade increased the survival rate of mice following cecal ligation and puncture (CLP)-induced sepsis and decreased IL-17 expression in vivo. IL-17 was secreted mainly by ,, T cells in this model. Importantly, our data suggest that C5a participates in the regulation of IL-17 secretion by ,, T cells. Dendritic cells (DC) were found to act as a "bridge" between C5a and ,, T cells in a mechanism involving IL-6 and transforming growth factor , (TGF-,). These results imply that C5a affects the crosstalk between DC and ,, T cells during sepsis development, and this may result in a large production of inflammatory mediators such as IL-17. [source] Lineage-specific transcription factors in unexpected placesEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 2 2010David H. Munn Abstract Foxp3 is a transcription factor closely associated with the Treg lineage in humans and mice. In the immune system, Foxp3 appears highly specific for Treg, and is not known to be expressed by other immune cell types. In this issue of the European Journal of Immunology, an article reports that human DC transfected with ectopic Foxp3 unexpectedly acquire an immunosuppressive phenotype. Foxp3-transfected DC suppressed proliferation of naive T cells, and biased the differentiation of CD4+ cells into Treg-like cells that themselves expressed Foxp3. The molecular mechanism of these effects required functional activity of the immunoregulatory enzyme IDO. Thus, a transcription factor not native to DC nevertheless conferred elements of a regulatory phenotype following ectopic expression. [source] IL-33 promotes DC development in BM culture by triggering GM-CSF productionEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 12 2009Nobuyasu Mayuzumi Abstract Short-term DC cultures generated with GM-CSF and other cytokines have markedly improved our ability to study the immunobiology of DC. Here, we tested 65 cytokines individually for their potential to promote the generation of CD11c+ cells in a murine BM culture system. In addition to several cytokines known to promote DC survival and/or growth, IL-33 was found to augment DC development time- and dose-dependently. Although the resulting CD11c+ cells generated in the presence of IL-33 exhibited a typical dendritic morphology, they expressed MHC class II molecules only at modest levels, showed negligible responses to TLR ligands, produced no detectable IL-12 p70, displayed PD-L1 and PD-L2 on the surface, and failed to activate immunologically naïve T cells efficiently. IL-33-induced expansion of CD11c+ cells was completely blocked by anti-GM-CSF mAb, and GM-CSF mRNA and protein expression in BM culture was markedly elevated by added IL-33, indicating that IL-33 promotes in vitro DC generation indirectly by a GM-CSF-dependent manner. With regard to the cellular source, IL-33-dependent GM-CSF production was observed exclusively within the CD45+/Fc,RI+ BM population. Not only do our results reinforce the notion that GM-CSF serves as a primary DC growth factor, but they also reveal a previously unrecognized mechanism supporting DC development. [source] Curcumin induces the tolerogenic dendritic cell that promotes differentiation of intestine-protective regulatory T cellsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 11 2009Yingzi Cong Abstract The gut is home to a large number of Treg, with both CD4+ CD25+ Treg and bacterial antigen-specific Tr1 cells present in normal mouse intestinal lamina propria. It has been shown recently that intestinal mucosal DC are able to induce Foxp3+ Treg through production of TGF-, plus retinoic acid (RA). However, the factors instructing DC toward this mucosal phenotype are currently unknown. Curcumin has been shown to possess a number of biologic activities including the inhibition of NF-,B signaling. We asked whether curcumin could modulate DC to be tolerogenic whose function could mimic mucosal DC. We report here that curcumin modulated BM-derived DC to express ALDH1a and IL-10. These curcumin-treated DC induced differentiation of naïve CD4+ T cells into Treg resembling Treg in the intestine, including both CD4+CD25+ Foxp3+ Treg and IL-10-producing Tr1 cells. Such Treg induction required IL-10, TGF-, and retinoic acid produced by curcumin-modulated DC. Cell contact as well as IL-10 and TGF-, production were involved in the function of such induced Treg. More importantly, these Treg inhibited antigen-specific T-cell activation in vitro and inhibited colitis due to antigen-specific pathogenic T cells in vivo. [source] |