Home About us Contact
|
Home About us Contact | ||
|
|
||
Local Production (local + production)
Selected AbstractsMicrovessels Promote Motor Nerve Survival and Regeneration Through Local VEGF Release Following Ectopic ReattachmentMICROCIRCULATION, Issue 8 2004SHAWN E. BEARDEN ABSTRACT Objectives: Nerves and blood vessels form a close association during embryogenesis. Growth and guidance factors initially attributed to either nerves or vessels are now known to affect both tissues; prominent among these is vascular endothelial growth factor (VEGF). The authors investigated whether axons would associate with blood vessels in a regenerating system and questioned whether VEGF is integral to neurotization following axotomy. Methods: In hamsters 8,12 weeks of age, the accessory nerve (CN XI) to the retractor muscle of the cheek pouch was cut and the proximal stump was reattached ectopically onto the muscle. Vascular casting and immunolabeling were used to quantify the extent of neurovascular association during regeneration. A role for VEGF was investigated using immunolocalization of VEGF and its receptor (sVEGFR2) as well as local sequestration of VEGF with soluble receptor (sVEGFR1). Results: Regenerating axons aligned with microvessels of the vasa nervorum along a "chaperone" region during outgrowth from the reattachment site and while entering the muscle. In this ,1-mm region, VEGF protein was expressed by growing microvessels despite a ,50% reduction (p < .05) in total muscle VEGF concentration. VEGFR2 was expressed by regenerating axons and growth cones. Sequestration of VEGF by sVEGFR1 impaired neurotization by ,40% (p < .05). The chaperone region ended where regenerating microvessels anastomosed with the native microcirculation and their expression of VEGF protein diminished. Conclusions: Regenerating axons and blood vessels align during outgrowth from ectopic reattachment. This interaction dissipates as vascular anastomoses form with established microvessels and axons target muscle fibers. Local production of VEGF by growing microvessels supports motor nerve survival and regeneration. [source] Insulin-like growth factor binding protein-3 (IGFBP-3) in the prostate and in prostate cancer: Local production, distribution and secretion pattern indicate a role in stromal-epithelial interactionTHE PROSTATE, Issue 11 2008Petra Massoner Abstract Background Insulin-like growth factor binding protein 3 (IGFBP-3) exerts inhibitory and proapoptotic effects on prostate cancer cells. Serum levels of IGFBP-3 were found to be associated with the risk of prostate cancer, but the data are still inconclusive. We present a detailed analysis of the expression and localization of IGFBP-3 in the prostate and a comparison with its expression pattern in tumors. Methods Expression and localization of IGFBP-3 were analyzed in cellular models and tissue by real-time RT-PCR, ELISA, immunohistochemistry, and immunofluorescence. Results All cell types of a panel of benign epithelial, stromal and tumor prostate cells expressed IGFBP-3. Significantly higher expression levels were registered in stromal cells. TGF-, stimulation boosted IGFBP-3 levels 60-fold in stromal cells. The pattern of expression was confirmed in microdissected tissue samples. Protein levels measured by ELISA paralleled the mRNA levels and more than 80% of IGFBP-3 was secreted. On tissue immunostaining, IGFBP-3 was found to be mainly located in the epithelium. The pattern suggested secretion of IGFBP-3, which was confirmed in prostate tissue cultured ex vivo and the ejaculate of vasectomized men. IGFBP-3 levels were increased in primary tumors but did not differ from benign epithelium in metastases and local recurrent tumors. Conclusions We registered a significant local production of IGFBP-3 in the prostate, which may well override the effect of protein entering from blood. The stroma,particularly reactivated stroma,is the main source of IGFBP-3 in the prostate, suggesting that this peptide acts as a mediator of stromal-epithelial interactions. Prostate 68: 1165,1178, 2008. © 2008 Wiley-Liss, Inc. [source] Exporting the German Model: The Establishment of a New Automobile Industry Cluster in ShanghaiECONOMIC GEOGRAPHY, Issue 1 2005Heiner Depner Abstract: Recent work has provided evidence that the establishment of new industry clusters cannot be jump-started through policy initiatives alone. This evidence does not imply, however, that the genesis of a new cluster cannot be planned at all. Especially in the context of a developing economy, it seems useful to reinvestigate the relation among economic development, the strategies of multinational firms, and state intervention in this respect. Drawing from the case of the automobile industry and its supplier system in Shanghai in which German firms play an important role, we provide empirical evidence of the evolution of a new cluster that is supported by the state in various forms and characterized by a focal, hierarchically structured production system. We use a multidimensional approach to clusters, which leads to a more nuanced understanding of the evolution and growth of a cluster than that provided by earlier accounts. This approach allows us to distinguish the development of the Shanghai automobile industry cluster along its vertical, horizontal, external, institutional, and power dimensions. We provide evidence that another dimension,"culture",plays an important role, especially in its relation to issues of power and institutions. The role of this dimension is demonstrated in the case of German firms, which tap into the Chinese innovation system. This system is characterized by particular business relations, institutions, norms, and various social practices that are new to German firms. We demonstrate how this difference creates problems in establishing local production and supplier relations and how these problems can be overcome. [source] How does the periapical inflammatory process compromise general health?ENDODONTIC TOPICS, Issue 1 2004Idikó. Several lines of evidence support the causative role of oral inflammatory lesions and certain systemic diseases, such as atherosclerosis and cardiovascular diseases, adverse pregnancy outcome and lung diseases. Properly executed epidemiologic studies identified increased odds ratios. Local or metastatic spread of oral microorganisms, local production of microbial or host-derived soluble regulatory molecules, that may initiate or sustain inflammatory events in remote tissues and organs and the presence of (a) common , extrinsic- or intrinsic-pathological mechanism(s) may result in or contribute to both local and systemic inflammation. A number of cross-sectional studies addressing a possible association between oral health and systemic diseases have also investigated the presence or the absence of periapical lesions. However, these studies cannot either confirm or refute a role of the periapical inflammatory lesion in the observed associations, since other variables of oral health might have exerted an inestimable influence on general health of the assessed population. The literature, dealing with patients with root canal infections and apical periodontitis as sole oral inflammatory lesions is extremely sparse. Our group has demonstrated that young adults with apical periodontitis exhibit certain biochemical changes, such as elevated levels of C-reactive protein and an increased whole blood chemiluminescence, which have been shown to elevate the risk for cardiovascular diseases. Future research will be required to determine whether and to what extent may endodontic diseases affect general health. [source] Endothelin receptor selectivity in chronic kidney disease: rationale and review of recent evidenceEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 2009W. Neuhofer Abstract Endothelin (ET) is a potent vasoconstrictory peptide with proinflammatory and profibrotic properties that exerts its biological effects through two pharmacologically distinct receptor subtypes, namely ETA and ETB. In addition to its substantial contribution to normal renal function, a large body of evidence suggests that derangement of the renal ET system is involved in the initiation and progression of chronic kidney disease (CKD) in diabetes, hypertension and glomerulonephritis. Thus, the use of ET receptor antagonists (ERAs) may offer potential novel treatment strategies in CKD. Recent literature on the role of the renal ET system in the healthy kidney was reviewed. In addition, an unbiased PubMed search was performed for studies published during the last 5 years that addressed the effects of ERAs in CKD. A particular objective was to extract information regarding whether selective or nonselective ERAs may have therapeutic potential in humans. ET-1 acts primarily as an autocrine or paracrine factor in the kidney. In normal physiology, ET-1 promotes diuresis and natriuresis by local production and action through ETB receptors in the renal medulla. In pathology, ET-1 mediates vasoconstriction, mesangial-cell proliferation, extracellular matrix production and inflammation, effects that are primarily conveyed by ETA receptors. Results obtained in animal models and in humans with the use of ERAs in CKD are encouraging; nevertheless, it is still under debate which receptor subtype should be targeted. According to most studies, selective inhibition of ETA receptors appears superior compared with nonselective ERAs because this approach does not interfere with the natriuretic, antihypertensive and ET clearance effects of ETB receptors. Although preliminary data in humans are promising, the potential role of ERAs in patients with CKD and the question of which receptor subtype should be targeted can only be clarified in randomized clinical trials. [source] A synthesis of biological and physical processes affecting the feeding environment of larval walleye pollock (Theragra chalcogramma) in the eastern Bering SeaFISHERIES OCEANOGRAPHY, Issue 2 2000Napp Biological and physical phenomena that affect conditions for larval survival and eventual recruitment differ in the oceanic and shelf regions. In the oceanic region, eddies are a common feature. While their genesis is not well known, eddies have unique biophysical characteristics and occur with such regularity that they likely affect larval survival. High concentrations of larval pollock often are associated with eddies. Some eddies are transported onto the shelf, thereby providing larvae to the Outer Shelf Domain. Advection, rather than local production, dominated the observed springtime increase in chlorophyll (often a correlate of larval food) in the oceanic region. Over two-thirds of the south-eastern shelf, eddies are absent and other phenomena are important. Sea ice is a feature of the shelf region: its interannual variability (time of arrival, persistence, and areal extent) affects developmental rate of larvae, timing of the phytoplankton bloom (and potentially the match/mismatch of larvae and prey), and abundance and distribution of juvenile pollock. In the oceanic region, interannual variation in food for first-feeding pollock larvae is determined by advection; in the shelf region, it is the coupled dynamics of the atmosphere,ice,ocean system. [source] Occurrence of Heterobasidion basidiocarps on cull pieces of Norway spruce left on cutting areas and in mature spruce standsFOREST PATHOLOGY, Issue 6 2007M. M. Müller Summary Fruiting of Heterobasidion on cull pieces and stumps of Norway spruce was investigated in cutting areas and mature spruce stands located in southern Finland. Cull pieces of variable size and showing butt rot were left on three clear-cut areas and in one thinned stand. Additionally, a part of the cull pieces was transported to mature forest sites with closed canopy. During the succeeding 3,4 years the cull pieces were investigated annually for sporocarps of Heterobasidion, and the area of actively sporulating pore layer of each sporocarp was measured. Root bases of spruce stumps in the logging areas were excavated and sporocarps found on the stumps also measured. At the onset of the experiment, Heterobasidion spp. were isolated from 76% of the cull pieces showing butt rot; 85% of the isolates were identified as H. parviporum and 15% as H. annosum s.s. During the following 3,4 years sporocarps were found on 20% of the 1938 cull pieces where Heterobasidion butt rot was initially detected visually. Sporocarp formation was promoted by advancement of butt rot, increasing cull piece diameter and end-to-end ground contact, but restricted by the colonization of the cull piece by Stereum sanguinolentum. Between-site differences were significant but could not be explained by differences in tree cover. At the end of the investigation period the average sporulating area of Heterobasidion sporocarp per metre of cull piece was higher than the average sporulating area per stump at three of four logging sites. Hence, leaving cull pieces containing Heterobasidion butt rot at logging areas in southern Finland can considerably increase local production of Heterobasidion spores. [source] Globalization and supply chain networks: the auto industry in Brazil and IndiaGLOBAL NETWORKS, Issue 2 2003John Humphrey The automotive industries of emerging markets were transformed in the 1990s by trade liberalization and large investments by global assemblers. The impact of these investments was decisively influenced by government policies aimed at promoting local production and assembly of vehicles and by changing assembler,supplier relationships in the global auto industry. The cases of Brazil and India show how the assemblers created new linkages between operations in emerging markets and their global operations through the adoption of follow design and follow sourcing policies. These policies were hard to implement in practice, but they decisively transformed the components industries in both countries. [source] Soluble Interleukin-2 Receptors Increase During the Active Periods in Cluster HeadacheHEADACHE, Issue 1 2003M. Empl MD Objective.,To investigate whether cytokines are altered during the active period of cluster headache. Background.,Patients with cluster headache show activation of the hypothalamus in PET studies and via endocrinologic parameters. Data also suggest an inflammatory process occurs in cluster headache. A connection between the presumed inflammatory cause, an immunological activation, and the hypothalamus could be generated by certain cytokines. Design and Methods.,ELISA was used to determine the serum levels of soluble interleukin-2 receptors, interleukin-1, interleukin-6, and 2 soluble interleukin-6 receptors (sIL-6R and soluble gp130) in 18 patients with cluster headache (6 women and 12 men) during the cluster period and in 17 healthy controls who were headache-free (3 women and 14 men). Results.,Patients with cluster headache had significantly increased soluble interleukin-2 receptors (413.6±223 U/mL vs. 290.0±112 U/mL; P < .05) compared with controls. Serum levels of interleukin-1 (0.29±0.30 pg/mL vs. 0.13±0.13 pg/mL, n.s.), interleukin-6 (0.87±0.6 pg/mL vs. 0.91±0.7 pg/ml; n.s.), soluble interleukin-6 receptors (33,131±8,349 pg/mL vs. 35,063±7,606 pg/mL; n.s.), or soluble gp130 (289±59 pg/mL vs. 283±20 pg/mL; n.s.) did not differ between the 2 groups, although patients with cluster tended to have higher interleukin-1 values. Conclusions.,Because elevated soluble interleukin-2 receptors indicate T cell activation, our findings suggest immune activation during cluster headache. Because interleukin-2 can activate the hypothalamus and stimulate the release of Corticotropin-releasing Factor (CRF), interleukin-2 could link a putative immunological cause of cluster headache with the observed hypothalamic activation. Systemic changes of interleukin-1 or the interleukin-6 system do not seem to play a role in cluster headache, as no alterations of serum levels were observed. Even so, unchanged serum levels do not exclude limited local production. [source] Roles of proinflammatory cytokines and the Fas/Fas ligand interaction in the pathogenesis of inflammatory myopathiesIMMUNOLOGY, Issue 1pt2 2009Masahiro Kondo Summary Within the lesions of inflammatory myopathies, muscle fibres and invading mononuclear cells express Fas and Fas ligand (FasL), respectively. However, the roles of the Fas/FasL interaction in the pathogenesis of inflammatory myopathies are not fully understood. In the present study, we investigated the roles of proinflammatory cytokines and the Fas/FasL system in the pathogenesis of inflammatory myopathies. In vitro culturing of muscle cells with the proinflammatory cytokines interferon-,, tumour necrosis factor-,, and interleukin (IL)-1, synergistically increased Fas expression, susceptibility to Fas-mediated apoptosis, and the expression of cytoplasmic caspases 8 and 3. In addition, culturing of muscle cells with activated CD4+ T cells induced muscle cell apoptosis, which was partially inhibited by anti-FasL antibody. We also tested the possibility that T helper (Th) 17, which is an IL-17-producing helper T-cell subset that plays crucial roles in autoimmune and inflammatory responses, participates in the pathogenesis of inflammatory myopathies. Interestingly, in vitro culturing of dendritic cells with anti-Fas immunoglobulin M (IgM) or activated CD4+ T cells induced the expression of mRNA for IL-23p19, but not for IL-12p35, in addition to proinflammatory cytokines. Furthermore, IL-23p19 and IL-17 mRNAs were detected in the majority of biopsy samples from patients with inflammatory myopathies. Taken together, these results suggest that proinflammatory cytokines enhance Fas-mediated apoptosis of muscle cells, and that the Fas/FasL interaction between invading dendritic cells and CD4+ T cells induces local production of IL-23 and proinflammatory cytokines, which can promote the proliferation of Th17 cells and enhance Fas-mediated apoptosis of muscle cells, respectively. [source] Histamine and prostaglandin E2 up-regulate the production of Th2-attracting chemokines (CCL17 and CCL22) and down-regulate IFN-,-induced CXCL10 production by immature human dendritic cellsIMMUNOLOGY, Issue 4 2006Anne McIlroy Summary Effector memory T helper 2 (Th2) cells that accumulate in target organs (i.e. skin or bronchial mucosa) have a central role in the pathogenesis of allergic disorders. To date, the factors that selectively trigger local production of Th2-attracting chemokines remain poorly understood. In mucosa, at the sites of allergen entry, immature dendritic cells (DC) are in close contact with mast cells. Histamine and prostaglandin E2 (PGE2) are two mediators released by allergen-activated mast cells that favour the polarization of maturing DC into Th2-polarizing cells. We analysed here the effects of histamine and PGE2 on the prototypic, Th2-(CCL17, CCL22) versus Th1-(CXCL10) chemokine production by human DC. We report that histamine and PGE2 dose-dependently up-regulate CCL17 and CCL22 by monocyte-derived immature DC. These effects were potentiated by tumour necrosis factor-,, still observed in the presence of the Th1-cytokine interferon-, (IFN-,) and abolished by the immunomodulatory cytokine interleukin-10. In addition, histamine and PGE2 down-regulated IFN-,-induced CXCL10 production by monocyte-derived DC. These properties of histamine and PGE2 were observed at the transcriptional level and were mediated mainly through H2 receptors for histamine and through EP2 and EP4 receptors for PGE2. Finally, histamine and PGE2 also up-regulated CCL17 and CCL22 and decreased IFN-,-induced CXCL10 production by purified human myeloid DC. In conclusion, these data show that, in addition to polarizing DC into mature cells that promote naďve T-cell differentiation into Th2 cells, histamine and PGE2 may act on immature DC to trigger local Th2 cell recruitment through a selective control of Th1/Th2-attracting chemokine production, thereby contributing to maintain a microenvironment favourable to persistent immunoglobulin E synthesis. [source] US Outward Foreign Direct Investment in the European Union and the Implementation of the Single Market: Empirical Evidence from a Cohesive FrameworkJCMS: JOURNAL OF COMMON MARKET STUDIES, Issue 5 2008FRAGKISKOS FILIPPAIOS In this article we investigate the determinants of US outward Foreign Direct Investment (FDI) in the European Union for the period 1982,2002. The data set allowed us to discern differences in the pattern of US FDI between EU core and EU periphery countries, as well as over different time periods during the last two decades. The results indicate that the US FDI pattern varies among different groups of countries and that there was a restructuring in multinational firms' investment activity after the implementation of the single market plan. Agglomeration factors, market size, qualified and productive labour and cost efficiency of local production seem to dominate in the location choice of US investors. [source] Spatial and temporal variation in the relative contribution of density dependence, climate variation and migration to fluctuations in the size of great tit populationsJOURNAL OF ANIMAL ECOLOGY, Issue 2 2009Vidar Grřtan Summary 1The aim of the present study is to model the stochastic variation in the size of five populations of great tit Parus major in the Netherlands, using a combination of individual-based demographic data and time series of population fluctuations. We will examine relative contribution of density-dependent effects, and variation in climate and winter food on local dynamics as well as on number of immigrants. 2Annual changes in population size were strongly affected by temporal variation in number of recruits produced locally as well as by the number of immigrants. The number of individuals recruited from one breeding season to the next was mainly determined by the population size in year t, the beech crop index (BCI) in year t and the temperature during March,April in year t. The number of immigrating females in year t + 1 was also explained by the number of females present in the population in year t, the BCI in autumn year t and the temperature during April,May in year t. 3By comparing predictions of the population model with the recorded number of females, the simultaneous modelling of local recruitment and immigration explained a large proportion of the annual variation in recorded population growth rates. 4Environmental stochasticity especially caused by spring temperature and BCI did in general contribute more to annual fluctuations in population size than density-dependent effects. Similar effects of climate on local recruitment and immigration also caused covariation in temporal fluctuations of immigration and local production of recruits. 5The effects of various variables in explaining fluctuations in population size were not independent, and the combined effect of the variables were generally non-additive. Thus, the effects of variables causing fluctuations in population size should not be considered separately because the total effect will be influenced by covariances among the explanatory variables. 6Our results show that fluctuations in the environment affect local recruitment as well as annual fluctuations in the number of immigrants. This effect of environment on the interchange of individuals among populations is important for predicting effects of global climate change on the pattern of population fluctuations. [source] Alkaline phosphatase isozyme activity in serum from patients with chronic periodontitisJOURNAL OF PERIODONTAL RESEARCH, Issue 4 2003P. Gibert Background:, High alkaline phosphatase activity (ALP) is shown in the periodontal ligament due to the constant renewal of this tissue or pathological circumstances. We have previously shown that the activity level of this enzyme could be reflected at the serum level. Objectives:, Because the local production of ALP in the periodontal ligament is often of the bone-type enzyme, we studied the activity of this isozyme among the other isoforms in the serum of patients with chronic periodontitis in comparison with that of control subjects. Material and methods:, This study included 83 patients (59 with periodontal disease, 24 as control group) and we determined the total seric ALP activity and the percentage of the different isoforms (essentially bone, kidney and intestinal-types) by Ektachem analyser and gel agarose electrophoresis respectively. Conclusions:, By comparisons between the two groups, our results showed a relationship between loss of attachment in periodontal disease and a drop in bone ALP activity in serum. Moreover, these results suggested a gender based difference as well, with lower activity more frequent in women than in men. [source] Cytological Alterations Produced by Sweet Potato Mild Speckling VirusJOURNAL OF PHYTOPATHOLOGY, Issue 7-8 2006C. F. Nome Abstract The potyvirus sweet potato mild speckling (SPMSV) has the biological properties and the coat protein sequence already described. In this work, cytological alterations and the intracellular localization in Ipomoea setosa and Ipomoea batatas was studied. The observations were carried out by means of transmission electron microscopy, complemented with immunogold techniques for the viral localization with SPMSV antiserum of local production. The observations carried out showed almost no alteration on cell components but the presence of cylindrical inclusion in the cytoplasm (bundles, laminate aggregates, and pinwheels, neither circles nor scrolls) belonging to the type-2 in the classification of Edwardson and Christie (Cylindrical Inclusions. Bulletin 894, 1996, pp. 1,11). Gold particles were localized in cytoplasms of all tissues of the leaf. [source] Micro-Raman spectroscopy of decorated pottery from the Iberian archaeological site of Puente Tablas (Jaén, Spain, 7th,4th century B.C.)JOURNAL OF RAMAN SPECTROSCOPY, Issue 1 2010D. Parras Abstract In this paper, Raman spectroscopy is used for the first time to identify the pigments on decorated antique Iberian pottery. Ceramic fragments of type Real and others from the archaeological excavation in the oppidum Puente Tablas were examined. Different types of iron oxide pigments (hematite and goethite) were identified, along with amorphous carbon. In some samples, the presence of chalk or gypsum could be demonstrated. Some unattributed Raman bands are believed to be associated either with post-burial organic deposition or with silicate materials that are present in red ochre. It was possible to relate the findings with geological data from the region and to make assumptions on a local production. Copyright © 2009 John Wiley & Sons, Ltd. [source] Psoriasis confined strictly to vitiligo areas , a Koebner-like phenomenon?JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 2 2006TG Berger Abstract Vitiligo and psoriasis are both common skin disorders. However, psoriasis strictly confined to pre-existing vitiligo areas is rare and suggests a causal relationship. We report here on two patients with a strict anatomical colocalization of vitiligo and psoriasis. The histopathological examinations showed typical changes for both diseases together with a dense infiltrate of CD4+ and CD8+ T cells. By immunohistochemistry, intracytoplasmatic granzyme B and tumour necrosis factor alpha (TNF-,) were detected within the T-cell population, suggesting the functional activity of these cells and the creation of a local T helper 1 (Th1)-cytokine milieu. Additionally, in one patient we could identify anti-melanocytic T cells by tetramer staining and enzyme-linked immunospot (ELISPOT) analysis. These skin-infiltrating lymphocytes might trigger, by the local production of Th-1 cytokines such as TNF-, and interferon-, (IFN-,), the eruption of psoriatic plaques in patients with a genetic predisposition for psoriasis. [source] Increasing the efficiency of photodynamic therapy by improved light delivery and oxygen supply using an anticoagulant in a solid tumor modelLASERS IN SURGERY AND MEDICINE, Issue 7 2010Liyong Yang MS Abstract Background and Objective The main factors in photodynamic therapy (PDT) are: photosensitizer retention, photon absorption, and oxygen supply. Each factor has its unique set of problems that poses limitation to the treatment. Both light delivery and oxygen supply are significant bottlenecks in PDT. Vascular closure during PDT reduces oxygen supply to the targeted tissue. On the other hand, with the changes in blood perfusion, the tissue optical properties change, and result in variation in irradiation light transmission. For these reasons, it becomes very important to avoid blood coagulation and vascular closure during PDT. Study Design/Materials and Methods The efficiency of PDT combined with the anticoagulant heparin was studied in a BALB/c mouse model with subcutaneous EMT6 mammary carcinomas. Mice were randomized into three groups: control, PDT-only, and PDT with heparin. The photosensitizer Photofrin® was used in our experiments. Light transmission, blood perfusion, and local production of reactive oxygen species (ROS) were monitored during the treatment. The corresponding histological examinations were performed to determine the thrombosis immediately after irradiation and to evaluate tumor necrosis 48,hours after the treatment. Results The results clearly demonstrated that PDT combined with pre-administered heparin can significantly reduce thrombosis during light irradiation. The blood perfusion, oxygen supply, and light delivery are all improved. Improved tumor responses in the combined therapy, as shown with the histological examination and tumor growth assay, are clearly demonstrated and related to an increased local ROS production. Conclusion Transitory anticoagulation treatment significantly enhances the antitumor effect of PDT. It is mainly due to the improvement of the light delivery and oxygen supply in tumor, and ultimately the amount of ROS produced during PDT. Lasers Surg. Med. 42:671,679, 2010. © 2010 Wiley-Liss, Inc. [source] Life of the mind: The interface of psychopharmaceuticals, domestic economies, and social abandonmentAMERICAN ETHNOLOGIST, Issue 4 2004Joăo Biehl ABSTRACT In this article, I address the embroilment of medical science in the lifeworlds of the urban poor in Brazil, particularly the place of psychopharmaceuticals within households. I explore how psychiatric diagnostics and treatments are integrated into a domestic "dramaturgy of the real" and how family members use them to assess human value and to mediate the disposal of persons considered unproductive or unsound. I focus on the life of Catarina, who was deemed mad and left by her family in an asylum in southern Brazil. Disabled and abandoned, Catarina began to compile a "dictionary" of words that have meaning for her. By tracing Catarina's words back to the people, households, and medical institutions that she had once been a part of, I illuminate the complex network in which her abandonment and pathology took form as well as the edges of human imagination that she keeps expanding. From this examination, one comes to understand how economic globalization, state and medical reform, and acceleration of claims over human rights and citizenship coincide with and impinge on a local production of social death. One also sees how mental disorders gain form at the juncture between the subject, her biology, and the technical and political coding of her sense of being alive. Hers is not just bare life, though: Thinking through her condition, Catarina anticipates social ties and one more chance. This is also a story of the methodological and ethical challenges I faced as I supported Catarina's search for consistency and her demands for continuity. [source] Combination Nonviral Interleukin-2 Gene Immunotherapy For Head and Neck Cancer: From Bench Top to BedsideTHE LARYNGOSCOPE, Issue 3 2005Bert W. O'Malley Jr MD Abstract Objective/Hypothesis: Intralesional delivery of cytokine genes has emerged as a promising therapeutic strategy for the treatment of cancer. In addition to the therapeutic effect of the delivered cytokine gene, the components of the gene delivery system also have been shown to induce beneficial immune responses. On the basis of these principles, we hypothesized that a molecular therapy could be developed that would provide synergistic antitumor activity by way of intralesional expression of interleukin (IL)-2 from a recombinant plasmid combined with induction of endogenous interferon (IFN)-, and IL-12 cytokines by immunostimulatory DNA. Our objective in these studies was to create and optimize a novel formulation of cationic lipid and DNA that generates local production of IL-2 protein within a targeted tumor environment with concomitant induction of the antitumor cytokines IFN-, and IL-12. Study Design: Prospective laboratory drug development plan that would produce human clinical trials. Materials and Methods: Engineered bacterial plasmids containing a cytomegalovirus promoter (CMV)-IL-2 expression cassette were specifically formulated with cationic lipids and optimized for antitumor effect in a floor of mouth murine tumor model. The treated tumors were assayed for local expression of IL-2 and concurrent expression of secondary cytokines IFN-, and IL-12. Established tumors in C3H/HeJ mice were treated with various IL-2 gene formulations, and clinical and immunologic responses were evaluated. Immunologic studies were performed and included cytolytic T-cell assays and cytokine expression profiles. For human clinical trials, a phase I 10 patient formulated IL-2 gene therapy study was completed. Subsequently, two large scale, phase II multi-institutional and multi-international studies were initiated comparing non-viral IL-2 gene therapy to palliative methotrexate chemotherapy or in combination with cisplatin. Results: In the preclinical stage, maximum tumor inhibition in animal models was obtained using IL-2 plasmid formulated with 1,2-dioleyloxypropyl-3-trimethyl ammonium chloride (DOTMA):cholesterol (1:1 mol:mol) at a plasmid:lipid charge ratio of 1:0.5 (,/+). Cationic lipid formulated IL-2 plasmid significantly inhibited tumor growth compared with formulated control plasmid (P < .01) or vehicle (lactose; P < .01). Consistent with previously reported studies of the immunostimulatory activity of DNA of bacterial origin, treatment of tumors with control plasmid in cationic lipid formulation induced production of endogenous IFN-, and IL-12 but not IL-2. Treatment of tumors with formulated IL-2 plasmid produced IL-2 protein levels that were 5-fold over background and increased IFN-, by 32-fold (P < .001) and IL-12 by 5.5-fold (P < .001) compared with control plasmid formulations. The phase I human trial demonstrated dose escalation safety, which was its primary objective, and there was one anecdotal reduction in tumor size. The phase II studies have been initiated and focus on either comparing the novel nonviral IL-2 gene immunotherapy formulation alone to methotrexate or comparing IL-2 gene therapy in combination with cisplatin in recurrent or unresectable patients with head and neck squamous cell carcinoma. Conclusions: The preclinical data provided proof of principle for matching a delivered IL-2 transgene with an immunostimulatory nonviral formulation to enhance intralesional production of therapeutic cytokines for the maximization of antitumor response. Human clinical trials have demonstrated this novel therapy to be safe in the human clinical setting. Phase II trials have been initiated to assess efficacy and feasibility as a single or combination therapy for head and neck cancer. [source] Insulin-like growth factor binding protein-3 (IGFBP-3) in the prostate and in prostate cancer: Local production, distribution and secretion pattern indicate a role in stromal-epithelial interactionTHE PROSTATE, Issue 11 2008Petra Massoner Abstract Background Insulin-like growth factor binding protein 3 (IGFBP-3) exerts inhibitory and proapoptotic effects on prostate cancer cells. Serum levels of IGFBP-3 were found to be associated with the risk of prostate cancer, but the data are still inconclusive. We present a detailed analysis of the expression and localization of IGFBP-3 in the prostate and a comparison with its expression pattern in tumors. Methods Expression and localization of IGFBP-3 were analyzed in cellular models and tissue by real-time RT-PCR, ELISA, immunohistochemistry, and immunofluorescence. Results All cell types of a panel of benign epithelial, stromal and tumor prostate cells expressed IGFBP-3. Significantly higher expression levels were registered in stromal cells. TGF-, stimulation boosted IGFBP-3 levels 60-fold in stromal cells. The pattern of expression was confirmed in microdissected tissue samples. Protein levels measured by ELISA paralleled the mRNA levels and more than 80% of IGFBP-3 was secreted. On tissue immunostaining, IGFBP-3 was found to be mainly located in the epithelium. The pattern suggested secretion of IGFBP-3, which was confirmed in prostate tissue cultured ex vivo and the ejaculate of vasectomized men. IGFBP-3 levels were increased in primary tumors but did not differ from benign epithelium in metastases and local recurrent tumors. Conclusions We registered a significant local production of IGFBP-3 in the prostate, which may well override the effect of protein entering from blood. The stroma,particularly reactivated stroma,is the main source of IGFBP-3 in the prostate, suggesting that this peptide acts as a mediator of stromal-epithelial interactions. Prostate 68: 1165,1178, 2008. © 2008 Wiley-Liss, Inc. [source] Variability in the summertime coastal marine atmospheric boundary-layer off California, USATHE QUARTERLY JOURNAL OF THE ROYAL METEOROLOGICAL SOCIETY, Issue 597 2004Linda Ström Abstract An analysis of boundary-layer structure and surface-layer turbulence from measurements off the California coast is presented from data collected by research aircraft during two field experiments: the Coastal Waves 1996 (CW96) and the Monterey Area Ship Track (MAST) experiments. CW96 covers the near-coast region, in particular in the vicinity of major headlands, whereas MAST extends offshore. Along the US west coast, coastal modification of the along-coast flow occurs on two main horizontal scales. Firstly, a large-scale variability is due to the interplay between the shallow near-coast marine atmospheric boundary-layer (MABL) and the coastal terrain, typically higher than the MABL depth. The MABL depth decreases smoothly towards the coast while the wind speed increases to a coastal jet in response to the sloping MABL inversion. Secondly, the flow is affected by supercritical flow dynamics. As the wind speed increases and the MABL depth decreases towards the coast, the MABL flow becomes supercritical in a shallow-water sense. As supercritical shallow-water flow interacts with major headlands, expansion fans form, affecting both the wind speed and the MABL depth. The combination of CW96 and MAST data reveals significant differences between the flow along the coast and that far offshore. MABL winds are stronger near the coast whereas aloft the winds are weaker than offshore. The near-coast MABL is also better mixed. Turbulence increases towards the coast while the sensible-heat flux decreases and often changes sign, leading to stable stratification near the coast. A length-scale determining the across-coast influence of the expansion fans is defined from simple inviscid and irrotational shallow-water theory. Data from four days of the CW96 experiment show that this simple theory describes the low-level wind speed adequately. Surface-layer turbulence also scales with this simple length-scale, but the results are complicated by upwelling of cold water, giving rise to strong internal boundary-layers. From terms in the turbulent-energy budgets it appears that dissipation of turbulence exceeds local production. Copyright © 2004 Royal Meteorological Society [source] MARBLE PROVENANCE INVESTIGATION OF ROMAN SARCOPHAGI FROM THESSALONIKI*ARCHAEOMETRY, Issue 1 2010Y. MANIATIS The provenance question of the marbles used for making the sarcophagi of local production of Thessaloniki in the Roman period had been posed by archaeologists in the past. The hypothesis was that the material came mainly from the quarries of Thassos Island. This paper presents the scientific analysis of 23 characteristic samples from selected sarcophagi at the Museum of Thessaloniki, using three different techniques: electron paramagnetic resonance (EPR) spectroscopy, stable isotope analysis and maximum grain size measurements, plus in-situ examination. New combinations of parameters were used in order to resolve fully the provenance of all samples. The results showed that the vast majority of the objects were indeed made in Thassian marble but from three different quarries, namely Vathy/Saliara (dolomitic marble), Aliki (calcitic marble) and Acropolis/Phanari (calcitic marble). The calcitic marbles from Aliki and to a lesser degree from Acropolis/Phanari are met in all the basic types of sarcophagi (framed type, plain type, garland sarcophagi). The use of the better quality and snow-white dolomitic marble from Vathy/Saliara quarries is relatively restricted and is often found in works that are above the average regarding the quality of their workmanship. In addition, two sarcophagi were made in Pentlelic marble and one in Proconnesian. The scientific analysis results provide a good confirmation of the archaeological estimates and, furthermore, the conclusions constitute henceforth a secure basis for the study of the entire sculptured works of Thessaloniki. [source] Enhanced Th1 and Th17 responses and arthritis severity in mice with a deficiency of myeloid cell,specific interleukin-1 receptor antagonistARTHRITIS & RHEUMATISM, Issue 2 2010Céline Lamacchia Objective The balance between interleukin-1 (IL-1) and its specific inhibitor, the IL-1 receptor antagonist (IL-1Ra), plays a major role in the development of arthritis. The purpose of this study was to investigate the role of IL-1Ra produced specifically by myeloid cells in the control of collagen-induced arthritis (CIA) by using myeloid cell,specific IL-1Ra,deficient mice (IL-1Ra,M). Methods IL-1Ra,M mice were generated by using the loxP/Cre recombinase system. CIA was induced in IL-1Ra,M mice and littermate control mice by a single immunization with bovine type II collagen (CII) in Freund's complete adjuvant. Arthritis severity was assessed by clinical and histologic scoring. Draining lymph node (DLN) cell responses were examined ex vivo, and ankle extracts were used in the quantification of cytokines and chemokines. Results Clinical and histopathologic evaluations revealed an early disease onset and a severe form of CIA in IL-1Ra,M mice. This was characterized by increased production of interferon-, (IFN,) and IL-17 by CII-stimulated DLN cells. We also observed that the CII-specific CD4+ T cell response shifted in vivo, from a dominant Th1 response early in the course of the arthritis to the presence of both Th1 and Th17 cytokines later in the disease course. Interestingly, IL-1Ra levels were higher in the arthritic joints of IL-1Ra,M mice as compared with the controls, indicating that nonmyeloid cells strongly contribute to the local production of IL-1Ra. However, this enhanced IL-1Ra production was not sufficient to limit joint inflammation and tissue damage. Conclusion Our results suggest that myeloid cell,derived IL-1Ra plays a critical role in the control of the development and the severity of CIA by modulating Th1 and Th17 responses in lymphoid organs. [source] The infrapatellar fat pad in knee osteoarthritis: An important source of interleukin-6 and its soluble receptorARTHRITIS & RHEUMATISM, Issue 11 2009Emilie Distel Objective Obesity is a potent risk factor in knee osteoarthritis (OA). It has been suggested that adipokines, secreted by adipose tissue (AT) and largely found in the synovial fluid of OA patients, derive in part from the infrapatellar fat pad (IFP), also known as Hoffa's fat pad. The goal of this study was to characterize IFP tissue in obese OA patients and to compare its features with thigh subcutaneous AT to determine whether the IFP contributes to local inflammation in knee OA via production of specific cytokines. Methods IFP and subcutaneous AT samples were obtained from 11 obese women (body mass index ,30 kg/m2) with knee femorotibial OA. Gene expression was measured by real-time quantitative polymerase chain reaction. Cytokine concentrations in plasma and in conditioned media of cultured AT explants were determined by enzyme-linked immunosorbent assay or by Luminex xMAP technology. Results In IFP tissue versus subcutaneous AT, there was a decrease in the expression of genes for key enzymes implicated in adipocyte lipid metabolism, whereas the expression levels of genes for AT markers remained similar. A 2-fold increase in the expression of the gene for interleukin-6 (IL-6), a 2-fold increase in the release of IL-6, and a 3.6-fold increase in the release of soluble IL-6 receptor (sIL-6R) were observed in IFP samples, compared with subcutaneous AT, but the rates of secretion of other cytokines in IFP samples were similar to the rates in subcutaneous AT. In addition, leptin secretion was decreased by 40%, whereas adiponectin secretion was increased by 70%, in IFP samples versus subcutaneous AT. Conclusion Our results indicate that the IFP cytokine profile typically found in OA patients could play a role in paracrine inflammation via the local production of IL-6/sIL-6R and that such a profile might contribute to damage in adjacent cartilage. [source] Mature antigen-experienced T helper cells synthesize and secrete the B cell chemoattractant CXCL13 in the inflammatory environment of the rheumatoid jointARTHRITIS & RHEUMATISM, Issue 11 2008Antonio Manzo Objective Synovial B cells play a critical role in rheumatoid arthritis (RA), being involved in autoantibody synthesis, T cell activation, and cytokine production. CXCL13 is a B cell chemoattractant that is instrumental in synovial B cell organization; the regulatory determinants of CXCL13 in inflammation are poorly characterized. This study was undertaken to investigate the functional involvement of synovial T cells in the ectopic expression of CXCL13 in RA. Methods CXCL13 production and regulation were addressed using immunohistochemistry, in situ hybridization, quantitative polymerase chain reaction, multicolor flow cytometry, and enzyme-linked immunosorbent assay, by in situ,ex vivo analysis and in vitro functional assays with rheumatoid synovial tissue and primary cells. Results CXCL13 messenger RNA and protein expression and spontaneous CXCL13 secretion were detected in RA synovial fluid T cells but were not detected (or were detected only occasionally) in peripheral blood T cells. Analysis of tissue expression confirmed cytoplasm localization of CXCL13 in T lymphocytes infiltrating B cell follicles and small perivascular aggregates. Multicolor characterizations in synovial fluid demonstrated CXCL13 expression in antigen-experienced T helper cells, frequently characterized by terminal differentiation and the lack of the follicular helper T cell markers CXCR5 and BCL6 protein. In vitro functional assays revealed the enhancing effect of T cell receptor,CD28 engagement on CXCL13 production and secretion in primary cells. Conclusion Our findings define a new functional property of synovial T cells, demonstrating their active involvement in the local production of B cell chemoattractants, and support a direct contribution of the adaptive immune system and antigen-dependent signals in the mechanisms of B cell localization in RA. [source] Association of interleukin-18 expression with enhanced levels of both interleukin-1, and tumor necrosis factor , in knee synovial tissue of patients with rheumatoid arthritisARTHRITIS & RHEUMATISM, Issue 2 2003Leo A. B. Joosten Objective To examine the expression patterns of interkeukin-18 (IL-18) in synovial biopsy tissue of patients with rheumatoid arthritis (RA), and to determine whether expression of this primary cytokine is related to the expression of other cytokines and adhesion molecules and related to the degree of joint inflammation. Methods Biopsy specimens of knee synovial tissue either without synovitis (n = 6) or with moderate or severe synovitis (n = 11 and n = 12, respectively) were obtained from 29 patients with active RA. Paraffin-embedded, snap-frozen sections were used for immunohistochemical detection of IL-18, tumor necrosis factor , (TNF,), IL-1,, IL-12, and IL-17. Furthermore, adhesion molecules, such as intercellular adhesion molecule 1, vascular cell adhesion molecule 1, and E-selectin, and cell markers CD3, CD14, and CD68 were stained. Results IL-18 staining was detectable in 80% of the RA patients, in both the lining and sublining of the knee synovial tissue. IL-18 expression in the synovial tissue was strongly correlated with the expression of IL-1, (in the sublining r = 0.72, in the lining r = 0.71; both P < 0.0001) and TNF, (in the sublining r = 0.59, P < 0.0007, and in the lining r = 0.68, P < 0.0001). In addition, IL-18 expression in the sublining correlated with macrophage infiltration (r = 0.64, P < 0.0007) and microscopic inflammation scores (r = 0.78, P < 0.0001), and with the acute-phase reaction as measured by the erythrocyte sedimentation rate (r = 0.61, P < 0.0004). Interestingly, RA synovial tissue that coexpressed IL-18 and IL-12 demonstrated enhanced levels of the Th1-associated cytokine IL-17. Conclusion Our results show that expression of IL-18 is associated with that of IL-1, and TNF, and with local inflammation in the synovial tissue of patients with RA. In addition, synovial IL-18 expression correlates with the acute-phase response. These data indicate that IL-18 is a primary proinflammatory cytokine in RA that drives the local production of IL-1, and TNF,. [source] Endothelial cell expression of adhesion molecules is induced by fetal plasma from pregnancies with umbilical placental vascular diseaseBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 7 2002Xin Wang Objective To test the hypothesis that local production with spill into the fetal circulation of factor(s) injurious to endothelium is responsible for the vascular pathology present when the umbilical artery Doppler study is abnormal. Expression of adhesion molecules is a feature of endothelial cell activation. Design Case,control study. Setting University teaching hospital. Samples Fetal plasma was collected from 27 normal pregnancies, 39 pregnancies with umbilical placental vascular disease defined by abnormal umbilical artery Doppler and 11 pregnancies with pre-eclampsia and normal umbilical artery Doppler. Methods Isolated and cultured human umbilical vein endothelial cells from normal pregnancies were incubated with fetal plasma from three study groups. mRNA expression of intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and platelet-endothelial cell adhesion molecule-1 (PECAM-1) were assessed by reverse transcription-polymerase chain reaction. To confirm the occurrence of this in vivo, we measured the levels of soluble fractions of sICAM-1, sVCAM-1 and sPECAM-1 in the fetal circulation in the fetal plasma used for endothelial cell incubation. Results The mRNA expression of ICAM-1 [median 1.1 (interquartile range 0.5,1.9) vs 0.7 (0.3,1.2), P < 0.05] and PECAM-1 [2.1 (1.2,3.0) vs 1.5 (0.7,2.1), P < 0.05] was significantly higher following incubation with fetal plasma from umbilical placental vascular disease compared with the normal group. There was no difference in the expression of VCAM-1 [1.2 (0.9,1.8) vs 1.1 (0.8,1.6), ns]. The group with maternal pre-eclampsia and normal umbilical artery Doppler did not differ from the normal group. In the umbilical placental vascular disease group, the results were similar in the presence or absence of pre-eclampsia. For soluble fractions of the adhesion molecules released into the fetal circulation, we found the levels (ng/mL) of sICAM-1 [median 248.5 (interquartile range 197.3,315.7) vs 174.2 (144.5,212.9), P < 0.05] and sPECAM-1 [9.3 (6.2,11.1) vs 6.1 (5.4,7.7), P < 0.05] in fetal plasma to be significantly increased in the presence of umbilical placental vascular disease compared with the normal. Conclusions Vascular disease in the fetal umbilical placental circulation is associated with an elevation in mRNA expression by endothelial cells of ICAM-1 and PECAM-1. Our study provides evidence for endothelial cell activation and dysfunction in umbilical placental vascular disease. We speculate that the plasma factor(s) affecting the vessels of the umbilical villous tree is locally released by the trophoblast. The occurrence of the maternal syndrome of pre-eclampsia appears to be independent of this. [source] Autocrine/paracrine involvement of insulin-like growth factor-I and its receptor in chronic lymphocytic leukaemiaBRITISH JOURNAL OF HAEMATOLOGY, Issue 1 2005Roxana Schillaci Summary Chronic lymphocytic leukaemia (CLL) is characterized by the accumulation of long-lived B lymphocytes blocked in G0/1 by impaired apoptosis. As insulin-like growth factor-I (IGF-I) is known for its antiapoptotic effects in different cell types, we investigated whether IGF-I and its receptor (IGF-IR) participate in autocrine/paracrine loops affecting the survival of CLL cells. IGF-IR protein and mRNA was present in CLL cells in 44% and 59% of patients respectively. IGF-IR expression in CLL patients was positively correlated with the expression of the antiapoptotic protein Bcl-2 and was involved in CLL cell survival in vitro. Serum IGF-I was elevated in CLL patients, but growth hormone (GH) was normal. CLL cells expressed IGF-I mRNA and secreted the growth factor in vitro. Therefore, local production of IGF-I can account for the increased levels of serum IGF-I, independently of GH, and may be related to autocrine/paracrine control of lymphocyte survival acting at IGF-IR. This is the first demonstration of IGF-IR expression in a subgroup of CLL patients and of its antiapoptotic effects in vitro, highlighting the importance of this growth factor receptor as a possible therapeutic target in CLL. [source] AT2 receptor-dependent vasodilation is mediated by activation of vascular kinin generation under flow conditionsBRITISH JOURNAL OF PHARMACOLOGY, Issue 4 2002Jun Katada Physiological roles of angiotensin II type 2 receptor (AT2) are not well defined. This study was designed to investigate the mechanisms of AT2 -dependent vascular relaxation by studying vasodilation in pressurized and perfused rat mesenteric arterial segments. Perfusion of angiotensin II in the presence of AT1 antagonist elicited vascular relaxation, which was completely dependent on AT2 receptors on endothelium. FR173657 (>1 ,M), a bradykinin (BK) B2 -specific antagonist, significantly suppressed AT2 -dependent vasodilation (maximum inhibition: 68.5% at 10 ,M). Kininogen-deficient Brown Norway Katholiek rats showed a significant reduction in AT2 -mediated vasodilatory response compared with normal wild-type Brown Norway rats. Indomethacin (>1 ,M), aprotinin (10 ,M) and soybean trypsin inhibitor (10 ,M) also reduced AT2 -dependent vasodilation. Our results demonstrated that stimulation of AT2 receptors caused a significant vasodilation through local production of BK in resistant arteries of rat mesentery in a flow-dependent manner. Such vasodilation counterbalances AT1 -dependent vasoconstriction to regulate the vascular tone. British Journal of Pharmacology (2002) 136, 484,491; doi:10.1038/sj.bjp.0704731 [source] | |||||||||||||||||||