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Promising Candidate (promising + candidate)
Kinds of Promising Candidate Terms modified by Promising Candidate Selected AbstractsThe Challenging Estrogen Receptor-Negative/ Progesterone Receptor-Negative/HER-2-Negative Patient: A Promising Candidate for Epidermal Growth Factor Receptor-Targeted Therapy?THE BREAST JOURNAL, Issue 4 2006Kalliopi P. Siziopikou MD Abstract: While epidermal growth factor receptor (EGFR)-targeted therapy has been very promising in a number of human malignancies, to date these targeted biologic agents have not proven effective in breast cancer. However, the EGFR tyrosinase inhibitors have been used indiscriminately against all types of breast tumors, perhaps missing a subpopulation of patients who may be prime candidates for EGFR-targeted therapy. In this communication we propose that patients with estrogen receptor (ER)-negative/progesterone receptor (PR)-negative/HER-2-negative tumors, which currently present a therapeutic challenge for the oncologist, may be the subgroup of breast cancer patients that might benefit from specific EGFR-targeted therapies., [source] The immunological monitoring of alloreactive responses in liver transplant recipients: A reviewLIVER TRANSPLANTATION, Issue 3 2006Raymond Reding The aim of this work is to review the current knowledge in the field of immunological monitoring of allogenic responsiveness in clinical liver transplantation. When compared to other solid-organ transplants, liver allografts are considered as immunologically privileged, and, accordingly, constitute a favorable setting to develop experimental as well as clinical strategies for minimization of immunosuppression and even induction of operational tolerance. The validation of simple, reliable, noninvasive assays exploring antidonor alloreactivity will constitute a crucial step toward implementing such approaches in the clinic. In contrast to research in rodents claiming the development of donor-specific tolerance in case of graft survivals of over 100 days without immunosuppression, it is impractical to confirm tolerance induction in this way in humans. Promising candidate assays include the detection of post-transplant immune deviation, of circulating precursors of dendritic cells subtypes, and of regulatory T cells. A conceptual framework for the development of tolerance assays in clinical liver transplantation is also proposed. Liver Transpl 12:373,383, 2006. © 2006 AASLD. [source] A Novel Polycatechol/Ordered Mesoporous Carbon Composite Film Modified Electrode and Its Electrocatalytic ApplicationELECTROANALYSIS, Issue 15 2010Jing Bai Abstract Polycatechol (PCC) was prepared by electropolymerizing catechol (CC) on the surface of an ordered mesoporous carbon (OMC) modified electrode for the first time. Scanning electron microscopy (SEM) and cyclic voltammetry (CV) were used to characterize the structure and electrochemical behaviors of PCC/OMC nanocomposite film. Compared with the bare GC and OMC/GC electrodes, the PCC/OMC/GC electrode exhibits a good electrocatalysis toward the oxidation of NADH at 0.0,V with a high sensitivity (8.7 mA/mM). These make PCC/OMC/GC electrode a promising candidate for stable and efficient electrochemical sensors for the detection of NADH. [source] Synthesis of Carbon Nanofibers for Mediatorless Sensitive Detection of NADHELECTROANALYSIS, Issue 15 2008Yang Liu Abstract Highly sensitive amperometric detection of dihydronicotinamide adenine dinucleotide (NADH) by using novel synthesized carbon nanofibers (CNFs) without addition of any mediator has been proposed. The CNFs were prepared by combination of electrospinning technique with thermal treatment method and were applied without any oxidation pretreatment to construct the electrochemical sensor. In amperometric detection of NADH, a linear range up to 11.45,,M with a low detection limit of 20,nM was obtained with the CNF-modified carbon paste electrode (CNF-CPE). Good selectivity was exhibited for the simultaneous detection of NADH and its common interferent of ascorbic acid (AA) by differential pulse voltammogram. The attractive electrochemical performance and the versatile preparation process of the CNF-CPE made it a promising candidate for designing effective NADH sensor. [source] Intravascular neural interface with nanowire electrodeELECTRONICS & COMMUNICATIONS IN JAPAN, Issue 7 2009Hirobumi Watanabe Abstract A minimally invasive electrical recording and stimulating technique capable of simultaneously monitoring the activity of a significant number (e.g., 103 to 104) of neurons is an absolute prerequisite in developing an effective brain,machine interface. Although there are many excellent methodologies for recording single or multiple neurons, there has been no methodology for accessing large numbers of cells in a behaving experimental animal or human individual. Brain vascular parenchyma is a promising candidate for addressing this problem. It has been proposed [1, 2] that a multitude of nanowire electrodes introduced into the central nervous system through the vascular system to address any brain area may be a possible solution. In this study we implement a design for such microcatheter for ex vivo experiments. Using Wollaston platinum wire, we design a submicron-scale electrode and develop a fabrication method. We then evaluate the mechanical properties of the electrode in a flow when passing through the intricacies of the capillary bed in ex vivo Xenopus laevis experiments. Furthermore, we demonstrate the feasibility of intravascular recording in the spinal cord of Xenopus laevis. © 2009 Wiley Periodicals, Inc. Electron Comm Jpn, 92(7): 29,37, 2009; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecj.10058 [source] Mesothelin, a possible target for immunotherapy, is expressed in primary AML cellsEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 4 2007Daniel Steinbach Abstract Background:, Mesothelin is a promising candidate for tumor-specific therapy because of its limited expression in normal tissues and high expression in several cancers. The expression of the protein mesothelin in hematological malignancies has not yet been analyzed. SS1(dsFv)PE38 is a recombinant anti-mesothelin immunotoxin which is undergoing clinical evaluation in patients with mesothelin-expressing tumors. Methods and Results:, In this study we show that the mesothelin protein is expressed in leukemic cells from children with acute myeloid leukemia (AML). This finding was confirmed by western blot, immunocytochemistry and real time polymerase chain reaction (PCR). Despite the expression of mesothelin, the patient samples were not sensitive to immunotoxin SS1(dsFv)PE38 in MTT assays. Conclusions:, Primary AML cells express mesothelin but SS1(dsFv)PE38 is not active in killing these cells. Other approaches that utilize mesothelin as a target might be more effective and should be tested against AML cells. [source] A comparison of 5-aminolaevulinic acid- and its heptyl ester: dark cytotoxicity and protoporphyrin IX synthesis in human adenocarcinoma WiDr cells and in athymic nude mice healthy skinEXPERIMENTAL DERMATOLOGY, Issue 11 2009Xiao Pudroma Abstract:, 5-aminolevulinic acid heptyl ester was investigated in human adenocarcinoma WiDr cells and in healthy skin of athymic nude mice in comparison with 5-aminolevulinic acid (ALA). Incubation of WiDr cells with ALA and ALA heptyl ester resulted in production of protoporphyrin IX (PpIX). Concentrations higher than 0.01 mm of ALA heptyl ester and higher than 1 mm of ALA were cytotoxic. The dark cytotoxicity was not related to PpIX. Intracellular localization, photocytoxicity and photobleaching rate of PpIX were the same for both drugs, although a 100 times lower concentration of ALA heptyl ester (0.01 mm) was needed in comparison with ALA (1 mm) to induce the same level of PpIX. ALA heptyl ester, topically (but not systemically) applied, is a promising candidate for fluorescence diagnosis and photodynamic therapy. Special attention must be focused on the concentrations of ALA heptyl ester; as excess may lead to cytotoxicity and inefficient PpIX generation. [source] Phosphorescent OLEDs: Synthesis and Characterization of Red-Emitting Iridium(III) Complexes for Solution-Processable Phosphorescent Organic Light-Emitting Diodes (Adv. Funct.ADVANCED FUNCTIONAL MATERIALS, Issue 14 2009Mater. On page 2205, S.H. Jin and co-workers report on the development of red-emitting iridium(III) complexes for solution-processable phosphorescent organic light-emitting diodes (PhOLEDs). This frontispiece image shows the fabrication of full-color PhOLEDs by an inkjet printing method. The combination of good efficiency and color purity identifies this material as a promising candidate for red phosphorescent doping of PhOLEDs. Structure-property relationships for improving the performance of such devices are also investigated. [source] Temperature-Induced Hydrogels Through Self-Assembly of Cholesterol-Substituted Star PEG- b -PLLA Copolymers: An Injectable Scaffold for Tissue Engineering,ADVANCED FUNCTIONAL MATERIALS, Issue 8 2008Koji Nagahama Abstract Partially cholesterol-substituted 8-arm poly(ethylene glycol)- block -poly(L -lactide) (8-arm PEG- b -PLLA-cholesterol) has been prepared as a novel star-shaped, biodegradable copolymer derivative. The amphiphilic 8-arm PEG- b -PLLA-cholesterol aqueous solution (polymer concentration, above 3,wt%) exhibits instantaneous temperature-induced gelation at 34,°C, but the virgin 8-arm PEG- b -PLLA does not, irrespective of concentration. Moreover, an extracellular matrix (ECM)-like micrometer-scale network structure has been created with favorable porosity for three-dimensional proliferation of cells inside the hydrogel. This network structure is mainly attributed to specific self-assembly between cholesterol groups. The 10 and 20,wt% hydrogels are eroded gradually in phosphate buffered saline at 37,°C over the course of a month, and after that the gel becomes completely dissociated. Moreover, L929 cells encapsulated into the hydrogel are viable and proliferate three-dimensionally inside the hydrogels. Thus, in-vitro cell culture studies demonstrate that 8-arm PEG- b -PLLA-cholesterol is a promising candidate as a novel injectable cellular scaffold. [source] A New Sol,Gel Material Doped with an Erbium Complex and Its Potential Optical-Amplification Application,ADVANCED FUNCTIONAL MATERIALS, Issue 6 2005L.-N. Sun Abstract The crystal structure of a ternary Er(DBM)3phen complex (DBM,=,dibenzoylmethane; phen,=,1,10-phenanthroline) and its in-situ synthesis via a sol,gel process are reported. The infrared (IR), diffuse reflectance (DR), and fluorescence spectra of the pure complex and the Er3+/DBM/phen co-doped luminescent hybrid gel, formed via an in-situ method (ErDP gel), have been investigated. The results reveal that the erbium complex is successfully synthesized in situ in the ErDP gel. Excitation at the maximum absorption wavelength of the ligands resulted in the typical near-IR luminescence (centered at around 1.54,,m) resulting from the 4I13/2,,,4I15/2 transition of the Er3+ ion, which contributes to the efficient energy transfer from the ligands to the Er3+ ion in both the Er(DBM)3phen complex and the ErDP gel (an antenna effect). The full width at half maximum (FWHM) centered at 1541,nm in the emission spectrum of the ErDP gel is 72,nm, which has potential for optical-amplification applications. Further theoretical analysis on the Er3+ ion in the ErDP gel shows that it appears to be a promising candidate for tunable lasers and planar optical amplifiers. [source] Synthesis and Characterization of Polypiridine-Based Rhenium(I) Complexes with Pyrazino[2,3- f][1,10]phenanthrolineHELVETICA CHIMICA ACTA, Issue 6 2006Ramiro Díaz Abstract A series of tricarbonyl rhenium(I) complexes of the type fac -[ReI(CO)3(ppl)(L)]0/+, where ppl is pyrazino[2,3- f][1,10]phenanthroline, and where L is Cl,, TfO,, 4-(tert -butyl)pyridine (tBu-py), 4-methoxypyridine (MeO-py), 4,4,-bipyridyl (bpy), or 10-(picolin-4-yl)phenothiazine (pptz), were synthesized and fully characterized. In all complexes, an increment in the electron-acceptor properties of ppl compared to the free ligand was observed. This effect was more significant for pyridine-type ligands, especially for pptz, compared to Cl, or TfO,. The properties of fac -[Re(CO)3(ppl)(pptz)]PF6 were compared with those of the analogous compound fac -[Re(CO)3(dppz)(pptz)]PF6, where dppz is dipyrido(3,2- a,: 2,,3,- c)phenazine, the goal being to generate long-lived excited charge-transfer (CT) states. In this respect, fac -[Re(CO)3(ppl)(pptz)]PF6 seems to be a promising candidate. [source] HIP/PAP accelerates liver regeneration and protects against acetaminophen injury in mice,HEPATOLOGY, Issue 3 2005Hanh-Tu Lieu Human hepatocarcinoma-intestine-pancreas/pancreatic-associated protein HIP/PAP is a secreted C-type lectin belonging to group VII, according to Drickamer's classification. HIP/PAP is overexpressed in liver carcinoma; however, its functional role remains unclear. In this study, we demonstrate that HIP/PAP is a paracrine hepatic growth factor promoting both proliferation and viability of liver cells in vivo. First, a low number of implanted hepatocytes deriving from HIP/PAP-transgenic mice (<1:1,000) was sufficient to stimulate overall recipient severe combined immunodeficiency liver regeneration after partial hepatectomy. After a single injection of HIP/PAP protein, the percentages of bromodeoxyuridine-positive nuclei and mitosis were statistically higher than after saline injection, indicating that HIP/PAP acts as a paracrine mitogenic growth factor for the liver. Comparison of the early events posthepatectomy in control and transgenic mice indicated that HIP/PAP accelerates the accumulation/degradation of nuclear phospho,signal transducer activator transcription factor 3 and tumor necrosis factor , level, thus reflecting that HIP/PAP accelerates liver regeneration. Second, we showed that 80% of the HIP/PAP-transgenic mice versus 25% of the control mice were protected against lethal acetaminophen-induced fulminate hepatitis. A single injection of recombinant HIP/PAP induced a similar cytoprotective effect, demonstrating the antiapoptotic effect of HIP/PAP. Comparison of Cu/Zn superoxide dismutase activity and glutathione reductase-like effects in control and transgenic liver mice indicated that HIP/PAP exerts an antioxidant activity and prevents reactive oxygen species-induced mitochondrial damage by acetaminophen overdose. In conclusion, the present data offer new insights into the biological functions of C-type lectins. In addition, HIP/PAP is a promising candidate for the prevention and treatment of liver failure. (HEPATOLOGY 2005;42:618,626.) [source] Carbon Nanotubes Carrying Cell-Adhesion Peptides do not Interfere with Neuronal Functionality,ADVANCED MATERIALS, Issue 28 2009Claire Gaillard Water-soluble carbon nanotubes functionalized with cell-adhesion peptides do not affect the viability of different cell types, including Jurkat cells, splenocytes, and neurons. They also do not modify the neuronal morphology and basic functions, thus representing a promising candidate for the exploitation of novel drug-delivery systems or for designing a new generation of self-assembling nerve bridges. [source] Biodegradation and Cytocompatibility Studies of a Triphasic Ceramic-Coated Porous Hydroxyapatite for Bone Substitute ApplicationsINTERNATIONAL JOURNAL OF APPLIED CERAMIC TECHNOLOGY, Issue 1 2008Annie John Bone defects due to trauma or disease have led to the need for biomaterials as substitutes for tissue regeneration and repair. Herein, we introduce a porous triphasic ceramic-coated hydroxyapatite scaffold (HASi) for such applications. Interestingly, in the degradation experiments with isotonic buffer, HASi showed a significant release of silica with the disappearance of the tricalcium phosphate phase. Furthermore, the material also exhibited cytocompatibility with cultured bone marrow-derived mesenchymal stem cells of human origin. The material chemistry, together with the favorable cellular characteristics, indicates HASi as a promising candidate for critical-size bony defects, which still remains a formidable clinical challenge in the orthopedic scenario. [source] Elevated plasma osteopontin level is predictive of cirrhosis in patients with hepatitis B infectionINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 7 2008L. Zhao Summary Background:, Osteopontin (OPN) was shown to play an important role in the pathogenesis of various inflammatory and fibrotic processes and elevated in fibrotic liver of mouse model. However, the significance of OPN in hepatitis B virus (HBV)-induced liver cirrhosis (LC) remains unclear and is therefore evaluated in this study. Methods:, Thirty-nine patients with HBV-induced LC, 30 patients with HBV infection but without cirrhosis, 11 patients with HBV-related hepatocellular carcinoma (HCC) and 14 additional healthy controls were enrolled in this study. Plasma levels of OPN were measured with enzyme-linked immunosorbent assay and the relationship between OPN and clinical parameters was evaluated. Results:, When compared to HBV infection group (median 2.16 ng/ml), plasma levels of OPN were significantly increased in cirrhosis (4.52 ng/ml, p < 0.001) and cancer group (13.38 ng/ml, p < 0.001). The OPN level was correlated with the severity of liver damage according to Child,Pugh classification (p = 0.003). It showed at least comparable sensitivity and specificity to predict cirrhosis as aspartate aminotransferase to platelet ratio index, a previously established non-invasive serum marker of cirrhosis. Conclusions:, These data suggest that OPN could be used to evaluate the existence of LC, as OPN has previously been reported to be increased in the HCC; this unique feature makes OPN a promising candidate for prediction biomarker in the long-time surveillance of patients with HBV infection to evaluate the risk of cirrhosis and cancer. [source] Highly Periodic Fullerene Nanomesh,ADVANCED MATERIALS, Issue 2 2006N. Néel Fullerene nanomesh: Fullerene islands with rectangular shapes organize themselves on a vicinal gold surface in an extraordinarily well-ordered mesh with unprecedented periodicity and low defect density (see Figure). This adsorbate system is a promising candidate for guiding subsequent deposition of functional units. [source] Efficient removal of hexavalent chromium by a tolerant Streptomyces sp. affected by the toxic effect of metal exposureJOURNAL OF APPLIED MICROBIOLOGY, Issue 6 2007D.K. Morales Abstract Aims:, To isolate and analyse chromium-resistant micro-organisms suitable for bioremediation. Methods and Results:, Strain CG252, with a minimal inhibitory concentration of 500 ,g ml,1, was isolated from contaminated soils and identified as a Streptomyces sp. by 16S rDNA sequence analysis. Assays carried out at various Cr(VI) concentrations indicated that chromium removal was more efficient at lower concentrations and that this activity resulted in accumulation of Cr(III). Atomic adsorption analysis indicated that the chromium removed was not associated with cell mass and activity assays showed that the capacity to reduce Cr(VI) was most probably due to a soluble cytosolic enzyme. Cells grown as biofilms showed enhanced removal of Cr(VI) with respect to planktonic cells, while analysis of growth and colony morphology indicated that Cr(VI) had a toxic effect on this strain. Conclusions:,Streptomyces sp. CG252 tolerated heavy metals and elevated levels of chromium, despite its negative effect on growth and development, and was efficient at removing Cr(VI) by promoting reduction to Cr(III). Significance and Impact of the Study:, Strain CG252's capacity to tolerate heavy metals and to reduce Cr(VI) to the less toxic Cr(III), especially when forming biofilms, makes it a promising candidate for detoxification of sites containing this heavy metal. [source] Skin sensitization potency of isoeugenol and its dimers evaluated by a non-radioisotopic modification of the local lymph node assay and guinea pig maximization testJOURNAL OF APPLIED TOXICOLOGY, Issue 4 2008Masahiro Takeyoshi Abstract Allergic contact dermatitis is the serious unwanted effect arising from the use of consumer products such as cosmetics. Isoeugenol is a fragrance chemical with spicy, carnation-like scent, is used in many kinds of cosmetics and is a well-known moderate human sensitizer. It was previously reported that the dimerization of eugenol yielded two types of dimer possessing different sensitization potencies. This study reports the differences in skin sensitization potencies for isoeugenol and two types of dimer, , -O-4-dilignol and dehydrodiisoeugenol (DIEG), as evaluated by the non-radioisotopic local lymph node assay (non-RI LLNA) and guinea pig maximization test. In the guinea pig maximization test, isoeugenol, , -O-4-dilignol and DIEG were classified as extreme, weak and moderate sensitizers, respectively. As for the results of non-RI LLNA, the EC3 for isoeugenol, , -O-4-dilignol and DIEG were calculated as 12.7%, >30% and 9.4%, respectively. The two types of isoeugenol dimer showed different sensitizing activities similar to the case for eugenol dimers. A reduction of sensitization potency achieved by dimerization may lead to developing safer cosmetic ingredients. Isoeugenol dimers are not currently used for fragrance chemicals. However, the dimerization of isoeugenol may yield a promising candidate as a cosmetic ingredient with low sensitization risk. The data may also provide useful information for the structure-activity relationship (SAR) in skin sensitization. Copyright © 2007 John Wiley & Sons, Ltd. [source] Chemical characteristics and cytocompatibility of collagen-based scaffold reinforced by chitin fibers for bone tissue engineeringJOURNAL OF BIOMEDICAL MATERIALS RESEARCH, Issue 2 2006Xiaoming Li Abstract Chitin is a kind of seemly material to match PLLA for a scaffold, which may create an appropriate environment for the regeneration of tissues. In this study, we prepared and evaluated a new nano-hydroxyapatite/collagen/PLLA (nHACP) scaffold reinforced by chitin fibers for bone-tissue engineering. The chitin fibers were crosslinked with PLLA by dicyclohexylcarbodimide (DCC). The chemical characteristics were evaluated by Fourier transformed infrared (FTIR) spectroscopy and X-ray photoelectron spectroscopy (XPS). The mechanical strength was measured by compressive tests. The fibers, crosslinked with PLLA, could enhance the compressive strength of the scaffold about four times. Human marrow mesenchymal stem cells (MSCs) culture showed that the reinforced nHACP scaffolds were more cytocompatible than that without reinforcement. The crosslinks hardly affected the cytocompatibility of the reinforced scaffolds. The results suggested that the reinforced scaffolds (DCC crosslinked) might be a promising candidate for bone-tissue engineering. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2006 [source] Interferon regulatory factor-1 acts as a powerful adjuvant in tat DNA based vaccination,JOURNAL OF CELLULAR PHYSIOLOGY, Issue 3 2010Arianna Castaldello Genetic vaccines are safe cost-effective approaches to immunization but DNA immunization is an inefficient process. There is, therefore, a pressing need for adjuvants capable of enhancing the immunogenicity and effectiveness of these vaccines. This is particularly important for diseases for which successful vaccines are still lacking, such as cancer and infectious diseases including HIV-1/AIDS. Here we report an approach to enhance the immunogenicity of DNA vaccines involving the use of transcription factors of the Interferon regulatory factor (IRF) family, specifically IRF-1, IRF-3, and IRF-7 using the tat gene as model antigen. Balb/c mice were immunized by three intramuscular inoculations, using a DNA prime-protein boost protocol, with a DNA encoding tat of HIV-1 and the indicated IRFs and immune responses were compared to those induced by vaccination with tat DNA alone. In vivo administration of plasmid DNA encoding IRF-1, or a mutated version of IRF-1 deleted of the DNA-binding domain, enhanced Tat-specific immune responses and shifted them towards a predominant T helper 1-type immune response with increased IFN-, production and cytotoxic T lymphocytes responses. Conversely, the use of IRF-3 or IRF-7 did not affect the tat -induced responses. These findings define IRF-1 and its mutated form as efficacious T helper 1-inducing adjuvants in the context of tat- based vaccination and also providing a new promising candidate for genetic vaccine development. J. Cell. Physiol. 224: 702,709, 2010. © 2010 Wiley-Liss, Inc. [source] BRD7, a novel bromodomain gene, inhibits G1,S progression by transcriptionally regulating some important molecules involved in ras/MEK/ERK and Rb/E2F pathwaysJOURNAL OF CELLULAR PHYSIOLOGY, Issue 1 2004Jie Zhou Bromodomain is a 110 amino acid domain. It is evolutionally conserved and is found in proteins strongly implicated in signal-dependent transcriptional regulation. BRD7 is a novel bromodomain gene and it is downexpressed in nasopharyngeal carcinoma (NPC) biopsies and cell lines; its function is poorly understood. In the present study, tet-on inducible expression system was used to investigate the role of BRD7 in cell growth and cell cycle progression. We found that ectopic expression of BRD7 in NPC cells inhibited cell growth and cell cycle progression from G1 to S. We further performed cell cycle cDNA array to screen potential transcriptional targets of BRD7 in cell cycle. Thirteen important signaling molecules, mainly implicated in ras/MEK/ERK and Rb/E2F pathways, were differentially expressed by induction of BRD7. Moreover, we observed that BRD7 could regulate the promoter activity of E2F3, one of its targets. Taken together, the present study indicated that BRD7 inhibited G1,S progression by transcriptionally regulating some important molecules involved in ras/MEK/ERK and Rb/E2F pathways and suggested that BRD7 may present a promising candidate of NPCÔ associated tumor suppressor gene. © 2004 Wiley-Liss, Inc. [source] SHIV89.6P pathogenicity in cynomolgus monkeys and control of viral replication and disease onset by human immunodeficiency virus type 1 Tat vaccineJOURNAL OF MEDICAL PRIMATOLOGY, Issue 3-4 2000Aurelio Cafaro The Tat protein of human immunodeficiency virus (HIV) is produced very early after infection, plays a key role in the virus life cycle and in acquired immunodeficiency syndrome (AIDS) pathogenesis, is immunogenic and well conserved among all virus clades. Notably, a Tat-specific immune response correlates with non-progression to AIDS. Here, we show that a vaccine based on the Tat protein of HIV blocks primary infection with the simian/human immunodeficiency virus (SHIV)89.6P and prevents the CD4 T cell decline and disease onset in cynomolgus monkeys. No signs of virus replication were found in five out of seven vaccinated macaques for almost 1 year of follow-up. Since the inoculated virus (derived from rhesus or from cynomolgus macaques) is shown to be highly pathogenic in cynomolgus macaques, the results indicate efficacy of Tat vaccination in protection against highly pathogenic virus challenge. Finally, the studies of the Tat-specific immunological responses indicate a correlation of protection with a cytotoxic T cell response. Thus, a Tat-based vaccine is a promising candidate for preventive and therapeutic vaccination in humans. [source] Glial cell line-derived neurotrophic factor protects astrocytes from staurosporine- and ischemia- induced apoptosisJOURNAL OF NEUROSCIENCE RESEARCH, Issue 15 2007Albert Cheung Hoi Yu Abstract Glial cell line-derived neurotrophic factor (GDNF) promotes the survival and functions of neurons. It has been shown to be a promising candidate in the treatment of ischemia and other neurodegenerative diseases. We transfected mouse astrocytes in primary cultures with a human GDNF gene and found that their conditioned medium could not only support the growth and survival of cultured dopaminergic neurons but also protect astrocytes from staurosporine- and ischemia-induced apoptosis. This indicated that these transfected astrocytes could release GDNF. A similar protective effect on astrocytes against apoptosis was evident when recombinant human GDNF was used. Moreover, GDNF reduced caspase-3 activity but not that of caspase-1 in cultured astrocytes after ischemia treatment. Thus, GDNF protects astrocytes from apoptosis by inhibiting the activation of caspase-3. © 2007 Wiley-Liss, Inc. [source] FGF23 is a putative marker for bone healing and regenerationJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 9 2009Sascha Goebel Abstract Besides numerous other factors, fibroblast growth factor receptor (FGFR) signaling is involved in fracture healing and bone remodeling. FGF23 is a phosphatonin produced by osteoblastic cells, which signals via FGFR1, thereby exerting effects in bone and kidney. We analyzed if serum FGF23 levels might be an indicator to predict fracture healing and union. FGF23 (C-Term) was elevated on day 3 postoperatively in 55 patients sustaining an exchange of total hip implants due to aseptic loosening. A prospective study of 40 patients undergoing primary hip arthroplasty also showed elevated FGF23 (C-Term) but no change in FGF23 (intact) levels on days 1, 4, and 10 postoperatively. Serum phosphate and phosphate clearance stayed within normal ranges. FGF23 mRNA expression in ovine callus was compared between a standard and delayed course of osteotomy healing. In the standard model, a marked increase in FGF23 mRNA expression compared to the delayed healing situation was observed. Immunohistochemical analysis showed FGF23 production of osteoblasts and granulation tissue in the fracture callus during bone healing. In conclusion, FGF23 is involved in bone healing, can be measured by a sensitive assay in peripheral blood, and is a promising candidate as an indicator for healing processes prone to reunion versus nonunion. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res [source] Gas-solids flow behavior: CFB riser vs. downerAICHE JOURNAL, Issue 9 2001H. Zhang Comparisons are made in a circulating fluidized-bed riser/downer system between a 15.1 m high, 0.10 m ID riser and a 9.3 m high, 0.10 m ID downer, based on the measurements of the radial distributions of the local solids holdups and local particle velocities along the two columns. Although the core-annulus flow structures exist in both the riser and downer, the radial flow structure in the downer differs largely from that in the riser. The radial distributions of solids holdup and particle velocity in the downer are much more uniform than those in the riser, thus ensuring the low back mixing and the narrow particle residence time distribution in the downer. The axial flow structure in the downer is also more uniform than that in the riser. Due to the high particle acceleration and the high particle velocity in the downer, the overall solids holdup is significantly lower than that in the riser. The microflow structure in the downer, characterized by the low intermittency indices, is also more uniform than that in the riser. These key properties of the downer make it a very promising candidate for industrial applications where short reaction times and high product selectivity are required. [source] Microstructure and Relaxor Behavior of Dense Fine-Grain FeTiTaO6 CeramicsJOURNAL OF THE AMERICAN CERAMIC SOCIETY, Issue 9 2010Yun Shi A new type of FeTiTaO6 ceramics with a high density was synthesized by the solid-state method. X-ray diffraction and scanning electron microscopy patterns indicate that the specimens exhibit a rutile structure and the mean particle size was about 200,300 nm. The heterovalent substitutions of Fe3+ and Ta5+ at Ti4+ site drive the incipient ferroelectric to the relaxor behavior, and a strong dispersion of the maximum dielectric permittivity appears around Tm, which shifts towards higher temperatures with the increasing frequency. The variation of Tm with frequency follows the Vogel,Fulcher relationship well, wherein Ea=0.068 eV, Tf=508 K, and f0=109 Hz. These results indicate that the nonperovskite-type FeTiTaO6 ceramic is a promising candidate for lead-free relaxor ferroelectrics in practical applications. [source] Formation of Silicon-Doped Boron Nitride Bamboo Structures Via Pyrolysis of a Polymeric PrecursorJOURNAL OF THE AMERICAN CERAMIC SOCIETY, Issue 2 2006Yi Fan In this paper, we report the growth of bamboo-like silicon-doped boron nitride nanotubes via catalyst-assisted pyrolysis of a boron-containing polymeric precursor. The morphologies and structures of the nanotubes were characterized using electron microscopy and Raman spectroscopy. Two types of nanotubes are observed, one from a base-growth mode and the other from a tip-growth mode. The type II nanotubes contain encapsulated catalytic nanoparticles at the tip of every compartment. This unique structure is a promising candidate for applications in many nanodevices. [source] Transparent Anatase Nanocomposite Films by the Sol,Gel Process at Low TemperaturesJOURNAL OF THE AMERICAN CERAMIC SOCIETY, Issue 1 2000Atsunori Matsuda We have successfully prepared transparent anatase nanocomposite films on various types of substrates, including organic polymers, using the sol,gel method at temperatures <100°C under ambient pressure. This novel process is based on the findings that (i) anatase nanocrystals are uniquely formed in sol,gel-derived SiO2,TiO2 films that have been subjected to a hot-water treatment, and (ii) the addition of an organic polymer such as poly(ethylene glycol) in the films accelerates the formation of anatase nanocrystals. The film coating on the substrates is a promising candidate for use as a photocatalyst to decompose environmental pollutants and harmful microorganisms. [source] Mesalazine inhibits the , -catenin signalling pathway acting through the upregulation of ,-protocadherin gene in colo-rectal cancer cellsALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 1 2010S. PARENTI Summary Background, Several reports indicate that mesalazine (5-aminosalicylic acid, 5-ASA) is a promising candidate for the chemoprevention of colo-rectal cancer because of its ability to reach the purpose avoiding the unwanted side effects usually associated with prolonged administration of nonsteroidal anti-inflammatory drugs. This activity of 5-ASA is probably the consequence of a number of effects determined on colo-rectal cancer cells, consisting of reduced proliferation, increased apoptosis and activation of cell cycle checkpoints and DNA repair processes. A recent observation has suggested that inhibition of ,-catenin signalling could induce these cellular effects. Aim, To characterize better the capacity of 5-ASA to inhibit the ,-catenin signalling pathway. Methods, Genes belonging to the ,-catenin signalling pathway were analysed in colo-rectal cancer cell lines treated with 5-ASA using a combination of laboratory assays that are able to detect their phenotypic expression and functional activity. Results, The results obtained indicated that 5-ASA induces the expression of a protein called ,-protocadherin that belongs to the cadherin superfamily and is able to sequester ,-catenin on the plasmatic membrane of treated cells hampering its function. Conclusion, These findings suggest that ,-protocadherin might be employed as a biological marker to monitor the chemopreventive efficacy of 5-ASA. [source] Immunogenicity of CIGB-230, a therapeutic DNA vaccine preparation, in HCV-chronically infected individuals in a Phase I clinical trialJOURNAL OF VIRAL HEPATITIS, Issue 3 2009L. Alvarez-Lajonchere Summary., Hepatitis C virus (HCV) is a worldwide health problem. No vaccine is available against this pathogen and therapeutic treatments currently in use are of limited efficacy. In the present study, the immunogenicity of the therapeutic vaccine candidate CIGB-230, based on the mixture of pIDKE2, a plasmid expressing HCV structural antigens, with a recombinant HCV core protein, Co.120, was evaluated. CIGB-230 was administered by intramuscular injection on weeks 0, 4, 8, 12, 16 and 20 to 15 HCV-chronically infected individuals, non-responders to previous treatment with interferon (IFN) plus ribavirin. Interestingly, following the final immunization, neutralizing antibody responses against heterologous viral pseudoparticles were modified in eight individuals, including six de novo responders. In addition, 73% of vaccinees exhibited specific T cell proliferative response and T cell IFN-gamma secretory response 24 weeks after primary immunization with CIGB-230. Furthermore, 33.3% of individuals developed de novo cellular immune response against HCV core and the number of patients (46.7% at the end of treatment) with cellular immune response against more than one HCV structural antigen increased during vaccination (P = 0.046). In addition, despite persistent detection of HCV RNA, more than 40% percent of vaccinated individuals improved or stabilized liver histology, particularly reducing fibrosis, which correlated with cellular immune response against more than one HCV antigen (P = 0.0053). In conclusion, CIGB-230 is a promising candidate for effective therapeutic interventions based on its ability for enhancing the immune response in HCV chronically infected individuals. [source] | ||||||||||||||||||||||||||||||||||||||||