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Selected AbstractsTumoral and tissue-specific expression of the major human ,-tubulin isotypes,CYTOSKELETON, Issue 4 2010Luis J. Leandro-García Abstract The ,-tubulins are microtubule components encoded by a multigene family, which produces slightly different proteins with complex expression patterns. Several widely used anticancer drugs base their activity on ,-tubulin binding, microtubule dynamics alteration, and cell division blockage. The expression of these drug targets in tumoral and normal cells could be of crucial importance for therapy outcome, unfortunately, the complex ,-tubulin expression patterns have been poorly characterized in human. In this study, we developed a quantitative RT-PCR technique that accurately determines the mRNA expression of the eight human ,-tubulin isotypes, encoding class I, IIa, IIb, III, IVa, IVb, V, and VI and applied it to 21 nontumoral tissues and 79 tumor samples belonging to seven cancer types. In the nontumoral tissues, we found that, overall, TUBB (I), TUBB2C (IVb), and TUBB6 (V) were ubiquitous, TUBB1(VI) was hematopoietic cell-specific, and TUBB2A (IIa), TUBB2B (IIb), TUBB3 (III), and TUBB4 (IVa) had high expression in brain; however, the contribution of the different isotypes to the total ,-tubulin content varied for each tissue and had a complex pattern. In tumoral tissues, most isotypes exhibited an altered expression in specific tumor types or related to tumoral characteristics. In general, TUBB3 showed a great increase in expression while TUBB6 expression was largely decreased in most tumors. Thus, normal tissues showed a complex ,-tubulin isotype distribution, which could contribute to the toxicity profile of the microtubule-binding drugs. In addition, the specific isotypes significantly altered in tumors might represent markers for drug response. © 2010 Wiley-Liss, Inc. [source] Expression of zebrafish nos2b surrounds oral cavityDEVELOPMENTAL DYNAMICS, Issue 6 2008Kar-Lai Poon Abstract Inducible nitric oxide synthase (NOS2) catalyzes the production of nitric oxide (NO), and is one of the factors establishing innate immunity. In zebrafish, Nos2 is represented by nos2a and nos2b. Here, we report the cloning and expression pattern of the zebrafish nos2b gene, which does not seem to participate in induced immune response. nos2b was mapped to zebrafish linkage group 15. The spatial and temporal expression pattern of nos2b in embryonic zebrafish was analyzed by whole-mount in situ hybridization. nos2b is expressed constitutively in two primordia located along the ventral midline. The first group of cells contributes to the neurohypophysis. Initially at the level of the ventral hindbrain, the second group of cells migrates closely with the thyroid primordium to its final position at the basihyal by 3 dpf. Thus, the analysis of expression pattern of nos2b reveals complex morphogenetic movements resulting in its expression surrounding the oral cavity. Developmental Dynamics 237:1662,1667, 2008. © 2008 Wiley-Liss, Inc. [source] Timing and duration of developmental nicotine exposure contribute to attenuation of the tadpole hypercapnic neuroventilatory responseDEVELOPMENTAL NEUROBIOLOGY, Issue 7 2009Cord M. Brundage Abstract The ability for air-breathing vertebrates to adjust ventilation in response to increased CO2 (hypercapnia) is fundamental to maintaining pH homeostasis. Developmental nicotine exposure has been shown to impair tadpole neuroventilatory responses to hypercapnia following 8,12 weeks of exposure. It is not clear, however, to what extent the timing of exposure during development and/or the duration over which the exposure takes place contribute to this impairment. Here, tadpoles were exposed to 30 ,g/L of nicotine for 3- or 10-week durations, either early or late in tadpole development. Correlates of tadpole lung neuroventilation were monitored during normocapnic (1.5% CO2) and hypercapnic (5% CO2) conditions of isolated brainstems. Preparations derived from early metamorphic tadpoles failed to increase lung neuroventilation in response to hypercapnia whether they had been exposed to nicotine for 3 or 10 weeks. Preparations derived from late metamorphic tadpoles failed to respond to hypercapnia after being exposed to nicotine for 10 weeks. These results suggest that both the developmental timing and duration of exposure are important when considering nicotine's effect on the hypercapnic neuroventilatory response. © 2009 Wiley Periodicals, Inc. Develop Neurobiol 2009 [source] Time course analysis of gene expression during light-induced photoreceptor cell death and regeneration in albino zebrafishDEVELOPMENTAL NEUROBIOLOGY, Issue 8 2007Sean C. Kassen Abstract Constant intense light causes apoptosis of rod and cone photoreceptors in adult albino zebrafish. The photoreceptors subsequently regenerate from proliferating inner nuclear layer (INL) progenitor cells that migrate to the outer nuclear layer (ONL) and differentiate into rods and cones. To identify gene expression changes during this photoreceptor regeneration response, a microarray analysis was performed at five time points during the light treatment. The time course included an early time point during photoreceptor death (16 h), later time points during progenitor cell proliferation and migration (31, 51, and 68 h) and a 96 h time point, which likely corresponds to the initial photoreceptor differentiation. Mean expression values for each gene were calculated at each time point relative to the control (0 h light exposure) and statistical analysis by one-way ANOVA identified 4567 genes exhibiting significant changes in gene expression along the time course. The genes within this data set were clustered based on their temporal expression patterns and proposed functions. Quantitative real-time PCR validated the microarray expression profiles for selected genes, including stat3 whose expression increased markedly during the light exposure. Based on immunoblots, both total and activated Stat3 protein expression also increased during the light treatment. Immunolocalization of Stat3 on retinal tissue sections demonstrated increased expression in photoreceptors and Müller glia by 16 h of light exposure. Some of the Stat3-positive Müller cells expressed PCNA at 31 h, suggesting that Stat3 may play a role in signaling a subset of Müller cells to proliferate during the regeneration response. © 2007 Wiley Periodicals, Inc. Develop Neurobiol, 2007. [source] Comparison of the effects of HGF, BDNF, CT-1, CNTF, and the branchial arches on the growth of embryonic cranial motor neuronsDEVELOPMENTAL NEUROBIOLOGY, Issue 2 2002Arifa Naeem Abstract In the developing embryo, axon growth and guidance depend on cues that include diffusible molecules. We have shown previously that the branchial arches and hepatocyte growth factor (HGF) are growth-promoting and chemoattractant for young embryonic cranial motor axons. HGF is produced in the branchial arches of the embryo, but a number of lines of evidence suggest that HGF is unlikely to be the only factor involved in the growth and guidance of these axons. Here we investigate whether other neurotrophic factors could be involved in the growth of young cranial motor neurons in explant cultures. We find that brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF) and cardiotrophin-1 (CT-1) all promote the outgrowth of embryonic cranial motor neurons, while glial cell line-derived neurotrophic factor (GDNF) and neurotrophin-3 (NT-3) fail to affect outgrowth. We next examined whether HGF and the branchial arches had similar effects on motor neuron subpopulations at different axial levels. Our results show that HGF acts as a generalized rather than a specific neurotrophic factor and guidance cue for cranial motor neurons. Although the branchial arches also had general growth-promoting effects on all motor neuron subpopulations, they chemoattracted different axial levels differentially, with motor neurons from the caudal hindbrain showing the most striking response. © 2002 Wiley Periodicals, Inc. J Neurobiol 51: 101,114, 2002 [source] Drosophila neuropeptide F mediates integration of chemosensory stimulation and conditioning of the nervous system by foodDEVELOPMENTAL NEUROBIOLOGY, Issue 1 2001Ping Shen Abstract The conserved neuropeptide Y (NPY) signaling pathway has been strongly implicated in the stimulation of food uptake in vertebrates as well as in the regulation of food conditioned foraging behaviors of Caenorhabditis elegans. Using in situ RNA hybridization and immunocytochemistry, we report the neuronal network of Drosophila neuropeptide F (dNPF), a human NPY homologue, in the larval central nervous system and its food-dependent modifications. We provide indications that gustatory stimulation by sugar, but not its ingestion or metabolism, is sufficient to trigger long-term, dose-dependent alterations of the dNPF neuronal circuit through both dnpf activation and increased synaptic transmission. Our results strongly suggest that the dNPF neuronal circuit is an integral part of the sensory system that mediates food signaling, providing the neural basis for understanding how invertebrate NPY regulates food response. © 2001 John Wiley & Sons, Inc. J Neurobiol 47: 16,25, 2001 [source] The 2004 Madrid train bombings: an analysis of pre-hospital managementDISASTERS, Issue 1 2008Alejandro López Carresi The terrorist train bombings in Madrid, Spain, on 11 March 2004 triggered a swift and massive medical response., This paper analyses the pre-hospital response to the attacks to gain insight into current trends in disaster management among Madrid's Emergency Medical Services (EMSs). To this end, the existing emergency planning framework is described, the basic structures of the different EMSs are presented, and the attacks are briefly depicted before consideration is given to pre-hospital management. Finally, an explanation of the main underlying misconceptions in emergency planning and management in Madrid is provided to aid understanding of the origins of some of the problems detected during the response. These are attributable mainly to inappropriate planning rather than to mistakes in field-level decision-making. By contrast, many of the successes are attributable to individual initiatives by frontline medics who compensated for the lack of clear command by senior managers by making adaptive and flexible decisions. [source] Hepatitis C virus escape from the interferon regulatory factor 3 pathway by a passive and active evasion strategy,HEPATOLOGY, Issue 5 2007Marco Binder Hepatitis C virus (HCV) has been known to replicate with extremely varying efficiencies in different host cells, even within different populations of a single human hepatoma cell line, termed Huh-7. Several reports have implicated the retinoic-acid inducible gene I (RIG-I)/ interferon regulatory factor 3 (IRF-3) pathway of the innate antiviral response with differences in host cell permissiveness to HCV. To investigate the general impact of the IRF-3 response onto HCV replication in cell culture, we generated an ample array of stable Huh-7 cell lines with altered IRF-3 responsiveness. Neither blocking IRF-3 activation in various host cells by expression of dominant negative RIG-I or HCV NS3/4A protease nor reconstitution of RIG-I signaling in Huh7.5, a cell clone known to be defective in this pathway, had any impact on HCV replication. Only by overexpressing constitutively active RIG-I or the signaling adaptor Cardif (also known as interferon-beta promoter stimulator 1, mitochondrial anti-viral signaling protein, or virus-induced signaling adaptor), both leading to a stimulation of the IRF-3 pathway in the absence of inducers, was HCV replication significantly inhibited. We therefore assessed the extent of RIG-I, dependent IRF-3 activation by different species of RNA, including full-length HCV genomes and HCV RNA duplexes, and observed strong induction only in response to double-stranded RNAs. Conclusion: Based on these findings, we propose a refined model of innate immune escape by HCV involving limited initial induction and stringent subsequent control of the IRF-3 response. (HEPATOLOGY 2007.) [source] Upregulation of the tumor suppressor gene menin in hepatocellular carcinomas and its significance in fibrogenesis,HEPATOLOGY, Issue 5 2006Pierre J. Zindy The molecular mechanisms underlying the progression of cirrhosis toward hepatocellular carcinoma were investigated by a combination of DNA microarray analysis and literature data mining. By using a microarray screening of suppression subtractive hybridization cDNA libraries, we first analyzed genes differentially expressed in tumor and nontumor livers with cirrhosis from 15 patients with hepatocellular carcinomas. Seventy-four genes were similarly recovered in tumor (57.8% of differentially expressed genes) and adjacent nontumor tissues (64% of differentially expressed genes) compared with histologically normal livers. Gene ontology analyses revealed that downregulated genes (n = 35) were mostly associated with hepatic functions. Upregulated genes (n = 39) included both known genes associated with extracellular matrix remodeling, cell communication, metabolism, and post-transcriptional regulation gene (e.g., ZFP36L1), as well as the tumor suppressor gene menin (multiple endocrine neoplasia type 1; MEN1). MEN1 was further identified as an important node of a regulatory network graph that integrated array data with array-independent literature mining. Upregulation of MEN1 in tumor was confirmed in an independent set of samples and associated with tumor size (P = .016). In the underlying liver with cirrhosis, increased steady-state MEN1 mRNA levels were correlated with those of collagen ,2(I) mRNA (P < .01). In addition, MEN1 expression was associated with hepatic stellate cell activation during fibrogenesis and involved in transforming growth factor beta (TGF-,),dependent collagen ,2(I) regulation. In conclusion, menin is a key regulator of gene networks that are activated in fibrogenesis associated with hepatocellular carcinoma through the modulation of TGF-, response. (HEPATOLOGY 2006;44:1296,1307.) [source] The antidepressant effects of running and escitalopram are associated with levels of hippocampal NPY and Y1 receptor but not cell proliferation in a rat model of depressionHIPPOCAMPUS, Issue 7 2010Astrid Bjřrnebekk Abstract One hypothesis of depression is that it is caused by reduced neuronal plasticity including hippocampal neurogenesis. In this study, we compared the effects of three long-term antidepressant treatments: escitalopram, voluntary running, and their combination on hippocampal cell proliferation, NPY and the NPY-Y1 receptor mRNAs, targets assumed to be important for hippocampal plasticity and mood disorders. An animal model of depression, the Flinders Sensitive Line (FSL) rat, was used and female rats were chosen because the majority of the depressed population is females. We investigated if these treatments were correlated to immobility, swimming, and climbing behaviors, which are associated with an overall, serotonergic-like and noradrenergic-like antidepressant response, in the Porsolt swim test (PST). Interestingly, while escitalopram, running and their combination increased the number of hippocampal BrdU immunoreactive cells, the antidepressant-like effect was only detected in the running group and the group with access both to running wheel and escitalopram. Hippocampal NPY mRNA and the NPY-Y1 receptor mRNA were elevated by running and the combined treatment. Moreover, correlations were detected between NPY mRNA levels and climbing and cell proliferation and NPY-Y1 receptor mRNA levels and swimming. Our results suggest that increased cell proliferation is not necessarily associated with an antidepressant effect. However, treatments that were associated with an antidepressant-like effect did regulate hippocampal levels of mRNAs encoding NPY and/or the NPY-Y1 receptor and support the notion that NPY can stimulate cell proliferation and induce an antidepressant-like response. © 2009 Wiley-Liss, Inc. [source] Magnitude and polarization of P53-specific T-helper immunity in connection to leukocyte infiltration of colorectal tumorsINTERNATIONAL JOURNAL OF CANCER, Issue 3 2003Sjoerd H. van der Burg Abstract The tumor antigen p53 is mutated frequently and overexpressed in colorectal cancer. As a result, patients with this type of cancer commonly display p53-specific T-helper (Th) immunity. Examination of the cytokines produced by these Th-cells showed that a majority of the proliferative p53-specific T cell cultures produced none of the key cytokines (IFN,, TNF,, IL-4, IL-5 or IL-10), indicating that these p53-specific Th-responses are not polarized. In patients who exhibited p53-specific reactivity against multiple p53-epitopes, non-polarized responses could be found side by side with polarized Th-responses that produced INF, or other cytokines such as IL-10. Patients who exhibited p53-specific IFN,-producing Th cell-immunity before surgical excision of the tumor displayed higher numbers of tumor infiltrating intraepithelial leukocytes (p = 0.04) than patients lacking such responses, suggesting that the systemic presence of p53-specific Th-cells positively affects local tumor-immunity. Our data concerning the polarization-state of p53-specific Th immunity in colorectal cancer patients support the use of vaccine formulations that induce strong Th1-polarized p53-specific immunity to ensure proper (re-)programming of the anti-tumor response. © 2003 Wiley-Liss, Inc. [source] Ionizing radiation as a response-enhancing agent for CD95-mediated apoptosisINTERNATIONAL JOURNAL OF CANCER, Issue 4 2001Michael A. Sheard Ph.D. Abstract CD95 (Fas/APO-1) is a death receptor on the surface of a wide variety of cell types. In most cells examined, ionizing radiation acts as a response-enhancing agent for CD95-mediated cell death. Although DNA-damaging radiation appears to modulate CD95-mediated signals through multiple mechanisms, the only well-characterized mechanism is activation of the tumor-suppressor protein p53, which transcriptionally regulates the expression of CD95 on various cell types. The ligand for CD95 is expressed by activated lymphocytes and natural-killer cells, which produce factors that sensitize cells resistant to CD95-mediated cell death. Ligation of CD95 on irradiated tumor cells might be achievable using emerging modalities that reactivate the stalled anti-tumor immune response. © 2001 Wiley-Liss, Inc. [source] A fast response resistive thin film humidity sensor based on poly(4-vinylpyridine) and poly(glycidyl methacrylate)JOURNAL OF APPLIED POLYMER SCIENCE, Issue 6 2007Y. S. Chen Abstract Humidity sensitive films with the structure of an interpenetrating network were prepared through simultaneous quaternization and crosslinking of poly(4-vinylpyridine) and poly(glycidyl methacrylate) with 1,4-dibromobutane and diethyltriamine, respectively, on the interdigital electrodes. The effect of the composition of humidity sensitive film and the concentration of dip-coating solution on the humidity sensitive properties of the sensors have been investigated. The humidity sensors so prepared exhibit little hysteresis (<1% RH [relative humidity]) and the response time for adsorption and desorption between 80% RH and 54% RH is about 21 s and 3 s, respectively, suggesting a very fast response. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2007 [source] Endogenous antioxidant defence system in rat liver following mercury chloride oral intoxicationJOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 3 2005Inmaculada Bando Abstract Mercury is a highly toxic metal which induces oxidative stress. Superoxide dismutases, catalase, and glutathion peroxidase are proteins involved in the endogenous antioxidant defence system. In the present study rats were administered orally, by gavage, a single daily dose of HgCl2 for three consecutive days. In order to find a relation between the proteins involved in the antioxidant defence and mercury intoxication, parameters of liver injury, redox state of the cells, as well as intracellular protein levels and enzyme activities of Mn-dependent superoxide dismutase (MnSOD), Cu-Zn-dependent superoxide dismutase (CuZnSOD), catalase, and glutathione peroxidase (GPx) were assayed both in blood and in liver homogenates. HgCl2 at the doses of 0.1 mg/kg produced liver damage which that was detected by a slight increase in serum alanine aminotransferase and gamma glutamyl transferase. Hepatic GSH/GSSG ratio was assayed as a parameter of oxidative stress and a significant decrease was detected, as well as significant increases in enzyme activities and protein levels of hepatic antioxidant defence systems. Changes in both MnSOD and CuZnSOD were parallel to those of liver injury and oxidative stress, while the changes detected in catalase and GPx activities were progressively increased along with the mercury intoxication. Other enzyme activities related to the glutathione redox cycle, such as glutathione reductase (GR) and glucose-6-phosphate dehydrogenase (G6PDH), also increased progressively. We conclude that against low doses of mercury that produce a slight oxidative stress and liver injury, the response of the liver was to induce the synthesis and activity of the enzymes involved in the endogenous antioxidant system. The activities of all the enzymes assayed showed a rapidly induced coordinated response. © 2005 Wiley Periodicals, Inc. J Biochem Mol Toxicol 19:154,161, 2005; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20067 [source] Timing of ibuprofen use and bone mineral density adaptations to exercise trainingJOURNAL OF BONE AND MINERAL RESEARCH, Issue 6 2010Wendy M Kohrt Abstract Prostaglandins (PGs) are essential signaling factors in bone mechanotransduction. In animals, inhibition of the enzyme responsible for PG synthesis (cyclooxygenase) by nonsteroidal anti-inflammatory drugs (NSAIDs) blocks the bone-formation response to loading when administered before, but not immediately after, loading. The aim of this proof-of-concept study was to determine whether the timing of NSAID use influences bone mineral density (BMD) adaptations to exercise in humans. Healthy premenopausal women (n,=,73) aged 21 to 40 years completed a supervised 9-month weight-bearing exercise training program. They were randomized to take (1) ibuprofen (400,mg) before exercise, placebo after (IBUP/PLAC), (2) placebo before, ibuprofen after (PLAC/IBUP), or (3) placebo before and after (PLAC/PLAC) exercise. Relative changes in hip and lumbar spine BMD from before to after exercise training were assessed using a Hologic Delphi-W dual-energy X-ray absorptiometry (DXA) instrument. Because this was the first study to evaluate whether ibuprofen use affects skeletal adaptations to exercise, only women who were compliant with exercise were included in the primary analyses (IBUP/PLAC, n,=,17; PLAC/PLAC, n,=,23; and PLAC/IBUP, n,=,14). There was a significant effect of drug treatment, adjusted for baseline BMD, on the BMD response to exercise for regions of the hip (total, p,<,.001; neck, p,=,.026; trochanter, p,=,.040; shaft, p,=,.019) but not the spine (p,=,.242). The largest increases in BMD occurred in the group that took ibuprofen after exercise. Total-hip BMD changes averaged ,0.2%,±,1.3%, 0.4%,±,1.8%, and 2.1%,±,1.7% in the IBUP/PLAC, PLAC/PLAC, and PLAC/IBUP groups, respectively. This preliminary study suggests that taking NSAIDs after exercise enhances the adaptive response of BMD to exercise, whereas taking NSAIDs before may impair the adaptive response. © 2010 American Society for Bone and Mineral Research [source] Loss of E-cadherin mediated cell,cell adhesion as an early trigger of apoptosis induced by photodynamic treatmentJOURNAL OF CELLULAR PHYSIOLOGY, Issue 1 2005Sergio Galaz Photodynamic treatment with different photosensitizers (PSs) can result in the specific induction of apoptosis in many cell types. It is commonly accepted that this apoptotic response depends on the mitochondrial accumulation of the PS. Accumulation in other cellular organelles, such as lysosomes or the Golgi complex, and subsequent photodamage resulting in an apoptotic process has been also described. However, the role played by cell adhesion in apoptosis induced in epithelial cells after photodynamic treatment is not well characterized. Here, we have used a murine keratinocyte line, showing a strong dependence on E-cadherin for cell,cell adhesion and survival, to analyze the relevance of this adhesion complex in the context of zinc(II)-phthalocyanine (ZnPc) photodynamic treatment. We report that under apoptotic conditions, ZnPc phototreatment induces a rapid disorganization of the E-cadherin mediated cell,cell adhesion, which largely preceded both the detachment of cells from the substrate, via ,-1 integrins and the induction of apoptotic mitochondrial markers. Therefore, the alteration in E-cadherin, ,- and ,-catenins adhesion proteins preceded the release of cytochrome c (cyt c) from mitochondria to the cytosol and the activation of caspase 3. In addition, blocking E-cadherin function with a specific antibody (Decma-1) induced apoptosis in this cell system. These results strongly suggest that the E-cadherin adhesion complex could be the primary target of ZnPc phototreatment, and that loss of E-cadherin mediated cell adhesion after early photodamage triggers an apoptotic response. © 2005 Wiley-Liss, Inc. [source] Superiority of a functional leukocyte adhesiveness/aggregation test over the white blood cell count to discriminate between mild and significant inflammatory response in patients with acute bacterial infectionsJOURNAL OF CLINICAL LABORATORY ANALYSIS, Issue 4 2002Ori Rogowski Abstract Electronic cell counters may underestimate the white blood cell count (WBCC) in the presence of aggregated leukocytes. In the present study we focused on the possibility of using a functional, as opposed to an anatomic, count to circumvent this eventual underestimation. A model of bacterial infection was used because of the importance of leukocytosis in the physician's clinical decision-making process. There were 35 patients with low C-reactive protein (CRP) concentrations (0.5,4.9 mg/dL), 45 with intermediate (5,9.9 mg/dL), and 120 with relatively high (>10 mg/dL) CRP concentrations. A significant (P=0.008) difference was noted between the state of leukocyte adhesiveness/aggregation in the peripheral blood of individuals with low CRP concentrations (3.5%±4.3%) and those with high CRP concentrations (7.4%±8%), while there was no significant difference in the respective number of WBCs per cubic millimeter (cmm) (11,600 ± 5,500 and 14,000 ± 7,200, respectively). We raise the possibility that a functional test might be superior over an anatomic count in patients with acute bacterial infection and a significant acute phase response. © 2002 Wiley-Liss, Inc. [source] A New Biological Matrix for Septal OcclusionJOURNAL OF INTERVENTIONAL CARDIOLOGY, Issue 2 2003CHRISTIAN JUX, M.D. The ideal septal occluder scaffold should promote the healthiest and most complete healing response possible while eventually facilitating the full resorption of the material, leaving "native" tissue behind. An excellent biocompatibility of the scaffold tissue is a prerequisite for quick, complete, and firm ingrowth of the device, optimizing outcomes and minimizing the potential for complications. Intestinal collagen layer (ICL) is a highly purified (acellular) bioengineered type-1 collagen derived from porcine submucosa. It is gradually resorbed by the host organism and subsequently replaced by the host tissue. CardioSEAL® occluders were modified by substituting the conventional polyester fabric for an intestinal collagen layer (ICL). Percutaneous transcatheter closure of interventionally created atrial septal defects was performed in lambs using these modified occluders. A complete pathomorphological investigation including histology was carried out after 2, 4, and 12 weeks follow-up. Standard CardioSEAL implants served as a control group. After 2 weeks in vivo the devices were already covered completely by neo-endothelium. Compared with the conventional synthetic scaffold, ICL devices showed a quicker endothelialization, decreased thrombogenicity, and superior biocompatibility with no significant cellular infiltration observed in the histology of explants with ICL fabrics. After 3 months in vivo the collagen layer remained mechanically intact, but began to show the first histological signs of mild disintegration, gradual resorption, and remodeling. In conclusion, short-term results from preliminary in vivo experiments using a bioengineered collagen matrix as the occluder tissue scaffold showed excellent biocompatibility. This resulted in superior overall results: quicker endothelialization, a decreased thrombogenicity, and decreased immunological host response. (J Interven Cardiol 2003;16:149,152) [source] Conserved cellular function and stress-mediated regulation among members of the proteolipid protein familyJOURNAL OF NEUROSCIENCE RESEARCH, Issue 6 2010María E. Fernández Abstract Chronic stress causes morphological alterations in the hippocampus of rodents and tree shrews, including atrophy of CA3 dendrites and loss of synapses. The molecular mechanisms underlying these structural changes remain largely unknown. We have previously identified M6a as a stress responsive gene and shown that M6a is involved in filopodium/spine outgrowth and, likely, synapse formation. M6a belongs to the proteolipid protein (PLP) family, all of their members having four transmembrane domains that allow their localization at the plasma membrane. In the present work, we analyzed other members of this family, the closely related M6b as well as PLP and its splice variant DM20. We found that chronic restraint stress in mice reduces M6b and DM20, but not PLP, mRNA levels in the hippocampus. In addition, M6b and DM20, but again not PLP, induce filopodium formation in primary cultures of hippocampal neurons. Several M6b protein isoforms were studied, all of them having similar effects except for the one lacking the transmembrane domains. Our results reveal a conserved cellular function and a stress-mediated regulation among members of the proteolipid protein family, suggesting an involvement of proteolipid proteins in the stress response. © 2009 Wiley-Liss, Inc. [source] Soluble and particulate Co-Cr-Mo alloy implant metals activate the inflammasome danger signaling pathway in human macrophages: A novel mechanism for implant debris reactivityJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 7 2009Marco S. Caicedo Abstract Immune reactivity to soluble and particulate implant debris remains the primary cause of aseptic inflammation and implant loosening. However, the intracellular mechanisms that trigger immune cells to sense and respond to exogenous nonbiological agents such as metal particles or metal ions released from orthopedic implants remain unknown. Recent studies in immunology have outlined the importance of the intracellular inflammasome complex of proteins in sensing danger/stress signals triggered by nonbiological agents in the cytosol of macrophages. We hypothesized that metal implant debris can activate the inflammasome pathway in macrophages that causes caspase-1-induced cleavage of intracellular pro-IL-1, into its mature form, resulting in IL-1, secretion and induction of a broader proinflammatory response. We tested this hypothesis by examining whether soluble cobalt, chromium, molybdenum, and nickel ions and Co-Cr-Mo alloy particles induce inflammasome- mediated macrophage reactivity. Our results demonstrate that these agents stimulate IL-1, secretion in human macrophages that is inflammasome mediated (i.e., NADPH-, caspase-1-, Nalp3-, and ASC-dependent). Thus, metal ion- and particle-induced activation of the inflammasome in human macrophages provides evidence of a novel pathway of implant debris-induced inflammation, where contact with implant debris is sensed and transduced by macrophages into a proinflammatory response. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27: 847,854, 2009 [source] Nucleobases modified azo-polysiloxanes, materials with potential application in biomolecules nanomanipulationJOURNAL OF POLYMER SCIENCE (IN TWO SECTIONS), Issue 18 2007Nicolae Hurduc Abstract Here we show the possibility to obtain azopolysiloxanes modified with nucleobases (adenine and thymine) with potential application in immobilization and nanomanipulation of biomolecules. We propose a photofluidization mechanism based on the concept of the conformational instability, which can explain the presence of the fluid state below the glass transition. The azopolymers were characterized by 1H NMR, GPC, DSC, DTG, UV spectroscopy, AFM analysis, and molecular simulations. Depending on the type of nucleobase used, the surface of the azopolysiloxane film can be structured in different ways under UV irradiation. Photoisomerization studies in solid state were carried out to demonstrate the influence of the operational conditions (presence or absence of natural visible light) on the polymeric film UV response. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 4240,4248, 2007 [source] Investigating science learning for rural elementary school teachers in a professional-development project through three distance-education strategiesJOURNAL OF RESEARCH IN SCIENCE TEACHING, Issue 10 2006Leonard A. Annetta Distance education is a significant topic of discussion within institutions at all levels of education. It is not only significant in terms of finances and student enrollment but also in terms of meaningful learning. The purpose of this study was to determine the relative effectiveness of three distance-education strategies for enhancing the science learning of 94 Midwestern elementary-school teachers participating in a 5-year professional-development project. The three distance-education strategies studied were interactive television with all presenters live in real time (live), interactive television with live discussions wrapped around videotaped presentations (video), and asynchronous, Web-based sessions with streamed videotaped presentations supported by interaction through discussion boards (Web). A repeated measures design was used to analyze the science learning and attitudes of the study participants. Analysis of variance of participants' postsession science scores yielded differences (p,<,0.05) on multiple-choice and constructed-response science subscales. Participants in the live mode outperformed participants in the Web and video modes on all three assessment types (multiple choice, constructed response, and vignettes). Participants in the Web mode outperformed participants in the video mode on multiple choice and constructed response. © 2006 Wiley Periodicals, Inc. J Res Sci Teach 43: 1019,1039, 2006 [source] Dopamine D2 Receptor Binding, Drd2 Expression and the Number of Dopamine Neurons in the BXD Recombinant Inbred Series: Genetic Relationships to Alcohol and Other Drug Associated PhenotypesALCOHOLISM, Issue 1 2003Robert Hitzemann Background: It has not been established to what extent the natural variation in dopamine systems contribute to the variation in ethanol response. The current study addresses this issue by measuring D2 dopamine (DA) receptor binding, the expression of Drd2, the number of midbrain DA neurons in the BXD recombinant inbred (RI) series and then compares these strain means with those previously reported for a variety of ethanol and other drug-related phenotypes. Methods: Data were collected for 21 to 23 of the BXD RI strains and the parental strains. D2 DA receptor autoradiography was performed using 125I-epidepride as the ligand [Kanes S, Dains K, Cipp L, Gatley J, Hitzemann B, Rasmussen E, Sanderson S, Silverman S, Hitzemann R (1996) Mapping the genes for haloperidol-induced catalepsy. J Pharmacol Exp Ther 277:1016,1025]. Drd2 expression was measured using the Affymetrix oligoarray system. Immunocytochemical techniques were used to determine the number of midbrain DA neurons [Hitzemann B, Dains K, Hitzemann R (1994) Further studies on the relationship between dopamine cell density and haloperidol response. J Pharmacol Exp Ther 271:969,976]. Results and Conclusions: The range of difference in receptor binding for the RI strains was approximately 2-fold in all regions examined, the core, the shell of the nucleus accumbens (NAc) and the dorsomedial caudate-putamen (CPu); heritability in all regions was moderate,(h 2,0.35). Drd2 expression in forebrain samples from the RI and parental strains ranged 1.5- to 2-fold and h2 was moderate,0.47. Variation in the number of tyrosine hydroxylase (TH) positive neurons was moderate, 41% and 26% and h2 was low,0.19 and 0.15 for the ventral tegmental area (VTA) and substantia nigra compacta (SNc), respectively. Significant correlations were found between D2 DA receptor binding and the low dose (1.33 g/kg) ethanol stimulant response. (p < 0.002) and between Drd2 expression and conditioned place preference (CPP) (p < 0.0005). No significant correlations were detected between ethanol preference and either receptor binding or Drd2 expression; however, a significant correlation was found between preference and Ncam expression. Ncam is approximately 0.2 Mb from Drd2. Overall, the data suggest ethanol preference and CPP are associated with the expression of Drd2 or closely linked genetic loci. [source] Infliximab dependency in children with Crohn's diseaseALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 7 2009D. DURICOVA Summary Background, Recently, infliximab dependency has been described. Aim, To assess frequency of ID in 82 consecutive Crohn's disease children treated with infliximab 2000,2006 and to describe clinical and genetic predictors of long-term infliximab response. Methods, A phenotype model of infliximab dependency was used to assess treatment response: ,immediate outcome' (30 days after infliximab start) , complete/partial/no response. ,Long-term outcome': (i) prolonged response: maintenance of complete/partial response; (ii) infliximab dependency: relapse ,90 days after intended infliximab cessation requiring repeated infusions to regain complete/partial response or need of infliximab >12 months to sustain response. Polymorphisms TNF -308 A>G, TNF -857 C>T, Casp9 93 C>T, FasL -844 C>T, LTA 252 C>T and CARD15 (R702W, G908R, 1007fs) were analysed. Results, Ninety-four per cent of children obtained complete/partial response. In long-term outcome, 22% maintained prolonged response, 12% had no response, while 66% became infliximab dependent. Perianal disease and no previous surgery were associated with infliximab dependency (OR 5.34, 95% CI: 1.24,22.55; OR 6.7, 95% CI: 1.67,26.61). No association was found with studied polymorphisms. The cumulative probability of surgery 50 months after starting infliximab was 10% in infliximab dependency, 30% in prolonged responders and 70% in nonresponders (P = 0.0002). Conclusions, Sixty-six per cent of children became infliximab dependent. Perianal disease and no surgery prior to infliximab were associated with infliximab dependency phenotype. [source] Outcomes of acute rejection after interferon therapy in liver transplant recipientsLIVER TRANSPLANTATION, Issue 7 2004Sammy Saab Interferon alfa has been increasingly used against recurrent hepatitis C (HCV) disease in post-liver transplant (LT) recipients. A serious potential adverse effect is acute rejection. We reviewed our experience using interferon-based therapy (interferon or pegylated interferon with or without ribavirin) for treating recurrent HCV in LT recipients. Forty-four LT recipients were treated with interferon for recurrent HCV. Five of the 44 patients developed acute rejection during interferon-based therapy. These 5 patients started treatment of 42.4 ± 33.89 months (mean ± SD) after LT. Mean (± SD) histological activity index and fibrosis scores before initiating antiviral therapy were 8.8 (± 1.92) and 2.6 (± 0.55), respectively. Patients were treated for 3.3 ± 2.28 months (mean ± SD) prior to rejection. At the time of rejection, HCV load was not detectable in 4 of the 5 recipients. All 5 patients had tolerated interferon therapy, and none had stopped therapy because of adverse effects. The rejection was successfully treated in 3 patients. In 2 of those 3 patients, cirrhosis eventually developed. In the 2 patients who did not respond to rejection treatment, immediate graft failure occurred, leading to re-LT in 1 patient and death from sepsis in the other. In conclusion, the results indicate that further studies are needed to assess the safety of interferon in LT recipients. Interferon-based therapy may lead to acute rejection and subsequent graft loss and should therefore be used with caution. Treated recipients may also develop progressive cirrhosis despite achieving a sustained virological response. (Liver Transpl 2004;10:859,867.) [source] Novel UWB planar monopole antenna with dual band-notched characteristicsMICROWAVE AND OPTICAL TECHNOLOGY LETTERS, Issue 1 2010Wentao Li Abstract A novel spade-shaped microstrip-fed ultrawideband planar monopole antenna with dual band-notched characteristics is presented. Dual narrow band-notched characteristics are achieved by employing an ,-shaped slot on the radiating patch and a split-ring resonator on the backed side. Experimental results demonstrate that the proposed antenna satisfies the voltage standing wave ratio requirement of less than 2.0 in the frequency band of 3,12 GHz, except two frequency stop-bands of 3.3,3.9 GHz and 5.70,6.05 GHz. Moreover, measured group delay and transmission characteristics indicate that the proposed antenna has good transient response. © 2009 Wiley Periodicals, Inc. Microwave Opt Technol Lett 52: 48,51, 2010; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.24827 [source] All optical multi-tap microwave filter with high sidelobe suppression using peak profile of ASE and one multiwavelength FBGMICROWAVE AND OPTICAL TECHNOLOGY LETTERS, Issue 10 2009Li Xia Abstract A new all optical 10-tap microwave filter is proposed using a broadband amplified spontaneous emission (ASE) light source and a single specially designed multiwavelength FBG. Measured results show that the sidelobe suppression is larger than 20 dB. The filter response is insensitive to the polarization state of light. This technique enables one to obtain a simple and low cost photonic microwave filter with a stable response. © 2009 Wiley Periodicals, Inc. Microwave Opt Technol Lett 51: 2522,2524, 2009; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.24666 [source] A second-order dual-band bandpass filter using a dual-band admittance inverterMICROWAVE AND OPTICAL TECHNOLOGY LETTERS, Issue 5 2008Hualiang Zhang Abstract In this article, a second-order dual-band bandpass filter is designed. The filter consists of two dual-band resonators connected by a dual-band admittance inverter. The dual-band resonator unit is made of two shunt stubs that coordinately produce two resonances. A novel dual-band quarter-wavelength line acts as the admittance inverter, providing suitable admittance transformations. To verify the design concept, a filter working at 2 and 5 GHz is devised and fabricated on Rogers' RO3006 printed circuit boards. In addition, the dual-band filter is connected with a bandstop filter to suppress the unwanted spurious response. © 2008 Wiley Periodicals, Inc. Microwave Opt Technol Lett 50: 1184,1187, 2008; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.23326 [source] A novel crossed slotted patch dual-mode bandpass filter with two transmission zerosMICROWAVE AND OPTICAL TECHNOLOGY LETTERS, Issue 3 2008Sean Wu Abstract This article presents a miniaturized dual-mode bandpass filter (BPF) with two transmission zeros and low insertion-loss using crossed slotted patch resonator. The BPF is mainly formed by a ,/2 patch resonator which is a pair of crossed slots with unequal widths is embedded in the center. By tuning the perturbation element, which resulted from the unequal slot widths along the diagonal, two resonant modes are excited and a pair of transmission zeros are generated to improve the selectivity of the BPF performance. The proposed filter at center frequency (f0) of 1.55 GHz has very good measured characteristics including the bandwidth of 1.49,1.62 GHz (3-dB fractional bandwidth of 8.4%), low insertion loss of 1.74 ± 0.35 dB. The measured filter performance is in good agreement with the simulated response. © 2008 Wiley Periodicals, Inc. Microwave Opt Technol Lett 50: 741,744, 2008; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.23219 [source] Generalized early-time/late-time evolutionary programming-based CLEANMICROWAVE AND OPTICAL TECHNOLOGY LETTERS, Issue 1 2008In-Sik Choi Abstract A novel method, which is called generalized early-time/late-time evolutionary programming (EP)-based CLEAN algorithm, is proposed for simultaneous extraction of the scattering centers and natural resonance frequencies of a radar target. This algorithm uses a duality between the temporal late-time response and spectral early-time response. © 2007 Wiley Periodicals, Inc. Microwave Opt Technol Lett 50: 208,210, 2008; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.23032 [source] | ||||||||||||||||||||||||||||