Naive

Distribution by Scientific Domains
Distribution within Medical Sciences

Terms modified by Naive

  • naive animals
  • naive b cell
  • naive cd4+ t cell
  • naive cell
  • naive control
  • naive individual
  • naive mouse
  • naive patient
  • naive rat
  • naive t cell

  • Selected Abstracts


    Altered primary CD8+ T,cell response to a modified virus Ankara(MVA)-vectored vaccine in the absence of CD4+ T,cell help

    EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 12 2005
    Marie
    Abstract T,cell receptor-transgenic F5 mice were used to assess primary CD8+ T,cell responses to a modified virus Ankara (MVA)-vectored vaccine in the absence of CD4+ T,cell help. Naive, CD8-enriched, CFSE-labelled F5 cells were transferred into normal or CD4+ cell-depleted mice and the mice were vaccinated with MVA.HIVA-NP. At different time points during the primary response, F5 cells were re-isolated and analysed on divisional basis for a number of parameters. We demonstrated that the primary CD8+ T,cell response in the absence of CD4+ T,cell help differed from that in normal CD4+ cell-undepleted mice. While in the absence of CD4+ T,cell help, the initial migratory progress from the local response to a systemic one was not grossly affected, the proportion of dying F5 cells during the expansion phase was markedly increased and resulted in an overall smaller expansion and significantly decreased frequency of CD8+ T,cell memory after contraction. T,cells primed without help displayed accelerated proliferation and activation, while expression of interferon-, remained similar. These phenomena were observed in the lymph nodes draining the MVA.HIVA-NP immunization site and were similar, but delayed by 2,3,days in spleen and non-draining lymph nodes. [source]


    Predicting project delivery rates using the Naive,Bayes classifier

    JOURNAL OF SOFTWARE MAINTENANCE AND EVOLUTION: RESEARCH AND PRACTICE, Issue 3 2002
    B. Stewart
    Abstract The importance of accurate estimation of software development effort is well recognized in software engineering. In recent years, machine learning approaches have been studied as possible alternatives to more traditional software cost estimation methods. The objective of this paper is to investigate the utility of the machine learning algorithm known as the Naive,Bayes classifier for estimating software project effort. We present empirical experiments with the Benchmark 6 data set from the International Software Benchmarking Standards Group to estimate project delivery rates and compare the performance of the Naive,Bayes approach to two other machine learning methods,model trees and neural networks. A project delivery rate is defined as the number of effort hours per function point. The approach described is general and can be used to analyse not only software development data but also data on software maintenance and other types of software engineering. The paper demonstrates that the Naive,Bayes classifier has a potential to be used as an alternative machine learning tool for software development effort estimation. Copyright © 2002 John Wiley & Sons, Ltd. [source]


    F. L. McDougall: Éminence grise of Australian Economic Diplomacy

    AUSTRALIAN ECONOMIC HISTORY REVIEW, Issue 1 2000
    Sean Turnell
    This paper examines the principal economic ideas of F. L. McDougall, a largely forgotten, sometime government official and ,amateur' economist who exercised an enigmatic influence upon Australia's economic diplomacy in the interwar years. Beginning with his conception of ,sheltered markets', the international manifestation of the Bruce Government's vision for Australia of ,men, money, and markets', the paper explores McDougall's later advocacy of a ,nutrition approach' to world agriculture and its extension into ,economic appeasement'. McDougall's ideas were theoretically unsophisticated, and realized little in the way of immediate achievements. In the longer run they could be viewed more favourably. Naive perhaps and idealistic certainly, McDougall's ideas were part of a broader movement that, after the Second World War, redefined the role of international economic institutions. If nothing else, McDougall's active proselytizing of his ideas lent Australia an unusual ,voice' in international forums at a time when it was scarcely heard. [source]


    Human B cells express a CD45 isoform that is similar to murine B220 and is downregulated with acquisition of the memory B-cell marker CD27,

    CYTOMETRY, Issue 1 2003
    Jack J. H. Bleesing
    Abstract Background Differences between human and murine B cells exist at all stages of B-cell development, including the stage of memory B-cell formation. B cells in mice are identified with the pan,B-cell,specific CD45 isoform, B220. In initial studies in humans, it appeared that B220 expression did not include all B cells. This study was performed to expand on those preliminary findings. Methods Multiparameter flow cytometric detection of B220 expression on B cells was combined with a variety of B-cell markers. Results In contrast to mice, B220 was not a pan,B-cell marker in humans but was downregulated in the majority of B cells that acquired the human memory B-cell marker, CD27, whereas a minor memory B-cell subset remained B220+, suggesting differences in differentiation. Conclusions The B220 isoform in humans is developmentally regulated in humans, tied to the acquisition of a memory phenotype, and as such can be used as a differentiation-specific CD45 isoform, akin to the use of CD45 isoforms to distinguish between naive and memory T-cell subsets. Patients with immunodeficiency disorders, associated with defective memory B-cell generation and absent or reduced CD27+ B cells, showed a corresponding lack of B220 downregulation consistent with altered differentiation of B-cell subsets. Cytometry Part B (Clin. Cytometry) 51B:1,8, 2003. Published 2002 Wiley-Liss, Inc. [source]


    Religious Persecution: And What To Do About It

    DIALOG, Issue 2 2002
    John Hilary Martin
    Hinduism, Islam, Christianity, Buddhism, and other religions can all be found in geographically diverse Indonesia. Adding to this layered society are many different ethnic groups, political groups, and socio,economic groups. The joining of all these factors led to different communities forming adats,religio,customary agreements. When talking about "religious persecution" in Indonesia, all of these factors must be taken into account. Even so, it would be extremely naive to think that religious belief is a peripheral motivation for violence. This article explores a method by which religious scholars, leaders, and communities can curtail religious persecution in Indonesia; the method includes: personal encounter; discussion of the scholarly agenda; a public engagement through dialogue that leads to commitment; and finally, the appeal of prayer and ritual. [source]


    Proteome analysis of the culture environment supporting undifferentiated mouse embryonic stem and germ cell growth

    ELECTROPHORESIS, Issue 10 2007
    Nicolas Buhr
    Abstract The therapeutical interest of pluripotent cells and ethical issues related to the establishment of human embryonic stem cell (ESC) or embryonic germ cell (EGC) lines raise the understanding of the mechanism underlying pluripotency to a fundamental issue. Establishing a protein pluripotency signature for these cells can be complicated by the presence of unrelated proteins produced by the culture environment. Here, we have analyzed the environment supporting ESC and EGC growth, and established 2-D reference maps for each constituent present in this culture environment: mouse embryonic fibroblast feeder cells, culture medium (CM) and gelatin. The establishment of these reference maps is essential prior to the study of ESC and EGC specific proteomes. Indeed, these maps can be subtracted from ESC or EGC maps to allow focusing on spots specific for ESCs or EGCs. Our study led to the identification of 110 unique proteins from fibroblast feeder cells and 23 unique proteins from the CM, which represent major contaminants of ESC and EGC proteomes. For gelatin, no collagen-specific proteins were identified, most likely due to difficulties in resolution and low quantities. Furthermore, no differences were observed between naive and conditioned CM. Finally, we compared these reference maps to ESC 2-D gels and isolated 17 ESC specific spots. Among these spots, proteins that had already been identified in previous human and mouse ESC proteomes were identified but no apparent ESC-specific pluripotency marker could be identified. This work represents an essential step in furthering the knowledge of environmental factors supporting ESC and EGC growth. [source]


    Kindling Limits the Interictal Neuronal Temporal Response Properties in Cat Primary Auditory Cortex

    EPILEPSIA, Issue 2 2005
    Pamela A. Valentine
    Summary:,Purpose: The present study examined the effect of electrical kindling on the interictal temporal response properties of single units recorded from primary auditory cortex (AI) of the adult cat. Methods: Cats were permanently implanted with electrodes in AI, kindled twice daily for 40 sessions, and the contralateral AI was subsequently mapped. Kindling stimulation consisted of 1-s trains of biphasic square-wave pulses applied at a frequency of 60 Hz, 100 ,A above the afterdischarge (AD) threshold. The EEG activity was recorded during each kindling session, and the behavioral manifestation was scored. Subsequent to kindling, multiple single-unit responses were recorded under ketamine anesthesia in response to 1-s-long periodic click trains, with click rates between 2 and 64 Hz. Neuronal responses were characterized according to their ability to respond in time-locked fashion to the clicks. Results: Kindling stimulation resulted in progression of the AD characteristics and seizure behavior, with six of 10 kindled cats reaching a fully generalized state. In the fully kindled cats, the best modulation frequencies and limiting following rates for the single-unit responses were significantly lower compared with those of naive and sham controls. Conclusions: Repeated epileptiform activity interferes with temporal processing in cat auditory cortex in the interictal state. This may have implications for people with epileptic foci in auditory-related areas. [source]


    Expression of the Multidrug Transporter P-glycoprotein in Brain Capillary Endothelial Cells and Brain Parenchyma of Amygdala-kindled Rats

    EPILEPSIA, Issue 7 2002
    Ulrike Seegers
    Summary: ,Purpose: Based on data from brain biopsy samples of patients with pharmacoresistant partial epilepsy, overexpression of the multidrug transporter P-glycoprotein (PGP) in brain capillary endothelium has recently been proposed as a potential mechanism of resistance to antiepileptic drugs (AEDs). We examined whether PGP is overexpressed in brain regions of amygdala-kindled rats, a widely used model of temporal lobe epilepsy (TLE), which is often resistant to AEDs. Methods: Rats were kindled by stimulation of the basolateral amygdala (BLA); electrode-implanted but nonkindled rats and naive (not implanted) rats served as controls. PGP was determined by immunohistochemistry either 1 or 2 weeks after the last kindled seizure, by using a monoclonal anti-PGP antibody. Six brain regions were examined ipsi- and contralateral to the BLA electrode: the BLA, the hippocampal formation, the piriform cortex, the substantia nigra, the frontal and parietal cortex, and the cerebellum. Results: In both kindled rats and controls, PGP staining was observed mainly in microvessel endothelial cells and, to a much lesser extent, in parenchymal cells. The distribution of PGP expression across brain regions was not homogeneous, but significant differences were found in both the endothelial and parenchymal expression of this protein. In kindled rats, ipsilateral PGP expression tended to be higher than contralateral expression in several brain regions, which was statistically significant in the piriform cortex and parietal cortex. However, compared with controls, no significant overexpression of PGP in capillary endothelial cells or brain parenchyma of kindled rats was seen in any ipsilateral brain region, including the BLA. For comparison with kindled rats, kainate-treated rats were used as positive controls. As reported previously, kainate-induced seizures significantly increased PGP expression in the hippocampus and other limbic brain regions. Conclusions: Amygdala-kindling does not induce any lasting overexpression of PGP in several brain regions previously involved in the kindling process. In view of the many pathophysiologic and pharmacologic similarities between the kindling model and TLE, these data may indicate that PGP overexpression in pharmacoresistant patients with TLE is a result of uncontrolled seizures but not of the processes underlying epilepsy. It remains to be determined whether transient PGP overexpression is present in kindled rats shortly after a seizure, and whether pharmacoresistant subgroups of kindled rats exhibit an increased expression of PGP. Furthermore, other multidrug transporters, such as multidrug resistance,associated protein, might be involved in the resistance of kindled rats to AEDs. [source]


    Innate and Learned Components of Defence by Flickers Against a Novel Nest Competitor, the European Starling

    ETHOLOGY, Issue 10 2004
    Karen L. Wiebe
    Defence against predators is an important component of fitness in wild birds but the first step of defence, predator recognition, is not well understood. Anti-predator behaviour may innate, in which case the individual responds without prior contact with that predator, and/or there may be a learned component that develops only after direct experience. In the wild, the development of anti-predator behaviour is studied by exposing naive individuals to novel predators. I studied responses of 71 naive and experienced northern flickers Colaptes auratus, to a novel nest predator and competitor, the European starling Sturnus vulgaris that was introduced to North America. Naive individuals responded more intensely to the model starling than to the control model suggesting an innate component to recognition. However, there was also a learned component to defence because flickers nesting near to starlings reacted more aggressively than naive individuals far from starlings. Consistent with theory on life histories and optimal defence levels, no significant differences in aggression were found between the sexes or between age classes. Selection should favour more intense, and possibly innate, defence against the introduced starling. Variation in responses of naive individuals suggests that there may already be some alleles in the population associated with higher defence, but that these may not be uniform within the population. [source]


    T-bet expression by dendritic cells is required for the repolarization of allergic airway inflammation,

    EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 9 2008
    Karin L. Heckman
    Abstract By cross-linking B7-DC on dendritic cells (DC) the human IgM antibody (B7-DC XAb) shifts polarized immune responses from Th2 to Th1 in an antigen-specific manner. The molecular determinants governing the ability of DC to reprogram the polarity of T cell recall responses are not yet known. In addition to the expected role of T-bet expressed by T cells in regulating Th1 responses, we find using in vitro assays and an established in vivo model of allergic airway inflammation that T-bet expression by DC is also required for the polarity shift promoted by B7-DC XAb. T-bet expression by both T cells and DC is critically important for B7-DC XAb-induced down-regulation of IL-4, up-regulation of IFN-, and suppression of allergic airway inflammation. Moreover, retroviral reconstitution of T-bet expression in T-bet-deficient DC rescued their ability to modulate both naive and memory T-cell responses from Th2 to Th1. Our observations further our understanding of the critical mediators controlling the ability of DC to modify the responses of previously activated T cells and reveal the interesting use of the same transcription factor to regulate the inductive phenotype of DC and the inducible phenotype of T cells. [source]


    The immune status of Kupffer cells profoundly influences their responses to infectious Plasmodium berghei sporozoites

    EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 8 2005
    Nick Steers
    Abstract Multi-factorial immune mechanisms underlie protection induced with radiation-attenuated Plasmodia sporozoites (,-spz). Spz pass through Kupffer cells (KC) before invading hepatocytes but the involvement of KC in protection is poorly understood. In this study we investigated whether ,-spz-immune KC respond to infectious spz in a manner that is distinct from the response of naive KC to infectious spz. KC were isolated from (1) naive, (2) spz-infected, (3) ,-spz-immune, and (4) ,-spz-immune-challenged C57BL/6 mice and examined for the expression of MHC class I and II, CD40 and CD80/CD86, IL-10 and IL-12 responses and antigen-presenting cell (APC) function. KC from ,-spz-immune-challenged mice up-regulated class I and costimulatory molecules and produced elevated IL-12p40, relative to naive KC. In contrast, KC from naive mice exposed to infectious spz down-modulated class I and IL-12p40 was undetectable. Accordingly, KC from spz-infected mice had reduced APC function, while KC from ,-spz-immune-challenged mice exhibited augmented APC activity. The nearly opposite responses are consistent with the fact that spz challenge of ,-spz-immune mice results in long-lasting sterile protection, while infection of naive mice always results in malaria. [source]


    Phenotypic classification of human CD8+ T,cells reflecting their function: inverse correlation between quantitative expression of CD27 and cytotoxic effector function

    EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 4 2004
    Hiroko Tomiyama
    Abstract Phenotypic classification of human CD8+ T,cells using three cell surface markers, CD27, CD28 and CD45RA, was recently suggested to be useful for identification of naive, memory and effector CD8+ T,cells. However, it still remains unclear whether such classification precisely reflects functional classification of CD8+ T,cells. To clarify this, we characterized each CD27CD28CD45RA subset of total and human cytomegalovirus (HCMV)-specific CD8+ T,cells by analyzing the expression of perforin and two chemokine receptors, CCR5 and CCR7, as well as their function. An inverse correlation between perforin and CD27 expression was found in all four CD28CD45RA subsets. Therefore, to achieve a phenotypic classification of CD8+ T,cells that moreprecisely reflects their function, the CD27+ subset was divided into CD27low and CD27high subsets based on the expression level of CD27. Functional and flow cytometric analyses of CD27CD28CD45RA subsets showed that this phenotypic classification reflects functional classification of CD8+ T,cells. HCMV-specific CD8+ T,cells from healthy HCMV-seropositive individuals were predominantly found in effector and memory/effector subsets, indicating that HCMV-specific effector CD8+ T,cells are actively induced by HCMV replication in healthy HCMV carriers. Phenotypic analyses of CD8+ T,cells using this classification will enable the characterization of antigen-specific CD8+ T,cells. [source]


    The Toll-like receptor ligand MALP-2 stimulates dendritic cell maturation and modulates proteasome composition and activity

    EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 3 2004
    Claudia Link
    Abstract A 2-kDa synthetic derivative of the macrophage-activating lipopeptide (MALP-2) from Mycoplasma fermentans is a potent inducer of monocytes/macrophages and improves the immunogenicity of antigens co-administered by systemic and mucosal routes. Dendritic cells (DC) are the most potent antigen-presenting cells, which are able to prime naive T cells in vivo. To elucidate the underlying mechanisms of MALP-2 adjuvanticity, we analyzed its activity on bone marrow-derived murine DC. In vitro stimulation of immature murine DC with MALP-2 resulted in the induction of maturation with up-regulated expression of MHC class II, costimulatory (CD80, CD86) and adhesion (CD40, CD54) molecules. MALP-2 also enhances the secretion of cytokines (IL-1,, IL-6 and IL-12), and increases DC stimulatory activity on naive and antigen-specific T cells. Further studies demonstrated that MALP-2 treatment of DC results in a dose-dependent shift from the protein pattern of proteasomes to immunoproteasomes (up-regulation of LMP2, LMP7 and MECL1), which correlates with an increased proteolytic activity. Thus, the adjuvanticity of MALP-2 can be mediated, at least in part, by the stimulation of DC maturation, which in turn leads to an improved antigen presentation. Therefore, MALP-2 is a promising molecule for the development of immune therapeutic or prophylactic interventions. [source]


    SHORT COMMUNICATION Learning-induced reduction in post-burst after-hyperpolarization (AHP) is mediated by activation of PKC

    EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 5 2002
    Yaron Seroussi
    Abstract We studied the role of protein kinase C (PKC) and protein kinase A (PKA) in mediating learning-related long lasting reduction of the post-burst after-hyperpolarization (AHP) in cortical pyramidal neurons. We have shown previously that pyramidal neurons in the rat piriform (olfactory) cortex from trained (TR) rats have reduced post-burst AHP for 3 days after odour-discrimination learning, and that this reduction is due to decreased conductance of calcium-dependent potassium current. In the present study, we examined whether this long-lasting reduction in AHP is mediated by second messenger systems. The broad-spectrum kinase inhibitor, H7, increased the AHP in neurons from TR rats, but not in neurons from pseudo-trained (pseudo-TR) and naive rats. Consequently, the difference in AHP amplitude between neurons from TR and control animals was diminished. This effect was also obtained by application of the specific PKC inhibitor, GF-109203x. The PKC activator, 1-Oleoyl-2-acetyl- sn -glycerol (OAG), significantly reduced the AHP in neurons from naive and pseudo-TR rats, but not in neurons from TR rats, so that the difference between the groups was abolished. The PKA-specific inhibitor, H-89, increased the AHP in neurons from all groups to a similar extent, and the difference in AHP amplitude between neurons from TR rats and neurons from controls was maintained. We suggest that while the post-burst AHP in piriform cortex pyramidal neurons is modulated by both PKC and PKA, a PKC-dependent process maintains the learning-related reduction of the AHP in these cells. [source]


    Corporate Social Responsibility European Style

    EUROPEAN LAW JOURNAL, Issue 2 2008
    Olivier De Schutter
    This article explains how, while CSR may have been initially an idea about the scope of the responsibility of companies towards their environment, it has now become a process in which the representatives of the business community have come to occupy the main role, and whose purpose is to promote learning among business organisations, rather than to identify the components of a regulatory framework for CSR. The central question now, therefore, is whether the so-called ,business case' for CSR is strong enough, so that we may hope that the forces of market will suffice to encourage companies to behave responsibly, over and above their obligation to comply with their legal obligations. The article shows, however, that this case rests on certain presuppositions about markets and the business environment, which cannot be simply assumed, but should be affirmatively created by a regulatory framework for CSR. Following the introduction, it proceeds in four stages. First, it examines the development of CSR in the EU. Second, it offers a critical examination of the so-called ,business case' for CSR, taking into account the growing diversity within the enlarged EU. It then discusses, as an alternative, what a regulatory framework for CSR could resemble, highlighting a number of initiatives which have been taken in this regard by the EU. The article finally concludes that, since the failure of the European Multi-Stakeholder Forum on CSR in 2004, the debate has made a turn in the wrong direction, both because of the mistaken view that the establishment of a regulatory framework for CSR would threaten the competitiveness of European companies, and because of the naive (and contradictory) view that reliance on market mechanisms will suffice to ensure that corporations will seek to minimise the negative social and environmental impacts of their activities, even in circumstances where they are not legally obliged to do so. [source]


    VACCINATION, WITHIN-HOST DYNAMICS, AND VIRULENCE EVOLUTION

    EVOLUTION, Issue 1 2006
    Jean-Baptiste André
    Abstract We explore the potential consequences of vaccination on parasite epidemiology and evolution. Our model combines a microscopic (within-host dynamics) and a macroscopic (epidemiological dynamics) description of the interaction between the parasite and its host. This approach allows relevant epidemiological traits such as parasite transmission, parasite virulence, and host recovery to emerge from a mechanistic model of acute infection describing the interaction between the parasite and the host immune system. We model the effect of a vaccine as an activator of immunity enhancing the replication rate of lymphocytes, their initial density at infection's initiation, their efficacy to kill the parasite, or their activation delay after infection. We analyze the evolution of the replication rate of parasites and show that vaccination may promote the evolution of faster replicating and, consequently, more virulent strains. We also show that intermediate vaccination coverage may lead to the coexistence of two different parasite strategies (a low-virulence strain adapted to naive hosts, and a high-virulence strain, more generalist, adapted to both naive and vaccinated hosts). We discuss the consequences of various vaccination strategies under different epidemiological situations using several distinct measures to evaluate the cost induced by the parasite on individuals and entire host populations. [source]


    PERSPECTIVE: THE EVOLUTION OF WARNING COLORATION IS NOT PARADOXICAL

    EVOLUTION, Issue 5 2005
    Nicola M. Marples
    Abstract Animals that are brightly colored have intrigued scientists since the time of Darwin, because it seems surprising that prey should have evolved to be clearly visible to predators. Often this self-advertisement is explained by the prey being unprofitable in some way, with the conspicuous warning coloration helping to protect the prey because it signals to potential predators that the prey is unprofitable. However, such signals only work in this way once predators have learned to associate the conspicuous color with the unprofitability of the prey. The evolution of warning coloration is still widely considered to be a paradox, because it has traditionally been assumed that the very first brightly colored individuals would be at an immediate selective disadvantage because of their greater conspicuousness to predators that are naive to the meaning of the signal. As a result, it has been difficult to understand how a novel conspicuous color morph could ever avoid extinction for long enough for predators to become educated about the signal. Thus, the traditional view that the evolution of warning coloration is difficult to explain rests entirely on assumptions about the foraging behavior of predators. However, we review recent evidence from a range of studies of predator foraging decisions, which refute these established assumptions. These studies show that: (1) Many predators are so conservative in their food preferences that even very conspicuous novel prey morphs are not necessarily at a selective disadvantage. (2) The survival and spread of novel color morphs can be simulated in field and aviary experiments using real predators (birds) foraging on successive generations of artificial prey populations. This work demostrates that the foraging preferences of predators can regularly (though not always) result in the increase to fixation of a novel morph appearing in a population of familiar-colored prey. Such fixation events occur even if both novel and familiar prey are fully palatable and despite the novel food being much more conspicuous than the familiar prey. These studies therefore provide strong empirical evidence that conspicuous coloration can evolve readily, and repeatedly, as a result of the conservative foraging decisions of predators. [source]


    Alloantigen gene therapy for head and neck cancer: Evaluation of animal models,

    HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 4 2003
    Lyon L. Gleich MD
    Abstract Background. Human trials of alloantigen gene therapy, using the class I major histocompatibility complex (MHC) HLA-B7, have demonstrated the potential efficacy of this treatment for head and neck cancer. Its mechanism remains unclear. An immune-competent mouse model of MHC gene therapy to test factors potentially important to the tumor response is needed. Methods. Two cell lines were used, B4B8 cells that grow in Balb/c mice and SCC-VII cells that grow in C3H mice. The mouse MHC H2-Kb was used as the therapeutic gene, because it is an alloantigen to both mice strains. Plasmids that encode the H2-Kb cDNA were prepared, and the cell lines were transfected. Mice were injected subcutaneously with naive cells to determine the tumor kinetics and serve as controls. Mice were injected with H2-Kb transfected cells and tumor growth was compared with controls. Mice that did not grow tumor were rechallenged with naive cells to assess for tumor immunity. Mice were injected with transfected and naive cells admixed to determine whether the concentration of the alloantigen is important. Results. B4B8 tumors grew slowly, whereas SCC-VII tumors grew rapidly. Transfection with H2-Kb plasmid prevented or inhibited tumor growth of both the B4B8 and SCC-VII tumors. This growth inhibition was independent of the number of cells injected. In the mice that did not grow tumor, tumor immunity was demonstrated after challenge with naive cells in both models. There was no relationship between induction of immunity and the timing of the challenge or initial cell quantity. The mice injected with a mixture of naive and transfected cells grew tumor, although growth was delayed in the B4B8 model. Conclusions. The results demonstrate that the two mouse models can serve as a rapid and slow growing tumor model of alloantigen gene therapy. In addition, it was noted that initial tumor cell number is not a significant factor for predicting tumor response and demonstrated that in both of these models alloantigen gene therapy results in significant antitumor immunity. © 2003 Wiley Periodicals, Inc. Head Neck 25: 274,279, 2003 [source]


    Enhanced T cell transmigration across the murine liver sinusoidal endothelium is mediated by transcytosis and surface presentation of chemokines,

    HEPATOLOGY, Issue 4 2008
    Arnhild Schrage
    Transmigration through the liver endothelium is a prerequisite for the homeostatic balance of intrahepatic T cells and a key regulator of inflammatory processes within the liver. Extravasation into the liver parenchyma is regulated by the distinct expression patterns of adhesion molecules and chemokines and their receptors on the lymphocyte and endothelial cell surface. In the present study, we investigated whether liver sinusoidal endothelial cells (LSEC) inhibit or support the chemokine-driven transmigration and differentially influence the transmigration of pro-inflammatory or anti-inflammatory CD4+ T cells, indicating a mechanism of hepatic immunoregulation. Finally, the results shed light on the molecular mechanisms by which LSEC modulate chemokine-dependent transmigration. LSEC significantly enhanced the chemotactic effect of CXC-motif chemokine ligand 12 (CXCL12) and CXCL9, but not of CXCL16 or CCL20, on naive and memory CD4+ T cells of a T helper 1, T helper 2, or interleukin-10,producing phenotype. In contrast, brain and lymphatic endothelioma cells and ex vivo isolated lung endothelia inhibited chemokine-driven transmigration. As for the molecular mechanisms, chemokine-induced activation of LSEC was excluded by blockage of Gi -protein,coupled signaling and the use of knockout mice. After preincubation of CXCL12 to the basal side, LSEC took up CXCL12 and enhanced transmigration as efficiently as in the presence of the soluble chemokine. Blockage of transcytosis in LSEC significantly inhibited this effect, and this suggested that chemokines taken up from the basolateral side and presented on the luminal side of endothelial cells trigger T cell transmigration. Conclusion: Our findings demonstrate a unique capacity of LSEC to present chemokines to circulating lymphocytes and highlight the importance of endothelial cells for the in vivo effects of chemokines. Chemokine presentation by LSEC could provide a future therapeutic target for inhibiting lymphocyte immigration and suppressing hepatic inflammation. (HEPATOLOGY 2008.) [source]


    Influence of angiotensin-converting enzyme I/D gene polymorphism on clinical and histological correlates of chronic hepatitis C

    HEPATOLOGY RESEARCH, Issue 8 2009
    Carlo Fabris
    Aim:, This study aimed to verify the relationship between the insertion,deletion (I/D) polymorphism of angiotensin-converting enzyme (ACE) and clinical and histological correlates of chronic hepatitis C. Methods:, Two-hundred and fifty-eight, treatment naive, unselected hepatitis C virus (HCV) RNA-positive patients and 210 controls were studied. ACE allelic variants were determined by polymerase chain reaction. Results:, Mean staging scores adjusted for age, body mass index (BMI) and alcohol consumption were: men, D/* = 2.283; men, I/I = 2.092; women, D/* = 2.241; and women, I/I = 3.283 (P = 0.028). Age-adjusted mean BMI were: men, D/* = 25.01; men, I/I = 24.87; women, D/* = 23.73; and women, I/I = 22.50 (P = 0.006). Age and BMI-adjusted mean low-density lipoprotein (LDL)/ high-density lipoprotein (HDL) cholesterol ratios were: men, D/* = 2.344; men, I/I = 2.283; women, D/* = 1.916; and women, I/I = 1.903 (P = 0.004). Histological grading correlated positively with triglycerides and negatively with HDL and LDL cholesterol (P < 0.0001). Conclusion:, Female ACE I/I homozygotes have higher liver fibrosis scores in comparison to D/* women and to men; moreover, they are leaner and have a lower LDL/HDL cholesterol ratio. These observations suggest a possible mutual influence between ACE polymorphism, serum lipid concentrations and outcome of chronic HCV infection. [source]


    KCa2 channels transiently downregulated during spatial learning and memory in rats

    HIPPOCAMPUS, Issue 3 2010
    Bedel Mpari
    Abstract Small-conductance calcium-activated potassium channels (KCa2) are essential components involved in the modulation of neuronal excitability, underlying learning and memory. Recent evidence suggests that KCa2 channel activity reduces synaptic transmission in a postsynaptic NMDA receptor-dependent manner and is modulated by long-term potentiation. We used radioactive in situ hybridization and apamin binding to investigate the amount of KCa2 subunit mRNA and KCa2 proteins in brain structures involved in learning and memory at different stages of a radial-arm maze task in naive, pseudoconditioned, and conditioned rats. We observed significant differences in KCa2.2 and KCa2.3, but not KCa2.1 mRNA levels, between conditioned and pseudoconditioned rats. KCa2.2 levels were transiently reduced in the dorsal CA fields of the hippocampus, whereas KCa2.3 mRNA levels were reduced in the dorsal and ventral CA fields of the hippocampus, entorhinal cortex, and basolateral amygdaloid nucleus in conditioned rats, during early stages of learning. Levels of apamin-binding sites displayed a similar pattern to KCa2 mRNA levels during learning. Spatial learning performance was positively correlated with levels of apamin-binding sites and KCa2.3 mRNA in the dorsal CA1 field and negatively correlated in the dorsal CA3 field. These findings suggest that KCa2 channels are transiently downregulated in the early stages of learning and that regulation of KCa2 channel levels is involved in the modification of neuronal substrates underlying new information acquisition. © 2009 Wiley-Liss, Inc. [source]


    Quantitative analysis of human mitochondrial DNA using a real-time PCR assay

    HIV MEDICINE, Issue 3 2003
    K Gourlain
    Objectives Known for their ability to inhibit the human DNA polymerase-,, nucleoside analogues induce toxic effects on mitochondria ranging from increased serum lactate levels to fatal lactic acidosis. DNA polymerase-, ensures the mitochondrial DNA (mtDNA) replication and, thus, its inhibition leads to the decrease of the mtDNA. We describe a real-time PCR assay for mtDNA quantification associating DNA extraction procedures applied on peripheral blood mononuclear cells (PBMCs) and subcutaneous adipose tissues and to study the antiretroviral effect on mitochondria. Methods Total DNA was extracted from PBMCs and subcutaneous adipose tissues. Nuclear and mitochondrial genes were amplified to determine the number of copies of mtDNA per cell using a cyt-b recombinant plasmid as standard control. We analysed eight HIV-infected asymptomatic patients never treated, four patients who had been treated for 6 months with highly active antiretroviral therapy (HAART) and six non-infected donors. Results The mtDNA quantification gave rise to reproducible results as the mean coefficients of variation were 1.09% for replicates of samples undertaken 10 times within the same run, and 5.78% and 3.7% for replicates tested in five different runs at 1:100 and 1:1000 dilutions, respectively. Median levels of mtDNA in PBMCs of healthy donors, naive and treated HIV-infected patients were 2.94, 2.78 and 1.93 log HIV-1 RNA copies/mL, respectively. Whereas DNA from PBMCs was shown to be devoid of inhibitors, subcutaneous adipose tissues needed an extra treatment as they were found to be highly inhibited. Conclusions The method generated consistent and reproducible results and was successfully applied to DNAs extracted from PBMCs and subcutaneous adipose tissues with adapted extraction. The mtDNA changes in PBMCs were found to be fast as they fall off after 6 months' therapy, decreasing from 2.78 to 1.93 log copies/mL. [source]


    Migration of naive, effector and memory T cells: implications for the regulation of immune responses

    IMMUNOLOGICAL REVIEWS, Issue 1 2001
    Jürgen Westermann
    Summary: T cells play an important role in protective immune responses and in the pathogenesis of many diseases. Understanding the mechanisms regulating their distribution in vivo may therefore be of therapeutic value. Reviewing studies that have followed the migration of labelled naive, effector and memory T cells in healthy animals reveals that all T-cell subsets enter all organs investigated. Within the tissue, two principally different migration patterns can be identified. First, naive and memory T cells accumulate in lymphoid organs for about 48 h after injection, as the time needed for migration through lymphoid organs is longer than through non-lymphoid organs. During this time, surface molecule expression is temporarily modified. These changes are reversed before leaving the lymphoid organs and entering the blood to start a new cycle of migration. Second, effector T cells are evenly distributed throughout the body, and most die in the tissues within 24 h. However, depending on the presence of cytokines, some are able to survive and to proliferate, and thereby accumulate in defined microenvironments of the body. Analysing the principles regulating T-cell migration and survival within the tissue may lead to the development of new options for the treatment of disease. [source]


    Phenotypic profile and functional characterization of rat lymph node-derived ,, T cells: implication in the immune response to cytomegalovirus

    IMMUNOLOGY, Issue 2 2003
    Larissa Dyugovskaya
    Summary ,, T cells are unique, and their localization at sites of infection is considered critical in immune defence. We demonstrate the accumulation of ,, T cells in rat regional popliteal lymph nodes (PLNi) starting 2 days after inoculation of cytomegalovirus (CMV) into the footpad. Early-appearance PLNi ,, T cells significantly inhibited plaque development and the spread of CMV infection. These ,, T cells were negative for CD4 and CD8beta receptors, proliferated in response to interleukin-2 (IL-2) and contained high levels of interferon-, (IFN-,), the appearance of which correlated with the curing of fibroblasts from virus infection. The addition of anti-IFN-, abolished the ability of fibroblast monolayers to be cured from CMV infection. In contrast, this protection was not abolished by the addition of anti-rat IL-2 or anti-rat TNF-,, or by the depletion of NKR-P1-bearing cells within ,, T cells. In addition, the present study shows that while ,, T cells derived from naive and CMV-infected rats are able to kill both YAC-1 targets and CMV-infected syngeneic fibroblasts in vitro, only the latter are able to clear CMV-infected fibroblast monolayers. Finally, our data suggest that the expression of NKR-P1 by ,, T cells is critical for cytotoxicity, but its contribution to the curing from CMV infection was limited. [source]


    Major histocompatibility complex class II, fetal skin dendritic cells are potent accessory cells of polyclonal T-cell responses

    IMMUNOLOGY, Issue 2 2000
    A. Elbe-Bürger
    Summary Whereas dendritic cells (DC) and Langerhans cells (LC) isolated from organs of adult individuals express surface major histocompatibility complex (MHC) class II antigens, DC lines generated from fetal murine skin, while capable of activating naive, allogeneic CD8+ T cells in a MHC class I-restricted fashion, do not exhibit anti-MHC class II surface reactivity and fail to stimulate the proliferation of naive, allogeneic CD4+ T cells. To test whether the CD45+ MHC class I+ CD80+ DC line 80/1 expresses incompetent, or fails to transcribe, MHC class II molecules, we performed biochemical and molecular studies using Western blot and polymerase chain reaction analysis. We found that 80/1 DC express MHC class II molecules neither at the protein nor at the transcriptional level. Ultrastructural examination of these cells revealed the presence of a LC-like morphology with indented nuclei, active cytoplasm, intermediate filaments and dendritic processes. In contrast to adult LC, no LC-specific cytoplasmic organelles (Birbeck granules) were present. Functionally, 80/1 DC in the presence, but not in the absence, of concanavalin A and anti-T-cell receptor monoclonal antibodies stimulated a vigorous proliferative response of naive CD4+ and CD8+ T cells. Furthermore, we found that the anti-CD3-induced stimulation of naive CD4+ and CD8+ T cells was critically dependent on the expression of Fc,R on 80/1 DC and that the requirement for co-stimulation depends on the intensity of T-cell receptor signalling. [source]


    Prospective evaluation of intestinal homing memory T cells in ulcerative colitis

    INFLAMMATORY BOWEL DISEASES, Issue 5 2004
    A. L. Hart
    Abstract Background: Intestinal homing (,7+) memory T cells reflect the mucosal environment in which they were primed. We hypothesized that prospective assessment of cytokine production by intestinal homing (,7+) memory T cells in ulcerative colitis patients followed from remission to early relapse may elucidate shifts in cytokine production relevant to the mucosal environment associated with the early phase of inflammation. Methods: Twelve patients with frequently relapsing ulcerative colitis (,2 relapses in the previous 12 months) were recruited in remission and followed prospectively until relapse. Antibody labeling of whole blood and flow cytometry were used to identify ,7+ cells and ,7, populations within CD3+CD45RA, leukocytes. Production of cytokines (IFN-,, TNF-,, IL-2, IL-10, TGF-,, and IL-4) was determined by intracellular labeling. Results: Early relapse of ulcerative colitis was associated with a shift of T cells from the naive to the memory T cell pool, and further the ratio of ,7+:,7, memory T cells was significantly reduced at relapse (p < 0.01). A greater proportion of intestinal homing ,7+ memory T cells produced IL-4 (p < 0.02) and TNF-, (p < 0.05) at disease relapse compared with remission. Non-intestinal homing ,7,memory T cells also showed a tendency toward an increased production of TH1 and TH2 cytokines. Conclusions: The earliest phase of intestinal inflammation in ulcerative colitis patients is associated with an increase in both TH1 (TNF-, and TH2 (IL-4) cytokines by intestinal homing ,7+ memory T cells. These data support the principles of targeting lymphocyte trafficking as therapies in ulcerative colitis. [source]


    Why is mimicry in cuckoo eggs sometimes so poor?

    JOURNAL OF AVIAN BIOLOGY, Issue 3 2002

    I propose that the existence of imperfect adaptations (e.g. egg mimicry) in brood parasites and their hosts (e.g. discrimination abilities) could reflect age-dependent territory and nest-site selection patterns of the host. Studies of various passerines indicate that (1) older breeders tend to occupy nest sites of higher quality than do young birds (ideal despotic distribution resulting from interference competition), (2) nest-site selection affects the risk of parasitism in various habitats, (3) egg recognition in passerines has a strong learning component (therefore naive breeders tend to accept whereas older birds tend to reject parasitic eggs). Because young naive birds, who tend to accept parasitic eggs, usually breed in low-quality areas where they are frequently parasitised, while old experienced birds, who tend to reject parasitic eggs, breed in high-quality areas where they are rarely parasitised, the distribution of acceptors and rejecters with respect to the risk of parasitism is non-random, i.e. populations of some host species may consist of heavily parasitised acceptors and weakly parasitised rejecters. Therefore, the selection pressure exerted by the host on the parasite should be weaker than if brood parasitism was randomly distributed among naive and experienced breeders and affect adaptations such as egg mimicry. This could explain the existence of imperfect adaptations in some brood parasite-host systems. [source]


    Changes in immunological and virological parameters in HIV-1 infected subjects following leukapheresis

    JOURNAL OF CLINICAL APHERESIS, Issue 2 2003
    M.R. Boulassel
    Abstract In order to assess immune responses during HIV-1 therapeutic immunization, a large number of blood mononuclear cells (PBMC) are needed. Clinical tolerance and safety, as well as changes in immunological and virological parameters, were assessed, following leukapheresis in HIV-1 infected subjects with CD4+ cell count >200 × 106/l. PBMC were collected using a Fenwal CS3000 cell separator in 29 subjects with mean CD4+ cell counts of 503 × 106/l (range 172,1,119) and viral load of 2.5 log10 copies/ml (range <1.7,5.4). Twenty-four (83%) subjects were on antiretroviral therapy while 5 (17%) were untreated. The blood volume processed was 7 L over a period of 3 hours. A mean value (± standard error) of 82 ± 26 × 109/l lymphocytes was collected by a single apheresis in a mean volume of 200 ± 1.8 ml, containing 9.0 ± 1.3 × 109/l CD4+ and 10.2 ± 1.3 × 109/l CD8+ cells. The leukapheresis procedures were well tolerated and no immediate or delayed side effects were observed within 90 days of follow-up. No changes from blood pre-leukapheresis values were detected for white blood cells, lymphocytes, monocytes, CD8+, CD34+, naive and memory CD4+ cell counts immediately after, 1 h, 7 days, or within 90 days after leukapheresis. However, absolute CD4+ cell counts and percentage significantly increased from pre-leukapheresis values after 1 h (530 ± 43 vs. 700 ± 75 cell × 106/l; 32.6 ± 1.6 vs. 36.9 ± 1.9%; P < 0.001 for both paired t -tests) before returning to pre-leukapheresis levels on day 7. No significant changes in viral load from pre-leukapheresis levels in treated or untreated subjects were detected at any time points. We conclude that leukapheresis in HIV-1 infected subjects with CD4+ cell counts >200 × 106/l is safe and induces a transient increase in the absolute and percentage of CD4+ cell count without enhancing viral replication. J. Clin. Apheresis 18:55,60, 2003. © 2003 Wiley-Liss, Inc. [source]


    Phenotypical and functional analysis of T cells in periodontitis

    JOURNAL OF PERIODONTAL RESEARCH, Issue 4 2001
    M. D. A. Petit
    To explore aspects of cellular immune responses in the pathogenesis of periodontitis we analyzed phenotype and function of peripheral T cells. Two groups of subjects participated: one group consisted of 10 highly susceptible patients with severe periodontitis (mean age 29 years) and a control group consisted of 10 age, gender and race matched subjects with gingivitis. From all subjects peripheral blood was collected. The results showed that the numbers of CD3+, CD4+ and CD8+ T cells as well as the CD4/CD8 ratio, and the proliferative capacity of T cells, were not different between the two groups of subjects. Also, proportions of naive and memory T cells for both the CD4+ and CD8+ subpopulations were not different. Functional heterogeneity within the CD4+ and CD8+ T cell compartments was determined by intracellular analysis of interferon- ,(IFN- ,) and interleukin-4 (IL-4) production. On the basis of these latter analyses among CD4+ and CD8+ cells, T helper (Th) 1 or Th2 function and T cytotoxic (Tc) 1 or Tc2 function, respectively, could be deduced. No significant differences in proportions of CD4+ and CD8+ T cells positive for intracellular IFN- , or IL-4 were observed between periodontitis patients and gingivitis controls; however a higher level of intracellular IL-4 in CD8+ T cells was seen in periodontitis patients. This might indicate that there is a shift towards a Tc2 function within the CD8+ T cell subpopulation. The current explorative study suggests that further research into the role of CD8+T cells in the pathogenesis of periodontitis is warranted. [source]


    Disruption of Maternal Behavior by Alcohol Intoxication in the Lactating Rat: A Behavioral and Metabolic Analysis

    ALCOHOLISM, Issue 8 2002
    Marta Yanina Pepino
    Background Preweanling rats exhibit clear behavioral signs of distress after interacting with an alcohol-intoxicated dam. Interestingly, behavioral reactivity of infants to the experience of alcohol in the nursing context decreases as a function of repeated alcohol administrations to the mother. In this study, maternal activities were examined when dams were exposed to repeated administrations of a subnarcoleptic alcohol dose. Maternal changes in alcohol metabolism were also analyzed as a function of repeated exposures to the drug. Methods During postpartum days 3, 5, 7, 9, 11, and 13, nursing dams received an intragastric administration of either 2.5 g/kg of alcohol or water. Maternal behaviors were evaluated (experiment 1). Blood alcohol levels (BALs) of the dams were determined on postpartum day 16 after all mothers received either an intragastric (experiment 2) or an intraperitoneal (experiment 3) dose of alcohol. The doses used (2.5 g/kg intragastrically and 1.5 g/kg intraperitoneally) were chosen because they promote similar peak BALs in dams naive to alcohol. Results Maternal behaviors were strongly affected by the state of intoxication. Nevertheless, these disruptions clearly subsided with progression of alcohol-related experiences (experiment 1). Chromatographic analysis of alcohol metabolism indicated the development of tolerance in dams that had prior experience with alcohol (experiment 2). Changes in BALs as a function of prior experience with alcohol seemed related to first-pass alcohol metabolism rather than hepatic oxidative processes of the drug (experiments 2 and 3). Conclusions When the dam first experiences a moderate state of alcohol intoxication, maternal behaviors are uniformly disrupted. Subsequent exposures to alcohol lead to maternal metabolic tolerance. In conjunction with previous studies, these data indicate that infantile reactivity to alcohol is dependent on how the members of the dam/pup dyad express or perceive ethanol's postabsorptive effects. [source]