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1 Pre-treatment TEP SCAN (a) and after 3 months of treatment (b) A PET scan was performed after the third cycle of association showing a complete metabolic remission (Fig. 1:CAS:528:DC%2BD1MXmvFyjur0%3D. 10.1111/j.1365-2141.2009.07679.x 2 Garnache-Ottou F, Vidal C, Biichlé S, Renosi F, Poret E, Pagadoy M. How should we diagnose and treat blastic plasmacytoid dendritic cell neoplasm patients? Recent papers [[6]-[8]] showed that venetoclax combined with decitabine or 5-Aza in treatment-naive elderly patients with AML was effective and well tolerated, leading this association to become a standard of treatment in this indication. [Extracted from the article]

Immunotherapy is considered as an effective method for cancer treatment owing to the induction of specific and long-lasting anti-cancer effects. Immunotherapeutic strategies have shown significant success in human malignancies, particularly in prostate cancer (PCa), a major global health issue regarding its high metastatic rates. In fact, the first cancer vaccine approved by FDA was Provenge, which has been successfully used for treatment of PCa. Despite the remarkable success of cancer immunotherapy in PCa, many of the developed immunotherapy methods show poor therapeutic outcomes. Immunosuppression in tumor microenvironment (TME) induced by non-functional T cells (CD4+ and CD8+), tolerogenic dendritic cells (DCs), and regulatory T cells, has been reported to be the main obstacle to the effectiveness of anti-tumor immune responses induced by an immunotherapy method. The present review particularly focuses on the latest findings of the immune checkpoints (ICPs), including CTLA-4, PD-1, PD-L1, LAG-3, OX40, B7-H3, 4-1BB, VISTA, TIM-3, and ICOS; these checkpoints are able to have immune modulatory effects on the TME of PCa. This paper further discusses different approaches in ICPs targeting therapy and summarizes the latest advances in the clinical application of ICP-targeted therapy as monotherapy or in combination with other cancer therapy modalities in PCa. [ABSTRACT FROM AUTHOR]

The dendritic cell algorithm (DCA) is a classification algorithm based on the behavior of natural dendritic cells (DCs). In literature, DCA has given good classification results. However, DCA was known to be sensitive to the order of the instance classes. To solve this limitation, a fuzzy DCA version was developed stating that the cause of such sensitivity is related to the DCA crisp classification task (hypothesis 1). In this paper, we hypothesize that there is a second possible cause of such DCA sensitivity which is related to the possible existence of noisy instances presented in the DCA signal data set (hypothesis 2). Thus, we aim, first of all, to test the trueness of the latter hypothesis, and second, we aim to develop an overall hybrid DCA taking both hypotheses into consideration. Based on hypothesis 1, our new DCA focuses on smoothing the crisp classification task using fuzzy set theory. Based on hypothesis 2, a data set cleaning technique is used to guarantee the quality of the DCA signal data set. Results show that our proposed hybrid fuzzy maintained algorithm succeeds in obtaining results of interest. [ABSTRACT FROM AUTHOR]

Lung cancer is currently the leading cause of cancer-related mortality with very limited effective therapy. Screening of a variety of traditional Chinese medicines (TCMs) for their capacity to inhibit the proliferation of human lung cancer A549 cells and to induce the in vitro maturation of human DCs led to the identification of cryptotanshinone (CT), a compound purified from the TCM Salvia miltiorrhiza Bunge. Here, CT was shown to inhibit the proliferation of mouse Lewis lung carcinoma (LLC) cells by upregulating p53, downregulating cyclin B1 and Cdc2, and, consequently, inducing G2/M cell-cycle arrest of LLC cells. In addition, CT promoted maturation of mouse and human DCs with upregulation of costimulatory and MHC molecules and stimulated DCs to produce TNFα, IL-1β, and IL-12p70, but not IL-10 in vitro. CT-induced maturation of DCs depended on MyD88 and also involved the activation of NF-κB, p38, and JNK. CT was effective in the treatment of LLC tumors and, when used in combination with low doses of anti-PD-L1, cured LLC-bearing mice with the induction of subsequent anti-LLC long-term specific immunity. CT treatment promoted T-cell infiltration and elevated the expression of genes typical of Th1 polarization in LLC tumor tissue. The therapeutic effect of CT and low doses of anti-PD-L1 was reduced by depletion of CD4 and CD8 T cells. This paper provides the first report that CT induces immunological antitumor activities and may provide a new promising antitumor immunotherapeutic. [ABSTRACT FROM AUTHOR]

Dendritic cell (DC)-based immunotherapies have been created for a broad expanse of cancers, and DC vaccines prepared with Wilms' tumor protein 1 (WT1) peptides have shown great therapeutic efficacy in these diseases. In this paper, we report the results of a phase I/II study of a DC-based vaccination for advanced breast, ovarian, and gastric cancers, and we offer evidence that patients can be effectively vaccinated with autologous DCs pulsed with WT1 peptide. There were ten patients who took part in this clinical study; they were treated biweekly with a WT1 peptide-pulsed DC vaccination, with toxicity and clinical and immunological responses as the principal endpoints. All of the adverse events to DC vaccinations were tolerable under an adjuvant setting. The clinical response was stable disease in seven patients. Karnofsky Performance Scale scores were enhanced, and computed tomography scans revealed tumor shrinkage in three of seven patients. Human leukocyte antigen (HLA)/WT1-tetramer and cytoplasmic IFN-γ assays were used to examine the induction of a WT-1-specific immune response. The immunological responses to DC vaccination were significantly correlated with fewer myeloid-derived suppressor cells (P = 0.045) in the pretreated peripheral blood. These outcomes offered initial clinical evidence that the WT1 peptide-pulsed DC vaccination is a potential treatment for advanced cancer. [ABSTRACT FROM AUTHOR]

This paper compared the applicability of nickel-copper and nickel-nickel oxide metallic foams as current collectors for supercapacitor. A comprehensive characterization of foams was presented and includes the analysis of their structural, chemical, and electrochemical properties. Several techniques such as structural characteristics and electrochemical methods were used to examine the surface morphology and surface chemical composition of these materials. The process was studied under well-defined experimental conditions using cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), and galvanostatic charge and discharge (GCD). The outcome of these experiments demonstrated that the Ni-NiO foam had a higher specific capacitance than Ni-Cu foam. The best specific capacitance for Ni-NiO foam was calculated to be 924 F/g at 1 A/g, which was higher than that obtained for Ni-Cu foam (536 F/g at 1 A/g). Ni-NiO foam maintained 81.8% of its specific capacitance at a current density of 20 A/g and after 3000 cycles, without significant loss of supercapacitor activity.Schematic illustration of the fabrication process of Ni-NiO foam arrays on the copper substrate. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]

It is well established that in problems featuring slow passage through a Hopf bifurcation (dynamic Hopf bifurcation) the transition to large-amplitude oscillations may not occur until the slowly changing parameter considerably exceeds the value predicted from the static Hopf bifurcation analysis (temporal delay effect), with the length of the delay depending upon the initial value of the slowly changing parameter (temporal memory effect). In this paper we introduce new delay and memory effect phenomena using both analytic (WKB method) and numerical methods. We present a reaction-diffusion system for which slowly ramping a stimulus parameter (injected current) through a Hopf bifurcation elicits large-amplitude oscillations confined to a location a significant distance from the injection site (spatial delay effect). Furthermore, if the initial current value changes, this location may change (spatial memory effect). Our reaction-diffusion system is Baer and Rinzel's continuum model of a spiny dendritic cable; this system consists of a passive dendritic cable weakly coupled to excitable dendritic spines. We compare results for this system with those for nerve cable models in which there is stronger coupling between the reactive and diffusive portions of the system. Finally, we show mathematically that Hodgkin and Huxley were correct in their assertion that for a sufficiently slow current ramp and a sufficiently large cable length, no value of injected current would cause their model of an excitable cable to fire; we call this phenomenon 'complete accommodation.' [ABSTRACT FROM AUTHOR]

Environmental variables responsible for the increasing allergic disease burden observed in developed countries over the last century have yet to be adequately characterized. Meta-analyses of epidemiological studies presented in the first half of this paper demonstrate a correlation between farm-associated exposures (i.e., livestock, pets, unpasteurized milk, and endotoxin) and a reduction in allergic risk during childhood. Laboratory investigations discussed in the second half of the paper characterize the intrinsic immunostimulatory activities of living environments. Considered together, experimental findings presented herein suggest a novel paradigm by which early life home exposures to microbial products and other allergen-nonspecific immunostimulants modify allergic risk. [ABSTRACT FROM AUTHOR]

Abstract  At present two growth models describe successfully the distribution of size and topological complexity in populations of dendritic trees with considerable accuracy and simplicity, the BE model (Van Pelt et al. in J. Comp. Neurol. 387:325–340, 1997) and the S model (Van Pelt and Verwer in Bull. Math. Biol. 48:197–211, 1986). This paper discusses the mathematical basis of these models and analyzes quantitatively the relationship between the BE model and the S model assumed in the literature by developing a new explicit equation describing the BES model (a dendritic growth model integrating the features of both preceding models; Van Pelt et al. in J. Comp. Neurol. 387:325–340, 1997). In numerous studies it is implicitly presupposed that the S model is conditionally linked to the BE model (Granato and Van Pelt in Brain Res. Dev. Brain Res. 142:223–227, 2003; Uylings and Van Pelt in Network 13:397–414, 2002; Van Pelt, Dityatev and Uylings in J. Comp. Neurol. 387:325–340, 1997; Van Pelt and Schierwagen in Math. Biosci. 188:147–155, 2004; Van Pelt and Uylings in Network. 13:261–281, 2002; Van Pelt, Van Ooyen and Uylings in Modeling Dendritic Geometry and the Development of Nerve Connections, pp 179, 2000). In this paper we prove the non-exactness of this assumption, quantify involved errors and determine the conditions under which the BE and S models can be separately used instead of the BES model, which is more exact but considerably more difficult to apply. This study leads to a novel expression describing the BE model in an analytical closed form, much more efficient than the traditional iterative equation (Van Pelt et al. in J. Comp. Neurol. 387:325–340, 1997) in many neuronal classes. Finally we propose a new algorithm in order to obtain the values of the parameters of the BE model when this growth model is matched to experimental data, and discuss its advantages and improvements over the more commonly used procedures. [ABSTRACT FROM AUTHOR]

Type 1 diabetes (T1D) is often triggered by a viral infection, but the T1D prevalence is rising among populations that have a lower exposure to viral infection. In an animal model of T1D, the NOD mouse, viral infection at different ages may either accelerate or delay disease depending on the age of infection and the type of virus. Viral infection may affect the progression of T1D via multiple mechanisms: triggering inflammation, bystander activation of self-reactive T-cells, inducing a competitive immune response, or inducing a regulatory immune response. In this paper, we create mathematical models of the interaction of viral infection with T1D progression, incorporating each of these four mechanisms. Our goal is to understand how each viral mechanism interacts with the age of infection. The model predicts that each viral mechanism has a unique pattern of interaction with disease progression. Viral inflammation always accelerates disease, but the effect decreases with age of infection. Bystander activation has little effect at younger ages and actually decreases incidence at later ages while accelerating disease in mice that do get the disease. A competitive immune response to infection can decrease incidence at young ages and increase it at older ages, with the effect decreasing over time. Finally, an induced Treg response decreases incidence at any age of infection, but the effect decreases with age. Some of these patterns resemble those seen experimentally. [ABSTRACT FROM AUTHOR]

The Dendritic Cell Algorithm (DCA) is an immune-inspired algorithm based on the behavior of natural dendritic cells. The DCA, as a binary classifier, classifies in a crisp manner each data item as either normal or anomalous. However, it was shown that DCA is sensitive to the input class data order. This problem was solved by the development of the fuzzy dendritic cell algorithm. The performance of the latter algorithm relies on its parameters tuning as this process is based on the use of a fuzzy clustering technique. We, thus, believe that the choice of the right fuzzy clustering technique is crucial for the system. In this paper, we try to review the fuzzy version of DCA and to investigate its performance when hybridized with different fuzzy clustering techniques. The aim of this hybridization is to select the most appropriate fuzzy clustering approach in order to generate an overall automated robust fuzzy DCA classifier. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]

Lipids are important in several biological processes because they act as signalling and regulating molecules, or, locally, as membrane components that modulate protein function. This paper reports the pattern of lipid composition of dendritic cells (DCs), a cell type of critical importance in inflammatory and immune responses. After activation by antigens, DCs undergo drastic phenotypical and functional transformations, in a process known as maturation. To better characterize this process, changes of lipid profile were evaluated by use of a lipidomic approach. As an experimental model of DCs, we used a foetal skin-derived dendritic cell line (FSDC) induced to mature by treatment with lipopolysaccharide (LPS). The results showed that LPS treatment increased ceramide (Cer) and phosphatidylcholine (PC) levels and reduced sphingomyelin (SM) and phosphatidylinositol (PI) content. Mass spectrometric analysis of a total lipid extract and of each class of lipids revealed that maturation promoted clear changes in ceramide profile. Quantitative analysis enabled identification of an increase in the total ceramide content and enhanced Cer at m/ z 646.6, identified as Cer(d18:1/24:1), and at m/ z 648.6, identified as Cer(d18:1/24:0). The pattern of change of these lipids give an extremely rich source of data for evaluating modulation of specific lipid species triggered during DC maturation. [ABSTRACT FROM AUTHOR]

In this paper, we present a biologically detailed mathematical model of tripartite synapses, where astrocytes modulate short-term synaptic plasticity. The model consists of a pre-synaptic bouton, a post-synaptic dendritic spine-head, a synaptic cleft and a peri-synaptic astrocyte controlling Ca dynamics inside the synaptic bouton. This in turn controls glutamate release dynamics in the cleft. As a consequence of this, glutamate concentration in the cleft has been modeled, in which glutamate reuptake by astrocytes has also been incorporated. Finally, dendritic spine-head dynamics has been modeled. As an application, this model clearly shows synaptic potentiation in the hippocampal region, i.e., astrocyte Ca mediates synaptic plasticity, which is in conformity with the majority of the recent findings (Perea and Araque (Science 317, 1083-1086, ); Henneberger et al. (Nature 463, 232-236, ); Navarrete et al. (PLoS Biol. 10, e1001259, )). [ABSTRACT FROM AUTHOR]

Neuronal membrane capacitance C is one of the prominent factors in action potential initiation and propagation and then influences the firing patterns of neurons. Exploring the roles that C plays in different firing patterns can facilitate the understanding of how different factors might influence neuronal firing behaviors. However, the impacts of variations in C on neuronal firing patterns have been only partly explored until now. In this study, the influence of C on burst firing behaviors of a two-compartment pyramidal neuron (including somatic compartment and dendritic compartment) was investigated by means of computer simulation, the value of C in each compartment was denoted as C and C, respectively. Two cases were considered, in the first case, we let C = C, and then changed them simultaneously. While in the second case, we assumed C ≠ C, and then changed them, respectively. From the simulation results obtained from these two cases, it was found that the variation of C in the somatic compartment and the dendritic compartment show much difference, simulated results obtained from the variation of C have much more similarities than that of C when comparing with the results obtained in the first case under which C = C. These different effects of C and C on neuronal firing behaviors may result from the different topology and functional roles of soma and dendrites. Numerical results demonstrated in this paper may give us some inspiration in understanding the possible roles of C in burst firing patterns, especially their transitions in compartmental neurons. [ABSTRACT FROM AUTHOR]

Cytotoxic T-lymphocyte (CTL) escape mutation is associated with long-term behaviors of human immunodeficiency virus type 1 (HIV-1). Recent studies indicate heterogeneous behaviors of reversible and conservative mutants while the selection pressure changes. The purpose of this study is to optimize the selection pressure to minimize the long-term virus load. The results can be used to assist in delivery of highly loaded cognate peptide-pulsed dendritic cells (DC) into lymph nodes that could change the selection pressure. This mechanism may be employed for controlled drug delivery. A mathematical model is proposed in this paper to describe the evolutionary dynamics involving viruses and T cells. We formulate the optimization problem into the framework of evolutionary game theory, and solve for the optimal control of the selection pressure as a neighborhood invader strategy. The strategy dynamics can be obtained to evolve the immune system to the best controlled state. The study may shed light on optimal design of HIV-1 therapy based on optimization of adaptive CTL immune response. [ABSTRACT FROM AUTHOR]

The use of Trojan Y chromosomes has been proposed as a genetic strategy for the eradication of invasive species. The strategy is particularly relevant to invasive fish species that have XY sex determination system and are amenable to sex-reversal. In this paper we study the dynamics of an invasive fish population occupying a dendritic domain in which Trojan individuals bearing multiple Y chromosomes have been released as a means of eradication. We demonstrate the existence of a bounded absorbing set that represents extinction of the invasive species irrespective of the dendritic configuration. The method of analysis used to obtain global estimates could be applied to other population problems and other geometries. [ABSTRACT FROM AUTHOR]

Purpose: This study seeks to assess the use of labeling with micron-sized iron oxide (MPIO) particles for the detection and quantification of the migration of dendritic cells (DCs) using cellular magnetic resonance imaging (MRI).Procedures: DCs were labeled with red fluorescent MPIO particles for detection by cellular MRI and a green fluorescent membrane dye (PKH67) for histological detection. MPIO-labeled DCs or unlabeled control DCs were injected into mice footpads at two doses (0.1 × 10(6) and 1 × 10(6)). Images were acquired at 3 Tesla before DC injection and 2, 3, and 7 days post-DC injection.Results: Labeling DCs with MPIO particles did not affect viability, but it did alter markers of DC activation and maturation. MRI and fluorescence microscopy allowed for the detection of MPIO-labeled DCs within the draining popliteal nodes after their injection into the footpad.Conclusions: This paper presents the first report of the successful use of fluorescent MPIO particles to label and track DC migration. [ABSTRACT FROM AUTHOR]

Effective cancer immunotherapy depends on the body’s ability to generate tumor antigen-presenting cells and tumor-reactive effector lymphocytes. As the most potent antigen presenting cells (APCs), dendritic cells (DCs) are capable of sensitizing T cells to new and recall antigens. Clinical trials of antigen-pulsed autologous DCs have been conducted in patients with a number of hematological and solid cancers, including malignant melanoma, lymphoma, myeloma, and non-small cell lung cancer. These studies suggest that antigen-loaded DC vaccination is a potentially safe and effective cancer therapy. However, the clinical results have been variable. Since the elderly are preferentially affected by diseases targeted by DC-directed immunotherapy, it is quite striking that few studies to date have focused on the effect of aging on DC function, a key aspect of optimal immunotherapy design in an aging population. In the present paper, we will discuss the consequences of aging on murine bone marrow-derived DC function and their use in cancer immunotherapy. [ABSTRACT FROM AUTHOR]

Although animals can be immunized against the growth of some tumor implants, most of the attempts to use immunotherapy to cause the regression of animal and human tumors once they have become established have been disappointing even when strongly immunogenic tumors were used as target. In this paper, we demonstrate that the failure to achieve an efficient immunological treatment against an established strongly immunogenic murine fibrosarcoma was paralleled with the emergence of a state of immunological unresponsiveness (immunological eclipse) against tumor antigens observed when the tumor surpassed the critical size of 500 mm3. In turn, the onset of the immunological eclipse was coincidental with the onset of a systemic inflammatory condition characterized by a high number of circulating and splenic polymorphonucleated neutrophils (PMN) displaying activation and Gr1+Mac1+ phenotype and an increasing serum concentration of the pro-inflammatory cytokines TNF-α, IL-1β and IL-6 cytokines and C-reactive protein (CRP) and serum A amyloid (SAA) phase acute proteins. Treatment of tumor-bearing mice with a single low dose (0.75 mg/kg) of the synthetic corticoid dexamethasone (DX) significantly reduced all the systemic inflammatory parameters and simultaneously reversed the immunological eclipse, as evidenced by the restoration of specific T-cell-dependent concomitant immunity, ability of spleen cells to transfer anti-tumor activity and recovery of T-cell signal transduction molecules. Two other anti-inflammatory treatments by using indomethacin or dimeric TNF-α receptor, also partially reversed the immunological eclipse although the effect was not as striking as that observed with DX. The reversion of the immunological eclipse was not enough on its own to inhibit the primary growing tumor. However, when we used the two-step strategy of inoculating DX to reverse the eclipse and then dendritic cells loaded with tumor antigens (DC) as an immunization booster, a significant inhibition of the growth of both established tumors and remnant tumor cells after excision of large established tumors was observed, despite the fact that the vaccination alone (DC) had no effect or even enhanced tumor growth in certain circumstances. The two-step strategy of tumor immunotherapy that we present is based on the rationale that it is necessary to eliminate or ameliorate the immunological eclipse as a precondition to allow an otherwise ineffective anti-tumor immunological therapy to have a chance to be successful. [ABSTRACT FROM AUTHOR]

Dendritic cells (DCs) 'pulsed' with an appropriate antigen may elicit an antitumour immune response in mouse models. However, while attempting to develop a DC immunotherapy protocol for the treatment of breast cancer based on the tumour-associated MUC1 glycoforms, we found that unpulsed DCs can affect tumour growth. Protection from RMA-MUC1 tumour challenge was achieved in C57Bl/6 MUC1 transgenic mice by immunising with syngeneic DCs pulsed with a MUC1 peptide. However, unpulsed DCs gave a similar level of protection, making it impossible to evaluate the effect of immunisation of mice with DCs pulsed with the specific peptide. Balb/C mice could also be protected from tumour challenge by immunisation with unpulsed DCs prior to challenge with murine mammary tumour cells (410.4) or these cells transfected with MUC1 (E3). Protection was achieved with as few as three injections of 50,000 naïve DCs per mouse per week, was not dependent on injection route, and was not specific to cell lines expressing human MUC1. However, the use of Rag2-knockout mice demonstrated that the adaptive immune response was required for tumour rejection. Injection of unpulsed DCs into mice bearing the E3 tumour slowed tumour growth. In vitro, production of IFN-gamma and IL-4 was increased in splenic cells isolated from mice immunised with DCs. Depleting CD4 T cells in vitro partially decreased cytokine production by splenocytes, but CD8 depletion had no effect. This paper shows that naïve syngeneic DCs may induce an antitumour immune response and has implications for DC immunotherapy preclinical and clinical trials. [ABSTRACT FROM AUTHOR]

The present paper shows, for the first time, the membrane expression of the dendritic cell maturation marker CD83 on tumor cells from lung cancer patients. CD83 was also detected on freshly cultured fibroblast-like cells from these tissues and on several adherent human tumor cell lines (lung adenocarcinomas P9, A459 and A549, melanomas A375 and C81-61, breast adenocarcinomas SKBR-3 and MCF-7 and colon carcinoma AR42-J), but not in the non-adherent MOT leukemia cell line. CD83 may have immunosuppressive properties and its expression by cancer cells could have a role in facilitating tumor growth. [ABSTRACT FROM AUTHOR]

We describe the ultrastructural organization of the vitellogenic follicle stages in two caecilian species. Monthly samples of slices of ovary of Ichthyophis tricolor and Gegeneophis ramaswamii from the Western Ghats of India were subjected to transmission electron-microscopic analysis, with special attention to the follicle cell/oocyte interface. In order to maintain uniformity of the stages among the amphibians, all the stages in the caecilian follicles were assigned to stages I–VI, the vitellogenic and post-vitellogenic follicles being assigned to stages III–VI. Stage III commences with the appearance of precursors of vitelline envelope material in the perivitelline space. Stages IV and V have been assigned appropriate substages. During the transition of stage III to stage VI oocytes, a sequential change occurs in the manifestations of follicle cells, perivitelline space, vitelline envelope and oocyte cortex. The vitelline envelope becomes a tough coat through the tunnels of which the macrovilli pass to interdigitate between the microvilli. The oocyte surface forms pinocytic vesicles that develop into coated pits and, later, coated vesicles. Contributions of the oocyte cortex to the vitelline envelope and of the follicle cells to yolk material via synthesis within them are indicated. The follicle cell/oocyte interface of vitellogenic follicles of these two caecilians resembles that in anurans and urodeles, with certain features being unique to caecilians. Thus, this paper throws light on the possible relationships of caecilians to anurans and urodeles with special reference to ovarian follicles. [ABSTRACT FROM AUTHOR]

Inappropriate T cell responses cause the four classical types of hypersensitivity immune reactions. All of these can target the kidney and cause distinct forms of glomerulonephritis. CD4+ T cells can mediate glomerular immunopathology by cytokine secretion, by activating effector cells such as macrophages or by inducing auto-antibodies or immune-complexes. Cytotoxic CD8+ T cell responses and failure of regulatory T cells may represent two additional types of anti-renal hypersensitivity. T cell activation is critically dependent on dendritic cells (DC), whose role in renal disease appears to be protective, but underlying mechanisms are largely unknown. In this paper, we summarized mechanistic information from rodent models on the roles of DC and T cells in glomerular immunopathology. [ABSTRACT FROM AUTHOR]

Rare monogenic dementias have repeatedly exposed novel pathways guiding to details of the molecular pathogenesis behind this complex clinical phenotype. In this paper, we have studied polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL), an early onset dementia with bone fractures caused by mutations in TYROBP (DAP12) and TREM2 genes, which encode important signaling molecules in human dendritic cells (DCs). To identify the pathways and biological processes associated with DAP12/TREM2-mediated signaling, we performed genome wide transcript analysis of in vitro differentiated DCs of PLOSL patients representing functional knockouts of either DAP12 or TREM2. Both DAP12- and TREM2-deficient cells differentiated into DCs and responded to pathogenic stimuli. However, the DCs showed morphological differences compared to control cells due to defects in the actin filaments. Not unexpectedly, transcript profiles of the patient DCs showed differential expression of genes involved in immune response. Importantly, significantly diverging transcript levels were also evident for genes earlier associated with other disorders of the central nervous system (CNS) and genes involved in the remodeling of bone, linking these two immunological genes with critical tissue phenotypes of patients. The data underline the functional diversity of the molecules of the innate immune system and implies their significant contribution also in demyelinating CNS disorders, including those resulting in dementia. [ABSTRACT FROM AUTHOR]

Dendritic cells (DC) are professional antigen-presenting cells that play a pivotal role in the induction of immunity. Ex vivo-generated, tumour antigen-loaded mature DC are currently exploited as cancer vaccines in clinical studies. However, antigen loading and maturation of DC directly in vivo would greatly facilitate the application of DC-based vaccines. We formerly showed in murine models that radiofrequency-mediated tumour destruction can provide an antigen source for the in vivo induction of anti-tumour immunity, and we explored the role of DC herein. In this paper we evaluate radiofrequency and cryo ablation for their ability to provide an antigen source for DC and compare this with an ex vivo-loaded DC vaccine. The data obtained with model antigens demonstrate that upon tumour destruction by radiofrequency ablation, up to 7% of the total draining lymph node (LN) DC contained antigen, whereas only few DC from the conventional vaccine reached the LN. Interestingly, following cryo ablation the amount of antigen-loaded DC is almost doubled. Analysis of surface markers revealed that both destruction methods were able to induce DC maturation. Finally, we show that in situ tumour ablation can be efficiently combined with immune modulation by anti-CTLA-4 antibodies or regulatory T-cell depletion. These combination treatments protected mice from the outgrowth of tumour challenges, and led to in vivo enhancement of tumour-specific T-cell numbers, which produced more IFN-γ upon activation. Therefore, in situ tumour destruction in combination with immune modulation creates a unique, ‘in situ DC-vaccine’ that is readily applicable in the clinic without prior knowledge of tumour antigens.British Journal of Cancer (2006) 95, 896–905. doi:10.1038/sj.bjc.6603341 www.bjcancer.com [ABSTRACT FROM AUTHOR]

Neuronal depolarization causes larger intracellular pH (pHi) shifts in axonal and dendritic regions than in the cell body. In this paper, we present evidence relating the time for collapse of these gradients to neuronal morphology. We have used ratiometric pHi measurements using 8-hydroxypyrene-1,3,6-trisulfonic acid (HPTS) in whole-cell patch-clamped snail neurons to study the collapse of longitudinal pH gradients. Using depolarization to open voltage-gated proton channels, we produced alkaline pHi microdomains. In the absence of added mobile buffers, facilitated H+ diffusion down the length of the axon plays a critical role in determining pHi microdomain lifetime, with axons of ∼100 μm allowing pH differences to be maintained for >60 s. An application of mobile, membrane-permeant pH buffers accelerated the collapse of the alkaline-pH gradients but, even at 30 mM, was unable to abolish them. Modeling of the pHi dynamics showed that both the relatively weak effect of the weak acid/base on the peak size of the pH gradient and the accelerated collapse of the pH gradient could be due to the time taken for equilibration of the weak acid and base across the cell. We propose that appropriate weak acid/base mixes may provide a simple method for studying the role of local pHi signals without perturbing steady-state pHi. Furthermore, an extrapolation of our in vitro data to longer and thinner neuronal structures found in the mammalian nervous system suggests that dendritic and axonal pHi are likely to be dominated by local pHi-regulating mechanisms rather than simply following the soma pHi. [ABSTRACT FROM AUTHOR]

Dendritic cells are the most potent antigen-presenting cells, and the possibility of their use for cancer vaccination has renewed the interest in this therapeutic modality. Nevertheless, the ideal immunization protocol with these cells has not been described yet. In this paper we describe the preliminary results of a protocol using autologous tumor and allogeneic dendritic hybrid cell vaccination every 6 weeks, for metastatic melanoma and renal cell carcinoma (RCC) patients. Thirty-five patients were enrolled between March 2001 and March 2003. Though all patients included presented with large tumor burdens and progressive diseases, 71% of them experienced stability after vaccination, with durations up to 19 months. Among RCC patients 3/22 (14%) presented objective responses. The median time to progression was 4 months for melanoma and 5.7 months for RCC patients; no significant untoward effects were noted. Furthermore, immune function, as evaluated by cutaneous delayed-type hypersensitivity reactions to recall antigens and by peripheral blood proliferative responses to tumor-specific and nonspecific stimuli, presented a clear tendency to recover in vaccinated patients. These data indicate that dendritic cell-tumor cell hybrid vaccination affects the natural history of advanced cancer and provide support for its study in less advanced patients, who should, more likely, benefit even more from this approach. [ABSTRACT FROM AUTHOR]

Cerebellar Purkinje neurons are arguably some of the most conspicuous neurons in the vertebrate central nervous system. They have characteristic planar fan-shaped dendrites which branch extensively and fill spaces almost completely with little overlap. This dendritic morphology is well suited to receiving a single or a few excitatory synaptic inputs from each of more than 100,000 parallel fibers which run orthogonally to Purkinje cell dendritic trees. In contrast, another type of excitatory input to a Purkinje neuron is provided by a single climbing fiber, which forms some hundreds to thousands of synapses with a Purkinje neuron. This striking contrast between the two types of synaptic inputs to a Purkinje neuron has attracted many neuroscientists. It is also to be noted that Purkinje neurons are the sole neurons sending outputs from the cerebellar cortex. In other words, all computational results within the cortex are transmitted by Purkinje cell axons, which inhibit neurons in the cerebellar or vestibular nucleus. Notably, Purkinje neurons show several forms of synaptic plasticity. Among them, long-term depression (LTD) at parallel fiber synapses has been regarded as a putatively essential mechanism for cerebellum-dependent learning. In this special issue on Purkinje neurons, you will find informative reviews and original papers on the development, characteristics and functions of Purkinje neurons, or related themes contributed by outstanding researchers. [ABSTRACT FROM AUTHOR]

The article presents several papers on viral neuropathogenesis that were presented at the Sixth International Symposium on NeuroVirology. Viral infections have been implicated in functional disturbances of the nervous system. These may be related to targeting of viruses to certain brain areas, and to the effects of viral components and/or host derived immune response molecules on neuronal functions. For targeting to distinct regions of the brain, viral components utilize the axonal and dendritic transport machineries of a neuron and the site of a virus attack is then partly related to its portal of entry.

The article presents papers selected from presentations at the 4th Progress in Vaccincation Against Cancer (PIVAC) conference held in Freudenstadt-Lauterbad, Black Forest, Germany on September 22-25, 2004. It includes a paper on the use of peptide-pulsed autologous dendritic cells in therapeutic cancer vaccination using synthetic peptides. Next is a paper that describes pre-clinical data on the use of modified whole-cell vaccines rather than defined antigens. Suggested advantages of adoptive as opposed to active immunotherapy are given in another paper.

Discusses a paper by G. Willimsky and T. Blankenstein which showed that sporadic tumors in mice, against which the immune system initially reacts, nevertheless manage to spread by molding the killer T cells into a state that tolerates them. Implications for the debate on whether the development of sporadic, nonviral tumors is really affected by so-called immunoediting; Concurrence of both sides of the controversy that both virus-induced and sporadic tumors do elicit immune responses, and that T-cell responses protect against viral carcinogenesis; Variation in the natural ability of tumors to activate dendritic cells; Need for tumors to be sensed by an exquisitely sensitive sentinel system, the dendritic cell network.

The article discusses papers which show that signals derived from basophils and eosinophils are directly involved in the induction of T helper 2 (TH2)-cell responses. It highlights the findings in "A mechanism for the initiation of allergen-induced T helper type 2 responses," by C.L. Sokol and colleagues, and "Eosinophil-derived neurotoxin acts as an alarm to activate the TLR2-MyD88 signal pathway in dendritic cells and enhances Th2 immune responses," by D. Yang and colleagues.

The article focuses on research on immune responses, regulatory T cells and T-cell signaling. Papers discussed which were published in other periodicals include "Dendritic Cell Stimulation By Mycobacterial Hsp70 is Mediated Through CCR5," by R. A. Floto et al and "Alterations in CD46-Mediated Tr1 Regulatory T Cells in Patients With Multiple Sclerosis," by A. L. Astier et al.

The article reviews a research paper, "Identification of E2/E3 ubiquitinating enzymes and caspase activity regulating Drosophila sensory neuron dendrite pruning," by C. T. Kuo et al., published in Neuron, vol. 51 (2006).

Presents an introduction to a series of papers on ultrastructural discoveries in pathophysiology of liver diseases, including one from H. Yoneyama and T. Ichida on the recruitment and fucntion of precursors of dendritic cells in the inflamed liver and another by Y. Ando on approaches in the treatment of familial amyloidotic polyneuropathy.

The article focuses on a research paper investigating whether it is possible to induce antitumor responses in vivo in cancer patients by activating natural killer T (NKT) cells, which are induced to proliferate by dendritic cells. The patients experienced temporary inflammatory symptoms as well as respiratory symptoms in individuals with pulmonary metastases. The study offers clinical evidence that NKT cells can bridge innate and acquired immunity to induce secondary antitumor immune responses.

Editorial. Introduces the articles published in the September 2003 issue of the journal 'Nature Medicine.' Retraction of the research paper 'Regression of human metastatic renal cell carcinoma after vaccination with tumor cell-dendritic cell hybrids'; Production of hybrid cells by the fusion of autologous tumor cells; Human applications of a hybrid cell vaccine.

Presents research highlights from the 'Nature' family of journals as of April 5, 2001. Study published in 'Nature Biotechnology,' which describes a prototype biosensor array of ribozymes; Papers published in 'Nature Medicine,' which pinpoint the key molecules involved in the follicular dendritic cell capture mechanism; Article published in 'Nature Immunology,' which explores the generation of T-cells; Others.