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Sample records for follicular dendritic cell-secreted

  1. Follicular dendritic cells in health and disease

    PubMed Central

    El Shikh, Mohey Eldin M.; Pitzalis, Costantino

    2012-01-01

    Follicular dendritic cells (FDCs) are unique immune cells that contribute to the regulation of humoral immune responses. These cells are located in the B-cell follicles of secondary lymphoid tissues where they trap and retain antigens (Ags) in the form of highly immunogenic immune complexes (ICs) consisting of Ag plus specific antibody (Ab) and/or complement proteins. FDCs multimerize Ags and present them polyvalently to B-cells in periodically arranged arrays that extensively crosslink the B-cell receptors for Ag (BCRs). FDC-FcγRIIB mediates IC periodicity, and FDC-Ag presentation combined with other soluble and membrane bound signals contributed by FDCs, like FDC-BAFF, -IL-6, and -C4bBP, are essential for the induction of the germinal center (GC) reaction, the maintenance of serological memory, and the remarkable ability of FDC-Ags to induce specific Ab responses in the absence of cognate T-cell help. On the other hand, FDCs play a negative role in several disease conditions including chronic inflammatory diseases, autoimmune diseases, HIV/AIDS, prion diseases, and follicular lymphomas. Compared to other accessory immune cells, FDCs have received little attention, and their functions have not been fully elucidated. This review gives an overview of FDC structure, and recapitulates our current knowledge on the immunoregulatory functions of FDCs in health and disease. A better understanding of FDCs should permit better regulation of Ab responses to suit the therapeutic manipulation of regulated and dysregulated immune responses. PMID:23049531

  2. Computer Tomography Imaging Findings of Abdominal Follicular Dendritic Cell Sarcoma

    PubMed Central

    Li, Jing; Geng, Zhi-Jun; Xie, Chuan-Miao; Zhang, Xin-Ke; Chen, Rui-Ying; Cai, Pei-Qiang; Lv, Xiao-Fei

    2016-01-01

    Abstract Follicular dendritic cell sarcoma (FDCS) is a neoplasm that arises from follicular dendritic cells. FDCSs originating in the abdomen are extremely rare. Clinically, they often mimic a wide variety of other abdominal tumors, and correct preoperative diagnosis is often a challenging task. To date, only scattered cases of abdominal FDCS have been reported and few data are available on their radiological features. Here we present the computer tomography imaging findings of 5 patients with surgically and pathologically demonstrated abdominal FDCS. An abdominal FDCS should be included in the differential diagnosis when single or multiple masses with relatively large size, well- or ill-defined borders, complex internal architecture with marked internal necrosis and/or focal calcification, and heterogeneous enhancement with “rapid wash-in and slow wash-out” or “progressive enhancement” enhancement patterns in the solid component are seen. PMID:26735543

  3. Cochlin produced by follicular dendritic cells promotes antibacterial innate immunity.

    PubMed

    Py, Bénédicte F; Gonzalez, Santiago F; Long, Kai; Kim, Mi-Sung; Kim, Young-A; Zhu, Hong; Yao, Jianhua; Degauque, Nicolas; Villet, Régis; Ymele-Leki, Patrick; Gadjeva, Mihaela; Pier, Gerald B; Carroll, Michael C; Yuan, Junying

    2013-05-23

    Cochlin, an extracellular matrix protein, shares homologies with the Factor C, a serine protease found in horseshoe crabs, which is critical for antibacterial responses. Mutations in the COCH gene are responsible for human DFNA9 syndrome, a disorder characterized by neurodegeneration of the inner ear that leads to hearing loss and vestibular impairments. The physiological function of cochlin, however, is unknown. Here, we report that cochlin is specifically expressed by follicular dendritic cells and selectively localized in the fine extracellular network of conduits in the spleen and lymph nodes. During inflammation, cochlin was cleaved by aggrecanases and secreted into blood circulation. In models of lung infection with Pseudomonas aeruginosa and Staphylococcus aureus, Coch(-/-) mice show reduced survival linked to defects in local cytokine production, recruitment of immune effector cells, and bacterial clearance. By producing cochlin, FDCs thus contribute to the innate immune response in defense against bacteria. PMID:23684986

  4. Follicular dendritic cells and human immunodeficiency virus infectivity

    NASA Astrophysics Data System (ADS)

    Heath, Sonya L.; Tew, J. Grant; Tew, John G.; Szakal, Andras K.; Burton, Gregory F.

    1995-10-01

    LARGE amounts of human immunodeficiency virus (HIV) localize on follicular dendritic cells (FDC) in the follicles of secondary lymphoid tissues following viral infection1,2. During clinical latency, active viral infection occurs primarily at these sites3,4. As HIV on FDC is in the form of immune complexes5, some of which may be formed with neutralizing antibody, we investigated whether HIV on FDC is infectious. We report here that HIV on FDC is highly infectious. Furthermore, FDC can convert neutralized HIV into an infectious form even in the presence of a vast excess of neutralizing antibody. Thus FDC may provide a mechanism whereby HIV infection can continue in the presence of neutralizing antibody.

  5. How Follicular Dendritic Cells Shape the B-Cell Antigenome

    PubMed Central

    Kranich, Jan; Krautler, Nike Julia

    2016-01-01

    Follicular dendritic cells (FDCs) are stromal cells residing in primary follicles and in germinal centers of secondary and tertiary lymphoid organs (SLOs and TLOs). There, they play a crucial role in B-cell activation and affinity maturation of antibodies. FDCs have the unique capacity to bind and retain native antigen in B-cell follicles for long periods of time. Therefore, FDCs shape the B-cell antigenome (the sum of all B-cell antigens) in SLOs and TLOs. In this review, we discuss recent findings that explain how this stromal cell type can arise in almost any tissue during TLO formation and, furthermore, focus on the mechanisms of antigen capture and retention involved in the generation of long-lasting antigen depots displayed on FDCs. PMID:27446069

  6. The Role of Dendritic Cells in S. pneumoniae Transport to Follicular Dendritic Cells.

    PubMed

    Heesters, Balthasar A; Carroll, Michael C

    2016-09-20

    Affinity-mature B cells require cognate antigen, retained by follicular dendritic cells (FDCs), for clonal selection within germinal centers. Studies on how FDCs in lymphoid tissues acquire antigen have relied primarily on model protein antigens. To examine delivery of intact bacteria to FDCs, we used inactivated Streptococcus pneumonia (SP). We found that both medullary macrophages and a subset of SIGN-R1-positive dendritic cells (DCs) in the lymph node capture SP from the draining afferent lymphatics. The presence of DCs is required for initial complement activation, opsonization of the bacteria, and efficient transport of SP to FDCs. Moreover, we observed a major role for transport of bacteria to FDCs by naive B cells via a CD21-dependent pathway. We propose a mechanism by which efficient transport of SP to FDCs is dependent on DCs for initial binding and activation of complement and either direct transport to FDCs or transfer to naive B cells. PMID:27653679

  7. Contribution of Follicular Dendritic Cells to Persistent HIV Viremia

    PubMed Central

    Zhang, Jingshan

    2013-01-01

    HIV-1 infections cannot be completely eradicated by drug therapy, as the virus persists in reservoirs. Low-level plasma viremia has been detected in patients treated for over 7 years, but the cellular compartments that support this low-level viremia have not been identified. The decay of HIV-1 during treatment appears to occur in four phases, with the 3rd and 4th phases occurring when the virus is below the limit of detection of conventional assays. Here, we focus on the 3rd phase of decay, which has been estimated to have a half-life of 39 months. We show that follicular dendritic cells (FDC), which have been identified as an HIV reservoir, can be the main source of the low-level viremia detected during the 3rd phase of decay and contribute to viremia at even longer times. Our calculations show that the kinetics of leakage of virus from FDC is consistent with three types of available clinical data. PMID:23658450

  8. HIV is trapped and masked in the cytoplasm of lymph node follicular dendritic cells.

    PubMed Central

    Tacchetti, C.; Favre, A.; Moresco, L.; Meszaros, P.; Luzzi, P.; Truini, M.; Rizzo, F.; Grossi, C. E.; Ciccone, E.

    1997-01-01

    To gain further insight into the pathogenesis of human immunodeficiency virus (HIV) infection, lymph nodes from seven asymptomatic HIV+ subjects were analyzed during the latent phase of disease. Both ultrastructural and immunohistochemical analyses revealed that, in all of the cases, plasma cells producing IgM/gamma were present in germinal centers. Secreted immunoglobulins formed extracellular deposits mimicking the follicular dendritic cell network. Immunoglobulin produced by germinal center plasma cells are specific for HIV because they bind the HIV env protein gp 120. Plasma cells producing antibodies with the same specificity were also abundant in the extrafollicular regions of lymph nodes. During the latent phase of infection, the virus largely accumulates within the germinal centers. Therefore, extracellular immunoglobulin may form immune complexes, as shown by the presence of HIV-specific antibodies, HIV particles, and complement components C3c, C3d, and C1q in the interdendritic spaces. When the ultrastructural localization of HIV in germinal centers was analyzed, abundant virus particles were found in the interdendritic spaces. In addition to this extracellular localization of HIV, receptor-mediated endocytosis of viral particles by follicular dendritic cells was observed. Complete HIV particles were found within the endosomal compartment of the follicular dendritic cells and, as complete viral particles, free in the cytoplasm, indicating that the virus may escape from the endocytic compartment. As the virus is abundant in the cytoplasm, this event leads to formation of a hidden reservoir within follicular dendritic cells. In this location, HIV escapes recognition by cytotoxic T lymphocytes. In contrast, virus budding indicating a productive infection of follicular dendritic cells that would render them susceptible to T-cell-mediated lysis has been seldom observed. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:9033269

  9. Targeted genomic sequencing of follicular dendritic cell sarcoma reveals recurrent alterations in NF-κB regulatory genes.

    PubMed

    Griffin, Gabriel K; Sholl, Lynette M; Lindeman, Neal I; Fletcher, Christopher D M; Hornick, Jason L

    2016-01-01

    Follicular dendritic cell sarcoma is a rare mesenchymal neoplasm with a variable and unpredictable clinical course. The genetic alterations that drive tumorigenesis in follicular dendritic cell sarcoma are largely unknown. One recent study performed BRAF sequencing and found V600E mutations in 5 of 27 (19%) cases. No other recurrent genetic alterations have been reported. The aim of the present study was to identify somatic alterations in follicular dendritic cell sarcoma by targeted sequencing of a panel of 309 known cancer-associated genes. DNA was isolated from formalin-fixed paraffin-embedded tissue from 13 cases of follicular dendritic cell sarcoma and submitted for hybrid capture-based enrichment and massively parallel sequencing with the Illumina HiSeq 2500 platform. Recurrent loss-of-function alterations were observed in tumor suppressor genes involved in the negative regulation of NF-κB activation (5 of 13 cases, 38%) and cell cycle progression (4 of 13 cases, 31%). Loss-of-function alterations in the NF-κB regulatory pathway included three cases with frameshift mutations in NFKBIA and two cases with bi-allelic loss of CYLD. Both cases with CYLD loss were metastases and carried concurrent alterations in at least one cell cycle regulatory gene. Alterations in cell cycle regulatory genes included two cases with bi-allelic loss of CDKN2A, one case with bi-allelic loss of RB1, and one case with a nonsense mutation in RB1. Last, focal copy-number gain of chromosome 9p24 including the genes CD274 (PD-L1) and PDCD1LG2 (PD-L2) was noted in three cases, which represents a well-described mechanism of immune evasion in cancer. These findings provide the first insight into the unique genomic landscape of follicular dendritic cell sarcoma and suggest shared mechanisms of tumorigenesis with a subset of other tumor types, notably B-cell lymphomas.

  10. Follicular dendritic cell sarcoma of the spleen: A case report and review of the literature

    PubMed Central

    Wang, Lifeng; Xu, Dongfeng; Qiao, Zhenguo; Shen, Li; Dai, Hongzhi; Ji, Yiding

    2016-01-01

    Follicular dendritic cell sarcoma (FDCS), which originates in antigen-presenting cells of the B-cell follicles of the lymph nodes, is an uncommon disease, particularly in a splenic location. In a number of cases, FDCS may easily be confused with other solid tumors and be underdiagnosed. The present study reports a case in which such as tumor occurred in a 64-year-old woman. The patient presented with an abdominal mass, and computed tomography was performed. Histological and immunohistochemical studies revealed a diagnosis of FDCS. The patient underwent surgical treatment and had a good remission. At the time of writing, the patient was in good condition. The present study also discusses the clinical characteristics, treatment methods and prognosis of FDCS, with particular reference to the main points of the imaging diagnosis. PMID:27602139

  11. Follicular dendritic cells help establish follicle identity and promote B cell retention in germinal centers.

    PubMed

    Wang, Xiaoming; Cho, Bryan; Suzuki, Kazuhiro; Xu, Ying; Green, Jesse A; An, Jinping; Cyster, Jason G

    2011-11-21

    Follicular dendritic cells (FDCs) retain and display opsonized antigens in primary follicles and germinal centers (GCs). However, their roles beyond antigen presentation have been incompletely defined. In this study, we tested the impact of selective FDC ablation on short-term follicle and GC function. Within 2 d of FDC ablation, primary follicles lost their homogeneity and became disorganized bands of cells around T zones. These B cell areas retained CXCL13-expressing stromal cells but often exhibited inappropriate ER-TR7 and CCL21 expression. Ablation of GC FDCs led to the disappearance of GCs. When B cell death was prevented using a Bcl2 transgene, FDC ablation led to splenic GC B cell dispersal. Mesenteric lymph node GCs were more resistant but became dispersed when sphingosine-1-phosphate receptor-2 was also removed. These experiments indicate that FDCs help maintain primary follicles as a B cell exclusive niche and define a critical role for FDCs in cell retention within GCs.

  12. Cochlin produced by follicular dendritic cells promotes anti-bacterial innate immunity

    PubMed Central

    Py, Bénédicte F.; Gonzalez, Santiago F.; Long, Kai; Kim, Mi-Sung; Kim, Young-A; Zhu, Hong; Yao, Jianhua; Degauque, Nicolas; Villet, Régis; Ymele-Leki, Patrick; Gadjeva, Mihaela; Pier, Gerald B.; Carroll, Michael C.; Yuan, Junying

    2013-01-01

    Cochlin, an extracellular matrix protein, shares homologies with the Factor C, a serine protease found in horseshoe crabs, which is critical for anti-bacterial responses. Mutations in the COCH gene are responsible for human DFNA9 syndrome, a disorder characterized by neurodegeneration of inner ear that leads to hearing loss and vestibular impairments. The physiological function of cochlin, however, is unknown. Here, we report that cochlin is specifically expressed by follicular dendritic cells, and selectively localized in the fine extracellular network of conduits in the spleen and lymph nodes. During inflammation, cochlin was cleaved by aggrecanases and secreted into blood circulation. In models of lung infection with Pseudomonas aeruginosa and Staphylococcus aureus, Coch−/− mice show reduced survival linked to defects in local cytokine production, recruitment of immune effector cells and bacterial clearance. By producing cochlin, FDCs thus contribute to the innate immune response in defense against bacteria. PMID:23684986

  13. Analysis of dendritic cell subpopulations in follicular lymphoma with respect to the tumor immune microenvironment.

    PubMed

    Chevalier, Nina; Mueller, Michael; Mougiakakos, Dimitrios; Ihorst, Gabriele; Marks, Reinhard; Schmitt-Graeff, Annette; Veelken, Hendrik

    2016-09-01

    The immune cell composition of the follicular lymphoma (FL) tumor microenvironment is increasingly recognized as an important determinant for clinical outcome. Here, we explored frequency and distribution of dendritic cell (DC) subtypes in relation to regulatory T cells (Treg) by immunohistochemistry in lymph node biopsies from patients with de novo FL. We found that neoplastic follicles contained lower DC and higher Treg frequencies than hyperplastic follicles in control lymph nodes. Treg numbers particularly correlated with the subset of conventional CD11c(+ )DCs. Additionally, both a high intra- to interfollicular ratio of CD11c(+ )DCs and increased intrafollicular Treg frequencies were associated with decreased overall survival. This suggests that functional interactions between these cells may be relevant for FL progression/recurrence. The presence of CD11c(+ )DCs in the tumor microenvironment may assist tumor infiltration by Tregs, thus contributing to the suppression of an otherwise beneficial T-cell-dominated FL microenvironment.

  14. Follicular dendritic cell disruption as a novel mechanism of virus-induced immunosuppression

    PubMed Central

    Melzi, Eleonora; Caporale, Marco; Rocchi, Mara; Martín, Verónica; Gamino, Virginia; di Provvido, Andrea; Marruchella, Giuseppe; Entrican, Gary; Sevilla, Noemí; Palmarini, Massimo

    2016-01-01

    Arboviruses cause acute diseases that increasingly affect global health. We used bluetongue virus (BTV) and its natural sheep host to reveal a previously uncharacterized mechanism used by an arbovirus to manipulate host immunity. Our study shows that BTV, similarly to other antigens delivered through the skin, is transported rapidly via the lymph to the peripheral lymph nodes. Here, BTV infects and disrupts follicular dendritic cells, hindering B-cell division in germinal centers, which results in a delayed production of high affinity and virus neutralizing antibodies. Moreover, the humoral immune response to a second antigen is also hampered in BTV-infected animals. Thus, an arbovirus can evade the host antiviral response by inducing an acute immunosuppression. Although transient, this immunosuppression occurs at the critical early stages of infection when a delayed host humoral immune response likely affects virus systemic dissemination and the clinical outcome of disease. PMID:27671646

  15. Fas signal links innate and adaptive immunity by promoting dendritic-cell secretion of CC and CXC chemokines.

    PubMed

    Guo, Zhenhong; Zhang, Minghui; Tang, Hua; Cao, Xuetao

    2005-09-15

    Dendritic cells (DCs) and chemokines are important in linking innate and adaptive immunity. We previously reported that Fas ligation induced interleukin 1beta (IL-1beta)-dependent maturation and IL-1beta-independent survival of DCs, with extracellular signal-regulated kinase (ERK) and nuclear factor-kappaB (NF-kappaB) signaling pathways involved, respectively. We describe here that Fas ligation induced DCs to rapidly produce both CXC and CC chemokines, including macrophage inflammatory protein 2 (MIP-2), MIP-1alpha, MIP-1beta, monocyte chemoattractant protein 1 (MCP-1), RANTES (regulated on activation normal T cell expressed and secreted), and TARC (thymus and activation-regulated chemokine), resulting in enhanced chemoattraction of neutrophils and T cells by Fas-ligated DCs in vivo or by its supernatant in vitro. These chemokines work synergistically in chemoattraction of neutrophils and T cells with MIP-2 more important for neutrophils, MIP-1alpha and TARC more important for T cells. Moreover, Fas-ligated DCs increased endocytosis by neutrophils and activation and proliferation of antigen-specific naive T cells. Fas ligation-induced DC secretion of chemokines involves Ras/Raf/mitogen-activated protein kinase kinase (MEK)/ERK activation and is ERK, but not NF-kappaB, dependent. Activation of caspases, including caspase 1, but not IL-1 autocrine action, is involved in this process. These data indicate that Fas signaling provides a key link between innate response and adaptive immunity by promoting DC chemokine production.

  16. B-cell follicle development remodels the conduit system and allows soluble antigen delivery to follicular dendritic cells

    PubMed Central

    Germain, Ronald N.

    2009-01-01

    Afferent lymph is transported throughout lymph nodes (LNs) by the conduit system. Whereas this conduit network is dense in the T-cell zone, it is sparse in B-cell follicles. In this study, we show that this differential organization emerges during lymph node development. Neonatal LNs lack B follicles, but have a developed T-cell zone and a dense conduit network. As new T and B cells enter the developing LN, the conduit network density is maintained in the T, but not the B zone, leading to a profound remodeling of the follicular network that nevertheless maintains its connectivity. In adults, the residual follicular conduits transport soluble antigen to deep regions, where follicular dendritic cells are abundant and appear to replace the fibroblastic reticular cells that enwrap conduits in the T zone. This strategic location correlates with the capacity of the follicular dendritic cells to capture antigen even in the absence of antigen-specific antibodies. Together, these results describe how the stromal organization of the T and B regions of LNs diverges during development, giving rise to distinct antigen transport and delivery modes in the 2 compartments. PMID:19713459

  17. Dysplastic follicular dendritic cells in hyaline-vascular Castleman disease: a rare occurrence creating diagnostic difficulty.

    PubMed

    Medina, Edward A; Fuehrer, Neil E; Miller, Frank R; Kinney, Marsha C; Higgins, Russell A

    2016-09-01

    Follicular dendritic cell (FDC) proliferations and dysplastic FDCs can be seen in Hyaline-vascular Castleman disease (HVCD). The association between HVCD and FDC sarcoma is well-documented; dysplastic FDCs may be precursors to FDC sarcoma. Herein, we describe a case of HVCD with strikingly large and dysplastic FDCs, which raised the differential of Hodgkin lymphoma and other neoplasms. Scattered dysplastic FDCs were predominantly in germinal centers and mantle zones, and rarely in interfollicular areas. Although occasional germinal centers contained increased FDCs, no mass forming proliferations were present to suggest FDC sarcoma. Immunostaining demonstrated that the atypical FDCs expressed CD21, clusterin and CXCL13, but not CD23, S100, pankeratin or CD30; they aberrantly expressed epidermal growth factor receptor (EGFR). The present case demonstrates that dysplastic FDCs may be present as isolated cells that require immunophenotyping to distinguish them from malignant entities with similar morphologic features. A variety of FDC markers is required to confirm their origin as the expression of any single marker is not assured, as occurred in this case. Pathologists need be aware of FDC proliferations in HVCD because of their association with FDC sarcoma. Aberrant EGFR expression by dysplastic FDCs may indicate that they are pre-neoplastic and necessitate long-term patient follow-up. PMID:27593552

  18. CD301b+ dendritic cells suppress T follicular helper cells and antibody responses to protein antigens

    PubMed Central

    Kumamoto, Yosuke; Hirai, Toshiro; Wong, Patrick W; Kaplan, Daniel H; Iwasaki, Akiko

    2016-01-01

    Strong antibody response is considered a hallmark of a successful vaccine. While dendritic cells (DCs) are important for T follicular helper (Tfh) cell priming, how this process is regulated in vivo is unclear. We show here that the depletion of CD301b+ DCs specifically enhanced the development of Tfh cells, germinal center B cells and antibody responses against protein antigens. Exaggerated antibody responses in mice depleted of CD301b+ DCs occurred in the absence of any adjuvants, and resulting antibodies had broader specificity and higher affinity to the immunogen. CD301b+ DCs express high levels of PD-1 ligands, PD-L1 and PD-L2. Blocking PD-1 or PD-L1 during priming in wild-type mice partially mimicked the phenotype of CD301b+ DC-depleted animals, suggesting their role in Tfh suppression. Transient depletion of CD301b+ DC results in the generation of autoreactive IgG responses. These results revealed a novel regulatory mechanism and a key role of CD301b+ DCs in blocking autoantibody generation. DOI: http://dx.doi.org/10.7554/eLife.17979.001 PMID:27657168

  19. Isolated lymphoid follicle maturation induces the development of follicular dendritic cells

    PubMed Central

    Glaysher, Bridget R; Mabbott, Neil A

    2007-01-01

    Isolated lymphoid follicles (ILFs) are recently identified lymphoid structures in the small intestine with features similar to Peyer's patches (PPs). Using immunohistochemistry we characterized the composition of ILFs in the small intestines of immunocompetent mice and of mice that lacked PPs as a result of either genetic deficiency of lymphotoxin or temporary in utero lymphotoxin-β receptor-signalling blockade. We showed that although both immature and mature ILFs were present in the intestines of immunocompetent mice, PP-deficiency induced a significantly greater number of mature ILFs. We found that in addition to B-lymphocyte-containing germinal centres, mature ILFs also possessed large networks of follicular dendritic cells (FDCs). These features were not detected within immature ILFs. Indeed, the presence of FDCs could be used to reliably distinguish ILF maturity. Further analysis revealed that the area occupied by the FDCs within mature ILFs was substantial. The total area occupied by FDCs in all the mature ILFs in mice lacking PPs was equivalent to the total area occupied by FDCs in all the PPs and the few mature ILFs in immunocompetent mice. Based on these data we reasoned that in the absence of PPs, mature ILFs are important inductive sites for intestinal immune responses. Indeed, in mice that lacked PPs, ILF maturation coincided with a restoration of faecal immunoglobulin A levels to values that were comparable to those found in immunocompetent mice. Taken together, these data imply that the induction of germinal centres and FDC networks within mature ILFs in response to PP deficiency provides an important compensatory mechanism. PMID:17163957

  20. Clinicopathologic characteristics of inflammatory pseudotumor-like follicular dendritic cell sarcoma

    PubMed Central

    Ge, Rong; Liu, Chuangfeng; Yin, Xiangang; Chen, Jinping; Zhou, Xincheng; Huang, Chunxin; Yu, Wenying; Shen, Xiaohan

    2014-01-01

    Inflammatory pseudotumor (IPT)-like follicular dendritic cell (FDC) sarcoma is a recently described rare tumor and considered a unique entity, with different histologic appearances and behavior from those of the classical FDC sarcoma. This study analyzed the clinical and pathological findings of two such cases that the authors encountered and 36 previously reported cases identified in the literature. Assessment of all 38 cases showed a slight female predominance (2.2:1) with a median age of 56.5 years. Seventeen patients complained of abdominal discomfort or pain, while fifteen patients had no clinical symptom. Almost all cases occurred in liver (n = 20) or spleen (n = 17). Except in one case, all patients underwent surgical resection of the tumor alone. Histologic features showed a mixture of chronic inflammatory cells and variable amounts of spindle cells with vesicular nuclei and distinct nucleoli. The tumor cells expressed conventional FDC markers such as CD21 (75%), CD35 (92%), CD23 (62%), clusterin (75%), and CNA.42 (100%). EBV was detected in thirty-five cases (92.1%) by Epstein-Barr virus (EBV)-encoded RNA in situ hybridization, and EBV-latent membrane protein-1 was expressed in 90% of the cases. With a median follow-up of 21 months, 29 patients (85.3%) were alive and well, 4 (11.8%) were alive with disease, one patient (2.9%) died of disease. Only four patients with hepatic tumors underwent recurrence or metastasis after initial treatment. Epstein-Barr virus is thought to play a role in the development of the tumor; however, the pathogenesis of the disease and the origin of tumor cells remain unclear. PMID:24966952

  1. Extranodal Follicular Dendritic Cell Sarcoma Originating in the Pancreas: A Case Report

    PubMed Central

    Liang, Wenjie; He, Wei; Li, Zhenwei

    2016-01-01

    Abstract Follicular dendritic cell (FDC) sarcoma is a type of malignant tumor that originates from immune system-related FDCs. Pancreatic FDC sarcoma is a rare disease, and the specificity of the clinical presentation and laboratory results is unknown. We report the clinical process and imaging features of one case of pancreatic FDC sarcoma. A 67-year-old woman presented with a hypoechoic mass between the spleen and left kidney during a medical examination. The patient was hospitalized for further diagnosis. Her laboratory results did not present any obvious abnormal changes. Unenhanced and contrast-enhanced pancreatic computed tomography scans indicated a round mass with heterogeneous attenuation in the pancreatic tail, and a 3.5 × 3.6-cm solid mass with a cystic component was noted. Clear-cut, slight contrast enhancement was present in the solid part, whereas contrast enhancement was not observed in the cystic part. In addition, no obvious dilation was observed in the pancreatic duct, and no swollen lymph nodes were noted in the posterior peritoneum. Routine and contrast-enhanced pancreatic magnetic resonance imaging scans showed an abnormal signal indicative of a mass in the pancreatic tail, with a diameter of ∼35 mm and a clear boundary. A T2-weighted imaging scan showed a slight hyperintensity coupled with part of a hyperintensity, whereas T1-weighted imaging showed a slight hypointensity coupled with part of a hypointensity, and diffusion-weighted imaging showed a heterogeneous hyperintensity. The solid part of the lesion showed poor contrast enhancement through contrast-enhanced scanning, but contrast enhancement was not observed in the cystic part. Surgical tumor resection was performed, and the pathological diagnosis was pancreatic FDC sarcoma. The tumor did not recur based on short-term CT reexamination. Pancreatic FDC sarcoma is a rare disease, and the established clinical examinations and laboratory tests lack specificity. Imaging reveals a

  2. Immune regulation by Fcα/μ receptor (CD351) on marginal zone B cells and follicular dendritic cells.

    PubMed

    Shibuya, Akira; Honda, Shin-ichiro

    2015-11-01

    Although both Fcα/μ receptor (Fcα/μR) and polymeric Ig receptor (poly-IgR) are Fc receptors for IgA and IgM and are functionally and genetically related, the expression profile of Fcα/μR is unique. Unlike poly-IgR, Fcα/μR is expressed on marginal zone (MZ) B cells and follicular dendritic cells, suggesting that Fcα/μR plays an important role in humoral immune responses. Fcα/μR mediates endocytosis of the IgM immune complex (IC). Recent research demonstrated that Fcα/μR downregulated retention of the IgM IC with a T-independent (TI) antigen on MZ B cells and follicular dendritic cells due to endocytosis of the IgM IC, suppressing germinal center formation, affinity maturation, and memory B-cell generation in response to TI antigen challenge. In addition, Fcα/μR physically associates with Toll-like receptor 4 (TLR4) and augments TLR4 oligomerization and signaling in MZ B cells upon lipopolysaccharide (LPS) challenge, leading to increased proinflammatory cytokine production by MZ B cells. Thus, Fcα/μR is a unique Fc receptor that is involved in humoral immune responses and inflammation. PMID:26497528

  3. Reversibility of the Pathological Changes in the Follicular Dendritic Cell Network with Treatment of HIV-1 Infection

    NASA Astrophysics Data System (ADS)

    Zhang, Zhi-Qiang; Schuler, Troy; Cavert, Winston; Notermans, Daan W.; Gebhard, Kristin; Henry, Keith; Havlir, Diane V.; Gunthard, Huldrych F.; Wong, Joseph K.; Little, Susan; Feinberg, Mark B.; Polis, Michael A.; Schrager, Lewis K.; Schacker, Timothy W.; Richman, Douglas D.; Corey, Lawrence; Danner, Sven A.; Haase, Ashley T.

    1999-04-01

    Over the course of HIV-1 infection, the lymphoid follicles where the humoral immune response is generated initially increase in size and number and then progressively involute. In advanced disease, the network of the processes of follicular dendritic cells (FDCs) that serve as antigen respositories and anatomical substrate for B and T cells and antigen to interact is destroyed, contributing to the breakdown of the immune system. Because destruction of FDCs is associated with deposition of HIV-1, and much of the virus can be cleared from the network with antiretroviral therapy, we investigated the reversibility of damage. We measured the immunohistochemically stainable FDC compartment by quantitative image analysis, and we documented changes in this compartment at different stages of disease. We show that treatment, initiated even at advanced stages of HIV-1 disease, can slowly reverse pathological changes in the FDC network.

  4. Toll-like receptor 4 signaling by follicular dendritic cells is pivotal for germinal center onset and affinity maturation.

    PubMed

    Garin, Alexandre; Meyer-Hermann, Michael; Contie, Mathias; Figge, Marc Thilo; Buatois, Vanessa; Gunzer, Matthias; Toellner, Kai-Michael; Elson, Greg; Kosco-Vilbois, Marie H

    2010-07-23

    Germinal centers (GCs) are specialized microenvironments where antigen-activated B cells undergo proliferation, immunoglobulin (Ig) class switch recombination, somatic hypermutation (SHM), and affinity maturation. Within GCs, follicular dendritic cells (FDCs) are key players in driving these events via direct interaction with GC B cells. Here, we provide in vivo evidence that FDCs express and upregulate Toll-like-receptor (TLR) 4 in situ during germinal center reactions, confirm that their maturation is driven by TLR4, and associate the role of FDC-expressed TLR4 with quantitative and qualitative affects of GC biology. In iterative cycles of predictions by in silico modeling subsequently verified by in vivo experiments, we demonstrated that TLR4 signaling modulates FDC activation, strongly impacting SHM and generation of Ig class-switched high-affinity plasma and memory B cells. Thus, our data place TLR4 in the heart of adaptive humoral immunity, providing further insight into mechanisms driving GCs arising in both health and disease.

  5. Female genital tract immunization: evaluation of candidate immunoadjuvants on epithelial cell secretion of CCL20 and dendritic/Langerhans cell maturation.

    PubMed

    Cremel, Magali; Hamzeh-Cognasse, Hind; Genin, Christian; Delézay, Olivier

    2006-07-17

    The female genital tract is an important site for numerous pathogens entry. Local immunization, generating specific mucosal IgA and systemic IgG, represents an interesting alternative immunization pathway. However, such a vaccine strategy needs mucosal adjuvants to obtain the best immune response. Considering that the immunization process is mainly dependent on the capture and on the transport of the antigen by Langerhans cells, we evaluated potential adjuvant molecules by analysing their effects on the CCL20 secretion by endocervical and exocervical/vaginal epithelial cells as well as on dendritic cell and Langerhans cell maturation. We demonstrated that DC-Chol and Zymosan are the most efficient mucosal candidate immunoadjuvants that generate a strong increase of CCL20 secretion by the two epithelial cell lines and the maturation of dendritic and Langerhans cells, respectively.

  6. Monocyte-derived dendritic cells identified as booster of T follicular helper cell differentiation

    PubMed Central

    Fillatreau, Simon

    2014-01-01

    Adjuvants play an essential role in the induction of acquired immunity upon vaccination with protein antigen. In this issue of EMBO Molecular Medicine, a classical type of adjuvant made of DNA oligonucleotide containing CpG motifs, which has already been used in humans, is shown to boost humoral immunity primarily by acting on monocyte-derived dendritic cells. This study provides novel insight on the mode of action of adjuvant targeting Toll-like receptors. PMID:24803394

  7. Interferon-γ stimulates human follicular dendritic cell-like cells to produce prostaglandins via the JAK-STAT pathway.

    PubMed

    Kim, Jini; Yoon, Yongdae; Jeoung, Dooil; Kim, Young-Myeong; Choe, Jongseon

    2015-08-01

    IFN-γ plays a critical role in the regulation of innate and adaptive immunity. Paying attention to the emerging role of prostaglandins (PGs) as immune regulators, we attempted to establish the effect of IFN-γ on PG production in human follicular dendritic cell-like HK cells and the underlying signaling pathway by using RNA interference technology. IFN-γ induced COX-2 protein expression in HK cells in a time- and dose-dependent manner, which was not observed in peripheral blood monocytes. Although IFN-γ induced phosphorylation of STAT1, STAT3, and STAT5, only STAT1 was essential for the COX-2 augmentation. The JAK kinases responsible for IFN-γ-triggered STAT1 phosphorylation were JAK1 and JAK2, which were also required for the COX-2 induction. The essential requirement of JAK1 and JAK2 was verified by confocal microscopic analysis, since STAT1 phosphorylation and nuclear translocation were impaired in HK cells with these two kinases knocked down. Finally, we demonstrated that JAK1, JAK2, and STAT1 were indispensable for the actual enhancement of PG production in response to IFN-γ stimulation. These results provide a novel insight into our understanding of IFN-γ under inflammatory conditions and support the emerging concept of PGs as important immune regulators.

  8. Opposing roles of TGF-β in prostaglandin production by human follicular dendritic cell-like cells.

    PubMed

    Choe, Jongseon; Park, Jihoon; Lee, Seungkoo; Kim, Young-Myeong; Jeoung, Dooil

    2016-08-01

    Prostaglandins (PGs) are recognized as important immune regulators. Using human follicular dendritic cell (FDC)-like HK cells, we have investigated the immunoregulatory role of PGs and their production mechanisms. The present study was aimed at determining the role of TGF-β in IL-1β-induced cyclooxygenase-2 (COX-2) expression by immunoblotting. COX-2 is the key enzyme responsible for PG production in HK cells. TGF-β, when added simultaneously with IL-1β, gave rise to an additive effect on COX-2 expression in a dose-dependent manner. However, TGF-β inhibited IL-1β-stimulated COX-2 expression when it was added at least 12h before IL-1β addition. The inhibitory effect of TGF-β was specific to IL-1β-induced COX-2 expression in HK cells. The stimulating and inhibitory effects of TGF-β were reproduced in IL-1β-stimulated PG production. Based on our previous results of the essential requirement of ERK and p38 MAPKs in TGF-β-induced COX-2 expression, we examined whether the differential activation of these MAPKs would underlie the opposing activities of TGF-β. The phosphorylation of ERK and p38 MAPKs was indeed enhanced or suppressed by the simultaneous treatment or pre-treatment, respectively. These results suggest that TGF-β exerts opposing effects on IL-1β-induced COX-2 expression in HK cells by differentially regulating activation of ERK and p38 MAPKs.

  9. Dendritic Cell-Secreted Cytotoxic T-Lymphocyte-Associated Protein-4 Regulates the T-cell Response by Downmodulating Bystander Surface B7.

    PubMed

    Halpert, Matthew M; Konduri, Vanaja; Liang, Dan; Chen, Yunyu; Wing, James B; Paust, Silke; Levitt, Jonathan M; Decker, William K

    2016-05-15

    The remarkable functional plasticity of professional antigen-presenting cells (APCs) allows the adaptive immune system to respond specifically to an incredibly diverse array of potential pathogenic insults; nonetheless, the specific molecular effectors and mechanisms that underpin this plasticity remain poorly characterized. Cytotoxic T-lymphocyte-associated protein-4 (CTLA-4), the target of the blockbuster cancer immunotherapeutic ipilimumab, is one of the most well-known and well-studied members of the B7 superfamily and negatively regulates T cell responses by a variety of known mechanisms. Although CTLA-4 is thought to be expressed almost exclusively among lymphoid lineage hematopoietic cells, a few reports have indicated that nonlymphoid APCs can also express the CTLA-4 mRNA transcript and that transcript levels can be regulated by external stimuli. In this study, we substantially build upon these critical observations, definitively demonstrating that mature myeloid lineage dendritic cells (DC) express significant levels of intracellular CTLA-4 that they constitutively secrete in microvesicular structures. CTLA-4(+) microvesicles can competitively bind B7 costimulatory molecules on bystander DC, resulting in downregulation of B7 surface expression with significant functional consequences for downstream CD8(+) T-cell responses. Hence, the data indicate a previously unknown role for DC-derived CTLA-4 in immune cell functional plasticity and have significant implication for the design and implementation of immunomodulatory strategies intended to treat cancer and infectious disease. PMID:26979751

  10. A benzenediamine derivate FC-99 attenuates lupus nephritis in MRL/lpr mice via inhibiting myeloid dendritic cell-secreted BAFF.

    PubMed

    Ji, Jianjian; Xu, Jingjing; Li, Fanlin; Li, Xiaojing; Gong, Wei; Song, Yuxian; Dou, Huan; Hou, Yayi

    2016-05-01

    Myeloid dendritic cells (DCs) can produce B-cell-activating factor (BAFF) that modulates survival and differentiation of B cells and plays a pivotal role in the pathogenesis of systemic lupus erythematosus (SLE). Toll-like receptor 4 (TLR4) signaling has important functions in the process of BAFF production. Our previous study showed that a benzenediamine derivate FC-99 possesses anti-inflammation activity and directly interacts with interleukin-1 receptor-associated kinase 4 (IRAK4), which was a pivotal molecule in TLR4 signaling. In this study, we demonstrated that FC-99 attenuated lupus nephritis in the MRL/lpr mice. FC-99 also decreased the levels of total immunoglobulin G (IgG), total IgG2a and IgM in sera, as well as the activation of B cells in the spleens of MRL/lpr mice. Moreover, FC-99 inhibited abnormal activation of myeloid DCs in spleens and reduced the levels of BAFF in sera, spleens, and kidneys of MRL/lpr mice. Furthermore, upon TLR4 stimulation with lipopolysaccharide in vitro, FC-99 inhibited IRAK4 phosphorylation, as well as the activation and BAFF production in murine bone marrow-derived DCs. These data indicate that FC-99 attenuates lupus nephritis in MRL/lpr mice via inhibiting DC-secreted BAFF, suggesting that FC-99 may be a potential therapeutic candidate for the treatment of SLE. PMID:27121231

  11. AIRE expressing marginal zone dendritic cells balances adaptive immunity and T-follicular helper cell recruitment.

    PubMed

    Lindmark, Evelina; Chen, Yunying; Georgoudaki, Anna-Maria; Dudziak, Diana; Lindh, Emma; Adams, William C; Loré, Karin; Winqvist, Ola; Chambers, Benedict J; Karlsson, Mikael C I

    2013-05-01

    Autoimmune polyendocrine syndrome Type I (APS I) results in multiple endocrine organ destruction and is caused by mutations in the Autoimmune regulator gene (AIRE). In the thymic stroma, cells expressing the AIRE gene dictate T cell education and central tolerance. Although this function is the most studied, AIRE is also expressed in the periphery in DCs and stromal cells. Still, how AIRE regulated transcription modifies cell behaviour in the periphery is largely unknown. Here we show that AIRE is specifically expressed by 33D1(+) DCs and dictates the fate of antibody secreting cell movement within the spleen. We also found that AIRE expressing 33D1(+) DCs expresses self-antigens as exemplified by the hallmark gene insulin. Also, as evidence for a regulatory function, absence of Aire in 33D1(+) DCs led to reduced levels of the chemokine CXCL12 and increased co-stimulatory properties. This resulted in altered activation and recruitment of T-follicular helper cells and germinal centre B cells. The altered balance leads to a change of the early response to a T cell-dependent antigen in Aire(-/-) mice. These findings add to the understanding of how specific DC subtypes regulate the early responses during T cell-dependent antibody responses within the spleen and further define the role of AIRE in the periphery as regulator of self-antigen expression and lymphocyte migration.

  12. Novel innate immune functions for galectin-1: galectin-1 inhibits cell fusion by Nipah virus envelope glycoproteins and augments dendritic cell secretion of proinflammatory cytokines.

    PubMed

    Levroney, Ernest L; Aguilar, Hector C; Fulcher, Jennifer A; Kohatsu, Luciana; Pace, Karen E; Pang, Mabel; Gurney, Kevin B; Baum, Linda G; Lee, Benhur

    2005-07-01

    Galectin-1 (gal-1), an endogenous lectin secreted by a variety of cell types, has pleiotropic immunomodulatory functions, including regulation of lymphocyte survival and cytokine secretion in autoimmune, transplant disease, and parasitic infection models. However, the role of gal-1 in viral infections is unknown. Nipah virus (NiV) is an emerging pathogen that causes severe, often fatal, febrile encephalitis. The primary targets of NiV are endothelial cells. NiV infection of endothelial cells results in cell-cell fusion and syncytia formation triggered by the fusion (F) and attachment (G) envelope glycoproteins of NiV that bear glycan structures recognized by gal-1. In the present study, we report that NiV envelope-mediated cell-cell fusion is blocked by gal-1. This inhibition is specific to the Paramyxoviridae family because gal-1 did not inhibit fusion triggered by envelope glycoproteins of other viruses, including two retroviruses and a pox virus, but inhibited fusion triggered by envelope glycoproteins of the related Hendra virus and another paramyxovirus. The physiologic dimeric form of gal-1 is required for fusion inhibition because a monomeric gal-1 mutant had no inhibitory effect on cell fusion. gal-1 binds to specific N-glycans on NiV glycoproteins and aberrantly oligomerizes NiV-F and NiV-G, indicating a mechanism for fusion inhibition. gal-1 also increases dendritic cell production of proinflammatory cytokines such as IL-6, known to be protective in the setting of other viral diseases such as Ebola infections. Thus, gal-1 may have direct antiviral effects and may also augment the innate immune response against this emerging pathogen.

  13. A case of t(14; 18)-negative follicular lymphoma with atypical immunophenotype: usefulness of immunoarchitecture of Ki67, CD79a and follicular dendritic cell meshwork in making the diagnosis.

    PubMed

    Wong, Yin- Ping; Abdul-Rahman, Faridah; Samsudin, Aamad Toha; Masir, Noraidah

    2014-08-01

    Follicular lymphoma is characterised by the t(14;18)(q32;q21) chromosomal translocation causing BCL2 protein overexpression. A proportion of follicular lymphomas do not carry the t(14;18) translocation and lacked BCL2 protein expression. We describe a case of a BCL2 protein- and t(14;18)-negative follicular lymphoma that caused diagnostic difficulty. The usefulness of several immunomarkers including Ki67, CD79a and CD21 in aiding the diagnosis is discussed. The patient is a 51-year-old male who presented with gradually enlarging lymphadenopathy. Histopathological examination of the lymph node showed complete architectural effacement by neoplastic follicles containing expanded CD21-positive follicular dendritic cell meshwork. The neoplastic cells expressed pan-B cell markers (CD20, CD79a) and germinal centre marker (BCL6) but not BCL2 and CD10. Of interest are the staining patterns of Ki67 and CD79a. We observed that the Ki67- positive proliferating cells were evenly distributed within the neoplastic follicles without zonation. In addition, CD79a was homogeneously strong within the neoplastic follicles. These staining patterns were distinctly different from that observed in reactive lymphoid follicles. Fluorescent insitu hybridisation (FISH) analysis however showed absence of BCL2 gene rearrangement. Despite the atypical immunophenotype and lack of BCL2 gene rearrangement, the diagnosis of follicular lymphoma was made based on careful observation of the morphology as well as immunoarchitecture of the Ki67, CD79a and CD21 markers. PMID:25194535

  14. Enhanced Follicular Dendritic Cell-B Cell Interaction in HIV and SIV Infections and its Potential Role in Polyclonal B Cell Activation

    PubMed Central

    Lewis, Mark. G.; Kosco-Vilbois, Marie H.

    1998-01-01

    Human immunodeficiency virus (HIV) infections have been characterized by both polyclonal Bcell activation and enhanced responsiveness to B-cell growth factors on one hand and the loss of specific antibody (Ab) responses and refractoriness to the normal signals for B-cell activation on the other. Histopathological studies of lymph node from HIV- and simian immunodeficiency virus (SIV)-infected individuals have indicated initial follicular hyperplasia and the appearance of large irregular germinal centers that undergo progressive involution concomitant with follicular dendritic-cell (FDC) disruption. During this process, follicular dendritic-cell -enriched lymph-node-cell cultures exhibit increased ability to induce cluster formation (“in vitro germinal centers”), lymphocyte proliferation and antibody production compared to uninfected controls. This paper discusses how enhanced FDC-B-cell interaction within SIV-infected germinal centers may result in a reduced ability to select high-affinity B cells and alter the dynamics of antibodyproducing- cell and memory-cell generation resulting in the observed hyperactivity. PMID:9716906

  15. Cell secretion: an update.

    PubMed

    Jeremic, A

    2008-08-01

    This past decade has witnessed the publication of a flurry of scientific papers and reports on the subject of cell secretion, following discovery of a permanent plasma membrane structure termed 'porosome' and its determination as the universal secretory machinery in cells. This discovery has led to a paradigm shift in our understanding of the secretory process, demonstrating that membrane-bound secretory vesicles transiently dock and fuse at the porosome base to release their contents to the cell exterior. The regulated release of intravesicular contents during cell secretion is governed by dilation of the porosome opening to the outside, and the extent of vesicle swelling. In agreement, a great number of articles have been written and studies performed, which are briefly discussed in this article.

  16. Cell secretion: an update

    PubMed Central

    Jeremic, A

    2008-01-01

    This past decade has witnessed the publication of a flurry of scientific papers and reports on the subject of cell secretion, following discovery of a permanent plasma membrane structure termed ‘porosome’ and its determination as the universal secretory machinery in cells. This discovery has led to a paradigm shift in our understanding of the secretory process, demonstrating that membrane-bound secretory vesicles transiently dock and fuse at the porosome base to release their contents to the cell exterior. The regulated release of intravesicular contents during cell secretion is governed by dilation of the porosome opening to the outside, and the extent of vesicle swelling. In agreement, a great number of articles have been written and studies performed, which are briefly discussed in this article. PMID:18363838

  17. Complement activation and complement receptors on follicular dendritic cells are critical for the function of a targeted adjuvant.

    PubMed

    Mattsson, Johan; Yrlid, Ulf; Stensson, Anneli; Schön, Karin; Karlsson, Mikael C I; Ravetch, Jeffrey V; Lycke, Nils Y

    2011-10-01

    A detailed understanding of how activation of innate immunity can be exploited to generate more effective vaccines is critically required. However, little is known about how to target adjuvants to generate safer and better vaccines. In this study, we describe an adjuvant that, through complement activation and binding to follicular dendritic cells (FDC), dramatically enhances germinal center (GC) formation, which results in greatly augmented Ab responses. The nontoxic CTA1-DD adjuvant hosts the ADP-ribosylating CTA1 subunit from cholera toxin and a dimer of the D fragment from Staphylococcus aureus protein A. We found that T cell-dependent, but not -independent, responses were augmented by CTA1-DD. GC reactions and serum Ab titers were both enhanced in a dose-dependent manner. This effect required complement activation, a property of the DD moiety. Deposition of CTA1-DD to the FDC network appeared to occur via the conduit system and was dependent on complement receptors on the FDC. Hence, Cr2(-/-) mice failed to augment GC reactions and exhibited dramatically reduced Ab responses, whereas Ribi adjuvant demonstrated unperturbed adjuvant function in these mice. Noteworthy, the adjuvant effect on priming of specific CD4 T cells was found to be intact in Cr2(-/-) mice, demonstrating that the CTA1-DD host both complement-dependent and -independent adjuvant properties. This is the first demonstration, to our knowledge, of an adjuvant that directly activates complement, enabling binding of the adjuvant to the FDC, which subsequently strongly promoted the GC reaction, leading to augmented serum Ab titers and long-term memory development. PMID:21880985

  18. Localization of collagen modifying enzymes on fibroblastic reticular cells and follicular dendritic cells in non-neoplastic and neoplastic lymphoid tissues.

    PubMed

    Ohe, Rintaro; Aung, Naing Ye; Meng, Hongxue; Kabasawa, Takanobu; Suto, Aya; Tamazawa, Nobuyuki; Yang, Suran; Kato, Tomoya; Yamakawa, Mitsunori

    2016-07-01

    The aim of this study was to evaluate the localization of collagen modifying enzymes (CMEs) on fibroblastic reticular cells (FRCs) and follicular dendritic cells (FDCs) in non-neoplastic lymphoid tissues and various malignant lymphomas. The expression of prolyl 4-hydroxylase 1 (P4H1), lysyl hydroxylase 3 (LH3), and protein disulfide isomerase (PDI) was frequently observed on FRCs and FDCs in the germinal center (GC), except for the mantle zone. The expression of CMEs was lower in most lymphomas than in their respective postulated normal counterparts. The ratio of transglutaminase II(+) FRCs/CD35(+) FDCs was also lower in follicular lymphomas (FL) than in other lymphomas. The mRNAs of some CMEs (P4H1, prolyl 4-hydroxylase 3, LH3, and heat shock protein 47) were confirmed in almost all lymphomas. These results indicate that lymphoma cell proliferation suppresses/decreases the number of CMEs expressing FRCs and FDCs in most lymphomas. PMID:26700650

  19. Heterogeneity of stromal cells in the human splenic white pulp. Fibroblastic reticulum cells, follicular dendritic cells and a third superficial stromal cell type

    PubMed Central

    Steiniger, Birte S; Wilhelmi, Verena; Seiler, Anja; Lampp, Katrin; Stachniss, Vitus

    2014-01-01

    At least three phenotypically and morphologically distinguishable types of branched stromal cells are revealed in the human splenic white pulp by subtractive immunohistological double-staining. CD271 is expressed in fibroblastic reticulum cells of T-cell zones and in follicular dendritic cells of follicles. In addition, there is a third CD271− and CD271+/− stromal cell population surrounding T-cell zones and follicles. At the surface of follicles the third population consists of individually variable partially overlapping shells of stromal cells exhibiting CD90 (Thy-1), MAdCAM-1, CD105 (endoglin), CD141 (thrombomodulin) and smooth muscle α-actin (SMA) with expression of CD90 characterizing the broadest shell and SMA the smallest. In addition, CXCL12, CXCL13 and CCL21 are also present in third-population stromal cells and/or along fibres. Not only CD27+ and switched B lymphocytes, but also scattered IgD++ B lymphocytes and variable numbers of CD4+ T lymphocytes often occur close to the third stromal cell population or one of its subpopulations at the surface of the follicles. In contrast to human lymph nodes, neither podoplanin nor RANKL (CD254) were detected in adult human splenic white pulp stromal cells. The superficial stromal cells of the human splenic white pulp belong to a widespread cell type, which is also found at the surface of red pulp arterioles surrounded by a mixed T-cell/B-cell population. Superficial white pulp stromal cells differ from fibroblastic reticulum cells and follicular dendritic cells not only in humans, but apparently also in mice and perhaps in rats. However, the phenotype of white pulp stromal cells is species-specific and more heterogeneous than described so far. PMID:24890772

  20. Intravital and whole-organ imaging reveals capture of melanoma-derived antigen by lymph node subcapsular macrophages leading to widespread deposition on follicular dendritic cells.

    PubMed

    Moalli, Federica; Proulx, Steven T; Schwendener, Reto; Detmar, Michael; Schlapbach, Christoph; Stein, Jens V

    2015-01-01

    Aberrant antigens expressed by tumor cells, such as in melanoma, are often associated with humoral immune responses, which may in turn influence tumor progression. Despite recent data showing the central role of adaptive immune responses on cancer spread or control, it remains poorly understood where and how tumor-derived antigen (TDA) induces a humoral immune response in tumor-bearing hosts. Based on our observation of TDA accumulation in B cell areas of lymph nodes (LNs) from melanoma patients, we developed a pre-metastatic B16.F10 melanoma model expressing a fluorescent fusion protein, tandem dimer tomato, as a surrogate TDA. Using intravital two-photon microscopy (2PM) and whole-mount 3D LN imaging of tumor-draining LNs in immunocompetent mice, we report an unexpectedly widespread accumulation of TDA on follicular dendritic cells (FDCs), which were dynamically scanned by circulating B cells. Furthermore, 2PM imaging identified macrophages located in the subcapsular sinus of tumor-draining LNs to capture subcellular TDA-containing particles arriving in afferent lymph. As a consequence, depletion of macrophages or genetic ablation of B cells and FDCs resulted in dramatically reduced TDA capture in tumor-draining LNs. In sum, we identified a major pathway for the induction of humoral responses in a melanoma model, which may be exploitable to manipulate anti-TDA antibody production during cancer immunotherapy. PMID:25821451

  1. Ablation of the cellular prion protein, PrPC, specifically on follicular dendritic cells has no effect on their maturation or function

    PubMed Central

    McCulloch, Laura; Brown, Karen L.; Mabbott, Neil A.

    2013-01-01

    Summary Follicular dendritic cells (FDC) are situated in the primary follicles of lymphoid tissues where they maintain the structural integrity of the B‐lymphocyte follicle, and help to drive immunoglobulin class‐switch recombination, somatic hypermutation and affinity maturation during the germinal centre response. FDC can also provide a reservoir for pathogens that infect germinal centres including HIV and prions. FDC express high levels of the normal cellular form of the prion protein (PrPC), which makes them susceptible to prion infection. The function of PrPC is uncertain and it is not known why FDC require such high levels of expression of a protein that is found mainly on cells of the central nervous system. In this study, the function of FDC was assessed in mice that had PrPC ablated specifically in their FDC. In mice with FDC‐specific PrPC ablation, our analysis revealed no observable deficits in lymphoid follicle microarchitecture and FDC status. No effects on FDC ability to trap immune complexes or drive antigen‐specific antibody responses and affinity maturation in B lymphocytes were observed. These data clearly demonstrate that PrPC expression is dispensable for the functional maturation of FDC and their ability to maintain antigen‐specific antibody responses and affinity maturation. PMID:23121447

  2. Fucose-based PAMPs prime dendritic cells for follicular T helper cell polarization via DC-SIGN-dependent IL-27 production.

    PubMed

    Gringhuis, Sonja I; Kaptein, Tanja M; Wevers, Brigitte A; van der Vlist, Michiel; Klaver, Elsenoor J; van Die, Irma; Vriend, Lianne E M; de Jong, Marein A W P; Geijtenbeek, Teunis B H

    2014-10-03

    Dendritic cells (DCs) orchestrate antibody-mediated responses to combat extracellular pathogens including parasites by initiating T helper cell differentiation. Here we demonstrate that carbohydrate-specific signalling by DC-SIGN drives follicular T helper cell (TFH) differentiation via IL-27 expression. Fucose, but not mannose, engagement of DC-SIGN results in activation of IKKε, which collaborates with type I IFNR signalling to induce formation and activation of transcription factor ISGF3. Notably, ISGF3 induces expression of IL-27 subunit p28, and subsequent IL-27 secreted by DC-SIGN-primed DCs is pivotal for the induction of Bcl-6(+)CXCR5(+)PD-1(hi)Foxp1(lo) TFH cells, IL-21 secretion by TFH cells and T-cell-dependent IgG production by B cells. Thus, we have identified an essential role for DC-SIGN-induced ISGF3 by fucose-based PAMPs in driving IL-27 and subsequent TFH polarization, which might be harnessed for vaccination design.

  3. Intravital and Whole-Organ Imaging Reveals Capture of Melanoma-Derived Antigen by Lymph Node Subcapsular Macrophages Leading to Widespread Deposition on Follicular Dendritic Cells

    PubMed Central

    Moalli, Federica; Proulx, Steven T.; Schwendener, Reto; Detmar, Michael; Schlapbach, Christoph; Stein, Jens V.

    2015-01-01

    Aberrant antigens expressed by tumor cells, such as in melanoma, are often associated with humoral immune responses, which may in turn influence tumor progression. Despite recent data showing the central role of adaptive immune responses on cancer spread or control, it remains poorly understood where and how tumor-derived antigen (TDA) induces a humoral immune response in tumor-bearing hosts. Based on our observation of TDA accumulation in B cell areas of lymph nodes (LNs) from melanoma patients, we developed a pre-metastatic B16.F10 melanoma model expressing a fluorescent fusion protein, tandem dimer tomato, as a surrogate TDA. Using intravital two-photon microscopy (2PM) and whole-mount 3D LN imaging of tumor-draining LNs in immunocompetent mice, we report an unexpectedly widespread accumulation of TDA on follicular dendritic cells (FDCs), which were dynamically scanned by circulating B cells. Furthermore, 2PM imaging identified macrophages located in the subcapsular sinus of tumor-draining LNs to capture subcellular TDA-containing particles arriving in afferent lymph. As a consequence, depletion of macrophages or genetic ablation of B cells and FDCs resulted in dramatically reduced TDA capture in tumor-draining LNs. In sum, we identified a major pathway for the induction of humoral responses in a melanoma model, which may be exploitable to manipulate anti-TDA antibody production during cancer immunotherapy. PMID:25821451

  4. NK Cell Activation in the Antitumor Response Induced by IFN-α Dendritic Cells Loaded with Apoptotic Cells from Follicular Lymphoma Patients.

    PubMed

    Lapenta, Caterina; Donati, Simona; Spadaro, Francesca; Castaldo, Paolo; Belardelli, Filippo; Cox, Maria C; Santini, Stefano M

    2016-08-01

    Follicular lymphoma (FL) is the most common form of indolent non-Hodgkin lymphoma. This malignancy is considered virtually incurable, with high response rates to therapy but frequent relapses. We investigated the ability of monocyte-derived dendritic cells generated in the presence of IFN-α and GM-CSF (IFN-DC) and loaded with apoptotic lymphoma cells to activate immune responses against FL cells, with the ultimate goal of designing novel patient-specific vaccination strategies for the treatment of FL. In this article, we show that apoptotic tumor cell-loaded IFN-DC from FL patients, which were cultured for 2 wk with autologous lymphocytes, led to Th1 response skewing, based on significantly higher levels of IFN-γ production and a remarkable increase in CD8(+) and NK cell frequency, consistent with the detection of enhanced cytotoxic effector function toward autologous FL cells. IFN-DC were found to promote efficient NK cell activation, increased expression of cytotoxicity receptors, and extensive IFN-γ production in the virtual absence of IL-10. Moreover, direct recognition and killing of primary autologous lymphoma cells by activated NK cells from FL patients was also demonstrated. A critical role was demonstrated for MHC class I-related chain A and B and membrane-bound IL-15 in IFN-DC-mediated NK cell activation and early IFN-γ production. The overall results indicate that IFN-DC loaded with autologous apoptotic FL cells represent a valuable tool for improving the potency of therapeutic cancer vaccines through the efficient induction of NK cell activation and promotion of CD8(+) T cell antitumor immunity. PMID:27357153

  5. Cell secretion and membrane fusion.

    PubMed

    Jena, Bhanu P

    2005-07-01

    Secretion occurs in all cells of multicellular organisms and involves the delivery of secretory products packaged in membrane-bound vesicles to the cell exterior. Specialized cells for neurotransmission, enzyme secretion or hormone release utilize a highly regulated secretory process. Secretory vesicles are transported to specific sites at the plasma membrane, where they dock and fuse to release their contents. Similar to other cellular processes, cell secretion is found to be highly regulated and a precisely orchestrated event. It has been demonstrated that membrane-bound secretory vesicles dock and fuse at porosomes, which are specialized supramolecular structures at the cell plasma membrane. Swelling of secretory vesicles results in a build-up of pressure, allowing expulsion of intravesicular contents. The extent of secretory vesicle swelling dictates the amount of intravesicular contents expelled during secretion. The discovery of the porosome, its isolation, its structure and dynamics at nm resolution and in real time, its biochemical composition and functional reconstitution into artificial lipid membrane, have been determined. The molecular mechanism of secretory vesicle fusion at the base of porosomes, and vesicle swelling, has also been resolved. These findings reveal the molecular mechanism of cell secretion.

  6. Modeling mechanisms of cell secretion.

    PubMed

    Tsaneva-Atanasova, Krasimira; Osinga, Hinke M; Tabak, Joël; Pedersen, Morten Gram

    2010-12-01

    Secretion is a fundamental cellular process involving the regulated release of intracellular products from cells. Physiological functions such as neurotransmission, or the release of hormones and digestive enzymes, are all governed by cell secretion. Anomalies in the processes involved in secretion contribute to the development and progression of diseases such as diabetes and other hormonal disorders. To unravel the mechanisms that govern such diseases, it is essential to understand how hormones, growth factors and neurotransmitters are synthesized and processed, and how their signals are recognized, amplified and transmitted by intracellular signaling pathways in the target cells. Here, we discuss diverse aspects of the detailed mechanisms involved in secretion based on mathematical models. The models range from stochastic ones describing the trafficking of secretory vesicles to deterministic ones investigating the regulation of cellular processes that underlie hormonal secretion. In all cases, the models are closely related to experimental results and suggest theoretical predictions for the secretion mechanisms.

  7. Progesterone inhibits mast cell secretion.

    PubMed

    Vasiadi, M; Kempuraj, D; Boucher, W; Kalogeromitros, D; Theoharides, T C

    2006-01-01

    Mast cells are involved in allergic reactions, where they secrete numerous vasoactive, inflammatory and nociceptive mediators in response to immunoglobulin E (IgE) and antigen. However, they have also been implicated in inflammatory conditions, such as painful bladder syndrome/interstitial cystitis (PBS/IC), irritable bowel syndrome (IBS) and migraines, all of which occur more often in women and are exacerbated during ovulation, but are suppressed during pregnancy. Mast cells express high affinity estrogen receptors and estradiol augments their secretion, while tamoxifen inhibits it. Here we report that progesterone (100 nM), but not the structurally related cholesterol, inhibits histamine secretion from purified rat peritoneal mast cells stimulated immunologically or by substance P (SP), an effect also documented by electron microscopy. These results suggest that mast cell secretion may be regulated by progesterone and may explain the reduced symptoms of certain inflammatory conditions during pregnancy.

  8. Follicular dendritic cell sarcoma: clinicopathologic study of 15 cases with emphasis on novel expression of MDM2, somatostatin receptor 2A, and PD-L1.

    PubMed

    Agaimy, Abbas; Michal, Michael; Hadravsky, Ladislav; Michal, Michal

    2016-08-01

    Follicular dendritic cell sarcoma (FDCS) is a rare low-grade neoplasm with the phenotype of FDC cells. This rare sarcoma has been well known for being mistaken for a variety of neoplasms (mainly meningioma), particularly at extranodal sites. Diagnosis of FDCS mainly relies on characteristic histologic appearance supplemented by immunohistochemistry and electron microscopy. In this study, we reviewed 15 FDCSs retrieved from our consultation files and stained them for newly reported or novel markers (PD-L1, Rb1, MDM2, and somatostatin receptor 2A [SSTR2A]) in addition to conventional FDC markers. Patients were 7 men and 7 women (1 unspecified) with a mean age of 47 years (20-75 years). The tumor site was lymph nodes (6) or spleen (2), both (1) and extranodal sites of head and neck (4) or abdominal cavity (2). Treatment was variable combinations of surgery and aggressive chemotherapy/radiotherapy. Four of 8 patients with follow-up died of disease within 1 to 10 years. All tumors expressed at least 1 FDC marker: CD21 (8/13), CD23 (2/13), CD35 (8/12), CNA.42 (13/14), Clusterin (8/13), Fascin (15/15) and D2-40/podoplanin (7/14). Epstein-Barr virus (EBER-1/2 in situ hybridization) was performed successfully in 10 conventional variants; all were negative. Five of 14 cases (36%) stained strongly for SSTR2A with a distinctive membranous pattern. Residual lymphoid follicles surrounding some of the tumors stained similarly for SSTR2A. Seven (54%) of 13 assessable cases showed moderate to strong membranous staining for PD-L1 in greater than 5% of the neoplastic cells. The Rb1 antigen was lost in 4 (28%) of 14 cases. MDM2 stained less than 5% to 20% of the tumor cells in 5 (36%) of 14 cases; 2 of them showed amplification by fluorescence in situ hybridization (FISH). CDK4 was negative except for weak staining in 1 of 14 cases. This study adds to the existing few clinicopathologic series on FDCS and represents the first study to show MDM2 amplification in this entity. Our results

  9. Expression of CD11c+HLA-DR+dendritic cells and related cytokines in the follicular fluid might be related to pathogenesis of ovarian hyperstimulation syndrome

    PubMed Central

    Shi, Sen-Lin; Peng, Zhao-Feng; Yao, Gui-Dong; Jin, Hai-Xia; Song, Wen-Yan; Yang, Hong-Yi; Xue, Ru-Yue; Sun, Ying-Pu

    2015-01-01

    Objective: To explore the expressions of CD11c+HLA-DR+dentritic cells in the follicular fluid of patients with OHSS and their significances. Subjects: 100 individuals. Treatment: embryos were observed. The distribution of dentritic cells in follicular fluid and the levels of IL-10, IL-12, IL-18 and IL-23 in follicular fluid were detected. Methods: There were ovarian hyperstimulation syndrome (OHSS) group and control group in this study. The OHSS group consisted of 50 patients with OHSS and the control group consisted of 50 patients who underwent in vitro fertilization-embryo transfer (IVF-ET) only due to male factors. The statuses of embryos were compared between the two groups. The distribution of dentritic cells in follicular fluid was determined with flow cytometry, and the levels of IL-10, IL-12, IL-18 and IL-23 in follicular fluid were detected with enzyme-linked immunosorbent assay (ELISA) in all patients. Results: The two-pronuclear (2PN) fertility rate, high-quality embryo rate and available embryo rate were all significantly lower in OHSS group than in control group (all P<0.05). The number of CD11c+HLA-DR+dentritic cells (P<0.05) and the levels of IL-10, IL-12, IL-18 and IL-23 were all significantly higher in OHSS group than in control group (all P<0.01). Conclusion: The follicular fluid of the patients with OHSS is in an inflammatory status, the inflammatory status may be involved in OHSS and the microenvironment of follicular fluid may affects oocyte quality and embryo development. PMID:26823856

  10. Immune and inflammatory responses in TNF alpha-deficient mice: a critical requirement for TNF alpha in the formation of primary B cell follicles, follicular dendritic cell networks and germinal centers, and in the maturation of the humoral immune response

    PubMed Central

    1996-01-01

    To investigate the role of TNF alpha in the development of in vivo immune response we have generated TNF alpha-deficient mice by gene targeting. Homozygous mutant mice are viable and fertile, develop lymph nodes and Peyer's patches and show no apparent phenotypic abnormalities, indicating that TNF alpha is not required for normal mouse development. In the absence of TNF alpha mice readily succumb to L. monocytogenes infections and show reduced contact hypersensitivity responses. Furthermore, TNF alpha knockout mice are resistant to the systemic toxicity of LPS upon D-galactosamine sensitization, yet they remain sensitive to high doses of LPS alone. Most interestingly, TNF alpha knockout mice completely lack splenic primary B cell follicles and cannot form organized follicular dendritic cell (FDC) networks and germinal centers. However, despite the absence of B cell follicles, Ig class-switching can still occur, yet deregulated humoral immune responses against either thymus-dependent (TD) or thymus-independent (TI) antigens are observed. Complementation of TNF alpha functioning by the expression of either human or murine TNF alpha transgenes is sufficient to reconstitute these defects, establishing a physiological role for TNF alpha in regulating the development and organization of splenic follicular architecture and in the maturation of the humoral immune response. PMID:8879212

  11. Cell secretion: current structural and biochemical insights.

    PubMed

    Trikha, Saurabh; Lee, Elizabeth C; Jeremic, Aleksandar M

    2010-10-12

    Essential physiological functions in eukaryotic cells, such as release of hormones and digestive enzymes, neurotransmission, and intercellular signaling, are all achieved by cell secretion. In regulated (calcium-dependent) secretion, membrane-bound secretory vesicles dock and transiently fuse with specialized, permanent, plasma membrane structures, called porosomes or fusion pores. Porosomes are supramolecular, cup-shaped lipoprotein structures at the cell plasma membrane that mediate and control the release of vesicle cargo to the outside of the cell. The sizes of porosomes range from 150 nm in diameter in acinar cells of the exocrine pancreas to 12 nm in neurons. In recent years, significant progress has been made in our understanding of the porosome and the cellular activities required for cell secretion, such as membrane fusion and swelling of secretory vesicles. The discovery of the porosome complex and the molecular mechanism of cell secretion are summarized in this article.

  12. Follicular dendritic cell–dependent drug resistance of non-Hodgkin lymphoma involves cell adhesion–mediated Bim down-regulation through induction of microRNA-181a

    PubMed Central

    Lwin, Tint; Lin, Jianhong; Choi, Yong Sung; Zhang, Xinwei; Moscinski, Lynn C.; Wright, Kenneth L.; Sotomayor, Eduardo M.; Dalton, William S.

    2010-01-01

    Follicular dendritic cells (FDCs), an essential component of the lymph node microenvironment, regulate and support B-lymphocyte differentiation, survival, and lymphoma progression. Here, we demonstrate that adhesion of mantle cell lymphoma and other non-Hodgkin lymphoma cells to FDCs reduces cell apoptosis and is associated with decreased levels of the proapoptotic protein, Bim. Bim down-regulation is posttranscriptionally regulated via up-regulation of microRNA-181a (miR-181a). miR-181a overexpression decreases, whereas miR-181a inhibition increases Bim levels by directly targeting Bim. Furthermore, we found that cell adhesion–up-regulated miR-181a contributes to FDC-mediated cell survival through Bim down-regulation, implicating miR-181a as an upstream effector of the Bim-apoptosis signaling pathway. miR-181a inhibition and Bim upregulation significantly suppressed FDC-mediated protection against apoptosis in lymphoma cell lines and primary lymphoma cells. Thus, FDCs protect B-cell lymphoma cells against apoptosis, in part through activation of a miR-181a–dependent mechanism involving down-regulation of Bim expression. We demonstrate, for the first time, that cell-cell contact controls tumor cell survival and apoptosis via microRNA in mantle cell and other non-Hodgkin lymphomas. Regulation of microRNAs by B-cell–FDC interaction may support B-cell survival, representing a novel molecular mechanism for cell adhesion–mediated drug resistance and a potential therapeutic target in B-cell lymphomas. PMID:20841506

  13. HIV Replication in CD4+ T Lymphocytes in the Presence and Absence of Follicular Dendritic Cells: Inhibition of Replication mediated by Alpha-1-Antitrypsin through Altered IκBα Ubiquitination1

    PubMed Central

    Zhou, Xueyuan; Shapiro, Leland; Fellingham, Gilbert; Willardson, Barry M.; Burton, Gregory F.

    2011-01-01

    Follicular dendritic cells (FDCs) increase HIV replication and virus production in lymphocytes by increasing the activation of NF-κB in infected cells. Because alpha-1-antitrypsin (AAT) decreases HIV replication in PBMCs and monocytic cells and decreases NF-κB activity, we postulated that AAT might also block FDC-mediated HIV replication. Primary CD4+ T cells were infected with HIV and cultured with FDCs or their supernatant with or without AAT, and ensuing viral RNA and p24 production were monitored. NF-κB activation in the infected cells was also assessed. Virus production was increased in the presence of FDC supernatant but the addition of AAT at concentrations above 0.5 mg/ml inhibited virus replication. AAT blocked the nuclear translocation of NF-κB p50/p65 despite an unexpected elevation in associated phosphorylated and ubiquitinated IκBα (Ub-IκBα). In the presence of AAT, degradation of cytoplasmic IκBα was dramatically inhibited compared to control cultures. AAT did not inhibit the proteasome; however, it altered the pattern of ubiquitination of IκBα. AAT decreased IκBα polyubiquitination linked through ubiquitin lysine residue 48 (K48) and increased ubiquitination linked through lysine residue 63 (K63). Moreover, K63 linked Ub-IκBα degradation was substantially slower than K48 linked Ub-IκBα in the presence of AAT, correlating altered ubiquitination with a prolonged IκBα half-life. Because AAT is naturally occurring and is available clinically, examination of its use as an inhibitory agent in HIV-infected subjects may be informative and lead to the development of similar agents that inhibit HIV replication using a novel mechanism. PMID:21263074

  14. The SNARE Machinery in Mast Cell Secretion.

    PubMed

    Lorentz, Axel; Baumann, Anja; Vitte, Joana; Blank, Ulrich

    2012-01-01

    Mast cells are known as inflammatory cells which exert their functions in allergic and anaphylactic reactions by secretion of numerous inflammatory mediators. During an allergic response, the high-affinity IgE receptor, FcεRI, becomes cross-linked by receptor-bound IgE and antigen resulting in immediate release of pre-synthesized mediators - stored in granules - as well as in de novo synthesis of various mediators like cytokines and chemokines. Soluble N-ethylmaleimide-sensitive factor attachment protein (SNAP) receptors (SNARE) proteins were found to play a central role in regulating membrane fusion events during exocytosis. In addition, several accessory regulators like Munc13, Munc18, Rab GTPases, secretory carrier membrane proteins, complexins, or synaptotagmins were found to be involved in membrane fusion. In this review we summarize our current knowledge about the SNARE machinery and its mechanism of action in mast cell secretion.

  15. The SNARE Machinery in Mast Cell Secretion

    PubMed Central

    Lorentz, Axel; Baumann, Anja; Vitte, Joana; Blank, Ulrich

    2012-01-01

    Mast cells are known as inflammatory cells which exert their functions in allergic and anaphylactic reactions by secretion of numerous inflammatory mediators. During an allergic response, the high-affinity IgE receptor, FcεRI, becomes cross-linked by receptor-bound IgE and antigen resulting in immediate release of pre-synthesized mediators – stored in granules – as well as in de novo synthesis of various mediators like cytokines and chemokines. Soluble N-ethylmaleimide-sensitive factor attachment protein (SNAP) receptors (SNARE) proteins were found to play a central role in regulating membrane fusion events during exocytosis. In addition, several accessory regulators like Munc13, Munc18, Rab GTPases, secretory carrier membrane proteins, complexins, or synaptotagmins were found to be involved in membrane fusion. In this review we summarize our current knowledge about the SNARE machinery and its mechanism of action in mast cell secretion. PMID:22679448

  16. Molecular machinery and mechanism of cell secretion.

    PubMed

    Jena, Bhanu P

    2005-05-01

    Secretion occurs in all living cells and involves the delivery of intracellular products to the cell exterior. Secretory products are packaged and stored in membranous sacs or vesicles within the cell. When the cell needs to secrete these products, the secretory vesicles containing them dock and fuse at plasma membrane-associated supramolecular structures, called porosomes, to release their contents. Specialized cells for neurotransmission, enzyme secretion, or hormone release use a highly regulated secretory process. Similar to other fundamental cellular processes, cell secretion is precisely regulated. During secretion, swelling of secretory vesicles results in a build-up of intravesicular pressure, allowing expulsion of vesicular contents. The extent of vesicle swelling dictates the amount of vesicular contents expelled. The discovery of the porosome as the universal secretory machinery, its isolation, its structure and dynamics at nanometer resolution and in real time, and its biochemical composition and functional reconstitution into artificial lipid membrane have been determined. The molecular mechanism of secretory vesicle swelling and the fusion of opposing bilayers, that is, the fusion of secretory vesicle membrane at the base of the porosome membrane, have also been resolved. These findings reveal, for the first time, the universal molecular machinery and mechanism of secretion in cells.

  17. Cell secretion machinery: studies using the AFM.

    PubMed

    Jena, Bhanu P

    2006-01-01

    A new field in biology, 'nano-cell biology', has emerged from the successful use of force microscopy in understanding the structure and dynamics of cells and biomolecules, at nm resolution and in real time. Atomic force microscopy, in combination with conventional tools and approaches (electron microscopy, electrophysiology, X-ray diffraction, photon correlation spectroscopy, mass spectroscopy, biochemistry, and molecular biology), has revealed for the first time, the universal molecular machinery and mechanism of secretion in cells. Secretion occurs in all living cells and involves the delivery of intracellular products to the cell exterior. Secretory products are packaged and stored in membranous sacs or vesicles within the cell. When the cell needs to secrete these products, the secretory vesicles containing them, dock and fuse at plasma membrane-associated supramolecular structures called Porosome, to release their contents. Specialized cells for neurotransmission, enzyme secretion, or hormone release utilize a highly regulated secretory process. During secretion, swelling of secretory vesicles results in a build-up of intravesicular pressure, allowing expulsion of vesicular contents. The extent of vesicle swelling dictates the amount of vesicular contents expelled. The discovery of the porosome as the universal secretory machinery, its isolation, its structure and dynamics at nm resolution and in real time, its biochemical composition and functional reconstitution into artificial lipid membrane, have been determined. The molecular mechanism of secretory vesicle swelling, and the fusion of opposing bilayers, i.e., the fusion of secretory vesicle membrane at the base of the porosome membrane, has also been resolved.

  18. Follicular occlusion tetrad.

    PubMed

    Vasanth, Vani; Chandrashekar, Byalakere Shivanna

    2014-10-01

    Follicular occlusion tetrad is a symptom complex consisting of four conditions having a similar pathophysiology. It includes Hidradenitis suppurativa, acne conglobata, dissecting cellulitis of the scalp and pilonidal sinus. The exact pathogenesis of this group of disease is unknown but evidence suggests that they share the same pathological process initiated by follicular occlusion in apocrine gland bearing areas. Though each of these conditions is commonly encountered singly, follicular occlusion tetrad as a symptom complex has been rarely reported in the literature. PMID:25396138

  19. Follicular occlusion tetrad

    PubMed Central

    Vasanth, Vani; Chandrashekar, Byalakere Shivanna

    2014-01-01

    Follicular occlusion tetrad is a symptom complex consisting of four conditions having a similar pathophysiology. It includes Hidradenitis suppurativa, acne conglobata, dissecting cellulitis of the scalp and pilonidal sinus. The exact pathogenesis of this group of disease is unknown but evidence suggests that they share the same pathological process initiated by follicular occlusion in apocrine gland bearing areas. Though each of these conditions is commonly encountered singly, follicular occlusion tetrad as a symptom complex has been rarely reported in the literature. PMID:25396138

  20. Porosome: the universal molecular machinery for cell secretion.

    PubMed

    Jena, Bhanu P

    2008-12-31

    Porosomes are supramolecular, lipoprotein structures at the cell plasma membrane, where membrane-bound secretory vesicles transiently dock and fuse to release inravesicular contents to the outside during cell secretion. The mouth of the porosome opening to the outside, range in size from 150 nm in diameter in acinar cells of the exocrine pancreas, to 12 nm in neurons, which dilates during cell secretion, returning to its resting size following completion of the process. In the past decade, the composition of the porosome, its structure and dynamics at nm resolution and in real time, and its functional reconstitution into artificial lipid membrane, have all been elucidated. In this mini review, the discovery of the porosome, its structure, function, isolation, chemistry, and reconstitution into lipid membrane, the molecular mechanism of secretory vesicle swelling and fusion at the base of porosomes, and how this new information provides a paradigm shift in our understanding of cell secretion, is discussed.

  1. Follicular penetration and targeting.

    PubMed

    Lademann, Jürgen; Otberg, Nina; Jacobi, Ute; Hoffman, Robert M; Blume-Peytavi, Ulrike

    2005-12-01

    In the past, intercellular penetration was assumed to be the most important penetration pathway of topically applied substances. First hints that follicular penetration needs to be taken into consideration were confirmed by recent investigations, presented during the workshop "Follicular Penetration and Targeting" at the 4th Intercontinental Meeting of Hair Research Societies", in Berlin 2004. Hair follicles represent an efficient reservoir for the penetration of topically applied substances with subsequent targeting of distinct cell populations, e.g., nestin-expressing follicular bulge cells. The volume of this reservoir can be determined by differential stripping technology. The follicular penetration processes are significantly influenced by the state of the follicular infundibulum; recent experimental investigations could demonstrate that it is essential to distinguish between open and closed hair follicles. Topically applied substances can only penetrate into open hair follicle. Knowledge of follicular penetration is of high clinical relevance for functional targeting of distinct follicular regions. Human hair follicles show a hair-cycle-dependent variation of the dense neuronal and vascular network. Moreover, during hair follicle cycling with initiation of anagen, newly formed vessels occur. Thus, the potential of nestin-expressing hair follicle stem cells to form neurons and blood vessels was investigated.

  2. Benign follicular tumors*

    PubMed Central

    Tellechea, Oscar; Cardoso, José Carlos; Reis, José Pedro; Ramos, Leonor; Gameiro, Ana Rita; Coutinho, Inês; Baptista, António Poiares

    2015-01-01

    Benign follicular tumors comprise a large and heterogeneous group of neoplasms that share a common histogenesis and display morphological features resembling one or several portions of the normal hair follicle, or recapitulate part of its embryological development. Most cases present it as clinically nondescript single lesions and essentially of dermatological relevance. Occasionally, however, these lesions be multiple and represent a cutaneous marker of complex syndromes associated with an increased risk of visceral neoplasms. In this article, the authors present the microscopic structure of the normal hair follicle as a basis to understand the type and level of differentiation of the various follicular tumors. The main clinicopathological features and differential diagnosis of benign follicular tumors are then discussed, including dilated pore of Winer, pilar sheath acanthoma, trichoadenoma, trichilemmoma, infundibuloma, proliferating trichilemmal cyst/tumor, trichoblastoma and its variants, pilomatricoma, trichodiscoma/fibrofolliculoma, neurofollicular hamartoma and trichofolliculoma. In addition, the main syndromes presenting with multiple follicular tumors are also discussed, namely Cowden, Birt-Hogg-Dubé, Rombo and Bazex-Dupré-Christol syndromes, as well as multiple tumors of follicular infundibulum (infundibulomatosis) and multiple trichoepitheliomas. Although the diagnosis of follicular tumors relies on histological examination, we highlight the importance of their knowledge for the clinician, especially when in presence of patients with multiple lesions that may be the cutaneous marker of a cancer-prone syndrome. The dermatologist is therefore in a privileged position to recognize these lesions, which is extremely important to provide further propedeutic, appropriate referral and genetic counseling for these patients. PMID:26734858

  3. Elucidation of cell secretion: pancreas led the way.

    PubMed

    Craciun, Constantin

    2004-01-01

    Secretion is a basic process in all cells and is required for several important functions such as neurotransmission, the secretion of digestive juices from the exocrine pancreas and the release of hormones from endocrine and neuroendocrine cells. Due to these important functions, the mechanism of cell secretion has been intensely investigated for over half a century. However, it is only in the last decade, with the discovery of a new cellular structure, the 'porosome' or 'fusion pore', and the elucidation of SNARE-induced membrane fusion, that has finally provided us with an understanding of cell secretion at the molecular level. The 'porosome', a supramolecular structure at the cell plasma membrane, was first discovered in the exocrine pancreas, and subsequently in endocrine/neuroendocrine cells and in neurons. The structure and dynamics of the 'porosome' in live cells at nanometer resolution and in real-time, its composition and functional reconstitution in lipid membrane, have all been determined. These findings have fundamentally changed our understanding of cell secretion and provide a clear understanding of this highly regulated process in cells.

  4. Insulin-like 3-induced rat preantral follicular growth is mediated by growth differentiation factor 9.

    PubMed

    Xue, Kai; Kim, Ji Young; Liu, Jia-yin; Tsang, Benjamin K

    2014-01-01

    The communication of somatic cells and oocytes by intrafollicular paracrine factors is essential for follicular growth in the ovary. Insulin-like 3 (INSL3) is a theca cell-secreted paracrine factor. Androgens and growth differentiation factor 9 (GDF9), an oocyte-derived growth factor, are essential for follicular development. Using a rat preantral follicle culture model, we examined in the present study the influence of INSL3 on preantral follicular growth and the molecular mechanisms involved. We have observed that the receptor for INSL3, relaxin/insulin-like family peptide receptor 2 (RXFP2), was exclusively expressed in oocytes. Recombinant INSL3 stimulated Gdf9 expression, preantral follicular growth, and testosterone synthesis in vitro. Inhibition of the cAMP/protein kinase A signaling pathway (with cAMP antagonist, 8-bromoadenosine 3',5'-cyclic monophosphorothioate, Rp-isomer) attenuated INSL3-induced Gdf9 expression and preantral follicular growth. Moreover, knocking down Gdf9 expression (with small interfering RNA) or inhibiting GDF9 signaling (with SB431542, an activin receptor-like kinase receptor 5 inhibitor, or specific inhibitor of mothers against decapentaplegic homolog 3) or androgen action (with flutamide, an androgen receptor antagonist) suppressed INSL3-induced preantral follicular growth. In addition, LH and DHT regulated the expression of Insl3 mRNA in preantral follicles. These observations suggest that INSL3 is a key theca cell-derived growth factor for preantral follicle and that its action is mediated by GDF9.

  5. Follicular jaw cysts.

    PubMed

    Sarac, Zdenko; Perić, Berislav; Filipović-Zore, Irina; Cabov, Tomislav; Biocić, Josip

    2010-03-01

    The aim of this study was to examine the occurrence, localization, size, ways of diagnosing and treatment of a foIlicular jaw cyst. Assessment of the patients' motives and their earlier health status was recorded, as well as their postoperative clinical course. Most of the patients were admitted because of pain, swelling, trismus, or other difficulties associated with cyst formation. Follicular cysts with persisting primary predecessor had an asymptomatic development, and were discovered after orthodontic examination or by chance. In most cases pathohistological finding and description of the formation have coincided with each other (p < 0.05). Cysts of different sizes were treated by different surgical approaches, most commonly alveolotomy and cystectomy in small cysts, while alveolotomy and cystectomy with suction or iodine tampon in large cysts. Cooperation of a dentist, an oral surgeon, a pathologist, and other specialists can lead to early diagnose and prevention of further growth of a follicular jaw cyst, thus preventing substantial bone damage.

  6. T follicular regulatory cells.

    PubMed

    Sage, Peter T; Sharpe, Arlene H

    2016-05-01

    Pathogen exposure elicits production of high-affinity antibodies stimulated by T follicular helper (Tfh) cells in the germinal center reaction. Tfh cells provide both costimulation and stimulatory cytokines to B cells to facilitate affinity maturation, class switch recombination, and plasma cell differentiation within the germinal center. Under normal circumstances, the germinal center reaction results in antibodies that precisely target foreign pathogens while limiting autoimmunity and excessive inflammation. In order to have this degree of control, the immune system ensures Tfh-mediated B-cell help is regulated locally in the germinal center. The recently identified T follicular regulatory (Tfr) cell subset can migrate to the germinal center and inhibit Tfh-mediated B-cell activation and antibody production. Although many aspects of Tfr cell biology are still unclear, recent data have begun to delineate the specialized roles of Tfr cells in controlling the germinal center reaction. Here we discuss the current understanding of Tfr-cell differentiation and function and how this knowledge is providing new insights into the dynamic regulation of germinal centers, and suggesting more efficacious vaccine strategies and ways to treat antibody-mediated diseases.

  7. Selective binding of human cumulus cell-secreted glycoproteins to human spermatozoa during capacitation in vitro

    SciTech Connect

    Tesarik, J.; Kopecny, V.; Dvorak, M.

    1984-06-01

    The results of this study demonstrate that glycoproteins manufactured by human cumulus cells can be detected bound to human spermatozoa incubated in capacitational medium containing the labeled cumulus-cell secretions. Cumulus-cell-secreted glycoproteins were labeled with a mixture of /sup 3/H-methionine and /sup 3/H-tryptophan or with 3H-fucose, and the binding of the labeled compounds to spermatozoa was evaluated by autoradiography. The binding was highly selective, involving only approximately 1% of the samples of spermatozoa used. The results suggest that the binding of cumulus-cell-secreted glycoproteins to spermatozoa may represent a final and highly selective step in human sperm capacitation.

  8. Integrin adhesion in regulation of lacrimal gland acinar cell secretion.

    PubMed

    Andersson, Sofia V; Hamm-Alvarez, Sarah F; Gierow, J Peter

    2006-09-01

    The extracellular microenvironment regulates lacrimal gland acinar cell secretion. Culturing isolated rabbit lacrimal gland acinar cells on different extracellular matrix proteins revealed that laminin enhances carbachol-stimulated secretion to a greater extent than other extracellular matrix proteins investigated. Furthermore, immunofluorescence indicated that integrin subunits, potentially functioning as laminin receptors are present in acinar cells. Among these, the integrin alpha6 and beta1 subunit mRNA expression was also confirmed by RT-PCR and sequence analysis. Secretion assays, which measured beta-hexosaminidase activity released in the culture media, demonstrated that function-blocking integrin alpha6 and beta1 monoclonal antibodies (mAbs) induce a rapid, transient and dose-dependent secretory response in cultured cells. To determine the intracellular pathways by which integrin alpha6 and beta1 mAbs could induce secretion, selected second messenger molecules were inhibited. Although inhibitors of protein kinase C and IP(3)-induced Ca(2+) mobilization attenuated carbachol-stimulated secretion, no effect on integrin mAb-induced release was observed. In addition, protein tyrosine kinases do not appear to have a role in transducing signals arising from mAb interactions. Our data clearly demonstrate, though, that cell adhesion through integrins regulates secretion from lacrimal gland acinar cells. The fact that the integrin mAbs affect the cholinergic response differently and that the integrin beta1 mAb secretion, but not the alpha6, was attenuated by the phosphatase inhibitor, sodium orthovanadate, suggests that each subunit utilizes separate intracellular signaling pathways to induce exocytosis. The results also indicate that the secretory response triggered by the beta1 integrin mAb is generated through dephosphorylation events.

  9. Immunoglobulin light chain immunohistochemistry revisited, with emphasis on reactive follicular hyperplasia versus follicular lymphoma.

    PubMed

    Weiss, Lawrence M; Loera, Sofia; Bacchi, Carlos E

    2010-05-01

    The identification of monotypic light chains is an important adjunct to the diagnosis of B-cell lymphoma, yet to reliably perform it on formalin-fixed paraffin sections is often difficult. We have evaluated a new set of monoclonal antibodies to kappa and lambda light chains that are reactive in paraffin sections. In reactive lymphoid tissues, polytypic staining was noted in greater than 95% of cases, with strong staining of plasma cells, moderate staining of the follicular dendritic cell network, and weak staining of mantle zone cells. Strong staining of the appropriate light chain was seen in each of the 7 cases of multiple myeloma. In a series of 58 cases of B-cell lymphoma, correlation between the results of immunohistochemistry and flow cytometry was obtained in 36 cases (62%), including 32 cases (21 kappa and 11 lambda) in which a single light chain was expressed. Monotypic staining was also seen in 6 additional cases (10%) in which flow cytometry was negative. Thirty of 46 cases (65%) of follicular lymphoma showed monotypic light chain expression, in contrast to 64 of 67 cases (95%) of reactive lymphoid hyperplasia, which showed polytypic light chain expression. These antibodies may provide an effective adjunct to the diagnosis of B-cell lymphoma in routine diagnostic work.

  10. Dendrite inhibitor

    DOEpatents

    Miller, W.E.

    1988-06-07

    An apparatus for removing dendrites or other crystalline matter from the surface of a liquid in a matter transport process, and an electrolytic cell including such an apparatus. A notch may be provided to allow continuous exposure of the liquid surface, and a bore may be further provided to permit access to the liquid. 2 figs.

  11. Dendrite inhibitor

    DOEpatents

    Miller, William E.

    1989-01-01

    An apparatus for removing dendrites or other crystalline matter from the surface of a liquid in a matter transport process, and an electrolytic cell including such an apparatus. A notch may be provided to allow continuous exposure of the liquid surface, and a bore may be further provided to permit access to the liquid.

  12. Follicular Unit Extraction Hair Transplant

    PubMed Central

    Dua, Aman; Dua, Kapil

    2010-01-01

    Hair transplantation has come a long way from the days of Punch Hair Transplant by Dr. Orentreich in 1950s to Follicular Unit Hair Transplant (FUT) of 1990s and the very recent Follicular Unit Extraction (FUE) technique. With the advent of FUE, the dream of ‘no visible scarring’ in the donor area is now looking like a possibility. In FUE, the grafts are extracted as individual follicular units in a two-step or three-step technique whereas the method of implantation remains the same as in the traditional FUT. The addition of latest automated FUE technique seeks to overcome some of the limitations in this relatively new technique and it is now possible to achieve more than a thousand grafts in one day in trained hands. This article reviews the methodology, limitations and advantages of FUE hair transplant. PMID:21031064

  13. Dendrite Model

    NASA Technical Reports Server (NTRS)

    1999-01-01

    Dr. Donald Gilles, the Discipline Scientist for Materials Science in NASA's Microgravity Materials Science and Applications Department, demonstrates to Carl Dohrman a model of dendrites, the branch-like structures found in many metals and alloys. Dohrman was recently selected by the American Society for Metals International as their 1999 ASM International Foundation National Merit Scholar. The University of Illinois at Urbana-Champaign freshman recently toured NASA's materials science facilities at the Marshall Space Flight Center.

  14. Cortisol levels in human follicular fluid.

    PubMed

    Fateh, M; Ben-Rafael, Z; Benadiva, C A; Mastroianni, L; Flickinger, G L

    1989-03-01

    This study shows that cortisol levels in follicular fluids in stimulated cycles were correlated with oocyte maturity and in vitro fertilizability. The levels were significantly higher than the concentrations found in spontaneous cycles. Our findings suggest that the presence of cortisol in follicular fluid may play a role in follicular development and oocyte maturation.

  15. Secretory vesicles transiently dock and fuse at the porosome to discharge contents during cell secretion.

    PubMed

    Jena, Bhanu P

    2009-12-16

    In contrast with the observation in electron micrographs of partially empty vesicles in cells following secretion, it has been believed since the 1950s that during cell secretion, secretory vesicles completely merge at the cell plasma membrane, resulting in the diffusion of intravesicular contents to the cell exterior and the compensatory retrieval of the excess membrane by endocytosis. In the interim, a large body of work has been published arguing both for and against the complete merger of secretory vesicle membrane at the cell plasma membrane during secretion. The only definitive determination of the mechanism of cell secretion remained in its direct observation at nanometre resolution in live cells. In the past decade, this finally became a reality through the power and scope of the atomic force microscope, which has made it possible to resolve a major conundrum in cell biology. This paradigm shift in our understanding of cell secretion is briefly outlined here.

  16. Cell secretion from the adult lamprey supraneural body tissues possesses cytocidal activity against tumor cells.

    PubMed

    Pang, Yue; Wang, Shiyue; Ba, Wei; Li, Qingwei

    2015-01-01

    The supraneural body was identified in the adult lamprey, and its secretions induced the death of a variety of tumor cells but had no effect on normal cells. The cell secretions from different lamprey tissues were separated, and these secretions killed human tumor cells to varying degrees. The cell secretions induced remarkable cell morphological alterations such as cell blebbing, and the plasma membrane was destroyed by the secretions. In addition, the secretions induced morphological alterations of the mitochondria, cytoskeletal structure, and endoplasmic reticulum, eventually leading to cell death. These observations suggest the presence of a novel protein in the lamprey and the possibility of new applications for the protein in the medical field.

  17. [Effect of heparin on airway goblet cell secretion in sensitized guinea pigs].

    PubMed

    Nakata, J; Tamaoki, J; Takeyama, K; Takeda, Y; Yamawaki, I; Kondo, M; Nagai, A

    1998-10-01

    Heparin and related proteoglycans are released from mast cells and possess anti-inflammatory and anti-complement activities. To elucidate whether heparin affects goblet cell secretion in asthmatic airways and, if so, what the mechanism of action is, we studied guinea pigs sensitized with ovalbumin (OVA) by determining the mucus score (MS) of tracheal goblet cells stained with Alcian blue and PAS. Inhalation of OVA caused a rapid decrease in MS in a dose-dependent manner, with the maximal decrease being from 545 +/- 26 to 192 +/- 35 (p < 0.001), indicating an increase in goblet cell mucus discharge. This effect was selectively inhibited by the histamine H2 receptor blockade with cimetidine. Prior inhalation of heparin inhibited OVA-induced goblet cell secretion in a dose-dependent fashion, but had no effect on histamine-induced goblet cell secretion. The OVA-induced histamine release from the tracheal tissue was likewise inhibited by heparin. These results suggest that allergic challenge stimulates airway goblet cell secretion mainly through the release of histamine and the concomitant activation of histamine H2 receptors on goblet cells, and that heparin protects against this effect by inhibiting the histamine release from mast cells.

  18. [Follicular conjunctivitis of unknown origin].

    PubMed

    Goebels, S; Hasenfus, A K; Kellner, B K; Löw, U; Seitz, B

    2012-01-01

    A 40-year-old female chemical laboratory assistant presented at our clinic with chronic conjunctivitis of 4 years' standing. We initially misdiagnosed her symptoms as giant papillary conjunctivitis. Topical treatment failed to produce an improvement and a biopsy was performed. Histopathological analysis showed bilateral follicular lymphoma, a subtype of the B-cell non-Hodgkin lymphoma. The patient was referred for radiotherapy. At follow-up 18 months later the patient was symptom-free.

  19. Rat bone marrow-derived dendritic cells generated with GM-CSF/IL-4 or FLT3L exhibit distinct phenotypical and functional characteristics.

    PubMed

    N'diaye, Marie; Warnecke, Andreas; Flytzani, Sevasti; Abdelmagid, Nada; Ruhrmann, Sabrina; Olsson, Tomas; Jagodic, Maja; Harris, Robert A; Guerreiro-Cacais, Andre Ortlieb

    2016-03-01

    Dendritic cells are professional APCs that play a central role in the initiation of immune responses. The limited ex vivo availability of dendritic cells inspires the widespread use of bone marrow-derived dendritic cells as an alternative in research. However, the functional characteristics of bone marrow-derived dendritic cells are incompletely understood. Therefore, we compared functional and phenotypic characteristics of rat bone marrow-derived dendritic cells generated with GM-CSF/IL-4 or FLT3 ligand bone marrow-derived dendritic cells. A comparison of surface markers revealed that FLT3 ligand-bone marrow-derived dendritic cells expressed signal regulatory protein α, CD103, and CD4 and baseline levels of MHC class II, CD40, and CD86, which were highly up-regulated upon stimulation. Conversely, GM-CSF/IL-4-bone marrow-derived dendritic cells constitutively expressed signal regulatory protein α, CD11c, and CD11b but only mildly up-regulated MHC class II, CD40, or CD86 following stimulation. Expression of dendritic cell-associated core transcripts was restricted to FLT3 ligand-bone marrow-derived dendritic cells . GM-CSF/IL-4-bone marrow-derived dendritic cells were superior at phagocytosis but were outperformed by FLT3 ligand-bone marrow-derived dendritic cells at antigen presentation and T cell stimulation in vitro. Stimulated GM-CSF/IL-4-bone marrow-derived dendritic cells secreted more TNF, CCL5, CCL20, and NO, whereas FLT3 ligand-bone marrow-derived dendritic cells secreted more IL-6 and IL-12. Finally, whereas GM-CSF/IL-4-bone marrow-derived dendritic cell culture supernatants added to resting T cell cultures promoted forkhead box p3(+) regulatory T cell populations, FLT3 ligand-bone marrow-derived dendritic cell culture supernatants drove Th17 differentiation. We conclude that rat GM-CSF/IL-4-bone marrow-derived dendritic cells and FLT3 ligand-bone marrow-derived dendritic cells are functionally distinct. Our data support the current rationale that FLT3

  20. Nanowell-based immunoassays for measuring single-cell secretion: characterization of transport and surface binding.

    PubMed

    Torres, Alexis J; Hill, Abby S; Love, J Christopher

    2014-12-01

    Arrays of subnanoliter wells (nanowells) provide a useful system to isolate single cells and analyze their secreted proteins. Two general approaches have emerged: one that uses open arrays and local capture of secreted proteins, and a second (called microengraving) that relies on closed arrays to capture secreted proteins on a solid substrate, which is subsequently removed from the array. However, the design and operating parameters for efficient capture from these two approaches to analyze single-cell secretion have not been extensively considered. Using numerical simulations, we analyzed the operational envelope for both open and closed formats, as a function of the spatial distribution of capture ligands, their affinities for the protein, and the rates of single-cell secretion. Based on these analyses, we present a modified approach to capture secreted proteins in-well for highly active secreting cells. This simple method for in-well detection should facilitate rapid identification of cell lines with high specific productivities.

  1. Inhibition of mast cell secretion by oxidation products of natural polyamines.

    PubMed

    Vliagoftis, H; Boucher, W S; Mak, L L; Theoharides, T C

    1992-05-28

    Mast cells secrete many biologically active compounds upon stimulation by immunoglobulin E (IgE) and specific antigen (Ag), anaphylatoxins, as well as a number of cationic compounds which include drugs, kinins and neuropeptides. The effects of the two naturally occurring polyamines, spermine (SP) and spermidine (SPD), on mast cell secretion were studied because they have been implicated in the modulation of cellular processes, possibly through their cationic charge or the regulation of calcium ions. SP and SPD over the range of 10(-7) to 10(-4) M inhibited the release of 5-hydroxytryptamine (5-HT, serotonin) triggered by compound 48/80 (C48/80) in a time- and concentration-dependent manner, as long as at least 2% calf serum (CS) was present. SP also inhibited secretion of both histamine and serotonin stimulated immunologically by using IgE and anti-rat IgE. This inhibition was not accompanied by cytotoxicity. The major available polyamine metabolites tested, N1-acetyl spermine (N1-acSP) and N8-acetyl spermidine (N8-acSPD), also showed inhibition in the presence of CS, whereas putrescine, N8,N1-hexamethylene-bis-acetamide (HMBA) and benzylamine did not. Fetal bovine serum (FBS), as well as human and rat serum, which do not contain polyamine oxidase, did not result in any inhibition with the polyamines tested. Inhibitors of the polyamine oxidase blocked the polyamine effect, indicating that the inhibition of mast cell secretion must derive from aldehydes produced from these polyamines. Addition of the aldehyde inhibitor phenylhydrazine (phi-HDZ), simultaneously with, but not following the polyamines, blocked their inhibitory effect, further strengthening the involvement of aldehydes. These results indicate that naturally occurring polyamines may regulate mast cell secretion through metabolic products of polyamine oxidase, a similar enzyme of which is also present in human liver, placenta and pregnant serum.

  2. Cholinergic agonists transactivate EGFR and stimulate MAPK to induce goblet cell secretion.

    PubMed

    Kanno, Harumi; Horikawa, Yoshitaka; Hodges, Robin R; Zoukhri, Driss; Shatos, Marie A; Rios, Jose D; Dartt, Darlene A

    2003-04-01

    Conjunctival goblet cells are the primary source of mucins in the mucous layer, the innermost layer of the tear film. Conjunctival goblet cell mucin secretion is under neural control because exogenous addition of parasympathetic agonists stimulates goblet cell secretion. To elucidate the intracellular signal pathways used by cholinergic agonists to stimulate goblet cell mucin secretion, we determined whether p42/p44 mitogen-activated protein kinase (MAPK) is activated during cholinergic agonist-stimulated mucin secretion. Rat conjunctiva was removed, preincubated with or without antagonists, and stimulated with the cholinergic agonist carbachol (10(-4) M). Carbachol statistically significantly stimulated the phosphorylation of MAPK in a time- and concentration-dependent manner. U-0126, an inhibitor of MAPK activation, completely inhibited both the activation of MAPK and goblet cell secretion stimulated by carbachol. The M(1) muscarinic antagonist pirenzepine, the M(2) muscarinic antagonist gallamine, and the M(1)/M(3) muscarinic receptor antagonist N-(3-chloropropyl)-4-piperidinyl diphenylacetate (4-DAMP) also inhibited carbachol-stimulated MAPK activation. Increasing the intracellular Ca(2+) concentration with a Ca(2+) ionophore increased MAPK activation, and chelation of extracellular Ca(2+) inhibited carbachol-stimulated activation. Carbachol also increased tyrosine phosphorylation of Pyk2, p60Src, and the epidermal growth factor receptor (EGFR). The Src inhibitor PP1 and the EGFR inhibitor AG-1478 completely inhibited carbachol-stimulated MAPK activation. AG-1478 also inhibited goblet cell secretion. We conclude that carbachol transactivates the EGFR to activate MAPK, leading to conjunctival goblet cell secretion. In addition, carbachol also activates Pyk2 and p60Src that could play a role in the transactivation of the EGFR.

  3. Droplet-based microfluidic platforms for single T cell secretion analysis of IL-10 cytokine.

    PubMed

    Konry, Tania; Dominguez-Villar, Margarita; Baecher-Allan, Clare; Hafler, David A; Yarmush, Martin L

    2011-01-15

    Here we present a microfluidic method for the analysis of single cell secretions. The method co-encapsulates cells with microspheres conjugated with capture antibodies and detection fluorescence-labeled antibodies. The secreted substance captured on the microsphere surface and detected via detection antibodies generating a localized fluorescent signal on a microsphere surface. Using this method, CD4+CD25+ regulatory T cells were encapsulated and assayed to detect IL-10 secreting cell in population.

  4. Dual effect of spermine on mast cell secretion exhibits different calcium and temperature requirements.

    PubMed

    Vliagoftis, H; Mak, L; Boucher, W; Theoharides, T C

    1999-09-01

    Mast cells release many biologically active molecules upon stimulation by a variety of molecules such as immunoglobulin E (IgE) and specific antigen, anaphylatoxins, as well as a number of cationic compounds which include drugs, kinins and neuropeptides. The effect of the naturally occurring polyamine spermine was studied because, even though it is polycationic, it has been implicated in the modulation of secretory processes in a variety of cells. In particular, it was previously shown that oxidation products of spermine inhibit mast cell secretion. High concentrations of spermine (5 x 10(-3) M) added at 37 degrees C induced mast cell secretion that had similar characteristics with that triggered by compound 48/80 (48/80). However, spermine inhibited mast cell secretion in a dose-dependent manner as long as it was added at 4-10 degrees C for at least 10 min in the absence of Ca++ before warming the cells to 37 degrees C and triggering them with 48/80. These findings were true both for purified rat peritoneal mast cells and for rat skin mast cells in situ. Addition of calcium after the cells had been warmed to 37 degrees C could not reverse this inhibition. The inhibition seen when spermine was added at 4 degrees C was, however, overcome if phorbol myristate acetate (PMA) or NaF, which activate PKC and G proteins respectively, were added to mast cells at 37 degrees C together with Ca++. These results indicate that polyamines could be important modulators of the activation state of mast cells and might help further define the biochemical events involved in mast cell secretion.

  5. Pollutants in human follicular fluid

    SciTech Connect

    Trapp, M.; Baukloh, V.; Bohnet, H.G.; Heeschen, W.

    1984-07-01

    The present study was initiated to clarify whether environmental pollutants can reach the human follicular fluid, an important biologic component for reproduction, in concentrations which could be harmful to the gamete. Fifteen patients with tubal malformations were treated in an in vitro fertilization program whereby 18 follicle aspirates were obtained for investigation. The substances which were measured in this study were alpha-, beta-, and gamma-hexachlorocyclohexane (HCH), dichlorodiphenyltrichlorethane (DDT), polychlorinated biphenyls (PCB), hexachlorobenzene (HCB), dieldrin, and heptachlorepoxide (HepE). None of the patients became pregnant during the treatment cycle.

  6. Bilateral follicular cysts in a water buffalo.

    PubMed

    Khan, F A; Nabi, S U; Pande, Megha; Das, G K; Sarkar, M

    2011-03-01

    The present short communication puts on record a case of bilateral, multiple follicular cysts in a water buffalo along with a detailed description of its ovarian biometry and follicular fluid composition. The ovarian weight and biometrical parameters were much higher than in normal cycling buffaloes. A total of three follicular cysts were observed, two on the right ovary and one on the left ovary, measuring 4.9, 3.0 and 2.6 cm yielding 21, 9 and 5 ml of follicular fluid, respectively. The cystic fluid was deep yellow in colour with a viscous consistency. The follicular fluid concentrations of glucose, total protein, cholesterol, acid phosphatase, calcium, phosphorus and progesterone in all the cysts were within the range reported previously in normal buffalo follicular fluid; however, the alkaline phosphatase concentration in cyst 1 and total bilirubin concentration in cysts 1 and 2 were higher than the values in normal follicular fluid. In contrast, the levels of urea nitrogen in cysts 1 and 3, and oestradiol in cyst 3 were lower than the normal values. All the three follicles had an oestradiol to progesterone ratio less than 1. The results of our study suggest that follicular cysts in buffalo are oestrogenically inactive and have an altered concentration of certain biochemical and hormonal constituents.

  7. Melatonin in human preovulatory follicular fluid

    NASA Technical Reports Server (NTRS)

    Brzezinski, Amnon; Seibel, Machelle M.; Lynch, Harry J.; Deng, Mei-Hua; Wurtman, Richard J.

    1987-01-01

    Melatonin, the major hormone of the pineal gland, has antigonadotrophic activity in many mammals and may also be involved in human reproduction. Melatonin suppresses steroidogenesis by ovarian granulosa and luteal cells in vitro. To determine if melatonin is present in the human ovary, preovulatory follicular fluids (n = 32) from 15 women were assayed for melatonin by RIA after solvent extraction. The fluids were obtained by laparoscopy or sonographically controlled follicular puncture from infertile women undergoing in vitro fertilization and embryo transfer. All patients had received clomiphene citrate, human menopausal gonadotropin, and hCG to stimulate follicle formation. Blood samples were obtained by venipuncture 30 rain or less after follicular aspiration. All of the follicular fluids contained melatonim, in concentrations substantially higher than those in the corresponding serum. A positive correlation was found between follicular fluid and serum melatonin levels in each woman; these observations indicate that preovulatory follicles contain substantial amounts of melatonin that may affect ovarian steroidogenesis.

  8. Rituximab With or Without Yttrium Y-90 Ibritumomab Tiuxetan in Treating Patients With Untreated Follicular Lymphoma

    ClinicalTrials.gov

    2016-06-15

    Stage I Grade 1 Follicular Lymphoma; Stage I Grade 2 Follicular Lymphoma; Stage II Grade 1 Contiguous Follicular Lymphoma; Stage II Grade 1 Non-Contiguous Follicular Lymphoma; Stage II Grade 2 Contiguous Follicular Lymphoma; Stage II Grade 2 Non-Contiguous Follicular Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma

  9. Treatment of thyroid follicular carcinoma.

    PubMed

    Ríos, Antonio; Rodríguez, José M; Parrilla, Pascual

    2015-12-01

    Differentiated thyroid carcinoma includes 2 different tumor types, papillary (PC) and follicular carcinoma (FC), and although similar, their prognosis is different. FC is uncommon, and this has led to it often being analyzed together with PC, and therefore the true reality of this tumor is difficult to know. As a result, the diagnostic and therapeutic management and the prognostic factors in differentiated carcinoma are more predictive of PC than FC. In this review we analyze the current state of many of the therapeutic aspects of this pathology. The best surgical technique and the usefulness of associated lymphadenectomy is also analyzed. Regarding post-surgical ablation with 131I, the indications, doses and usefulness are discussed. For the remaining therapies we analyze the few indications for radiotherapy and chemotherapy, and of new drugs such as tyrosine kinase inhibitors.

  10. New drugs for follicular lymphoma.

    PubMed

    Sorigue, Marc; Ribera, Josep-Maria; Motlló, Cristina; Sancho, Juan-Manuel

    2016-10-01

    Despite the improvement in prognosis since the advent of rituximab, follicular lymphoma is still incurable and remains the cause of death of most afflicted patients. With the expanding knowledge of the pathogenesis of B-cell malignancies, in the last few years a plethora of new therapies acting through a variety of mechanisms have shown promising results. This review attempts to analyze the evidence available on these new drugs, which include new monoclonal antibodies and immunoconjugates, the anti-angiogenic and immunomodulatory agent lenalidomide, the proteasome inhibitor bortezomib, inhibitors of B-cell receptor pathway enzymes, such as ibrutinib, idelalisib, duvelisib and entospletinib, BCL2 inhibitors and checkpoint inhibitors. We conclude that despite the high expectations around the new therapeutic options for patients with refractory disease, these new drugs have side effects that require caution with their use, particularly in light of the still short follow up and the lack of both randomized trials and data on combination regimens.

  11. Isothermal Dendritic Growth Experiment - PVA Dendrites

    NASA Technical Reports Server (NTRS)

    1997-01-01

    The Isothermal Dendritic Growth Experiment (IDGE), flown on three Space Shuttle missions, is yielding new insights into virtually all industrially relevant metal and alloy forming operations. IDGE used transparent organic liquids that form dendrites (treelike structures) similar to those inside metal alloys. Comparing Earth-based and space-based dendrite growth velocity, tip size and shape provides a better understanding of the fundamentals of dentritic growth, including gravity's effects. Shalowgraphic images of pivalic acid (PVA) dendrites forming from the melt show the subtle but distinct effects of gravity-driven heat convection on dentritic growth. In orbit, the dendrite grows as its latent heat is liberated by heat conduction. This yields a blunt dendrite tip. On Earth, heat is carried away by both conduction and gravity-driven convection. This yields a sharper dendrite tip. In addition, under terrestrial conditions, the sidebranches growing in the direction of gravity are augmented as gravity helps carry heat out of the way of the growing sidebranches as opposed to microgravity conditions where no augmentation takes place. IDGE was developed by Rensselaer Polytechnic Institute and NASA/Glenn Research Center. Advanced follow-on experiments are being developed for flight on the International Space Station. Photo Credit: NASA/Glenn Research Center

  12. Follicular contact dermatitis revisited: A review emphasizing neomycin-associated follicular contact dermatitis

    PubMed Central

    Cohen, Philip R

    2014-01-01

    Follicular contact dermatitis clinically presents as individual papules that include a central hair follicle. Pathologic features involve the follicle and the surrounding dermis: spongiosis and vesicle formation of the follicular epithelium associated with perifollicular and perivascular lymphocytic inflammation. Using the PubMed database, an extensive literature search was performed on follicular contact dermatitis and neomycin. Relevant papers were reviewed and the clinical and pathologic features, the associated chemicals (including a more detailed description of neomycin), the hypothesized pathogenesis, and the management of follicular contact dermatitis were described. Several agents-either as allergens or irritants-have been reported to elicit follicular contact dermatitis. Several hypotheses have been suggested for the selective involvement of the follicles in follicular contact dermatitis: patient allergenicity, characteristics of the agent, vehicle containing the agent, application of the agent, and external factors. The differential diagnosis of follicular contact dermatitis includes not only recurrent infundibulofolliculitis, but also drug eruption, mite infestation, viral infection, and dermatoses that affect hair follicles. The primary therapeutic intervention for follicular contact dermatitis is withdrawal of the causative agent; treatment with a topical corticosteroid preparation may also promote resolution of the dermatitis. In conclusion, follicular contact dermatitis may be secondary to allergens or irritants; topical antibiotics, including neomycin, may cause this condition. Several factors may account for the selective involvement of the hair follicle in this condition. Treatment of the dermatitis requires withdrawal of the associated topical agent; in addition, topical corticosteroids may be helpful to promote resolution of lesions. PMID:25516854

  13. A mathematical method for extracting cell secretion rate from affinity biosensors continuously monitoring cell activity.

    PubMed

    Gao, Yandong; Zhou, Qing; Matharu, Zimple; Liu, Ying; Kwa, Timothy; Revzin, Alexander

    2014-03-01

    Our laboratory has previously developed miniature aptasensors that may be integrated at the site of a small group of cells for continuous detection of cell secreted molecules such as inflammatory cytokine interferon gamma (IFN-γ). In a system such as this, the signal measured at the sensor surfaces is a complex function of transport, reaction, as well as of cellular activity. Herein, we report on the development of a mathematical framework for extracting cell production rates from binding curves generated with affinity biosensors. This framework consisted of a diffusion-reaction model coupled to a root finding algorithm for determining cell production rates values causing convergence of a predetermined criterion. To experimentally validate model predictions, we deployed a microfluidic device with an integrated biosensor for measuring the IFN-γ release from CD4 T cells. We found close agreement between secretion rate observed theoretically and those observed experimentally. After taking into account the differences in sensor geometry and reaction kinetics, the method for cell secretion rate determination described in this paper may be broadly applied to any biosensor continuously measuring cellular activity.

  14. Rituximab, Lenalidomide, and Ibrutinib in Treating Patients With Previously Untreated Stage II-IV Follicular Lymphoma

    ClinicalTrials.gov

    2016-09-26

    Stage II Grade 1 Contiguous Follicular Lymphoma; Stage II Grade 1 Non-Contiguous Follicular Lymphoma; Stage II Grade 2 Contiguous Follicular Lymphoma; Stage II Grade 2 Non-Contiguous Follicular Lymphoma; Stage II Grade 3 Contiguous Follicular Lymphoma; Stage II Grade 3 Non-Contiguous Follicular Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma

  15. Free dendritic growth

    NASA Technical Reports Server (NTRS)

    Glicksman, M. E.

    1984-01-01

    Free dendritic growth refers to the unconstrained development of crystals within a supercooled melt, which is the classical 'dendrite problem'. Great strides have been taken in recent years in both the theoretical understanding of dendritic growth and its experimental status. The development of this field will be sketched, showing that transport theory and interfacial thermodynamics (capillarity theory) were sufficient ingredients to develop a truly predictive model of dendrite formation. The convenient, but incorrect, notion of 'maximum velocity' was used for many years to estimate the behavior of dendritic transformations until supplanted by modern dynamic stability theory. The proper combinations of transport theory and morphological stability seem to able to predict the salient aspects of dendritic growth, especially in the neighborhood of the tip. The overall development of cast microstructures, such as equiaxed zone formation, rapidly solidified microstructures, etc., also seems to contain additional non-deterministic features which lie outside the current theories discussed here.

  16. Dendritic polyurea polymers.

    PubMed

    Tuerp, David; Bruchmann, Bernd

    2015-01-01

    Dendritic polymers, subsuming dendrimers as well as hyperbranched or highly branched polymers are well established in the field of polymer chemistry. This review article focuses on urea based dendritic polymers and summarizes their synthetic routes through both isocyanate and isocyanate-free processes. Furthermore, this article highlights applications where dendritic polyureas show their specific chemical and physical potential. For these purposes scientific publications as well as patent literature are investigated to generate a comprehensive overview on this topic.

  17. Regulation of conjunctival goblet cell secretion by Ca(2+)and protein kinase C.

    PubMed

    Dartt, D A; Rios, J D; Kanno, H; Rawe, I M; Zieske, J D; Ralda, N; Hodges, R R; Zoukhri, D; Rios, J R

    2000-12-01

    Conjunctival goblet cells secrete mucus in response to cholinergic (muscarinic) agonists, but the underlying signaling pathways activated in this tissue are not well understood. Cholinergic agonists usually activate phospholipase C to produce inositol 1,4,5 trisphosphate and diacylglycerol. Inositol 1,4,5 trisphosphate increases the intracellular Ca(2+)concentration ([Ca2(+)](i)) while diacylglycerol activates protein kinase C (PKC). PKC and Ca(2+), either by itself or with calmodulin, activate cellular functions. Goblet cell glycoprotein secretion, our index of mucin secretion, was measured from pieces of rat conjunctiva with an enzyme-linked lectin assay using the lectin Ulex europaeus agglutinin I (UEA-I). UEA-I selectively recognizes high molecular weight glycoproteins secreted by the goblet cells. Increasing the [Ca(+)](i)with the Ca(2+)ionophore ionomycin stimulated glycoprotein secretion from conjunctival goblet cells. Cholinergic agonist-induced secretion was completely blocked by chelation of extracellular Ca(2+)and by the Ca(2+)/calmodulin-dependent protein kinase inhibitors KN93 and W7 as well as their inactive analogs KN92 and W5. Activation of classical and novel PKC isozymes by phorbol 12-myristate 13-acetate and phorbol 12,13-dibutyrate stimulated goblet cell glycoprotein secretion. When ionomycin and PMA were added simultaneously, secretion was additive. PKC isozymes were identified by Western blotting analyses with antibodies specific to nine of the 11 PKC isozymes (PKCgamma and zeta were not tested). All nine PKC isozymes were identified in the conjunctival epithelium. The cellular location of the PKC isozymes was determined by immunofluorescence microscopy. Goblet cells contained the classical PKC isozymes PKCalpha, -betaI and -betaII, the novel PKC isozymes PKCepsilon, -theta;, and - mu, and the atypical PKC isozyme PKCzeta. We were unable to determine if PKC activation is required for cholinergic-agonist induced secretion because the PKC

  18. Individualized management of follicular lymphoma.

    PubMed

    Bai, Bing; Huang, Hui-Qiang

    2015-03-01

    Follicular lymphoma (FL) is the most common indolent non-hodgkin lymphoma. Most patients with FL are diagnosed with advanced disease and are considered incurable. The classical prognostic index in FL is the FL international prognostic index (FLIPI). The management of FL is mainly determined by histologic grading, clinical stage, and tumor burden. For patients with stage I and II disease, an involved-site radiation therapy (ISRT) is recommended and may be potentially curative approach with 60% to 80% of 10-year overall survival (OS) rates, while patients with stage III and IV should be treated with systemic therapy. The watchful waiting is still an option for patients without symptoms or/and low tumor burden. Induction of immuno-chemotherapy combined with consolidation of rituximab maintenance (MR) is standard care for patients with symptomatic disease or with high tumor burden when treatment indicated. The major indication for systemic therapy is including candidate for clinical trials, threatened end organ function, cytopenia secondary to lymphoma bulky disease and steady progress etc. at present time. Routine baseline and regular hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (HBcAb) testing is strongly recommended for all patients before the initiation of immuno-chemotherapy in order to minimize the risk of hepatitis B virus (HBV) reactivation which has been observed approximately 20% to 50% of patients with positive HBsAg and 3% to 45% of patients with positive HBcAb. Prophylactic antiviral treatment in patients who are HBsAg-positive or HBcAb-positive is indicated before immuno-chemotherapy. The management for elderly patients should be carefully selected to avoid overtreatment and severe toxicities. Individualized dose adjustment for chemotherapy and an adequate supportive treatment are essential for this special population. Novel agents such as lenalidomide, ibrutinib and idelalisib are promising. In conclusion, individualized management

  19. Pancreatic Tumor Cell Secreted CCN1/Cyr61 Promotes Endothelial cell migration and Aberrant Neovascularization

    PubMed Central

    Maity, Gargi; Mehta, Smita; Haque, Inamul; Dhar, Kakali; Sarkar, Sandipto; Banerjee, Sushanta K.; Banerjee, Snigdha

    2014-01-01

    The complex signaling networks between cancer cells and adjacent endothelial cells make it challenging to unravel how cancer cells send extracellular messages to promote aberrant vascularization or tumor angiogenesis. Here, in vitro and in vivo models show that pancreatic cancer cell generated unique microenvironments can underlie endothelial cell migration and tumor angiogenesis. Mechanistically, we find that pancreatic cancer cell secreted CCN1/Cyr61 matricellular protein rewires the microenvironment to promote endothelial cell migration and tumor angiogenesis. This event can be overcome by Sonic Hedgehog (SHh) antibody treatment. Collectively, these studies identify a novel CCN1 signaling program in pancreatic cancer cells which activates SHh through autocrine-paracrine circuits to promote endothelial cell migration and tumor angiogenesis and suggests that CCN1 signaling of pancreatic cancer cells is vital for the regulation of tumor angiogenesis. Thus CCN1 signaling could be an ideal target for tumor vascular disruption in pancreatic cancer. PMID:24833309

  20. Roles of extracellular matrix in follicular development.

    PubMed

    Rodgers, R J; van Wezel, I L; Irving-Rodgers, H F; Lavranos, T C; Irvine, C M; Krupa, M

    1999-01-01

    The cellular biology and changes in the extracellular matrix of ovarian follicles during their development are reviewed. During growth of the bovine ovarian follicle the follicular basal lamina doubles 19 times in surface area. It changes in composition, having collagen IV alpha 1-26 and laminin alpha 1, beta 2 and gamma 1 at the primordial stage, and collagen IV alpha 1 and alpha 2, reduced amounts of alpha 3-alpha 5, and a higher content of laminin alpha 1, beta 2 and gamma 1 at the antral stage. In atretic antral follicles laminin alpha 2 was also detected. The follicular epithelium also changes from one layer to many layers during follicular growth. It is clear that not all granulosal cells have equal potential to divide, and we have evidence that the granulosal cells arise from a population of stem cells. This finding has important ramifications and supports the concept that different follicular growth factors can act on different subsets of granulosal cells. In antral follicles, the replication of cells occurs in the middle layers of the membrana granulosa, with older granulosal cells towards the antrum and towards the basal lamina. The basal cells in the membrana granulosa have also been observed to vary in shape between follicies. In smaller antral follicles, they were either columnar or rounded, and in follicles > 5 mm the cells were all rounded. The reasons for these changes in matrix and cell shapes are discussed in relation to follicular development. PMID:10692866

  1. Melatonin in human preovulatory follicular fluid

    NASA Technical Reports Server (NTRS)

    Brzezinski, Amnon; Seibel, Machelle M.; Lynch, Harry J.; Deng, Mei-Hua; Wurtman, Richard J.

    1987-01-01

    Melatonin, the major hormone of the pineal gland, has antigonadotrophic activity in many mammals and may also be involved in human reproduction. Melatonin suppresses steroidogenesis by ovarian granulosa and luteal cells in vitro. To determine if melatonin is present in the human ovary, preovulatory follicular fluids (n = 32) from 15 women were assayed for melatonin by RIA after solvent extraction. The fluids were obtained by laparoscopy or sonographically controlled follicular puncture from infertile women undergoing in vitro fertilization and embryo transfer. All patients had received clomiphene citrate, human menopausal gonadotropin, and hCG to stimulate follicle formation. Blood samples were obtained by venipuncture 30 min or less after follicular aspiration. All of the follicular fluids contained melatonin, in concentrations (35.6 plus or minus 4.8 (plus or minus SEM) pg/mL) substantially higher than those in the corresponding serum (10.0 plus or minus 1.4 pg/mL). A positive correlation was found between follicular fluid and serum melatonin levels in each woman (r = 0.770; P less than 0.001). These observations indicate that preovulatory follicles contain substantial amounts of melatonin that may affect ovarian steroidogenesis.

  2. Mechanism of follicular trapping: similarities and differences in trapping of antibody-complexed antigens and carbon particles in the follicles of the spleen

    SciTech Connect

    Groeneveld, P.H.; Eikelenboom, P.; van Rooijen, N.

    1983-02-01

    Both immune complexes and carbon particles were trapped in spleen follicles soon after intravenous injection. The localization pattern of carbon particles and immune complexes were identical 24 hr after injection. Since there is no reason to believe that lymphocytes are involved in the transport of carbon particles from the marginal zone towards the follicle centers, these results indicate that follicular trapping is based on a purely mechanical process. Pretreatment with endotoxin completely prevented the trapping of immune complexes but not carbon particles. Endotoxin administered after the injection of immune complexes caused the rapid removal of trapped complexes from the follicles. However, the effect of endotoxin on trapped carbon particles was less pronounced. Apart from a mechanical trapping of diffusing compounds in the follicular web, a distinct phase is suggested in which immune complexes are fixed to and retained on the surface of the follicular dendritic cells.

  3. Molecular mechanisms of dendrite stability

    PubMed Central

    Koleske, Anthony J.

    2014-01-01

    In the developing brain, dendrite branches and dendritic spines form and turn over dynamically. By contrast, most dendrite arbors and dendritic spines in the adult brain are stable for months, years and possibly even decades. Emerging evidence reveals that dendritic spine and dendrite arbor stability have crucial roles in the correct functioning of the adult brain and that loss of stability is associated with psychiatric disorders and neurodegenerative diseases. Recent findings have provided insights into the molecular mechanisms that underlie long-term dendrite stabilization, how these mechanisms differ from those used to mediate structural plasticity and how they are disrupted in disease. PMID:23839597

  4. Impact of Mesenchymal Stem Cell secreted PAI-1 on colon cancer cell migration and proliferation

    SciTech Connect

    Hogan, Niamh M.; Joyce, Myles R.; Murphy, J. Mary; Barry, Frank P.; O’Brien, Timothy; Kerin, Michael J.; Dwyer, Roisin M.

    2013-06-14

    Highlights: •MSCs were directly co-cultured with colorectal cancer (CRC) cells on 3D scaffolds. •MSCs influence CRC protein/gene expression, proliferation and migration. •We report a significant functional role of MSC-secreted PAI-1 in colon cancer. -- Abstract: Mesenchymal Stem Cells are known to engraft and integrate into the architecture of colorectal tumours, with little known regarding their fate following engraftment. This study aimed to investigate mediators of Mesenchymal Stem Cell (MSC) and colon cancer cell (CCC) interactions. Mesenchymal Stem Cells and colon cancer cells (HT29 and HCT-116) were cultured individually or in co-culture on 3-dimensional scaffolds. Conditioned media containing all secreted factors was harvested at day 1, 3 and 7. Chemokine secretion and expression were analyzed by Chemi-array, ELISA (Macrophage migration inhibitory factor (MIF), plasminogen activator inhibitor type 1 (PAI-1)) and RQ-PCR. Colon cancer cell migration and proliferation in response to recombinant PAI-1, MSCs and MSCs + antibody to PAI-1 was analyzed using Transwell inserts and an MTS proliferation assay respectively. Chemi-array revealed secretion of a wide range of factors by each cell population, including PAI-1and MIF. ELISA analysis revealed Mesenchymal Stem Cells to secrete the highest levels of PAI-1 (MSC mean 10.6 ng/mL, CCC mean 1.01 ng/mL), while colon cancer cells were the principal source of MIF. MSC-secreted PAI-1 stimulated significant migration of both CCC lines, with an antibody to the chemokine shown to block this effect (67–88% blocking,). A cell-line dependant effect on CCC proliferation was shown for Mesenchymal Stem Cell-secreted PAI-1 with HCT-116 cells showing decreased proliferation at all concentrations, and HT29 cells showing increased proliferation in the presence of higher PAI-1 levels. This is the first study to identify PAI-1 as an important mediator of Mesenchymal Stem Cell/colon cancer cell interactions and highlights the

  5. Molecular signatures of thyroid follicular neoplasia.

    PubMed

    Borup, Rehannah; Rossing, Maria; Henao, Ricardo; Yamamoto, Yohei; Krogdahl, Annelise; Godballe, Christian; Winther, Ole; Kiss, Katalin; Christensen, Lise; Høgdall, Estrid; Bennedbaek, Finn; Nielsen, Finn Cilius

    2010-09-01

    The molecular pathways leading to thyroid follicular neoplasia are incompletely understood, and the diagnosis of follicular tumors is a clinical challenge. To provide leads to the pathogenesis and diagnosis of the tumors, we examined the global transcriptome signatures of follicular thyroid carcinoma (FC) and normofollicular adenoma (FA) as well as fetal/microFA (fetal adenoma). Carcinomas were strongly enriched in transcripts encoding proteins involved in DNA replication and mitosis corresponding to increased number of proliferating cells and depleted number of transcripts encoding factors involved in growth arrest and apoptosis. In the latter group, the combined loss of transcripts encoding the nuclear orphan receptors NR4A1 and NR4A3, which were recently shown to play a causal role in hematopoetic neoplasia, was noteworthy. The analysis of differentially expressed transcripts provided a mechanism for cancer progression, which is why we exploited the results in order to generate a molecular classifier that could identify 95% of all carcinomas. Validation employing public domain and cross-platform data demonstrated that the signature was robust and could diagnose follicular nodules originating from different geographical locations and platforms with similar accuracy. We came to the conclusion that down-regulation of factors involved in growth arrest and apoptosis may represent a decisive step in the pathogenesis of FC. Moreover, the described molecular pathways provide an accurate and robust genetic signature for the diagnosis of FA and FC. PMID:20668010

  6. Development of the ovarian follicular epithelium.

    PubMed

    Rodgers, R J; Lavranos, T C; van Wezel, I L; Irving-Rodgers, H F

    1999-05-25

    A lot is known about the endocrine control of the development of ovarian follicles, but a key question now facing researchers is which molecular and cellular processes take part in control of follicular growth and development. The growth and development of ovarian follicles occurs postnatally and throughout adult life. In this review, we focus on the follicular epithelium (membrana granulosa) and its basal lamina. We discuss a model of how granulosa cells arise from a population of stem cells and then enter different lineages before differentiation. The structure of the epithelium at the antral stage of development is presented, and the effects that follicle growth has on the behavior of the granulosa cells are discussed. Finally, we discuss the evidence that during follicle development the follicular basal lamina changes in composition. This would be expected if the behavior of the granulosa cells changes, or if the permeability of the basal lamina changes. It will be evident that the follicular epithelium has similarities to other epithelia in the body, but that it is more dynamic, as gross changes occur during the course of follicle development. This basic information will be important for the development of future reproductive technologies in both humans and animals, and possibly for understanding polycystic ovarian syndrome in women. PMID:10411332

  7. Avian dendritic cells: Phenotype and ontogeny in lymphoid organs.

    PubMed

    Nagy, Nándor; Bódi, Ildikó; Oláh, Imre

    2016-05-01

    Dendritic cells (DC) are critically important accessory cells in the innate and adaptive immune systems. Avian DCs were originally identified in primary and secondary lymphoid organs by their typical morphology, displaying long cell processes with cytoplasmic granules. Several subtypes are known. Bursal secretory dendritic cells (BSDC) are elongated cells which express vimentin intermediate filaments, MHC II molecules, macrophage colony-stimulating factor 1 receptor (CSF1R), and produce 74.3+ secretory granules. Avian follicular dendritic cells (FDC) highly resemble BSDC, express the CD83, 74.3 and CSF1R molecules, and present antigen in germinal centers. Thymic dendritic cells (TDC), which express 74.3 and CD83, are concentrated in thymic medulla while interdigitating DC are found in T cell-rich areas of secondary lymphoid organs. Avian Langerhans cells are a specialized 74.3-/MHC II+ cell population found in stratified squamous epithelium and are capable of differentiating into 74.3+ migratory DCs. During organogenesis hematopoietic precursors of DC colonize the developing lymphoid organ primordia prior to immigration of lymphoid precursor cells. This review summarizes our current understanding of the ontogeny, cytoarchitecture, and immunophenotype of avian DC, and offers an antibody panel for the in vitro and in vivo identification of these heterogeneous cell types.

  8. Cell secretion mediated by granule-associated vesicle transport: a glimpse at evolution.

    PubMed

    Crivellato, Enrico; Nico, Beatrice; Gallo, Valentina Patrizia; Ribatti, Domenico

    2010-07-01

    Regulated secretion allows extrusion of cell products stored in specialized membrane-bound organelles called secretory granules or secretory vesicles. Regulated secretion provides basic functions in living organisms, and in a phylogenetic perspective, it is recognizable in the most primitive eukaryotic forms. This article is an attempt to trace the evolutionary history of a special type of secretory pattern, which has been referred to as vesicle-mediated degranulation or piecemeal degranulation (PMD). First described in the early 70s of the last century in inflammatory cells, such as the basophils, mast cells, and eosinophils, this regulated secretory route has subsequently been recognized in endocrine cells, in particular in the chromaffin cells of the adrenal medulla. This vesicle-mediated degranulation is held to mobilize small and specific aliquots of granule-associated material for selective paracrine or endocrine transport to the cell exterior. PMD has been identified in many vertebrate classes. By contrast, no data are available for invertebrates. We speculate that this pattern of cell secretion emerged early in phylogenesis, when the first metazoans appeared. In this review article, we will first revise the concept of vesicle-mediated degranulation in the light of the most recent experimental discoveries and theoretical implications. Then, the distribution of this secretory mode among vertebrates and its molecular basis will be highlighted. Finally, the potential occurrence of PMD in invertebrates, its biological significance from an evolutionary perspective and the future direction of investigations will be briefly sketched.

  9. Tumor cell secretion of soluble factor(s) for specific immunosuppression.

    PubMed

    Kano, Arihiro

    2015-03-09

    Studies of tumor models using syngeneic transplantation have advanced our understanding of tumor immunity, including both immune surveillance and evasion. Murine mammary carcinoma 4T1 cells secrete immunosuppressive soluble factors as demonstrated in splenocyte culture. Cultured primary splenocytes secrete IFN-γ, which was strikingly elevated when the cells were isolated from 4T1 tumor-bearing mice. The secretion of IFN-γ peaked a week after 4T1 inoculation and then declined. This reduction may be due to the relatively decreased lymphocytes and increased granulocytes in a spleen accompanied by splenomegaly with time after the 4T1 inoculation. IFN-γ production was further suppressed with the addition of the conditioned media from 4T1 cells to the splenocyte culture. This suppressive effect was more evident in the splenocytes isolated from mice that had 4T1 tumors for a longer period of time and was not observed in the conditioned medium either from CT26 cells or with splenocytes isolated from CT26 tumor-bearing mice. These results suggest that the IFN-γ suppression is 4T1 tumor-specific. The soluble factor(s) in the 4T1-conditioned media was a protein between 10 to 100 kDa. The cytokine tip assay demonstrated several known cytokines that negatively regulate immune responses and may be candidates for this immunosuppression activity.

  10. An integrated microfluidic chip system for single-cell secretion profiling of rare circulating tumor cells.

    PubMed

    Deng, Yuliang; Zhang, Yu; Sun, Shuai; Wang, Zhihua; Wang, Minjiao; Yu, Beiqin; Czajkowsky, Daniel M; Liu, Bingya; Li, Yan; Wei, Wei; Shi, Qihui

    2014-12-16

    Genetic and transcriptional profiling, as well as surface marker identification of single circulating tumor cells (CTCs) have been demonstrated. However, quantitatively profiling of functional proteins at single CTC resolution has not yet been achieved, owing to the limited purity of the isolated CTC populations and a lack of single-cell proteomic approaches to handle and analyze rare CTCs. Here, we develop an integrated microfluidic system specifically designed for streamlining isolation, purification and single-cell secretomic profiling of CTCs from whole blood. Key to this platform is the use of photocleavable ssDNA-encoded antibody conjugates to enable a highly purified CTC population with <75 'contaminated' blood cells. An enhanced poly-L-lysine barcode pattern is created on the single-cell barcode chip for efficient capture rare CTC cells in microchambers for subsequent secreted protein profiling. This system was extensively evaluated and optimized with EpCAM-positive HCT116 cells seeded into whole blood. Patient blood samples were employed to assess the utility of the system for isolation, purification and single-cell secretion profiling of CTCs. The CTCs present in patient blood samples exhibit highly heterogeneous secretion profile of IL-8 and VEGF. The numbers of secreting CTCs are found not in accordance with CTC enumeration based on immunostaining in the parallel experiments.

  11. Design of experiments approach to engineer cell-secreted matrices for directing osteogenic differentiation.

    PubMed

    Decaris, Martin L; Leach, J Kent

    2011-04-01

    The presentation of extracellular matrix (ECM) proteins provides an opportunity to instruct the phenotype and behavior of responsive cells. Decellularized cell-secreted matrix coatings (DM) represent a biomimetic culture surface that retains the complexity of the natural ECM. Microenvironmental culture conditions alter the composition of these matrices and ultimately the ability of DMs to direct cell fate. We employed a design of experiments (DOE) multivariable analysis approach to determine the effects and interactions of four variables (culture duration, cell seeding density, oxygen tension, and media supplementation) on the capacity of DMs to direct the osteogenic differentiation of human mesenchymal stem cells (hMSCs). DOE analysis revealed that matrices created with extended culture duration, ascorbate-2-phosphate supplementation, and in ambient oxygen tension exhibited significant correlations with enhanced hMSC differentiation. We validated the DOE model results using DMs predicted to have superior (DM1) or lesser (DM2) osteogenic potential for naïve hMSCs. Compared to cells on DM2, hMSCs cultured on DM1 expressed 2-fold higher osterix levels and deposited 3-fold more calcium over 3 weeks. Cells on DM1 coatings also exhibited greater proliferation and viability compared to DM2-coated substrates. This study demonstrates that DOE-based analysis is a powerful tool for optimizing engineered systems by identifying significant variables that have the greatest contribution to the target output.

  12. Isothermal Dendritic Growth Experiment - SCN Dendrites

    NASA Technical Reports Server (NTRS)

    1995-01-01

    The Isothermal Dendritic Growth Experiment (IDGE), flown on three Space Shuttle missions, is yielding new insights into virtually all industrially relevant metal and alloy forming operations. IDGE used transparent organic liquids that form dendrites (treelike structures) similar to the crystals that form inside metal alloys. Comparing Earth-based and space-based dentrite growth velocity, tip size and shape provid a better understanding of the fundamentals of dentritic growth, including gravity's effects. These shadowgraphic images show succinonitrile (SCN) dentrites growing in a melt (liquid). The space-grown crystals also have cleaner, better defined sidebranches. IDGE was developed by Rensselaer Polytechnic Institude (RPI) and NASA/ Glenn Research Center(GRC). Advanced follow-on experiments are being developed for flight on the International Space Station. Photo gredit: NASA/Glenn Research Center

  13. On the dendrites and dendritic transitions in undercooled germanium

    SciTech Connect

    Lau, C.F.; Kui, H.W. . Dept. of Physics)

    1993-07-01

    Undercooled molten Ge was allowed to solidify at initial bulk undercoolings, [Delta]T, from 10 to 200C under dehydrated boron oxide flux. It turned out that in addition to the (211) twin dendrite found by Billig and the (100) twin-free dendrite discovered by Devaud and Turnbill, there is a third novel twin dendrite, the (110) twin dendrite. The twin planes in a (110) dendrite always appear in multiple numbers and the orientation is (111). These different kinds of dendrites exist at different initial interfacial undercoolings and the transition temperatures for (110) to (211), (211) to (100) are [Delta]T = 61 and 93C, respectively.

  14. Optimization principles of dendritic structure

    PubMed Central

    Cuntz, Hermann; Borst, Alexander; Segev, Idan

    2007-01-01

    Background Dendrites are the most conspicuous feature of neurons. However, the principles determining their structure are poorly understood. By employing cable theory and, for the first time, graph theory, we describe dendritic anatomy solely on the basis of optimizing synaptic efficacy with minimal resources. Results We show that dendritic branching topology can be well described by minimizing the path length from the neuron's dendritic root to each of its synaptic inputs while constraining the total length of wiring. Tapering of diameter toward the dendrite tip – a feature of many neurons – optimizes charge transfer from all dendritic synapses to the dendritic root while housekeeping the amount of dendrite volume. As an example, we show how dendrites of fly neurons can be closely reconstructed based on these two principles alone. PMID:17559645

  15. Ofatumumab and Bendamustine Hydrochloride With or Without Bortezomib in Treating Patients With Untreated Follicular Non-Hodgkin Lymphoma

    ClinicalTrials.gov

    2016-10-05

    Grade 3a Follicular Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma

  16. Proteomic analysis of mare follicular fluid during late follicle development

    PubMed Central

    2011-01-01

    Background Follicular fluid accumulates into the antrum of follicle from the early stage of follicle development. Studies on its components may contribute to a better understanding of the mechanisms underlying follicular development and oocyte quality. With this objective, we performed a proteomic analysis of mare follicular fluid. First, we hypothesized that proteins in follicular fluid may differ from those in the serum, and also may change during follicle development. Second, we used four different approaches of Immunodepletion and one enrichment method, in order to overcome the masking effect of high-abundance proteins present in the follicular fluid, and to identify those present in lower abundance. Finally, we compared our results with previous studies performed in mono-ovulant (human) and poly-ovulant (porcine and canine) species in an attempt to identify common and/or species-specific proteins. Methods Follicular fluid samples were collected from ovaries at three different stages of follicle development (early dominant, late dominant and preovulatory). Blood samples were also collected at each time. The proteomic analysis was carried out on crude, depleted and enriched follicular fluid by 2D-PAGE, 1D-PAGE and mass spectrometry. Results Total of 459 protein spots were visualized by 2D-PAGE of crude mare follicular fluid, with no difference among the three physiological stages. Thirty proteins were observed as differentially expressed between serum and follicular fluid. Enrichment method was found to be the most powerful method for detection and identification of low-abundance proteins from follicular fluid. Actually, we were able to identify 18 proteins in the crude follicular fluid, and as many as 113 in the enriched follicular fluid. Inhibins and a few other proteins involved in reproduction could only be identified after enrichment of follicular fluid, demonstrating the power of the method used. The comparison of proteins found in mare follicular fluid

  17. Treatment approaches to asymptomatic follicular lymphoma.

    PubMed

    Sarkozy, Clémentine; Salles, Gilles

    2013-12-01

    Follicular lymphoma is a heterogeneous disease in which some patients present an indolent evolution for decades and others, a rather aggressive form of the disease requiring immediate therapy. While immunochemotherapy has emerged as a standard of care for symptomatic patients, treatment of the asymptomatic population remains controversial. Since the disease is still considered incurable, delayed initiation of therapy is an acceptable option. However, four single injections of rituximab can result in an acceptable clinical response and can improve the duration of the interval without cytotoxic therapy. With recent therapeutic approaches that enable substantial improvements in life expectancy for follicular lymphoma patients, limiting short- or long-term treatment toxicities appears as a new concern in the asymptomatic population. Based on these options, the challenge is to preserve patient quality of life and prolong survival: from the patient's perspective, his/her opinion is therefore of significant importance. PMID:24219551

  18. Pre- and postnatal nutrition in sheep affects β-cell secretion and hypothalamic control.

    PubMed

    Kongsted, Anna H; Husted, Sanne V; Thygesen, Malin P; Christensen, Vibeke G; Blache, Dominique; Tolver, Anders; Larsen, Torben; Quistorff, Bjørn; Nielsen, Mette O

    2013-11-01

    Maternal undernutrition increases the risk of type 2 diabetes and metabolic syndrome later in life, particularly upon postnatal exposure to a high-energy diet. However, dysfunctions of, for example, the glucose-insulin axis are not readily detectable by conventional tests early in life, making it difficult to identify individuals at risk. Thus, other methods are required. We hypothesised that prenatally undernourished individuals (but not postnatally overnourished ones) are adapted to a life with limited food availability, which would be evident under conditions reflecting starvation, stress and short-term abundance of food. In this study, twin-pregnant sheep were fed diets meeting 100% (NORM) or 50% (LOW) of energy and protein requirements during the last trimester. Twin offspring were fed either a normal moderate (CONV) diet or a high-carbohydrate-high-fat (HCHF) diet from 3 days to 6 months of age (approximately puberty) and the same moderate diet thereafter until 2 years of age (young adulthood; only females), resulting in four groups: NORM-CONV, LOW-CONV, NORM-HCHF and LOW-HCHF. At the age of 6 months and 2 years respectively, they were subjected to fasting and propionate (nutrient abundance) and adrenalin challenges. At 6 months of age, postnatal HCHF diet exposure caused metabolic alterations, reflecting hypertriglyceridaemia and altered pancreatic β-cell secretion. Irrespective of postnatal diet, prenatal undernutrition was found to be associated with unexpected endocrine responses of leptin, IGF1 and cortisol during fasting (lack of or the opposite response compared with the controls) in 2-year-old adults. In conclusion, a HCHF diet interfered with β-cell function, whereas maternal undernutrition did not lead to any changes in the LOW offspring, except to abnormal hormone responses, suggesting that fetal programming interferes with hypothalamic integration of important endocrine axis.

  19. Bladder cancer cells secrete while normal bladder cells express but do not secrete AGR2.

    PubMed

    Ho, Melissa E; Quek, Sue-Ing; True, Lawrence D; Seiler, Roland; Fleischmann, Achim; Bagryanova, Lora; Kim, Sara R; Chia, David; Goodglick, Lee; Shimizu, Yoshiko; Rosser, Charles J; Gao, Yuqian; Liu, Alvin Y

    2016-03-29

    Anterior gradient 2 (AGR2) is a cancer-associated secreted protein found predominantly in adenocarcinomas. Given its ubiquity in solid tumors, cancer-secreted AGR2 could be a useful biomarker in urine or blood for early detection. However, normal organs express and might also secrete AGR2, which would impact its utility as a cancer biomarker. Uniform AGR2 expression is found in the normal bladder urothelium. Little AGR2 is secreted by the urothelial cells as no measurable amounts could be detected in urine. The urinary proteomes of healthy people contain no listing for AGR2. Likewise, the blood proteomes of healthy people also contain no significant peptide counts for AGR2 suggesting little urothelial secretion into capillaries of the lamina propria. Expression of AGR2 is lost in urothelial carcinoma, with only 25% of primary tumors observed to retain AGR2 expression in a cohort of lymph node-positive cases. AGR2 is secreted by the urothelial carcinoma cells as urinary AGR2 was measured in the voided urine of 25% of the cases analyzed in a cohort of cancer vs. non-cancer patients. The fraction of AGR2-positive urine samples was consistent with the fraction of urothelial carcinoma that stained positive for AGR2. Since cancer cells secrete AGR2 while normal cells do not, its measurement in body fluids could be used to indicate tumor presence. Furthermore, AGR2 has also been found on the cell surface of cancer cells. Taken together, secretion and cell surface localization of AGR2 are characteristic of cancer, while expression of AGR2 by itself is not. PMID:26894971

  20. Bladder cancer cells secrete while normal bladder cells express but do not secrete AGR2

    PubMed Central

    Ho, Melissa E.; Quek, Sue-Ing; True, Lawrence D.; Seiler, Roland; Fleischmann, Achim; Bagryanova, Lora; Kim, Sara R.; Chia, David; Goodglick, Lee; Shimizu, Yoshiko; Rosser, Charles J.; Gao, Yuqian; Liu, Alvin Y.

    2016-01-01

    Anterior gradient 2 (AGR2) is a cancer-associated secreted protein found predominantly in adenocarcinomas. Given its ubiquity in solid tumors, cancer-secreted AGR2 could be a useful biomarker in urine or blood for early detection. However, normal organs express and might also secrete AGR2, which would impact its utility as a cancer biomarker. Uniform AGR2 expression is found in the normal bladder urothelium. Little AGR2 is secreted by the urothelial cells as no measurable amounts could be detected in urine. The urinary proteomes of healthy people contain no listing for AGR2. Likewise, the blood proteomes of healthy people also contain no significant peptide counts for AGR2 suggesting little urothelial secretion into capillaries of the lamina propria. Expression of AGR2 is lost in urothelial carcinoma, with only 25% of primary tumors observed to retain AGR2 expression in a cohort of lymph node-positive cases. AGR2 is secreted by the urothelial carcinoma cells as urinary AGR2 was measured in the voided urine of 25% of the cases analyzed in a cohort of cancer vs. non-cancer patients. The fraction of AGR2-positive urine samples was consistent with the fraction of urothelial carcinoma that stained positive for AGR2. Since cancer cells secrete AGR2 while normal cells do not, its measurement in body fluids could be used to indicate tumor presence. Furthermore, AGR2 has also been found on the cell surface of cancer cells. Taken together, secretion and cell surface localization of AGR2 are characteristic of cancer, while expression of AGR2 by itself is not. PMID:26894971

  1. The story of cell secretion: events leading to the discovery of the 'porosome' - the universal secretory machinery in cells.

    PubMed

    Jeftinija, S

    2006-01-01

    Cell secretion has come of age, and a century old quest has been elegantly solved. We have come a long way since earlier observations of what appeared to be 'fibrillar regions' at the cell plasma membrane, and electrophysiological studies suggesting the presence of 'fusion pores' at the cell plasma membrane where secretion occurs. Finally, the fusion pore or 'porosome' has been discovered, and its morphology and dynamics determined at nm resolution and in real time in live secretory cells. The porosome has been isolated, its composition determined and it has been both structurally and functionally reconstituted in artificial lipid membrane. The discovery of the porosome as the universal secretory machinery in cells and the discovery of the molecular mechanism of vesicular content expulsion during cell secretion have finally enabled a clear understanding of this important cellular process. This review outlines the fascinating and exciting journey leading to the discovery of the porosome, ultimately solving one of the most difficult, significant, and fundamental cellular process -cell secretion.

  2. Multiscale modelling of ovarian follicular selection.

    PubMed

    Clément, Frédérique; Monniaux, Danielle

    2013-12-01

    In mammals, the number of ovulations at each ovarian cycle is determined during the terminal phase of follicular development by a tightly controlled follicle selection process. The mechanisms underlying follicle selection take place on different scales and different levels of the gonadotropic axis. These include the endocrine loops between the ovary and the hypothalamic-pituitary complex, the dynamics of follicle populations within the ovary and the dynamics of cell populations within ovarian follicles. A compartmental modelling approach was first designed to describe the cell dynamics in the selected follicle. It laid the basis for a multiscale model formulated with partial differential equations of conservation law type, resulting in the structuring of the follicular cell populations according to cell age and cell maturity. In this model, the selection occurs as a FSH (follicle stimulating hormone)-driven competition between simultaneously developing follicles. The selection output (mono-ovulation, poly-ovulation or anovulation) results from a subtle interplay between the hypothalamus, the pituitary gland and the ovaries, combined with slight differences in the initial conditions or ageing and maturation velocities of the competing follicles. This modelling approach is proposed as a useful complement to experimental studies of follicular development and in turn, the mechanisms of follicle selection raise challenging questions on the mathematical ground.

  3. Induction of multiple follicular development for IVF.

    PubMed

    Fleming, R; Coutts, J R

    1990-07-01

    It is now accepted, almost universally, that multiple follicular development is a pre-requisite for a successful assisted conception programme. The reasons for this are based on abundant clinical evidence from the major IVF and GIFT centres of the world indicating the benefits of having multiple gametes available for transfer. The more embryos transferred, the better the pregnancy rate; the more embryos available for cryopreservation the better the chances of subsequent survival and replacement. However, the vast majority of patients in IVF/GIFT programmes have normal ovarian and pituitary function designed to produce a single dominant follicle and oocyte each month. Obtaining multiple follicular growth requires pharmacological manipulation of ovarian function and complicating factors may arise from both ovarian and pituitary sources. Methods employed to achieve multiple follicular growth vary considerably in the different centres and experiments continue in attempts to find either the simplest or the perfect system, or both. This would provide abundant oocytes and the ideal hormone environment for implantation, with no interfering factors at either the ovarian or endometrial level, while avoiding the drawbacks commonly encountered such as pre-operative ovulation or hyperstimulation syndrome. It should also be inexpensive, although in reality cost-effectiveness is more important. PMID:2207596

  4. Dendritic Polymers for Theranostics

    PubMed Central

    Ma, Yuan; Mou, Quanbing; Wang, Dali; Zhu, Xinyuan; Yan, Deyue

    2016-01-01

    Dendritic polymers are highly branched polymers with controllable structures, which possess a large population of terminal functional groups, low solution or melt viscosity, and good solubility. Their size, degree of branching and functionality can be adjusted and controlled through the synthetic procedures. These tunable structures correspond to application-related properties, such as biodegradability, biocompatibility, stimuli-responsiveness and self-assembly ability, which are the key points for theranostic applications, including chemotherapeutic theranostics, biotherapeutic theranostics, phototherapeutic theranostics, radiotherapeutic theranostics and combined therapeutic theranostics. Up to now, significant progress has been made for the dendritic polymers in solving some of the fundamental and technical questions toward their theranostic applications. In this review, we briefly summarize how to control the structures of dendritic polymers, the theranostics-related properties derived from their structures and their theranostics-related applications. PMID:27217829

  5. Lithium Dendrite Formation

    SciTech Connect

    2015-03-06

    Scientists at the Department of Energy’s Oak Ridge National Laboratory have captured the first real-time nanoscale images of lithium dendrite structures known to degrade lithium-ion batteries. The ORNL team’s electron microscopy could help researchers address long-standing issues related to battery performance and safety. Video shows annular dark-field scanning transmission electron microscopy imaging (ADF STEM) of lithium dendrite nucleation and growth from a glassy carbon working electrode and within a 1.2M LiPF6 EC:DM battery electrolyte.

  6. Isothermal Dendritic Growth Experiment Video

    NASA Technical Reports Server (NTRS)

    1997-01-01

    This video, captured during the Isothermal Dendritic Growth Experiment (IDGE) flown on STS-87 as a part of the fourth United States Microgravity payload, shows the growth of a dendrite, and the surface solidification that occurred on the front and back windows of the growth chamber. Dendrites are tiny, tree like structures that form as metals solidify.

  7. Signaling pathways used by EGF to stimulate conjunctival goblet cell secretion.

    PubMed

    Hodges, Robin R; Bair, Jeffrey A; Carozza, Richard B; Li, Dayu; Shatos, Marie A; Dartt, Darlene A

    2012-10-01

    The purpose of this study was to identify the signaling pathways that epidermal growth factor (EGF) uses to stimulate mucin secretion from cultured rat conjunctival goblet cells and to compare the pathways used by EGF with those used by the known secretagogue muscarinic, cholinergic agonists. To this end, goblet cells from rat conjunctiva were grown in culture using RPMI media. For immunofluorescence experiments, antibodies against EGF receptor (EGFR) and ERK 2 as well as muscarinic receptors (M(1)AchR, M(2)AchR, and M(3)AchR) were used, and the cells viewed by fluorescence microscopy. Intracellular [Ca(2+)] ([Ca(2+)](i)) was measured using fura 2/AM. Glycoconjugate secretion was determined after cultured goblet cells were preincubated with inhibitors, and then stimulated with EGF or the cholinergic agonist carbachol (Cch). Goblet cell secretion was measured using an enzyme-linked lectin assay with UEA-I or ELISA for MUC5AC. In cultured goblet cells EGF stimulated an increase in [Ca(2+)](i) in a concentration-dependent manner. EGF-stimulated increase in [Ca(2+)](i) was blocked by inhibitors of the EGF receptor and removal of extracellular Ca(2+). Inhibitors against the EGFR and ERK 1/2 blocked EGF-stimulated mucin secretion. In addition, cultured goblet cells expressed M(1)AchR, M(2)AchR, and M(3)AchRs. Cch-stimulated increase in [Ca(2+)](i) was blocked by inhibitors for the M(1)AchRs, matrix metalloproteinases, and EGF receptors. Inhibitors against the EGF receptor and ERK 1/2 also blocked Cch-stimulated mucin secretion. We conclude that in conjunctival goblet cells, EGF itself increases [Ca(2+)](i) and activates ERK 1/2 to stimulate mucin secretion. EGF-stimulated secretion is dependent on extracellular Ca(2+). This mechanism of action is similar to cholinergic agonists that use muscarinic receptors to transactivate the EGF receptor, increase [Ca(2+)](i), and activate ERK 1/2 leading to an increase in mucin secretion.

  8. Functional expression of CD137 (4-1BB) on T helper follicular cells

    PubMed Central

    Alfaro, Carlos; Echeveste, Jose I; Rodriguez-Ruiz, Maria E; Solorzano, Jose L; Perez-Gracia, Jose L; Idoate, Miguel A; Lopez-Picazo, Jose M; Sanchez-Paulete, Alfonso R; Labiano, Sara; Rouzaut, Ana; Oñate, Carmen; Aznar, Angela; Lozano, Maria D; Melero, Ignacio

    2015-01-01

    CD137 (4-1BB) is a surface protein initially discovered to mark activated T lymphocytes. However, its broader expression pattern also encompasses activated NK cells, B cells and myeloid cells, including mature dendritic cells. In this study, we have immunostained for CD137 on paraffin-embedded lymphoid tissues including tonsils, lymph nodes, ectopic tertiary lymphoid tissue in Hashimoto thyroiditis and cancer. Surprisingly, immunostaining mainly decorated intrafollicular lymphocytes in the tissues analyzed, with only scattered staining in interfollicular areas. Moreover, pathologic lymphoid follicles in follicular lymphoma and tertiary lymphoid tissue associated with non-small cell lung cancer showed a similar pattern of immunostaining. Multispectral fluorescence cytometry demonstrated that CD137 expression was restricted to CD4+ CXCR5+ follicular T helper lymphocytes (TFH cells) in tonsils and lymph nodes. Short-term culture of lymph node cell suspensions in the presence of either an agonistic anti-CD137 monoclonal antibody (mAb) or CD137-ligand stimulated the functional upregulation of TFH cells in 3 out of 6 cases, as indicated by CD40L surface expression and cytokine production. As a consequence, immunostimulatory monoclonal antibodies targeting CD137 (such as urelumab and PF-05082566) should be expected to primarily act on this lymphocyte subset, thus modifying ongoing humoral immune responses in patients with autoimmune disease and cancer. PMID:26587331

  9. The tumour microenvironment influences survival and time to transformation in follicular lymphoma in the rituximab era.

    PubMed

    Blaker, Yngvild Nuvin; Spetalen, Signe; Brodtkorb, Marianne; Lingjaerde, Ole Christian; Beiske, Klaus; Østenstad, Bjørn; Sander, Birgitta; Wahlin, Björn Engelbrekt; Melen, Christopher Michael; Myklebust, June Helen; Holte, Harald; Delabie, Jan; Smeland, Erlend Bremertun

    2016-10-01

    The tumour microenvironment influences outcome in patients with follicular lymphoma (FL), but its impact on transformation is less studied. We investigated the prognostic significance of the tumour microenvironment on transformation and survival in FL patients treated in the rituximab era. We examined diagnostic and transformed biopsies from 52 FL patients using antibodies against CD3, CD4, CD8, CD21 (CR2), CD57 (B3GAT1), CD68, FOXP3, TIA1, PD-1 (PDCD1), PD-L1 (CD274) and PAX5. Results were compared with a second cohort of 40 FL patients without signs of transformation during a minimum of five years observation time. Cell numbers and localization were semi-quantitatively assessed. Better developed CD21+  follicular dendritic cell (FDC) meshworks at diagnosis was a negative prognostic factor for overall survival (OS), progression-free survival (PFS) and time to transformation (TTT) in patients with subsequently transformed FL. Remnants of FDC meshworks at transformation were associated with shorter OS and PFS from transformation. High degrees of intrafollicular CD68+ and PD-L1+  macrophage infiltration, high total area scores and an extrafollicular/diffuse pattern of FOXP3+  T cells and high intrafollicular scores of CD4+  T cells at diagnosis were associated with shorter TTT. Scores of several T-cell subset markers from the combined patient cohorts were predictive for transformation, especially CD4 and CD57. PMID:27341313

  10. Two-photon microscopy for imaging germinal centers and T follicular helper cells.

    PubMed

    Clatworthy, Menna R

    2015-01-01

    One of the principle features of immune cells is their dynamic nature. Lymphocytes circulate in the blood between secondary lymphoid organs and tissues in an effort to maximize the likelihood of a rapid and appropriate immune response to invading pathogens and tissue damage. Conventional experimental techniques such as histology and flow cytometry have greatly increased our understanding of immune cells, but in the last decade, two-photon microscopy has revolutionized our ability to interrogate the dynamic behavior of immune cells, a facet so critical to their function. Two-photon microscopy relies on the excitation of fluorophores by simultaneous application of two photons of longer wavelength light. This allows a greater depth of imaging with minimal photodamage. Thus, living tissues can be imaged, including immune cells in lymph nodes. This technique has been used to interrogate the events occurring in a germinal center response and the interactions between cells in the germinal center, including T follicular helper cells (Tfh), germinal center B cells, and follicular dendritic cells (FDC). Herein, a method is described by which the interactions between Tfh and B cells within a germinal center in a popliteal lymph node can be imaged in a live mouse. PMID:25836302

  11. Transport Processes in Dendritic Crystallization

    NASA Technical Reports Server (NTRS)

    Glicksman, M. E.

    1984-01-01

    Free dentritic growth refers to the unconstrained development of crystals within a supercooled melt, which is the classical dendrite problem. The development of theoretical understanding of dendritic growth and its experimental status is sketched showing that transport theory and interfacial thermodynamics (capillarity theory) are insufficient ingredients to develop a truly predictive model of dendrite formation. The convenient, but incorrect, notion of maximum velocity was used for many years to estimate the behavior of dendritic transformations until supplanted by modern dynamic stability theory. The proper combinations of transport theory and morphological stability seem to be able to predict the salient aspects of dendritic growth, especially in the neighborhood of the tip.

  12. Modification of dendritic development.

    PubMed

    Feria-Velasco, Alfredo; del Angel, Alma Rosa; Gonzalez-Burgos, Ignacio

    2002-01-01

    Since 1890 Ramón y Cajal strongly defended the theory that dendrites and their processes and spines had a function of not just nutrient transport to the cell body, but they had an important conductive role in neural impulse transmission. He extensively discussed and supported this theory in the Volume 1 of his extraordinary book Textura del Sistema Nervioso del Hombre y de los Vertebrados. Also, Don Santiago significantly contributed to a detailed description of the various neural components of the hippocampus and cerebral cortex during development. Extensive investigation has been done in the last Century related to the functional role of these complex brain regions, and their association with learning, memory and some limbic functions. Likewise, the organization and expression of neuropsychological qualities such as memory, exploratory behavior and spatial orientation, among others, depend on the integrity and adequate functional activity of the cerebral cortex and hippocampus. It is known that brain serotonin synthesis and release depend directly and proportionally on the availability of its precursor, tryptophan (TRY). By using a chronic TRY restriction model in rats, we studied their place learning ability in correlation with the dendritic spine density of pyramidal neurons in field CA1 of the hippocampus during postnatal development. We have also reported alterations in the maturation pattern of the ability for spontaneous alternation and task performance evaluating short-term memory, as well as adverse effects on the density of dendritic spines of hippocampal CA1 field pyramidal neurons and on the dendritic arborization and the number of dendritic spines of pyramidal neurons from the third layer of the prefrontal cortex using the same model of TRY restriction. The findings obtained in these studies employing a modified Golgi method, can be interpreted as a trans-synaptic plastic response due to understimulation of serotoninergic receptors located in the

  13. Localized Low-Dose Radiotherapy for Follicular Lymphoma: History, Clinical Results, Mechanisms of Action, and Future Outlooks

    SciTech Connect

    Ganem, Gerard; Cartron, Guillaume; Girinsky, Theodore; Haas, Rick L.M.; Cosset, Jean Marc; Solal-Celigny, Philippe

    2010-11-15

    The extreme radiosensitivity of indolent lymphomas was reported in the early years of radiotherapy (RT). The efficacy of low-dose total body irradiation (1.5-2 Gy) was particularly demonstrative. Higher doses were considered appropriate for localized disease. The optimal (or conventional) dose of curative RT derived from the early studies was determined to be 30-35 Gy. Nevertheless, in older series addressing the tumoricidal radiation dose in non-Hodgkin's lymphomas, investigators noted that a significant number of 'nodular' lymphomas were controlled with a dose of <22 Gy for >3 years. The idea of reintroducing localized low-dose radiotherapy (LDRT) for indolent non-Hodgkin's lymphomas came from a clinical observation. The first study showing the high efficacy of LDRT (4 Gy in two fractions of 2 Gy within 3 days) in selected patients with chemoresistant, indolent, non-Hodgkin's lymphomas was published in 1994. Since this first report, at least eight series of patients treated with localized LDRT have been published, showing a 55% complete response rate in irradiated sites, with a median duration of 15-42 months. How LDRT induces lymphoma cell death remains partly unknown. However, some important advances have recently been reported. Localized LDRT induces an apoptosis of follicular lymphoma cells. This apoptotic cell death elicits an immune response mediated by macrophages and dendritic cells. Follicular lymphoma is probably an ideal model to explore these mechanisms. This review also discusses the future of LDRT for follicular lymphoma.

  14. [Follicular conjunctivitis due to Chlamydia trachomatis].

    PubMed

    Basualdo, J A; Huarte, L; Bautista, E; Niedfeld, G; Alfonso, G; Rosso, N; Geronés, M; Galeppi, I

    2001-01-01

    During two years (1997-1999) an investigation of possible infections of chlamydial etiology in outpatients with follicular conjunctivitis was carried out, through the use of specific assays. Fifty-seven selected patients with presumptive inclusion conjunctivitis were diagnosed by means of ophthalmoscopic examination and bilateral tarsal-conjunctiva swabbing for microorganisms. The possible presence of Chlamydia trachomatis was tested by immunofluorescence microscopy and isolation in cell culture of McCoy line. Of the 57 conjunctivitis patients screened, 37 (65%) proved to be positive by cell culture (CC) and 27 (47%) by direct immunofluorescence (IFD). A good agreement between the two assays was observed, where the CC was more sensitive than IFD. Of these 37 patients with chlamydial conjunctivitis, 23 (62%) were women, with over one-third of them ranging in age from 45 to 65 years. Their clinical records revealed an evolution period of 1 to 12 months. Eighteen (78%) of these women reported previous genital pathology, while 4 (29%) of the 14 men had a history of urethritis by Chlamydia trachomatis. A high frequency of follicular conjunctivitis by Chlamydia (65%) in the screened patients was observed, without any evidence of urogenital signs and symptoms at the moment of the study.

  15. Human mesenchymal stromal cell-secreted lactate induces M2-macrophage differentiation by metabolic reprogramming

    PubMed Central

    Civini, Sara; Pacelli, Consiglia; Dieng, Mame Massar; Lemieux, William; Jin, Ping; Bazin, Renée; Patey, Natacha; Marincola, Francesco M.; Moldovan, Florina; Zaouter, Charlotte; Trudeau, Louis-Eric; Benabdhalla, Basma; Louis, Isabelle; Beauséjour, Christian; Stroncek, David; Le Deist, Françoise; Haddad, Elie

    2016-01-01

    Human mesenchymal stromal cells (MSC) have been shown to dampen immune response and promote tissue repair, but the underlying mechanisms are still under investigation. Herein, we demonstrate that umbilical cord-derived MSC (UC-MSC) alter the phenotype and function of monocyte-derived dendritic cells (DC) through lactate-mediated metabolic reprogramming. UC-MSC can secrete large quantities of lactate and, when present during monocyte-to-DC differentiation, induce instead the acquisition of M2-macrophage features in terms of morphology, surface markers, migratory properties and antigen presentation capacity. Microarray expression profiling indicates that UC-MSC modify the expression of metabolic-related genes and induce a M2-macrophage expression signature. Importantly, monocyte-derived DC obtained in presence of UC-MSC, polarize naïve allogeneic CD4+ T-cells into Th2 cells. Treatment of UC-MSC with an inhibitor of lactate dehydrogenase strongly decreases lactate concentration in culture supernatant and abrogates the effect on monocyte-to-DC differentiation. Metabolic analysis further revealed that UC-MSC decrease oxidative phosphorylation in differentiating monocytes while strongly increasing the spare respiratory capacity proportional to the amount of secreted lactate. Because both MSC and monocytes are recruited in vivo at the site of tissue damage and inflammation, we propose the local increase of lactate concentration induced by UC-MSC and the consequent enrichment in M2-macrophage generation as a mechanism to achieve immunomodulation. PMID:27070086

  16. Magnetic and dendritic catalysts.

    PubMed

    Wang, Dong; Deraedt, Christophe; Ruiz, Jaime; Astruc, Didier

    2015-07-21

    The recovery and reuse of catalysts is a major challenge in the development of sustainable chemical processes. Two methods at the frontier between homogeneous and heterogeneous catalysis have recently emerged for addressing this problem: loading the catalyst onto a dendrimer or onto a magnetic nanoparticle. In this Account, we describe representative examples of these two methods, primarily from our research group, and compare them. We then describe new chemistry that combines the benefits of these two methods of catalysis. Classic dendritic catalysis has involved either attaching the catalyst covalently at the branch termini or within the dendrimer core. We have used chelating pyridyltriazole ligands to insolubilize catalysts at the termini of dendrimers, providing an efficient, recyclable heterogeneous catalysts. With the addition of dendritic unimolecular micelles olefin metathesis reactions catalyzed by commercial Grubbs-type ruthenium-benzylidene complexes in water required unusually low amounts of catalyst. When such dendritic micelles include intradendritic ligands, both the micellar effect and ligand acceleration promote faster catalysis in water. With these types of catalysts, we could carry out azide alkyne cycloaddition ("click") chemistry with only ppm amounts of CuSO4·5H2O and sodium ascorbate under ambient conditions. Alternatively we can attach catalysts to the surface of superparamagnetic iron oxide nanoparticles (SPIONs), essentially magnetite (Fe3O4) or maghemite (γ-Fe2O3), offering the opportunity to recover the catalysts using magnets. Taking advantage of the merits of both of these strategies, we and others have developed a new generation of recyclable catalysts: dendritic magnetically recoverable catalysts. In particular, some of our catalysts with a γ-Fe2O3@SiO2 core and 1,2,3-triazole tethers and loaded with Pd nanoparticles generate strong positive dendritic effects with respect to ligand loading, catalyst loading, catalytic activity and

  17. Silicon dendritic web material

    NASA Technical Reports Server (NTRS)

    Meier, D. L.; Campbell, R. B.; Sienkiewicz, L. J.; Rai-Choudhury, P.

    1982-01-01

    The development of a low cost and reliable contact system for solar cells and the fabrication of several solar cell modules using ultrasonic bonding for the interconnection of cells and ethylene vinyl acetate as the potting material for module encapsulation are examined. The cells in the modules were made from dendritic web silicon. To reduce cost, the electroplated layer of silver was replaced with an electroplated layer of copper. The modules that were fabricated used the evaporated Ti, Pd, Ag and electroplated Cu (TiPdAg/Cu) system. Adherence of Ni to Si is improved if a nickel silicide can be formed by heat treatment. The effectiveness of Ni as a diffusion barrier to Cu and the ease with which nickel silicide is formed is discussed. The fabrication of three modules using dendritic web silicon and employing ultrasonic bonding for interconnecting calls and ethylene vinyl acetate as the potting material is examined.

  18. Isolation of dendritic cells.

    PubMed

    Inaba, K; Swiggard, W J; Steinman, R M; Romani, N; Schuler, G

    2001-05-01

    This unit presents two methods for preparing dendritic cells (DCs), a highly specialized type of antigen-presenting cell (APC). The first method involves the isolation of DCs from mouse spleen, resulting in a cell population that is highly enriched in accessory cell and APC function. A support protocol for collagenase digestion of splenocyte suspensions is described to increase the yield of dendritic cells. The second method involves generating large numbers of DCs from mouse bone marrow progenitor cells. In that technique, bone marrow cells are cultured in the presence of granulocyte/macrophage colony-stimulating factor (GM-CSF) to yield 5-10 10(6) cells, 60% of which express DC surface markers (e.g., B-7-2/CD86). Additional techniques for isolating DCs from mouse spleens or other mouse tissues, as well as from human tissues, are also discussed.

  19. Isolation of dendritic cells.

    PubMed

    Inaba, Kayo; Swiggard, William J; Steinman, Ralph M; Romani, Nikolaus; Schuler, Gerold; Brinster, Carine

    2009-08-01

    This unit presents two methods for preparing dendritic cells (DCs), a highly specialized type of antigen-presenting cell (APC). The first method involves the isolation of DCs from mouse spleen, resulting in a cell population that is highly enriched in accessory cell and APC function. A support protocol for collagenase digestion of splenocyte suspensions is described to increase the yield of dendritic cells. The second method involves generating large numbers of DCs from mouse bone marrow progenitor cells. In that technique, bone marrow cells are cultured in the presence of granulocyte/macrophage colony-stimulating factor (GM-CSF) to yield 5-10 x 10(6) cells, 60% of which express DC surface markers (e.g., B-7-2/CD86). Additional techniques for isolating DCs from mouse spleens or other mouse tissues, as well as from human tissues, are also discussed.

  20. Silicon dendritic web growth

    NASA Technical Reports Server (NTRS)

    Duncan, S.

    1984-01-01

    Technological goals for a silicon dendritic web growth program effort are presented. Principle objectives for this program include: (1) grow long web crystals front continuously replenished melt; (2) develop temperature distribution in web and melt; (3) improve reproductibility of growth; (4) develop configurations for increased growth rates (width and speed); (5) develop new growth system components as required for improved growth; and (6) evaluate quality of web growth.

  1. Automated microfluidic platform of bead-based electrochemical immunosensor integrated with bioreactor for continual monitoring of cell secreted biomarkers

    NASA Astrophysics Data System (ADS)

    Riahi, Reza; Shaegh, Seyed Ali Mousavi; Ghaderi, Masoumeh; Zhang, Yu Shrike; Shin, Su Ryon; Aleman, Julio; Massa, Solange; Kim, Duckjin; Dokmeci, Mehmet Remzi; Khademhosseini, Ali

    2016-04-01

    There is an increasing interest in developing microfluidic bioreactors and organs-on-a-chip platforms combined with sensing capabilities for continual monitoring of cell-secreted biomarkers. Conventional approaches such as ELISA and mass spectroscopy cannot satisfy the needs of continual monitoring as they are labor-intensive and not easily integrable with low-volume bioreactors. This paper reports on the development of an automated microfluidic bead-based electrochemical immunosensor for in-line measurement of cell-secreted biomarkers. For the operation of the multi-use immunosensor, disposable magnetic microbeads were used to immobilize biomarker-recognition molecules. Microvalves were further integrated in the microfluidic immunosensor chip to achieve programmable operations of the immunoassay including bead loading and unloading, binding, washing, and electrochemical sensing. The platform allowed convenient integration of the immunosensor with liver-on-chips to carry out continual quantification of biomarkers secreted from hepatocytes. Transferrin and albumin productions were monitored during a 5-day hepatotoxicity assessment in which human primary hepatocytes cultured in the bioreactor were treated with acetaminophen. Taken together, our unique microfluidic immunosensor provides a new platform for in-line detection of biomarkers in low volumes and long-term in vitro assessments of cellular functions in microfluidic bioreactors and organs-on-chips.

  2. Automated microfluidic platform of bead-based electrochemical immunosensor integrated with bioreactor for continual monitoring of cell secreted biomarkers

    PubMed Central

    Riahi, Reza; Shaegh, Seyed Ali Mousavi; Ghaderi, Masoumeh; Zhang, Yu Shrike; Shin, Su Ryon; Aleman, Julio; Massa, Solange; Kim, Duckjin; Dokmeci, Mehmet Remzi; Khademhosseini, Ali

    2016-01-01

    There is an increasing interest in developing microfluidic bioreactors and organs-on-a-chip platforms combined with sensing capabilities for continual monitoring of cell-secreted biomarkers. Conventional approaches such as ELISA and mass spectroscopy cannot satisfy the needs of continual monitoring as they are labor-intensive and not easily integrable with low-volume bioreactors. This paper reports on the development of an automated microfluidic bead-based electrochemical immunosensor for in-line measurement of cell-secreted biomarkers. For the operation of the multi-use immunosensor, disposable magnetic microbeads were used to immobilize biomarker-recognition molecules. Microvalves were further integrated in the microfluidic immunosensor chip to achieve programmable operations of the immunoassay including bead loading and unloading, binding, washing, and electrochemical sensing. The platform allowed convenient integration of the immunosensor with liver-on-chips to carry out continual quantification of biomarkers secreted from hepatocytes. Transferrin and albumin productions were monitored during a 5-day hepatotoxicity assessment in which human primary hepatocytes cultured in the bioreactor were treated with acetaminophen. Taken together, our unique microfluidic immunosensor provides a new platform for in-line detection of biomarkers in low volumes and long-term in vitro assessments of cellular functions in microfluidic bioreactors and organs-on-chips. PMID:27098564

  3. High LIN28A Expressing Ovarian Cancer Cells Secrete Exosomes That Induce Invasion and Migration in HEK293 Cells.

    PubMed

    Enriquez, Vanessa A; Cleys, Ellane R; Da Silveira, Juliano C; Spillman, Monique A; Winger, Quinton A; Bouma, Gerrit J

    2015-01-01

    Epithelial ovarian cancer is the most aggressive and deadly form of ovarian cancer and is the most lethal gynecological malignancy worldwide; therefore, efforts to elucidate the molecular factors that lead to epithelial ovarian cancer are essential to better understand this disease. Recent studies reveal that tumor cells release cell-secreted vesicles called exosomes and these exosomes can transfer RNAs and miRNAs to distant sites, leading to cell transformation and tumor development. The RNA-binding protein LIN28 is a known marker of stem cells and when expressed in cancer, it is associated with poor tumor outcome. We hypothesized that high LIN28 expressing ovarian cancer cells secrete exosomes that can be taken up by nontumor cells and cause changes in gene expression and cell behavior associated with tumor development. IGROV1 cells were found to contain high LIN28A and secrete exosomes that were taken up by HEK293 cells. Moreover, exposure to these IGROV1 secreted exosomes led to significant increases in genes involved in Epithelial-to-Mesenchymal Transition (EMT), induced HEK293 cell invasion and migration. These changes were not observed with exosomes secreted by OV420 cells, which contain no detectable amounts of LIN28A or LIN28B. No evidence was found of LIN28A transfer from IGROV1 exosomes to HEK293 cells.

  4. Web-dendritic ribbon growth

    NASA Technical Reports Server (NTRS)

    Hilborn, R. B., Jr.; Faust, J. W., Jr.

    1976-01-01

    A web furnace was constructed for pulling dendritic-web samples. The effect of changes in the furnace thermal geometry on the growth of dendritic-web was studied. Several attempts were made to grow primitive dendrites for use as the dendritic seed crystals for web growth and to determine the optimum twin spacing in the dendritic seed crystal for web growth. Mathematical models and computer programs were used to determine the thermal geometries in the susceptor, crucible melt, meniscus, and web. Several geometries were determined for particular furnace geometries and growth conditions. The information obtained was used in conjunction with results from the experimental growth investigations in order to achieve proper conditions for sustained pulling of two dendrite web ribbons. In addition, the facilities for obtaining the following data were constructed: twin spacing, dislocation density, web geometry, resistivity, majority charge carrier type, and minority carrier lifetime.

  5. IDGE: Isothermal Dendritic Growth Experiment

    NASA Technical Reports Server (NTRS)

    1994-01-01

    The Isothermal Dendritic Growth Experiment (IDGE) flew on STS-62 to study the microscopic, tree-like structures (dendrites) that form within metals as they solidify from molten materials. The size, shape, and orientation of these dendrites affect the strength and usefulness of metals. Data from this experiment will be used to test and improve the mathematical models that support the industrial production of metals.

  6. Crowding and Follicular Fate: Spatial Determinants of Follicular Reserve and Activation of Follicular Growth in the Mammalian Ovary

    PubMed Central

    Gaytan, Francisco; Morales, Concepcion; Leon, Silvia; Garcia-Galiano, David; Roa, Juan; Tena-Sempere, Manuel

    2015-01-01

    Initiation of growth of resting ovarian follicles is a key phenomenon for providing an adequate number of mature oocytes in each ovulation, while preventing premature exhaustion of primordial follicle reserve during the reproductive lifespan. Resting follicle dynamics strongly suggest that primordial follicles are under constant inhibitory influences, by mechanisms and factors whose nature remains ill defined. In this work, we aimed to assess the influence of spatial determinants, with special attention to clustering patterns and crowding, on the fate of early follicles in the adult mouse and human ovary. To this end, detailed histological and morphometric analyses, targeting resting and early growing follicles, were conducted in ovaries from mice, either wild type (WT) or genetically modified to lack kisspeptin receptor expression (Kiss1r KO), and healthy adult women. Kiss1r KO mice were studied as model of persistent hypogonadotropism and anovulation. Different qualitative and quantitative indices of the patterns of spatial distribution of resting and early growing follicles in the mouse and human ovary, including the Morisita’s index of clustering, were obtained. Our results show that resting primordial follicles display a clear-cut clustered pattern of spatial distribution in adult mouse and human ovaries, and that resting follicle aggrupation is inversely correlated with the proportion of follicles initiating growth and entering into the growing pool. As a whole, our data suggest that resting follicle crowding, defined by changes in density and clustered pattern of distribution, is a major determinant of follicular activation and the fate of ovarian reserve. Uneven follicle crowding would constitute the structural counterpart of the major humoral regulators of early follicular growth, with potential implications in ovarian ageing and pathophysiology. PMID:26642206

  7. Dendritic spine alterations in schizophrenia.

    PubMed

    Moyer, Caitlin E; Shelton, Micah A; Sweet, Robert A

    2015-08-01

    Schizophrenia is a chronic illness affecting approximately 0.5-1% of the world's population. The etiology of schizophrenia is complex, including multiple genes, and contributing environmental effects that adversely impact neurodevelopment. Nevertheless, a final common result, present in many subjects with schizophrenia, is impairment of pyramidal neuron dendritic morphology in multiple regions of the cerebral cortex. In this review, we summarize the evidence of reduced dendritic spine density and other dendritic abnormalities in schizophrenia, evaluate current data that informs the neurodevelopment timing of these impairments, and discuss what is known about possible upstream sources of dendritic spine loss in this illness.

  8. Dendrite development: a surprising origin.

    PubMed

    Ehlers, Michael D

    2005-08-15

    Neurons extend elaborate dendrites studded with spines. Unexpectedly, this cellular sculpting is regulated by the origin recognition complex -- the core machinery for initiating DNA replication. PMID:16103221

  9. [Assessment of follicular development and ovulation by ultrasound].

    PubMed

    Sengoku, K; Ishikawa, M; Yamashita, K; Mizoguchi, H; Kasamo, M; Shimizu, T; Tanaka, K

    1982-12-01

    The relation between ultrasonographic signs of ovulation and serum estradiol (E2) rise and luteinizing hormone (LH) surge were studied. Forty-eight cycles were examined in Twenty-eight infertile patients. The correlation between the follicular diameter as measured by ultrasound and actual follicular diameter under direct visualization was also determined in 19 follicles of the 25 patients who had undergone laparotomy. In 34 of the 48 cycles, growing follicles and follicular rupture could be observed by ultrasound (72.3%). The mean diameter of the follicles measured the day before estimated ovulation was 22.4 +/- 2.75 mm(range 16-27mm). The ultrasonographic ovulation period (UOP) occurred within 24 hours from the day of maximal LH levels in 24 of the 34 cycles, and within 48 hours from the day of the E2 peak in 25 of the 34 cycles. The follicular diameter measured by ultrasound was greater than the actual diameter found during laparotomy, but there was a high degree of correlation (r = 0.900). Furthermore, the E2 and P levels in follicular fluid were high in large follicles and correlated well with the ultrasound assessments of follicular size. These results suggested that ultrasonic monitoring provides a reliable measure of follicular growth and prediction of ovulation, and offers a highly sophisticated scientific tool for the study of reproductive endocrinology.

  10. Hyperthyroidism with metastatic follicular thyroid carcinoma

    SciTech Connect

    Chapman, C.N.; Sziklas, J.J.; Spencer, R.P.; Bower, B.F.; Rosenberg, R.J.

    1984-04-01

    A 70-yr-old woman presented with hyperthyroidism and metastatic follicular carcinoma of the thyroid. The blood level of thyroid stimulating immunoglobulin (TSIg) was elevated. A total thyroidectomy was performed. One month later she remained hyperthyroid. Three weeks after therapy with 218 mCi of I-131 sodium iodide, the patient was euthyroid. Six months after the initial radioiodide therapy, she was again hyperthyroid and was given a second oral treatment dose of I-131 (220 mCi). Five months later, the patient had again become euthyroid. It is likely that initially the woman's metastases were producing sufficient hormone to render her hyperthyroid. After thyroidectomy and two large doses of radioiodide, she has remained euthyroid without having to take exogenous hormone.

  11. FOLLICULAR HELPER T CELLS: LINEAGE AND LOCATION

    PubMed Central

    Fazilleau, Nicolas; Mark, Linda; McHeyzer-Williams, Louise J.; McHeyzer-Williams, Michael G.

    2009-01-01

    Follicular helper T (TFH) cells are the class of effector TH cells that regulates the stepwise development of antigen-specific B cell immunity in vivo. Deployment of CXCR5+ TFH cells to B cell zones of lymphoid tissues and stable cognate interactions with B cells are central to the delivery of antigen-specific TFH function. Recent advances help to unravel distinctive elements of developmental programming for TFH cells and unique effector TFH functions focused on antigen-primed B cells. Understanding the regulatory functions of TFH cells in the germinal center and the subsequent regulation of memory B cell responses to antigen recall represent the frontiers of this research area with the potential to alter fundamentally the design of future vaccines. PMID:19303387

  12. Risk assessment of thyroid follicular cell tumors.

    PubMed Central

    Hill, R N; Crisp, T M; Hurley, P M; Rosenthal, S L; Singh, D V

    1998-01-01

    Thyroid follicular cell tumors arise in rodents from mutations, perturbations of thyroid and pituitary hormone status with increased stimulation of thyroid cell growth by thyroid-stimulating hormone (TSH), or a combination of the two. The only known human thyroid carcinogen is ionizing radiation. It is not known for certain whether chemicals that affect thyroid cell growth lead to human thyroid cancer. The U.S. Environmental Protection Agency applies the following science policy positions: 1) chemically induced rodent thyroid tumors are presumed to be relevant to humans; 2) when interspecies information is lacking, the default is to assume comparable carcinogenic sensitivity in rodents and humans; 3) adverse rodent noncancer thyroid effects due to chemically induced thyroid-pituitary disruption are presumed to be relevant to humans; 4) linear dose-response considerations are applied to thyroid cancer induced by chemical substances that either do not disrupt thyroid functioning or lack mode of action information; 5) nonlinear thyroid cancer dose-response considerations are applied to chemicals that reduce thyroid hormone levels, increase TSH and thyroid cell division, and are judged to lack mutagenic activity; and 6) nonlinear considerations may be applied in thyroid cancer dose-response assessments on a case-by-case basis for chemicals that disrupt thyroid-pituitary functioning and demonstrate some mutagenic activity. Required data for risk assessment purposes is mode of action information on mutagenicity, increases in follicular cell growth (cell size and number) and thyroid gland weight, thyroid-pituitary hormones, site of action, correlations between doses producing thyroid effects and cancer, and reversibility of effects when dosing ceases. Images Figure 1 Figure 2 Figure 3 PMID:9681971

  13. Dendritic Alloy Solidification Experiment (DASE)

    NASA Technical Reports Server (NTRS)

    Beckermann, C.; Karma, A.; Steinbach, I.; deGroh, H. C., III

    2001-01-01

    A space experiment, and supporting ground-based research, is proposed to study the microstructural evolution in free dendritic growth from a supercooled melt of the transparent model alloy succinonitrile-acetone (SCN-ACE). The research is relevant to equiaxed solidification of metal alloy castings. The microgravity experiment will establish a benchmark for testing of equiaxed dendritic growth theories, scaling laws, and models in the presence of purely diffusive, coupled heat and solute transport, without the complicating influences of melt convection. The specific objectives are to: determine the selection of the dendrite tip operating state, i.e. the growth velocity and tip radius, for free dendritic growth of succinonitrile-acetone alloys; determine the growth morphology and sidebranching behavior for freely grown alloy dendrites; determine the effects of the thermal/solutal interactions in the growth of an assemblage of equiaxed alloy crystals; determine the effects of melt convection on the free growth of alloy dendrites; measure the surface tension anisotropy strength of succinon itrile -acetone alloys establish a theoretical and modeling framework for the experiments. Microgravity experiments on equiaxed dendritic growth of alloy dendrites have not been performed in the past. The proposed experiment builds on the Isothermal Dendritic Growth Experiment (IDGE) of Glicksman and coworkers, which focused on the steady growth of a single crystal from pure supercooled melts (succinonitrile and pivalic acid). It also extends the Equiaxed Dendritic Solidification Experiment (EDSE) of the present investigators, which is concerned with the interactions and transients arising in the growth of an assemblage of equiaxed crystals (succinonitrile). However, these experiments with pure substances are not able to address the issues related to coupled heat and solute transport in growth of alloy dendrites.

  14. Dendritic cell metabolism

    PubMed Central

    Pearce, Edward J.; Everts, Bart

    2015-01-01

    The past 15 years have seen enormous advances in our understanding of the receptor and signalling systems that allow dendritic cells (DCs) to respond to pathogens or other danger signals and initiate innate and adaptive immune responses. We are now beginning to appreciate that many of these pathways not only stimulate changes in the expression of genes that control DC immune functions, but also affect metabolic pathways, thereby integrating the cellular requirements of the activation process. In this Review, we focus on this relatively new area of research and attempt to describe an integrated view of DC immunometabolism. PMID:25534620

  15. 'Porosome' discovered nearly 20 years ago provides molecular insights into the kiss-and-run mechanism of cell secretion.

    PubMed

    Jena, Bhanu P

    2015-07-01

    Secretion is a fundamental cellular process in living organisms, from yeast to cells in humans. Since the 1950s, it was believed that secretory vesicles completely merged with the cell plasma membrane during secretion. While this may occur, the observation of partially empty vesicles in cells following secretion suggests the presence of an additional mechanism that allows partial discharge of intra-vesicular contents during secretion. This proposed mechanism requires the involvement of a plasma membrane structure called 'porosome', which serves to prevent the collapse of secretory vesicles, and to transiently fuse with the plasma membrane (Kiss-and-run), expel a portion of its contents and disengage. Porosomes are cup-shaped supramolecular lipoprotein structures at the cell plasma membrane ranging in size from 15 nm in neurons and astrocytes to 100-180 nm in endocrine and exocrine cells. Neuronal porosomes are composed of nearly 40 proteins. In comparison, the 120 nm nuclear pore complex is composed of >500 protein molecules. Elucidation of the porosome structure, its chemical composition and functional reconstitution into artificial lipid membrane, and the molecular assembly of membrane-associated t-SNARE and v-SNARE proteins in a ring or rosette complex resulting in the establishment of membrane continuity to form a fusion pore at the porosome base, has been demonstrated. Additionally, the molecular mechanism of secretory vesicle swelling, and its requirement for intra-vesicular content release during cell secretion has also been elucidated. Collectively, these observations provide a molecular understanding of cell secretion, resulting in a paradigm shift in our understanding of the secretory process.

  16. Rituximab Retreatment for Low-Tumor Burden Follicular Lymphoma

    Cancer.gov

    A summary of results from a randomized clinical trial of patients with low–tumor burden follicular lymphoma that compared maintenance therapy with rituximab versus retreatment with rituximab only when there was evidence of disease progression.

  17. Primary follicular lymphoma of the cervix uteri: a review.

    PubMed

    Korcum, Aylin Fidan; Karadogan, Ihsan; Aksu, Gamze; Aralasmak, Ayse; Erdogan, Gulgun

    2007-09-01

    Primary non-Hodgkin's lymphoma of the cervix is a rare disease, of which a subgroup of follicular lymphoma constitutes only 8.5%. There is not an established treatment protocol neither for primary cervical lymphoma nor for its follicular subgroup. We presented a case with Ann Arbor stage IEA (Extra-nodal involvement and absence of weight loss, fever, night sweat) primary follicular lymphoma of the cervix. She was treated with chemotherapy followed by pelvic radiotherapy. Upon relapse with a nodal neck mass, she was treated with rituximab alone. She remained well for 23 months after rituximab. In the 39 months of follow-up, there was no evidence of disease. In the light of our case, we reviewed the reported cases of primary follicular lymphoma of the cervix while discussing their treatment protocols and the cases of primary cervix lymphoma treated with rituximab.

  18. Thyrotoxicosis associated with distant metastatic follicular carcinoma of the thyroid

    SciTech Connect

    Bowden, W.D.; Jones, R.E.

    1986-04-01

    In a man with metastatic follicular carcinoma of the thyroid, thyrotoxicosis developed after total thyroidectomy and was successfully treated with antithyroid medications. Treatment with radioactive iodine decreased the size of the distant metastasis and eventually diminished thyroid hormone production. Follicular carcinoma complicated by hyperthyroidism requires vigorous control of the hypermetabolic state. Treatment with radioactive iodine can effectively reduce metabolic complications and tumor bulk, and yields a remission rate as high as 33%.

  19. Lenalidomide and Rituximab in Treating Patients With Previously Untreated Stage II, Stage III, or Stage IV Follicular Non-Hodgkin Lymphoma

    ClinicalTrials.gov

    2016-07-28

    Stage II Grade 1 Contiguous Follicular Lymphoma; Stage II Grade 1 Non-Contiguous Follicular Lymphoma; Stage II Grade 2 Contiguous Follicular Lymphoma; Stage II Grade 2 Non-Contiguous Follicular Lymphoma; Stage II Grade 3 Contiguous Follicular Lymphoma; Stage II Grade 3 Non-Contiguous Follicular Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma

  20. Follicular Helper T Cells in Autoimmunity.

    PubMed

    Scherm, Martin G; Ott, Verena B; Daniel, Carolin

    2016-08-01

    The development of multiple disease-relevant autoantibodies is a hallmark of autoimmune diseases. In autoimmune type 1 diabetes (T1D), a variable time frame of autoimmunity precedes the clinically overt disease. The relevance of T follicular helper (TFH) cells for the immune system is increasingly recognized. Their pivotal contribution to antibody production by providing help to germinal center (GC) B cells facilitates the development of a long-lived humoral immunity. Their complex differentiation process, involving various stages and factors like B cell lymphoma 6 (Bcl6), is strictly controlled, as anomalous regulation of TFH cells is connected with immunopathologies. While the adverse effects of a TFH cell-related insufficient humoral immunity are obvious, the role of increased TFH frequencies in autoimmune diseases like T1D is currently highlighted. High levels of autoantigen trigger an excessive induction of TFH cells, consequently resulting in the production of autoantibodies. Therefore, TFH cells might provide promising approaches for novel therapeutic strategies. PMID:27324759

  1. Dendritic Growth Velocities in Microgravity

    NASA Technical Reports Server (NTRS)

    Glicksman, M. E.; Koss, M. B.; Winsa, E. A.

    1994-01-01

    We measured dendritic tip velocities in pure succinonitrile (SCN) in microgravity. using a sequence of telemetered binary images sent to Earth from the Space Shuttle Columbia (STS-62). Growth velocities were measured as a function of the supercooling over the range 0.05-1.5 K. Microgravity observations show that buoyancy-induced convection alters the growth kinetics of SCN dendrites at supercooling as high as 1.3 K. Also, the dendrite velocity data measured under microgravity agree well with the Ivantsov paraboloidal diffusion solution when coupled to a scaling constant of sigma(sup *) = 0.0157.

  2. Transient Dendritic Solidification Experiment (TDSE)

    NASA Technical Reports Server (NTRS)

    2000-01-01

    The Transient Dendritic Solidification Expepriment (TDSE) is being developed as a candidate for flight aboard the International Space Station. TDSE will study the growth of dendrites (treelike crystalline structures) in a transparent material (succinonitrile or SCN) that mimics the behavior of widely used iron-based metals. Basic work by three Space Shuttle missions of the Isothermal Dendritic Growth Expepriment (IDGE) is yielding new insights into virtually all industrially relevant metal and alloy forming operations. The TDSE is similar to IDGE, but will maintain a constant temperature while varying pressure on the dendrites. Shown here is an exploded view of major elements of TDSE. A similar view is available with labels. The principal investigator is Matthew Koss of College of the Holy Cross in Worcester, MA. Photo credit: NASA/Marshall Space Flight Center (MSFC)

  3. Transient Dendritic Solidification Experiment (TDSE)

    NASA Technical Reports Server (NTRS)

    2000-01-01

    The Transient Dendritic Solidification Experiment (TDSE) is being developed as a candidate for flight aboard the International Space Station. TDSE will study the growth of dendrites (treelike crystalline structures) in a transparent material (succinonitrile or SCN) that mimics the behavior or widely used iron-based metals. Basic work by three Space Shuttle missions of the Isothermal Dendritic Growth Experiment (IDGE) is yielding new insights into virtually all industrially relevant metal and alloy forming operations. The TDSE is similar to IDGE, but will maintain a constant temperature while varying pressure on the dendrites. Shown here is an exploded view of major elements of the TDSE. A similar view is availble without labels. The principal investigator is Matthew Koss of College of the Holy Cross in Worcester, MA. Photo credit: NASA/Marshall Space Flight Center (MSFC)

  4. Optimal Current Transfer in Dendrites

    PubMed Central

    Bird, Alex D.

    2016-01-01

    Integration of synaptic currents across an extensive dendritic tree is a prerequisite for computation in the brain. Dendritic tapering away from the soma has been suggested to both equalise contributions from synapses at different locations and maximise the current transfer to the soma. To find out how this is achieved precisely, an analytical solution for the current transfer in dendrites with arbitrary taper is required. We derive here an asymptotic approximation that accurately matches results from numerical simulations. From this we then determine the diameter profile that maximises the current transfer to the soma. We find a simple quadratic form that matches diameters obtained experimentally, indicating a fundamental architectural principle of the brain that links dendritic diameters to signal transmission. PMID:27145441

  5. EBI2 augments Tfh cell fate by promoting interaction with IL-2-quenching dendritic cells.

    PubMed

    Li, Jianhua; Lu, Erick; Yi, Tangsheng; Cyster, Jason G

    2016-05-01

    T follicular helper (Tfh) cells are a subset of T cells carrying the CD4 antigen; they are important in supporting plasma cell and germinal centre responses. The initial induction of Tfh cell properties occurs within the first few days after activation by antigen recognition on dendritic cells, although how dendritic cells promote this cell-fate decision is not fully understood. Moreover, although Tfh cells are uniquely defined by expression of the follicle-homing receptor CXCR5 (refs 1, 2), the guidance receptor promoting the earlier localization of activated T cells at the interface of the B-cell follicle and T zone has been unclear. Here we show that the G-protein-coupled receptor EBI2 (GPR183) and its ligand 7α,25-dihydroxycholesterol mediate positioning of activated CD4 T cells at the interface of the follicle and T zone. In this location they interact with activated dendritic cells and are exposed to Tfh-cell-promoting inducible co-stimulator (ICOS) ligand. Interleukin-2 (IL-2) is a cytokine that has multiple influences on T-cell fate, including negative regulation of Tfh cell differentiation. We demonstrate that activated dendritic cells in the outer T zone further augment Tfh cell differentiation by producing membrane and soluble forms of CD25, the IL-2 receptor α-chain, and quenching T-cell-derived IL-2. Mice lacking EBI2 in T cells or CD25 in dendritic cells have reduced Tfh cells and mount defective T-cell-dependent plasma cell and germinal centre responses. These findings demonstrate that distinct niches within the lymphoid organ T zone support distinct cell fate decisions, and they establish a function for dendritic-cell-derived CD25 in controlling IL-2 availability and T-cell differentiation.

  6. Cell of origin of transformed follicular lymphoma

    PubMed Central

    Kridel, Robert; Mottok, Anja; Farinha, Pedro; Ben-Neriah, Susana; Ennishi, Daisuke; Zheng, Yvonne; Chavez, Elizabeth A.; Shulha, Hennady P.; Tan, King; Chan, Fong Chun; Boyle, Merrill; Meissner, Barbara; Telenius, Adele; Sehn, Laurie H.; Marra, Marco A.; Shah, Sohrab P.; Steidl, Christian; Connors, Joseph M.; Scott, David W.

    2015-01-01

    Follicular lymphoma (FL) is an indolent disease but transforms in 2% to 3% of patients per year into aggressive, large cell lymphoma, a critical event in the course of the disease associated with increased lymphoma-related mortality. Early transformation cannot be accurately predicted at the time of FL diagnosis and the biology of transformed FL (TFL) is poorly understood. Here, we assembled a cohort of 126 diagnostic FL specimens including 40 patients experiencing transformation (<5 years) and 86 patients not experiencing transformation for at least 5 years. In addition, we assembled an overlapping cohort of 155 TFL patients, including 114 cases for which paired samples were available, and assessed temporal changes of routinely available biomarkers, outcome after transformation, as well as molecular subtypes of TFL. We report that the expression of IRF4 is an independent predictor of early transformation (Hazard ratio, 13.3; P < .001). We also show that composite histology at the time of transformation predicts favorable prognosis. Moreover, applying the Lymph2Cx digital gene expression assay for diffuse large B-cell lymphoma (DLBCL) cell-of-origin determination to 110 patients with DLBCL-like TFL, we demonstrate that TFL is of the germinal-center B-cell–like subtype in the majority of cases (80%) but that a significant proportion of cases is of the activated B-cell–like (ABC) subtype (16%). These latter cases are commonly negative for BCL2 translocation and arise preferentially from BCL2 translocation-negative and/or IRF4-expressing FLs. Our study demonstrates the existence of molecular heterogeneity in TFL as well as its relationship to the antecedent FL. PMID:26307535

  7. Computerized microscopic image analysis of follicular lymphoma

    NASA Astrophysics Data System (ADS)

    Sertel, Olcay; Kong, Jun; Lozanski, Gerard; Catalyurek, Umit; Saltz, Joel H.; Gurcan, Metin N.

    2008-03-01

    Follicular Lymphoma (FL) is a cancer arising from the lymphatic system. Originating from follicle center B cells, FL is mainly comprised of centrocytes (usually middle-to-small sized cells) and centroblasts (relatively large malignant cells). According to the World Health Organization's recommendations, there are three histological grades of FL characterized by the number of centroblasts per high-power field (hpf) of area 0.159 mm2. In current practice, these cells are manually counted from ten representative fields of follicles after visual examination of hematoxylin and eosin (H&E) stained slides by pathologists. Several studies clearly demonstrate the poor reproducibility of this grading system with very low inter-reader agreement. In this study, we are developing a computerized system to assist pathologists with this process. A hybrid approach that combines information from several slides with different stains has been developed. Thus, follicles are first detected from digitized microscopy images with immunohistochemistry (IHC) stains, (i.e., CD10 and CD20). The average sensitivity and specificity of the follicle detection tested on 30 images at 2×, 4× and 8× magnifications are 85.5+/-9.8% and 92.5+/-4.0%, respectively. Since the centroblasts detection is carried out in the H&E-stained slides, the follicles in the IHC-stained images are mapped to H&E-stained counterparts. To evaluate the centroblast differentiation capabilities of the system, 11 hpf images have been marked by an experienced pathologist who identified 41 centroblast cells and 53 non-centroblast cells. A non-supervised clustering process differentiates the centroblast cells from noncentroblast cells, resulting in 92.68% sensitivity and 90.57% specificity.

  8. Activating STAT6 mutations in follicular lymphoma

    PubMed Central

    Yildiz, Mehmet; Li, Hongxiu; Bernard, Denzil; Amin, Nisar A.; Ouillette, Peter; Jones, Siân; Saiya-Cork, Kamlai; Parkin, Brian; Jacobi, Kathryn; Shedden, Kerby; Wang, Shaomeng; Chang, Alfred E.; Kaminski, Mark S.

    2015-01-01

    Follicular lymphoma (FL) is the second most common non-Hodgkin lymphoma in the Western world. FL cell-intrinsic and cell-extrinsic factors influence FL biology and clinical outcome. To further our understanding of the genetic basis of FL, we performed whole-exome sequencing of 23 highly purified FL cases and 1 transformed FL case and expanded findings to a combined total of 114 FLs. We report recurrent mutations in the transcription factor STAT6 in 11% of FLs and identified the STAT6 amino acid residue 419 as a novel STAT6 mutation hotspot (p.419D/G, p.419D/A, and p.419D/H). FL-associated STAT6 mutations were activating, as evidenced by increased transactivation in HEK293T cell–based transfection/luciferase reporter assays, heightened interleukin-4 (IL-4) –induced activation of target genes in stable STAT6 transfected lymphoma cell lines, and elevated baseline expression levels of STAT6 target genes in primary FL B cells harboring mutant STAT6. Mechanistically, FL-associated STAT6 mutations facilitated nuclear residency of STAT6, independent of IL-4–induced STAT6-Y641 phosphorylation. Structural modeling of STAT6 based on the structure of the STAT1-DNA complex revealed that most FL-associated STAT6 mutants locate to the STAT6-DNA interface, potentially facilitating heightened interactions. The genetic and functional data combined strengthen the recognition of the IL-4/JAK/STAT6 axis as a driver of FL pathogenesis. PMID:25428220

  9. Cell of origin of transformed follicular lymphoma.

    PubMed

    Kridel, Robert; Mottok, Anja; Farinha, Pedro; Ben-Neriah, Susana; Ennishi, Daisuke; Zheng, Yvonne; Chavez, Elizabeth A; Shulha, Hennady P; Tan, King; Chan, Fong Chun; Boyle, Merrill; Meissner, Barbara; Telenius, Adele; Sehn, Laurie H; Marra, Marco A; Shah, Sohrab P; Steidl, Christian; Connors, Joseph M; Scott, David W; Gascoyne, Randy D

    2015-10-29

    Follicular lymphoma (FL) is an indolent disease but transforms in 2% to 3% of patients per year into aggressive, large cell lymphoma, a critical event in the course of the disease associated with increased lymphoma-related mortality. Early transformation cannot be accurately predicted at the time of FL diagnosis and the biology of transformed FL (TFL) is poorly understood. Here, we assembled a cohort of 126 diagnostic FL specimens including 40 patients experiencing transformation (<5 years) and 86 patients not experiencing transformation for at least 5 years. In addition, we assembled an overlapping cohort of 155 TFL patients, including 114 cases for which paired samples were available, and assessed temporal changes of routinely available biomarkers, outcome after transformation, as well as molecular subtypes of TFL. We report that the expression of IRF4 is an independent predictor of early transformation (Hazard ratio, 13.3; P < .001). We also show that composite histology at the time of transformation predicts favorable prognosis. Moreover, applying the Lymph2Cx digital gene expression assay for diffuse large B-cell lymphoma (DLBCL) cell-of-origin determination to 110 patients with DLBCL-like TFL, we demonstrate that TFL is of the germinal-center B-cell-like subtype in the majority of cases (80%) but that a significant proportion of cases is of the activated B-cell-like (ABC) subtype (16%). These latter cases are commonly negative for BCL2 translocation and arise preferentially from BCL2 translocation-negative and/or IRF4-expressing FLs. Our study demonstrates the existence of molecular heterogeneity in TFL as well as its relationship to the antecedent FL. PMID:26307535

  10. Cell of origin of transformed follicular lymphoma.

    PubMed

    Kridel, Robert; Mottok, Anja; Farinha, Pedro; Ben-Neriah, Susana; Ennishi, Daisuke; Zheng, Yvonne; Chavez, Elizabeth A; Shulha, Hennady P; Tan, King; Chan, Fong Chun; Boyle, Merrill; Meissner, Barbara; Telenius, Adele; Sehn, Laurie H; Marra, Marco A; Shah, Sohrab P; Steidl, Christian; Connors, Joseph M; Scott, David W; Gascoyne, Randy D

    2015-10-29

    Follicular lymphoma (FL) is an indolent disease but transforms in 2% to 3% of patients per year into aggressive, large cell lymphoma, a critical event in the course of the disease associated with increased lymphoma-related mortality. Early transformation cannot be accurately predicted at the time of FL diagnosis and the biology of transformed FL (TFL) is poorly understood. Here, we assembled a cohort of 126 diagnostic FL specimens including 40 patients experiencing transformation (<5 years) and 86 patients not experiencing transformation for at least 5 years. In addition, we assembled an overlapping cohort of 155 TFL patients, including 114 cases for which paired samples were available, and assessed temporal changes of routinely available biomarkers, outcome after transformation, as well as molecular subtypes of TFL. We report that the expression of IRF4 is an independent predictor of early transformation (Hazard ratio, 13.3; P < .001). We also show that composite histology at the time of transformation predicts favorable prognosis. Moreover, applying the Lymph2Cx digital gene expression assay for diffuse large B-cell lymphoma (DLBCL) cell-of-origin determination to 110 patients with DLBCL-like TFL, we demonstrate that TFL is of the germinal-center B-cell-like subtype in the majority of cases (80%) but that a significant proportion of cases is of the activated B-cell-like (ABC) subtype (16%). These latter cases are commonly negative for BCL2 translocation and arise preferentially from BCL2 translocation-negative and/or IRF4-expressing FLs. Our study demonstrates the existence of molecular heterogeneity in TFL as well as its relationship to the antecedent FL.

  11. Decitabine in Treating Patients With Metastatic Papillary Thyroid Cancer or Follicular Thyroid Cancer Unresponsive to Iodine I 131

    ClinicalTrials.gov

    2014-08-20

    Recurrent Thyroid Cancer; Stage IVA Follicular Thyroid Cancer; Stage IVA Papillary Thyroid Cancer; Stage IVB Follicular Thyroid Cancer; Stage IVB Papillary Thyroid Cancer; Stage IVC Follicular Thyroid Cancer; Stage IVC Papillary Thyroid Cancer

  12. Follicular progesterone elevations with ovulation induction for IVF.

    PubMed

    Kasum, Miro; Simunić, Velimir; Vrčić, Hrvoje; Stanić, Patrik; Orešković, Slavko; Beketić-Orešković, Lidija

    2014-08-01

    The purpose of this review is to analyse the sources and effects of follicular progesterone elevations during ovarian stimulation, with the underlying mechanisms and preventive strategies on the in vitro fertilisation pregnancy outcome. In the early follicular phase, a flare-up effect of gonadotrophin releasing hormone (GnRH) agonists and incomplete luteolysis in GnRH antagonist regimens can result in significant elevations of progesterone. In the late follicular phase, progesterone elevations in GnRH analogue cycles are the result of the ovarian stimulation itself, driven by high follicle stimulating hormone dosage, estradiol levels, the number of follicles and oocytes. It seems that progesterone elevations (> or = 1.5 ng/mL or 4.77 nmol/L) have a detrimental effect on the outcome of pregnancy, accelerating the endometrial maturation. The most appropriate choice to avoid the negative effects of follicular progesterone elevations is to cancel fresh embryo transfer and to transfer frozen-thawed embryos in natural cycles. To prevent follicular phase elevations it might be preferable to use milder stimulation protocols, earlier trigger of ovulation in high responders and single-blastocyst transfer on day 5. The optimal GnRH analogue protocols during the entire stimulation period appear to be the long agonist as well as "long" and long GnRH antagonist regimens.

  13. Metformin down-regulates endometrial carcinoma cell secretion of IGF-1 and expression of IGF-1R.

    PubMed

    Zhang, Yu; Li, Meng-Xiong; Wang, Huan; Zeng, Zheng; Li, Xiao-Mao

    2015-01-01

    As metformin can inhibit endometrial carcinoma (EC) cell growth and the insulin growth factor (IGF) system is active in EC, the question of whether t can regulate endometrial carcinoma cell secretion of IGF-1 or expression of IGF-1 receptor (IGF-1R) is of interest. In this study, serum IGF-1 levels in EC patients were found to be comparable with that in the non EC patients (p>0.05). However, the IGF-1 level in the medium of cultured cells after treatment with metformin was decreased (p<0.05). IGF-1R was highly expressed in human endometrial carcinoma paraffin sections, but IGF-1R and phosphor-protein kinase B/protein kinase B (p-Akt/ Akt) expression was down-regulated after metformin treatment (p<0.05). In summary, metformin can reduce the secretion of IGF-1 by Ishikawa and JEC EC cell lines and their expression of IGF-1R to deactivate downstream signaling involving the PI-3K/Akt pathway to inhibit endometrial carcinoma cell growth.

  14. Epithelial Cell Secretions from the Human Female Reproductive Tract Inhibit Sexually Transmitted Pathogens and Candida albicans but not Lactobacillus

    PubMed Central

    Wira, CR; Ghosh, M; Smith, JM; Shen, L; Connor, RI; Sundstrom, P; Frechette, Gregory M.; Hill, EM; Fahey, JV

    2011-01-01

    Female reproductive tract (FRT) epithelial cells protect against potential pathogens and sexually transmitted infections. The purpose of this study was to determine if epithelial cells from the upper FRT secrete antimicrobials that inhibit reproductive tract pathogens which threaten women's health. Apical secretions from primary cultures of Fallopian tube, uterine, cervical and ectocervical epithelial cells were incubated with Neisseria gonorrhoeae, Candida albicans (yeast and hyphal forms), HIV-1, and Lactobacillus crispatus, prior to being tested for their ability to grow and/or infect target cells. Epithelial cell secretions from the upper FRT inhibit N. gonorrhoeae and both forms of Candida, as well as reduce HIV-1 (R5) infection of target cells. In contrast, none had an inhibitory effect on L. crispatus. Cytokines and chemokines analysis in uterine secretions revealed several molecules that could account for pathogen inhibition. These findings provide definitive evidence for the critical role of epithelial cells in protecting the FRT from infections, without comprising the beneficial presence of L. crispatus, which is part of the normal vaginal microflora of humans. PMID:21048705

  15. Adipose Tissue-Derived Stem Cell Secreted IGF-1 Protects Myoblasts from the Negative Effect of Myostatin

    PubMed Central

    Gehmert, Sebastian; Nerlich, Michael; Gosau, Martin; Klein, Silvan; Schreml, Stephan; Prantl, Lukas

    2014-01-01

    Myostatin, a TGF-β family member, is associated with inhibition of muscle growth and differentiation and might interact with the IGF-1 signaling pathway. Since IGF-1 is secreted at a bioactive level by adipose tissue-derived mesenchymal stem cells (ASCs), these cells (ASCs) provide a therapeutic option for Duchenne Muscular Dystrophy (DMD). But the protective effect of stem cell secreted IGF-1 on myoblast under high level of myostatin remains unclear. In the present study murine myoblasts were exposed to myostatin under presence of ASCs conditioned medium and investigated for proliferation and apoptosis. The protective effect of IGF-1 was further examined by using IGF-1 neutralizing and receptor antibodies as well as gene silencing RNAi technology. MyoD expression was detected to identify impact of IGF-1 on myoblasts differentiation when exposed to myostatin. IGF-1 was accountable for 43.6% of the antiapoptotic impact and 48.8% for the proliferative effect of ASCs conditioned medium. Furthermore, IGF-1 restored mRNA and protein MyoD expression of myoblasts under risk. Beside fusion and transdifferentiation the beneficial effect of ASCs is mediated by paracrine secreted cytokines, particularly IGF-1. The present study underlines the potential of ASCs as a therapeutic option for Duchenne muscular dystrophy and other dystrophic muscle diseases. PMID:24575400

  16. Pegfilgrastim and Rituximab in Treating Patients With Untreated, Relapsed, or Refractory Follicular Lymphoma, Small Lymphocytic Lymphoma, or Marginal Zone Lymphoma

    ClinicalTrials.gov

    2016-09-20

    Contiguous Stage II Grade 1 Follicular Lymphoma; Contiguous Stage II Grade 2 Follicular Lymphoma; Contiguous Stage II Grade 3 Follicular Lymphoma; Contiguous Stage II Marginal Zone Lymphoma; Contiguous Stage II Small Lymphocytic Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Grade 1 Follicular Lymphoma; Noncontiguous Stage II Grade 2 Follicular Lymphoma; Noncontiguous Stage II Grade 3 Follicular Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Splenic Marginal Zone Lymphoma; Stage I Grade 1 Follicular Lymphoma; Stage I Grade 2 Follicular Lymphoma; Stage I Grade 3 Follicular Lymphoma; Stage I Marginal Zone Lymphoma; Stage I Small Lymphocytic Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Small Lymphocytic Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Small Lymphocytic Lymphoma

  17. Ovarian Follicular Atresia of Ewes during Spring Puerperium

    PubMed Central

    Vlčková, Radoslava; Sopková, Drahomíra; Pošivák, Ján; Valocký, Igor

    2012-01-01

    The distribution of healthy and atretic follicles on the ovarian surface of improved Valachian ewes 17, 24, and 32 days postpartum is reported in this study. The number of healthy follicles was higher on day 24 postpartum and their mean diameter tended to increase to day 32 (P < 0.05) with the greatest diameter of 5 mm. 78–81% of atretic follicles ≥3 mm in diameter was observed where apoptosis began in the follicular cells situated at the follicular cavity. The early atretic follicles are characterized by the presence of mitotic pictures. In one ewe 24 days postpartum, small regressive follicular cysts were observed. Contracting atresia is characterized by thickening of the theca interna even to 190 μm. Progesterone and oestradiol-17β concentrations were maintained at relatively low levels, but with no significant difference between the days postpartum. PMID:22567543

  18. Hyperfunctioning metastatic follicular thyroid carcinoma in Pendred's syndrome

    SciTech Connect

    Abs, R.; Verhelst, J.; Schoofs, E.; De Somer, E. )

    1991-04-15

    A 66-year-old woman with Pendred's syndrome underwent a partial thyroidectomy when she was 17 years old. At the age of 52 years, she had a second thyroid operation because of hyperthyroidism due to a toxic multinodular goiter with a mediastinal extension consisting of several separate nodules. Five years later a hyperfunctioning metastatic follicular carcinoma was diagnosed histologically. After treatment with radioactive iodine, the patient was well. To the authors' knowledge, this is the first description of a metastatic follicular thyroid carcinoma in Pendred's syndrome and the first report of hyperthyroidism occurring after malignant degeneration of a dyshormonogenetic goiter.

  19. Lysophosphatidic acid induces osteocyte dendrite outgrowth

    SciTech Connect

    Karagiosis, Sue A.; Karin, Norm J.

    2007-05-25

    A method was developed to measure dendrite formation in bone cells. Lysophosphatidic acid (LPA) was found to stimulate dendrite outgrowth. It is postulated that LPA plays a role in regulating the osteocyte network in vivo.

  20. Gravitational effects in dendritic growth

    NASA Technical Reports Server (NTRS)

    Glicksman, M. E.; Singh, N. B.; Chopra, M.

    1983-01-01

    The theories of diffusion-controlled dendritic crystallization will be reviewed briefly, along with recently published critical experiments on the kinetics and morphology of dendritic growth in pure substances. The influence of the gravitational body force on dendrite growth kinetics will be shown to be highly dependent on the growth orientation with respect to the gravity vector and on the level of the thermal supercooling. In fact, an abrupt transition occurs at a critical supercooling, above which diffusional transport dominates the growth process and below which convective transport dominates. Our most recent work on binary mixtures shows that dilute solute additions influence the crystallization process indirectly, by altering the interfacial stability, rather than by directly affecting the transport mode. Directions for future studies in this field will also be discussed.

  1. Induction of Protective Immunity against Eimeria tenella, Eimeria maxima, and Eimeria acervulina Infections Using Dendritic Cell-Derived Exosomes

    PubMed Central

    Gallego, Margarita; Lee, Sung Hyen; Lillehoj, Hyun Soon; Quilez, Joaquin; Lillehoj, Erik P.; Sánchez-Acedo, Caridad

    2012-01-01

    This study describes a novel immunization strategy against avian coccidiosis using exosomes derived from Eimeria parasite antigen (Ag)-loaded dendritic cells (DCs). Chicken intestinal DCs were isolated and pulsed in vitro with a mixture of sporozoite-extracted Ags from Eimeria tenella, E. maxima, and E. acervulina, and the cell-derived exosomes were isolated. Chickens were nonimmunized or immunized intramuscularly with exosomes and subsequently noninfected or coinfected with E. tenella, E. maxima, and E. acervulina oocysts. Immune parameters compared among the nonimmunized/noninfected, nonimmunized/infected, and immunized/infected groups were the numbers of cells secreting Th1 cytokines, Th2 cytokines, interleukin-16 (IL-16), and Ag-reactive antibodies in vitro and in vivo readouts of protective immunity against Eimeria infection. Cecal tonsils, Peyer's patches, and spleens of immunized and infected chickens had increased numbers of cells secreting the IL-16 and the Th1 cytokines IL-2 and gamma interferon, greater Ag-stimulated proliferative responses, and higher numbers of Ag-reactive IgG- and IgA-producing cells following in vitro stimulation with the sporozoite Ags compared with the nonimmunized/noninfected and nonimmunized/infected controls. In contrast, the numbers of cells secreting the Th2 cytokines IL-4 and IL-10 were diminished in immunized and infected chickens compared with the nonimmunized/noninfected and the nonimmunized/infected controls. Chickens immunized with Ag-loaded exosomes and infected in vivo with Eimeria oocysts had increased body weight gains, reduced feed conversion ratios, diminished fecal oocyst shedding, lessened intestinal lesion scores, and reduced mortality compared with the nonimmunized/infected controls. These results suggest that successful field vaccination against avian coccidiosis using exosomes derived from DCs incubated with Ags isolated from Eimeria species may be possible. PMID:22354026

  2. Ovarian follicular dynamics after aromatizable or non aromatizable neonatal androgenization.

    PubMed

    Anesetti, Gabriel; Chávez-Genaro, Rebeca

    2016-10-01

    The effects of neonatal testosterone or dihydrotestosterone exposure on ovarian follicular dynamics were analysed at prepubertal, pubertal or adult age in Wistar rats. Both androgens induced a transitory increase on follicular endowment that was partially corrected at puberty. At adult age testosterone prevented ovulation, without significant modifications on follicular dynamics. An increased number of cystic structures were observed from puberty to adult age. However, ovaries of rats treated with dihydrotestosterone showed follicles with evident morphological alterations in granulosa and thecal layers although several corpora lutea were observed. A significant increase in preantral follicles and few cystic structures were detected at advanced adulthood. The size of cyst increased with age. No immunohistochemical changes on growth factors or enzymes related to steroidogenesis in growing follicles were obvious in any group. In both androgenized groups, cysts shared immunohistochemical characteristics exhibited by preovulatory follicles but they were unable to ovulate spontaneously. Our results provide an insight into the role of different androgens in female reproductive system development, indicating a direct effect of dihydrotestosterone on ovarian tissues whereas a central effect would be the main feature of neonatal testosterone exposure. Heterogeneous clinical manifestations seen in pathologies such as polycystic ovary syndrome among women could be associated with subtle hormonal changes during follicular population development. PMID:27541036

  3. A fine romance: T follicular helper cells and B cells.

    PubMed

    King, Cecile

    2011-06-24

    T follicular helper (Tfh) cells help B cells to generate affinity-matured antibodies. Three papers in this issue of Immunity (Choi et al., 2011; Kerfoot et al., 2011; Kitano et al., 2011) provide information about the reciprocal relationship between B cells and Tfh cells.

  4. Advances in hair transplantation: longitudinal partial follicular unit transplantation.

    PubMed

    Gho, Coen G; Neumann, H A Martino

    2015-01-01

    There are different techniques of hair transplantation. The most common and known hair transplantation methods are the 'strip' method, where a strip of skin containing hair follicles is removed, cut into grafts and implanted in the recipient area, and the follicle unit extraction (FUE) method, in which whole follicle units are extracted one by one and implanted one by one back into the recipient area. The FUE method is more patient friendly and leaves only tiny scars compared to the strip method, which leaves visible linear scars at the donor area. Both methods, however, have the major disadvantage that the extracted hair follicles are removed and the availability of donor hair follicles are limited and results in a decrease in hair density, as no re-grow will occur in the donor area. Since partial longitudinal-follicular unit transplantation (PL-FUT) extracts partial longitudinal follicular units that can be used as complete follicular units to regenerate completely differentiated hair growth and the partial follicular units that remain in the dermis in the donor area can survive and produce hair, PL-FUT enables us to multiply hair follicles in vivo while preserving the donor area. Although this technique is suitable for androgenic alopecia, PL-FUT could also be suitable in persons who have a relative small donor area compared to the recipient area like burn victims, as well as scarring alopecia's like frontal fibrosing alopecia.

  5. A fine romance: T follicular helper cells and B cells.

    PubMed

    King, Cecile

    2011-06-24

    T follicular helper (Tfh) cells help B cells to generate affinity-matured antibodies. Three papers in this issue of Immunity (Choi et al., 2011; Kerfoot et al., 2011; Kitano et al., 2011) provide information about the reciprocal relationship between B cells and Tfh cells. PMID:21703537

  6. Proteomic profiling of follicular and papillary thyroid tumors

    PubMed Central

    Sofiadis, Anastasios; Becker, Susanne; Hellman, Ulf; Hultin-Rosenberg, Lina; Dinets, Andrii; Hulchiy, Mykola; Zedenius, Jan; Wallin, Göran; Foukakis, Theodoros; Höög, Anders; Auer, Gert; Lehtiö, Janne; Larsson, Catharina

    2012-01-01

    Objective Thyroid proteomics is a new direction in thyroid cancer research aiming at etiological understanding and biomarker identification for improved diagnosis. Methods Two-dimensional electrophoresis was applied to cytosolic protein extracts from frozen thyroid samples (ten follicular adenomas, nine follicular carcinomas, ten papillary carcinomas, and ten reference thyroids). Spots with differential expression were revealed by image and multivariate statistical analyses, and identified by mass spectrometry. Results A set of 25 protein spots significant for discriminating between the sample groups was identified. Proteins identified for nine of these spots were studied further including 14-3-3 protein beta/alpha, epsilon, and zeta/delta, peroxiredoxin 6, selenium-binding protein 1, protein disulfide-isomerase precursor, annexin A5 (ANXA5), tubulin alpha-1B chain, and α1-antitrypsin precursor. This subset of protein spots carried the same predictive power in differentiating between follicular carcinoma and adenoma or between follicular and papillary carcinoma, as compared with the larger set of 25 spots. Protein expression in the sample groups was demonstrated by western blot analyses. For ANXA5 and the 14-3-3 proteins, expression in tumor cell cytoplasm was demonstrated by immunohistochemistry both in the sample groups and an independent series of papillary thyroid carcinomas. Conclusion The proteins identified confirm previous findings in thyroid proteomics, and suggest additional proteins as dysregulated in thyroid tumors. PMID:22275472

  7. Comparative Proteomic Analysis of Yak Follicular Fluid during Estrus

    PubMed Central

    Guo, Xian; Pei, Jie; Ding, Xuezhi; Chu, Min; Bao, Pengjia; Wu, Xiaoyun; Liang, Chunnian; Yan, Ping

    2016-01-01

    The breeding of yaks is highly seasonal, there are many crucial proteins involved in the reproduction control program, especially in follicular development. In order to isolate differential proteins between mature and immature follicular fluid (FF) of yak, the FF from yak follicles with different sizes were sampled respectively, and two-dimensional gel electrophoresis (2-DE) of the proteins was carried out. After silver staining, the Image Master 2D platinum software was used for protein analysis and matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS) was performed for differential protein identification. The expression level of transferrin and enolase superfamily member 1 (ENOSF1) was determined by Western blotting for verification analysis. The results showed that 2-DE obtained an electrophoresis map of proteins from mature and immature yak FF with high resolution and repeatability. A comparison of protein profiles identified 12 differently expressed proteins, out of which 10 of them were upregulated while 2 were downregulated. Western blotting showed that the expression of transferrin and ENOSF1 was enhanced with follicular development. Both the obtained protein profiles and the differently expressed proteins identified in this study provided experimental data related to follicular development during yak breeding seasons. This study also laid the foundation for understanding the microenvironment during oocyte development. PMID:26954118

  8. Pattern and manipulation of follicular development in Bos indicus cattle.

    PubMed

    Bó, G A; Baruselli, P S; Martínez, M F

    2003-10-15

    Bos indicus cattle are widespread in tropical regions due to their adaptation to these environments. Although data on reproductive performance have indicated both inferior and superior results for B. indicus cattle, there is little doubt that B. indicus cattle are superior than Bos taurus cattle when they are both kept in tropical or subtropical environments, where stressors like hot temperatures, humidity, ectoparasites and low quality forages are greater. Reproductive endocrinology and oestrus behaviour of the B. indicus cattle have been studied for over 30 years; however, the application of technologies such as real time ultrasonography and Heat-Watch systems has expanded our knowledge on the ovarian follicular-wave dynamics during the oestrous cycle and the time of ovulation. Ovarian follicular dynamics in B. indicus cattle is characterised by the occurrence of two, three or sometimes four waves of follicular development. While dominance is similar to that in B. taurus cattle, maximum diameters of the dominant follicle and CL are smaller than those reported in B. taurus and are probably due to a lower capacity for LH secretion than in B. taurus. Duration of oestrus is approximately 10 h and the interval from oestrus to ovulation is about 27 h. However, the variability in response to prostaglandin F2alpha (PGF) treatments and the difficulty for oestrus detection in B. indicus cattle have limited the widespread application of artificial insemination (AI) and emphasizes the need for treatments that control follicular development and ovulation. Follicular-wave development in B. indicus cattle can be controlled mechanically by ultrasound-guided follicle ablation, or hormonally by treatments with GnRH or oestradiol and progestogen/progesterone in combination. Treatments with GnRH plus PGF and a second GnRH (synchronization protocol known as Ovsynch) or oestradiol benzoate (known as GPE) have resulted in acceptable pregnancy rates after fixed-time AI (FTAI) in cycling

  9. [DIAGNOSTIC AND TREATMENT STRATEGY IN FOLLICULAR TUMOR OF THYROID GLAND].

    PubMed

    Mikhaĭlova, M V; Zubarovskiĭ, I N; Osipenko, S K

    2015-01-01

    The article is based on the treatment results of 44 patients with follicular tunor of thyroid gland. A staged morphological assessment of thyroid nodes was performed for all patients: in case of preoperative fine-needle biopsy, urgent intraoperative study and according to results of final histological research. The urgent histological study of surgical material was conducted for 44 patients with diagnosis "follicular tumor" according to fine-needle biopsy. The data of final histological study were matched with findings of intraoperative research. A micro-follicular adenoma was detected in 22 patients (50%) and 6 (13,6%) patients had this diagnosis combined with autoimmune thyroiditis. The general part of patients didn't changed in final study, but the rate of diagnosis "micro-follicular adenoma against the background of autoimmune thyroiditis" increased. Papillary carcinoma was revealed in 5 (11,4%) patients and follicular cancer had 4 (9,1%) patients detected in intraoperative study and 3 (6,8%) more patients according to data of final research. The histopathologic feature of colloid goiter was observed in 7 (15,9%) cases and a part of such patients reduced to 6,8% during final study. One of the patients (2,3%) had final diagnosis "oncocytoma". In case of thyroid nodules detection the needle biopsy should be carried out regardless to the size of nodule. The authors recommended performing the surgery with the urgent histological study in case of undetermined histological report. The following surgical strategy was specified by the results of the urgent histological report.

  10. Antioxidant defense in the follicular fluid of water buffalo.

    PubMed

    Cassano, E; Tosto, L; Balestrieri, M; Zicarelli, L; Abrescia, P

    1999-01-01

    Oxidative damages to the oocyte or follicular cells were suggested to trigger atresia. In water buffalo, loss of the blood-follicle barrier sieving effect on the diffusion of plasma haptoglobin was previously found to be associated with atretic oocytes. The redox status of water buffalo follicles was evaluated by measuring in follicular fluid both the total antioxidant capacity (TAC), expressed as Trolox equivalents, and the concentration of specific free radical scavengers, determined by high-performance liquid chromatography. Among follicles at random stages of the reproductive cycle (n = 74), a number (n = 32) were analyzed also for the cumulus-oocyte morphology or plasma haptoglobin penetration. The haptoglobin follicular concentration compatible with the barrier selectivity function was calculated to be less than 53% of the concentration in plasma. The data on TAC, retinol, alpha-tocopherol, gamma-tocopherol, ascorbic acid, and uric acid fluctuated in a wide range. The relative (follicular vs. plasmatic) levels of alpha-tocopherol were found to be negatively correlated with those of retinol (p < 0.01). In the follicles, the alpha-tocopherol levels were 1.25 +/- 0.35 or 1.99 +/- 0.72 microM when the haptoglobin concentration was <53 or >53% of the concentration in plasma, respectively. The concentration of ascorbic acid or uric acid was higher (up to 10- or 30-fold, respectively) in follicular fluid than in plasma. Fluids containing haptoglobin >53% or associated with cumulus-oocyte complexes of bad quality displayed levels of uric acid about 20-fold higher than in plasma. The results suggest that a high penetration of haptoglobin in the follicle and cumulus-oocyte degradation is associated with alterations of the level of the major antioxidants, particularly with enhancement of the uric acid concentration.

  11. Dendritic polyglycerols for biomedical applications.

    PubMed

    Calderón, Marcelo; Quadir, Mohiuddin Abdul; Sharma, Sunil Kumar; Haag, Rainer

    2010-01-12

    The application of nanotechnology in medicine and pharmaceuticals is a rapidly advancing field that is quickly gaining acceptance and recognition as an independent area of research called "nanomedicine". Urgent needs in this field, however, are biocompatible and bioactive materials for antifouling surfaces and nanoparticles for drug delivery. Therefore, extensive attention has been given to the design and development of new macromolecular structures. Among the various polymeric architectures, dendritic ("treelike") polymers have experienced an exponential development due to their highly branched, multifunctional, and well-defined structures. This Review describes the diverse syntheses and biomedical applications of dendritic polyglycerols (PGs). These polymers exhibit good chemical stability and inertness under biological conditions and are highly biocompatible. Oligoglycerols and their fatty acid esters are FDA-approved and are already being used in a variety of consumer applications, e.g., cosmetics and toiletries, food industries, cleaning and softening agents, pharmaceuticals, polymers and polymer additives, printing photographing materials, and electronics. Herein, we present the current status of dendritic PGs as functional dendritic architectures with particular focus on their application in nanomedicine, in drug, dye, and gene delivery, as well as in regenerative medicine in the form of non-fouling surfaces and matrix materials.

  12. Advanced dendritic web growth development

    NASA Technical Reports Server (NTRS)

    Hopkins, R. H.

    1985-01-01

    A program to develop the technology of the silicon dendritic web ribbon growth process is examined. The effort is being concentrated on the area rate and quality requirements necessary to meet the JPL/DOE goals for terrestrial PV applications. Closed loop web growth system development and stress reduction for high area rate growth is considered.

  13. Wiring dendrites in layers and columns.

    PubMed

    Luo, Jiangnan; McQueen, Philip G; Shi, Bo; Lee, Chi-Hon; Ting, Chun-Yuan

    2016-06-01

    The most striking structure in the nervous system is the complex yet stereotyped morphology of the neuronal dendritic tree. Dendritic morphologies and the connections they make govern information flow and integration in the brain. The fundamental mechanisms that regulate dendritic outgrowth and branching are subjects of extensive study. In this review, we summarize recent advances in the molecular and cellular mechanisms for routing dendrites in layers and columns, prevalent organizational structures in the brain. We highlight how dendritic patterning influences the formation of synaptic circuits. PMID:27315108

  14. Dendritic solidification of alloys in low gravity

    NASA Astrophysics Data System (ADS)

    Curreri, P. A.; Lee, J. E.; Stefanescu, D. M.

    1988-11-01

    Gravity-driven convective flow influences dendrite morphology, interdendritic fluid flow, dendrite interface morphology, casting macrosegregation, formation of channel type casting defects, and casting grain structure. Dendritic solidification experiments during multiple parabolic aircraft maneuvers for iron-carbon type alloys and superalloys show increased dendritic spacing in low-gravity periods. Larger dendrite spacings for low-gravity solidification have also been reported for sounding rocket and space laboratory experiments for metal-model and binary alloys. Convection decreases local solidification time and increases the rate of interdendritic solute removal. The elimination of convection in low gravity is thus expected to increase dendritic spacing. Convection's effect on dendritic arm coarsening is expected to be dependent on the coarsening mechanism. Decreased coarsening in low gravity found for Al-Cu is indicative of coarsening predominately by arm coalescence.

  15. [Follicular development during menstrual cycle and the levels of steroid hormones in the follicular fluid of women with infertility of inflammatory origin].

    PubMed

    Ivaniuta, L I; Travianko, T D; Raksha, I I

    1990-06-01

    Gonadal hormone levels have been evaluated in the follicular fluid of 67 women with tubal and peritoneal infertility. Follicular fluid concentrations of estradiol, progesterone and testosterone were compared with sonographically ascertained follicle sizes and growth rates. The results indicate a high incidence of peripheral damage of the hypothalamic-pituitary-ovarian axis in women with inflammatory diseases of the internal genitalia.

  16. Molecular and cellular mechanisms for the regulation of ovarian follicular function in cows

    PubMed Central

    SHIMIZU, Takashi

    2016-01-01

    Ovary is an important organ that houses the oocytes (reproductive cell). Oocyte growth depends on the function of follicular cells such as the granulosa and theca cells. Two-cell two gonadotropin systems are associated with oocyte growth and follicular cell functions. In addition to these systems, it is also known that several growth factors regulate oocyte growth and follicular cell functions. Vascular endothelial growth factor (VEGF) is involved in thecal vasculature during follicular development and the suppression of granulosa cell apoptosis. Metabolic factors such as insulin, growth hormone (GH) and insulin-like growth factor 1 (IGF-1) also play critical roles in the process of follicular development and growth. These factors are associated not only with follicular development, but also with follicular cell function. Steroid hormones (estrogens, androgens, and progestins) that are secreted from follicular cells influence the function of the female genital tract and its affect the susceptibility to bacterial infection. This review covers our current understanding of the mechanisms by which gonadotrophins and/or steroid hormones regulate the growth factors in the follicular cells of the bovine ovary. In addition, this review describes the effect of endotoxin on the function of follicular cells. PMID:27097851

  17. Molecular and cellular mechanisms for the regulation of ovarian follicular function in cows.

    PubMed

    Shimizu, Takashi

    2016-08-25

    Ovary is an important organ that houses the oocytes (reproductive cell). Oocyte growth depends on the function of follicular cells such as the granulosa and theca cells. Two-cell two gonadotropin systems are associated with oocyte growth and follicular cell functions. In addition to these systems, it is also known that several growth factors regulate oocyte growth and follicular cell functions. Vascular endothelial growth factor (VEGF) is involved in thecal vasculature during follicular development and the suppression of granulosa cell apoptosis. Metabolic factors such as insulin, growth hormone (GH) and insulin-like growth factor 1 (IGF-1) also play critical roles in the process of follicular development and growth. These factors are associated not only with follicular development, but also with follicular cell function. Steroid hormones (estrogens, androgens, and progestins) that are secreted from follicular cells influence the function of the female genital tract and its affect the susceptibility to bacterial infection. This review covers our current understanding of the mechanisms by which gonadotrophins and/or steroid hormones regulate the growth factors in the follicular cells of the bovine ovary. In addition, this review describes the effect of endotoxin on the function of follicular cells. PMID:27097851

  18. CYTOCHEMICAL LOCALIZATION OF ENDOGENOUS PEROXIDASE IN THYROID FOLLICULAR CELLS

    PubMed Central

    Strum, Judy M.; Karnovsky, Morris J.

    1970-01-01

    Endogenous peroxidase activity in rat thyroid follicular cells is demonstrated cytochemically. Following perfusion fixation of the thyroid gland, small blocks of tissue are incubated in a medium containing substrate for peroxidase, before being postfixed in osmium tetroxide, and processed for electron microscopy. Peroxidase activity is found in thyroid follicular cells in the following sites: (a) the perinuclear cisternae, (b) the cisternae of the endoplasmic reticulum, (c) the inner few lamellae of the Golgi complex, (d) within vesicles, particularly those found apically, and (e) associated with the external surfaces of the microvilli that project apically from the cell into the colloid. In keeping with the radioautographic evidence of others and the postulated role of thyroid peroxidase in iodination, it is suggested that the microvillous apical cell border is the major site where iodination occurs. However, that apical vesicles also play a role in iodination cannot be excluded. The in vitro effect of cyanide, aminotriazole, and thiourea is also discussed. PMID:4190069

  19. Microtubule nucleation and organization in dendrites.

    PubMed

    Delandre, Caroline; Amikura, Reiko; Moore, Adrian W

    2016-07-01

    Dendrite branching is an essential process for building complex nervous systems. It determines the number, distribution and integration of inputs into a neuron, and is regulated to create the diverse dendrite arbor branching patterns characteristic of different neuron types. The microtubule cytoskeleton is critical to provide structure and exert force during dendrite branching. It also supports the functional requirements of dendrites, reflected by differential microtubule architectural organization between neuron types, illustrated here for sensory neurons. Both anterograde and retrograde microtubule polymerization occur within growing dendrites, and recent studies indicate that branching is enhanced by anterograde microtubule polymerization events in nascent branches. The polarities of microtubule polymerization events are regulated by the position and orientation of microtubule nucleation events in the dendrite arbor. Golgi outposts are a primary microtubule nucleation center in dendrites and share common nucleation machinery with the centrosome. In addition, pre-existing dendrite microtubules may act as nucleation sites. We discuss how balancing the activities of distinct nucleation machineries within the growing dendrite can alter microtubule polymerization polarity and dendrite branching, and how regulating this balance can generate neuron type-specific morphologies. PMID:27097122

  20. A comparison of the effects of gastrin, somatostatin and dopamine receptor ligands on rat gastric enterochromaffin-like cell secretion and proliferation.

    PubMed

    Kidd, M; Modlin, I M; Black, J W; Boyce, M; Culler, M

    2007-10-01

    Gastrin regulates ECL cell histamine release and is a critical determinant of acid secretion. ECL cell secretion and proliferation is inhibited by gastrin antagonists and somatostatin but little is known about the role of dopamine agonists in this process. Since the ECL cell exhibits all three classes of receptor we evaluated and compared the effects of the gastrin receptor antagonist, (YF476), lanreotide (SST agonist) and novel dopaminergic agents (BIM53061 and BIM27A760) on ECL cell histamine secretion and proliferation. Highly enriched (>98%) ECL cell preparations prepared from rat gastric mucosa using a FACS approach were studied. Real-time PCR confirmed presence of the CCK2, SS2 and SS5 and D1 receptors on ECL cells. YF476 inhibited histamine secretion and proliferation with IC(50)s of 1.25 nM and 1.3 x 10(-11) M respectively, values 10-1000x more potent than L365,260. Lanreotide inhibited secretion and proliferation (2.2 nM, 1.9 x 10(-10) M) and increased YF476-inhibited proliferation a further 5-fold. The dopamine agonist, BIM53061, inhibited gastrin-mediated ECL cell secretion and proliferation (17 nM, 6 x 10(-10) M) as did the novel dopamine/somatostatin chimera BIM23A760 (22 nM, 4.9 x 10(-10) M). Our studies demonstrate that the gastrin receptor antagonist, YF476, is the most potent inhibitor of ECL cell histamine secretion and proliferation. Lanreotide, a dopamine agonist and a dopamine/somatostatin chimera inhibited ECL cell function but were 10-1000x less potent than YF476. Agents that selectively target the CCK2 receptor may provide alternative therapeutic strategies for gastrin-mediated gastrointestinal cell secretion and proliferation such as evident in the hypergastrinemic gastric carcinoids associated with low acid states.

  1. Conjunctival goblet cell secretion stimulated by leukotrienes is reduced by resolvins D1 and E1 to promote resolution of inflammation.

    PubMed

    Dartt, Darlene A; Hodges, Robin R; Li, Dayu; Shatos, Marie A; Lashkari, Kameran; Serhan, Charles N

    2011-04-01

    The conjunctiva is a mucous membrane that covers the sclera and lines the inside of the eyelids. Throughout the conjunctiva are goblet cells that secrete mucins to protect the eye. Chronic inflammatory diseases such as allergic conjunctivitis and early dry eye lead to increased goblet cell mucin secretion into tears and ocular surface disease. The purpose of this study was to determine the actions of the inflammatory mediators, the leukotrienes and the proresolution resolvins, on secretion from cultured rat and human conjunctival goblet cells. We found that both cysteinyl leukotriene (CysLT) receptors, CysLT(1) and CysLT(2,) were present in rat conjunctiva and in rat and human cultured conjunctival goblet cells. All leukotrienes LTB(4), LTC(4), LTD(4), and LTE(4), as well as PGD(2), stimulated goblet cell secretion in rat goblet cells. LTD(4) and LTE(4) increased the intracellular Ca(2+) concentration ([Ca(2+)](i)), and LTD(4) activated ERK1/2. The CysLT(1) receptor antagonist MK571 significantly decreased LTD(4)-stimulated rat goblet cell secretion and the increase in [Ca(2+)](i). Resolvins D1 (RvD1) and E1 (RvE1) completely reduced LTD(4)-stimulated goblet cell secretion in cultured rat goblet cells. LTD(4)-induced secretion from human goblet cells was blocked by RvD1. RvD1 and RvE1 prevented LTD(4)- and LTE(4)-stimulated increases in [Ca(2+)](i), as well as LTD(4) activation of ERK1/2. We conclude that cysteinyl leukotrienes stimulate conjunctival goblet cell mucous secretion with LTD(4) using the CysLT(1) receptor. Stimulated secretion is terminated by preventing the increase in [Ca(2+)](i) and activation of ERK1/2 by RvD1 and RvE1.

  2. Lipid dynamics at dendritic spines.

    PubMed

    Dotti, Carlos Gerardo; Esteban, Jose Antonio; Ledesma, María Dolores

    2014-01-01

    Dynamic changes in the structure and composition of the membrane protrusions forming dendritic spines underlie memory and learning processes. In recent years a great effort has been made to characterize in detail the protein machinery that controls spine plasticity. However, we know much less about the involvement of lipids, despite being major membrane components and structure determinants. Moreover, protein complexes that regulate spine plasticity depend on specific interactions with membrane lipids for proper function and accurate intracellular signaling. In this review we gather information available on the lipid composition at dendritic spine membranes and on its dynamics. We pay particular attention to the influence that spine lipid dynamism has on glutamate receptors, which are key regulators of synaptic plasticity.

  3. Convective flow during dendritic growth

    NASA Technical Reports Server (NTRS)

    Glicksman, M. E.; Huang, S. C.

    1979-01-01

    A review is presented of the major experimental findings obtained from recent ground-based research conducted under the SPAR program. Measurements of dendritic growth at small supercoolings indicate that below approximately 1.5 K a transition occurs from diffusive control to convective control in succinonitrile, a model system chosen for this study. The key theoretical ideas concerning diffusive and convective heat transport during dendritic growth are discussed, and it is shown that a transition in the transport control should occur when the characteristic length for diffusion becomes larger than the characteristic length for convection. The experimental findings and the theoretical ideas discussed suggest that the Fluid Experiment System could provide appropriate experimental diagnostics for flow field visualization and quantification of the fluid dynamical effects presented here.

  4. Follicular transport route--research progress and future perspectives.

    PubMed

    Knorr, Fanny; Lademann, Jürgen; Patzelt, Alexa; Sterry, Wolfram; Blume-Peytavi, Ulrike; Vogt, Annika

    2009-02-01

    The important role of hair follicles as penetration pathways and reservoir structures for topically applied compounds has been validated in numerous animal models as well as in humans. Follicular penetration rates are modulated by regional variations in size and proportions and the functional status. Advances have especially been made in the targeting of hair follicle-associated cell populations including antigen-presenting cells and stem cells. Improved investigative methods based on differential stripping, spectrophotometry and confocal laser scanning microscopy have led to the determination of the penetration profiles and kinetics for a multiplicity of drugs and drug delivery systems. The observation that particulate delivery systems aggregate and remain in hair follicle openings and their penetration along the follicular duct occurs in a size-dependent manner, which has led to advanced concepts of targeted drug delivery of bioactive compounds in the field of solid particles, as well as semi-solid particles, such as liposomes. This review summarizes the recent progress in this field, and underlines the necessity for pilot studies in human volunteers to further the development of clinical applications for follicular targeting. PMID:19041720

  5. Method of inhibiting dislocation generation in silicon dendritic webs

    DOEpatents

    Spitznagel, John A.; Seidensticker, Raymond G.; McHugh, James P.

    1990-11-20

    A method of tailoring the heat balance of the outer edge of the dendrites adjacent the meniscus to produce thinner, smoother dendrites, which have substantially less dislocation sources contiguous with the dendrites, by changing the view factor to reduce radiation cooling or by irradiating the dendrites with light from a quartz lamp or a laser to raise the temperature of the dendrites.

  6. VEGF expression, microvessel density and dendritic cell decrease in thyroid cancer

    PubMed Central

    Gulubova, Maya; Ivanova, Koni; Ananiev, Julian; Gerenova, Julieta; Zdraveski, Aleksandar; Stoyanov, Hristo; Vlaykova, Tatyana

    2014-01-01

    Thyroid cancer is one of the five most common cancers in the age between 20 and 50 years. Many factors including the potent angiogenic vascular endothelial growth factor (VEGF) and different dendritic cell types are known to be related to thyroid tumourogenesis. The study was performed to address the expression of VEGF and microvessel density in thyroid cancers and to evaluate the effect of VEGF expression in thyroid tumour cells on the dendritic cells. We investigated 65 patients with different types of thyroid carcinomas: papillary (PTC), oncocytic (OTC), follicular (FTC) and anaplastic (ATC), immunohistochemically with antibodies against VEGF, CD1a, CD83, S100 and CD31. Our results suggest that the expression of VEGF is significantly more often in PTC than ATC (92.3% vs. 60.0%, p = 0.025). The microvessel density marked with CD31 in the tumour border of PTC was significantly higher as compared to FTC (p = 0.039), but not to ATC and OTC (p = 0.337 and 0.134). We found that CD1a- and CD83-positive cells were dispersed with variable density and in OC CD31+ vessel numbers were positively correlated with CD83+ dendritic cells in tumour stroma (R = 0.847, p = 0.016). We did not find statistically significant associations of the survival of patients with PTC after the surgical therapy with VEGF expression and MVD. In conclusion we may state that VEGF expression in tumour cells of thyroid cancer can induce neovascularization and suppress dendritic cells. PMID:26019537

  7. Transcranial magnetic stimulation (TMS) inhibits cortical dendrites.

    PubMed

    Murphy, Sean C; Palmer, Lucy M; Nyffeler, Thomas; Müri, René M; Larkum, Matthew E

    2016-03-18

    One of the leading approaches to non-invasively treat a variety of brain disorders is transcranial magnetic stimulation (TMS). However, despite its clinical prevalence, very little is known about the action of TMS at the cellular level let alone what effect it might have at the subcellular level (e.g. dendrites). Here, we examine the effect of single-pulse TMS on dendritic activity in layer 5 pyramidal neurons of the somatosensory cortex using an optical fiber imaging approach. We find that TMS causes GABAB-mediated inhibition of sensory-evoked dendritic Ca(2+) activity. We conclude that TMS directly activates fibers within the upper cortical layers that leads to the activation of dendrite-targeting inhibitory neurons which in turn suppress dendritic Ca(2+) activity. This result implies a specificity of TMS at the dendritic level that could in principle be exploited for investigating these structures non-invasively.

  8. Dendritic web silicon for solar cell application

    NASA Technical Reports Server (NTRS)

    Seidensticker, R. G.

    1977-01-01

    The dendritic web process for growing long thin ribbon crystals of silicon and other semiconductors is described. Growth is initiated from a thin wirelike dendrite seed which is brought into contact with the melt surface. Initially, the seed grows laterally to form a button at the melt surface; when the seed is withdrawn, needlelike dendrites propagate from each end of the button into the melt, and the web portion of the crystal is formed by the solidification of the liquid film supported by the button and the bounding dendrites. Apparatus used for dendritic web growth, material characteristics, and the two distinctly different mechanisms involved in the growth of a single crystal are examined. The performance of solar cells fabricated from dendritic web material is indistinguishable from the performance of cells fabricated from Czochralski grown material.

  9. Cell-intrinsic drivers of dendrite morphogenesis

    PubMed Central

    Puram, Sidharth V.; Bonni, Azad

    2013-01-01

    The proper formation and morphogenesis of dendrites is fundamental to the establishment of neural circuits in the brain. Following cell cycle exit and migration, neurons undergo organized stages of dendrite morphogenesis, which include dendritic arbor growth and elaboration followed by retraction and pruning. Although these developmental stages were characterized over a century ago, molecular regulators of dendrite morphogenesis have only recently been defined. In particular, studies in Drosophila and mammalian neurons have identified numerous cell-intrinsic drivers of dendrite morphogenesis that include transcriptional regulators, cytoskeletal and motor proteins, secretory and endocytic pathways, cell cycle-regulated ubiquitin ligases, and components of other signaling cascades. Here, we review cell-intrinsic drivers of dendrite patterning and discuss how the characterization of such crucial regulators advances our understanding of normal brain development and pathogenesis of diverse cognitive disorders. PMID:24255095

  10. Non FcεR-bearing Mast Cells Secrete Sufficient Interleukin-4 to Control Francisella tularensis Replication within Macrophages

    PubMed Central

    Thathiah, Prea; Sanapala, Shilpa; Rodriguez, Annette R.; Yu, Jieh-Juen; Murthy, Ashlesh K.; Guentzel, M. Neal; Forsthuber, Thomas G.; Chambers, James P.; Arulanandam, Bernard P.

    2011-01-01

    Mast cells have classically been implicated in the triggering of allergic and anaphylactic reactions. However, recent findings have elucidated the ability of these cells to selectively release a variety of cytokines leading to bacterial clearance through neutrophil and dendritic cell mobilization, and suggest an important role in innate host defenses. Our laboratory has established a primary bone marrow derived mast cell-macrophage co-culture system and found that mast cells mediated a significant inhibition of Francisella tularensis LVS uptake and replication within macrophages through contact and the secreted product interleukin-4 (IL-4). In this study, we utilized P815 mast cells and J774 macrophages to further investigate whether mast cell activation by non-FcεR driven signals could produce IL-4 and control intramacrophage LVS replication. P815 supernatants collected upon activation by the mast cell activating peptide MP7, as well as P815 cells co-cultured with J774 macrophages, exhibited marked inhibition of bacterial uptake and replication, which correlated with the production of IL-4. The inhibition noted in vitro was titratable and preserved at ratios relevant to cellular infiltration events following pulmonary challenge. Collectively, our data suggest that both primary mast cell and P815 mast cell (lacking FcεR) secreted IL-4 can control intramacrophage Francisella replication. PMID:21565523

  11. The Equiaxed Dendritic Solidification Experiment (EDSE)

    NASA Technical Reports Server (NTRS)

    1999-01-01

    The Equiaxed Dendritic Solidification Experiment (EDSE) is a material sciences investigation under the Formation of Microstructures/pattern formation discipline. The objective is to study the microstructural evolution of and thermal interactions between several equiaxed crystals growing dendritically in a supercooled melt of a pure and transparent substance under diffusion controlled conditions. Dendrites growing at .4 supercooling from a 2 stinger growth chamber for the EDSE in the Microgravity Development Lab (MDL).

  12. Dendrite preventing separator for secondary lithium batteries

    NASA Technical Reports Server (NTRS)

    Shen, David H. (Inventor); Surampudi, Subbarao (Inventor); Huang, Chen-Kuo (Inventor); Halpert, Gerald (Inventor)

    1993-01-01

    Dendrites are prevented from shorting a secondary lithium battery by use of a first porous separator, such as porous polypropylene, adjacent to the lithium anode that is unreactive with lithium and a second porous fluoropolymer separator between the cathode and the first separator, such as polytetrafluoroethylene, that is reactive with lithium. As the tip of a lithium dendrite contacts the second separator, an exothermic reaction occurs locally between the lithium dendrite and the fluoropolymer separator. This results in the prevention of the dendrite propagation to the cathode.

  13. Dendrite preventing separator for secondary lithium batteries

    NASA Technical Reports Server (NTRS)

    Shen, David H. (Inventor); Surampudi, Subbarao (Inventor); Huang, Chen-Kuo (Inventor); Halpert, Gerald (Inventor)

    1995-01-01

    Dendrites are prevented from shorting a secondary lithium battery by use of a first porous separator such as porous polypropylene adjacent the lithium anode that is unreactive with lithium and a second porous fluoropolymer separator between the cathode and the first separator such as polytetrafluoroethylene that is reactive with lithium. As the tip of a lithium dendrite contacts the second separator, an exothermic reaction occurs locally between the lithium dendrite and the fluoropolymer separator. This results in the prevention of the dendrite propagation to the cathode.

  14. Hierarchical assembly of diphenylalanine into dendritic nanoarchitectures.

    PubMed

    Han, Tae Hee; Oh, Jun Kyun; Lee, Gyoung-Ja; Pyun, Su-Il; Kim, Sang Ouk

    2010-09-01

    Highly ordered, multi-dimensional dendritic nanoarchitectures were created via self-assembly of diphenylalanine from an acidic buffer solution. The self-similarity of dendritic structures was characterized by examining their fractal dimensions with the box-counting method. The fractal dimension was determined to be 1.7, which demonstrates the fractal dimension of structures generated by diffusion limited aggregation on a two-dimensional substrate surface. By confining the dendritic assembly of diphenylalanine within PDMS microchannels, the self-similar dendritic growth could be hierarchically directed to create linearly assembled nanoarchitectures. Our approach offers a novel pathway for creating and directing hierarchical nanoarchitecture from biomolecular assembly. PMID:20605423

  15. Precipitation dendrites in turbulent pipe flows

    NASA Astrophysics Data System (ADS)

    Angheluta, Luiza; Hawkins, Christopher; Hammer, Øyvind; Jamtveit, Bjørn

    2013-04-01

    Surface precipitation in pipelines, as well as freezing in water pipes is of great concern in many industrial applications where scaling phenomena becomes a control problem of pipe-clogging or an efficiency reduction in transport. Flow blockage often occurs even when only a small fraction is deposited non-uniformly on the walls in the form of dendrites. Dendritic patterns are commonly encountered in surface precipitation from supersaturated solutions, e.g. calcite dendrites, as well as in solidification from undercooled liquids, e.g. freezing of water into ice dendrites. We explore the mathematical similarities between precipitation and freezing processes and, in particular, investigate the effect of fluid flow on the precipitation dendrites on pipe walls. We use a phase field approach to model surface growth coupled with a lattice Boltzmann method that simulates a channel flow at varying Reynolds number. The dendrites orientation and shape depend non-trivially on the ratio between advection and diffusion, i.e. the Peclet number, as well as the Reynolds number. Roughness induced vortices near growing dendrites at high flow rates further affect the branch splitting of dendrites. We show how the transport rate in a pipeline may depend on the different dendritic morphologies, and provide estimates for the flow conditions that correspond to most efficient transport regimes.

  16. Electrical dual-sensing method for real-time quantitative monitoring of cell-secreted MMP-9 and cellular morphology during migration process.

    PubMed

    Tran, Trong Binh; Nguyen, Phuong Diem; Baek, Changyoon; Min, Junhong

    2016-03-15

    MMP-9 (92 kDa gelatinease), which is member of matrix metalloproteinases (MMPs) family, plays a crucial role in the breakdown of extracellular matrix (ECM) by degrading the major components of ECM that lead to tumor cell invasion and metastasis through the basement membrane. Our study presents the on-chip dual-sensing device for rapid detection of cell-secreted MMP-9 and corresponding cell morphology changes in real-time domain. The device consists of 2 sensing platforms (both are interdigitated array microelectrodes - IDAMs) within 1 common fluidic chamber: one detects the cell morphology responses via Electric Cell-substrate Impedance Sensing (ECIS) technique, meanwhile the other records the cleavage effect between cell-secreted MMP-9 and the surface immobilized peptide via the capacitance-based sensing method. Thanks to the selectivity of designed peptide, this approach allows the rapid and specific detection of MMP-9. In comparison with gold standard ELISA assay, the detection time was significantly reduced from over 4h to within 30 min with the wide detection range from 10 pM to 10nM. Finally, this study provides the novel model for MMP-9 protease direct detection from living cell and new insights in multi-purpose detection of cancer associated enzyme and cell migration behavior. PMID:26485177

  17. Mode of dendrite growth in undercooled alloy melts

    SciTech Connect

    Li, J.; Yang, G.; Zhou, Y.

    1998-01-01

    The mode of dendrite growth in the undercooled Ni-50 at% Cu alloy was investigated. At lower undercoolings, the dendrite growth is mainly controlled by solute diffusion, and the formed dendritic morphologies are similar to those of the conventional as-cast equiaxed crystals, except that here the branches are much denser. At higher undercoolings, however, the severe solutal trapping that results from high dendrite growth velocity weakens the effect of solute diffusion on the dendrite growth. In this case, the dendrites branch in the bunching form. The dendrite spacings were measured, and the results were interpreted with the current dendrite growth theories.

  18. In vivo dendrite regeneration after injury is different from dendrite development.

    PubMed

    Thompson-Peer, Katherine L; DeVault, Laura; Li, Tun; Jan, Lily Yeh; Jan, Yuh Nung

    2016-08-01

    Neurons receive information along dendrites and send signals along axons to synaptic contacts. The factors that control axon regeneration have been examined in many systems, but dendrite regeneration has been largely unexplored. Here we report that, in intact Drosophila larvae, a discrete injury that removes all dendrites induces robust dendritic growth that recreates many features of uninjured dendrites, including the number of dendrite branches that regenerate and responsiveness to sensory stimuli. However, the growth and patterning of injury-induced dendrites is significantly different from uninjured dendrites. We found that regenerated arbors cover much less territory than uninjured neurons, fail to avoid crossing over other branches from the same neuron, respond less strongly to mechanical stimuli, and are pruned precociously. Finally, silencing the electrical activity of the neurons specifically blocks injury-induced, but not developmental, dendrite growth. By elucidating the essential features of dendrites grown in response to acute injury, our work builds a framework for exploring dendrite regeneration in physiological and pathological conditions. PMID:27542831

  19. Hypertrophic Osteoarthropathy and Follicular Thyroid Cancer: A Rare Paraneoplastic Syndrome

    PubMed Central

    Tavarelli, Martina; Sarfati, Julie; De Gennes, Christian; Haroche, Julien; Buffet, Camille; Ghander, Cécile; Simon, Jean Marc; Ménégaux, Fabrice; Leenhardt, Laurence

    2015-01-01

    Background Hypertrophic osteoarthropathy (HOA) is a rare condition characterized by bone and joint pain and digital clubbing usually associated with bronchopulmonary diseases. Primary HOA is rare and the pathogenesis remains unclear. Objectives Cases of HOA as a paraneoplastic syndrome associated with thyroid carcinoma are very rare – only 2 cases have been described in the literature. Results We present the first case of a 40-year-old patient affected by HOA associated with invasive differentiated follicular thyroid carcinoma operated in 2 stages. Both operations were followed by radioiodine ablation, and then a rapid unresectable local recurrence developed requiring cervical radiotherapy (70 Gy). A second treatment with 100 mCi of 131I confirmed it was a refractory thyroid cancer. Further surgery confirmed a poorly differentiated follicular cancer and 12 cycles of chemotherapy by gemcitabine and oxaliplatin followed. During the 8 years of follow-up, cervical recurrence was stable, but severe episodes of hemoptysis occurred requiring iterative embolization of the bronchial and tracheal arteries. Other lung diseases were excluded. Digital clubbing appeared, which was associated with arthritis, bone pain and inflammatory syndrome. X-rays and magnetic resonance imaging found periosteal apposition in the long bones; bone scintigraphy confirmed the HOA diagnosis. Other causes of arthritis were eliminated. She was treated with colchicine, corticosteroids and nonsteroidal anti-inflammatory drugs, but only the combination of methotrexate and hydroxychloroquine reduced the morphine requirements. Conclusion HOA is exceptionally associated with thyroid cancer and we raised the hypothesis of the secretion of a circulating factor in a patient with invasive and recurrent follicular thyroid cancer, refractory to radioiodine. PMID:26835431

  20. Tumor of follicular infundibulum: an unsuspected cause of macular hypopigmentation.

    PubMed

    Kubba, Asha; Batrani, Meenakshi; Taneja, Atul; Jain, Vivek

    2014-01-01

    We present three cases of a rare eruptive variant of tumor of follicular infundibulum. Two patients presented with hypopigmented macules. The clinical differential diagnoses considered in these two cases were vitiligo, lichen sclerosus et atrophicus, and idiopathic guttate hypomelanosis. In the third case, the lesions were hypopigmented flat topped maculo-papules diagnosed clinically as verruca plana. In all three cases, the histopathological features of plate like growth of pale keratinocytes connected to the epidermis and peritumoral condensation of elastic fibers were diagnostic. Although no satisfactory treatment is available, the exclusion of other clinical differential diagnosis particularly vitiligo with its psychosocial implications underscores the importance of skin biopsy. PMID:24685851

  1. A case of follicular lymphoma associated with paraneoplastic cerebellar degeneration.

    PubMed

    Shimazu, Yayoi; Minakawa, Eiko N; Nishikori, Momoko; Ihara, Masafumi; Hashi, Yuichiro; Matsuyama, Hirofumi; Hishizawa, Masakatsu; Yoshida, Sonoyo; Kitano, Toshiyuki; Kondo, Tadakazu; Ishikawa, Takayuki; Takahashi, Ryosuke; Takaori-Kondo, Akifumi

    2012-01-01

    Paraneoplastic neurological disorders (PND) are neurological effects of malignancy that are recognized as immune-mediated disorders caused by aberrant expression of a tumor antigen that is normally expressed in the nervous system. We report a case of cerebellar ataxia which turned out to be paraneoplastic cerebellar degeneration, a subtype of PND that develops cerebellar symptoms, that was caused by follicular lymphoma. After chemotherapy, the patient attained sufficient improvement of cerebellar symptoms along with complete remission of lymphoma. Paraneoplastic cerebellar degeneration should be recognized as a rare complication of lymphoma as it is important to start proper treatment before the neurological symptoms become irreversible.

  2. Follicular DEAs for two-way tactile communication

    NASA Astrophysics Data System (ADS)

    Knoop, Lars E.; Rossiter, Jonathan; Assaf, Tareq

    2015-04-01

    Follicular structures in skin combine sensing and actuation in a soft and compliant continuous surface. We have developed a tactile display device inspired by this structure, using a Dielectric Elastomer Actuator (DEA). DEAs allow for combined sensing and actuation, making possible two-way tactile communication between the user and the device. The device can obtain tactile information about the environment, or a user touching it, and it can also present tactile information to the user. We characterise the sensing properties of the tactile display device, and perform classification of tactile stimuli. We demonstrate two-way tactile interaction between a user and the device.

  3. Neuroblastoma triggers an immunoevasive program involving galectin-1-dependent modulation of T cell and dendritic cell compartments.

    PubMed

    Soldati, Rocio; Berger, Elisa; Zenclussen, Ana C; Jorch, Gerhard; Lode, Holger N; Salatino, Mariana; Rabinovich, Gabriel A; Fest, Stefan

    2012-09-01

    The immunosuppressive strategies devised by neuroblastoma (NB), the most common solid extracranial childhood cancer, are poorly understood. Here, we identified an immunoevasive program triggered by NB through secretion of galectin-1 (Gal-1), a multifunctional glycan-binding protein. Human and mouse NB cells express and secrete Gal-1, which negatively regulates T cell and dendritic cell function. When injected subcutaneously in syngeneic A/J mice, knockdown transfectants expressing low amounts of Gal-1 (NXS2/L) showed reduction of primary tumor growth by 83-90% and prevented spontaneous liver metastases in contrast to NXS2 cell variants (NXS2/H, NXS2 wildtype) expressing high amounts of Gal-1. Splenocytes from mice receiving Gal-1 knockdown NXS2/L cells secreted higher amounts of IFN-γ and displayed enhanced cytotoxic T-cell function compared to NXS2/H or NXS2 controls. Immunohistochemical analysis revealed a six- to tenfold increase in the frequency of CD4+ and CD8+ T cells infiltrating tumors from mice receiving knockdown transfectants. This effect was confirmed by in vitro migration assays. Finally, supernatants of NXS2/H or NXS2 cells suppressed dendritic cell (DC) maturation and induce T cell apoptosis, whereas these effects were only marginal on DCs and T cells exposed to supernatants from NXS2/L cells. These results demonstrate a novel immunoinhibitory role of the Gal-1-glycan axis in NB, highlighting an alternative target for novel immunotherapeutic modalities.

  4. Early events in axon/dendrite polarization.

    PubMed

    Cheng, Pei-lin; Poo, Mu-ming

    2012-01-01

    Differentiation of axons and dendrites is a critical step in neuronal development. Here we review the evidence that axon/dendrite formation during neuronal polarization depends on the intrinsic cytoplasmic asymmetry inherited by the postmitotic neuron, the exposure of the neuron to extracellular chemical factors, and the action of anisotropic mechanical forces imposed by the environment. To better delineate the functions of early signals among a myriad of cellular components that were shown to influence axon/dendrite formation, we discuss their functions by distinguishing their roles as determinants, mediators, or modulators and consider selective degradation of these components as a potential mechanism for axon/dendrite polarization. Finally, we examine whether these early events of axon/dendrite formation involve local autocatalytic activation and long-range inhibition, as postulated by Alan Turing for the morphogenesis of patterned biological structure.

  5. Early events in axon/dendrite polarization.

    PubMed

    Cheng, Pei-lin; Poo, Mu-ming

    2012-01-01

    Differentiation of axons and dendrites is a critical step in neuronal development. Here we review the evidence that axon/dendrite formation during neuronal polarization depends on the intrinsic cytoplasmic asymmetry inherited by the postmitotic neuron, the exposure of the neuron to extracellular chemical factors, and the action of anisotropic mechanical forces imposed by the environment. To better delineate the functions of early signals among a myriad of cellular components that were shown to influence axon/dendrite formation, we discuss their functions by distinguishing their roles as determinants, mediators, or modulators and consider selective degradation of these components as a potential mechanism for axon/dendrite polarization. Finally, we examine whether these early events of axon/dendrite formation involve local autocatalytic activation and long-range inhibition, as postulated by Alan Turing for the morphogenesis of patterned biological structure. PMID:22715881

  6. Natural CD8{sup +}25{sup +} regulatory T cell-secreted exosomes capable of suppressing cytotoxic T lymphocyte-mediated immunity against B16 melanoma

    SciTech Connect

    Xie, Yufeng; Zhang, Xueshu; Zhao, Tuo; Li, Wei; Xiang, Jim

    2013-08-16

    Highlights: •CD8{sup +}25{sup +} regulatory T cells secrete tolerogenic exosomes. •CD8{sup +}25{sup +} regulatory T cell-derived exosomes exhibit immunosuppressive effect. •CD8{sup +}25{sup +} regulatory T cell-derived exosomes inhibit antitumor immunity. -- Abstract: Natural CD4{sup +}25{sup +} and CD8{sup +}25{sup +} regulatory T (Tr) cells have been shown to inhibit autoimmune diseases. Immune cells secrete exosomes (EXOs), which are crucial for immune regulation. However, immunomodulatory effect of natural Tr cell-secreted EXOs is unknown. In this study, we purified natural CD8{sup +}25{sup +} Tr cells from C57BL/6 mouse naive CD8{sup +} T cells, and in vitro amplified them with CD3/CD28 beads. EXOs (EXO{sub Tr}) were purified from Tr cell’s culture supernatants by differential ultracentrifugation and analyzed by electron microscopy, Western blot and flow cytometry. Our data showed that EXO{sub Tr} had a “saucer” or round shape with 50–100 nm in diameter, contained EXO-associated markers LAMP-1 and CD9, and expressed natural Tr cell markers CD25 and GITR. To assess immunomodulatory effect, we i.v. immunized C57BL/6 mice with ovalbumin (OVA)-pulsed DCs (DC{sub OVA}) plus Tr cells or EXO{sub Tr}, and then assessed OVA-specific CD8{sup +} T cell responses using PE-H-2K{sup b}/OVA tetramer and FITC-anti-CD8 antibody staining by flow cytometry and antitumor immunity in immunized mice with challenge of OVA-expressing BL6–10{sub OVA} melanoma cells. We demonstrated that DC{sub OVA}-stimulated CD8{sup +} T cell responses and protective antitumor immunity significantly dropped from 2.52% to 1.08% and 1.81% (p < 0.05), and from 8/8 to 2/8 and 5/8 mice DC{sub OVA} (p < 0.05) in immunized mice with co-injection of Tr cells and EXO{sub Tr}, respectively. Our results indicate that natural CD8{sup +}25{sup +} Tr cell-released EXOs, alike CD8{sup +}25{sup +} Tr cells, can inhibit CD8{sup +} T cell responses and antitumor immunity. Therefore, EXOs derived from

  7. Altered theca and cumulus oocyte complex gene expression, follicular arrest and reduced fertility in cows with dominant follicle follicular fluid androgen excess

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To date, animal models with naturally occurring androgen excess have not been identified. Serendipitously, we discovered two subpopulations of cows with dramatically different follicular fluid androgen concentrations in dominant follicles within our research herd. In the cow, androstenedione is the...

  8. Angiogenic, mitogenic, and chemotactic activity in human follicular fluid (HFF)

    SciTech Connect

    Bryant, S.M.; Frederick, J.L.; Gale, J.A.; Campeau, J.D.; diZerega, G.S.

    1986-03-01

    The capacity of human follicular fluid to induce neovascularization was investigated. Three parameters were employed to assess the extent of angiogenic activity: (1) new vessel formation on the chick chorioallantoic membrane (CAM); (2) mitogenesis and (3) chemotaxis of bovine aortic endothelial cells. HFF resuspended in hydron induced new blood vessel formation on the CAM, as manifested by a spoke-wheel pattern of vessels radiating from the locus of application after two to six days. Endothelial cells cultured with a 1:10 dilution of HFF for two days demonstrated an enhanced incorporation of /sup 3/H-thymidine into acid-precipitable material when compared to control cells. The ratio of counts-per-minute for HFF stimulated cells versus control cells was 3.02 +/- 0.53 (anti S.E.M., n = 5). Endothelial cells also exhibited a directional migration towards HFF through a polycarbonate membrane with 8..mu..m pores. The ratio of the number of cells migrating completely through the filter towards a 1:10 dilution of HFF compared to those migrating towards medium alone was 5.61 +/- 0.61 (anti +/- S.E.M., n = 3). Human serum at an equivalent protein concentration as HFF demonstrated no activity in the CAM, mitogenic, and chemotaxis assays. These results demonstrate specific angiogenic, mitogenic and chemotactic activity in human follicular fluid.

  9. Paraneoplastic retinopathy associated with systemic follicular cell lymphoma.

    PubMed

    Bhavsar, Kavita V; Hedges, Thomas; Thirkill, Charles E; Reichel, Elias

    2015-03-01

    The authors describe two rare cases of autoimmune retinopathy associated with follicular cell lymphoma, including a 54-year-old man who experienced nyctalopia for 1 year (patient 1) and a 59-year-old man who had bilateral loss of central vision for 6 months (patient 2). Visual field testing of patient 1 revealed nonspecific defects, and multifocal electroretinogram (ERG) testing showed mildly subnormal amplitudes more pronounced in the left than the right eye. Serologic testing detected antibodies against a 47-kD protein, presumed to be alpha-enolase. Goldmann perimetry of patient 2 showed dense central scotomas, and a full-field ERG revealed reduced amplitudes of bright scotopic responses. Serological testing yielded anti-bipolar cell antibodies. A variable presentation of autoimmune retinopathy can occur in the setting of follicular cell lymphoma. Disparate serum autoantibodies may have mediated the pathogenesis of retinal degeneration in these two patients and could explain the difference in course and severity of retinopathy. PMID:25835308

  10. Follicular Thyroid Carcinoma Presenting as Bilateral Cheek Masses

    PubMed Central

    Kim, Dong-Wook; Hah, J. Hun; An, Soo-Youn; Chang, Hak

    2013-01-01

    Mandibular metastasis of thyroid carcinoma is extremely rare. We present the case of a 46-year-old woman who had bilateral huge cheek masses that had grown rapidly over several years. Intra-oral mucosal tissue biopsy and imaging work-up including computed tomography scan and magnetic resonance imaging were performed and the initial diagnosis was presumed to be central giant cell granuloma. Incidentally detected thyroid lesions were studied with ultra-sonography guided fine needle aspiration and diagnosed as simple benign nodules. Due to continuous oral bleeding and the locally destructive feature of the lesions, we decided to excise the mass surgically. To avoid functional deficit, a stepwise approach was performed: Firstly, the larger left mass was excised and the mandible was reconstructed with a fibular free flap. The final pathologic diagnosis was follicular thyroid cancer. Postoperative I-131 thyroid scan and whole body positron-emissions-tomography were performed. Right side mass was revealed as a thyroid malignancy. Multiple bony metastases were detected. Since further radioactive iodine therapy was required, additional total thyroidectomy and right side mandibulectomy with fibular free flap reconstruction was performed. The patient also underwent high dose radioactive iodine therapy and palliative extra-beam radiotherapy for the metastatic lumbar lesion. Follicular thyroid carcinoma should be considered as a differential diagnosis for mandibular mass lesions. PMID:23526730

  11. A Study of Donor Area in Follicular Unit Hair Transplantation

    PubMed Central

    Nirmal, Balakrishnan; Somiah, Savitha; Sacchidanand, Sarvajnamurthy A

    2013-01-01

    Background: The advent of follicular unit transplantation (FUT) has given a natural appearance in the recipient area in the past two decades, but has left behind an unsightly scar in the donor area. A study of donor area and techniques to make it cosmetically acceptable is lacking. Aim: The aim of this study was to evaluate the donor area after follicular unit hair transplantation and to show a few techniques to make the donor scar aesthetically pleasing. Materials and Methods: The donor area was examined for scar width and patient satisfaction scores of donor area in 30 consecutive patients from March 2012 to February 2013 retrospectively after a minimum of 3 months after the procedure. Complications such as effluvium along suture line, wound infection, dehiscence, necrosis, folliculitis, keloids and wide scars were also noted. Results: Scar width increased with increase in width of the donor strip. Patient satisfaction scores declined with larger strip widths. The most common complication seen was folliculitis-like lesions. Double trichophytic closure yielded the most aesthetically acceptable scar. Conclusion: FUT produces a linear scar in the donor area, which can be a significant concern in patients wishing to cut their hair short. Restricting the width of the donor strip and trichophytic closure has greatly improved the appearance of the scar. PMID:24470718

  12. Trefoil factor 3 (TFF3): a promising indicator for diagnosing thyroid follicular carcinoma.

    PubMed

    Takano, Toru; Yamada, Hiroya

    2009-01-01

    Since the introduction of fine needle aspiration biopsy (FNAB) in the 1970's, a preoperative diagnostic technique for thyroid follicular carcinoma has long been awaited. Many markers that distinguish follicular carcinomas from adenomas have been reported; however, most of them have not been confirmed to be beneficial for clinical use. Trefoil factor 3 (TFF3) is a relatively new family of peptides that bears the three-loop trefoil domain. Several groups have reported that the suppression of TFF3 mRNA expression is related to malignant characteristics of thyroid follicular cell-derived tumors and the expression level of TFF3 mRNA is the most promising indicator for diagnosing follicular carcinoma. Development of TFF3-based diagnostic methods is now ongoing and it may not be long before thyroid follicular carcinoma can be diagnosed preoperatively using an aspirated sample from the tumor.

  13. Impact of dendritic size and dendritic topology on burst firing in pyramidal cells.

    PubMed

    van Elburg, Ronald A J; van Ooyen, Arjen

    2010-05-13

    Neurons display a wide range of intrinsic firing patterns. A particularly relevant pattern for neuronal signaling and synaptic plasticity is burst firing, the generation of clusters of action potentials with short interspike intervals. Besides ion-channel composition, dendritic morphology appears to be an important factor modulating firing pattern. However, the underlying mechanisms are poorly understood, and the impact of morphology on burst firing remains insufficiently known. Dendritic morphology is not fixed but can undergo significant changes in many pathological conditions. Using computational models of neocortical pyramidal cells, we here show that not only the total length of the apical dendrite but also the topological structure of its branching pattern markedly influences inter- and intraburst spike intervals and even determines whether or not a cell exhibits burst firing. We found that there is only a range of dendritic sizes that supports burst firing, and that this range is modulated by dendritic topology. Either reducing or enlarging the dendritic tree, or merely modifying its topological structure without changing total dendritic length, can transform a cell's firing pattern from bursting to tonic firing. Interestingly, the results are largely independent of whether the cells are stimulated by current injection at the soma or by synapses distributed over the dendritic tree. By means of a novel measure called mean electrotonic path length, we show that the influence of dendritic morphology on burst firing is attributable to the effect both dendritic size and dendritic topology have, not on somatic input conductance, but on the average spatial extent of the dendritic tree and the spatiotemporal dynamics of the dendritic membrane potential. Our results suggest that alterations in size or topology of pyramidal cell morphology, such as observed in Alzheimer's disease, mental retardation, epilepsy, and chronic stress, could change neuronal burst firing and

  14. Immunity to Pathogens Taught by Specialized Human Dendritic Cell Subsets

    PubMed Central

    Geginat, Jens; Nizzoli, Giulia; Paroni, Moira; Maglie, Stefano; Larghi, Paola; Pascolo, Steve; Abrignani, Sergio

    2015-01-01

    Dendritic cells (DCs) are specialized antigen-presenting cells (APCs) that have a key role in immune responses because they bridge the innate and adaptive arms of the immune system. They mature upon recognition of pathogens and upregulate MHC molecules and costimulatory receptors to activate antigen-specific CD4+ and CD8+ T cells. It is now well established that DCs are not a homogeneous population but are composed of different subsets with specialized functions in immune responses to specific pathogens. Upon viral infections, plasmacytoid DCs (pDCs) rapidly produce large amounts of IFN-α, which has potent antiviral functions and activates several other immune cells. However, pDCs are not particularly potent APCs and induce the tolerogenic cytokine IL-10 in CD4+ T cells. In contrast, myeloid DCs (mDCs) are very potent APCs and possess the unique capacity to prime naive T cells and consequently to initiate a primary adaptive immune response. Different subsets of mDCs with specialized functions have been identified. In mice, CD8α+ mDCs capture antigenic material from necrotic cells, secrete high levels of IL-12, and prime Th1 and cytotoxic T-cell responses to control intracellular pathogens. Conversely, CD8α− mDCs preferentially prime CD4+ T cells and promote Th2 or Th17 differentiation. BDCA-3+ mDC2 are the human homologue of CD8α+ mDCs, since they share the expression of several key molecules, the capacity to cross-present antigens to CD8+ T-cells and to produce IFN-λ. However, although several features of the DC network are conserved between humans and mice, the expression of several toll-like receptors as well as the production of cytokines that regulate T-cell differentiation are different. Intriguingly, recent data suggest specific roles for human DC subsets in immune responses against individual pathogens. The biology of human DC subsets holds the promise to be exploitable in translational medicine, in particular for the development of vaccines against

  15. Cigarette Smoke Decreases the Maturation of Lung Myeloid Dendritic Cells

    PubMed Central

    Calero-Acuña, Carmen; Moreno-Mata, Nicolás; Gómez-Izquierdo, Lourdes; Sánchez-López, Verónica; López-Ramírez, Cecilia; Tobar, Daniela; López-Villalobos, José Luis; Gutiérrez, Cesar; Blanco-Orozco, Ana; López-Campos, José Luis

    2016-01-01

    Background Conflicting data exist on the role of pulmonary dendritic cells (DCs) and their maturation in patients with chronic obstructive pulmonary disease (COPD). Herein, we investigated whether disease severity and smoking status could affect the distribution and maturation of DCs in lung tissues of patients undergoing elective pneumectomy or lobectomy for suspected primary lung cancer. Materials and Methods A total of 75 consecutive patients were included. Spirometry testing was used to identify COPD. Lung parenchyma sections anatomically distant from the primary lesion were examined. We used flow cytometry to identify different DCs subtypes—including BDCA1-positive myeloid DCs (mDCs), BDCA3-positive mDCs, and plasmacytoid DCs (pDCs)—and determine their maturation markers (CD40, CD80, CD83, and CD86) in all participants. We also identified follicular DCs (fDCs), Langerhans DCs (LDCs), and pDCs in 42 patients by immunohistochemistry. Results COPD was diagnosed in 43 patients (16 current smokers and 27 former smokers), whereas the remaining 32 subjects were classified as non-COPD (11 current smokers, 13 former smokers, and 8 never smokers). The number and maturation of DCs did not differ significantly between COPD and non-COPD patients. However, the results of flow cytometry indicated that maturation markers CD40 and CD83 of BDCA1-positive mDCs were significantly decreased in smokers than in non-smokers (P = 0.023 and 0.013, respectively). Immunohistochemistry also revealed a lower number of LDCs in COPD patients than in non-COPD subjects. Conclusions Cigarette smoke, rather than airflow limitation, is the main determinant of impaired DCs maturation in the lung. PMID:27058955

  16. Modulation of Cytokine Secretion Allows CD4 T Cells Secreting IL-10 and IL-17 to Simultaneously Participate in Maintaining Tolerance and Immunity.

    PubMed

    Saito, Kanako; Pignon, Pascale; Ayyoub, Maha; Valmori, Danila

    2015-01-01

    CD4 T cells secreting IL-10 or IL-17 are frequent at mucosal sites, where their equilibrium is important for simultaneously maintaining tolerance and immunity to the resident microbiota. The mode of action of these cells, however, is as yet incompletely understood. In this study, we have combined ex vivo analysis of CD4 T cells producing IL-10 or/and IL-17 with assessment of clonal populations isolated ex vivo using a cytokine catch assay. We found that circulating CD4 T cells secreting IL-10 or/and IL-17 ex vivo include both conventional FOXP3- CD4 T cells and FOXP3+ Helios- Treg. Upon assessment of clonal populations derived from single ex vivo isolated cytokine secreting cells, we found that IL-10 or/and IL-17 secreting cells prevalently secrete one or the other cytokine depending on the type of stimulation, the time after stimulation and the presence of microbial products. Namely, IL-10 secretion by clonal cells was prevalent at early time points after TCR mediated stimulation, was independent of co-stimulation and was increased in the presence of the microbial fermentation product butyrate. In contrast, IL-17 secretion was higher at later time points after TCR mediated stimulation and in the presence of co-stimulatory signals. Taken together, these results provide insights into the mechanisms that, through modulation of cytokine secretion depending on conditions, allow IL-10 and IL-17 producing CD4 T cells to contribute to maintain tolerance to microbes locally, while retaining the ability to participate in protective immune responses at distant sites.

  17. ‘Porosome’ discovered nearly 20 years ago provides molecular insights into the kiss-and-run mechanism of cell secretion

    PubMed Central

    Jena, Bhanu P

    2015-01-01

    Secretion is a fundamental cellular process in living organisms, from yeast to cells in humans. Since the 1950s, it was believed that secretory vesicles completely merged with the cell plasma membrane during secretion. While this may occur, the observation of partially empty vesicles in cells following secretion suggests the presence of an additional mechanism that allows partial discharge of intra-vesicular contents during secretion. This proposed mechanism requires the involvement of a plasma membrane structure called ‘porosome’, which serves to prevent the collapse of secretory vesicles, and to transiently fuse with the plasma membrane (Kiss-and-run), expel a portion of its contents and disengage. Porosomes are cup-shaped supramolecular lipoprotein structures at the cell plasma membrane ranging in size from 15 nm in neurons and astrocytes to 100–180 nm in endocrine and exocrine cells. Neuronal porosomes are composed of nearly 40 proteins. In comparison, the 120 nm nuclear pore complex is composed of >500 protein molecules. Elucidation of the porosome structure, its chemical composition and functional reconstitution into artificial lipid membrane, and the molecular assembly of membrane-associated t-SNARE and v-SNARE proteins in a ring or rosette complex resulting in the establishment of membrane continuity to form a fusion pore at the porosome base, has been demonstrated. Additionally, the molecular mechanism of secretory vesicle swelling, and its requirement for intra-vesicular content release during cell secretion has also been elucidated. Collectively, these observations provide a molecular understanding of cell secretion, resulting in a paradigm shift in our understanding of the secretory process. PMID:26033351

  18. Ovarian follicular atresia is mediated by heterophagy, autophagy, and apoptosis in Prochilodus argenteus and Leporinus taeniatus (Teleostei: Characiformes).

    PubMed

    Santos, H B; Thomé, R G; Arantes, F P; Sato, Y; Bazzoli, N; Rizzo, E

    2008-12-01

    We investigated apoptosis, cell proliferation antigen (PCNA), and heat shock protein (HSP70) during ovarian follicular atresia in two freshwater teleost species from the São Francisco River basin, Brazil: curimatã-pacu, Prochilodus argenteus and piau-jejo, Leporinus taeniatus. Fishes were maintained in captivity after the reproductive period and ovarian regression was assessed by gonadosomatic index for three stages: early, advanced, and late regression. Follicular atresia was analysed by light and transmission electron microscopy, as well as by TUNEL and immunohistochemistry for HSP70 and PCNA. During early regression, atretic follicles exhibited zona pellucida breakdown, yolk degeneration, and hypertrophied follicular cells (e.g., granulosa in mammals). Intense heterophagy to engulf the yolk, and autophagy were detected in the follicular cells during advanced and late atresia. The TUNEL assay detected DNA fragmentation, mainly in late follicular atresia. The apoptosis rate of the follicular cells increased up to 10% during follicular atresia in both species and was negatively correlated with follicular area. Immunohistochemistry reaction for HSP70 stained the follicular cells strongly during advanced atresia, when they are intensively involved in yolk engulfment, whereas the reaction for PCNA labelled theca cells. We inferred that heterophagy, autophagy, and apoptosis contributed to follicular atresia in teleost ovaries, thereby achieving a more efficient removal of the degenerating oocyte and dying follicular cells. Additionally, HSP70 may protect the follicular cells before apoptosis when they are involved in yolk engulfment, and cell proliferation in the theca contributed to ovarian remodelling. PMID:18701155

  19. Clinicopathologic Characteristics and Outcomes of Histiocytic and Dendritic Cell Neoplasms: The Moffitt Cancer Center Experience Over the Last Twenty Five Years

    PubMed Central

    Dalia, Samir; Jaglal, Michael; Chervenick, Paul; Cualing, Hernani; Sokol, Lubomir

    2014-01-01

    Neoplasms of histiocytic and dendritic cells are rare disorders of the lymph node and soft tissues. Because of this rarity, the corresponding biology, prognosis and terminologies are still being better defined and hence historically, these disorders pose clinical and diagnostic challenges. These disorders include Langerhans cell histiocytosis (LCH), histiocytic sarcoma (HS), follicular dendritic cell sarcoma (FDCS), interdigtating cell sarcoma (IDCS), indeterminate cell sarcoma (INDCS), and fibroblastic reticular cell tumors (FRCT). In order to gain a better understanding of the biology, diagnosis, and treatment in these rare disorders we reviewed our cases of these neoplasms over the last twenty five years and the pertinent literature in each of these rare neoplasms. Cases of histiocytic and dendritic cell neoplasms diagnosed between 1989–2014 were identified using our institutional database. Thirty two cases were included in this analysis and were comprised of the following: Langerhans cell histiocytosis (20/32), histiocytic sarcoma (6/32), follicular dendritic cell sarcoma (2/32), interdigitating dendritic cell sarcoma (2/32), indeterminate dendritic cell sarcoma (1/32), and fibroblastic reticular cell tumor (1/32). Median overall survival was not reached in cases with LCH and showed 52 months in cases with HS, 12 months in cases with FDCS, 58 months in cases with IDCS, 13 months in the case of INDCS, and 51 months in the case of FRCT. The majority of patients had surgical resection as initial treatment (n = 18). Five patients had recurrent disease. We conclude that histiocytic and dendritic cell neoplasms are very rare and perplexing disorders that should be diagnosed with a combination of judicious morphology review and a battery of immunohistochemistry to rule out mimics such as carcinoma, lymphoma, neuroendocrine tumors and to better sub-classify these difficult to diagnose lesions. The mainstay of treatment for localized disease remains surgical resection

  20. Application of mid-infrared (MIR) microscopy imaging for discrimination between follicular hyperplasia and follicular lymphoma in transgenic mice.

    PubMed

    Woess, C; Drach, M; Villunger, A; Tappert, R; Stalder, R; Pallua, J D

    2015-09-21

    Mid-infrared (MIR) microscopy imaging is a vibrational spectroscopic technique that uses infrared radiation to image molecules of interest in thin tissue sections. A major advantage of this technology is the acquisition of local molecular expression profiles, while maintaining the topographic integrity of the tissue. Therefore, this technology has become an essential tool for the detection and characterization of the molecular components of many biological processes. Using this method, it is possible to investigate the spatial distribution of proteins and small molecules within biological systems by in situ analysis. In this study, we have evaluated the potential of mid-infrared microscopy imaging to study biochemical changes which distinguish between reactive lymphadenopathy and cancer in genetically modified mice with different phenotypes. We were able to demonstrate that MIR microscopy imaging and multivariate image analyses of different mouse genotypes correlated well with the morphological tissue features derived from HE staining. Using principal component analyses, we were also able to distinguish spectral clusters from different phenotype samples, particularly from reactive lymphadenopathy (follicular hyperplasia) and cancer (follicular lymphoma).

  1. Double dendrite growth in solidification.

    PubMed

    Utter, Brian; Bodenschatz, E

    2005-07-01

    We present experiments on the doublon growth morphology in directional solidification. Samples used are succinonitrile with small amounts of poly(ethylene oxide), acetone, or camphor as the solute. Doublons, or symmetry-broken dendrites, are generic diffusion-limited growth structures expected at large undercooling and low anisotropy. Low anisotropy growth is achieved by selecting a grain near the {111} plane leading to either seaweed (dense branching morphology) or doublon growth depending on experimental parameters. We find selection of doublons to be strongly dependent on solute concentration and sample orientation. Doublons are selected at low concentrations (low solutal undercooling) in contrast to the prediction of doublons at large thermal undercooling in pure materials. Doublons also exhibit preferred growth directions and changing the orientation of a specific doublonic grain changes the character and stability of the doublons. We observe transitions between seaweed and doublon growth with changes in concentration and sample orientation.

  2. Dendritic cell immunotherapy: clinical outcomes

    PubMed Central

    Apostolopoulos, Vasso; Pietersz, Geoffrey A; Tsibanis, Anastasios; Tsikkinis, Annivas; Stojanovska, Lily; McKenzie, Ian FC; Vassilaros, Stamatis

    2014-01-01

    The use of tumour-associated antigens for cancer immunotherapy studies is exacerbated by tolerance to these self-antigens. Tolerance may be broken by using ex vivo monocyte-derived dendritic cells (DCs) pulsed with self-antigens. Targeting tumour-associated antigens directly to DCs in vivo is an alternative and simpler strategy. The identification of cell surface receptors on DCs, and targeting antigens to DC receptors, has become a popular approach for inducing effective immune responses against cancer antigens. Many years ago, we demonstrated that targeting the mannose receptor on macrophages using the carbohydrate mannan to DCs led to appropriate immune responses and tumour protection in animal models. We conducted Phase I, I/II and II, clinical trials demonstrating the effectiveness of oxidised mannan-MUC1 in patients with adenocarcinomas. Here we summarise DC targeting approaches and their efficacy in human clinical trials. PMID:25505969

  3. Evidence for Eigenfrequencies in Dendritic Growth Dynamics

    NASA Astrophysics Data System (ADS)

    Lacombe, Jeffrey C.; Koss, Matthew B.; Giummarra, Cindie; Frei, Julie E.; Lupulescu, Afina O.; Glicksman, Martin E.

    Microgravity dendritic growth experiments, conducted aboard the space shuttle Columbia, are described. In-situ video images reveal that pivalic acid dendrites growing in the diffusion-controlled environment of low-earth orbit exhibit a range of transient or non-steady-state behaviors. The observed transient features of the growth process are being studied with the objective of understanding the mechanisms responsible for these behaviors. Included in these observations is possible evidence for characteristic frequencies or limit cycles in the growth behavior near the tip of the dendrites. These data, and their interpretations, will be discussed.

  4. Active dendrites support efficient initiation of dendritic spikes in hippocampal CA3 pyramidal neurons

    PubMed Central

    Kim, Sooyun; Guzman, Segundo J; Hu, Hua; Jonas, Peter

    2013-01-01

    CA3 pyramidal neurons are important for memory formation and pattern completion in the hippocampal network. It is generally thought that proximal synapses from the mossy fibers activate these neurons most efficiently, whereas distal inputs from the perforant path have a weaker modulatory influence. We used confocally targeted patch-clamp recording from dendrites and axons to map the activation of rat CA3 pyramidal neurons at the subcellular level. Our results reveal two distinct dendritic domains. In the proximal domain, action potentials initiated in the axon backpropagate actively with large amplitude and fast time course. In the distal domain, Na+ channel–mediated dendritic spikes are efficiently initiated by waveforms mimicking synaptic events. CA3 pyramidal neuron dendrites showed a high Na+-to-K+ conductance density ratio, providing ideal conditions for active backpropagation and dendritic spike initiation. Dendritic spikes may enhance the computational power of CA3 pyramidal neurons in the hippocampal network. PMID:22388958

  5. Ovarian follicular activity during late gestation and postpartum in guanaco (Lama guanicoe).

    PubMed

    Riveros, J L; Schuler, G; Urquieta, B; Hoffmann, B; Bonacic, C

    2015-02-01

    This study evaluated ovarian activity in late gestation and post-partum in guanacos in captivity. Follicular dynamics was monitored every second day from 40 days before and other 40 after delivery by transrectal sonography and by plasma steroids concentrations. Seven out of eight (87.5%) of gestating females presented ovarian follicular activity under progesterone levels >3 nmol/l with maximum follicular size of 8.42 ± 0.83 mm from days 23 to 1 before delivery. After delivery, all females have follicular wave development from day 0 to 38, with larger follicular size and longer follicular wave phases and interwave interval when compared with pre-partum data. During post-partum period, there was a close relationship between follicle size and estradiol-17β concentration, with r = 0.69 at the beginning of growth phase and r = 0.86 in association with the largest dominant follicle. Plasma estradiol-17β concentration varied from 11.92 to 198.55 pmol/l. Plasma estrone sulfate, free estrone and progesterone returned to baseline concentrations during peripartal period and remained basal thereafter. The results described follicular activity during late gestation and early post-partum period. These findings provide relevant information to understand physiological changes occurring during this reproductive key period in seasonal breeders with long gestation duration as New and Old World camelids.

  6. Extending the Impact of RAC1b Overexpression to Follicular Thyroid Carcinomas

    PubMed Central

    Faria, Márcia; Capinha, Liliana; Simões-Pereira, Joana; Bugalho, Maria João; Silva, Ana Luísa

    2016-01-01

    RAC1b is a hyperactive variant of the small GTPase RAC1 known to be a relevant molecular player in different cancers. Previous studies from our group lead to the evidence that its overexpression in papillary thyroid carcinoma (PTC) is associated with an unfavorable prognosis. In the present study, we intended to extend the analysis of RAC1b expression to thyroid follicular neoplasms and to seek for clinical correlations. RAC1b expression levels were determined by RT-qPCR in thyroid follicular tumor samples comprising 23 follicular thyroid carcinomas (FTCs) and 33 follicular thyroid adenomas (FTAs). RAC1b was found to be overexpressed in 33% of carcinomas while no RAC1b overexpression was documented among follicular adenomas. Patients with a diagnosis of FTC were divided into two groups based on longitudinal evolution and final outcome. RAC1b overexpression was significantly associated with both the presence of distant metastases (P = 0.01) and poorer clinical outcome (P = 0.01) suggesting that, similarly to that previously found in PTCs, RAC1b overexpression in FTCs is also associated with worse outcomes. Furthermore, the absence of RAC1b overexpression in follicular adenomas hints its potential as a molecular marker likely to contribute, in conjunction with other putative markers, to the preoperative differential diagnosis of thyroid follicular lesions. PMID:27127508

  7. Extending the Impact of RAC1b Overexpression to Follicular Thyroid Carcinomas.

    PubMed

    Faria, Márcia; Capinha, Liliana; Simões-Pereira, Joana; Bugalho, Maria João; Silva, Ana Luísa

    2016-01-01

    RAC1b is a hyperactive variant of the small GTPase RAC1 known to be a relevant molecular player in different cancers. Previous studies from our group lead to the evidence that its overexpression in papillary thyroid carcinoma (PTC) is associated with an unfavorable prognosis. In the present study, we intended to extend the analysis of RAC1b expression to thyroid follicular neoplasms and to seek for clinical correlations. RAC1b expression levels were determined by RT-qPCR in thyroid follicular tumor samples comprising 23 follicular thyroid carcinomas (FTCs) and 33 follicular thyroid adenomas (FTAs). RAC1b was found to be overexpressed in 33% of carcinomas while no RAC1b overexpression was documented among follicular adenomas. Patients with a diagnosis of FTC were divided into two groups based on longitudinal evolution and final outcome. RAC1b overexpression was significantly associated with both the presence of distant metastases (P = 0.01) and poorer clinical outcome (P = 0.01) suggesting that, similarly to that previously found in PTCs, RAC1b overexpression in FTCs is also associated with worse outcomes. Furthermore, the absence of RAC1b overexpression in follicular adenomas hints its potential as a molecular marker likely to contribute, in conjunction with other putative markers, to the preoperative differential diagnosis of thyroid follicular lesions. PMID:27127508

  8. Functional impact of dendritic branch point morphology

    PubMed Central

    Ferrante, Michele; Migliore, Michele; Ascoli, Giorgio A.

    2013-01-01

    Cortical pyramidal cells store multiple features of complex synaptic input in individual dendritic branches and independently regulate the coupling between dendritic and somatic spikes. Branch points in apical trees exhibit wide ranges of sizes and shapes, and the large diameter ratio between trunk and oblique dendrites exacerbates impedance mismatch. The morphological diversity of dendritic bifurcations could thus locally tune neuronal excitability and signal integration. However, these aspects have never been investigated. Here, we first quantified the morphological variability of branch points from two-photon images of rat CA1 pyramidal neurons. We then investigated the geometrical features affecting spike initiation, propagation, and timing with a computational model validated by glutamate uncaging experiments. The results suggest that even subtle membrane readjustments at branch point could drastically alter the ability of synaptic input to generate, propagate, and time action potentials. PMID:23365251

  9. Dendritic spine dysgenesis in Autism Related Disorders

    PubMed Central

    Phillips, Mary; Pozzo-Miller, Lucas

    2015-01-01

    The activity-dependent structural and functional plasticity of dendritic spines has led to the long-standing belief that these neuronal compartments are the subcellular sites of learning and memory. Of relevance to human health, central neurons in several neuropsychiatric illnesses, including autism related disorders, have atypical numbers and morphologies of dendritic spines. These so-called dendritic spine dysgeneses found in individuals with autism related disorders are consistently replicated in experimental mouse models. Dendritic spine dysgenesis reflects the underlying synaptopathology that drives clinically relevant behavioral deficits in experimental mouse models, providing a platform for testing new therapeutic approaches. By examining molecular signaling pathways, synaptic deficits, and spine dysgenesis in experimental mouse models of autism related disorders we find strong evidence for mTOR to be a critical point of convergence and promising therapeutic target. PMID:25578949

  10. Dendritic cells are stressed out in tumor.

    PubMed

    Maj, Tomasz; Zou, Weiping

    2015-09-01

    A recently paper published in Cell reports that dendritic cells (DCs) are dysfunctional in the tumor environment. Tumor impairs DC function through induction of endoplasmic reticulum stress response and subsequent disruption of lipid metabolic homeostasis.

  11. Dendritic Growth in Nematic Liquid Crystals

    NASA Astrophysics Data System (ADS)

    Martin, Joshua; Garg, Shila

    2000-03-01

    The experimental study of the onset of electrohydrodynamic convection (EHC) through a dendritic growth is reported. If a magnetic Freedericksz-distorted liquid crystal of negative dielectric anisotropy is subjected to an electric field parallel to the magnetic field, EHC sets in through the nucleation of dendrites [1,2]. Measurements of tip speeds of the dendrites as a function of applied voltage at a fixed magnetic field are made. The goal is to explore the effect of the magnetic and electric fields on the dendritic growth. In addition, pattern dynamics is monitored once the final state of spatio-temporal chaos is reached by the system. [1] J. T. Gleeson, Nature 385, 511 (1997). [2] J. T. Gleeson, Physica A 239, 211 (1997). This research was supported by NSF grants DMR 9704579 and DMR 9619406.

  12. Dendritic spine dysgenesis in autism related disorders.

    PubMed

    Phillips, Mary; Pozzo-Miller, Lucas

    2015-08-01

    The activity-dependent structural and functional plasticity of dendritic spines has led to the long-standing belief that these neuronal compartments are the subcellular sites of learning and memory. Of relevance to human health, central neurons in several neuropsychiatric illnesses, including autism related disorders, have atypical numbers and morphologies of dendritic spines. These so-called dendritic spine dysgeneses found in individuals with autism related disorders are consistently replicated in experimental mouse models. Dendritic spine dysgenesis reflects the underlying synaptopathology that drives clinically relevant behavioral deficits in experimental mouse models, providing a platform for testing new therapeutic approaches. By examining molecular signaling pathways, synaptic deficits, and spine dysgenesis in experimental mouse models of autism related disorders we find strong evidence for mTOR to be a critical point of convergence and promising therapeutic target. PMID:25578949

  13. Dendritic spine dysgenesis in Rett syndrome

    PubMed Central

    Xu, Xin; Miller, Eric C.; Pozzo-Miller, Lucas

    2014-01-01

    Spines are small cytoplasmic extensions of dendrites that form the postsynaptic compartment of the majority of excitatory synapses in the mammalian brain. Alterations in the numerical density, size, and shape of dendritic spines have been correlated with neuronal dysfunction in several neurological and neurodevelopmental disorders associated with intellectual disability, including Rett syndrome (RTT). RTT is a progressive neurodevelopmental disorder associated with intellectual disability that is caused by loss of function mutations in the transcriptional regulator methyl CpG-binding protein 2 (MECP2). Here, we review the evidence demonstrating that principal neurons in RTT individuals and Mecp2-based experimental models exhibit alterations in the number and morphology of dendritic spines. We also discuss the exciting possibility that signaling pathways downstream of brain-derived neurotrophic factor (BDNF), which is transcriptionally regulated by MeCP2, offer promising therapeutic options for modulating dendritic spine development and plasticity in RTT and other MECP2-associated neurodevelopmental disorders. PMID:25309341

  14. Selective follicular targeting by modification of the particle sizes.

    PubMed

    Patzelt, Alexa; Richter, Heike; Knorr, Fanny; Schäfer, Ulrich; Lehr, Claus-Michael; Dähne, Lars; Sterry, Wolfram; Lademann, Juergen

    2011-02-28

    Hair follicles represent interesting target sites for topically applied substances such as topical vaccinations or agents used in the field of regenerative medicine. In recent years, it could be shown that particles penetrate very effectively into the hair follicles. In the present study, the influence of particle size on the follicular penetration depths was examined. The penetration depths of two different types of particles sized 122 to 1000 nm were determined in vitro on porcine skin. The results revealed that the particles of medium size (643 and 646 nm, respectively) penetrated deeper into the porcine hair follicles than smaller or larger particles. It was concluded that by varying the particle size, different sites within the porcine hair follicle can be targeted selectively. For the human terminal hair follicle, the situation can be expected to be similar due to a similar size ratio of the hair follicles. PMID:21087645

  15. Rare case of sclerosing mesenteritis and low grade follicular lymphoma

    PubMed Central

    Shah, Seema; Mahy, Gillian; Roche, Enrico

    2016-01-01

    An unusual case of long standing sclerosing mesenteritis; initially presented with recurrent abdominal pain and a mesenteric mass with surrounding fat oedema and stranding with a pseudocapsule and fat ring sign were clearly visualised on the initial computed tomography scan. Laparotomy showed diffuse thickening at the root of the mesentery and histology from this specimen revealed fat necrosis and reactive lymphoid tissue consistent with sclerosing mesenteritis. Initial treatment with steroids and tamoxifen relieved the symptoms and the mass. He was maintained on tamoxifen. Three years later he developed a recurrence of his symptoms and abdominal mass that responded to a course of steroids. Two years following this, he developed a follicular Hodgkin’s lymphoma. PMID:27099861

  16. Selective follicular targeting by modification of the particle sizes.

    PubMed

    Patzelt, Alexa; Richter, Heike; Knorr, Fanny; Schäfer, Ulrich; Lehr, Claus-Michael; Dähne, Lars; Sterry, Wolfram; Lademann, Juergen

    2011-02-28

    Hair follicles represent interesting target sites for topically applied substances such as topical vaccinations or agents used in the field of regenerative medicine. In recent years, it could be shown that particles penetrate very effectively into the hair follicles. In the present study, the influence of particle size on the follicular penetration depths was examined. The penetration depths of two different types of particles sized 122 to 1000 nm were determined in vitro on porcine skin. The results revealed that the particles of medium size (643 and 646 nm, respectively) penetrated deeper into the porcine hair follicles than smaller or larger particles. It was concluded that by varying the particle size, different sites within the porcine hair follicle can be targeted selectively. For the human terminal hair follicle, the situation can be expected to be similar due to a similar size ratio of the hair follicles.

  17. Stromal Cell Contribution to Human Follicular Lymphoma Pathogenesis

    PubMed Central

    Mourcin, Frédéric; Pangault, Céline; Amin-Ali, Rada; Amé-Thomas, Patricia; Tarte, Karin

    2012-01-01

    Follicular lymphoma (FL) is the prototypical model of indolent B cell lymphoma displaying a strong dependence on a specialized cell microenvironment mimicking normal germinal center. Within malignant cell niches in invaded lymph nodes and bone marrow, external stimuli provided by infiltrating stromal cells make a pivotal contribution to disease development, progression, and drug resistance. The crosstalk between FL B cells and stromal cells is bidirectional, causing activation of both partners. In agreement, FL stromal cells exhibit specific phenotypic, transcriptomic, and functional properties. This review highlights the critical pathways involved in the direct tumor-promoting activity of stromal cells but also their role in the organization of FL cell niche through the recruitment of accessory immune cells and their polarization to a B cell supportive phenotype. Finally, deciphering the interplay between stromal cells and FL cells provides potential new therapeutic targets with the aim to mobilize malignant cells outside their protective microenvironment and increase their sensitivity to conventional treatment. PMID:22973275

  18. Follicular contact dermatitis due to coloured permanent-pressed sheets

    PubMed Central

    Panaccio, François; Montgomery, D. C.; Adam, J. E.

    1973-01-01

    A delayed hypersensitivity type of allergic contact dermatitis was observed following exposure to certain brands of 50% cotton, 50% polyester coloured permanent-pressed sheets produced by a particular manufacturer. The dermatitis presented as an extremely pruritic follicular eczema of the body and vesicular edema of the ears and face. Patch testing excluded formalin as the allergen but suggested permanent-pressing chemicals as a possibility. Several washings of the sheets did not prevent the development of the dermatitis. The removal of sheets did not immediately result in improvement: the condition could persist for up to eight weeks after their discontinuance. ImagesFIG. 1FIG. 2FIG. 3FIG. 4FIG. 5 PMID:4268628

  19. Beneficial effects of GnRH agonist administration prior to ovarian stimulation for patients with a short follicular phase.

    PubMed

    Cédrin-Durnerin, I; Bstandig, B; Galey, J; Bry-Gauillard, H; Massin, N; Hugues, J-N

    2003-09-01

    A short follicular phase is an early clinical feature of declining reproductive competence. The shortening of the follicular phase length is related to both advanced recruitment and selection of the dominant follicle secondary to an earlier and higher FSH rise during the luteal-follicular transition, while the late follicular growth is normal. As a short follicular phase may be detrimental for reproduction, it was postulated that increasing the duration of follicular phase could improve conception rate. For that purpose, gonadotrophin-releasing hormone agonist minidoses were administered in the mid-luteal phase to prevent the intercycle FSH rise before tailoring follicular growth by controlled exogenous FSH administration. This regimen, applied to 69 infertile ovulatory women with a short follicular phase (9.6 +/- 1.2 days) actually lengthened the follicular phase by about 3 days. It proved to be effective in 179 cycles to induce paucifollicular development (1.8 +/- 0.9 follicles) with a low cancellation rate (4%) and a moderate requirement for gonadotrophins [13.3 +/- 6.3 ampoules (75 IU)]. In those women with a high frequency (80%) of elevated basal FSH or oestradiol concentrations, the pregnancy rate reached 15.1%/cycle but the miscarriage rate remained high (44%). Thus, increasing the follicular phase length in patients with a short follicular phase may partially restore fecundity.

  20. Dendritic cells in autoimmune thyroid disease.

    PubMed

    Kabel, P J; Voorbij, H A; van der Gaag, R D; Wiersinga, W M; de Haan, M; Drexhage, H A

    1987-01-01

    Dendritic cells form a morphologically distinct class of cells characterized by shape, reniform nucleus, absent to weak acid-phosphatase activity and strong Class II MHC determinant positivity. Functionally they are the most efficient cells in antigen presentation to T-lymphocytes which indicates their role in the initiation of an immune response. Using immunehistochemical techniques we studied the presence of dendritic cells in normal Wistar rat and human thyroids, in thyroids of BBW rats developing thyroid autoimmunity and in Graves' goitres. Dendritic cells could be identified in all thyroids studied and were positioned underneath the thyrocytes in between the follicles. Skin dendritic cells travel via lymphatics to draining lymph nodes, thus forming an antigen presenting cell system. It is likely that a similar cell system exists on the level of the thyroid for dendritic cells have also been detected in thyroid draining lymph nodes. In normal thyroid tissue of both human and rat dendritic cells were relatively scarce. During the initial phases of the thyroid autoimmune response in the BBW rat (before the appearance of Tg-antibodies in the circulation) numbers of thyroid dendritic cells increased. Intrathyroidal T-helper cells, B-cells or plasma cells could not be found. The thyroid draining lymph node contained large numbers of plasma cells. During the later stages of the thyroid autoimmune response in the BB/W rat (after the appearance of Tg-antibodies in the circulation) and in Graves' goitres dendritic cells were not only present in high number, but 20-30% were seen in contact with now-present intrathyroidal T-helper lymphocytes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3475920

  1. Non-synaptic dendritic spines in neocortex.

    PubMed

    Arellano, J I; Espinosa, A; Fairén, A; Yuste, R; DeFelipe, J

    2007-03-16

    A long-held assumption states that each dendritic spine in the cerebral cortex forms a synapse, although this issue has not been systematically investigated. We performed complete ultrastructural reconstructions of a large (n=144) population of identified spines in adult mouse neocortex finding that only 3.6% of the spines clearly lacked synapses. Nonsynaptic spines were small and had no clear head, resembling dendritic filopodia, and could represent a source of new synaptic connections in the adult cerebral cortex.

  2. Dendritic cells in autoimmune thyroid disease.

    PubMed

    Kabel, P J; Voorbij, H A; van der Gaag, R D; Wiersinga, W M; de Haan, M; Drexhage, H A

    1987-01-01

    Dendritic cells form a morphologically distinct class of cells characterized by shape, reniform nucleus, absent to weak acid-phosphatase activity and strong Class II MHC determinant positivity. Functionally they are the most efficient cells in antigen presentation to T-lymphocytes which indicates their role in the initiation of an immune response. Using immunehistochemical techniques we studied the presence of dendritic cells in normal Wistar rat and human thyroids, in thyroids of BBW rats developing thyroid autoimmunity and in Graves' goitres. Dendritic cells could be identified in all thyroids studied and were positioned underneath the thyrocytes in between the follicles. Skin dendritic cells travel via lymphatics to draining lymph nodes, thus forming an antigen presenting cell system. It is likely that a similar cell system exists on the level of the thyroid for dendritic cells have also been detected in thyroid draining lymph nodes. In normal thyroid tissue of both human and rat dendritic cells were relatively scarce. During the initial phases of the thyroid autoimmune response in the BBW rat (before the appearance of Tg-antibodies in the circulation) numbers of thyroid dendritic cells increased. Intrathyroidal T-helper cells, B-cells or plasma cells could not be found. The thyroid draining lymph node contained large numbers of plasma cells. During the later stages of the thyroid autoimmune response in the BB/W rat (after the appearance of Tg-antibodies in the circulation) and in Graves' goitres dendritic cells were not only present in high number, but 20-30% were seen in contact with now-present intrathyroidal T-helper lymphocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

  3. Cortisol concentrations in follicular fluid of 'low responder' patients.

    PubMed

    Bider, D; Shine, S; Tur-Kaspa, I; Levron, J; Dor, J

    1998-01-01

    The study was undertaken to examine any differences existing in total cortisol concentrations in the follicular fluid (FF) of pre-ruptured follicles between 'low responder' patients (group 1, n = 20) and 'good responder' patients (group 2, n = 15). The groups were defined according to how many oocytes had been retrieved during the previous in-vitro fertilization procedure (group 1: three or fewer; group 2: more than three) and total oestradiol concentration at previous in-vitro fertilization (IVF) (group 1: < or = 500 pg/ml; group 2: > 500 pg/ml). All patients were aged 36-43 years (group 1 mean +/- SD: 38.2 +/- 4.7; group 2: 32.1 +/- 3.8 years) and were diagnosed with tubal or unexplained infertility. The total FF cortisol concentrations obtained in conjunction with an IVF procedure were assayed and related to oocyte fertilization. Follicular fluid was analysed for total cortisol content. Only follicles between 19 and 20 mm diameter were analysed in both groups. After aspiration of blood-free FF, total cortisol concentrations were measured by radioimmunoassay, designed for the quantitative measurement of cortisol, and related to oocyte fertilization. Total cortisol concentration in FF from fertilized oocytes was 9.7 +/- 0.6 microg/ml (mean +/- SD) in group 1 compared to 9.2 +/- 4.4 microg/ml in group 2 (not statistically significant). Total cortisol concentrations were not associated with oocyte fertilization and no difference between the groups was found in total cortisol concentrations in the FF of unfertilized oocytes or empty follicles.

  4. Transcranial magnetic stimulation (TMS) inhibits cortical dendrites

    PubMed Central

    Murphy, Sean C; Palmer, Lucy M; Nyffeler, Thomas; Müri, René M; Larkum, Matthew E

    2016-01-01

    One of the leading approaches to non-invasively treat a variety of brain disorders is transcranial magnetic stimulation (TMS). However, despite its clinical prevalence, very little is known about the action of TMS at the cellular level let alone what effect it might have at the subcellular level (e.g. dendrites). Here, we examine the effect of single-pulse TMS on dendritic activity in layer 5 pyramidal neurons of the somatosensory cortex using an optical fiber imaging approach. We find that TMS causes GABAB-mediated inhibition of sensory-evoked dendritic Ca2+ activity. We conclude that TMS directly activates fibers within the upper cortical layers that leads to the activation of dendrite-targeting inhibitory neurons which in turn suppress dendritic Ca2+ activity. This result implies a specificity of TMS at the dendritic level that could in principle be exploited for investigating these structures non-invasively. DOI: http://dx.doi.org/10.7554/eLife.13598.001 PMID:26988796

  5. Silver nanowire interactions with primary human alveolar type-II epithelial cell secretions: contrasting bioreactivity with human alveolar type-I and type-II epithelial cells

    PubMed Central

    Sweeney, Sinbad; Theodorou, Ioannis G.; Zambianchi, Martina; Chen, Shu; Gow, Andrew; Schwander, Stephan; Zhang, Junfeng (Jim); Chung, Kian Fan; Shaffer, Milo S.; Ryan, Mary P.; Porter, Alexandra E.; Tetley, Teresa D.

    2015-01-01

    Inhaled nanoparticles have a high deposition rate in the alveolar units of the deep lung. The alveolar epithelium is composed of type-I and type-II epithelial cells (ATI and ATII respectively) and is bathed in pulmonary surfactant. The effect of native human ATII cell secretions on nanoparticle toxicity is not known. We investigated the cellular uptake and toxicity of silver nanowires (AgNWs; 70 nm diameter, 1.5 μm length) with human ATI-like cells (TT1), in the absence or presence of Curosurf® (a natural porcine pulmonary surfactant with a low amount of protein) or harvested primary human ATII cell secretions (HAS; containing both the complete lipid as well as the full protein complement of human pulmonary surfactant i.e. SP-A, SP-B, SP-C and SP-D). We hypothesised that Curosurf® or HAS would confer improved protection for TT1 cells, limiting the toxicity of AgNWs. In agreement with our hypothesis, HAS reduced the inflammatory and reactive oxygen species (ROS)-generating potential of AgNWs with exposed TT1 cells. For example, IL-8 release and ROS generation was reduced by 38% and 29%, respectively, resulting in similar levels to that of the non-treated controls. However in contrast to our hypothesis, Curosurf® had no effect. We found a significant reduction in AgNW uptake by TT1 cells in the presence of HAS but not Curosurf. Furthermore, we show that the SP-A and SP-D are likely to be involved in this process as they were found to be specifically bound to the AgNWs. While ATI cells appear to be protected by HAS, evidence suggested that ATII cells, despite no uptake, were vulnerable to AgNW exposure (indicated by increased IL-8 release and ROS generation and decreased intracellular SP-A levels one day post-exposure). This study provides unique findings that may be important for the study of lung epithelial-endothelial translocation of nanoparticles in general and associated toxicity within the alveolar unit. PMID:25996248

  6. Architecture of apical dendrites in the murine neocortex: dual apical dendritic systems.

    PubMed

    Escobar, M I; Pimienta, H; Caviness, V S; Jacobson, M; Crandall, J E; Kosik, K S

    1986-04-01

    A monoclonal antibody (5F9) against microtubule-associated protein 2 is a selective and sensitive marker for neocortical dendrites in the mouse. The marker stains all dendrites. It affords a particularly comprehensive picture of the patterns of arrangements of apical dendrites which are most intensely stained with this antibody. Dual systems of apical dendrites arise from the polymorphic neurons of layer VI, on the one hand, and the pyramidal neurons of layers II-V, on the other. Terminal arborization of the former is concentrated principally at the interface of layers V and IV, while that of the latter is in the molecular layer. Apical dendrites of both systems are grouped into fascicles. In supragranular layers and in upper layer VI-lower layer V, where apical dendrites are most abundant, the fascicles coalesce into septa. These generate a honeycomb-like pattern, subdividing these cortical levels into columnar spaces of approximately 20-40 micron diameter. At the level of layer IV, where the number of apical dendrites is greatly reduced, the fascicles are isolated bundles. These bundles have the form of circular, elliptical or rectangular columns in the primary somatosensory, temporal and frontal regions, respectively. Those in the barrel field are preferentially concentrated in the sides of barrels and the interbarrel septa. The configurations of the dendritic fascicles, particularly the midcortical bundles, may conform to the spatial configuration of investing axons of interneurons.

  7. Neuroblastoma and dendritic cell function.

    PubMed

    Redlinger, Richard E; Mailliard, Robbie B; Barksdale, Edward M

    2004-02-01

    Neuroblastoma, the most common extracranial solid tumor of childhood, remains a challenge for clinicians and investigators in pediatric surgical oncology. The absence of effective conventional therapies for most patients with neuroblastoma justifies the application of novel, biology-based, experimental approaches to the treatment of this deadly disease. The observation that some aggressive neuroblastomas, particularly in infants, may spontaneously regress suggested that immune-mediated mechanisms may be important in the biology of this disease. Advances in the understanding of the cognate interactions between T cells, antigen-presenting cells and tumors have demonstrated the sentinel role of dendritic cells (DC), the most potent antigen presenting cells, in initiating the cellular immune response to cancer. Until recently the function of DC in pediatric solid tumors, especially neuroblastoma, had not been extensively studied. This review discusses the role of DC in initiating and coordinating the immune response against cancer, the ability of neuroblastoma to induce DC dysregulation at multiple levels by inhibiting DC maturation and function, and the current vaccine strategies being designed to employ the unique ability of DC to promote neuroblastoma regression.

  8. Targeting vaccines to dendritic cells.

    PubMed

    Foged, Camilla; Sundblad, Anne; Hovgaard, Lars

    2002-03-01

    Dendritic cells (DC) are specialized antigen presenting cells (APC) with a remarkable ability to take up antigens and stimulate major histocompatibility complex (MHC)-restricted specific immune responses. Recent discoveries have shown that their role in initiating primary immune responses seems to be far superior to that of B-cells and macrophages. DC are localized at strategic places in the body at sites used by pathogens to enter the organism, and are thereby in an optimal position to capture antigens. In general, vaccination strategies try to mimic the invasiveness of the pathogens. DC are considered to play a central role for the provocation of primary immune responses by vaccination. A rational way of improving the potency and safety of new and already existing vaccines could therefore be to direct vaccines specifically to DC. There is a need for developing multifunctional vaccine drug delivery systems (DDS) with adjuvant effect that target DC directly and induce optimal immune responses. This paper will review the current knowledge of DC physiology as well as the progress in the field of novel vaccination strategies that directly or indirectly aim at targeting DC.

  9. Perinatal opiate treatment delays growth of cortical dendrites.

    PubMed

    Ricalde, A A; Hammer, R P

    1990-07-31

    Basilar dendritic arborizations of layer II-III pyramidal neurons in primary somatosensory cortex of 5-day-old male rats were reconstructed following perinatal morphine, morphine/naltrexone, or saline vehicle administration. Morphine treatment was observed to reduce total dendritic length. This effect was limited to higher order dendritic branches, with terminal dendrites manifesting the greatest reduction of length. The action of morphine was presumably mediated by opiate receptors, since concurrent naltrexone administration completely reversed morphine effects on dendritic length and branching. These results suggest that opiates act during late ontogenesis to affect dendritic growth in cerebral cortex. PMID:2172870

  10. Dendritic crystal growth in pure /sup 4/He

    SciTech Connect

    Franck, J.P.; Jung, J.

    1986-08-01

    Dendritic crystal growth of pure hcp and fcc /sup 4/He was observed at pressures between 210 and 6500 bar. Dendrite morphology depends on fluid supercooling and crystal phase. At large supercooling, dendrites with side arms are observed, whereas at low supercooling dendrites grow without side arms. The morpholpogy of hcp /sup 4/He dendrites is strongly influenced by crystalline anisotropy. Comparison with present theories of dendrite growth show good agreement with the power law dependencies of velocity, tip radius, and Peclet number on supercooling. Numerically, theory predicts much larger velocities than are observed. The stability parameter sigma is found to be much smaller than theoretically predicted.

  11. Effect of sheep and human follicular fluid on the maturation of sheep oocytes in vitro.

    PubMed

    Sun, F J; Holm, P; Irvine, B; Seamark, R F

    1994-01-01

    This study examines the effect of sheep and human follicular fluid on the in vitro maturation (IVM) of sheep follicular oocytes. Oocyte cumulus complexes recovered post mortem were matured for 24 to 26 h at 38.6 degrees C, 5% CO(2) in air, in TCM-199 bicarbonate medium supplemented with 20% fetal calf serum (FCS) and, where stated, with maturation hormones, including FSH (5.0 microg/ml), LH (5.0 microg/ml) and estradiol (1 microg/ml), or with sheep follicular fluid recovered from large (>5 mm) or small (2 to 5 mm) ovarian follicles post mortem, or with human periovular follicular fluid obtained during routine IVF procedures. The matured oocytes were then denuded, and their maturation stage and developmental capacity were assessed by in vitro fertilization (IVF) and culture (IVC). It was found that inclusion of sheep or human follicular fluid or hormone supplements in the IVM media more than doubled the number of oocytes completing maturation (FCS alone 33%, compared with 76.2% for maturation hormones, 84.2% for fluid from large and 69.6% for fluid from small sheep follicles and 82.6% for human follicular fluid), and significantly increased fertilization rates (FCS alone 51.6%, compared with 71.9% for maturation hormones, 78.4% for fluid from the large and 75.7% for fluid from small sheep follicles and 73.1% for human follicular fluid) without discernible adverse effects on the development of the cleaving embryos to the morula or blastocyst stage in culture. Omission of FCS and supplements from the IVM medium resulted in a marked reduction (56%) in the number of oocytes maturing. This reduction could be offset to a large part, but not completely, by inclusion of human follicular fluid or human follicular fluid plus LH (5 microg/ml) in the medium. The results of this study show that addition of sheep or human follicular fluid to maturation medium can enhance rather than inhibit the maturation and fertilizability of sheep follicular oocytes in vitro. PMID:16727451

  12. Effect of the stage of estrous cycle on follicular population, oocyte yield and quality, and biochemical composition of serum and follicular fluid in Anatolian water buffalo.

    PubMed

    Baki Acar, Duygu; Birdane, Muhammed Kursad; Dogan, Nurhan; Gurler, Hande

    2013-02-01

    This study was designed to investigate the effects that the different stages of the estrous cycle had on the number of surface ovarian follicles and oocyte yield and quality of Anatolian water buffalo during peak breeding season. Assessments were made on the basis of ovarian morphology, serum and follicular fluid concentrations of variety of biochemical parameters. Following slaughter, blood samples were collected from each animal. The stage of estrous cycle was classified as either the luteal or follicular phase, and surface ovarian follicles were classified as small, medium, or large. The follicular fluid was aspirated, and oocytes were evaluated microscopically for classification into four categories. No statistical differences (p>0.05) were observed regarding the total number of follicles or quality of oocytes relative to the stage of the estrous cycle. Serum high-density lipoprotein cholesterol (HDL), alkaline phosphatase (ALP) and progesterone (P4) concentrations were significantly higher in the luteal phase than in the follicular phase (P<0.05). Significant correlations were observed in the luteal phase between the total number of oocytes and cholesterol (Cho), HDL, sodium (Na), chloride (Cl); A-quality oocytes and Na, Cl, Mg; C-quality oocytes and Cho, HDL, and Mg in follicular fluid. These results offer new information concerning Anatolian water buffalo reproductive physiology, which may be useful for improving oocyte quality in buffalo. This is the first study to describe the number of ovarian follicles, oocyte yield and quality, and a variety of biochemical parameters in the serum and follicular fluid of Anatolian water buffalo during peak breeding season in Turkey.

  13. Ureteral lesion secondary to vaginal ultrasound follicular puncture for oocyte recovery in in-vitro fertilization.

    PubMed

    Coroleu, B; Lopez Mourelle, F; Hereter, L; Veiga, A; Calderón, G; Martinez, F; Carreras, O; Barri, P N

    1997-05-01

    Techniques of oocyte retrieval have progressed from laparoscopy to transvaginal follicular aspiration under ultrasonographic control. This highly efficient method, routinely used nowadays, is not free of complications. We present a case of a ureteral lesion secondary to vaginal ultrasound follicular puncture for oocyte recovery in in-vitro fertilization. Despite the surgical procedure to reimplant the ureter, the patient achieved a twin pregnancy which is ongoing uneventfully.

  14. Vascular expression of E-selectin is increased in estrogen-receptor-negative breast cancer: a role for tumor-cell-secreted interleukin-1 alpha.

    PubMed Central

    Nguyen, M.; Corless, C. L.; Kräling, B. M.; Tran, C.; Atha, T.; Bischoff, J.; Barsky, S. H.

    1997-01-01

    Angiogenesis plays an important role in breast cancer growth and metastasis. Multiple adhesion molecules have been shown to perform critical functions in the process of angiogenesis. In this study, we analyzed 15 benign and 22 malignant estrogen-receptor-negative and estrogen-receptor-positive breast specimens for the presence of the endothelial cell adhesion molecules E-selectin and P-selectin. We found that E-selectin's expression was increased in the malignant breast tumors compared with their benign counterparts (23.86% of blood vessels versus 2.47%; P = 0.0005). Furthermore, E-selectin staining was found to be significantly increased in the estrogen-receptor-negative carcinomas compared with the estrogen-receptor-positive ones (P = 0.005). In vitro findings strongly correlated with the in vivo findings and showed a higher degree of E-selectin induction in endothelial cells exposed to conditioned media from estrogen-receptor-negative breast cancer cell lines than from estrogen-receptor-positive ones. The degree of E-selectin induction correlated with the amount of interleukin-1 alpha in the tumor-conditioned media. Neutralizing antibodies to interleukin-1 alpha significantly inhibited the E-selectin expression in endothelial cells exposed to tumor-conditioned media. The results indicate that the endothelial E-selectin expression during angiogenesis is related to breast carcinoma progression in vivo and that this component of angiogenesis may be due directly to tumor-cell-secreted interleukin-1 alpha. Images Figure 1 PMID:9094987

  15. Freestanding graphene paper decorated with 2D-assembly of Au@Pt nanoparticles as flexible biosensors to monitor live cell secretion of nitric oxide.

    PubMed

    Zan, Xiaoli; Fang, Zheng; Wu, Jin; Xiao, Fei; Huo, Fengwei; Duan, Hongwei

    2013-11-15

    We report the development of a new type of flexible electrochemical biosensors based on graphene paper loaded with closely-packed Au@Pt core-shell nanoparticles as a freestanding cell culture substrate for real-time monitoring cell secretion of nitric oxide. The hybrid electrode was fabricated through a modular approach in which 2D-assembly of nanoparticles formed at the oil-water interface was transferred onto graphene paper by dip-coating. We have shown that the independently optimized metal nanostructures and graphene paper were integrated into functional electrodes with high electrocatalytic activity. When used for the detection of nitric oxide, the flexible electrodes have demonstrated high sensitivity, a wide linear range, and a low detection limit, which, in combination with its biocompatibility, offer unique opportunities for the real-time monitoring of nitric oxide secretion by human endothelial vein cells grown on the electrode. These interesting findings collectively demonstrate the potential of our modular approach for designing high-performance flexible electrodes with tailored surface properties.

  16. Silver nanowire interactions with primary human alveolar type-II epithelial cell secretions: contrasting bioreactivity with human alveolar type-I and type-II epithelial cells

    NASA Astrophysics Data System (ADS)

    Sweeney, Sinbad; Theodorou, Ioannis G.; Zambianchi, Marta; Chen, Shu; Gow, Andrew; Schwander, Stephan; Zhang, Junfeng (Jim); Chung, Kian Fan; Shaffer, Milo S. P.; Ryan, Mary P.; Porter, Alexandra E.; Tetley, Teresa D.

    2015-06-01

    Inhaled nanoparticles have a high deposition rate in the alveolar units of the deep lung. The alveolar epithelium is composed of type-I and type-II epithelial cells (ATI and ATII respectively) and is bathed in pulmonary surfactant. The effect of native human ATII cell secretions on nanoparticle toxicity is not known. We investigated the cellular uptake and toxicity of silver nanowires (AgNWs; 70 nm diameter, 1.5 μm length) with human ATI-like cells (TT1), in the absence or presence of Curosurf® (a natural porcine pulmonary surfactant with a low amount of protein) or harvested primary human ATII cell secretions (HAS; containing both the complete lipid as well as the full protein complement of human pulmonary surfactant i.e. SP-A, SP-B, SP-C and SP-D). We hypothesised that Curosurf® or HAS would confer improved protection for TT1 cells, limiting the toxicity of AgNWs. In agreement with our hypothesis, HAS reduced the inflammatory and reactive oxygen species (ROS)-generating potential of AgNWs with exposed TT1 cells. For example, IL-8 release and ROS generation was reduced by 38% and 29%, respectively, resulting in similar levels to that of the non-treated controls. However in contrast to our hypothesis, Curosurf® had no effect. We found a significant reduction in AgNW uptake by TT1 cells in the presence of HAS but not Curosurf. Furthermore, we show that the SP-A and SP-D are likely to be involved in this process as they were found to be specifically bound to the AgNWs. While ATI cells appear to be protected by HAS, evidence suggested that ATII cells, despite no uptake, were vulnerable to AgNW exposure (indicated by increased IL-8 release and ROS generation and decreased intracellular SP-A levels one day post-exposure). This study provides unique findings that may be important for the study of lung epithelial-endothelial translocation of nanoparticles in general and associated toxicity within the alveolar unit.Inhaled nanoparticles have a high deposition rate in

  17. Cell-secreted flavins bound to membrane cytochromes dictate electron transfer reactions to surfaces with diverse charge and pH.

    PubMed

    Okamoto, Akihiro; Kalathil, Shafeer; Deng, Xiao; Hashimoto, Kazuhito; Nakamura, Ryuhei; Nealson, Kenneth H

    2014-01-01

    The variety of solid surfaces to and from which microbes can deliver electrons by extracellular electron transport (EET) processes via outer-membrane c-type cytochromes (OM c-Cyts) expands the importance of microbial respiration in natural environments and industrial applications. Here, we demonstrate that the bifurcated EET pathway of OM c-Cyts sustains the diversity of the EET surface in Shewanella oneidensis MR-1 via specific binding with cell-secreted flavin mononucleotide (FMN) and riboflavin (RF). Microbial current production and whole-cell differential pulse voltammetry revealed that RF and FMN enhance EET as bound cofactors in a similar manner. Conversely, FMN and RF were clearly differentiated in the EET enhancement by gene-deletion of OM c-Cyts and the dependency of the electrode potential and pH. These results indicate that RF and FMN have specific binding sites in OM c-Cyts and highlight the potential roles of these flavin-cytochrome complexes in controlling the rate of electron transfer to surfaces with diverse potential and pH. PMID:25012073

  18. Neural Stem Cells Secreting Anti-HER2 Antibody Improve Survival in a Preclinical Model of HER2 Overexpressing Breast Cancer Brain Metastases.

    PubMed

    Kanojia, Deepak; Balyasnikova, Irina V; Morshed, Ramin A; Frank, Richard T; Yu, Dou; Zhang, Lingjiao; Spencer, Drew A; Kim, Julius W; Han, Yu; Yu, Dihua; Ahmed, Atique U; Aboody, Karen S; Lesniak, Maciej S

    2015-10-01

    The treatment of human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer has been revolutionized by trastuzumab. However, longer survival of these patients now predisposes them to forming HER2 positive brain metastases, as the therapeutic antibodies cannot cross the blood brain barrier. The current oncologic repertoire does not offer a rational, nontoxic targeted therapy for brain metastases. In this study, we used an established human neural stem cell line, HB1.F3 NSCs and generated a stable pool of cells secreting a high amount of functional full-length anti-HER2 antibody, equivalent to trastuzumab. Anti-HER2Ab secreted by the NSCs (HER2Ab-NSCs) specifically binds to HER2 overexpressing human breast cancer cells and inhibits PI3K-Akt signaling. This translates to HER2Ab-NSC inhibition of breast cancer cell growth in vitro. Preclinical in vivo experiments using HER2Ab overexpressing NSCs in a breast cancer brain metastases (BCBM) mouse model demonstrate that intracranial injection of HER2Ab-NSCs significantly improves survival. In effect, these NSCs provide tumor localized production of HER2Ab, minimizing any potential off-target side effects. Our results establish HER2Ab-NSCs as a novel, nontoxic, and rational therapeutic approach for the successful treatment of HER2 overexpressing BCBM, which now warrants further preclinical and clinical investigation.

  19. Follicular Oocytes Better Support Development in Rabbit Cloning Than Oviductal Oocytes

    PubMed Central

    Sung, Li-Ying; Chen, Chien-Hong; Xu, Jie; Lin, Tzu-An; Su, Hwa-Yun; Chang, Wei-Fang; Liu, Chia-Chia; Sung, Yun-Shao; Cheng, Winston T.K.; Zhang, Jifeng; Tian, X. Cindy; Ju, Jyh-Cherng; Chen, Y. Eugene

    2011-01-01

    Abstract This study was conducted to determine the effect of rabbit oocytes collected from ovaries or oviducts on the developmental potential of nuclear transplant embryos. Donor nuclei were obtained from adult skin fibroblasts, cumulus cells, and embryonic blastomeres. Rabbit oocytes were flushed from the oviducts (oviductal oocytes) or aspirated from the ovaries (follicular oocytes) of superovulated does at 10, 11, or 12 h post-hCG injection. The majority of collected oocytes were still attached to the sites of ovulation on the ovaries. We found that follicular oocytes had a significantly higher rate of fusion with nuclear donor cells than oviductal oocytes. There was no difference in the cleavage rate between follicular and oviductal groups, but morula and blastocyst development was significantly higher in the follicular group than in the oviductal group. Two live clones were produced in follicular group using blastomere and cumulus nuclear donors, whereas one live clone was produced in the oviductal group using a cumulus nuclear donor. These results demonstrate that cloned rabbit embryos derived from follicular oocytes have better developmental competence than those derived from oviductal oocytes. PMID:22029417

  20. Elucidation and Pharmacological Targeting of Novel Molecular Drivers of Follicular Lymphoma Progression.

    PubMed

    Bisikirska, Brygida; Bansal, Mukesh; Shen, Yao; Teruya-Feldstein, Julie; Chaganti, Raju; Califano, Andrea

    2016-02-01

    Follicular lymphoma, the most common indolent subtype of non-Hodgkin lymphoma, is associated with a relatively long overall survival rate ranging from 6 to 10 years from the time of diagnosis. However, in 20% to 60% of follicular lymphoma patients, transformation to aggressive diffuse large B-cell lymphoma (DLBCL) reduces median survival to only 1.2 years. The specific functional and genetic determinants of follicular lymphoma transformation remain elusive, and genomic alterations underlying disease advancement have only been identified for a subset of cases. Therefore, to identify candidate drivers of follicular lymphoma transformation, we performed systematic analysis of a B-cell-specific regulatory model exhibiting follicular lymphoma transformation signatures using the Master Regulator Inference algorithm (MARINa). This analysis revealed FOXM1, TFDP1, ATF5, HMGA1, and NFYB to be candidate master regulators (MR) contributing to disease progression. Accordingly, validation was achieved through synthetic lethality assays in which RNAi-mediated silencing of MRs individually or in combination reduced the viability of (14;18)-positive DLBCL (t-DLBCL) cells. Furthermore, specific combinations of small-molecule compounds targeting synergistic MR pairs induced loss of viability in t-DLBCL cells. Collectively, our findings indicate that MR analysis is a valuable method for identifying bona fide contributors to follicular lymphoma transformation and may therefore guide the selection of compounds to be used in combinatorial treatment strategies. PMID:26589882

  1. Age and body size of captive hawksbill turtles at the onset of follicular development.

    PubMed

    Kawazu, Isao; Kino, Masakatsu; Maeda, Konomi; Teruya, Hideshi

    2015-01-01

    The aim of this study was to record the age and body size of 23 captive female hawksbill turtles at the onset of follicular development. The age, straight carapace length (SCL), and body mass (BM) of the turtles were recorded between 2006 and 2014 at follicular development (determined via ultrasonography) these parameters were 17.7 ± 1.7 years (range: 13-20 years), 77.7 ± 3.3 cm (73.3-83.5 cm), and 61.1 ± 8.0 kg (48.2-76.1 kg), respectively. When the year of the onset of follicular development was designated year 0, the increase in SCL in years -7-0 and 0-3 averaged 2.2 cm and 1.0 cm, respectively. Correspondingly, the increase in BM in years -7-0 and 0-3 averaged 5.0 kg and 2.2 kg, respectively. This is the first study to report the age and body size of captive female hawksbill turtles at the onset of follicular development, which indicates the beginning of sexual maturation. The reduction in growth after follicular development suggests that at the onset of sexual maturation, female hawksbills may utilize energy for follicular development rather than growth.

  2. Biochemical and hormonal composition of follicular cysts in water buffalo (Bubalus bubalis).

    PubMed

    Khan, F A; Das, G K; Pande, Megha; Pathak, M K; Sarkar, M

    2011-03-01

    The objective of this study was to examine the follicular fluid biochemical and hormonal changes associated with ovarian follicular cysts in buffalo. Follicular fluid was aspirated from eight cysts and eight preovulatory follicles, and subjected to biochemical and hormonal analyses. Cysts were characterized by a greater (P<0.01) concentration of nitric oxide and lesser concentrations of ascorbic acid and glucose than that of preovulatory follicles (P<0.01 and P<0.05, respectively). Furthermore, follicular cysts had greater concentrations of progesterone (P<0.001), triiodothyronine (T(3)) and cortisol (P<0.05) and lesser concentrations of insulin (P<0.001) than preovulatory follicles. The results indicate follicular cysts in buffalo have an altered biochemical and hormonal composition. The alterations include increases in nitric oxide, progesterone, cortisol and T(3) concentrations with a concurrent reduction in ascorbic acid, insulin and glucose concentrations. The study suggests that greater progesterone concentrations possibly inhibit the onset of LH surge resulting in formation of follicular cysts in buffalo. In addition, it implies the plausible role of intra-ovarian regulators such as nitric oxide, ascorbic acid and insulin in development of the condition.

  3. Hydroxypropyl-β-Cyclodextrin Spikes Local Inflammation That Induces Th2 Cell and T Follicular Helper Cell Responses to the Coadministered Antigen

    PubMed Central

    Onishi, Motoyasu; Ozasa, Koji; Kobiyama, Kouji; Ohata, Keiichi; Kitano, Mitsutaka; Taniguchi, Keiichi; Homma, Tomoyuki; Kobayashi, Masanori; Sato, Akihiko; Katakai, Yuko; Yasutomi, Yasuhiro; Wijaya, Edward; Igarashi, Yoshinobu; Nakatsu, Noriyuki; Ise, Wataru; Inoue, Takeshi; Yamada, Hiroshi; Vandenbon, Alexis; Standley, Daron M.; Kurosaki, Tomohiro; Coban, Cevayir; Aoshi, Taiki; Kuroda, Etsushi

    2015-01-01

    Cyclodextrins are commonly used as a safe excipient to enhance the solubility and bioavailability of hydrophobic pharmaceutical agents. Their efficacies and mechanisms as drug-delivery systems have been investigated for decades, but their immunological properties have not been examined. In this study, we reprofiled hydroxypropyl-β-cyclodextrin (HP-β-CD) as a vaccine adjuvant and found that it acts as a potent and unique adjuvant. HP-β-CD triggered the innate immune response at the injection site, was trapped by MARCO+ macrophages, increased Ag uptake by dendritic cells, and facilitated the generation of T follicular helper cells in the draining lymph nodes. It significantly enhanced Ag-specific Th2 and IgG Ab responses as potently as did the conventional adjuvant, aluminum salt (alum), whereas its ability to induce Ag-specific IgE was less than that of alum. At the injection site, HP-β-CD induced the temporary release of host dsDNA, a damage-associated molecular pattern. DNase-treated mice, MyD88-deficient mice, and TBK1-deficient mice showed significantly reduced Ab responses after immunization with this adjuvant. Finally, we demonstrated that HP-β-CD–adjuvanted influenza hemagglutinin split vaccine protected against a lethal challenge with a clinically isolated pandemic H1N1 influenza virus, and the adjuvant effect of HP-β-CD was demonstrated in cynomolgus macaques. Our results suggest that HP-β-CD acts as a potent MyD88- and TBK1-dependent T follicular helper cell adjuvant and is readily applicable to various vaccines. PMID:25681338

  4. Splenic Long-Lived Plasma Cells Promote the Development of Follicular Helper T Cells during Autoimmune Responses.

    PubMed

    Jang, Eunkyeong; Cho, Wang Sik; Oh, Yeon-Kyung; Cho, Mi-La; Kim, Jung Mogg; Paik, Doo-Jin; Youn, Jeehee

    2016-02-01

    Long-lived plasma cells (LLPCs) develop under the help of follicular helper T (Tfh) cells and reside mainly in the bone marrow. However, these cells are unusually abundant in the spleen of several autoimmune models including K/BxNsf mice, yet their pathogenic impact remains unknown. To investigate a previously unappreciated role of splenic LLPCs, we sorted splenic plasma cells (PCs) from K/BxNsf and K/BxN mice, corresponding to LLPCs and conventional short-lived PCs, respectively, and compared their phenotypes and ability to prime and induce the differentiation of naive CD4(+) T cells into effector cells in vitro and in vivo. We found that K/BxNsf PCs had lower levels of the Ag presentation machinery and costimulators than K/BxN PCs, and also a lower CD4(+) T cell priming capacity. Autoantigen-pulsed K/BxNsf PCs selectively polarized cognate CD4(+) T cells toward the expression of molecules necessary for Tfh development and function. As a result, the K/BxNsf PC-primed CD4(+) T cells were more effective in stimulating B cells to produce autoantigen-specific IgGs than K/BxN PCs or even dendritic cells. Adoptive transfer of K/BxNsf PCs, but not K/BxN PCs, to K/BxN mice increased numbers of Tfh cells in draining lymph nodes. These results propose that abnormal accumulation of LLPCs in the spleen of autoimmune models drives the differentiation of autoantigen-primed CD4(+) T cells to Tfh cells. This positive feedback loop between splenic LLPCs and Tfh cells may contribute to the persistence of humoral autoimmunity. PMID:26729802

  5. DC-SIGN–expressing macrophages trigger activation of mannosylated IgM B-cell receptor in follicular lymphoma

    PubMed Central

    Amin, Rada; Mourcin, Frédéric; Uhel, Fabrice; Pangault, Céline; Ruminy, Philippe; Dupré, Loic; Guirriec, Marion; Marchand, Tony; Fest, Thierry; Lamy, Thierry

    2015-01-01

    Follicular lymphoma (FL) results from the accumulation of malignant germinal center (GC) B cells leading to the development of an indolent and largely incurable disease. FL cells remain highly dependent on B-cell receptor (BCR) signaling and on a specific cell microenvironment, including T cells, macrophages, and stromal cells. Importantly, FL BCR is characterized by a selective pressure to retain surface immunoglobulin M (IgM) BCR despite an active class-switch recombination process, and by the introduction, in BCR variable regions, of N-glycosylation acceptor sites harboring unusual high-mannose oligosaccharides. However, the relevance of these 2 FL BCR features for lymphomagenesis remains unclear. In this study, we demonstrated that IgM+ FL B cells activated a stronger BCR signaling network than IgG+ FL B cells and normal GC B cells. BCR expression level and phosphatase activity could both contribute to such heterogeneity. Moreover, we underlined that a subset of IgM+ FL samples, displaying highly mannosylated BCR, efficiently bound dendritic cell–specific intercellular adhesion molecule-3–grabbing nonintegrin (DC-SIGN), which could in turn trigger delayed but long-lasting BCR aggregation and activation. Interestingly, DC-SIGN was found within the FL cell niche in situ. Finally, M2 macrophages induced a DC-SIGN–dependent adhesion of highly mannosylated IgM+ FL B cells and triggered BCR-associated kinase activation. Interestingly, pharmacologic BCR inhibitors abolished such crosstalk between macrophages and FL B cells. Altogether, our data support an important role for DC-SIGN–expressing infiltrating cells in the biology of FL and suggest that they could represent interesting therapeutic targets. PMID:26272216

  6. Activity affects dendritic shape and synapse elimination during steroid controlled dendritic retraction in Manduca sexta.

    PubMed

    Duch, Carsten; Mentel, Tim

    2004-11-01

    Insect metamorphosis is a compelling example for dendritic and synaptic remodeling as larval and adult behaviors place distinct demands on the CNS. During the metamorphosis of the moth, Manduca sexta, many larval motoneurons are remodeled to serve a new function in the adult. During late larval life, steroid hormones trigger axonal and dendritic regression as well as larval synapse elimination. These regressive events are accompanied by stereotypical changes in motor behavior during the so-called wandering stages. Both normally occurring changes in dendritic shape and in motor output have previously been analyzed quantitatively for the individually identified motoneuron MN5. This study tested whether activity affected steroid-induced dendritic regression and synapse disassembly in MN5 by means of chronically implanted extracellular electrodes. Stimulating MN5 in vivo in intact, normally developing animals during a developmental period when it usually shows no activity significantly slowed the regression of high-order dendrites. Both physiological and anatomical analysis demonstrated that reduced dendritic regression was accompanied by a significant reduction in larval synapse disassembly. Therefore, steroid-induced alterations of dendritic shape and synaptic connectivity are modified by activity-dependent mechanisms. This interaction might be a common mechanism for rapid adjustments of rigid, inflexible, hormonal programs.

  7. Successful Isothermal Dendritic Growth Experiment (IDGE) Proves Current Theories of Dendritic Solidification are Flawed

    NASA Technical Reports Server (NTRS)

    1996-01-01

    The scientific objective of the Isothermal Dendritic Growth Experiment (IDGE) is to test fundamental assumptions about dendritic solidification of molten materials. "Dendrites"-- from the ancient Greek word for tree--are tiny branching structures that form inside molten metal alloys when they solidify during manufacturing. The size, shape, and orientation of the dendrites have a major effect on the strength, ductility (ability to be molded or shaped), and usefulness of an alloy. Nearly all of the cast metal alloys used in everyday products (such as automobiles and airplanes) are composed of thousands to millions of tiny dendrites. Gravity, present on Earth, causes convection currents in molten alloys that disturb dendritic solidification and make its precise study impossible. In space, gravity is negated by the orbiting of the space shuttle. Consequently, IDGE (which was conducted on the space shuttle) gathered the first precise data regarding undisturbed dendritic solidification. IDGE is a microgravity materials science experiment that uses an apparatus which was designed, built, tested, and operated by people from the NASA Lewis Research Center. This experiment was conceived by the principal investigator, Professor Martin E. Glicksman, from Rensselaer Polytechnic Institute in Troy, New York. The experiment was a team effort of Lewis civil servants, contractors from Aerospace Design & Fabrication Inc. (ADF), and personnel at Rensselaer.

  8. Suppression of zinc dendrites in zinc electrode power cells

    NASA Technical Reports Server (NTRS)

    Damjanovic, A.; Diggle, J. W.

    1970-01-01

    Addition of various tetraalkyl quarternary ammonium salts, to alkaline zincate electrolyte of cell, prevents formation of zinc dendrites during charging of zinc electrode. Electrode capacity is not impaired and elimination of dendrites prolongs cell life.

  9. Roxithromycin-loaded lipid nanoparticles for follicular targeting.

    PubMed

    Wosicka-Frąckowiak, Hanna; Cal, Krzysztof; Stefanowska, Justyna; Główka, Eliza; Nowacka, Magdalena; Struck-Lewicka, Wiktoria; Govedarica, Biljana; Pasikowska, Monika; Dębowska, Renata; Jesionowski, Teofil; Srčič, Stane; Markuszewski, Michał Jan

    2015-11-30

    Particulate drug carriers e.g. nanoparticles (NPs) have been shown to penetrate and accumulate preferentially in skin hair follicles creating high local concentration of a drug. In order to develop such a follicle targeting system we obtained and characterized solid lipid nanoparticles (SLN) loaded with roxithromycin (ROX). The mean particle size (172±2 nm), polydisperisty index (0.237±0.007), zeta potential (-31.68±3.10 mV) and incorporation efficiency (82.1±3.0%) were measured. The long term stability of ROX-loaded SLN suspensions was proved up to 26 weeks. In vitro drug release study was performed using apparatus 4 dialysis adapters. Skin irritation test conducted using the EpiDerm™ tissue model demonstrated no irritation potential for ROX-loaded SLN. Ex vivo human skin penetration studies, employing rhodamine B hexyl ester perchlorate (RBHE) as a fluorescent dye to label the particles, revealed fluorescence deep in the skin, specifically around the hair follicles up to over 1mm depth. The comparison of fluorescence intensities after application of RBHE solution and RBHE-labelled ROX-loaded SLN was done. Then cyanoacrylate follicular biopsies were obtained in vivo and analyzed for ROX content, proving the possibility of penetration to human pilosebaceous units and delivering ROX by using SLN with the size below 200 nm. PMID:26456292

  10. Progesterone Upregulates Gene Expression in Normal Human Thyroid Follicular Cells.

    PubMed

    Bertoni, Ana Paula Santin; Brum, Ilma Simoni; Hillebrand, Ana Caroline; Furlanetto, Tania Weber

    2015-01-01

    Thyroid cancer and thyroid nodules are more prevalent in women than men, so female sex hormones may have an etiological role in these conditions. There are no data about direct effects of progesterone on thyroid cells, so the aim of the present study was to evaluate progesterone effects in the sodium-iodide symporter NIS, thyroglobulin TG, thyroperoxidase TPO, and KI-67 genes expression, in normal thyroid follicular cells, derived from human tissue. NIS, TG, TPO, and KI-67 mRNA expression increased significantly after TSH 20 μUI/mL, respectively: 2.08 times, P < 0.0001; 2.39 times, P = 0.01; 1.58 times, P = 0.0003; and 1.87 times, P < 0.0001. In thyroid cells treated with 20 μUI/mL TSH plus 10 nM progesterone, RNA expression of NIS, TG, and KI-67 genes increased, respectively: 1.78 times, P < 0.0001; 1.75 times, P = 0.037; and 1.95 times, P < 0.0001, and TPO mRNA expression also increased, though not significantly (1.77 times, P = 0.069). These effects were abolished by mifepristone, an antagonist of progesterone receptor, suggesting that genes involved in thyroid cell function and proliferation are upregulated by progesterone. This work provides evidence that progesterone has a direct effect on thyroid cells, upregulating genes involved in thyroid function and growth. PMID:26089899

  11. Follicular helper T cell in immunity and autoimmunity.

    PubMed

    Mesquita, D; Cruvinel, W M; Resende, L S; Mesquita, F V; Silva, N P; Câmara, N O S; Andrade, L E C

    2016-01-01

    The traditional concept that effector T helper (Th) responses are mediated by Th1/Th2 cell subtypes has been broadened by the recent demonstration of two new effector T helper cells, the IL-17 producing cells (Th17) and the follicular helper T cells (Tfh). These new subsets have many features in common, such as the ability to produce IL-21 and to express the IL-23 receptor (IL23R), the inducible co-stimulatory molecule ICOS, and the transcription factor c-Maf, all of them essential for expansion and establishment of the final pool of both subsets. Tfh cells differ from Th17 by their ability to home to B cell areas in secondary lymphoid tissue through interactions mediated by the chemokine receptor CXCR5 and its ligand CXCL13. These CXCR5+ CD4+ T cells are considered an effector T cell type specialized in B cell help, with a transcriptional profile distinct from Th1 and Th2 cells. The role of Tfh cells and its primary product, IL-21, on B-cell activation and differentiation is essential for humoral immunity against infectious agents. However, when deregulated, Tfh cells could represent an important mechanism contributing to exacerbated humoral response and autoantibody production in autoimmune diseases. This review highlights the importance of Tfh cells by focusing on their biology and differentiation processes in the context of normal immune response to infectious microorganisms and their role in the pathogenesis of autoimmune diseases. PMID:27096200

  12. Roxithromycin-loaded lipid nanoparticles for follicular targeting.

    PubMed

    Wosicka-Frąckowiak, Hanna; Cal, Krzysztof; Stefanowska, Justyna; Główka, Eliza; Nowacka, Magdalena; Struck-Lewicka, Wiktoria; Govedarica, Biljana; Pasikowska, Monika; Dębowska, Renata; Jesionowski, Teofil; Srčič, Stane; Markuszewski, Michał Jan

    2015-11-30

    Particulate drug carriers e.g. nanoparticles (NPs) have been shown to penetrate and accumulate preferentially in skin hair follicles creating high local concentration of a drug. In order to develop such a follicle targeting system we obtained and characterized solid lipid nanoparticles (SLN) loaded with roxithromycin (ROX). The mean particle size (172±2 nm), polydisperisty index (0.237±0.007), zeta potential (-31.68±3.10 mV) and incorporation efficiency (82.1±3.0%) were measured. The long term stability of ROX-loaded SLN suspensions was proved up to 26 weeks. In vitro drug release study was performed using apparatus 4 dialysis adapters. Skin irritation test conducted using the EpiDerm™ tissue model demonstrated no irritation potential for ROX-loaded SLN. Ex vivo human skin penetration studies, employing rhodamine B hexyl ester perchlorate (RBHE) as a fluorescent dye to label the particles, revealed fluorescence deep in the skin, specifically around the hair follicles up to over 1mm depth. The comparison of fluorescence intensities after application of RBHE solution and RBHE-labelled ROX-loaded SLN was done. Then cyanoacrylate follicular biopsies were obtained in vivo and analyzed for ROX content, proving the possibility of penetration to human pilosebaceous units and delivering ROX by using SLN with the size below 200 nm.

  13. Follicular targeting--a promising tool in selective dermatotherapy.

    PubMed

    Vogt, Annika; Mandt, Nathalie; Lademann, Juergen; Schaefer, Hans; Blume-Peytavi, Ulrike

    2005-12-01

    The penetration of topically applied compounds varies considerably in the different regions of the human body. The presence of hair follicles significantly contributes to this effect by an increase in surface area and a disruption of the epidermal barrier towards the lower parts of the hair follicle. The human hair follicle, hereby, serves not only as a reservoir, but also as a major entry point for topically applied compounds. Topical delivery of active compounds to specific targets within the skin may help reduce side-effects caused by unspecific reactions, and may help develop new strategies in the prevention and treatment of skin diseases. Various drug carrier and drug delivery systems are currently being investigated. The aim of these investigational efforts is to direct topically applied compounds to the different types of hair follicles and, ideally, to specific compartments and cell populations within the hair follicles. Follicular targeting offers opportunities for new developments, not only in hair therapy and in the treatment of hair follicle associated diseases but also in gene therapy and immunotherapy.

  14. Chemotherapy-free treatment in patients with follicular lymphoma.

    PubMed

    Sarkozy, Clémentine; Salles, Gilles; Bachy, Emmanuel

    2015-04-01

    The outcome of patients with follicular lymphoma (FL) has improved over the last two decades through the introduction of anti-CD20 monoclonal antibodies, usually used in combination with chemotherapy. However, patients with FL still experience multiple relapses, requiring several lines of treatment. Early toxicity of chemotherapy is a significant concern and as the life expectancy of patients with FL is increasing, late toxicities become an increasingly important concern. Progress made in understanding the biology of FL, especially dysregulation of intracellular pathways and immunological antitumor responses, recently allowed for the development of innovative chemo-free therapeutic approaches. In this report, different options such as new anti-CD20 antibodies, antibodies targeting other cell surface antigens, bi-specific antibodies, immunomodulation, idiotype vaccine and other targeted therapies are presented. The article also highlights how, although promising in early phase studies, the cost-effectiveness of new agents will have to be justified in Phase III trials. Furthermore, chemo-free regimen might not mean toxicity-free treatment and monitoring of early and late toxicities is required. PMID:25585961

  15. Progesterone Upregulates Gene Expression in Normal Human Thyroid Follicular Cells

    PubMed Central

    Bertoni, Ana Paula Santin; Brum, Ilma Simoni; Hillebrand, Ana Caroline; Furlanetto, Tania Weber

    2015-01-01

    Thyroid cancer and thyroid nodules are more prevalent in women than men, so female sex hormones may have an etiological role in these conditions. There are no data about direct effects of progesterone on thyroid cells, so the aim of the present study was to evaluate progesterone effects in the sodium-iodide symporter NIS, thyroglobulin TG, thyroperoxidase TPO, and KI-67 genes expression, in normal thyroid follicular cells, derived from human tissue. NIS, TG, TPO, and KI-67 mRNA expression increased significantly after TSH 20 μUI/mL, respectively: 2.08 times, P < 0.0001; 2.39 times, P = 0.01; 1.58 times, P = 0.0003; and 1.87 times, P < 0.0001. In thyroid cells treated with 20 μUI/mL TSH plus 10 nM progesterone, RNA expression of NIS, TG, and KI-67 genes increased, respectively: 1.78 times, P < 0.0001; 1.75 times, P = 0.037; and 1.95 times, P < 0.0001, and TPO mRNA expression also increased, though not significantly (1.77 times, P = 0.069). These effects were abolished by mifepristone, an antagonist of progesterone receptor, suggesting that genes involved in thyroid cell function and proliferation are upregulated by progesterone. This work provides evidence that progesterone has a direct effect on thyroid cells, upregulating genes involved in thyroid function and growth. PMID:26089899

  16. Follicular helper T cell in immunity and autoimmunity

    PubMed Central

    Mesquita, D.; Cruvinel, W.M.; Resende, L.S.; Mesquita, F.V.; Silva, N.P.; Câmara, N.O.S.; Andrade, L.E.C.

    2016-01-01

    The traditional concept that effector T helper (Th) responses are mediated by Th1/Th2 cell subtypes has been broadened by the recent demonstration of two new effector T helper cells, the IL-17 producing cells (Th17) and the follicular helper T cells (Tfh). These new subsets have many features in common, such as the ability to produce IL-21 and to express the IL-23 receptor (IL23R), the inducible co-stimulatory molecule ICOS, and the transcription factor c-Maf, all of them essential for expansion and establishment of the final pool of both subsets. Tfh cells differ from Th17 by their ability to home to B cell areas in secondary lymphoid tissue through interactions mediated by the chemokine receptor CXCR5 and its ligand CXCL13. These CXCR5+ CD4+ T cells are considered an effector T cell type specialized in B cell help, with a transcriptional profile distinct from Th1 and Th2 cells. The role of Tfh cells and its primary product, IL-21, on B-cell activation and differentiation is essential for humoral immunity against infectious agents. However, when deregulated, Tfh cells could represent an important mechanism contributing to exacerbated humoral response and autoantibody production in autoimmune diseases. This review highlights the importance of Tfh cells by focusing on their biology and differentiation processes in the context of normal immune response to infectious microorganisms and their role in the pathogenesis of autoimmune diseases. PMID:27096200

  17. Theca interna: the other side of bovine follicular atresia.

    PubMed

    Clark, Leigh J; Irving-Rodgers, Helen F; Dharmarajan, Arun M; Rodgers, Raymond J

    2004-10-01

    Currently, histological classifications of ovarian follicular atresia are almost exclusively based on the morphology of the membrana granulosa without reference to the theca interna. Atresia in the bovine small antral ovarian follicle has been redefined into antral or basal atresia where cell death commences initially within antral or basal regions of the membrana granulosa, respectively. To examine cell death in the theca interna in the two types of atretic follicles, bovine ovaries were collected and processed for immunohistochemistry and light microscopy. Follicles were classified as healthy, antral atretic, or basal atretic. Follicle diameter was recorded and sections stained with lectin from Bandeiraea simplicifolia to identify endothelial cells or with an antibody to cytochrome P450 cholesterol side-chain cleavage to identify steroidogenic cells and combined with TUNEL labeling to identify dead cells. The numerical density of steroidogenic cells within the theca interna was significantly reduced (P < 0.001) in basal atretic follicles in comparison with other follicles. Cell death was greater in both endothelial cells (P < 0.05) and steroidogenic cells (P < 0.01) of the theca interna of basal atretic follicles compared with healthy and antral atretic follicles. Thus, we conclude that the theca interna is susceptible to cell death early in atresia, particularly in basal atretic follicles. PMID:15175236

  18. X-ray and radioiodine dose to thyroid follicular cells

    SciTech Connect

    Faw, R.E. . Dept. of Nuclear Engineering); Eckerman, K.F.; Ryman, J.C. )

    1991-01-01

    Radiation doses to the epithelial cells of thyroid follicles have been calculated for internal exposure by radionuclides of iodine and by secondary radiations created as a result of interactions of externally administered x rays with iodine naturally occurring in the thyroid. Calculations were performed for the thyroids of subjects ranging from the newborn to the adult male. Results for internal radionuclides are reported as the dose rate to follicular-cell nuclei per unit specific activity of the radionuclide in the thyroid as a whole, i.e., as the specific S value'' as used in the MIRD method for internal dosimetry. Results for x rays are reported as the response function, i.e., the absorbed dose per unit fluence of primary x rays. Dose rates are subdivided into internal and external components, the former from radiations emitted within the colloid volume of any one follicle, and the latter from radiations emitted throughout the thyroid in follicles surrounding that one follicle. 37 refs., 5 figs., 3 tabs.

  19. Follicular lymphoid hyperplasia of the hard palate simulating lymphoma.

    PubMed

    Harsany, D L; Ross, J; Fee, W E

    1980-01-01

    Follicular lymphoid hyperplasia of the hard palate is a slowly growing, soft, nontender swelling that may grow to involve the entire hard palate. The overlying mucosa is normal. This appearance naturally prompts biopsy, and both clinically and microscopically might be confused with lymphoma. Four case histories are presented with histologic description: normal palatal submucosal structures are replaced with benign reactive lymphoid tissue replete with well-developed germinal centers. Surrounding these centers are dense populations of small, regular, bland lymphocytes. Minor salivary glands, except for some atrophied residue, are notably absent; also absent are the epimyoepithelial islands characteristic of the benign lymphoepithelial lesion (Mikulicz's disease). Etiologic factors remain obscure. One of our patients had two recurrences following local excision; in another patient nodules of benign lymphoid hyperplasia developed in the cheek and upper neck. These four patients are alive and free of any malignant process 4, 7, 9, and 12 years after the onset of their palatal swellings. We urge caution in distinguishing these lesions from palatal lymphoma, and recommend local excision as the treatment of choice.

  20. Forward- and backpropagation in a silicon dendrite.

    PubMed

    Rasche, C; Douglas, R J

    2001-01-01

    We have developed an analog very-large-scale integrated (aVLSI) electronic circuit that emulates a compartmental model of a neuronal dendrite. The horizontal conductances of the compartmental model are implemented as a switched capacitor network. The transmembrane conductances are implemented as transconductance amplifiers. The electrotonic properties of our silicon cable are qualitatively similar to those of the ideal passive cable that is commonly used to model mathematically the electrotonic behavior of neurons. In particular the propagation of excitatory postsynaptic potentials is realistic, and we are easily able to emulate such classical synaptic integration models as direction selectivity. We are also able to emulate the backpropagation into the dendrite of single somatic spikes and bursts of spikes. Thus, this silicon dendrite is suitable for incorporation in detailed silicon neurons operating in real-time; in particular for the emulation of forward- and backpropagating electrical activities found in real neurons. PMID:18244392

  1. Studying Signal Transduction in Single Dendritic Spines

    PubMed Central

    Yasuda, Ryohei

    2012-01-01

    Many forms of synaptic plasticity are triggered by biochemical signaling that occurs in small postsynaptic compartments called dendritic spines, each of which typically houses the postsynaptic terminal associated with a single glutamatergic synapse. Recent advances in optical techniques allow investigators to monitor biochemical signaling in single dendritic spines and thus reveal the signaling mechanisms that link synaptic activity and the induction of synaptic plasticity. This is mostly in the study of Ca2+-dependent forms of synaptic plasticity for which many of the steps between Ca2+ influx and changes to the synapse are now known. This article introduces the new techniques used to investigate signaling in single dendritic spines and the neurobiological insights that they have produced. PMID:22843821

  2. Comparison of microarray expression profiles between follicular variant of papillary thyroid carcinomas and follicular adenomas of the thyroid

    PubMed Central

    2015-01-01

    Background Follicular variant of papillary thyroid carcinoma (FVPTC) and follicular adenoma (FA) are histologically closely related tumors and differential diagnosis remains challenging. RNA expression profiling is an established method to unravel molecular mechanisms underlying the histopathology of diseases. Methods BRAF mutational status was established by direct sequencing the hotspot region of exon 15 in six FVPTCs and seven FAs. Whole-transcript arrays were employed to generate expression profiles in six FVPTCs, seven FAs and seven normal thyroid tissue samples. The threshold of significance for differential expression on the gene and exon level was a p-value with a false discovery rate (FDR) < 0.05 and a fold change cutoff > 2. Two dimensional average linkage hierarchical clustering was generated using differentially expressed genes. Network, pathway, and alternative splicing utilities were employed to interpret significance of expression data on the gene and exon level. Results Expression profiling in FVPTCs and FAs, all of which were negative for a BRAF mutation, revealed 55 transcripts that were significantly differentially expressed, 40 of which were upregulated and 15 downregulated in FVPTCs vs. FAs. Amongst the most significantly upregulated genes in FVPTCs were GABA B receptor, 2 (GABBR2), neuronal cell adhesion molecule (NRCAM), extracellular matrix protein 1 (ECM1), heparan sulfate 6-O-sulfotransferase 2 (HS6ST2), and retinoid X receptor, gamma (RXRG). The most significantly downregulated genes in FVPTCs included interaction protein for cytohesin exchange factors 1 (IPCEF1), G protein-coupled receptor 155 (GPR155), Purkinje cell protein 4 (PCP4), chondroitin sulfate N-acetylgalactosaminyltransferase 1 (CSGALNACT1), and glutamate receptor interacting protein 1 (GRIP1). Alternative splicing analysis detected 87 genes, 52 of which were also included in the list of 55 differentially expressed genes. Network analysis demonstrated multiple interactions

  3. Dendritic Cells Stimulated by Cationic Liposomes.

    PubMed

    Vitor, Micaela Tamara; Bergami-Santos, Patrícia Cruz; Cruz, Karen Steponavicius Piedade; Pinho, Mariana Pereira; Barbuto, José Alexandre Marzagão; De La Torre, Lucimara Gaziola

    2016-01-01

    Immunotherapy of cancer aims to harness the immune system to detect and destroy cancer cells. To induce an immune response against cancer, activated dendritic cells (DCs) must present tumor antigens to T lymphocytes of patients. However, cancer patients' DCs are frequently defective, therefore, they are prone to induce rather tolerance than immune responses. In this context, loading tumor antigens into DCs and, at the same time, activating these cells, is a tempting goal within the field. Thus, we investigated the effects of cationic liposomes on the DCs differentiation/maturation, evaluating their surface phenotype and ability to stimulate T lymphocytes proliferation in vitro. The cationic liposomes composed by egg phosphatidylcholine, 1,2-dioleoyl-3-trimethylammonium propane and 1,2-dioleoylphosphatidylethanolamine (50/25/25% molar) were prepared by the thin film method followed by extrusion (65 nm, polydispersity of 0.13) and by the dehydration-rehydration method (95% of the population 107 nm, polydispersity of 0.52). The phenotypic analysis of dendritic cells and the analysis of T lymphocyte proliferation were performed by flow cytometry and showed that both cationic liposomes were incorporated and activated dendritic cells. Extruded liposomes were better incorporated and induced higher CD86 expression for dendritic cells than dehydrated-rehydrated vesicles. Furthermore, dendritic cells which internalized extruded liposomes also provided stronger T lymphocyte stimulation. Thus, cationic liposomes with a smaller size and polydispersity seem to be better incorporated by dendritic cells. Hence, these cationic liposomes could be used as a potential tool in further cancer immunotherapy strategies and contribute to new strategies in immunotherapy. PMID:27398454

  4. Convection Effects in Three-dimensional Dendritic Growth

    NASA Technical Reports Server (NTRS)

    Lu, Yili; Beckermann, C.; Karma, A.

    2003-01-01

    A phase-field model is developed to simulate free dendritic growth coupled with fluid flow for a pure material in three dimensions. The preliminary results presented here illustrate the strong influence of convection on the three-dimensional (3D) dendrite growth morphology. The detailed knowledge of the flow and temperature fields in the melt around the dendrite from the simulations allows for a detailed understanding of the convection effects on dendritic growth.

  5. Seaweed to dendrite transition in directional solidification.

    PubMed

    Provatas, Nikolas; Wang, Quanyong; Haataja, Mikko; Grant, Martin

    2003-10-10

    We simulate directional solidification using a phase-field model solved with adaptive mesh refinement. For small surface tension anisotropy directed at 45 degrees relative to the pulling direction we observe a crossover from a seaweed to a dendritic morphology as the thermal gradient is lowered, consistent with recent experimental findings. We show that the morphology of crystal structures can be unambiguously characterized through the local interface velocity distribution. We derive semiempirically an estimate for the crossover from seaweed to dendrite as a function of thermal gradient and pulling speed.

  6. Apparatus for growing a dendritic web

    DOEpatents

    Duncan, Charles S.; Piotrowski, Paul A.; Skutch, Maria E.; McHugh, James P.

    1983-06-21

    A melt system including a susceptor-crucible assembly having improved gradient control when melt replenishment is used during dendritic web growth. The improvement lies in the formation of a thermal barrier in the base of the receptor which is in the form of a vertical slot in the region of the susceptor underlying the crucible at the location of a compartmental separator dividing the crucible into a growth compartment and a melt replenishment compartment. The result achieved is a step change in temperature gradient in the melt thereby providing a more uniform temperature in the growth compartment from which the dendritic web is drawn.

  7. The Isothermal Dendritic Growth Experiment (IDGE)

    NASA Technical Reports Server (NTRS)

    Glicksman, Martin E.; Koss, M. B.; Lupulescu, A. O.; LaCombe, J. C.; Frei, J. E.; Malarik, D. C.

    1999-01-01

    The Isothermal Dendritic Growth Experiment (IDGE) constituted a series of three NASA-supported microgravity experiments, all of which flew aboard the space shuttle, Columbia. This experimental space flight series was designed and operated to grow and record dendrite solidification in the absence of gravity-induced convective heat transfer, and thereby produce a wealth of benchmark-quality data for testing solidification scaling laws. The data and analysis performed on the dendritic growth speed and tip size in Succinontrie (SCN) demonstrates that although the theory yields predictions that are reasonably in agreement with experiment, there are significant discrepancies. However, some of these discrepancies can be explained by accurately describing the diffusion of heat. The key finding involves recognition that the actual three-dimensional shape of dendrites includes time-dependent side-branching and a tip region that is not a paraboloid of revolution. Thus, the role of heat transfer in dendritic growth is validated, with the caveat that a more realistic model of the dendrite then a paraboloid is needed to account for heat flow in an experimentally observed dendrite. We are currently conducting additional analysis to further confirm and demonstrate these conclusions. The data and analyses for the growth selection physics remain much less definitive. From the first flight, the data indicated that the selection parameter, sigma*, is not exactly a constant, but exhibits a slight dependence on the supercooling. Additional data from the second flight are being examined to investigate the selection of a unique dendrite speed, tip size and shape. The IDGE flight series is now complete. We are currently completing analyses and moving towards final data archiving. It is gratifying to see that the IDGE published results and archived data sets are being used actively by other scientists and engineers. In addition, we are also pleased to report that the techniques and IDGE

  8. Dendritic microstructure in argon atomized superalloy powders

    NASA Technical Reports Server (NTRS)

    Tewari, S. N.; Kumar, Mahundra

    1986-01-01

    The dendritic microstructure of atomized nickel base superalloy powders (Ni-20 pct Cr, NIMONIC-80A, ASTROALOY, and ZHS6-K) was studied. Prealloyed vacuum induction melted ingots were argon-atomized, the powders were cooled to room temperature, and various powder-size fractions were examined by optical metallography. Linear correlations were obtained for the powder size dependence of the secondary dendrite arm spacing, following the expected d-alpha (R) to the m power dependence on the particle size for all four superalloy compositions. However, the Ni-20 pct Cr alloy, which had much coarser arm spacing as compared to the other three alloys, had a much larger value of m.

  9. Silicon dendritic web growth thermal analysis task

    NASA Technical Reports Server (NTRS)

    Richter, R.; Bhandari, P.

    1985-01-01

    A thermal analysis model is presented which describes the dendritic ribbon process. The model uses a melt-dendrite interface which projects out of the bulk melt as the basic interpretation of the ribbon production process. This is a marked departure from the interpretations of the interface phenomena which were used previously. The model was extensively illustrated with diagrams and pictures of ribbon samples. This model should have great impact on the analyses of experimental data as well as on future design modifications of ribbon-pulling equipment.

  10. [Application of dendritic cells in clinical tumor therapy].

    PubMed

    Li, Yan; Xian, Li-jian

    2002-04-01

    The active immunotherapy of dendritic cells is hot in tumor therapy research area. This article is a review of the source of dendritic cells, loading antigen, immunotherapy pathway, clinical application, choice of patients, and so on. It makes preparation for further research of dendritic cells. PMID:12452029

  11. Follicular Mucinosis in a Male Adolescent with a History of Acute Myelogenous Leukemia and Graft-versus-Host Disease.

    PubMed

    Jefferson, Julie; Taube, Janis; Grossberg, Anna

    2016-01-01

    Although many cases of follicular mucinosis are idiopathic, numerous others are associated with mycosis fungoides or, rarely, other neoplastic or inflammatory disorders. There are only three reported cases, all in adults, of follicular mucinosis arising in association with acute myelogenous leukemia, two of which involved mycosis fungoides-associated follicular mucinosis, including one case in which the patient had a preceding bone marrow transplant. We present the first reported case of follicular mucinosis arising in an adolescent with acute myelogenous leukemia and acute graft-versus-host disease after an allogeneic bone marrow transplantation. PMID:26645410

  12. Regulation of rat basophilic leukemia-2H3 mast cell secretion by a constitutive Lyn kinase interaction with the high affinity IgE receptor (Fc epsilon RI).

    PubMed

    Vonakis, Becky M; Gibbons, Scott P; Rotté, Masashi J; Brothers, Elizabeth A; Kim, Seok C; Chichester, Kristin; MacDonald, Susan M

    2005-10-01

    Signaling through the high affinity IgE receptor is initiated by noncovalently associated Lyn kinase, resulting in the secretion of inflammatory mediators from mast cells. A fraction of the total cellular Lyn is associated via its N-terminal unique domain with the cytoplasmic domain of the Fc epsilonRI beta subunit before receptor aggregation. In the current study, we stably transfected the unique domain of Lyn into rat basophilic leukemia-2H3 mast cells and examined the consequences on Fc epsilonRI-induced signal transduction and mediator secretion to further define the role of the unique domain of Lyn in mast cell secretion. Tyrosine phosphorylation of Fc epsilonRI beta and gamma subunits was partially inhibited in the Lyn unique domain transfectants after Ag stimulation. Ag stimulation of Lyn unique domain transfectants was accompanied by enhanced phosphorylation of MEK and ERK-2, which are required for leukotriene C4 (LTC4) release, and production of LTC4 was increased 3- to 5-fold, compared with cells transfected with vector alone. Conversely, tyrosine phosphorylation of the adaptor protein Gab2, which is essential for mast cell degranulation, was inhibited after Ag stimulation of Lyn unique domain transfectants, and Ag-induced release of histamine was inhibited up to 48%. In rat basophilic leukemia-2H3 cells, Lyn thus plays a dual role by positively regulating Fc epsilonRI phosphorylation and degranulation while negatively regulating LTC4 production. This study provides further evidence that the constitutive interaction between the unique domain of Lyn and the Fc epsilonRI beta subunit is a crucial step in the initiation of Fc epsilonRI signaling and that Lyn is limiting for Fc epsilonRI-induced secretion of inflammatory mediators.

  13. Efficient internalization of silica-coated iron oxide nanoparticles of different sizes by primary human macrophages and dendritic cells

    SciTech Connect

    Kunzmann, Andrea; Andersson, Britta; Vogt, Carmen; Feliu, Neus; Ye Fei; Gabrielsson, Susanne; Toprak, Muhammet S.; Buerki-Thurnherr, Tina; Laurent, Sophie; Vahter, Marie; Krug, Harald; Muhammed, Mamoun; Scheynius, Annika; Fadeel, Bengt

    2011-06-01

    Engineered nanoparticles are being considered for a wide range of biomedical applications, from magnetic resonance imaging to 'smart' drug delivery systems. The development of novel nanomaterials for biomedical applications must be accompanied by careful scrutiny of their biocompatibility. In this regard, particular attention should be paid to the possible interactions between nanoparticles and cells of the immune system, our primary defense system against foreign invasion. On the other hand, labeling of immune cells serves as an ideal tool for visualization, diagnosis or treatment of inflammatory processes, which requires the efficient internalization of the nanoparticles into the cells of interest. Here, we compare novel monodispersed silica-coated iron oxide nanoparticles with commercially available dextran-coated iron oxide nanoparticles. The silica-coated iron oxide nanoparticles displayed excellent magnetic properties. Furthermore, they were non-toxic to primary human monocyte-derived macrophages at all doses tested whereas dose-dependent toxicity of the smaller silica-coated nanoparticles (30 nm and 50 nm) was observed for primary monocyte-derived dendritic cells, but not for the similarly small dextran-coated iron oxide nanoparticles. No macrophage or dendritic cell secretion of pro-inflammatory cytokines was observed upon administration of nanoparticles. The silica-coated iron oxide nanoparticles were taken up to a significantly higher degree when compared to the dextran-coated nanoparticles, irrespective of size. Cellular internalization of the silica-coated nanoparticles was through an active, actin cytoskeleton-dependent process. We conclude that these novel silica-coated iron oxide nanoparticles are promising materials for medical imaging, cell tracking and other biomedical applications.

  14. Targeting Toll-like receptor signaling in plasmacytoid dendritic cells and autoreactive B cells as a therapy for lupus.

    PubMed

    Lenert, Petar S

    2006-01-01

    This review focuses on the role of Toll-like receptors (TLRs) in lupus and on possibilities to treat lupus using TLR modulating inhibitory oligodeoxynucleotides (INH-ODNs). TLRs bridge innate and adaptive immune responses and may play an important role in the pathogenesis of systemic lupus erythematosus. Of particular interest are TLR3, -7, -8, and -9, which are localized intracellularly. These TLRs recognize single-stranded or double-stranded RNA or hypomethylated CpG-DNA. Exposure to higher order CpG-DNA ligands or to immune complexed self-RNA triggers activation of autoreactive B cells and plasmacytoid dendritic cells. INH-ODNs were recently developed that block all downstream signaling events in TLR9-responsive cells. Some of these INH-ODNs can also target TLR7 signaling pathways. Based on their preferential cell reactivity, we classify INH-ODNs into class B and class R. Class B ('broadly reactive') INH-ODNs target a broad range of TLR-expressing cells. Class R ('restricted') INH-ODNs easily form DNA duplexes or higher order structures, and are preferentially recognized by autoreactive B cells and plasmacytoid dendritic cells, rather than by non-DNA specific follicular B cells. Both classes of INH-ODNs can block animal lupus. Hence, therapeutic application of these novel INH-ODNs in human lupus, particularly class R INH-ODNs, may result in more selective and disease-specific immunosuppression.

  15. Radiation therapy for localized duodenal low-grade follicular lymphoma

    PubMed Central

    Harada, Arisa; Oguchi, Masahiko; Terui, Yasuhito; Takeuchi, Kengo; Igarashi, Masahiro; Kozuka, Takuyo; Harada, Ken; Uno, Takashi; Hatake, Kiyohiko

    2016-01-01

    The aim of this study was to evaluate the initial treatment results and toxicities of radiation therapy for patients with early stage low-grade follicular lymphoma (FL) arising from the duodenum. We reviewed 21 consecutive patients with early stage duodenal FL treated with radiation therapy between January 2005 and December 2013 at the Cancer Institute Hospital, Tokyo. The characteristics of patients were: median age 62 years (range, 46–79 years), gender (male, 6; female, 15), clinical stage (I, 20; II1, 1), histological grade (I, 17; II, 4). All patients were treated with radiation therapy alone. The median radiation dose was 30.6 Gy (range, 30.6–39.6) in 17 fractions. The involved-site radiation therapy was delivered to the whole duodenum. The median follow-up time was 43.2 months (range 21.4–109.3). The 3-year overall survival (OS), relapse-free survival (RFS) and local control (LC) rates were 94.7%, 79.3% and 100%, respectively. There were four relapses documented outside the treated volumes: two in the gastrointestinal tract (jejunum, terminal ileum), one in an abdominal lymph node (mesenteric lymph node) and one in the bone marrow. None died of the disease; one death was due to acute myeloid leukemia. No toxicities greater than Grade 1 were observed during treatment and over the follow-up time. The 30.6 Gy of involved-site radiation therapy provided excellent local control with very low toxicities. Radiation therapy could be an effective and safe treatment option for patients with localized low grade FL arising from the duodenum. PMID:27009323

  16. Hyper-dendritic nanoporous zinc foam anodes

    SciTech Connect

    Chamoun, Mylad; Hertzberg, Benjamin J.; Gupta, Tanya; Davies, Daniel; Bhadra, Shoham; Van Tassell, Barry.; Erdonmez, Can; Steingart, Daniel A.

    2015-04-24

    The low cost, significant reducing potential, and relative safety of the zinc electrode is a common hope for a reductant in secondary batteries, but it is limited mainly to primary implementation due to shape change. In this work we exploit such shape change for the benefit of static electrodes through the electrodeposition of hyper-dendritic nanoporous zinc foam. Electrodeposition of zinc foam resulted in nanoparticles formed on secondary dendrites in a three-dimensional network with a particle size distribution of 54.1 - 96.0 nm. The nanoporous zinc foam contributed to highly oriented crystals, high surface area and more rapid kinetics in contrast to conventional zinc in alkaline mediums. The anode material presented had a utilization of ~ 88% at full depth-of-discharge at various rates indicating a superb rate-capability. The rechargeability of Zn⁰/Zn²⁺ showed significant capacity retention over 100 cycles at a 40% depth-of-discharge to ensure that the dendritic core structure was imperforated. The dendritic architecture was densified upon charge-discharge cycling and presented superior performance compared to bulk zinc electrodes.

  17. Hyper-dendritic nanoporous zinc foam anodes

    DOE PAGES

    Chamoun, Mylad; Hertzberg, Benjamin J.; Gupta, Tanya; Davies, Daniel; Bhadra, Shoham; Van Tassell, Barry.; Erdonmez, Can; Steingart, Daniel A.

    2015-04-24

    The low cost, significant reducing potential, and relative safety of the zinc electrode is a common hope for a reductant in secondary batteries, but it is limited mainly to primary implementation due to shape change. In this work we exploit such shape change for the benefit of static electrodes through the electrodeposition of hyper-dendritic nanoporous zinc foam. Electrodeposition of zinc foam resulted in nanoparticles formed on secondary dendrites in a three-dimensional network with a particle size distribution of 54.1 - 96.0 nm. The nanoporous zinc foam contributed to highly oriented crystals, high surface area and more rapid kinetics in contrastmore » to conventional zinc in alkaline mediums. The anode material presented had a utilization of ~ 88% at full depth-of-discharge at various rates indicating a superb rate-capability. The rechargeability of Zn⁰/Zn²⁺ showed significant capacity retention over 100 cycles at a 40% depth-of-discharge to ensure that the dendritic core structure was imperforated. The dendritic architecture was densified upon charge-discharge cycling and presented superior performance compared to bulk zinc electrodes.« less

  18. Detecting Danger: The Dendritic Cell Algorithm

    NASA Astrophysics Data System (ADS)

    Greensmith, Julie; Aickelin, Uwe; Cayzer, Steve

    The "Dendritic Cell Algorithm" (DCA) is inspired by the function of the dendritic cells of the human immune system. In nature, dendritic cells are the intrusion detection agents of the human body, policing the tissue and organs for potential invaders in the form of pathogens. In this research, an abstract model of dendritic cell (DC) behavior is developed and subsequently used to form an algorithm—the DCA. The abstraction process was facilitated through close collaboration with laboratory-based immunologists, who performed bespoke experiments, the results of which are used as an integral part of this algorithm. The DCA is a population-based algorithm, with each agent in the system represented as an "artificial DC". Each DC has the ability to combine multiple data streams and can add context to data suspected as anomalous. In this chapter, the abstraction process and details of the resultant algorithm are given. The algorithm is applied to numerous intrusion detection problems in computer security including the detection of port scans and botnets, where it has produced impressive results with relatively low rates of false positives.

  19. Characterization of chicken dendritic cell markers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Animal and Natural Resources Institute, ARS-USDA, Beltsville, MD, USA. New mouse monoclonal antibodies which detect CD80 and CD83 were developed to characterize chicken dendritic cells (DCs). The characteristics of these molecules have been studied in human, swine, ovine, feline, and canine but not ...

  20. Thermosolutal convection and macrosegregation in dendritic alloys

    NASA Technical Reports Server (NTRS)

    Poirier, David R.; Heinrich, J. C.

    1993-01-01

    A mathematical model of solidification, that simulates the formation of channel segregates or freckles, is presented. The model simulates the entire solidification process, starting with the initial melt to the solidified cast, and the resulting segregation is predicted. Emphasis is given to the initial transient, when the dendritic zone begins to develop and the conditions for the possible nucleation of channels are established. The mechanisms that lead to the creation and eventual growth or termination of channels are explained in detail and illustrated by several numerical examples. A finite element model is used for the simulations. It uses a single system of equations to deal with the all-liquid region, the dendritic region, and the all-solid region. The dendritic region is treated as an anisotropic porous medium. The algorithm uses the bilinear isoparametric element, with a penalty function approximation and a Petrov-Galerkin formulation. The major task was to develop the solidification model. In addition, other tasks that were performed in conjunction with the modeling of dendritic solidification are briefly described.

  1. Defect characterization of silicon dendritic web ribbons

    NASA Technical Reports Server (NTRS)

    Cheng, L. J.

    1985-01-01

    Progress made in the study of defect characterization of silicon dendritic web ribbon is presented. Chemical etching is used combined with optical microscopy, as well as the electron beam induced current (EBIC) technique. Thermal annealing effect on carrier lifetime is examined.

  2. Sinus-lining cells of the lymph nodes recognized as a dendritic cell type by the new monoclonal antibody Ki-M9.

    PubMed Central

    Wacker, H. H.; Frahm, S. O.; Heidebrecht, H. J.; Parwaresch, R.

    1997-01-01

    In the immunobiological characterization of lymph node cells, sinus-lining cells (SLCs) have been given little attention mainly due to the difficulties in their recognition. Ki-M9 is a new monoclonal antibody (MAb) selected for its unique capability to visualize SLCs in human lymph nodes. The details were established by light and electron microscopy and immunoprecipitation of the corresponding biosynthetically labeled antigen. Ki-M9 recognizes a 70-kd protein localized on the surface membrane of SLCs. In the lymphoid tissue, a mild reactivity was exclusively encountered on follicular dendritic reticulum cells in the germinal centers of secondary lymphoid follicles. In other organs, some squamous epithelial and myoepithelial cells were recognized by this antibody. Immunomonitoring of SLCs on light and electron microscopic levels revealed their dendritic morphology, lack of phagosomes, and their close association with type IV collagen fibers. Considering the occurrence of typical dendritic SLCs on the front line of antigen flood, we propose that SLCs be investigated for a possible antigen-binding property. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 PMID:9250155

  3. Perfluoroalkyl acid contamination of follicular fluid and its consequence for in vitro oocyte developmental competence.

    PubMed

    Petro, Evi M L; D'Hollander, Wendy; Covaci, Adrian; Bervoets, Lieven; Fransen, Erik; De Neubourg, Diane; De Pauw, Ingrid; Leroy, Jo L M R; Jorssen, Ellen P A; Bols, Peter E J

    2014-10-15

    Perfluoroalkyl acids (PFAAs) have been shown to induce negative effects in laboratory animals and in vitro experiments. Also, PFAAs have been detected in human tissues and body fluids. The ovarian follicle constitutes a fragile micro-environment where interactions between hormones, growth factors, the oocyte and surrounding somatic cells are essential to generate a fully competent oocyte. In vitro experiments suggest that PFAAs can influence this balance, but very scarce in vivo data are available to confirm this assumption. In fact, the potential PFAA-presence in the follicular micro-environment is currently unknown. Therefore, we investigated if PFAAs are present in human follicular fluid and if their presence could be a risk factor for in vivo exposed developing oocytes. Furthermore, we compared the PFAA-distribution within serum and follicular fluid. PFAAs were analyzed by LC/MS in follicular fluid (n=38) and serum (n=20) samples from women undergoing assisted reproductive technologies (ARTs). Statistical models were used to investigate PFAA-distribution in both body fluids, to compare this behavior with the distribution of lipophilic organic pollutants and to explore the relationship between patient characteristics, ART-results and follicular fluid contamination. Perfluorooctane sulfonate (PFOS) was the PFAA found in the highest concentration in follicular fluid [7.5 (0.1-30.4) ng/mL] and serum [7.6 (2.8-12.5) ng/mL]. A new variable, Principal Component 1, representing the overall PFAA-contamination of the follicular fluid samples, was associated with a higher fertilization rate (p<0.05) and a higher proportion of top embryos relative to the amount of retrieved oocytes (p<0.05), after adjusting for age, estradiol-concentration, BMI, male subfertility and the presence of other organic pollutants as explanatory variables. To conclude, overall higher PFAA-contamination in the follicular micro-environment was associated with a higher chance of an oocyte to develop

  4. Supramolecular dendritic polymers: from synthesis to applications.

    PubMed

    Dong, Ruijiao; Zhou, Yongfeng; Zhu, Xinyuan

    2014-07-15

    CONSPECTUS: Supramolecular dendritic polymers (SDPs), which perfectly combine the advantages of dendritic polymers with those of supramolecular polymers, are a novel class of non-covalently bonded, highly branched macromolecules with three-dimensional globular topology. Because of their dynamic/reversible nature, unique topological structure, and exceptional physical/chemical properties (e.g., low viscosity, high solubility, and a large number of functional terminal groups), SDPs have attracted increasing attention in recent years in both academic and industrial fields. In particular, the reversibility of non-covalent interactions endows SDPs with the ability to undergo dynamic switching of structure, morphology, and function in response to various external stimuli, such as pH, temperature, light, stress, and redox agents, which further provides a flexible and robust platform for designing and developing smart supramolecular polymeric materials and functional supramolecular devices. The existing SDPs can be systematically classified into the following six major types according to their topological features: supramolecular dendrimers, supramolecular dendronized polymers, supramolecular hyperbranched polymers, supramolecular linear-dendritic block copolymers, supramolecular dendritic-dendritic block copolymers, and supramolecular dendritic multiarm copolymers. These different types of SDPs possess distinct morphologies, unique architectures, and specific functions. Benefiting from their versatile topological structures as well as stimuli-responsive properties, SDPs have displayed not only unique characteristics or advantages in supramolecular self-assembly behaviors (e.g., controllable morphologies, specific performance, and facile functionalization) but also great potential to be promising candidates in various fields. In this Account, we summarize the recent progress in the synthesis, functionalization, and self-assembly of SDPs as well as their potential

  5. Concurrent Medullary, Papillary, and Follicular Thyroid Carcinomas and Simultaneous Cushing's Syndrome

    PubMed Central

    Mazeh, Haggi; Orlev, Amir; Mizrahi, Ido; Gross, David J.; Freund, Herbert R.

    2015-01-01

    Background Papillary thyroid carcinoma is the most common thyroid cancer (85%). Follicular thyroid carcinoma is the second most common type of thyroid cancer, accounting for up to 10% of all thyroid cancers. Medullary thyroid carcinoma accounts for only 5-8% of thyroid cancers. Concurrent medullary, follicular, and papillary carcinomas of the thyroid gland are extremely rare and reported scarcely. Case Report A 72-year-old male presented with nonspecific neck pain. The workup revealed a nodular thyroid gland with a follicular lesion on fine-needle aspiration. Total thyroidectomy was performed and pathological examination identified a 25-mm follicular carcinoma, two papillary microcarcinomas, and two medullary microcarcinomas. The genetic workup was negative and no other family members were diagnosed with any endocrinopathy. Two months after surgery, the patient was diagnosed with Cushing's syndrome that was treated with laparoscopic left adrenalectomy. On 3-year follow-up, the patient is asymptomatic with no evidence of recurrent disease. Conclusion We present a rare case of a patient with follicular, papillary, and medullary thyroid carcinoma, and Cushing's syndrome. To date, no known genetic mutation or syndrome can account for this combination of neoplastic thyroid and adrenal pathologies, although future research may prove differently. PMID:25960965

  6. Effect of environmental heat stress on follicular development and steroidogenesis in lactating Holstein cows.

    PubMed

    Badinga, L; Thatcher, W W; Diaz, T; Drost, M; Wolfenson, D

    1993-04-01

    Lactating Holstein cows were utilized over two replicate periods (July and September, 1990) to examine the effect of summer heat stress on follicular growth and steroidogenesis. On day of synchronized ovulations, cows were assigned to shade (n=11) or no shade (n=12) management systems. Follicular development was monitored daily by ultrasonography until ovariectomy on Day 8 post estrus. At time of ovariectomy, dominant and second largest follicles were dissected from the ovary. Aromatase activity and steroid concentrations in dominant and subordinate follicles were measured. Acute heat stress had no effects on patterns of growth of first wave dominant and subordinate follicles between Days 1 and 7 of the cycle. Compared with shaded cows, the heat stressed cows did not have suppression of medium size (6 to 9 mm) follicles between Days 5 and 7. A treatment x follicle interaction was detected (P<0.01) for follicular diameter and fluid volume at Day 8. Dominant follicles in shade were bigger (16.4>14.5 mm) and contained more fluid (1.9>1.1 ml) than dominant follicles in no shade. Conversely, subordinate follicles in no shade were bigger (10.1>7.9 mm) and contained more fluid (0.4>0.2 ml) than subordinate follicles in shade. Concentrations of estradiol in plasma and follicular fluid were higher (P<0.01) in July than in September. Heat stress appears to alter the efficiency of follicular selection and dominance, and to have adverse effects on the quality of ovarian follicles. PMID:16727254

  7. C cells evolve at the same rhythm as follicular cells when thyroidal status changes in rats

    PubMed Central

    Martín-Lacave, Inés; Borrero, María J; Utrilla, José C; Fernández-Santos, José M; de Miguel, Manuel; Morillo, Jesús; Guerrero, Juan M; García-Marín, Rocío; Conde, Esperanza

    2009-01-01

    C cells are primarily known for producing calcitonin, a hypocalcemic and hypophosphatemic hormone. Nevertheless, besides their role in calcium homeostasis, C cells may be involved in the intrathyroidal regulation of follicular cells, suggesting a possible interrelationship between the two endocrine populations. If this premise is true, massive changes induced by different agents in the activity of follicular cells may also affect calcitonin-producing cells. To investigate the behaviour of C cells in those circumstances, we have experimentally induced two opposite functional thyroid states. We hyperstimulated the follicular cells using a goitrogen (propylthiouracil), and we suppressed thyroid hormone synthesis by oral administration of thyroxine. In both scenarios, we measured T4, TSH, calcitonin, and calcium serum levels. We also completely sectioned the thyroid gland, specifically immunostained the C cells, and rigorously quantified this endocrine population. In hypothyroid rats, not only follicular cells but also C cells displayed hyperplastic and hypertrophic changes as well as increased calcitonin levels. When exogenous thyroxine was administered to the rats, the opposite effect was noted as a decrease in the number and size of C cells, as well as decreased calcitonin levels. Additionally, we noted that the two cell types maintain the same numerical relation (10 ± 2.5 follicular cells per C cell), independent of the functional activity of the thyroid gland. Considering that TSH serum levels are increased in hypothyroid rats and decreased in thyroxine-treated rats, we discuss the potential involvement of thyrotropin in the observed results. PMID:19245497

  8. Novel follicular fluid factors influencing oocyte developmental potential in IVF: a review.

    PubMed

    Baka, Stavroula; Malamitsi-Puchner, Ariadne

    2006-04-01

    The aim of IVF centres today is to obtain high quality, developmentally competent embryos, and thus increase live birth rates. Apoptosis in the patient's follicles in among the factors that will determine IVF outcome. Follicular fluid constitutes an important microenvironment, containing apoptotic factors and others, which influence oocyte growth. The sFas-sFas ligand system is present in the follicular fluid and may play a role in preventing oocyte aresia during folliculogenesis. Levels of the anti-apoptotic molecule sFas may be related positively to oocyte maturation and negatively to fertilization and embryo quality. Reactive oxygen species exert a toxic effect when found in high concentrations in the follicular fluid, whereas in low concentrations they might be indispensable for pregnancy and therefore serve as a potential marker for successful IVF outcome. Nitric oxide plays a dual role; in some cells promoting and in others inhibiting apoptosis. Nitric oxide production is stimulated by TNF-alpha, so the latter is also implicated in the apoptotic process. Hyaluronan, a disaccharide, whose functions have not been fully elucidated, is a valuable predictor of oocyte fertilization. Gelatinases are responsible for remodelling during follicular atresia. In conclusion, a number of factors found in the follicular fluid, some involved in apoptosis, can infulence assisted reproduction.

  9. Change of anti-Mullerian-hormone levels during follicular phase in PCOS patients.

    PubMed

    Köninger, A; Koch, L; Enekwe, A; Birdir, C; Kasimir-Bauer, S; Kimmig, R; Strowitzki, T; Schmidt, B

    2015-01-01

    Anti-Mullerian-hormone (AMH) does not seem to fluctuate significantly during the menstrual cycle in healthy women. However, little is known about cycle fluctuations of AMH levels in patients with polycystic ovarian syndrome (PCOS). The purpose of this study was to examine AMH fluctuations during the follicular phase in PCOS patients receiving antiestrogens or recombinant follicle-stimulating hormone (FSH). About 40 PCOS patients diagnosed according to Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group 2003 and 19 controls were prospectively enrolled. PCOS patients received either antiestrogens or recombinant FSH for monoovulation induction and controls received antiestrogens. AMH levels were determined (1) between the 2nd and the 5th day of follicular phase and (2) when a single large dominant follicle ≥18 mm had appeared. Our study shows that AMH levels do not change during follicular development in controls as well as in PCOS patients with AMH levels < 5 ng/ml, irrespective of antiestrogen or FSH therapy. However, in PCOS patients with AMH levels ≥5 ng/ml, AMH declines significantly during follicular development (p < 0.01). We conclude that AMH levels should be determined in the early follicular phase in PCOS patients without the influence of antiestrogens or exogenous FSH, because these interventions may lower AMH values in patients with high levels.

  10. Insular carcinoma: a distinct de novo entity among follicular carcinomas of the thyroid gland.

    PubMed

    Pilotti, S; Collini, P; Mariani, L; Placucci, M; Bongarzone, I; Vigneri, P; Cipriani, S; Falcetta, F; Miceli, R; Pierotti, M A; Rilke, F

    1997-12-01

    We reclassified 720 nonmedullary invasive thyroid carcinomas diagnosed and treated between 1975 and 1993. Twenty-seven cases met the criteria of insular carcinoma and 29 cases those of widely invasive follicular carcinoma. Comparison of these histotypes with respect to pathologic stage and overall, relative, and visceral metastasis-free survival showed a significant association between histotype and pT and pN categories. In particular, pT4 (p < 0.001) and pN1 (p < 0.001) categories were more frequent in the insular carcinoma histotype. By contrast, no significant differences in overall, relative, or visceral metastasis-free survival were observed between insular carcinoma and widely invasive follicular carcinoma. Molecular analysis by polymerase chain reaction-single-strand conformation polymorphism demonstrated RAS gene family point mutations in five of eight cases analyzed in each of the two histotypes, with a high proportion of CAA-->AAA transversion at codon 61 of the N-RAS gene in insular carcinoma. These findings suggest that insular carcinoma represents a de novo entity distinct from widely invasive follicular carcinoma, that widely invasive follicular carcinoma has biologic characteristics more consistent with poorly differentiated than well-differentiated carcinomas, and that both insular carcinoma and widely invasive follicular carcinoma share similar molecular alterations.

  11. Relationship between endometritis and oxidative stress in the follicular fluid and luteal function in the buffalo.

    PubMed

    Behera, B K; Sharma, C G; Singh, S K; Kumar, H; Chaudhari, R K; Mahla, A S; Das, G K; Krishnaswamy, N

    2016-10-01

    In this study, alteration in the follicular fluid composition and luteal function was investigated in the buffalo with endometritis. Genitalia were classified into cytological and purulent endometritis on the basis of polymorphonuclear cell cut off while non-endometritis served as control (n = 10/group). In the follicular phase, the number of surface follicles was counted, diameter of the largest follicle was measured and the follicular fluid was assayed for total protein, cholesterol, malondialdehyde (MDA), total antioxidant capacity (TAC), oestradiol (E2 ) and progesterone (P4 ). The P4 content of corpus luteum during mid-luteal phase was estimated by radioimmunoassay. Ovaries from the follicular phase of oestrous cycle showed no significant difference in the total number of surface follicles, size of the largest follicle and volume of follicular fluid in the buffaloes with and without endometritis (p > .05). However, the antral fluid of the largest follicle from the genitalia of buffalo with cytological and purulent endometritis showed a significant decrease in the concentration of total protein, cholesterol, TAC and E2 and a significant increase in the concentration of MDA and P4 (p < .05). The results indicated that there is an association between endometritis and decreased ovarian function. PMID:27554926

  12. Phenotypes of the ovarian follicular basal lamina predict developmental competence of oocytes

    PubMed Central

    Irving-Rodgers, Helen F.; Morris, Stephanie; Collett, Rachael A.; Peura, Teija T.; Davy, Margaret; Thompson, Jeremy G.; Mason, Helen D.; Rodgers, Raymond J.

    2009-01-01

    BACKGROUND The ovarian follicular basal lamina underlies the epithelial membrana granulosa and maintains the avascular intra-follicular compartment. Additional layers of basal lamina occur in a number of pathologies, including pili annulati and diabetes. We previously found additional layers of follicular basal lamina in a significant percentage of healthy bovine follicles. We wished to determine if this phenomenon existed in humans, and if it was related to oocyte function in the bovine. METHODS AND RESULTS We examined follicles from human ovaries (n = 18) by electron microscopy and found that many follicles had additional layers of basal lamina. Oocytes (n = 222) from bovine follicles with normal or unusual basal laminas were isolated and their ability to undergo in vitro maturation, fertilization and culture to blastocyst was compared. Healthy bovine follicles with a single layer of basal lamina had oocytes with significantly (P < 0.01) greater developmental competence than healthy follicles with additional layers of follicular basal lamina (65% versus 28%). CONCLUSIONS These findings provide direct evidence that the phenotype of the follicular basal lamina is related to oocyte competence. PMID:19095662

  13. Immunohistochemical Detection of p75 Neurotrophin Receptor (p75-NTR) in Follicular and Plexiform Ameloblastoma

    PubMed Central

    Madhavan, Nirmal Ramadas; Mohan, Sunil Paramel; Kumar, Srichinthu Kenniyan

    2016-01-01

    Introduction Ameloblastoma holds a unique position among benign tumours by its locally destructive and invasive nature. Recently improvised molecular techniques helped researchers to unravel the myth behind such biologic behaviour. Though interesting findings have been delivered, the rhythmic correlation regarding the exact mechanism still remains lacking. Neurotrophins and their receptor mediated pathways play a crucial role in survival, death and differentiation of many neuroectoderm derived cells. With this background, the study has been aimed to investigate the expression of p75-NTR (Neurotrophin Receptor) in follicular and plexiform ameloblastoma. Aim To analyze the immunohistochemical expression pattern of p75-NTR in ameloblastoma and to compare the immunohistochemical expression pattern of p75-NTR among the histological types of ameloblastoma, follicular and plexiform patterns. Materials and Methods Total 22 ameloblastomas (12 follicular, 10 plexiform) were immuno-stained with anti-human p75-NTR mouse IgG monoclonal antibody and the pattern of staining is statistically analyzed. Results Only 11 (10 follicular, 1 plexiform) out of 22 ameloblastomas showed immuno-reactivity to p75-NTR. In ameloblastoma, only the peripheral pre-ameloblast like tall columnar cells showed reactivity whereas the stellate reticulum-like cells were immuno-negative. The staining pattern was membranous in the immuno-reactive cells. The results were studied with the downstream pathways from the literature and a possible mechanism has been proposed. Conclusion The expression pattern of p75-NTR was found to be more in follicular ameloblastoma than plexiform. PMID:27656566

  14. The comprehensive mechanisms underlying nonhierarchical follicular development in geese (Anser cygnoides).

    PubMed

    Liu, Hehe; Zhang, Wenjie; Li, Qingqing; Liu, Junying; Zhang, Tao; Zhou, Tianyu; Li, Liang; Wang, Jiwen; Xu, Hengyong; He, Hua

    2015-08-01

    The laying performance of poultry primarily depends on the growth and development of the ovarian follicles. Yet, little is known about the underlying mechanisms responsible for nonhierarchical follicular development in avian species. The aim of the present study is identify genes that are differentially expressed during nonhierarchical follicular development in geese by performing a transcriptome screen. A sequencing depth of 13.9 and 14.9 million mapped tags was obtained in pools of small white follicles (SWF) and small yellow follicles (SYF), respectively, and a total of 160 differentially expressed genes were identified. The fold-changes of eight differentially expressed genes, identified using qRT-PCR, were consistent with the Digital Gene Expression Profiling (DGE) data. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) analyses showed that lipid metabolism, steroid secretion, extracellular ligand reactions, enzyme activities, the cell cycle, ECM-receptor interactions and the extracellular matrix are involved in follicular development. The majority of the newly identified genes could be considered to be new candidate genes with potential roles in regulating follicular development. These results provide useful information for future in-depth studies associated with nonhierarchical follicular development in goose reproduction.

  15. Follicular thyroid adenoma dominated by spindle cells: report of two unusual cases and literature review

    PubMed Central

    Abbas, Agaimy; Thomas, Hahn; Josef, Schroeder; Afaf, Elhag

    2012-01-01

    Primary spindle cell neoplasms of the thyroid gland are quite rare. They encompass a heterogeneous group of benign and malignant lesions of mesenchymal and epithelial origin. We herein describe two unusual follicular thyroid adenomas dominated by spindle cells with occasional areas of colloid-forming follicular differentiation. The tumors affected a 77-year woman and a 70-year old man; both had a long-history of monoclonal gammopathy of unknown significance (MGUS). One tumor presented as a large cold thyroid nodule and the other was an autopsy finding. The tumors were predominantly composed of fibroblast-like spindled cells. One case showed prominent meningioma-like concentric perivascular arrangement and contained cytoplasmic melanin-like pigment. Stromal hyalinization was a prominent feature of both. By immunohistochemistry, the spindled cells expressed vimentin, pankeratin (KL1), thyroglobulin and TTF1 consistent with a follicular differentiation. They did not stain with calcitonin, CEA and other lineage-specific mesenchymal, neuroendocrine and melanocytic markers. There was no evidence of metastasis at autopsy (case 2) or at last follow-up 2 years after surgery (case 1). These cases demonstrate the diversity of follicular thyroid neoplasms and the unusual occurrence of extensive spindle cell metaplasia. These uncommon lesions need to be distinguished from spindle cell medullary carcinoma, paucicellular spindle cell anaplastic carcinoma, spindle cell foci in papillary and follicular carcinoma, solitary fibrous tumor and other rare benign and malignant mesenchymal lesions. PMID:22400075

  16. Ovarian follicular development and the follicular fluid hormones and growth factors in normal women of advanced reproductive age.

    PubMed

    Klein, N A; Battaglia, D E; Miller, P B; Branigan, E F; Giudice, L C; Soules, M R

    1996-05-01

    Reproductive aging in women (a physiological decline in the function of the hypothalamic-pituitary-ovarian axis) is an infrequently investigated and poorly understood biological phenomenon. Although menstrual irregularity and anovulation are known to precede the menopause, normal women in their fifth decade experience a profound decrease in fertility while still experiencing regular menstrual cycles. To further our understanding of the physiological changes associated with reproductive aging, this study examined the spontaneous development and function of ovarian follicles in normal women, aged 40-45 yr. The subjects were women (n = 21), aged 40-45 yr, who had regular 25- to 35-day ovulatory menstrual cycles, were not infertile, had no medical problems, and met specific criteria for weight, diet, and exercise. The controls were normal women (n = 20), age 20-25 yr, who met the same criteria. The subjects were monitored with daily hormone measurements [LH, FSH, estradiol (E), progesterone (P), and inhibin] and pelvic sonograms from day 1 of their study cycle until the dominant ovarian follicle reached a mean diameter of 15 mm and/or a serum E level of 550 pmol/L or higher was attained. At that time, 10,000 U hCG were given, and a transvaginal sonographic follicle aspiration was performed 32 h later. The follicular fluid (FF) was collected, stored frozen at -70 C, and later analyzed for E, P, testosterone (T), androstenedione, inhibin, insulin-like growth factor I (IGF-I), and IGF-II. The number of cycle days to aspiration was lower (11.6 vs. 15.6 days; P < 0.001) and the early follicular phase mean FSH and mean E levels were higher (9.3 vs. 6.6 mIU/mL and 305 vs. 160 pmol/L; P < 0.01) in the older (O) group compared to the younger group. There was a strong trend toward higher FF mean E (2280 vs. 1931 nmol/L) and lower FF mean T (978 vs. 2361 pmol/L) levels in group O. The E/T ratio was significantly higher (5253 vs. 2408; P < 0.03) in group O. In group O, the mean FF

  17. Ovarian follicular development and the follicular fluid hormones and growth factors in normal women of advanced reproductive age.

    PubMed

    Klein, N A; Battaglia, D E; Miller, P B; Branigan, E F; Giudice, L C; Soules, M R

    1996-05-01

    Reproductive aging in women (a physiological decline in the function of the hypothalamic-pituitary-ovarian axis) is an infrequently investigated and poorly understood biological phenomenon. Although menstrual irregularity and anovulation are known to precede the menopause, normal women in their fifth decade experience a profound decrease in fertility while still experiencing regular menstrual cycles. To further our understanding of the physiological changes associated with reproductive aging, this study examined the spontaneous development and function of ovarian follicles in normal women, aged 40-45 yr. The subjects were women (n = 21), aged 40-45 yr, who had regular 25- to 35-day ovulatory menstrual cycles, were not infertile, had no medical problems, and met specific criteria for weight, diet, and exercise. The controls were normal women (n = 20), age 20-25 yr, who met the same criteria. The subjects were monitored with daily hormone measurements [LH, FSH, estradiol (E), progesterone (P), and inhibin] and pelvic sonograms from day 1 of their study cycle until the dominant ovarian follicle reached a mean diameter of 15 mm and/or a serum E level of 550 pmol/L or higher was attained. At that time, 10,000 U hCG were given, and a transvaginal sonographic follicle aspiration was performed 32 h later. The follicular fluid (FF) was collected, stored frozen at -70 C, and later analyzed for E, P, testosterone (T), androstenedione, inhibin, insulin-like growth factor I (IGF-I), and IGF-II. The number of cycle days to aspiration was lower (11.6 vs. 15.6 days; P < 0.001) and the early follicular phase mean FSH and mean E levels were higher (9.3 vs. 6.6 mIU/mL and 305 vs. 160 pmol/L; P < 0.01) in the older (O) group compared to the younger group. There was a strong trend toward higher FF mean E (2280 vs. 1931 nmol/L) and lower FF mean T (978 vs. 2361 pmol/L) levels in group O. The E/T ratio was significantly higher (5253 vs. 2408; P < 0.03) in group O. In group O, the mean FF

  18. Impact of surgery, radiation and systemic therapy on the outcomes of patients with dendritic cell and histiocytic sarcomas

    PubMed Central

    Gounder, Mrinal; Desai, Ved; Kuk, Deborah; Agaram, Narasimhan; Arcila, Maria; Durham, Benjamin; Keohan, Mary L.; Dickson, Mark A.; D’Angelo, Sandra P.; Shukla, Neerav; Moskowitz, Craig; Noy, Ariela; Maki, Robert G.; Herrera, Diego Adrianzen; Sanchez, Armando; Krishnan, Anita; Pourmoussa, Andrew; Qin, Li-Xuan; Tap, William D.

    2016-01-01

    Background Neoplasms of histiocytic and dendritic cell origin, including follicular dendritic cell sarcoma (FDCS), histiocytic sarcoma (HS) and interdigitating dendritic cell sarcoma (IDCS), are extremely rare, and data on their natural history and treatment outcomes are sparse. We evaluated the impact of surgery, radiation and systemic therapies on overall survival (OS). Methods We conducted a retrospective chart review of patients with FDCS, IDCS and HS treated at Memorial Sloan Kettering Cancer Center between 1995 and 2014. Results We identified 31, 15 and 7 patients with FDCS, HS and IDCS, respectively. Median age was 48.7, 42.3 and 58.8 years for FDCS, HS and IDCS, respectively. Only a slight disparity in gender distribution existed for FDCS and HS; however, IDCS predominantly affected males (6:1). The most common sites of presentation were abdomen and pelvis (42%), extremities (33%) and head and neck (57%) for FDCS, HS and IDCS, respectively. At diagnosis, 74%, 40% and 86% of patients presented with localised disease in FDCS, HS and IDCS, respectively. Patients with localised disease had significantly improved OS than those with metastatic disease in FDCS (P = 0.04) and IDCS (P = 0.014) but not in HS (P = 0.95). In FDCS and HS, adjuvant or neo-adjuvant therapy was not associated with improved OS compared with observation. In IDCS, surgery alone provided a 5-year overall survival rate of 71%. Conclusions Adjuvant or neo-adjuvant treatment in FDCS and HS did not affect OS. Patients with IDCS had an excellent outcome with surgery. In the metastatic setting, chemotherapy and small molecule inhibitors may provide benefit. PMID:26298731

  19. Mechanisms of Disruptive Action of Dichlorodiphenyltrichloroethane (DDT) on the Function of Thyroid Follicular Epitheliocytes.

    PubMed

    Yaglova, N V; Yaglov, V V

    2015-12-01

    The mechanism of disruptive action of dichlorodiphenyltrichloroethane (DDT) on the function of thyroid follicular epitheliocytes was examined in mature male Wistar rats administered with a daily dose of DDT (2 μg/kg) for 6 or 10 weeks. In 6 weeks, the serum level of Na(+)/I(-) symporter responsible for the transport of iodides into follicular thyrocytes decreased, while serum concentration of thyroperoxidase increased. In 10 weeks, both the number of follicles in the thyroid gland and serum level of Na(+)/I(-) symporter increased. In circulating blood, the concentrations of thyroglobulin as well as α and β receptors of the thyroid hormones did not change. DDT down-regulated the iodine-accumulated function of follicular thyrocytes by suppressing Na(+)/I(-) symporter synthesis. Recovery of Na(+)/I (-) symporter production resulted from up-regulation of the proliferative processes in thyroid gland. PMID:26621281

  20. Value of quantitative nucleolar features in the preoperative cytological diagnosis of follicular neoplasias of the thyroid.

    PubMed Central

    Montironi, R; Braccischi, A; Scarpelli, M; Matera, G; Alberti, R

    1991-01-01

    Nucleolar prevalence, size, and outline were investigated on cytological material from cold thyroid nodules obtained by fine needle aspiration. The percentage of nucleolated nuclei in follicular adenoma (32 cases) was less than in follicular carcinoma (26 cases). In adenoma most nuclei contained one nucleolus, and nuclei with two or more nucleoli were less common than in carcinoma where most cases showed the highest nucleolar diameter values. There was some overlap between adenomas and carcinomas, however, when the mean of the 10 largest values of the major nucleolar diameter was considered. In follicular carcinoma the percentage of marginated nucleoli--that is, those touching the nuclear membrane--was, in general, greater than 20%; in adenoma the values were equal to or lower than 16%. The overlap index showed that the percentages of marginated nucleoli and nucleolated nuclei are the two best discriminatory features between adenoma and carcinoma. PMID:2066431

  1. Induction of follicular luteinization by equine chorionic gonadotropin in cyclic guinea pigs*

    PubMed Central

    Li, Jun-rong; Wang, Wei; Shi, Fang-xiong

    2015-01-01

    The effects of equine chorionic gonadotropin (eCG) on follicular development and ovulation in cyclic guinea pigs were investigated by histological and immunohistochemical analyses. Three groups of guinea pigs (n=12) were administrated subcutaneously with saline, 20 or 50 IU of eCG, respectively, on cyclic Day 12 (Day 1=vaginal openings). Ovaries were collected at 4 and 8 d after administration (6 animals per group each time). The eCG administration induced significant and distinct morphological changes in the ovaries, as it promoted the luteinization of granulosa cells, but not follicular development. In addition, proliferating cell nuclear antigen (PCNA) and steroidogenic acute regulatory protein (StAR) were immunolocalized specifically in luteinized follicles. Our experiments together indicate that eCG administration can induce follicular luteinization but not superovulation in guinea pigs. The eCG in cyclic guinea pigs functions similar to that of luteinizing hormone (LH), but not follicle-stimulating hormone (FSH). PMID:26642181

  2. Mechanisms of Disruptive Action of Dichlorodiphenyltrichloroethane (DDT) on the Function of Thyroid Follicular Epitheliocytes.

    PubMed

    Yaglova, N V; Yaglov, V V

    2015-12-01

    The mechanism of disruptive action of dichlorodiphenyltrichloroethane (DDT) on the function of thyroid follicular epitheliocytes was examined in mature male Wistar rats administered with a daily dose of DDT (2 μg/kg) for 6 or 10 weeks. In 6 weeks, the serum level of Na(+)/I(-) symporter responsible for the transport of iodides into follicular thyrocytes decreased, while serum concentration of thyroperoxidase increased. In 10 weeks, both the number of follicles in the thyroid gland and serum level of Na(+)/I(-) symporter increased. In circulating blood, the concentrations of thyroglobulin as well as α and β receptors of the thyroid hormones did not change. DDT down-regulated the iodine-accumulated function of follicular thyrocytes by suppressing Na(+)/I(-) symporter synthesis. Recovery of Na(+)/I (-) symporter production resulted from up-regulation of the proliferative processes in thyroid gland.

  3. Free vitamin D does not vary through the follicular phase of the menstrual cycle.

    PubMed

    Franasiak, J M; Wang, X; Molinaro, T A; Green, K; Sun, W; Werner, M D; Juneau, C R; Scott, R T

    2016-07-01

    The importance of vitamin D (25OHD) in general health and reproductive success has been a focus in the setting of the 25OHD deficiency epidemic. However, there are challenges to understanding 25OHD's effects. The free and bioavailable levels are affected by 25OHD binding protein (DBP) and it is not known how estradiol fluctuations during the menstrual cycle affect these binding parameters. This may impact the most appropriate time to measure 25OHD when determining deficiency. This study characterizes 25OHD throughout the follicular phase of the menstrual cycle. Patients undergoing natural cycle IVF were included. Serum was drawn throughout the follicular phase of the menstrual cycle; 25OHD, DBP, albumin, and estrogen levels were determined for each time point allowing for mathematical calculation of free and bioavailable 25OHD. Early, mid, and late follicular phases were designated by estrogen tertiles among patients. Mean Levels of 25OHD (total, free, bioavailable) and DBP for each tertile were compared with Kruskil-Wallis test for non-parametric groups. Linear regression with GEE was employed due to repeated measures within participants. A total of 33 patients were included with 202 total serum measurements. There was no difference in mean levels of 25OHD (p = 0.77), free 25OHD (p = 0.91), and bioavailable 25OHD (p = 0.76) when measured throughout the follicular phase of the menstrual cycle. Vitamin D metabolism does not fluctuate as estradiol changes in the follicular phase of the menstrual cycle. This data indicates that assessment of 25OHD, in particular when assessed for associations with reproductive outcomes, can be measured reliably at any point during the follicular phase of the menstrual cycle.

  4. Is the short follicular phase in older women secondary to advanced or accelerated dominant follicle development?

    PubMed

    Klein, Nancy A; Harper, Andrew J; Houmard, Brenda S; Sluss, Patrick M; Soules, Michael R

    2002-12-01

    This study sought to determine whether the shortened follicular phase in ovulatory older women is secondary to advanced (i.e. earlier) or accelerated (i.e. more rapid) folliculogenesis. Normal ovulatory women, aged 40-45 yr (n = 15) and 20-25 yr (n = 13), underwent daily venipuncture and transvaginal ultrasonography throughout the follicular phase of a spontaneous menstrual cycle (control cycle) and after pituitary down-regulation with a GnRH agonist (study cycle). As expected, the older subjects in the control cycles demonstrated an elevated d 3 FSH and a shortened follicular phase compared with the younger subjects. After release from hypothalamic-pituitary-ovarian axis suppression, the early follicular phase FSH peak occurred earlier (6.8 vs. 9.8 d; P < 0.01) and was of a greater magnitude (12.1 vs. 6.5 mIU/ml; P < 0.01) in the older subjects. The time from release of suppression until the subsequent LH surge was also shorter (17.5 vs. 20.8 d; P < 0.01) in the older group. However, the time from FSH peak to LH surge was similar in the older and younger groups (10.7 vs. 11.0 d; P = 0.74). Compared with younger women, older subjects had normal follicular phase levels of estradiol and inhibin A and lower levels of inhibin B in both control and study cycles. We conclude that the shortened follicular phase observed in older ovulatory women is due to earlier dominant follicle selection, independent of hormonal influences from the preceding luteal phase.

  5. Computerized nuclear morphometry in the diagnosis of thyroid lesions with predominant follicular pattern

    PubMed Central

    Aiad, HA; Abdou, AG; Bashandy, MA; Said, AN; Ezz-Elarab, SS; Zahran, AA

    2009-01-01

    Background: Differential diagnosis of thyroid lesions with predominantly follicular pattern is one of the most common problems in thyroid pathology. Development of more objective and reproducible tools for diagnosis is needed. This work is aimed at studying the role of nuclear morphometry in differential diagnosis of different thyroid lesions having predominant follicular pattern. Material and methods: Semiautomatic image analysis system was used to measure a total of 8 nuclear parameters in 48 thyroid lesions including seven nodular goiter (NG), 14 follicular adenoma (FA), 14 follicular carcinoma (FC) and 13 follicular variant papillary carcinoma (FVPC). Results: The parameters related to nuclear size (area, perimeter, MaxD, MinD, nuclear size) and shape (L/S ratio, Form_AR) were significantly higher in neoplastic group (FA, FC, FVPC) when compared to non-neoplastic group (NG) P<0.05. The perimeter was the most reliable parameter (area under the cure (AUC)=97%) followed by area, MaxD, and size (all have AUC= 96%) then form-AR (90%), LS ratio (86%) and the least reliable was Min D (79%). Within the neoplastic group, most parameters related to size and shape of the nuclei was significantly higher in FVPC than in FA and FC (p ≤ 0.05). Nuclear area and size (AUC 77%) were the most reliable parameters for differentiation between FVPC and FA. The best cut off values for diagnosing FVPC are nuclear area ≥39.9μm2 and nuclear size ≥27.7μm2. However, there was no quantitative difference between FC and FA. Conclusion: Nuclear morphometric parameters may help in the differentiation between neoplastic and non-neoplastic thyroid lesions and between FVPC and follicular neoplasms (FC and FA) but they have no value in the differentiation between FC and FA. PMID:22276011

  6. Ovarian follicular development in the hawksbill turtle (Cheloniidae: Eretmochelys imbricata L.).

    PubMed

    Pérez-Bermúdez, Emir; Ruiz-Urquiola, Ariel; Lee-González, Idania; Petric, Benjamin; Almaguer-Cuenca, Nilda; Sanz-Ochotorena, Ana; Espinosa-López, Georgina

    2012-12-01

    Ovarian follicular development is an essential process in the determination of maturation stages associated with size. This association acquires importance when managing populations of threatened species. We histologically processed 11 prepubescent ovaries, four pubescent ovaries, and one breeding adult ovary with vitellogenic follicles using specific staining techniques to identify the follicular stages of Eretmochelys imbricata. Follicular stages were compared with maturation stages [including straight carapace length (SCL)]. The ovary presented several germinal beds and a lacunar system less histochemically and morphologically heterogeneous than that of crocodiles. During previtellogenesis (four stages), the oocyte grows rapidly due to the strong transcriptional activity of lampbrush chromosomes and numerous nucleoli, and the strong metabolism associated with lipid synthesis. The Stage III ooplasm showed a Sudan positive band. This stage was the most frequent in all ovarian sections and it was independent of maximal follicular stage. Stage IV, more frequent in pubescent and adult ovaries, presented a lipid vacuole-rich ooplasm and a broadening of the zona pellucida and the theca. The vitellogenesis begins with the penetration and accumulation of spherical glycoprotein yolk platelets and chemically neutral lipid droplets which are observed to be mixed, but spatially and chemically segregated. Both the yolk platelets and lipid droplets increase in size, density, and proximity to the periphery of the oocyte due to their coalescence. The SCL of the immature females did not determine the maximal follicular stage nor its frequency in the ovaries. Straight carapace length turned out to be an imprecise measure in identifying the presence of follicular stages in females larger than the minimum legal size limit in Cuba. Consequently, for a national conservation program to be successful, it must emphasize the critically endangered status of E. imbricata, as well as the

  7. CD45 epitope mapping of human CD1a+ dendritic cells and peripheral blood dendritic cells.

    PubMed Central

    Wood, G. S.; Freudenthal, P. S.; Edinger, A.; Steinman, R. M.; Warnke, R. A.

    1991-01-01

    The authors studied the pattern of leukocyte common antigen (CD45) epitope expression on dendritic cells in sections of human epidermis, tonsillar epithelium, dermatopathic lymph nodes, and in isolates from blood. The monoclonal antibodies (MAb) used were specific for all known CD45 epitopes, including the seven different CD45 common epitopes as well as the four known CD45R epitopes (two CD45RA, one CD45RB, and one CD45RO). Dendritic cells in all sites were uniformly reactive for the CD45 common epitopes tested except 2B11, which may recognize a CD45R rather than CD45 epitope. By single-label immunoperoxidase and double-label immunofluorescence epitope mapping of CD1a+ dendritic cells in tissue sections, it was generally difficult or impossible to detect expression of CD45RA, CD45RB, CD45RO, or 2B11. In blood dendritic cells, however, low levels of these CD45R epitopes were detected consistently using single-label immunoperoxidase staining of cytocentrifuge preparations. Monocytes were similar to blood dendritic cells except that the staining with MAb to CD45RO and 2B11 was slightly stronger. The authors conclude that dendritic cells differ from most subpopulations of lymphocytes in that CD45 common epitopes are readily detectable but the existing RA, RB, and RO epitopes are either undetectable or expressed at relatively low levels. These studies raise the possibility that CD1a+ dendritic cells may express a novel dominant CD45 isoform. Images Figure 1 Figure 2 PMID:1711291

  8. Dramatic response of follicular thyroid carcinoma with superior vena cava syndrome and tracheal obstruction to external-beam radiotherapy

    SciTech Connect

    Wilford, M.R.; Chertow, B.S.; Lepanto, P.B.; Leidy, J.W. Jr. )

    1991-06-01

    We report a patient with follicular thyroid carcinoma progressing to superior vena cava (SVC) syndrome and tracheal obstruction despite multiple doses of radioactive iodine therapy but subsequently responding dramatically to external-beam radiotherapy (RT). Although RT is not considered to be the treatment of choice for follicular carcinoma, RT in our patient produced unequivocal improvement of SVC syndrome and tracheal obstruction.

  9. Economic burden of follicular non-Hodgkin's lymphoma.

    PubMed

    Foster, Talia; Miller, Jeffrey D; Boye, Mark E; Russell, Mason W

    2009-01-01

    Follicular non-Hodgkin's lymphoma (FNHL), a slow-growing cancer of the immune system, constitutes about 15-30% of all incident non-Hodgkin's lymphoma in developed countries. Its incidence is rising worldwide. Patients can live many years, but FNHL is considered incurable. We systematically reviewed the English-language MEDLINE-indexed and non-indexed economic literature published in the past 10 years on FNHL, identifying 23 primary economic studies. The economic burden of FNHL is significant, but available data are generally limited to retrospective considerations of hospital-based direct treatment costs, with little information available regarding societal cost of illness. Most direct cost information originates from the US, with one estimate of $US36 000 for the per-patient incremental cost of FNHL care during the first year following diagnosis. The most studied treatment is rituximab, which may offer similar overall costs to fludarabine considering higher resource use with fludarabine complications. Nearly all cost-effectiveness models identified by this review evaluated rituximab for relapsed/refractory FNHL responding to chemotherapy induction. Rituximab is supported as a cost-effective addition to standard chemotherapy by two models in the UK and one in the US, as maintenance therapy instead of stem-cell transplant by one UK model, and as maintenance therapy instead of observation alone by one model each in France, Spain and Canada. The UK National Institute for Health and Clinical Excellence updated guidance on rituximab in February 2008, concluding that it is cost effective when added to induction chemotherapy, and when used as maintenance therapy. No studies of per-patient or national indirect costs of illness were identified, with the only study of indirect costs a Canadian survey documenting lost work productivity. Across all study types identified by our review, the most common focus was on the direct costs of rituximab. As new treatments for FNHL come

  10. Fertility Preservation Among the Cancer Patients by Ovarian Tissue Cryopreservation, Transplantation, and Follicular Development

    PubMed Central

    Abedelahi, Ali; Rezaei-Tavirani, Mostafa; Mohammadnejad, Daryosh

    2013-01-01

    Ovarian tissue freezing or cryopreservation might be the only acceptable method for preserving the young women fertility, before radiotherapy or chemotherapy. This technology might be used for patients with recurrent ovarian cysts or endometriosis, without ovarian stimulation. Many efforts have made to improve cryopreservation conditions that should be seriously considered for cancer patients. Vitrification is a process which prevents ovarian tissue from cryo damage, then preserves cell viability. Both methods have used for evaluating not only the follicular development, but also the fertility after freezing and thawing. In this manuscript, we have discussed the techniques of ovarian tissue vitrification, then graft and maturation or follicular development is also mentioned. PMID:25250122

  11. Regression of follicular lymphoma of the duodenum following eradication of H. pylori infection.

    PubMed

    Hayashi, Hiroki; Onishi, Yutaka; Mitsuoka, Hiroshi; Ogura, Takeshi; Maeda, Mitsuo; Nishigami, Takashi; Harada, Masaru

    2013-01-01

    A 64-year-old woman was referred for an examination of the upper gastrointestinal (GI) tract. Endoscopy showed an elevated lesion in the duodenum with central depression and multiple white granules. Biopsy specimens revealed lymphoid follicles composed predominantly of centrocytes with scattered centroblasts. The tumor cells were positive for bcl-2. The patient was diagnosed with follicular lymphoma and underwent antibiotic therapy for Helicobacter pylori (H. pylori) infection. The regression of the lesion was obvious. After 5.5 years of follow-up, there has been no evidence of recurrence. This case suggests that H. pylori eradication therapy is effective for treating follicular lymphoma in the duodenum. PMID:24292749

  12. Follicular carcinoma of the thyroid with functioning metastases and clinical hyperthyroidism.

    PubMed Central

    McConnon, J. K.; von Westarp, C.; Mitchell, R. I.

    1975-01-01

    Hyperthyroidism associated with metastatic follicular carcinoma of the thyroid gland is rare. In one patient the mass of functioning follicular tissue in the primary and metastatic tumour was so great that excessive amounts of thyroxine and triiodothyronine were produced and, as a result, clinical hyperthyroidism developed. This was in spite of the fact that the activity per unit of tissue was not supranormal and may even have been slightly subnormal. The initial response of the metastases to 131I ablative therapy was excellent. Images FIG. 1 FIG. 2 FIG. 3A FIG. 3B FIG. 4 FIG. 5 PMID:1122444

  13. Dendritic development of newly generated neurons in the adult brain.

    PubMed

    Ribak, Charles E; Shapiro, Lee A

    2007-10-01

    Ramon y Cajal described the fundamental morphology of the dendritic and axonal growth cones of neurons during development. However, technical limitations at the time prevented him from describing such growth cones from newborn neurons in the adult brain. The phenomenon of adult neurogenesis is briefly reviewed, and the structural description of dendritic and axonal outgrowth for these newly generated neurons in the adult brain is discussed. Axonal outgrowth into the hilus and CA3 region of the hippocampus occurs later than the outgrowth of dendrites into the molecular layer, and the ultrastructural analysis of axonal outgrowth has yet to be completed. In contrast, growth cones on dendrites from newborn neurons in the adult dentate gyrus have been described and this observation suggests that dendrites in adult brains grow in a similar way to those found in immature brains. However, dendrites in adult brains have to navigate through a denser neuropil and a more complex cell layer. Therefore, some aspects of dendritic outgrowth of neurons born in the adult dentate gyrus are different as compared to that found in development. These differences include the radial process of radial glial cells acting as a lattice to guide apical dendritic growth through the granule cell layer and a much thinner dendrite to grow through the neuropil of the molecular layer. Therefore, similarities and differences exist for dendritic outgrowth from newborn neurons in the developing and adult brain.

  14. Developmental mechanisms that regulate retinal ganglion cell dendritic morphology

    PubMed Central

    Tian, Ning

    2011-01-01

    One of the fundamental features of retinal ganglion cells (RGCs) is that dendrites of individual RGCs are confined to one or a few narrow strata within the inner plexiform layer (IPL), and each RGC synapses only with a small group of presynaptic bipolar and amacrine cells with axons/dendrites ramified in the same strata to process distinct visual features. The underlying mechanisms which control the development of this laminar-restricted distribution pattern of RGC dendrites have been extensively studied, and it is still an open question whether the dendritic pattern of RGCs is determined by molecular cues or by activity-dependent refinement. Accumulating evidence suggests that both molecular cues and activity-dependent refinement might regulate RGC dendrites in a cell subtype-specific manner. However, identification of morphological subtypes of RGCs before they have achieved their mature dendritic pattern is a major challenge in the study of RGC dendritic development. This problem is now being circumvented through the use of molecular markers in genetically engineered mouse lines to identify RGC subsets early during development. Another unanswered fundamental question in the study of activity-dependent refinement of RGC dendrites is how changes in synaptic activity lead to the changes in dendritic morphology. Recent studies have started to shed light on the molecular basis of activity-dependent dendritic refinement of RGCs by showing that some molecular cascades control the cytoskeleton reorganization of RGCs. PMID:21542137

  15. Dendritic growth tip velocities and radii of curvature in microgravity

    SciTech Connect

    Koss, M.B.; LaCombe, J.C.; Tennenhouse, L.A.; Glicksman, M.E.; Winsa, E.A.

    1999-12-01

    Dendritic growth is the common mode of solidification encountered when metals and alloys freeze under low thermal gradients. The growth of dendrites in pure melts depends on the transport of latent heat from the moving crystal-melt interface and the influence of weaker effects like the interfacial energy. Experimental data for critical tests of dendritic growth theories remained limited because dendritic growth can be complicated by convection. The Isothermal Dendritic Growth Experiment (IDGE) was developed specifically to test dendritic growth theories by performing measurements with succinonitrile (SCN) in microgravity, thus eliminating buoyancy-induced convection. The first flight of the IDGE in 1994 operated for 9 days at a mean quasi-static acceleration of 0.7 x 10{sup {minus}6} g{sub 0}. The velocity and radius data show that at supercoolings above approximately 0.4 K, dendritic growth in SCN under microgravity conditions is diffusion limited. By contrast, under terrestrial conditions, dendritic growth of SCN is dominated y convection for supercoolings below 1.7 K. The theoretical and experimental Peclet numbers exhibit modest disagreement, indicating that transport theories of dendritic solidification require some modification. Finally, the kinetic selection rule for dendritic growth, VR{sup 2} = constant, where V is the velocity of the tip and R is the radius of curvature at the tip, appears to be independent of the gravity environment, with a slight dependence on the supercooling.

  16. Altered Theca and Cumulus Oocyte Complex Gene Expression, Follicular Arrest and Reduced Fertility in Cows with Dominant Follicle Follicular Fluid Androgen Excess

    PubMed Central

    Summers, Adam F.; Pohlmeier, William E.; Sargent, Kevin M.; Cole, Brizett D.; Vinton, Rebecca J.; Kurz, Scott G.; McFee, Renee M.; Cushman, Robert A.; Cupp, Andrea S.; Wood, Jennifer R.

    2014-01-01

    Aspiration of bovine follicles 12–36 hours after induced corpus luteum lysis serendipitously identified two populations of cows, one with High androstenedione (A4; >40 ng/ml; mean = 102) and another with Low A4 (<20 ng/ml; mean = 9) in follicular fluid. We hypothesized that the steroid excess in follicular fluid of dominant follicles in High A4 cows would result in reduced fertility through altered follicle development and oocyte maternal RNA abundance. To test this hypothesis, estrous cycles of cows were synchronized and ovariectomy was performed 36 hours later. HPLC MS/MS analysis of follicular fluid showed increased dehydroepiandrosterone (6-fold), A4 (158-fold) and testosterone (31-fold) in the dominant follicle of High A4 cows. However, estrone (3-fold) and estradiol (2-fold) concentrations were only slightly elevated, suggesting a possible inefficiency in androgen to estrogen conversion in High A4 cows. Theca cell mRNA expression of LHCGR, GATA6, CYP11A1, and CYP17A1 was greater in High A4 cows. Furthermore, abundance of ZAR1 was decreased 10-fold in cumulus oocyte complexes from High A4 cows, whereas NLRP5 abundance tended to be 19.8-fold greater (P = 0.07). There was a tendency for reduction in stage 4 follicles in ovarian cortex samples from High A4 cows suggesting that progression to antral stages were impaired. High A4 cows tended (P<0.07) to have a 17% reduction in calving rate compared with Low A4 cows suggesting reduced fertility in the High A4 population. These data suggest that the dominant follicle environment of High A4 cows including reduced estrogen conversion and androgen excess contributes to infertility in part through altered follicular and oocyte development. PMID:25330369

  17. Evaluating Local Primary Dendrite Arm Spacing Characterization Techniques Using Synthetic Directionally Solidified Dendritic Microstructures

    NASA Astrophysics Data System (ADS)

    Tschopp, Mark A.; Miller, Jonathan D.; Oppedal, Andrew L.; Solanki, Kiran N.

    2015-10-01

    Microstructure characterization continues to play an important bridge to understanding why particular processing routes or parameters affect the properties of materials. This statement certainly holds true in the case of directionally solidified dendritic microstructures, where characterizing the primary dendrite arm spacing is vital to developing the process-structure-property relationships that can lead to the design and optimization of processing routes for defined properties. In this work, four series of simulations were used to examine the capability of a few Voronoi-based techniques to capture local microstructure statistics (primary dendrite arm spacing and coordination number) in controlled (synthetically generated) microstructures. These simulations used both cubic and hexagonal microstructures with varying degrees of disorder (noise) to study the effects of length scale, base microstructure, microstructure variability, and technique parameters on the local PDAS distribution, local coordination number distribution, bulk PDAS, and bulk coordination number. The Voronoi tesselation technique with a polygon-side-length criterion correctly characterized the known synthetic microstructures. By systematically studying the different techniques for quantifying local primary dendrite arm spacings, we have evaluated their capability to capture this important microstructure feature in different dendritic microstructures, which can be an important step for experimentally correlating with both processing and properties in single crystal nickel-based superalloys.

  18. Somato-dendritic Synaptic Plasticity and Error-backpropagation in Active Dendrites

    PubMed Central

    Schiess, Mathieu; Urbanczik, Robert; Senn, Walter

    2016-01-01

    In the last decade dendrites of cortical neurons have been shown to nonlinearly combine synaptic inputs by evoking local dendritic spikes. It has been suggested that these nonlinearities raise the computational power of a single neuron, making it comparable to a 2-layer network of point neurons. But how these nonlinearities can be incorporated into the synaptic plasticity to optimally support learning remains unclear. We present a theoretically derived synaptic plasticity rule for supervised and reinforcement learning that depends on the timing of the presynaptic, the dendritic and the postsynaptic spikes. For supervised learning, the rule can be seen as a biological version of the classical error-backpropagation algorithm applied to the dendritic case. When modulated by a delayed reward signal, the same plasticity is shown to maximize the expected reward in reinforcement learning for various coding scenarios. Our framework makes specific experimental predictions and highlights the unique advantage of active dendrites for implementing powerful synaptic plasticity rules that have access to downstream information via backpropagation of action potentials. PMID:26841235

  19. Simulation of dendritic growth reveals necessary and sufficient parameters to describe the shapes of dendritic trees

    NASA Astrophysics Data System (ADS)

    Trottier, Olivier; Ganguly, Sujoy; Bowne-Anderson, Hugo; Liang, Xin; Howard, Jonathon

    For the last 120 years, the development of neuronal shapes has been of great interest to the scientific community. Over the last 30 years, significant work has been done on the molecular processes responsible for dendritic development. In our ongoing research, we use the class IV sensory neurons of the Drosophila melanogaster larva as a model system to understand the growth of dendritic arbors. Our main goal is to elucidate the mechanisms that the neuron uses to determine the shape of its dendritic tree. We have observed the development of the class IV neuron's dendritic tree in the larval stage and have concluded that morphogenesis is defined by 3 distinct processes: 1) branch growth, 2) branching and 3) branch retraction. As the first step towards understanding dendritic growth, we have implemented these three processes in a computational model. Our simulations are able to reproduce the branch length distribution, number of branches and fractal dimension of the class IV neurons for a small range of parameters.

  20. A Genome-Wide Screen for Dendritically Localized RNAs Identifies Genes Required for Dendrite Morphogenesis.

    PubMed

    Misra, Mala; Edmund, Hendia; Ennis, Darragh; Schlueter, Marissa A; Marot, Jessica E; Tambasco, Janet; Barlow, Ida; Sigurbjornsdottir, Sara; Mathew, Renjith; Vallés, Ana Maria; Wojciech, Waldemar; Roth, Siegfried; Davis, Ilan; Leptin, Maria; Gavis, Elizabeth R

    2016-01-01

    Localizing messenger RNAs at specific subcellular sites is a conserved mechanism for targeting the synthesis of cytoplasmic proteins to distinct subcellular domains, thereby generating the asymmetric protein distributions necessary for cellular and developmental polarity. However, the full range of transcripts that are asymmetrically distributed in specialized cell types, and the significance of their localization, especially in the nervous system, are not known. We used the EP-MS2 method, which combines EP transposon insertion with the MS2/MCP in vivo fluorescent labeling system, to screen for novel localized transcripts in polarized cells, focusing on the highly branched Drosophila class IV dendritic arborization neurons. Of a total of 541 lines screened, we identified 55 EP-MS2 insertions producing transcripts that were enriched in neuronal processes, particularly in dendrites. The 47 genes identified by these insertions encode molecularly diverse proteins, and are enriched for genes that function in neuronal development and physiology. RNAi-mediated knockdown confirmed roles for many of the candidate genes in dendrite morphogenesis. We propose that the transport of mRNAs encoded by these genes into the dendrites allows their expression to be regulated on a local scale during the dynamic developmental processes of dendrite outgrowth, branching, and/or remodeling. PMID:27260999

  1. Sensitivity of Dendritic Cells to Microenvironment Signals

    PubMed Central

    Motta, Juliana Maria; Rumjanek, Vivian Mary

    2016-01-01

    Dendritic cells are antigen-presenting cells capable of either activating the immune response or inducing and maintaining immune tolerance. They do this by integrating stimuli from the environment and changing their functional status as a result of plasticity. The modifications suffered by these cells have consequences in the way the organism may respond. In the present work two opposing situations known to affect dendritic cells are analyzed: tumor growth, leading to a microenvironment that favors the induction of a tolerogenic profile, and organ transplantation, which leads to a proinflammatory profile. Lessons learned from these situations may help to understand the mechanisms of modulation resulting not only from the above circumstances, but also from other pathologies. PMID:27088097

  2. Asteroid core crystallization by inward dendritic growth

    NASA Technical Reports Server (NTRS)

    Haack, Henning; Scott, Edward R. D.

    1992-01-01

    The physics of the asteroid core crystallization process in metallic asteroids is investigated, with special attention given to the initial conditions for core crystallization, the manner of crystallization, the mechanisms acting in the stirring of the liquid, and the effects of elements such as sulfur on crystallization of Fe-Ni. On the basis of theoretical considerations and the published data on iron meteorites, it is suggested that the mode of crystallization in asteroid core was different from the apparent outward concentric crystallization of the earth core, in that the crystallization of asteroidal cores commenced at the base of the mantle and proceeded inward. The inward crystallization resulted in complex dendritic growth. These dendrites may have grown to lengths of hundreds of meters or perhaps even as large as the core radius, thereby dividing the core into separate magma chambers.

  3. Lid for improved dendritic web growth

    DOEpatents

    Duncan, Charles S.; Kochka, Edgar L.; Piotrowski, Paul A.; Seidensticker, Raymond G.

    1992-03-24

    A lid for a susceptor in which a crystalline material is melted by induction heating to form a pool or melt of molten material from which a dendritic web of essentially a single crystal of the material is pulled through an elongated slot in the lid and the lid has a pair of generally round openings adjacent the ends of the slot and a groove extends between each opening and the end of the slot. The grooves extend from the outboard surface of the lid to adjacent the inboard surface providing a strip contiguous with the inboard surface of the lid to produce generally uniform radiational heat loss across the width of the dendritic web adjacent the inboard surface of the lid to reduce thermal stresses in the web and facilitate the growth of wider webs at a greater withdrawal rate.

  4. Endoplasmic reticulum calcium stores in dendritic spines

    PubMed Central

    Segal, Menahem; Korkotian, Eduard

    2014-01-01

    Despite decades of research, the role of calcium stores in dendritic spines structure, function and plasticity is still debated. The reasons for this may have to do with the multitude of overlapping calcium handling machineries in the neuron, including stores, voltage and ligand gated channels, pumps and transporters. Also, different cells in the brain are endowed with calcium stores that are activated by different receptor types, and their differential compartmentalization in dendrites, spines and presynaptic terminals complicates their analysis. In the present review we address several key issues, including the role of calcium stores in synaptic plasticity, their role during development, in stress and in neurodegenerative diseases. Apparently, there is increasing evidence for a crucial role of calcium stores, especially of the ryanodine species, in synaptic plasticity and neuronal survival. PMID:25071469

  5. Bortezomib, Rituximab, and Dexamethasone With or Without Temsirolimus in Treating Patients With Untreated or Relapsed Waldenstrom Macroglobulinemia or Relapsed or Refractory Mantle Cell or Follicular Lymphoma

    ClinicalTrials.gov

    2016-07-11

    Cognitive Side Effects of Cancer Therapy; Fatigue; Neurotoxicity Syndrome; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Therapy-Related Toxicity; Waldenstrom Macroglobulinemia

  6. The discovery of dendritic spines by Cajal.

    PubMed

    Yuste, Rafael

    2015-01-01

    Dendritic spines were considered an artifact of the Golgi method until a brash Spanish histologist, Santiago Ramón y Cajal, bet his scientific career arguing that they were indeed real, correctly deducing their key role in mediating synaptic connectivity. This article reviews the historical context of the discovery of spines and the reasons behind Cajal's obsession with them, all the way till his deathbed. PMID:25954162

  7. Role of Dendritic Cells in Immune Dysfunction

    NASA Technical Reports Server (NTRS)

    Savary, Cherylyn A.

    1997-01-01

    Specific aims include: (1) Application of the bioreactor to enhance cytokine-regulated proliferation and maturation of dendritic cells (DC); (2) Based on clues from spaceflight: compare the frequency and function of DC in normal donors and immunocompromised cancer patients; and (3) Initiate studies on the efficiency of cytokine therapy and DC-assisted immunotherapy (using bioreactor-expanded DC) in animal models of experimental fungal infections.

  8. In vitro production of estradiol by bovine granulosa cells: evaluation of culture condition, stage of follicular development, and location of cells within follicles.

    PubMed

    Roberts, A J; Echternkamp, S E

    1994-08-01

    In vitro estradiol (E2) production by bovine granulosa cells was evaluated under several culture conditions, which included the presence or absence of fetal bovine serum (FBS; 2.5 and 10%), serum substitutes (1% Nutridoma [Boehringer-Mannheim, Indianapolis, IN], 2% UltroSer G [IBF Biotechnics, Villenue-la Garenne, France]), selenium (Se; 10 ng/ml), lipoprotein (0.25% Excyte/ml), O2 concentration (5 and 20%), and two attachment factors (Pronectin F and PepTite-2000). Dulbecco's Modified Eagle's medium:Ham's F-12 medium (1:1 mixture) containing 1 microM androstenedione, 1 microgram/ml insulin, and 0.1% BSA was the basal medium evaluated. The optimum conditions determined were the basal medium in 5% O2. These conditions were then used to ascertain whether or not E2 production by granulosa cells varied with respect to location of cells within a follicle. Follicular fluid was aspirated and centrifuged to obtain granulosa cells expected to be primarily luminal and cumulus cells. Follicles were then bisected, and remaining mural granulosa cells were removed by scraping the follicle wall with a fine plastic loop. Aspirated granulosa cells secreted more (p < 0.01) E2 than scraped cells. Production of E2 during Days 0 to 2 of culture by aspirated (0.15 +/- 0.05 ng/microgram DNA) and scraped (0.02 +/- 0.01 ng/microgram DNA) granulosa cells from small follicles (< 8 mm) was less than that by aspirated (6.30 +/- 2.20 ng/micrograms DNA) and scraped cells (1.90 +/- 1.00 ng/microgram DNA) from large follicles (> or = 8 mm). During Days 2 to 4 of culture when compared to Days 0 to 2, E2 production increased for aspirated (but not scraped) granulosa cells from small follicles (0.66 +/- 0.23 ng/microgram DNA)). In contrast, E2 production decreased (p < 0.05) over time in culture for aspirated (2.10 +/- 0.50 ng/microgram DNA) and scraped (0.16 +/- 0.07 ng/microgram DNA) granulosa cells from large follicles. Thus, granulosa cells proximal to the basement membrane may be less

  9. In vitro production of estradiol by bovine granulosa cells: evaluation of culture condition, stage of follicular development, and location of cells within follicles.

    PubMed

    Roberts, A J; Echternkamp, S E

    1994-08-01

    In vitro estradiol (E2) production by bovine granulosa cells was evaluated under several culture conditions, which included the presence or absence of fetal bovine serum (FBS; 2.5 and 10%), serum substitutes (1% Nutridoma [Boehringer-Mannheim, Indianapolis, IN], 2% UltroSer G [IBF Biotechnics, Villenue-la Garenne, France]), selenium (Se; 10 ng/ml), lipoprotein (0.25% Excyte/ml), O2 concentration (5 and 20%), and two attachment factors (Pronectin F and PepTite-2000). Dulbecco's Modified Eagle's medium:Ham's F-12 medium (1:1 mixture) containing 1 microM androstenedione, 1 microgram/ml insulin, and 0.1% BSA was the basal medium evaluated. The optimum conditions determined were the basal medium in 5% O2. These conditions were then used to ascertain whether or not E2 production by granulosa cells varied with respect to location of cells within a follicle. Follicular fluid was aspirated and centrifuged to obtain granulosa cells expected to be primarily luminal and cumulus cells. Follicles were then bisected, and remaining mural granulosa cells were removed by scraping the follicle wall with a fine plastic loop. Aspirated granulosa cells secreted more (p < 0.01) E2 than scraped cells. Production of E2 during Days 0 to 2 of culture by aspirated (0.15 +/- 0.05 ng/microgram DNA) and scraped (0.02 +/- 0.01 ng/microgram DNA) granulosa cells from small follicles (< 8 mm) was less than that by aspirated (6.30 +/- 2.20 ng/micrograms DNA) and scraped cells (1.90 +/- 1.00 ng/microgram DNA) from large follicles (> or = 8 mm). During Days 2 to 4 of culture when compared to Days 0 to 2, E2 production increased for aspirated (but not scraped) granulosa cells from small follicles (0.66 +/- 0.23 ng/microgram DNA)). In contrast, E2 production decreased (p < 0.05) over time in culture for aspirated (2.10 +/- 0.50 ng/microgram DNA) and scraped (0.16 +/- 0.07 ng/microgram DNA) granulosa cells from large follicles. Thus, granulosa cells proximal to the basement membrane may be less

  10. Epidermis-Derived Semaphorin Promotes Dendrite Self-Avoidance by Regulating Dendrite-Substrate Adhesion in Drosophila Sensory Neurons.

    PubMed

    Meltzer, Shan; Yadav, Smita; Lee, Jiae; Soba, Peter; Younger, Susan H; Jin, Peng; Zhang, Wei; Parrish, Jay; Jan, Lily Yeh; Jan, Yuh-Nung

    2016-02-17

    Precise patterning of dendritic arbors is critical for the wiring and function of neural circuits. Dendrite-extracellular matrix (ECM) adhesion ensures that the dendrites of Drosophila dendritic arborization (da) sensory neurons are properly restricted in a 2D space, and thereby facilitates contact-mediated dendritic self-avoidance and tiling. However, the mechanisms regulating dendrite-ECM adhesion in vivo are poorly understood. Here, we show that mutations in the semaphorin ligand sema-2b lead to a dramatic increase in self-crossing of dendrites due to defects in dendrite-ECM adhesion, resulting in a failure to confine dendrites to a 2D plane. Furthermore, we find that Sema-2b is secreted from the epidermis and signals through the Plexin B receptor in neighboring neurons. Importantly, we find that Sema-2b/PlexB genetically and physically interacts with TORC2 complex, Tricornered (Trc) kinase, and integrins. These results reveal a novel role for semaphorins in dendrite patterning and illustrate how epidermal-derived cues regulate neural circuit assembly.

  11. Synergistic action of dendritic mitochondria and creatine kinase maintains ATP homeostasis and actin dynamics in growing neuronal dendrites.

    PubMed

    Fukumitsu, Kansai; Fujishima, Kazuto; Yoshimura, Azumi; Wu, You Kure; Heuser, John; Kengaku, Mineko

    2015-04-01

    The distribution of mitochondria within mature, differentiated neurons is clearly adapted to their regional physiological needs and can be perturbed under various pathological conditions, but the function of mitochondria in developing neurons has been less well studied. We have studied mitochondrial distribution within developing mouse cerebellar Purkinje cells and have found that active delivery of mitochondria into their dendrites is a prerequisite for proper dendritic outgrowth. Even when mitochondria in the Purkinje cell bodies are functioning normally, interrupting the transport of mitochondria into their dendrites severely disturbs dendritic growth. Additionally, we find that the growth of atrophic dendrites lacking mitochondria can be rescued by activating ATP-phosphocreatine exchange mediated by creatine kinase (CK). Conversely, inhibiting cytosolic CKs decreases dendritic ATP levels and also disrupts dendrite development. Mechanistically, this energy depletion appears to perturb normal actin dynamics and enhance the aggregation of cofilin within growing dendrites, reminiscent of what occurs in neurons overexpressing the dephosphorylated form of cofilin. These results suggest that local ATP synthesis by dendritic mitochondria and ATP-phosphocreatine exchange act synergistically to sustain the cytoskeletal dynamics necessary for dendritic development.

  12. Plasmacytoid dendritic cell role in cutaneous malignancies.

    PubMed

    Saadeh, Dana; Kurban, Mazen; Abbas, Ossama

    2016-07-01

    Plasmacytoid dendritic cells (pDCs) correspond to a specialized dendritic cell population that exhibit plasma cell morphology, express CD4, CD123, HLA-DR, blood-derived dendritic cell antigen-2 (BDCA-2), and Toll-like receptor (TLR)7 and TLR9 within endosomal compartments. Through their production of type I interferons (IFNs) and other pro-inflammatory cytokines, pDCs provide anti-viral resistance and link the innate and adaptive immunity by controlling the function of myeloid DCs, lymphocytes, and natural killer (NK) cells. While lacking from normal skin, pDCs are usually recruited to the skin in several cutaneous pathologies where they appear to be involved in the pathogenesis of several infectious, inflammatory/autoimmune, and neoplastic entities. Among the latter group, pDCs have the potential to induce anti-tumour immunity; however, the complex interaction of pDCs with tumor cells and their micro-environment appears to contribute to immunologic tolerance. In this review, we aim at highlighting the role played by pDCs in cutaneous malignancies with special emphasis on the underlying mechanisms.

  13. The Isothermal Dendritic Growth Experiment Archive

    NASA Astrophysics Data System (ADS)

    Koss, Matthew

    2009-03-01

    The growth of dendrites is governed by the interplay between two simple and familiar processes---the irreversible diffusion of energy, and the reversible work done in the formation of new surface area. To advance our understanding of these processes, NASA sponsored a project that flew on the Space Shuttle Columbia is 1994, 1996, and 1997 to record and analyze benchmark data in an apparent-microgravity ``laboratory.'' In this laboratory, energy transfer by gravity driven convection was essentially eliminated and one could test independently, for the first time, both components of dendritic growth theory. The analysis of this data shows that although the diffusion of energy can be properly accounted for, the results from interfacial physics appear to be in disagreement and alternate models should receive increased attention. Unfortunately, currently and for the foreseeable future, there is no access or financial support to develop and conduct additional experiments of this type. However, the benchmark data of 35mm photonegatives, video, and all supporting instrument data are now available at the IDGE Archive at the College of the Holy Cross. This data may still have considerable relevance to researchers working specifically with dendritic growth, and more generally those working in the synthesis, growth & processing of materials, multiscale computational modeling, pattern formation, and systems far from equilibrium.

  14. Location-dependent synaptic plasticity rules by dendritic spine cooperativity.

    PubMed

    Weber, Jens P; Andrásfalvy, Bertalan K; Polito, Marina; Magó, Ádám; Ujfalussy, Balázs B; Makara, Judit K

    2016-01-01

    Nonlinear interactions between coactive synapses enable neurons to discriminate between spatiotemporal patterns of inputs. Using patterned postsynaptic stimulation by two-photon glutamate uncaging, here we investigate the sensitivity of synaptic Ca(2+) signalling and long-term plasticity in individual spines to coincident activity of nearby synapses. We find a proximodistally increasing gradient of nonlinear NMDA receptor (NMDAR)-mediated amplification of spine Ca(2+) signals by a few neighbouring coactive synapses along individual perisomatic dendrites. This synaptic cooperativity does not require dendritic spikes, but is correlated with dendritic Na(+) spike propagation strength. Furthermore, we show that repetitive synchronous subthreshold activation of small spine clusters produces input specific, NMDAR-dependent cooperative long-term potentiation at distal but not proximal dendritic locations. The sensitive synaptic cooperativity at distal dendritic compartments shown here may promote the formation of functional synaptic clusters, which in turn can facilitate active dendritic processing and storage of information encoded in spatiotemporal synaptic activity patterns. PMID:27098773

  15. Special fractal growth of dendrite copper using a hydrothermal method

    NASA Astrophysics Data System (ADS)

    Zheng, Yan; Zhang, Zhejuan; Guo, Pingsheng; He, Pingang; Sun, Zhuo

    2011-08-01

    Special fractal dendrite Cu nanostructures have been synthesized through a simple hydrothermal method, and the effects of the volume ratio between glycerol and water and the concentration of H 3PO 3 on the morphologies of dendrite Cu have been studied in detail. The Field emission scanning electron microscopy (FESEM), Transmission electron microscopy (TEM) and X-ray diffraction (XRD) have been used to characterize these Cu products. The results indicate that rhombic diamond and different morphologies of fractal dendrite were prepared because of the accumulation of Cu nuclei based on the diffusion-limited aggregation (DLA) and the nucleation-limited aggregation (NLA) model. Fortunately, symmetrical leaf-like dendrite Cu nanostructures different from Cu dendrites reported before have been obtained. Additionally, an explanation for the growth of fractal dendrite Cu has been discussed carefully.

  16. Neural pattern formation in networks with dendritic structure

    NASA Astrophysics Data System (ADS)

    Bressloff, P. C.; De Souza, B.

    1998-04-01

    We present a detailed analysis of a recently proposed model of neural pattern formation that is based on the combined effect of diffusion along a neuron's dendritic tree and recurrent interactions along axo-dendritic synaptic connections. For concreteness, we consider a one-dimensional array of analog neurons with the dendritic tree idealized as a one-dimensional cable. Linear stability analysis and bifurcation theory together with numerical simulations are used to establish conditions for the onset of a Turing instability leading to the formation of stable spatial patterns of network output activity. It is shown that the presence of dendritic structure can induce dynamic (time-periodic) spatial pattern formation. Moreover, correlations between the dendritic location of a synapse and the relative positions of neurons in the network are shown to result in spatially oscillating patterns of activity along the dendrites of each neuron.

  17. Location-dependent synaptic plasticity rules by dendritic spine cooperativity

    PubMed Central

    Weber, Jens P.; Andrásfalvy, Bertalan K.; Polito, Marina; Magó, Ádám; Ujfalussy, Balázs B.; Makara, Judit K.

    2016-01-01

    Nonlinear interactions between coactive synapses enable neurons to discriminate between spatiotemporal patterns of inputs. Using patterned postsynaptic stimulation by two-photon glutamate uncaging, here we investigate the sensitivity of synaptic Ca2+ signalling and long-term plasticity in individual spines to coincident activity of nearby synapses. We find a proximodistally increasing gradient of nonlinear NMDA receptor (NMDAR)-mediated amplification of spine Ca2+ signals by a few neighbouring coactive synapses along individual perisomatic dendrites. This synaptic cooperativity does not require dendritic spikes, but is correlated with dendritic Na+ spike propagation strength. Furthermore, we show that repetitive synchronous subthreshold activation of small spine clusters produces input specific, NMDAR-dependent cooperative long-term potentiation at distal but not proximal dendritic locations. The sensitive synaptic cooperativity at distal dendritic compartments shown here may promote the formation of functional synaptic clusters, which in turn can facilitate active dendritic processing and storage of information encoded in spatiotemporal synaptic activity patterns. PMID:27098773

  18. Random positions of dendritic spines in human cerebral cortex.

    PubMed

    Morales, Juan; Benavides-Piccione, Ruth; Dar, Mor; Fernaud, Isabel; Rodríguez, Angel; Anton-Sanchez, Laura; Bielza, Concha; Larrañaga, Pedro; DeFelipe, Javier; Yuste, Rafael

    2014-07-23

    Dendritic spines establish most excitatory synapses in the brain and are located in Purkinje cell's dendrites along helical paths, perhaps maximizing the probability to contact different axons. To test whether spine helixes also occur in neocortex, we reconstructed >500 dendritic segments from adult human cortex obtained from autopsies. With Fourier analysis and spatial statistics, we analyzed spine position along apical and basal dendrites of layer 3 pyramidal neurons from frontal, temporal, and cingulate cortex. Although we occasionally detected helical positioning, for the great majority of dendrites we could not reject the null hypothesis of spatial randomness in spine locations, either in apical or basal dendrites, in neurons of different cortical areas or among spines of different volumes and lengths. We conclude that in adult human neocortex spine positions are mostly random. We discuss the relevance of these results for spine formation and plasticity and their functional impact for cortical circuits.

  19. Dendritic spine detection using curvilinear structure detector and LDA classifier.

    PubMed

    Zhang, Yong; Zhou, Xiaobo; Witt, Rochelle M; Sabatini, Bernardo L; Adjeroh, Donald; Wong, Stephen T C

    2007-06-01

    Dendritic spines are small, bulbous cellular compartments that carry synapses. Biologists have been studying the biochemical pathways by examining the morphological and statistical changes of the dendritic spines at the intracellular level. In this paper a novel approach is presented for automated detection of dendritic spines in neuron images. The dendritic spines are recognized as small objects of variable shape attached or detached to multiple dendritic backbones in the 2D projection of the image stack along the optical direction. We extend the curvilinear structure detector to extract the boundaries as well as the centerlines for the dendritic backbones and spines. We further build a classifier using Linear Discriminate Analysis (LDA) to classify the attached spines into valid and invalid types to improve the accuracy of the spine detection. We evaluate the proposed approach by comparing with the manual results in terms of backbone length, spine number, spine length, and spine density.

  20. Random Positions of Dendritic Spines in Human Cerebral Cortex

    PubMed Central

    Morales, Juan; Benavides-Piccione, Ruth; Dar, Mor; Fernaud, Isabel; Rodríguez, Angel; Anton-Sanchez, Laura; Bielza, Concha; Larrañaga, Pedro; DeFelipe, Javier

    2014-01-01

    Dendritic spines establish most excitatory synapses in the brain and are located in Purkinje cell's dendrites along helical paths, perhaps maximizing the probability to contact different axons. To test whether spine helixes also occur in neocortex, we reconstructed >500 dendritic segments from adult human cortex obtained from autopsies. With Fourier analysis and spatial statistics, we analyzed spine position along apical and basal dendrites of layer 3 pyramidal neurons from frontal, temporal, and cingulate cortex. Although we occasionally detected helical positioning, for the great majority of dendrites we could not reject the null hypothesis of spatial randomness in spine locations, either in apical or basal dendrites, in neurons of different cortical areas or among spines of different volumes and lengths. We conclude that in adult human neocortex spine positions are mostly random. We discuss the relevance of these results for spine formation and plasticity and their functional impact for cortical circuits. PMID:25057209

  1. Random positions of dendritic spines in human cerebral cortex.

    PubMed

    Morales, Juan; Benavides-Piccione, Ruth; Dar, Mor; Fernaud, Isabel; Rodríguez, Angel; Anton-Sanchez, Laura; Bielza, Concha; Larrañaga, Pedro; DeFelipe, Javier; Yuste, Rafael

    2014-07-23

    Dendritic spines establish most excitatory synapses in the brain and are located in Purkinje cell's dendrites along helical paths, perhaps maximizing the probability to contact different axons. To test whether spine helixes also occur in neocortex, we reconstructed >500 dendritic segments from adult human cortex obtained from autopsies. With Fourier analysis and spatial statistics, we analyzed spine position along apical and basal dendrites of layer 3 pyramidal neurons from frontal, temporal, and cingulate cortex. Although we occasionally detected helical positioning, for the great majority of dendrites we could not reject the null hypothesis of spatial randomness in spine locations, either in apical or basal dendrites, in neurons of different cortical areas or among spines of different volumes and lengths. We conclude that in adult human neocortex spine positions are mostly random. We discuss the relevance of these results for spine formation and plasticity and their functional impact for cortical circuits. PMID:25057209

  2. Galectin-1 Regulates Tissue Exit of Specific Dendritic Cell Populations*

    PubMed Central

    Thiemann, Sandra; Man, Jeanette H.; Chang, Margaret H.; Lee, Benhur; Baum, Linda G.

    2015-01-01

    During inflammation, dendritic cells emigrate from inflamed tissue across the lymphatic endothelium into the lymphatic vasculature and travel to regional lymph nodes to initiate immune responses. However, the processes that regulate dendritic cell tissue egress and migration across the lymphatic endothelium are not well defined. The mammalian lectin galectin-1 is highly expressed by vascular endothelial cells in inflamed tissue and has been shown to regulate immune cell tissue entry into inflamed tissue. Here, we show that galectin-1 is also highly expressed by human lymphatic endothelial cells, and deposition of galectin-1 in extracellular matrix selectively regulates migration of specific human dendritic cell subsets. The presence of galectin-1 inhibits migration of immunogenic dendritic cells through the extracellular matrix and across lymphatic endothelial cells, but it has no effect on migration of tolerogenic dendritic cells. The major galectin-1 counter-receptor on both dendritic cell populations is the cell surface mucin CD43; differential core 2 O-glycosylation of CD43 between immunogenic dendritic cells and tolerogenic dendritic cells appears to contribute to the differential effect of galectin-1 on migration. Binding of galectin-1 to immunogenic dendritic cells reduces phosphorylation and activity of the protein-tyrosine kinase Pyk2, an effect that may also contribute to reduced migration of this subset. In a murine lymphedema model, galectin-1−/− animals had increased numbers of migratory dendritic cells in draining lymph nodes, specifically dendritic cells with an immunogenic phenotype. These findings define a novel role for galectin-1 in inhibiting tissue emigration of immunogenic, but not tolerogenic, dendritic cells, providing an additional mechanism by which galectin-1 can dampen immune responses. PMID:26216879

  3. Evidence for tip velocity oscillations in dendritic solidification

    NASA Astrophysics Data System (ADS)

    Lacombe, J. C.; Koss, M. B.; Frei, J. E.; Giummarra, C.; Lupulescu, A. O.; Glicksman, M. E.

    2002-03-01

    Dendritic growth experiments were conducted in the reduced-convection environment aboard the space shuttle Columbia on STS-87. Spectral analysis was performed on 30-frame/s video data during growths of isothermal dendrites. Results indicate that pivalic acid dendrites exhibit a subtle oscillatory behavior of the axial growth velocity near the tip, with a frequency component that is associated with the sidebranch formation process.

  4. Evidence for tip velocity oscillations in dendritic solidification.

    PubMed

    LaCombe, J C; Koss, M B; Frei, J E; Giummarra, C; Lupulescu, A O; Glicksman, M E

    2002-03-01

    Dendritic growth experiments were conducted in the reduced-convection environment aboard the space shuttle Columbia on STS-87. Spectral analysis was performed on 30-frame/s video data during growths of isothermal dendrites. Results indicate that pivalic acid dendrites exhibit a subtle oscillatory behavior of the axial growth velocity near the tip, with a frequency component that is associated with the sidebranch formation process. PMID:11909070

  5. Magnifying Endoscopic Features of Follicular Lymphoma Involving the Stomach: A Report of Two Cases

    PubMed Central

    Takata, Katsuyoshi; Kawano, Seiji; Fujii, Nobuharu; Kawahara, Yoshiro; Yoshino, Tadashi; Okada, Hiroyuki

    2016-01-01

    A 70-year-old woman presented with follicular lymphoma involving the stomach, duodenum, jejunum, bone, and lymph nodes. Esophagogastroduodenoscopy revealed multiple depressed lesions in the stomach. Examination with magnifying endoscopy showed branched abnormal vessels along with gastric pits, which were irregularly shaped but were preserved. The second case was a 45-year-old man diagnosed with stage II1 follicular lymphoma with duodenal, ileal, and colorectal involvement, as well as lymphadenopathy of the mesenteric lymph nodes. Esophagogastroduodenoscopy performed six years after the diagnosis revealed multiple erosions in the gastric body and angle. Magnifying endoscopic observation with narrow-band imaging showed that the gastric pits were only partially preserved and were destroyed in most of the stomach. Branched abnormal vessels were also seen. Pathological features were consistent with follicular lymphoma in both cases. The structural differences reported between the two cases appear to reflect distinct pathologies. Disappearance of gastric pits in the latter case seems to result from loss of epithelial cells, probably due to chronic inflammation. In both cases, branched abnormal vasculature was observed. These two cases suggest that magnified observations of abnormal branched microvasculature may facilitate endoscopic detection and recognition of the extent of gastric involvement in patients with follicular lymphoma. PMID:27747111

  6. Demonstration of neuropeptide Y and its precursor in plasma and follicular fluid.

    PubMed

    Jørgensen, J C; O'Hare, M M; Andersen, C Y

    1990-10-01

    The present investigation provides three lines of evidence for the presence of a pro-form of neuropeptide Y (NPY) in plasma and follicular fluid. First, by the demonstration of NPY-immunoreactive material of a size corresponding to the estimated mol wt of pro-NPY. Second, an antiserum specific for the C-terminal tyrosine amide of NPY and peptide YY does not react with this material. Third, it was possible to convert the pro-NPY extracted from plasma and follicular fluid using the protease, Endoproteinase-Lys C, to a NPY-immunoreactive form eluting slightly before NPY on a G-50 column. The size of the digested product was consistent with a cleavage of pro-NPY resulting in an immunoreactive species, NPY-Gly-Lys. Pro-NPY was also found in tissue culture media from the human neuroendocrine cell line SH-SY5Y. As in the case of plasma and follicular fluid, another NPY immunoreactive species eluted from a G-50 gel filtration column slightly before synthetic human NPY. Analysis of this material with an antibody directed against the tyrosine amide of NPY in combination with isoelectric focusing revealed that this peak consisted of at least two immunoreactive forms of NPY. In conclusion, at least three different forms of NPY immunoreactivity are likely to be present in plasma, follicular fluid, and cell tissue culture media; pro-NPY, a degradation form of pro-NPY, or a biosynthetic intermediate and NPY.

  7. Intra-cellular mechanism of Anti-Müllerian hormone (AMH) in regulation of follicular development.

    PubMed

    Hayes, Emily; Kushnir, Vitaly; Ma, Xiaoting; Biswas, Anindita; Prizant, Hen; Gleicher, Norbert; Sen, Aritro

    2016-09-15

    Anti-Müllerian hormone (AMH) is a member of the transforming growth factor-β superfamily and plays a crucial role in testicular and ovarian functions. In clinical practice, AMH is used as a diagnostic and/or prognostic marker in women in association with ovulation induction and in various pathophysiological conditions. Despite widespread clinical use of AMH, our mechanistic understanding of AMH actions in regulating follicular development is limited. Using a mouse model, we in this study report that in vivo AMH treatment while stalls follicular development and inhibits ovulation, also prevents follicular atresia. We further show that these AMH actions are mediated through induction of two miRNAs, miR-181a and miR-181b, which regulate various aspects of FSH signaling and follicular growth, ultimately affecting downstream gene expression and folliculogenesis. We also report that in this mouse model AMH pre-treatment prior to superovulation improves oocyte yield. These studies, therefore, offer new mechanistic insight into AMH actions in folliculogenesis and point toward potential utilization of AMH as a therapeutic agent. PMID:27235859

  8. The use of radiotherapy in the management of follicular cystitis refractory to conservative and surgical management

    PubMed Central

    Trombetta, Mark; Packard, Matthew; Ferrara, Dominic; Werts, E. Day

    2012-01-01

    Follicular cysitis is a proliferative benign lesion which can act locally malignant. Conservative management is best; however, when this fails, surgical resection is necessary up to and including cystectomy in extreme refractory cases. We present a clinical review and our results using radiation in this disease in a woman facing cystectomy. PMID:22826782

  9. Follicular lymphoma in young adults: a clinicopathological and molecular study of 200 patients.

    PubMed

    Duarte, Ivison X; Domeny-Duarte, Pollyanna; Wludarski, Sheila C L; Natkunam, Yasodha; Bacchi, Carlos E

    2013-09-01

    Follicular lymphoma is clinically heterogenous, and therefore necessitates the identification of prognostic markers to stratify risk groups and optimize clinical management. It is relatively rare in patients younger than 40 years, and the clinicopathologic characteristics and biological behavior in this age group are poorly understood. In the current study, samples from a cohort of 200 patients between 19 and 40 years were evaluated retrospectively with respect to clinical, histologic, and genetic features. These were then correlated with clinical outcome. The median age at presentation was 35 years with a slight female prepoderance (56%). Most of the cases are presented with nodal disease (90%). Concomitant follicular lymphoma and diffuse large B-cell lymphoma were observed in 7 (4%) patients. Immunohistologic studies showed the expression of CD10 (91%), BCL6 (97%), BCL2 (95%), MUM1/IRF4 (12%), MDM2 (17%), and CD23 (25%). BCL2 rearrangement was present in 74%, and BCL6 in 20%. The estimated overall survival of patients was 13 years (mean). The presence of anemia, elevated lactose dehydrogenase, bone marrow involvement, and high-risk follicular lymphoma international prognostic index correlated with adverse overall survival. Our findings revealed that follicular lymphoma in young adults demonstrate similarities with that of older adults, including the frequency of presentation at various anatomic sites, grade, and adverse prognostic factors.

  10. Effects of neonatal litter size and age on ovarian gene expression and follicular development in gilts

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Gilts raised in small litters have greater ovulation rate, stay in the herd longer and produce more pigs. The objective was to understand how neonatal litter size affects gilt development. The hypothesis is that gilts reared in smaller litters have greater ovarian follicular development. Within 24 h...

  11. Evaluation of Follicular Synchronization Caused by Estrogen Administration and Its Reproductive Outcome

    PubMed Central

    Wu, Bi; Shi, Yan; Gong, Xia; Yu, Lin; Chen, Qiuju; Wang, Jian; Sun, Zhaogui

    2015-01-01

    To evaluate multiple follicular development synchronization after estrogen stimulation in prepubertal mice, follicular responsiveness to gonadotropin superovulation, the prospective reproductive potential and ovarian polycystic ovary syndrome (PCOS)-like symptoms at adulthood, prepubertal mice were intraperitoneally injected with estrogen to establish an animal model with solvent as control. When synchronized tertiary follicles in ovaries, in vitro oocyte maturation and fertilization rates, blastocyst formation rate, developmental potential into offspring by embryo transfer, adult fertility and PCOS-like symptoms, and involved molecular mechanisms were focused, it was found that estrogen stimulation (10μg/gBW) leads to follicular development synchronization at the early tertiary stage in prepubertal mice; reproduction from oocytes to offspring could be realized by means of the artificial reproductive technology though the model mice lost their natural fertility when they were reared to adulthood; and typical symptoms of PCOS, except changes in inflammatory pathways, were not remained up to adulthood. So in conclusion, estrogen can lead to synchronization in follicular development in prepubertal mice, but does not affect reproductive outcome of oocytes, and no typical symptoms of PCOS remained at adulthood despite changes related to inflammation. PMID:26010950

  12. Hormonal dynamics and follicular turnover in prepuberal Mediterranean Italian buffaloes (Bubalus bubalis).

    PubMed

    Presicce, Giorgio Antonio; Parmeggiani, Albamaria; Senatore, Elena Maria; Stecco, Romana; Barile, Vittoria Lucia; De Mauro, Guillermo Javier; De Santis, Giuseppe; Maria Terzano, Giuseppina

    2003-08-01

    The aim of this study was the investigation of hormonal and ovarian follicular dynamics in prepuberal buffaloes (Bubalus bubalis) bred in Italy. Eleven 5-9-month old buffalo calves ranging in weight from 122 to 270kg, maintained under controlled nutritional and environmental conditions, underwent 50 days of ultrasonographic ovarian follicular monitoring in the months of October-December. Blood sampling for E(2) and FSH determination and ultrasonographic monitoring using a 7.5MHz linear probe and an ALOKA SSD-500 monitor were performed daily. No differences in any of the parameters under study were highlighted when calves were divided into two weight categories (<200 and >200kg) and thus data were pooled. In this study, values are reported as mean+/-S.D. A range of two-six regular follicular waves was reported among calves with an average of 4+/-1.1. Overall interval (days) between wave emergence was 9.9+/-2.8 and largest diameters (mm) of dominant and first subordinate follicles were 8.4+/-1.2 and 4.8+/-0.6, respectively (P<0.05). With the exception of one calf, some minor follicular waves (short waves or SWs; 1.6+/-1), lasting <10 days (6.1+/-1.2) were reported. They were monitored contemporaneously on the ovary contralateral (n=7) or ipsilateral (n=3) to the main follicular wave. Growth rate (mm per day) of dominant follicles (DF) was significantly faster than for corresponding subordinate follicles (SF) and follicles of SWs (1.08+/-0.2 versus 0.79+/-0.1 and 0.83+/-0.1, respectively, P<0.05). The static phase (days) lasted longer in DF compared to SF and SW (5.4+/-1.8 versus 2.4+/-1.2 and 2.6+/-1, respectively, P<0.05). The regressing phase (mm per day) was similar among DF, SF and SW (0.86+/-0.2, 0.94+/-0.2 and 0.84+/-0.1, respectively, P=0.09). Episodic spikes of E(2) and FSH were reported, corresponding to wave development throughout the course of investigation. In conclusion, the majority of buffalo calves displayed a typical pattern of regular follicular

  13. Hormonal dynamics and follicular turnover in prepuberal Mediterranean Italian buffaloes (Bubalus bubalis).

    PubMed

    Presicce, Giorgio Antonio; Parmeggiani, Albamaria; Senatore, Elena Maria; Stecco, Romana; Barile, Vittoria Lucia; De Mauro, Guillermo Javier; De Santis, Giuseppe; Maria Terzano, Giuseppina

    2003-08-01

    The aim of this study was the investigation of hormonal and ovarian follicular dynamics in prepuberal buffaloes (Bubalus bubalis) bred in Italy. Eleven 5-9-month old buffalo calves ranging in weight from 122 to 270kg, maintained under controlled nutritional and environmental conditions, underwent 50 days of ultrasonographic ovarian follicular monitoring in the months of October-December. Blood sampling for E(2) and FSH determination and ultrasonographic monitoring using a 7.5MHz linear probe and an ALOKA SSD-500 monitor were performed daily. No differences in any of the parameters under study were highlighted when calves were divided into two weight categories (<200 and >200kg) and thus data were pooled. In this study, values are reported as mean+/-S.D. A range of two-six regular follicular waves was reported among calves with an average of 4+/-1.1. Overall interval (days) between wave emergence was 9.9+/-2.8 and largest diameters (mm) of dominant and first subordinate follicles were 8.4+/-1.2 and 4.8+/-0.6, respectively (P<0.05). With the exception of one calf, some minor follicular waves (short waves or SWs; 1.6+/-1), lasting <10 days (6.1+/-1.2) were reported. They were monitored contemporaneously on the ovary contralateral (n=7) or ipsilateral (n=3) to the main follicular wave. Growth rate (mm per day) of dominant follicles (DF) was significantly faster than for corresponding subordinate follicles (SF) and follicles of SWs (1.08+/-0.2 versus 0.79+/-0.1 and 0.83+/-0.1, respectively, P<0.05). The static phase (days) lasted longer in DF compared to SF and SW (5.4+/-1.8 versus 2.4+/-1.2 and 2.6+/-1, respectively, P<0.05). The regressing phase (mm per day) was similar among DF, SF and SW (0.86+/-0.2, 0.94+/-0.2 and 0.84+/-0.1, respectively, P=0.09). Episodic spikes of E(2) and FSH were reported, corresponding to wave development throughout the course of investigation. In conclusion, the majority of buffalo calves displayed a typical pattern of regular follicular

  14. Dendritic integration in pyramidal neurons during network activity and disease.

    PubMed

    Palmer, Lucy M

    2014-04-01

    Neurons have intricate dendritic morphologies which come in an array of shapes and sizes. Not only do they give neurons their unique appearance, but dendrites also endow neurons with the ability to receive and transform synaptic inputs. We now have a wealth of information about the functioning of dendrites which suggests that the integration of synaptic inputs is highly dependent on both dendritic properties and neuronal input patterns. It has been shown that dendrites can perform non-linear processing, actively transforming synaptic input into Na(+) spikes, Ca(2+) plateau spikes and NMDA spikes. These membrane non-linearities can have a large impact on the neuronal output and have been shown to be regulated by numerous factors including synaptic inhibition. Many neuropathological diseases involve changes in how dendrites receive and package synaptic input by altering dendritic spine characteristics, ion channel expression and the inhibitory control of dendrites. This review focuses on the role of dendrites in integrating and transforming input and what goes wrong in the case of neuropathological diseases.

  15. Mapping homeostatic synaptic plasticity using cable properties of dendrites.

    PubMed

    Queenan, B N; Lee, K J; Tan, H; Huganir, R L; Vicini, S; Pak, D T S

    2016-02-19

    When chronically silenced, cortical and hippocampal neurons homeostatically upregulate excitatory synaptic function. However, the subcellular position of such changes on the dendritic tree is not clear. We exploited the cable-filtering properties of dendrites to derive a parameter, the dendritic filtering index (DFI), to map the spatial distribution of synaptic currents. Our analysis indicates that young rat cortical neurons globally scale AMPA receptor-mediated currents, while mature hippocampal neurons do not, revealing distinct homeostatic strategies between brain regions and developmental stages. The DFI presents a useful tool for mapping the dendritic origin of synaptic currents and the location of synaptic plasticity changes.

  16. The Evolution of Dendrite Morphology during Isothermal Coarsening

    NASA Technical Reports Server (NTRS)

    Alkemper, Jens; Mendoza, Roberto; Kammer, Dimitris; Voorhees, Peter W.

    2003-01-01

    Dendrite coarsening is a common phenomenon in casting processes. From the time dendrites are formed until the inter-dendritic liquid is completely solidified dendrites are changing shape driven by variations in interfacial curvature along the dendrite and resulting in a reduction of total interfacial area. During this process the typical length-scale of the dendrite can change by orders of magnitude and the final microstructure is in large part determined by the coarsening parameters. Dendrite coarsening is thus crucial in setting the materials parameters of ingots and of great commercial interest. This coarsening process is being studied in the Pb-Sn system with Sn-dendrites undergoing isothermal coarsening in a Pb-Sn liquid. Results are presented for samples of approximately 60% dendritic phase, which have been coarsened for different lengths of times. Presented are three-dimensional microstructures obtained by serial-sectioning and an analysis of these microstructures with regard to interface orientation and interfacial curvatures. These graphs reflect the evolution of not only the microstructure itself, but also of the underlying driving forces of the coarsening process. As a visualization of the link between the microstructure and the driving forces a three-dimensional microstructure with the interfaces colored according to the local interfacial mean curvature is shown.

  17. Actin in dendritic spines: connecting dynamics to function

    PubMed Central

    2010-01-01

    Dendritic spines are small actin-rich protrusions from neuronal dendrites that form the postsynaptic part of most excitatory synapses and are major sites of information processing and storage in the brain. Changes in the shape and size of dendritic spines are correlated with the strength of excitatory synaptic connections and heavily depend on remodeling of its underlying actin cytoskeleton. Emerging evidence suggests that most signaling pathways linking synaptic activity to spine morphology influence local actin dynamics. Therefore, specific mechanisms of actin regulation are integral to the formation, maturation, and plasticity of dendritic spines and to learning and memory. PMID:20457765

  18. Bent dendrite growth in undercooled Fe-B alloy melts

    NASA Astrophysics Data System (ADS)

    Karrasch, C.; Volkmann, T.; Valloton, J.; Kolbe, M.; Herlach, DM

    2016-03-01

    Dendritic growth is the main solidification mode in alloy casting. In order to control dendrite growth for materials design from the melt it is important to fully understand the influence of process conditions. This study stands as an experimental note observing bent dendrite growth in Fe-B alloys and suggesting possible explanations as induced by fluid flow, thermal, and concentrational diffusion or impurities. Electromagnetic levitation technique (EML) is used for containerless processing of undercooled melts under 1g and reduced gravity conditions in parabolic flight. Further investigations are needed to find a suitable explanation for the observed bent dendrite growth behaviour.

  19. Proteome Profile and Quantitative Proteomic Analysis of Buffalo (Bubalusbubalis) Follicular Fluid during Follicle Development.

    PubMed

    Fu, Qiang; Huang, Yulin; Wang, Zhiqiang; Chen, Fumei; Huang, Delun; Lu, Yangqing; Liang, Xianwei; Zhang, Ming

    2016-01-01

    Follicular fluid (FF) accumulates in the antrum of the ovarian follicle and provides the microenvironment for oocyte development. FF plays an important role in follicle growth and oocyte maturation. The FF provides a unique window to investigate the processes occurring during buffalo follicular development. The observed low quality of buffalo oocytes may arise from the poor follicular microenvironment. Investigating proteins found in buffalo FF (BFF) should provide insight into follicular development processes and provide further understanding of intra-follicular maturation and oocytes quality. Here, a proteomic-based approach was used to analyze the proteome of BFF. SDS-PAGE separation combined with mass spectrometry was used to generate the proteomic dataset. In total, 363 proteins were identified and classified by Gene Ontology terms. The proteins were assigned to 153 pathways, including signaling pathways. To evaluate difference in proteins expressed between BFF with different follicle size (small, <4 mm; and large, >8 mm), a quantitative proteomic analysis based on multi-dimensional liquid chromatography pre-fractionation tandem Orbitrap mass spectrometry identification was performed. Eleven differentially expressed proteins (six downregulated and five upregulated in large BFF) were identified and assigned to a variety of functional processes, including serine protease inhibition, oxidation protection and the complement cascade system. Three differentially expressed proteins, Vimentin, Peroxiredoxin-1 and SERPIND1, were verified by Western blotting, consistent with the quantitative proteomics results. Our datasets offers new information about proteins present in BFF and should facilitate the development of new biomarkers. These differentially expressed proteins illuminate the size-dependent protein changes in follicle microenvironment. PMID:27136540

  20. Down-regulation of microRNAs controlling tumourigenic factors in follicular thyroid carcinoma.

    PubMed

    Rossing, Maria; Borup, Rehannah; Henao, Ricardo; Winther, Ole; Vikesaa, Jonas; Niazi, Omid; Godballe, Christian; Krogdahl, Annelise; Glud, Martin; Hjort-Sørensen, Christian; Kiss, Katalin; Bennedbæk, Finn Noe; Nielsen, Finn Cilius

    2012-02-01

    The molecular determinants of thyroid follicular nodules are incompletely understood and assessment of malignancy is a diagnostic challenge. Since microRNA (miRNA) analyses could provide new leads to malignant progression, we characterised the global miRNA expression in follicular adenoma (FA) and follicular carcinoma (FC). Comparison of carcinoma and adenoma with normal thyroid revealed 150 and 107 differentially expressed miRNAs respectively. Most miRNAs were down-regulated and especially miR-199b-5p and miR-144 which were essentially lost in the carcinomas. Integration of the changed miRNAs with differentially expressed mRNAs demonstrated an enrichment of seed sites among up-regulated transcripts encoding proteins implicated in thyroid tumourigenesis. This was substantiated by the demonstration that pre-miR-199b reduced proliferation when added to cultured follicular thyroid carcinoma cells. The down-regulated miRNAs in FC exhibited a substantial similarity with down-regulated miRNAs in anaplastic carcinoma (AC) and by gene set enrichment analysis, we observed a significant identity between target mRNAs in FC and transcripts up-regulated in AC. To examine the diagnostic potential of miRNA expression pattern in distinguishing malignant from benign nodules we employed a supervised learning algorithm and leave-one-out-cross-validation. By this procedure, FA and FC were identified with a negative predicted value of 83% (data generated by microarray platform) and of 92% (data generated by qRT-PCR platform). We conclude that follicular neoplasia is associated with major changes in miRNA expression that may promote malignant transformation by increasing the expression of transcripts encoding tumourigenic factors. Moreover, miRNA profiling may facilitate the diagnosis of carcinoma vs adenoma. PMID:22049245

  1. Predictive value of bovine follicular components as markers of oocyte developmental potential.

    PubMed

    Matoba, Satoko; Bender, Katrin; Fahey, Alan G; Mamo, Solomon; Brennan, Lorraine; Lonergan, Patrick; Fair, Trudee

    2014-01-01

    The follicle is a unique micro-environment within which the oocyte can develop and mature to a fertilisable gamete. The aim of this study was to investigate the ability of a panel of follicular parameters, including intrafollicular steroid and metabolomic profiles and theca, granulosa and cumulus cell candidate gene mRNA abundance, to predict the potential of bovine oocytes to develop to the blastocyst stage in vitro. Individual follicles were dissected from abattoir ovaries, carefully ruptured under a stereomicroscope and the oocyte was recovered and individually processed through in vitro maturation, fertilisation and culture. The mean (±s.e.m.) follicular concentrations of testosterone (62.8±4.8 ngmL(-1)), progesterone (616.8±31.9 ngmL(-1)) and oestradiol (14.4±2.4 ngmL(-1)) were not different (P>0.05) between oocytes that formed (competent) or failed to form (incompetent) blastocysts. Principal-component analysis of the quantified aqueous metabolites in follicular fluid showed differences between oocytes that formed blastocysts and oocytes that degenerated; l-alanine, glycine and l-glutamate were positively correlated and urea was negatively correlated with blastocyst formation. Follicular fluid associated with competent oocytes was significantly lower in palmitic acid (P=0.023) and total fatty acids (P=0.031) and significantly higher in linolenic acid (P=0.036) than follicular fluid from incompetent oocytes. Significantly higher (P<0.05) transcript abundance of LHCGR in granulosa cells, ESR1 and VCAN in thecal cells and TNFAIP6 in cumulus cells was associated with competent compared with incompetent oocytes.

  2. Serum and follicular fluid concentrations of polybrominated diphenyl ethers and in-vitro fertilization outcome

    PubMed Central

    Johnson, Paula I.; Altshul, Larisa; Cramer, Daniel W.; Missmer, Stacey A.; Hauser, Russ; Meeker, John D.

    2012-01-01

    There is evidence of endocrine disruption and reproductive effects in animals following exposure to certain PBDEs, but human studies are limited. The goal of this study was to investigate the use of serum and follicular fluid as biomarkers of exposure to PBDEs and to explore whether a relationship between PBDE exposure and early pregnancy loss exists. We measured 8 PBDE congeners in archived serum and ovarian follicular fluid samples from 65 women undergoing in-vitro fertilization (IVF). Logistic regression models were used to predict the odds of failed embryo implantation associated with higher levels of PBDEs among the women in the study. There were moderate Kendall’s Tau-beta correlations between serum and follicular fluid concentrations of BDE 28, 47, 100 and 154 (Tβ =0.29–0.38, all p-values<0.005), but BDE 99 and 153 were not correlated between the two matrices (Tβ<0.2, p-values>0.05). Women with detectable concentrations of BDE 153 (39% had detectable levels) in follicular fluid had elevated odds of failed implantation compared with women who had non-detectable concentrations (adjusted OR=10.0; 95%CI: 1.9 to 52; p=0.006; adjusted by age and body mass index). These findings suggest that exposure to BDE 153 may be associated with failed embryo implantation. Due to our observation of only moderate correlations between matrices, serum PBDE concentrations may not be a good indicator of follicular fluid concentrations when studying early pregnancy endpoints in women undergoing IVF. PMID:22572111

  3. The control of follicular wave development for self-appointed embryo transfer programs in cattle.

    PubMed

    Bó, G A; Baruselli, P S; Moreno, D; Cutaia, L; Caccia, M; Tríbulo, R; Tríbulo, H; Mapletoft, R J

    2002-01-01

    Our expanding knowledge of the control of follicular wave dynamics during the bovine estrous cycle has resulted in renewed enthusiasm for the prospects of precisely controlling the follicular and luteal dynamics and finely controlling the time of ovulation. Follicular wave development can be controlled mechanically by ultrasound-guided follicle ablation or hormonally by treatments with GnRH or estradiol and progestogen/progesterone in combination. Treatment of cattle with GnRH in combination with prostaglandin F2 alpha (PGF) 7 d later and a second GnRH 48 h after PGF (known as Ovsynch) has resulted in acceptable pregnancy rates after fixed-time AI in lactating dairy cows and in recipients in which embryos were transferred without estrus detection. Alternatively, treatments with estradiol and progestogen/progesterone-releasing devices resulted in synchronous emergence of a new follicular wave and, when a second estradiol treatment was given 24 h after device removal, synchronous ovulation and high pregnancy rates to fixed-time AI. Self-appointed embryo transfer (without estrus detection) using estradiol and progesterone treatments have resulted in pregnancy rates comparable with those obtained with recipients transferred 7 d after estrus. Furthermore, estradiol and progesterone treatments combined with PGF and eCG (given 1 d after the expected time of wave emergence) have resulted in high rates of recipients selected for transfer (84.6%) and an overall pregnancy rate of 48.7% (recipients pregnant/recipients treated). Estradiol and progestogen/progesterone treatments have also been widely used for self-appointed superstimulation protocols with equivalent embryo production to that of donor cows superstimulated using the traditional approach beginning 8 to 12 d after estrus. In summary, exogenous control of luteal and follicular development facilitates the application of assisted reproductive technologies in cattle by offering the possibility of planning the

  4. Proteome Profile and Quantitative Proteomic Analysis of Buffalo (Bubalusbubalis) Follicular Fluid during Follicle Development

    PubMed Central

    Fu, Qiang; Huang, Yulin; Wang, Zhiqiang; Chen, Fumei; Huang, Delun; Lu, Yangqing; Liang, Xianwei; Zhang, Ming

    2016-01-01

    Follicular fluid (FF) accumulates in the antrum of the ovarian follicle and provides the microenvironment for oocyte development. FF plays an important role in follicle growth and oocyte maturation. The FF provides a unique window to investigate the processes occurring during buffalo follicular development. The observed low quality of buffalo oocytes may arise from the poor follicular microenvironment. Investigating proteins found in buffalo FF (BFF) should provide insight into follicular development processes and provide further understanding of intra-follicular maturation and oocytes quality. Here, a proteomic-based approach was used to analyze the proteome of BFF. SDS-PAGE separation combined with mass spectrometry was used to generate the proteomic dataset. In total, 363 proteins were identified and classified by Gene Ontology terms. The proteins were assigned to 153 pathways, including signaling pathways. To evaluate difference in proteins expressed between BFF with different follicle size (small, <4 mm; and large, >8 mm), a quantitative proteomic analysis based on multi-dimensional liquid chromatography pre-fractionation tandem Orbitrap mass spectrometry identification was performed. Eleven differentially expressed proteins (six downregulated and five upregulated in large BFF) were identified and assigned to a variety of functional processes, including serine protease inhibition, oxidation protection and the complement cascade system. Three differentially expressed proteins, Vimentin, Peroxiredoxin-1 and SERPIND1, were verified by Western blotting, consistent with the quantitative proteomics results. Our datasets offers new information about proteins present in BFF and should facilitate the development of new biomarkers. These differentially expressed proteins illuminate the size-dependent protein changes in follicle microenvironment. PMID:27136540

  5. Proteome Profile and Quantitative Proteomic Analysis of Buffalo (Bubalusbubalis) Follicular Fluid during Follicle Development.

    PubMed

    Fu, Qiang; Huang, Yulin; Wang, Zhiqiang; Chen, Fumei; Huang, Delun; Lu, Yangqing; Liang, Xianwei; Zhang, Ming

    2016-01-01

    Follicular fluid (FF) accumulates in the antrum of the ovarian follicle and provides the microenvironment for oocyte development. FF plays an important role in follicle growth and oocyte maturation. The FF provides a unique window to investigate the processes occurring during buffalo follicular development. The observed low quality of buffalo oocytes may arise from the poor follicular microenvironment. Investigating proteins found in buffalo FF (BFF) should provide insight into follicular development processes and provide further understanding of intra-follicular maturation and oocytes quality. Here, a proteomic-based approach was used to analyze the proteome of BFF. SDS-PAGE separation combined with mass spectrometry was used to generate the proteomic dataset. In total, 363 proteins were identified and classified by Gene Ontology terms. The proteins were assigned to 153 pathways, including signaling pathways. To evaluate difference in proteins expressed between BFF with different follicle size (small, <4 mm; and large, >8 mm), a quantitative proteomic analysis based on multi-dimensional liquid chromatography pre-fractionation tandem Orbitrap mass spectrometry identification was performed. Eleven differentially expressed proteins (six downregulated and five upregulated in large BFF) were identified and assigned to a variety of functional processes, including serine protease inhibition, oxidation protection and the complement cascade system. Three differentially expressed proteins, Vimentin, Peroxiredoxin-1 and SERPIND1, were verified by Western blotting, consistent with the quantitative proteomics results. Our datasets offers new information about proteins present in BFF and should facilitate the development of new biomarkers. These differentially expressed proteins illuminate the size-dependent protein changes in follicle microenvironment.

  6. Effect of different doses of monosodium glutamate on the thyroid follicular cells of adult male albino rats: a histological study

    PubMed Central

    Khalaf, Hanaa A; Arafat, Eetmad A

    2015-01-01

    Monosodium glutamate (MSG) is a major flavor enhancer used as a food additive. The present study investigates the effects of different doses of MSG on the morphometric and histological changes of the thyroid gland. 28 male albino rats were used. The rats were divided into four groups: group I control, group II, III and IV treated with MSG (0.25 g/kg, 3 g/kg, 6 g/kg daily for one month) respectively. The thyroid glands were dissected out and prepared for light and electron microscopic examination. Light microscopic examination of thyroid gland of group II revealed increase in follicular epithelial height. Groups III & IV showed decrease in the follicular diameter and irregularity in the shape of some follicles with discontinuity of basement membrane. Follicular hyperplasia was detected in some follicles with appearance of multiple pyknotic nuclei in follicular and interfollicular cells and multiple exfoliated cells in the colloid. In addition, areas of loss of follicular pattern were appeared in group IV. Immunohistochemical examination of BCL2 immunoexpression of the thyroid glands of groups III & IV reveals weak positive reaction in the follicular cells cytoplasm. Ultrathin sections examination of groups III & IV revealed follicular cells with irregular hyperchromatic nuclei, marked dilatation of rER and increased lysosomes with areas of short or lost apical microvilli. In addition, vacuolation of mitochondria was detected in group IV. The results displayed that MSG even at low doses is capable of producing alterations in the body weights and thyroid tissue function and histology. PMID:26884820

  7. Intestinal bacteria trigger T cell-independent immunoglobulin A(2) class switching by inducing epithelial-cell secretion of the cytokine APRIL.

    PubMed

    He, Bing; Xu, Weifeng; Santini, Paul A; Polydorides, Alexandros D; Chiu, April; Estrella, Jeannelyn; Shan, Meimei; Chadburn, Amy; Villanacci, Vincenzo; Plebani, Alessandro; Knowles, Daniel M; Rescigno, Maria; Cerutti, Andrea

    2007-06-01

    Bacteria colonize the intestine shortly after birth and thereafter exert several beneficial functions, including induction of protective immunoglobulin A (IgA) antibodies. The distal intestine contains IgA(2), which is more resistant to bacterial proteases than is IgA(1). The mechanism by which B cells switch from IgM to IgA(2) remains unknown. We found that human intestinal epithelial cells (IECs) triggered IgA(2) class switching in B cells, including IgA(1)-expressing B cells arriving from mucosal follicles, through a CD4(+) T cell-independent pathway involving a proliferation-inducing ligand (APRIL). IECs released APRIL after sensing bacteria through Toll-like receptors (TLRs) and further increased APRIL production by activating dendritic cells via thymic stromal lymphopoietin. Our data indicate that bacteria elicit IgA(2) class switching by linking lamina propria B cells with IECs through a TLR-inducible signaling program requiring APRIL. Thus, mucosal vaccines should activate IECs to induce more effective IgA(2) responses.

  8. A study of the mutational landscape of pediatric-type follicular lymphoma and pediatric nodal marginal zone lymphoma

    PubMed Central

    Ozawa, Michael G; Bhaduri, Aparna; Chisholm, Karen M; Baker, Steven A; Ma, Lisa; Zehnder, James L; Luna-Fineman, Sandra; Link, Michael P; Merker, Jason D; Arber, Daniel A; Ohgami, Robert S

    2016-01-01

    Pediatric-type follicular lymphoma and pediatric marginal zone lymphoma are two of the rarest B-cell lymphomas. These lymphomas occur predominantly in the pediatric population and show features distinct from their more common counterparts in adults: adult-type follicular lymphoma and adult-type nodal marginal zone lymphoma. Here we report a detailed whole-exome deep sequencing analysis of a cohort of pediatric-type follicular lymphomas and pediatric marginal zone lymphomas. This analysis revealed a recurrent somatic variant encoding p.Lys66Arg in the transcription factor interferon regulatory factor 8 (IRF8) in 3 of 6 cases (50%) of pediatric-type follicular lymphoma. This specific point mutation was not detected in pediatric marginal zone lymphoma or in adult-type follicular lymphoma. Additional somatic point mutations in pediatric-type follicular lymphoma were observed in genes involved in transcription, intracellular signaling, and cell proliferation. In pediatric marginal zone lymphoma, no recurrent mutation was identified; however, somatic point mutations were observed in genes involved in cellular adhesion, cytokine regulatory elements, and cellular proliferation. A somatic variant in AMOTL1, a recurrently mutated gene in splenic marginal zone lymphoma, was also identified in a case of pediatric marginal zone lymphoma. The overall non-synonymous mutational burden was low in both pediatric-type follicular lymphoma and pediatric marginal zone lymphoma (4.6 mutations per exome). Altogether, these findings support a distinctive genetic basis for pediatric-type follicular lymphoma and pediatric marginal zone lymphoma when compared with adult subtypes and to one another. Moreover, identification of a recurrent point mutation in IRF8 provides insight into a potential driver mutation in the pathogenesis of pediatric-type follicular lymphoma with implications for novel diagnostic or therapeutic strategies. PMID:27338637

  9. Developmental programming: Prenatal BPA treatment disrupts timing of LH surge and ovarian follicular wave dynamics in adult sheep

    SciTech Connect

    Veiga-Lopez, A.; Beckett, E.M.; Abi Salloum, B.; Ye, W.; Padmanabhan, V.

    2014-09-01

    Developmental exposure to BPA adversely affects reproductive function. In sheep, prenatal BPA treatment induces reproductive neuroendocrine defects, manifested as LH excess and dampened LH surge and perturbs early ovarian gene expression. In this study we hypothesized that prenatal BPA treatment will also disrupt ovarian follicular dynamics. Pregnant sheep were treated from days 30 to 90 of gestation with 3 different BPA doses (0.05, 0.5, or 5 mg/kg BW/day). All female offspring were estrus synchronized and transrectal ultrasonography was performed daily for 22 days to monitor ovarian follicular and corpora lutea dynamics. Blood samples were collected to assess preovulatory hormonal changes and luteal progesterone dynamics. Statistical analysis revealed that the time interval between the estradiol rise and the preovulatory LH surge was shortened in the BPA-treated females. None of the three BPA doses had an effect on corpora lutea, progestogenic cycles, and mean number or duration of ovulatory and non-ovulatory follicles. However, differences in follicular count trajectories were evident in all three follicular size classes (2–3 mm, 4–5 mm, and ≥ 6 mm) of prenatal BPA-treated animals compared to controls. Number of follicular waves tended also to be more variable in the prenatal BPA-treated groups ranging from 2 to 5 follicular waves per cycle, while this was restricted to 3 to 4 waves in control females. These changes in ovarian follicular dynamics coupled with defects in time interval between estradiol rise and preovulatory LH release are likely to lead to subfertility in prenatal BPA-treated females. - Highlights: • Prenatal BPA shortens interval between estradiol rise and preovulatory LH surge. • Prenatal BPA affects follicular count trajectory and follicular wave occurrence. • Prenatal BPA does not affect ovulatory rate and progesterone dynamics.

  10. miR-31 and miR-17-5p levels change during transformation of follicular lymphoma.

    PubMed

    Thompson, Mary Ann; Edmonds, Mick D; Liang, Shan; McClintock-Treep, Sara; Wang, Xuan; Li, Shaoying; Eischen, Christine M

    2016-04-01

    The 30% of patients whose indolent follicular lymphoma transforms to aggressive diffuse large B-cell lymphoma (DLBCL) have poor survival. Reliable predictors of follicular B-cell lymphoma transformation to DLBCL are lacking, and diagnosis of those that will progress is challenging. MicroRNA, which regulates gene expression, has critical functions in the growth and progression of many cancers and contributes to the pathogenesis of lymphoma. Using 5 paired samples from patients who presented with follicular lymphoma and progressed to DLBCL, we identified specific microRNA differentially expressed between the two. Specifically, miR-17-5p levels were low in follicular lymphoma and increased as the disease transformed. In contrast, miR-31 expression was high in follicular lymphoma and decreased as the lymphoma progressed. These results were confirmed in additional unpaired cases of low-grade follicular lymphoma (n = 13) and high-grade follicular lymphoma grade 3 or DLBCL (n = 17). Loss of miR-31 expression in DLBCL was not due to deletion of the locus. Changes in miR-17-5p and miR-31 were not correlated with immunophenotype, genetics, or status of the MYC oncogene. However, increased miR-17-5p expression did significantly correlate with increased expression of p53 protein, which is indicative of mutant TP53. Two pro-proliferative genes, E2F2 and PI3KC2A, were identified as direct messenger RNA targets of miR-31, suggesting that these may contribute to follicular lymphoma transformation. Our results indicate that changes in miR-31 and miR-17-5p reflect the transformation of follicular lymphoma to an aggressive large B-cell lymphoma and may, along with their targets, be viable markers for this process.

  11. Ternary eutectic dendrites: Pattern formation and scaling properties

    SciTech Connect

    Rátkai, László; Szállás, Attila; Pusztai, Tamás; Mohri, Tetsuo; Gránásy, László

    2015-04-21

    Extending previous work [Pusztai et al., Phys. Rev. E 87, 032401 (2013)], we have studied the formation of eutectic dendrites in a model ternary system within the framework of the phase-field theory. We have mapped out the domain in which two-phase dendritic structures grow. With increasing pulling velocity, the following sequence of growth morphologies is observed: flat front lamellae → eutectic colonies → eutectic dendritesdendrites with target pattern → partitionless dendrites → partitionless flat front. We confirm that the two-phase and one-phase dendrites have similar forms and display a similar scaling of the dendrite tip radius with the interface free energy. It is also found that the possible eutectic patterns include the target pattern, and single- and multiarm spirals, of which the thermal fluctuations choose. The most probable number of spiral arms increases with increasing tip radius and with decreasing kinetic anisotropy. Our numerical simulations confirm that in agreement with the assumptions of a recent analysis of two-phase dendrites [Akamatsu et al., Phys. Rev. Lett. 112, 105502 (2014)], the Jackson-Hunt scaling of the eutectic wavelength with pulling velocity is obeyed in the parameter domain explored, and that the natural eutectic wavelength is proportional to the tip radius of the two-phase dendrites. Finally, we find that it is very difficult/virtually impossible to form spiraling two-phase dendrites without anisotropy, an observation that seems to contradict the expectations of Akamatsu et al. Yet, it cannot be excluded that in isotropic systems, two-phase dendrites are rare events difficult to observe in simulations.

  12. Anaplastic Transformation in Mandibular Metastases of Follicular Variant of Papillary Thyroid Carcinoma: A Case Report and Review of the Literature.

    PubMed

    Ambelil, Manju; Sultana, Sadia; Roy, Suvra; Gonzalez, Maria M

    2016-09-01

    Anaplastic transformation of well-differentiated thyroid carcinomas at distant metastatic sites is a rare condition. Most cases described in the literature have occurred in the thyroid or regional lymph nodes. We report a case of anaplastic transformation of the follicular variant of papillary thyroid carcinoma in mandibular metastases. A 76-year-old female presented with a painful and enlarging mandibular mass. She had been treated in the past for the follicular variant of papillary thyroid carcinoma. A palliative hemi-mandibulectomy was performed. Histology revealed a metastatic papillary thyroid carcinoma, follicular variant, with an unusual finding of solid pleomorphic epithelioid and spindle cell areas, consistent with anaplastic transformation. PMID:27650625

  13. Dendritic Polyglycerol Sulfate Inhibits Microglial Activation and Reduces Hippocampal CA1 Dendritic Spine Morphology Deficits.

    PubMed

    Maysinger, Dusica; Gröger, Dominic; Lake, Andrew; Licha, Kai; Weinhart, Marie; Chang, Philip K-Y; Mulvey, Rose; Haag, Rainer; McKinney, R Anne

    2015-09-14

    Hyperactivity of microglia and loss of functional circuitry is a common feature of many neurological disorders including those induced or exacerbated by inflammation. Herein, we investigate the response of microglia and changes in hippocampal dendritic postsynaptic spines by dendritic polyglycerol sulfate (dPGS) treatment. Mouse microglia and organotypic hippocampal slices were exposed to dPGS and an inflammogen (lipopolysaccharides). Measurements of intracellular fluorescence and confocal microscopic analyses revealed that dPGS is avidly internalized by microglia but not CA1 pyramidal neurons. Concentration and time-dependent response studies consistently showed no obvious toxicity of dPGS. The adverse effects induced by proinflammogen LPS exposure were reduced and dendritic spine morphology was normalized with the addition of dPGS. This was accompanied by a significant reduction in nitrite and proinflammatory cytokines (TNF-α and IL-6) from hyperactive microglia suggesting normalized circuitry function with dPGS treatment. Collectively, these results suggest that dPGS acts anti-inflammatory, inhibits inflammation-induced degenerative changes in microglia phenotype and rescues dendritic spine morphology. PMID:26218295

  14. Organization of TNIK in dendritic spines

    PubMed Central

    Burette, Alain C.; Phend, Kristen D.; Burette, Susan; Lin, Qingcong; Liang, Musen; Foltz, Gretchen; Taylor, Noël; Wang, Qi; Brandon, Nicholas J.; Bates, Brian; Ehlers, Michael D.; Weinberg, Richard J.

    2015-01-01

    TRAF2- and NCK-interacting kinase (TNIK) has been identified as an interactor of the psychiatric risk factor, Disrupted in Schizophrenia 1 (DISC1). As a step toward deciphering its function in the brain, we performed high-resolution light and electron microscopic immunocytochemistry. We demonstrate here that TNIK is expressed in neurons throughout the adult mouse brain. In striatum and cerebral cortex, TNIK concentrates in dendritic spines, especially in the vicinity of the lateral edge of the synapse. Thus, TNIK is highly enriched at a microdomain critical for glutamatergic signaling and implicated in the regulation of synaptic strength. PMID:25753355

  15. Plasticity of Dendritic Spines: Subcompartmentalization of Signaling

    PubMed Central

    Colgan, Lesley A.; Yasuda, Ryohei

    2014-01-01

    The ability to induce and study neuronal plasticity in single dendritic spines has greatly advanced our understanding of the signaling mechanisms that mediate long-term potentiation. It is now clear that in addition to compartmentalization by the individual spine, subcompartmentalization of biochemical signals occurs at specialized microdomains within the spine. The spatiotemporal coordination of these complex cascades allows for the concomitant remodeling of the postsynaptic density actin spinoskeleton and for the regulation of membrane traffic to express functional and structural plasticity. Here, we highlight recent findings in the signaling cascades at spine microdomains as well as the challenges and approaches to studying plasticity at the spine level. PMID:24215443

  16. Decreased follicular phase gonadotropin secretion is associated with impaired estradiol and progesterone secretion during the follicular and luteal phases in normally menstruating women.

    PubMed

    Schweiger, U; Laessle, R G; Tuschl, R J; Broocks, A; Krusche, T; Pirke, K M

    1989-05-01

    We tested the hypothesis that disturbed follicular development and disturbed luteal progesterone (P4) secretion are associated with reduced gonadotropin secretion in the early follicular phase by measuring pulsatile LH and FSH secretion at that time in 53 normally menstruating women. Three groups of women were identified on the basis of serum sex steroid concentrations (measured daily throughout the cycle) and luteal phase length. Group A (n = 27) had normal ovarian hormone secretion with peak serum estradiol (E2) concentrations of 440 pmol/L or more, peak serum P4 concentrations of 19 nmol/L or more, and luteal phase length of 9 days or more. Group B (n = 16) had normal peak serum E2 values, but peak serum P4 values less than 19 nmol/L and/or luteal phase length less than 9 days. Group C (n = 10) had peak serum E2 values below 440 pmol/L. Risk factors for the disturbances found in groups B and C were exercise and/or intermittent dieting. Compared to group A, both groups B and C had reduced mean serum LH concentrations (3.1 +/- 1.5 vs. 2.3 +/- 1.4 and 2.0 +/- 1.0 IU/L; P less than 0.05) and reduced LH pulse frequencies (5.2 +/- 2.1 vs. 3.5 +/- 1.8 and 3.3 +/- 2.3 pulses/12 h; P less than 0.02). LH amplitude was similar in all 3 groups. Mean serum FSH concentrations were slightly but not significantly lower in group C. We conclude that reduced gonadotropin secretion during the follicular phase may indeed affect E2 and P4 secretion at later stages of the menstrual cycle. The patterns of alteration associated with disturbed E2 and P4 secretion in normally menstruating women are similar to those that occur in women with hypothalamic amenorrhea.

  17. Contribution of sublinear and supralinear dendritic integration to neuronal computations.

    PubMed

    Tran-Van-Minh, Alexandra; Cazé, Romain D; Abrahamsson, Therése; Cathala, Laurence; Gutkin, Boris S; DiGregorio, David A

    2015-01-01

    Nonlinear dendritic integration is thought to increase the computational ability of neurons. Most studies focus on how supralinear summation of excitatory synaptic responses arising from clustered inputs within single dendrites result in the enhancement of neuronal firing, enabling simple computations such as feature detection. Recent reports have shown that sublinear summation is also a prominent dendritic operation, extending the range of subthreshold input-output (sI/O) transformations conferred by dendrites. Like supralinear operations, sublinear dendritic operations also increase the repertoire of neuronal computations, but feature extraction requires different synaptic connectivity strategies for each of these operations. In this article we will review the experimental and theoretical findings describing the biophysical determinants of the three primary classes of dendritic operations: linear, sublinear, and supralinear. We then review a Boolean algebra-based analysis of simplified neuron models, which provides insight into how dendritic operations influence neuronal computations. We highlight how neuronal computations are critically dependent on the interplay of dendritic properties (morphology and voltage-gated channel expression), spiking threshold and distribution of synaptic inputs carrying particular sensory features. Finally, we describe how global (scattered) and local (clustered) integration strategies permit the implementation of similar classes of computations, one example being the object feature binding problem. PMID:25852470

  18. BC1 RNA motifs required for dendritic transport in vivo

    PubMed Central

    Robeck, Thomas; Skryabin, Boris V.; Rozhdestvensky, Timofey S.; Skryabin, Anastasiya B.; Brosius, Jürgen

    2016-01-01

    BC1 RNA is a small brain specific non-protein coding RNA. It is transported from the cell body into dendrites where it is involved in the fine-tuning translational control. Due to its compactness and established secondary structure, BC1 RNA is an ideal model for investigating the motifs necessary for dendritic localization. Previously, microinjection of in vitro transcribed BC1 RNA mutants into the soma of cultured primary neurons suggested the importance of RNA motifs for dendritic targeting. These ex vivo experiments identified a single bulged nucleotide (U22) and a putative K-turn (GA motif) structure required for dendritic localization or distal transport, respectively. We generated six transgenic mouse lines (three founders each) containing neuronally expressing BC1 RNA variants on a BC1 RNA knockout mouse background. In contrast to ex vivo data, we did not find indications of reduction or abolition of dendritic BC1 RNA localization in the mutants devoid of the GA motif or the bulged nucleotide. We confirmed the ex vivo data, which showed that the triloop terminal sequence had no consequence on dendritic transport. Interestingly, changing the triloop supporting structure completely abolished dendritic localization of BC1 RNA. We propose a novel RNA motif important for dendritic transport in vivo. PMID:27350115

  19. Dendrites and Cognition: A Negative Pilot Study in the Rat.

    ERIC Educational Resources Information Center

    Anderson, Britt

    1995-01-01

    The dendritic structure of layer II-III pyramidal neurons of the parietal cortex in 41 Long-Evans rats was compared to behavioral assessments of attention to novelty, response flexibility, and reasoning. A significant correlation between dendritic arborization and behavioral performance was not demonstrated. (SLD)

  20. BC1 RNA motifs required for dendritic transport in vivo.

    PubMed

    Robeck, Thomas; Skryabin, Boris V; Rozhdestvensky, Timofey S; Skryabin, Anastasiya B; Brosius, Jürgen

    2016-01-01

    BC1 RNA is a small brain specific non-protein coding RNA. It is transported from the cell body into dendrites where it is involved in the fine-tuning translational control. Due to its compactness and established secondary structure, BC1 RNA is an ideal model for investigating the motifs necessary for dendritic localization. Previously, microinjection of in vitro transcribed BC1 RNA mutants into the soma of cultured primary neurons suggested the importance of RNA motifs for dendritic targeting. These ex vivo experiments identified a single bulged nucleotide (U22) and a putative K-turn (GA motif) structure required for dendritic localization or distal transport, respectively. We generated six transgenic mouse lines (three founders each) containing neuronally expressing BC1 RNA variants on a BC1 RNA knockout mouse background. In contrast to ex vivo data, we did not find indications of reduction or abolition of dendritic BC1 RNA localization in the mutants devoid of the GA motif or the bulged nucleotide. We confirmed the ex vivo data, which showed that the triloop terminal sequence had no consequence on dendritic transport. Interestingly, changing the triloop supporting structure completely abolished dendritic localization of BC1 RNA. We propose a novel RNA motif important for dendritic transport in vivo. PMID:27350115

  1. Contribution of sublinear and supralinear dendritic integration to neuronal computations

    PubMed Central

    Tran-Van-Minh, Alexandra; Cazé, Romain D.; Abrahamsson, Therése; Cathala, Laurence; Gutkin, Boris S.; DiGregorio, David A.

    2015-01-01

    Nonlinear dendritic integration is thought to increase the computational ability of neurons. Most studies focus on how supralinear summation of excitatory synaptic responses arising from clustered inputs within single dendrites result in the enhancement of neuronal firing, enabling simple computations such as feature detection. Recent reports have shown that sublinear summation is also a prominent dendritic operation, extending the range of subthreshold input-output (sI/O) transformations conferred by dendrites. Like supralinear operations, sublinear dendritic operations also increase the repertoire of neuronal computations, but feature extraction requires different synaptic connectivity strategies for each of these operations. In this article we will review the experimental and theoretical findings describing the biophysical determinants of the three primary classes of dendritic operations: linear, sublinear, and supralinear. We then review a Boolean algebra-based analysis of simplified neuron models, which provides insight into how dendritic operations influence neuronal computations. We highlight how neuronal computations are critically dependent on the interplay of dendritic properties (morphology and voltage-gated channel expression), spiking threshold and distribution of synaptic inputs carrying particular sensory features. Finally, we describe how global (scattered) and local (clustered) integration strategies permit the implementation of similar classes of computations, one example being the object feature binding problem. PMID:25852470

  2. Musical representation of dendritic spine distribution: a new exploratory tool.

    PubMed

    Toharia, Pablo; Morales, Juan; de Juan, Octavio; Fernaud, Isabel; Rodríguez, Angel; DeFelipe, Javier

    2014-04-01

    Dendritic spines are small protrusions along the dendrites of many types of neurons in the central nervous system and represent the major target of excitatory synapses. For this reason, numerous anatomical, physiological and computational studies have focused on these structures. In the cerebral cortex the most abundant and characteristic neuronal type are pyramidal cells (about 85 % of all neurons) and their dendritic spines are the main postsynaptic target of excitatory glutamatergic synapses. Thus, our understanding of the synaptic organization of the cerebral cortex largely depends on the knowledge regarding synaptic inputs to dendritic spines of pyramidal cells. Much of the structural data on dendritic spines produced by modern neuroscience involves the quantitative analysis of image stacks from light and electron microscopy, using standard statistical and mathematical tools and software developed to this end. Here, we present a new method with musical feedback for exploring dendritic spine morphology and distribution patterns in pyramidal neurons. We demonstrate that audio analysis of spiny dendrites with apparently similar morphology may "sound" quite different, revealing anatomical substrates that are not apparent from simple visual inspection. These morphological/music translations may serve as a guide for further mathematical analysis of the design of the pyramidal neurons and of spiny dendrites in general.

  3. Mechanisms underlying subunit independence in pyramidal neuron dendrites

    PubMed Central

    Behabadi, Bardia F.; Mel, Bartlett W.

    2014-01-01

    Pyramidal neuron (PN) dendrites compartmentalize voltage signals and can generate local spikes, which has led to the proposal that their dendrites act as independent computational subunits within a multilayered processing scheme. However, when a PN is strongly activated, back-propagating action potentials (bAPs) sweeping outward from the soma synchronize dendritic membrane potentials many times per second. How PN dendrites maintain the independence of their voltage-dependent computations, despite these repeated voltage resets, remains unknown. Using a detailed compartmental model of a layer 5 PN, and an improved method for quantifying subunit independence that incorporates a more accurate model of dendritic integration, we first established that the output of each dendrite can be almost perfectly predicted by the intensity and spatial configuration of its own synaptic inputs, and is nearly invariant to the rate of bAP-mediated “cross-talk” from other dendrites over a 100-fold range. Then, through an analysis of conductance, voltage, and current waveforms within the model cell, we identify three biophysical mechanisms that together help make independent dendritic computation possible in a firing neuron, suggesting that a major subtype of neocortical neuron has been optimized for layered, compartmentalized processing under in-vivo–like spiking conditions. PMID:24357611

  4. Musical representation of dendritic spine distribution: a new exploratory tool.

    PubMed

    Toharia, Pablo; Morales, Juan; de Juan, Octavio; Fernaud, Isabel; Rodríguez, Angel; DeFelipe, Javier

    2014-04-01

    Dendritic spines are small protrusions along the dendrites of many types of neurons in the central nervous system and represent the major target of excitatory synapses. For this reason, numerous anatomical, physiological and computational studies have focused on these structures. In the cerebral cortex the most abundant and characteristic neuronal type are pyramidal cells (about 85 % of all neurons) and their dendritic spines are the main postsynaptic target of excitatory glutamatergic synapses. Thus, our understanding of the synaptic organization of the cerebral cortex largely depends on the knowledge regarding synaptic inputs to dendritic spines of pyramidal cells. Much of the structural data on dendritic spines produced by modern neuroscience involves the quantitative analysis of image stacks from light and electron microscopy, using standard statistical and mathematical tools and software developed to this end. Here, we present a new method with musical feedback for exploring dendritic spine morphology and distribution patterns in pyramidal neurons. We demonstrate that audio analysis of spiny dendrites with apparently similar morphology may "sound" quite different, revealing anatomical substrates that are not apparent from simple visual inspection. These morphological/music translations may serve as a guide for further mathematical analysis of the design of the pyramidal neurons and of spiny dendrites in general. PMID:24395057

  5. Special fractal growth of dendrite copper using a hydrothermal method

    SciTech Connect

    Zheng Yan; Zhang Zhejuan; Guo Pingsheng; He Pingang; Sun Zhuo

    2011-08-15

    Special fractal dendrite Cu nanostructures have been synthesized through a simple hydrothermal method, and the effects of the volume ratio between glycerol and water and the concentration of H{sub 3}PO{sub 3} on the morphologies of dendrite Cu have been studied in detail. The Field emission scanning electron microscopy (FESEM), Transmission electron microscopy (TEM) and X-ray diffraction (XRD) have been used to characterize these Cu products. The results indicate that rhombic diamond and different morphologies of fractal dendrite were prepared because of the accumulation of Cu nuclei based on the diffusion-limited aggregation (DLA) and the nucleation-limited aggregation (NLA) model. Fortunately, symmetrical leaf-like dendrite Cu nanostructures different from Cu dendrites reported before have been obtained. Additionally, an explanation for the growth of fractal dendrite Cu has been discussed carefully. - Graphical abstract: Uniform dendritic Cu are grown through controlling V{sub glycerol/water} in range of 0.6-1.2 and the concentration of H{sub 3}PO{sub 3} in range of 0.06-0.3 M. The rhombic cluster Cu are obtained by decreasing the amount of glycerol. Highlights: > Volume ratio of glycerol/water and concentration of H{sub 3}PO{sub 3} were varied, respectively. > Morphologies of dendritic Cu have some changes. > Leaf-like and rhombic cluster Cu were obtained. > The concentration changes affect the aggregation of Cu crystallites. > The aggregation and crystallographic orientation cause leaf-like Cu nanostructures.

  6. Contribution of sublinear and supralinear dendritic integration to neuronal computations.

    PubMed

    Tran-Van-Minh, Alexandra; Cazé, Romain D; Abrahamsson, Therése; Cathala, Laurence; Gutkin, Boris S; DiGregorio, David A

    2015-01-01

    Nonlinear dendritic integration is thought to increase the computational ability of neurons. Most studies focus on how supralinear summation of excitatory synaptic responses arising from clustered inputs within single dendrites result in the enhancement of neuronal firing, enabling simple computations such as feature detection. Recent reports have shown that sublinear summation is also a prominent dendritic operation, extending the range of subthreshold input-output (sI/O) transformations conferred by dendrites. Like supralinear operations, sublinear dendritic operations also increase the repertoire of neuronal computations, but feature extraction requires different synaptic connectivity strategies for each of these operations. In this article we will review the experimental and theoretical findings describing the biophysical determinants of the three primary classes of dendritic operations: linear, sublinear, and supralinear. We then review a Boolean algebra-based analysis of simplified neuron models, which provides insight into how dendritic operations influence neuronal computations. We highlight how neuronal computations are critically dependent on the interplay of dendritic properties (morphology and voltage-gated channel expression), spiking threshold and distribution of synaptic inputs carrying particular sensory features. Finally, we describe how global (scattered) and local (clustered) integration strategies permit the implementation of similar classes of computations, one example being the object feature binding problem.

  7. miR-24, miR-30b and miR-142-3p interfere with antigen processing and presentation by primary macrophages and dendritic cells

    PubMed Central

    Naqvi, Afsar Raza; Fordham, Jezrom B.; Ganesh, Balaji; Nares, Salvador

    2016-01-01

    Antigen uptake, processing and presentation by antigen presenting cells (APCs) are tightly coupled processes which consequently lead to the activation of innate and adaptive immune responses. However, the regulatory role of microRNA (miRNAs) in these critical pathways is poorly understood. In this study, we show that overexpression of miR-24, miR-30b and miR-142-3p attenuates uptake and processing of soluble antigen ovalbumin (Ova) in primary human macrophages and dendritic cells. MiRNA mimic transfected APCs exhibit defects in antigen presentation (Ova and CMV antigen) to CD4+ T-cells leading to reduced cell proliferation. Using transgenic OT-II mice we demonstrated that this impairment in T-cell proliferation is specific to antigen provided i.e., Ova. Further, human T-cells co-cultured with miRNA transfected dendritic cells secrete low levels of T helper (Th)-1 polarization associated cytokines. Analysis of molecules regulating APC and T-cell receptor interaction shows miRNA-mediated induced expression of Programmed Death-Ligand 1 (PD-L1) which inhibits T-cell proliferation. Blocking PD-L1 with antibodies rescues miRNA-mediated inhibition of T cell priming by DCs. These results uncover regulatory functions of miR-24, miR-30b and miR-142-3p in pairing innate and adaptive components of immunity. PMID:27611009

  8. miR-24, miR-30b and miR-142-3p interfere with antigen processing and presentation by primary macrophages and dendritic cells.

    PubMed

    Naqvi, Afsar Raza; Fordham, Jezrom B; Ganesh, Balaji; Nares, Salvador

    2016-01-01

    Antigen uptake, processing and presentation by antigen presenting cells (APCs) are tightly coupled processes which consequently lead to the activation of innate and adaptive immune responses. However, the regulatory role of microRNA (miRNAs) in these critical pathways is poorly understood. In this study, we show that overexpression of miR-24, miR-30b and miR-142-3p attenuates uptake and processing of soluble antigen ovalbumin (Ova) in primary human macrophages and dendritic cells. MiRNA mimic transfected APCs exhibit defects in antigen presentation (Ova and CMV antigen) to CD4+ T-cells leading to reduced cell proliferation. Using transgenic OT-II mice we demonstrated that this impairment in T-cell proliferation is specific to antigen provided i.e., Ova. Further, human T-cells co-cultured with miRNA transfected dendritic cells secrete low levels of T helper (Th)-1 polarization associated cytokines. Analysis of molecules regulating APC and T-cell receptor interaction shows miRNA-mediated induced expression of Programmed Death-Ligand 1 (PD-L1) which inhibits T-cell proliferation. Blocking PD-L1 with antibodies rescues miRNA-mediated inhibition of T cell priming by DCs. These results uncover regulatory functions of miR-24, miR-30b and miR-142-3p in pairing innate and adaptive components of immunity. PMID:27611009

  9. Immune Monitoring Using mRNA-Transfected Dendritic Cells.

    PubMed

    Borch, Troels Holz; Svane, Inge Marie; Met, Özcan

    2016-01-01

    Dendritic cells are known to be the most potent antigen presenting cell in the immune system and are used as cellular adjuvants in therapeutic anticancer vaccines using various tumor-associated antigens or their derivatives. One way of loading antigen into the dendritic cells is by mRNA electroporation, ensuring presentation of antigen through major histocompatibility complex I and potentially activating T cells, enabling them to kill the tumor cells. Despite extensive research in the field, only one dendritic cell-based vaccine has been approved. There is therefore a great need to elucidate and understand the immunological impact of dendritic cell vaccination in order to improve clinical benefit. In this chapter, we describe a method for performing immune monitoring using peripheral blood mononuclear cells and autologous dendritic cells transfected with tumor-associated antigen-encoding mRNA. PMID:27236804

  10. Synthesis and field emission properties of Cu dendritic nanostructures

    NASA Astrophysics Data System (ADS)

    Xu, Jianwen; Yu, Ke; Zhu, Ziqiang

    2010-03-01

    Cu dendritic nanostructures were synthesized on ITO glass substructure by electrochemical deposition. SEM images showed that these Cu dendritic nanostuctures revealed a clear and well-defined dendritic fractal structure with a pronounced trunk and highly ordered branches distributed on both sides of the trunk. The diffusion-limited aggregation (DLA) model was used to explain the fractal growth of Cu dendritic nanostructures. Field emission properties of these Cu dendritic nanostructures were measured, which have possessed good performance with the turn-on field of 7.5 V/μm (defined as the electric field required to be detected at a current density of 0.1 mA/cm 2) and the field enhancement factor β of 1094.

  11. Regulation of Th2 Cell Immunity by Dendritic Cells.

    PubMed

    Na, Hyeongjin; Cho, Minkyoung; Chung, Yeonseok

    2016-02-01

    Th2 cell immunity is required for host defense against helminths, but it is detrimental in allergic diseases in humans. Unlike Th1 cell and Th17 cell subsets, the mechanism by which dendritic cells modulate Th2 cell responses has been obscure, in part because of the inability of dendritic cells to provide IL-4, which is indispensable for Th2 cell lineage commitment. In this regard, immune cells other than dendritic cells, such as basophils and innate lymphoid cells, have been suggested as Th2 cell inducers. More recently, multiple independent researchers have shown that specialized subsets of dendritic cells mediate Th2 cell responses. This review will discuss the current understanding related to the regulation of Th2 cell responses by dendritic cells and other immune cells. PMID:26937227

  12. Dendrite coherency during equiaxed solidification in binary aluminum alloys

    SciTech Connect

    Chai, G.; Baeckerud, L.; Roelland, T.; Arnberg, L.

    1995-04-01

    Dendrite coherency, or dendrite impingement, is important to the formation of the solidification structure and castability of alloys. Dendrite coherency in the systems Al-xMn, Al-xCu, Al-xFe, and Al-xSi (x = 0 to 5 wt pct) has been studied by continuous torque measurement in solidifying samples. The fraction solid at the dendrite coherency point, fs*, varies with the alloy system and the solute concentration in the alloy, from 18 to 56 pct for the present alloys investigated. An increase in solute concentration decreases the coherency fraction solid, fs*. An alloy system with a large slope of the liquidus line has a high coherency fraction solid. A theoretical approach has been developed to account for the effects of the alloy system and solute concentration on the dendrite coherency in the alloy. The grain sizes of the alloys were evaluated using the parameters at coherency point.

  13. Human dendritic cells as targets of dengue virus infection.

    PubMed

    Marovich, M; Grouard-Vogel, G; Louder, M; Eller, M; Sun, W; Wu, S J; Putvatana, R; Murphy, G; Tassaneetrithep, B; Burgess, T; Birx, D; Hayes, C; Schlesinger-Frankel, S; Mascola, J

    2001-12-01

    Dengue virus infections are an emerging global threat. Severe dengue infection is manifested as dengue hemorrhagic fever and dengue shock syndrome, both of which can be fatal complications. Factors predisposing to complicated disease and pathogenesis of severe infections are discussed. Using immunohistochemistry, immunofluorescence, flow cytometry, and ELISA techniques, we studied the cellular targets of dengue virus infection, at both the clinical (in vivo) and the laboratory (in vitro) level. Resident skin dendritic cells are targets of dengue virus infection as demonstrated in a skin biopsy from a dengue vaccine recipient. We show that factors influencing infection of monocytes/macrophages and dendritic cells are different. Immature dendritic cells were found to be the cells most permissive for dengue infection and maybe early targets for infection. Immature dendritic cells exposed to dengue virus produce TNF-alpha protein. Some of these immature dendritic cells undergo TNF-alpha mediated maturation as a consequence of exposure to the dengue virus. PMID:11924831

  14. Spatially Distributed Dendritic Resonance Selectively Filters Synaptic Input

    PubMed Central

    Segev, Idan; Shamma, Shihab

    2014-01-01

    An important task performed by a neuron is the selection of relevant inputs from among thousands of synapses impinging on the dendritic tree. Synaptic plasticity enables this by strenghtening a subset of synapses that are, presumably, functionally relevant to the neuron. A different selection mechanism exploits the resonance of the dendritic membranes to preferentially filter synaptic inputs based on their temporal rates. A widely held view is that a neuron has one resonant frequency and thus can pass through one rate. Here we demonstrate through mathematical analyses and numerical simulations that dendritic resonance is inevitably a spatially distributed property; and therefore the resonance frequency varies along the dendrites, and thus endows neurons with a powerful spatiotemporal selection mechanism that is sensitive both to the dendritic location and the temporal structure of the incoming synaptic inputs. PMID:25144440

  15. Concurrent and Clonally Related Pediatric Follicular Lymphoma and Burkitt Lymphoma in a 5-Year-Old Boy.

    PubMed

    Shaver, Aaron C; Zimmerman, David; Liu, Mingya; Vnencak-Jones, Cindy; Kim, Annette S

    2016-02-01

    Pediatric follicular lymphoma shares morphologic similarities with the adult form of the disease but lacks other classic features of adult lymphoma, including t(14;18) translocation, BCL2 overexpression, and transformation to aggressive higher-grade lymphoma. Herein, we report a novel case in which a 5-year-old boy (ethnicity unknown) had follicular lymphoma, along with concurrent high-grade and clonally related disease that fulfilled all of the morphologic, immunophenotypic, and genetic criteria for Burkitt lymphoma, including a t(8;14) translocation involving the MYC gene. To our knowledge, this case is the first reported instance of transformation of follicular lymphoma of any sort into true Burkitt lymphoma and the first reported instance of acquisition of MYC abnormalities in pediatric follicular lymphoma.

  16. Dendritic Cells: Cellular Mediators for Immunological Tolerance

    PubMed Central

    Chung, Chun Yuen J.; Ysebaert, Dirk; Berneman, Zwi N.

    2013-01-01

    In general, immunological tolerance is acquired upon treatment with non-specific immunosuppressive drugs. This indiscriminate immunosuppression of the patient often causes serious side-effects, such as opportunistic infectious diseases. Therefore, the need for antigen-specific modulation of pathogenic immune responses is of crucial importance in the treatment of inflammatory diseases. In this perspective, dendritic cells (DCs) can have an important immune-regulatory function, besides their notorious antigen-presenting capacity. DCs appear to be essential for both central and peripheral tolerance. In the thymus, DCs are involved in clonal deletion of autoreactive immature T cells by presenting self-antigens. Additionally, tolerance is achieved by their interactions with T cells in the periphery and subsequent induction of T cell anergy, T cell deletion, and induction of regulatory T cells (Treg). Various studies have described, modulation of DC characteristics with the purpose to induce antigen-specific tolerance in autoimmune diseases, graft-versus-host-disease (GVHD), and transplantations. Promising results in animal models have prompted researchers to initiate first-in-men clinical trials. The purpose of current review is to provide an overview of the role of DCs in the immunopathogenesis of autoimmunity, as well as recent concepts of dendritic cell-based therapeutic opportunities in autoimmune diseases. PMID:23762100

  17. Astrocytes refine cortical connectivity at dendritic spines

    PubMed Central

    Risher, W Christopher; Patel, Sagar; Kim, Il Hwan; Uezu, Akiyoshi; Bhagat, Srishti; Wilton, Daniel K; Pilaz, Louis-Jan; Singh Alvarado, Jonnathan; Calhan, Osman Y; Silver, Debra L; Stevens, Beth; Calakos, Nicole; Soderling, Scott H; Eroglu, Cagla

    2014-01-01

    During cortical synaptic development, thalamic axons must establish synaptic connections despite the presence of the more abundant intracortical projections. How thalamocortical synapses are formed and maintained in this competitive environment is unknown. Here, we show that astrocyte-secreted protein hevin is required for normal thalamocortical synaptic connectivity in the mouse cortex. Absence of hevin results in a profound, long-lasting reduction in thalamocortical synapses accompanied by a transient increase in intracortical excitatory connections. Three-dimensional reconstructions of cortical neurons from serial section electron microscopy (ssEM) revealed that, during early postnatal development, dendritic spines often receive multiple excitatory inputs. Immuno-EM and confocal analyses revealed that majority of the spines with multiple excitatory contacts (SMECs) receive simultaneous thalamic and cortical inputs. Proportion of SMECs diminishes as the brain develops, but SMECs remain abundant in Hevin-null mice. These findings reveal that, through secretion of hevin, astrocytes control an important developmental synaptic refinement process at dendritic spines. DOI: http://dx.doi.org/10.7554/eLife.04047.001 PMID:25517933

  18. Morphological change tracking of dendritic spines based on structural features.

    PubMed

    Son, J; Song, S; Lee, S; Chang, S; Kim, M

    2011-03-01

    Identification and tracking of dendritic spine morphology from two-dimensional time-lapsed images plays an important role in neurobiological research. Such analysis can enable us to derive a correlation between morphological characteristics and molecular mechanism of dendritic spine development and remodelling. Moreover, Neuronal morphology of hippocampal Cornu Ammonis 1 region is critical for understanding the Alzheimer's disease. Therefore, we need to extract and trace the dendritic spines accurately for examining their development and remodelling processes, which are related to functions of hippocampal Cornu Ammonis 1. There are some problems to be solved in related researches. Noise due to the properties of optical microscopes makes it difficult to identify and trace dendritic spines accurately. To solve these problems, in this paper we present a local spine detection technique minimizing noise influence in two-dimensional optical microscopy images. Also, we suggest an efficient mapping method for tracking the dynamics of dendritic spines to measure their morphological changes quantitatively. First, to utilize structural feature of spines, which are small protrusions of tree-like dendrites, we extract the tips of each dendritic branch and use this position as an initial contour position for a deformable model-based segmentation. We then use a geodesic active contour model to detect the spines accurately. Secondly, we apply an optical flow method, which takes into account both structure and movement of objects, to map every time-series image frame. Proposed method provides accurate measurements of dendritic spine length, volume, shape classification for time-lapse images of dendrites of hippocampal neurons. We compared the proposed spine detection algorithm with manual method performed by biologists and noncommercial software NeuronIQ. In particular, this method is able to segment dendritic spines better than existing methods with high sensitivity in adjacent

  19. Recurrence rate in regional lymph nodes in 737 patients with follicular or Hürthle cell neoplasms

    PubMed Central

    Vogrin, Andrej; Besic, Hana; Besic, Nikola

    2016-01-01

    Abstract Background Preoperative ultrasound (US) evaluation of central and lateral neck compartments is recommended for all patients undergoing a thyroidectomy for malignant or suspicious for malignancy cytologic or molecular findings. Our aim was to find out how frequent was recurrence in regional lymph nodes in patients with follicular or Hürthle cell neoplasm and usefulness of preoperative neck US investigation in patients with neoplasm. Patients and methods Altogether 737 patients were surgically treated because of follicular or Hürthle cell neoplasms from 1995 to 2014 at our cancer comprehensive center, among them 207 patients (163 females, 44 males; mean age 52 years) had thyroid carcinoma. Results Carcinoma was diagnosed in follicular and Hürthle cell neoplasm in 143/428 and 64/309 of cases, respectively. A recurrence in regional lymph nodes occurred in 12/207 patients (6%) during a median follow-up of 55 months. Among patients with carcinoma a recurrence in regional lymph nodes was diagnosed in follicular and Hürthle cell neoplasms in 2% and 14%, respectively (p = 0.002). Recurrence in regional lymph nodes was diagnosed in 3/428 of all patients with follicular neoplasm and 9/309 of all patients with Hürthle cell neoplasm. Conclusions Recurrence in lymph nodes was diagnosed in 0.7% of patients with a preoperative diagnosis of follicular neoplasm and 3% of patients with a Hürthle cell neoplasm. A recurrence in regional lymph nodes is rare in patients with carcinoma and preoperative diagnosis of follicular neoplasm. Preoperative neck ultrasound examination in patients with a follicular neoplasm is probably not useful, but in patients with Hurtle cell neoplasm it may be useful.

  20. Iontophoresis of minoxidil sulphate loaded microparticles, a strategy for follicular drug targeting?

    PubMed

    Gelfuso, Guilherme M; Barros, M Angélica de Oliveira; Delgado-Charro, M Begoña; Guy, Richard H; Lopez, Renata F V

    2015-10-01

    The feasibility of targeting drugs to hair follicles by a combination of microencapsulation and iontophoresis has been evaluated. Minoxidil sulphate (MXS), which is used in the treatment of alopecia, was selected as a relevant drug with respect to follicular penetration. The skin permeation and disposition of MXS encapsulated in chitosan microparticles (MXS-MP) was evaluated in vitro after passive and iontophoretic delivery. Uptake of MXS was quantified at different exposure times in the stratum corneum (SC) and hair follicles. Microencapsulation resulted in increased (6-fold) drug accumulation in the hair follicles relative to delivery from a simple MXS solution. Application of iontophoresis enhanced follicular delivery for both the solution and the microparticle formulations. It appears, therefore, that microencapsulation and iontophoresis can act synergistically to enhance topical drug targeting to hair follicles. PMID:26222406

  1. Eosinophilic follicular reaction induced by Demodex folliculorum mite: a different disease from eosinophilic folliculitis.

    PubMed

    Sabater-Marco, V; Escutia-Muñoz, B; Botella-Estrada, R

    2015-06-01

    Eosinophilic folliculitis (EF) is an idiopathic dermatitis included in the spectrum of eosinophilic pustular follicular reactions. Demodex folliculorum has been implicated as contributing to the pathogenesis of human immunodeficiency virus-associated EF, but it has not been described outside this context. We present an immunocompetent 65-year-old white man with a 5-year history of recurrent pruritic erythematous and oedematous lesions on his face, neck and scalp. Histopathologically, an eosinophilic microabcess with Demodex folliculorum mite within a pilosebaceous follicle was seen, and considered the causal agent. There were also accumulations of eosinophil granules on collagen bundles, and flame figure formations in the dermis. We believe that 'eosinophilic follicular reaction' is an appropriate term to describe this case of EF induced by D. folliculorum and thus distinguish it from the idiopathic form of EF. Moreover, this case suggests that D. folliculorum can sometimes induce an eosinophilic immune reaction. PMID:25623943

  2. Antisepsis of the follicular reservoir by treatment with tissue-tolerable plasma (TTP)

    NASA Astrophysics Data System (ADS)

    Lademann, O.; Kramer, A.; Richter, H.; Patzelt, A.; Meinke, M. C.; Roewert-Huber, J.; Czaika, V.; Weltmann, K.-D.; Hartmann, B.; Koch, S.

    2011-04-01

    The application of tissue-tolerable electrical plasma (TTP) is highly efficient in skin antisepsis. However, the germs are not only located on the skin surface, but also in the hair follicles, from where they re-colonize the skin surface after antisepsis, e.g. The objective of the present study was to show that plasma is able to reach the follicular reservoir for antisepsis. For this purpose, a solution containing particulate chlorophyll dye had been applied onto porcine skin samples. The fluorescent properties of the dye changed during the plasma tissue interaction. The results demonstrate that TTP penetrates deep into the hair follicles, whereupon the hairs act as a conductor for the plasma. Therefore, it can be concluded that micro-organisms of the follicular reservoir are destroyed more efficiently by the plasma than by conventional liquid antiseptics.

  3. Sciatica as a presenting feature of thyroid follicular adenocarcinoma in a 79-year-old woman.

    PubMed

    Ogbodo, Elisha; Kaliaperumal, Chandrasekaran; Keohane, Catherine; Bermingham, Niamh; Kaar, George

    2011-12-01

    The authors describe an unusual case of metastatic thyroid follicular adenocarcinoma presenting with sciatica in a 79-year-old woman. The primary thyroid tumour was undiagnosed until this clinical presentation. The patient gave a short history of back pain and right-sided sciatica, which was progressive and nocturnal in nature. Neuroimaging revealed an enhancing intradural mass lesion, which was completely excised through a right L1-L3 hemilaminectomy. Histopathological examination of the excised tissue revealed a follicular thyroid carcinoma. Subsequent metastatic investigation revealed a heterogeneously attenuating mixed solid cystic mass in a retrosternal thyroid gland, with multiple solid pulmonary nodules suggestive of metastatic disease. She opted for palliative radiotherapy for the primary thyroid cancer and made remarkable postoperative improvement. The authors conclude that surgical treatment of solitary metastatic lesion may produce good symptomatic relief irrespective of patient's age and primary pathology, while emphasising the need for detailed clinical evaluation of patients with 'red flag' symptoms.

  4. Iontophoresis of minoxidil sulphate loaded microparticles, a strategy for follicular drug targeting?

    PubMed

    Gelfuso, Guilherme M; Barros, M Angélica de Oliveira; Delgado-Charro, M Begoña; Guy, Richard H; Lopez, Renata F V

    2015-10-01

    The feasibility of targeting drugs to hair follicles by a combination of microencapsulation and iontophoresis has been evaluated. Minoxidil sulphate (MXS), which is used in the treatment of alopecia, was selected as a relevant drug with respect to follicular penetration. The skin permeation and disposition of MXS encapsulated in chitosan microparticles (MXS-MP) was evaluated in vitro after passive and iontophoretic delivery. Uptake of MXS was quantified at different exposure times in the stratum corneum (SC) and hair follicles. Microencapsulation resulted in increased (6-fold) drug accumulation in the hair follicles relative to delivery from a simple MXS solution. Application of iontophoresis enhanced follicular delivery for both the solution and the microparticle formulations. It appears, therefore, that microencapsulation and iontophoresis can act synergistically to enhance topical drug targeting to hair follicles.

  5. Intraovarian control of selective follicular growth and induction of oocyte maturation in mammals

    PubMed Central

    SATO, Eimei

    2015-01-01

    In newborn mammals, most of the germ cell population rests in a pool of quiescent small follicles in the ovaries. Regularly throughout adulthood, a small percentage of these oocytes and follicles grows to a certain stage of development and then either degenerates or matures and ovulates. This entire process is under both exogenous and endogenous control. Recent work, including my laboratory’s, has clarified that cytokines and glycosaminoglycans are involved as exogenous and endogenous factors in ovarian follicular development, atresia, and maturation in mammals. The present article describes our contribution regarding the cytokines and ovarian glycosaminoglycans that act as intraovarian regulators of follicular development and oogenesis, including oocyte maturation, in mammals. PMID:25765010

  6. Scanning electron microscopic changes in granulosa cells during follicular atresia in Caprine ovary.

    PubMed

    Bhardwaj, J K; Sharma, R K

    2011-01-01

    During this study, topographic changes in healthy and atretic granulosa cells have been investigated during follicular atresia in goat ovary. Under scanning electron microscopy atresia was marked by asymmetrical shrinkage and vacuolization of cytoplasm. The specific topographical alterations observed in atretic cells were loss of micro extensions, disruption of cell-cell interaction, and smooth-textured membrane with a number of uneven depressions and ruffles. Some portions of the cell membrane were marked by extensive shrinkage due to condensation of cytosol. Irregular membrane at occasions was studded with blunt microextensions. The findings of present investigation will help in understanding the cellular changes in granulosa cells during follicular atresia and will find applications in screening of follicles for in vitro culture, in vitro fertilization and Embryo transfer technology. PMID:21254113

  7. Follicular Thyroid Carcinoma Characterized by Abundant Stromal Components with Chondroid and Osseous Metaplasia in a Dog

    PubMed Central

    KOBAYASHI, Ryosuke; YAMADA, Naoaki; KITAMORI, Takashi; KITAMORI, Fumiyo; SATO, Kazunari; DOI, Takuya; WAKO, Yumi; SATO, Junko; TSUCHITANI, Minoru

    2014-01-01

    ABSTRACT A dog developed a cervical mass, and computed tomography verified a mass surrounding the trachea with some pulmonary masses. Histopathologically, the cervical mass was composed of malignant neoplastic cells showing follicular appearance which reacted positive for thyroglobulin on immunohistochemistry. A characteristic feature of the tumor was abundant and metaplastic stromal components. Anastomosed collagenous tissues connecting to capsule of the tumor were abundant in the stroma. In parts of the collagenous tissues, mature cartilages and bones were continuously formed. There was no cellular atypia or invasion in the components. We diagnosed this case as follicular thyroid carcinoma with metaplastic stroma. This is the first case report that characterizes stromal components with chondroid and osseous metaplasia in a canine thyroid carcinoma. PMID:24805905

  8. Expression of hypoxia-inducible factor-1α during ovarian follicular growth and development in Sprague-Dawley rats.

    PubMed

    Zhang, Z H; Chen, L Y; Wang, F; Wu, Y Q; Su, J Q; Huang, X H; Wang, Z C; Cheng, Y

    2015-06-01

    Hypoxia-inducible factor-1α (HIF-1α) has been identified as a transcription factor that is involved in diverse physiological and pathological processes in the ovary. In this study, we examined whether HIF-1α is expressed in a cell- and stage-specific manner during follicular growth and development in the mammalian ovaries. Using immunohistochemistry and Western blot analysis, HIF-1α expression was observed in granulosa cells specifically and was significantly increased during the follicular growth and development of postnatal rats. Furthermore, pregnant mare serum gonadotropin also induced HIF-1α expression in granulosa cells and ovaries during the follicular development of immature rats primed with gonadotropin. Moreover, we also examined proliferation cell nuclear antigen, a cell proliferation marker, during follicular growth and development and found that its expression pattern was similar to that of HIF-1α protein. Granulosa cell culture experiments revealed that proliferation cell nuclear antigen expression may be regulated by HIF-1α. These results indicated that HIF-1α plays an important role in the follicular growth and development of these 2 rat models. The HIF-1α-mediated signaling pathway may be an important mechanism regulating follicular growth and development in mammalian ovaries in vivo.

  9. Incidental Detection of Follicular Thyroid Carcinoma in 68Ga-PSMA PET/CT Imaging.

    PubMed

    Sager, Sait; Vatankulu, Betül; Uslu, Lebriz; Sönmezoglu, Kerim

    2016-09-01

    Prostate-specific membrane antigen (PSMA) is a type II transmembrane protein. It has been shown to be expressed in various solid malignant neoplasms. We report a case of a prostate cancer patient who underwent (68)Ga-PSMA PET/CT imaging. There is a large thyroid nodule in the right thyroid gland, which had intense PSMA accumulation. Follicular thyroid lesions can be seen on (68)Ga-PSMA PET/CT imaging. PMID:26966127

  10. Comprehensive Analysis of the Transcriptional and Mutational Landscape of Follicular and Papillary Thyroid Cancers.

    PubMed

    Yoo, Seong-Keun; Lee, Seungbok; Kim, Su-Jin; Jee, Hyeon-Gun; Kim, Byoung-Ae; Cho, Hyesun; Song, Young Shin; Cho, Sun Wook; Won, Jae-Kyung; Shin, Jong-Yeon; Park, Do Joon; Kim, Jong-Il; Lee, Kyu Eun; Park, Young Joo; Seo, Jeong-Sun

    2016-08-01

    Follicular thyroid carcinoma (FTC) and benign follicular adenoma (FA) are indistinguishable by preoperative diagnosis due to their similar histological features. Here we report the first RNA sequencing study of these tumors, with data for 30 minimally invasive FTCs (miFTCs) and 25 FAs. We also compared 77 classical papillary thyroid carcinomas (cPTCs) and 48 follicular variant of PTCs (FVPTCs) to observe the differences in their molecular properties. Mutations in H/K/NRAS, DICER1, EIF1AX, IDH1, PTEN, SOS1, and SPOP were identified in miFTC or FA. We identified a low frequency of fusion genes in miFTC (only one, PAX8-PPARG), but a high frequency of that in PTC (17.60%). The frequencies of BRAFV600E and H/K/NRAS mutations were substantially different in miFTC and cPTC, and those of FVPTC were intermediate between miFTC and cPTC. Gene expression analysis demonstrated three molecular subtypes regardless of their histological features, including Non-BRAF-Non-RAS (NBNR), as well as BRAF-like and RAS-like. The novel molecular subtype, NBNR, was associated with DICER1, EIF1AX, IDH1, PTEN, SOS1, SPOP, and PAX8-PPARG. The transcriptome of miFTC or encapsulated FVPTC was indistinguishable from that of FA, providing a molecular explanation for the similarly indolent behavior of these tumors. We identified upregulation of genes that are related to mitochondrial biogenesis including ESRRA and PPARGC1A in oncocytic follicular thyroid neoplasm. Arm-level copy number variations were correlated to histological and molecular characteristics. These results expanded the current molecular understanding of thyroid cancer and may lead to new diagnostic and therapeutic approaches to the disease.

  11. Effects of melatonin on follicular atresia and granulosa cell apoptosis in the porcine.

    PubMed

    He, Yamei; Deng, Honghui; Jiang, Zhongliang; Li, Qingwang; Shi, Meihong; Chen, Huali; Han, Zengsheng

    2016-08-01

    The accumulation of reactive oxygen species is detrimental to the health of the ovarian follicle. The protective, antioxidant properties of melatonin, an endogenous component of porcine follicular fluid, on apoptosis of granulosa cells were evaluated in this study. Porcine granulosa cells from medium-sized (3-5 mm), healthy follicles were cultured in serum-free conditions with melatonin (0, 0.01, 0.1, 1.0, 10, and 100 ng/mL) with or without its receptor antagonist, luzindole, followed by evaluation of apoptotic markers in the treated cells. Results revealed that endogenous, intrafollicular melatonin concentration decreased as follicular atresia progressed, whereas the percentage of apoptotic granulosa cells increased. Spontaneous apoptosis of granulosa cells, triggered by serum deprivation in vitro, was remarkably blocked by melatonin (1.0 ng/mL melatonin, 32.7 ± 0.5%, vs. control, 47.0 ± 1.0%; P < 0.05). Treatment with 1.0 ng/mL of melatonin also significantly elevated MT2, SOD1, and GPX4 while lowering FASL, CHOP, and GRP78 mRNA abundance compared to the untreated control. The anti-apoptotic effect and some changes of apoptotic-relevant genes in granulosa cells invoked by melatonin supplementation were markedly blocked by luzindole, suggesting that melatonin could prevent the apoptosis of porcine granulosa cells during follicular atresia via its membrane receptors and its free-radical-scavenging activity. These findings provide new insights into the regulatory mechanism of melatonin in follicular atresia-related functions. Mol. Reprod. Dev. 83: 692-700, 2016 © 2016 Wiley Periodicals, Inc. PMID:27391761

  12. Comprehensive Analysis of the Transcriptional and Mutational Landscape of Follicular and Papillary Thyroid Cancers

    PubMed Central

    Jee, Hyeon-Gun; Kim, Byoung-Ae; Cho, Hyesun; Song, Young Shin; Cho, Sun Wook; Shin, Jong-Yeon; Kim, Jong-Il; Lee, Kyu Eun; Seo, Jeong-Sun

    2016-01-01

    Follicular thyroid carcinoma (FTC) and benign follicular adenoma (FA) are indistinguishable by preoperative diagnosis due to their similar histological features. Here we report the first RNA sequencing study of these tumors, with data for 30 minimally invasive FTCs (miFTCs) and 25 FAs. We also compared 77 classical papillary thyroid carcinomas (cPTCs) and 48 follicular variant of PTCs (FVPTCs) to observe the differences in their molecular properties. Mutations in H/K/NRAS, DICER1, EIF1AX, IDH1, PTEN, SOS1, and SPOP were identified in miFTC or FA. We identified a low frequency of fusion genes in miFTC (only one, PAX8–PPARG), but a high frequency of that in PTC (17.60%). The frequencies of BRAFV600E and H/K/NRAS mutations were substantially different in miFTC and cPTC, and those of FVPTC were intermediate between miFTC and cPTC. Gene expression analysis demonstrated three molecular subtypes regardless of their histological features, including Non–BRAF–Non–RAS (NBNR), as well as BRAF–like and RAS–like. The novel molecular subtype, NBNR, was associated with DICER1, EIF1AX, IDH1, PTEN, SOS1, SPOP, and PAX8–PPARG. The transcriptome of miFTC or encapsulated FVPTC was indistinguishable from that of FA, providing a molecular explanation for the similarly indolent behavior of these tumors. We identified upregulation of genes that are related to mitochondrial biogenesis including ESRRA and PPARGC1A in oncocytic follicular thyroid neoplasm. Arm-level copy number variations were correlated to histological and molecular characteristics. These results expanded the current molecular understanding of thyroid cancer and may lead to new diagnostic and therapeutic approaches to the disease. PMID:27494611

  13. Human T Follicular Helper Cells in Primary Immunodeficiency: Quality Just as Important as Quantity.

    PubMed

    Ma, Cindy S

    2016-05-01

    T follicular helper (Tfh) cells are a subset of effector CD4(+) T cells specialised to induce Ab production by B cells. This review highlights some of the recent advances in the field of human Tfh cells that have come from the study of primary immunodeficiencies. In particular it is increasingly evident that the quality of the Tfh cells that are generated, is just as important as the quantity.

  14. Randomized controlled trials in relapsed/refractory follicular lymphoma: a systematic review and meta-analysis.

    PubMed

    Police, Rachel L; Trask, Peter C; Wang, Jianmin; Olivares, Robert; Khan, Shahnaz; Abbe, Adeline; Colosia, Ann; Njue, Annete; Sherril, Beth; Ruiz-Soto, Rodrigo; Kaye, James A; Hamadani, Mehdi

    2016-10-01

    This systematic literature review evaluated the clinical efficacy and safety of interventions used in relapsed/refractory follicular lymphoma. Primary efficacy outcomes were objective response rate, progression-free survival and overall survival. Safety endpoints were grade 3/4 toxicities, serious adverse events and withdrawals or deaths due to toxicity. Studies were selected if they were randomized controlled trials reporting on the efficacy or safety of treatments for relapsed or refractory follicular lymphoma, and if outcomes were reported separately from trials that included other lymphoid neoplasms. We used the Bucher method for conducting adjusted indirect comparisons within a meta-analysis. We identified 10 randomized controlled trials of treatments for relapsed/refractory follicular lymphoma. The most prominent drug investigated (alone or in combination) was rituximab. Most trials did not report median overall survival. Two trials reported median event-free survival (range, 1.2-23.2 months). Six of ten trials reported objective response rate (range, 9-93%). Meta-analysis showed only one statistically significant result: rituximab + bortezomib yielded a significantly higher objective response rate than rituximab monotherapy (relative risk, 1.28; 95% confidence interval, 1.11-1.47). Otherwise, there were no discernable differences in overall survival or progression-free survival, partly due to insufficient reporting of results in the clinical trials. The relatively small number of randomized controlled trials, few overlapping treatment arms, and variability in the randomized controlled trial features and in the endpoints studied complicate the formal comparison of therapies for relapsed/refractory follicular lymphoma. Additional well-designed randomized controlled trials are needed to fully understand the relative outcomes of older and more recently developed therapies. PMID:26320127

  15. Treatment of distant metastases from follicular cell-derived thyroid cancer.

    PubMed

    Schlumberger, Martin; Leboulleux, Sophie

    2015-01-01

    Distant metastases from thyroid cancer of follicular origin are uncommon. Treatment includes levothyroxine administration at suppressive doses, focal treatment modalities with surgery, external radiation therapy and thermal ablation, and radioiodine in patients with uptake of (131)I in their metastases. Two thirds of distant metastases will become refractory to radioiodine at some point, and when there is a significant tumor burden and documented progression on imaging, a treatment with a kinase inhibitor may provide benefits. PMID:25750740

  16. Treatment of distant metastases from follicular cell-derived thyroid cancer

    PubMed Central

    Leboulleux, Sophie

    2015-01-01

    Distant metastases from thyroid cancer of follicular origin are uncommon. Treatment includes levothyroxine administration at suppressive doses, focal treatment modalities with surgery, external radiation therapy and thermal ablation, and radioiodine in patients with uptake of 131I in their metastases. Two thirds of distant metastases will become refractory to radioiodine at some point, and when there is a significant tumor burden and documented progression on imaging, a treatment with a kinase inhibitor may provide benefits. PMID:25750740

  17. Roles of thyroid hormones in follicular development in the ovary of neonatal and immature rats.

    PubMed

    Fedail, Jaafar Sulieman; Zheng, Kaizhi; Wei, Quanwei; Kong, Lingfa; Shi, Fangxiong

    2014-08-01

    Thyroid hormones (TH) play a critical role in ovarian follicular development, maturation and the maintenance of various endocrine functions. However, whether TH can affect ovarian follicular development in neonatal and immature rats remains unclear. Therefore, the aim of the present study was to elucidate the effect of TH on ovarian follicular development in neonatal and immature rats. Thirty female post-lactation mothers of Sprague-Dawley rat pups were randomly divided into three groups: control, hyperthyroid (hyper), and hypothyroid (hypo). On postnatal days (PND) 10 and 21, body weights, serum hormones, ovarian histologic changes, and immunohistochemistry of thyroid hormone receptor alpha 1 (TRα1) and nitric oxide synthase types (NOS), and NOS activities, were determined. The data showed that body weights significantly decreased in both hyper and hypo groups compared with the control group (P < 0.05). In addition, the hyper group had increased serum concentrations of T3, T4, and E2; whereas the hypo group manifested reduced serum concentrations of T3, T4, and E2 on PND 10 and 21. The hyper and hypo groups showed significantly reduced total number of primordial, primary and secondary follicles on PND 10 and 21 compared with the control group (P < 0.05). Similarly, antral follicle numbers in the hyper and hypo groups were significantly decreased on PND 21 compared with the control group (P < 0.05). Immunostaining indicated that TRα1 and NOS were expressed in ovarian surface epithelium and oocytes of growing and antral follicles, with strong staining of the granulosa and theca cells of follicles. NOS activities were significantly augmented in the hyper, but diminished in the hypo groups on PND 10 and 21. In summary, our findings suggest that TH play important roles in ovarian functions and in the regulation of NOS activity. Our results also indicate that a relationship exists between the TH and NO signaling pathways during the process of ovarian follicular

  18. Mucinous Variant of Follicular Carcinoma of the Thyroid Gland: Case Report and Review of the Literature.

    PubMed

    Squillaci, Salvatore; Pitino, Antonio; Spairani, Cinzia; Ferrari, Mauro; Carlon, Eugenio; Cosimi, Maria Fabia

    2016-04-01

    The rare reports of mucinous variant of follicular carcinoma of the thyroid gland have not provided enough evidence to support the recognition of these tumors as a distinct clinicopathologic entity or to understand their etiopathogenesis. We report the fourth case of mucinous variant of follicular carcinoma displaying a minimally invasive tumor with diffuse expression of thyroglobulin, TTF-1, CD56, PAX-8, cytokeratins 7 and 19, in the absence of monoclonal carcinoembryonic antigen (CEA), cytokeratin 20, chromogranin, HBME-1, P63 expression, and BRAF gene mutation, in a 51-year-old woman who is alive without signs of disease 13 months after total thyroidectomy, bilateral neck dissection, and radioactive iodine. Herein, fine-needle aspiration cytology disclosed "worrisome" cytologic features consisting of large epithelial cells arranged in clusters or singularly, with high nucleocytoplasmic ratio, nuclear grooves and evident nucleoli which were shared by those of mucin-producing papillary thyroid carcinoma. Therefore, knowledge of the cytological and histopathological spectrum of this lesion is important to avoid misdiagnosis. The morphologic clues leading to the correct diagnosis of mucinous variant of follicular neoplasm have been correlated with the data of the literature, and the differential diagnosis is briefly discussed.

  19. Accurate diagnosis of thyroid follicular lesions from nuclear morphology using supervised learning.

    PubMed

    Ozolek, John A; Tosun, Akif Burak; Wang, Wei; Chen, Cheng; Kolouri, Soheil; Basu, Saurav; Huang, Hu; Rohde, Gustavo K

    2014-07-01

    Follicular lesions of the thyroid remain significant diagnostic challenges in surgical pathology and cytology. The diagnosis often requires considerable resources and ancillary tests including immunohistochemistry, molecular studies, and expert consultation. Visual analyses of nuclear morphological features, generally speaking, have not been helpful in distinguishing this group of lesions. Here we describe a method for distinguishing between follicular lesions of the thyroid based on nuclear morphology. The method utilizes an optimal transport-based linear embedding for segmented nuclei, together with an adaptation of existing classification methods. We show the method outputs assignments (classification results) which are near perfectly correlated with the clinical diagnosis of several lesion types' lesions utilizing a database of 94 patients in total. Experimental comparisons also show the new method can significantly outperform standard numerical feature-type methods in terms of agreement with the clinical diagnosis gold standard. In addition, the new method could potentially be used to derive insights into biologically meaningful nuclear morphology differences in these lesions. Our methods could be incorporated into a tool for pathologists to aid in distinguishing between follicular lesions of the thyroid. In addition, these results could potentially provide nuclear morphological correlates of biological behavior and reduce health care costs by decreasing histotechnician and pathologist time and obviating the need for ancillary testing.

  20. Accurate diagnosis of thyroid follicular lesions from nuclear morphology using supervised learning

    PubMed Central

    Ozolek, John A.; Tosun, Akif Burak; Wang, Wei; Chen, Cheng; Kolouri, Soheil; Basu, Saurav; Huang, Hu; Rohde, Gustavo K.

    2014-01-01

    Follicular lesions of the thyroid remain significant diagnostic challenges in surgical pathology and cytology. The diagnosis often requires considerable resources and ancillary tests including immunohistochemistry, molecular studies, and expert consultation. Visual analyses of nuclear morphological features, generally speaking, have not been helpful in distinguishing this group of lesions. Here we describe a method for distinguishing between follicular lesions of the thyroid based on nuclear morphology. The method utilizes an optimal transport-based linear embedding for segmented nuclei, together with an adaptation of existing classification methods. We show the method outputs assignments (classification results) which are near perfectly correlated with the clinical diagnosis of several lesion types' lesions utilizing a database of 94 patients in total. Experimental comparisons also show the new method can significantly outperform standard numerical feature-type methods in terms of agreement with the clinical diagnosis gold standard. In addition, the new method could potentially be used to derive insights into biologically meaningful nuclear morphology differences in these lesions. Our methods could be incorporated into a tool for pathologists to aid in distinguishing between follicular lesions of the thyroid. In addition, these results could potentially provide nuclear morphological correlates of biological behavior and reduce health care costs by decreasing histotechnician and pathologist time and obviating the need for ancillary testing. PMID:24835183

  1. Somatic mutation profiling of follicular thyroid cancer by next generation sequencing.

    PubMed

    Swierniak, Michal; Pfeifer, Aleksandra; Stokowy, Tomasz; Rusinek, Dagmara; Chekan, Mykola; Lange, Dariusz; Krajewska, Jolanta; Oczko-Wojciechowska, Małgorzata; Czarniecka, Agnieszka; Jarzab, Michal; Jarzab, Barbara; Wojtas, Bartosz

    2016-09-15

    The molecular etiology of follicular thyroid tumors is largely unknown, rendering the diagnostics of these tumors challenging. The somatic alterations present in these tumors apart from RAS gene mutations and PAX8/PPARG translocations are not well described. To evaluate the profile of somatic alteration in follicular thyroid tumors, a total of 82 thyroid tissue samples derived from 48 patients were subjected to targeted Illumina HiSeq next generation sequencing of 372 cancer-related genes. New somatic alterations were identified in oncogenes (MDM2, FLI1), transcription factors and repressors (MITF, FLI1, ZNF331), epigenetic enzymes (KMT2A, NSD1, NCOA1, NCOA2), and protein kinases (JAK3, CHEK2, ALK). Single nucleotide and large structural variants were most and least frequently identified, respectively. A novel translocation in DERL/COX6C was detected. Many somatic alterations in non-coding gene regions with high penetrance were observed. Thus, follicular thyroid tumor somatic alterations exhibit complex patterns. Most tumors contained distinct somatic alterations, suggesting previously unreported heterogeneity.

  2. Follicular and scarring disorders in skin of color: presentation and management.

    PubMed

    Madu, Pamela; Kundu, Roopal V

    2014-08-01

    Skin of color, also known as ethnic skin, is described as skin of individuals of African, Asian, Hispanic, Native-American, Middle Eastern, and Pacific Island backgrounds. Differences in hair morphology, hair grooming, cultural practices, and susceptibility to keloid scarring exist within these populations and have been implicated in hair, scalp, and skin disorders. Acne keloidalis (AK), central centrifugal cicatricial alopecia (CCCA), dissecting cellulitis of the scalp (DCS), pseudofolliculitis barbae (PFB), traction alopecia (TA), and keloids are the most prevalent follicular and scarring disorders in skin of color. They have been associated with disfigurement, permanent hair loss, emotional distress, and decreased quality of life. Hair grooming practices, such as the use of chemical relaxers, heat straightening, and tight braiding and weaving can cause scalp irritation and follicular damage and are linked to the pathogenesis of some of these conditions. Consequently, patient education and behavior modifications are integral to the prevention and management of these disorders. Scarring disorders are also of concern in ethnic populations. Keloid scarring is more prevalent in individuals of African, Asian, and Hispanic descent. The scarring alopecia CCCA is almost exclusively seen in patients of African descent. Therapeutic regimens such as intralesional corticosteroids, surgical excision, and laser therapy can be effective for these follicular and scarring disorders, but carry a risk of dyspigmentation and keloid scarring. Ethnic skin and hair may present unique challenges to the clinician, and knowledge of these differences is essential to providing quality care. PMID:24820821

  3. Proteome dataset of pre-ovulatory follicular fluids from less fertile dairy cows.

    PubMed

    Zachut, Maya; Sood, Pankaj; Livshitz, Lilya; Kra, Gitit; Levin, Yishai; Moallem, Uzi

    2016-06-01

    This article contains raw and processed data related to research published in Zachut et al. (2016) [1]. Proteomics data from preovulatory follicles in cows was obtained by liquid chromatography-mass spectrometry following protein extraction. Differential expression between controls and less fertile cows (LFC) was quantified using MS1 intensity based label-free. The only previous proteomic analysis of bovine FF detected merely 40 proteins in follicular cysts obtained from the slaughterhouse (Maniwa et al., 2005) [2], and the abundance of proteins in the bovine preovulatory FF remains unknown. Therefore, the objectives were to establish the first dataset of FF proteome in preovulatory follicles of cows, and to examine differentially expressed proteins in FF obtained in-vivo from preovulatory follicles of less fertile cows (also termed "repeat breeder") and control (CTL) cows. The proteome of FF from 10 preovulatory follicles that were aspirated in vivo (estradiol/progesterone>1) was analyzed. This novel dataset contains 219 identified and quantified proteins in FF, consisting mainly of binding proteins, proteases, receptor ligands, enzymes and transporters. In addition, differential abundance of 8 proteins relevant to follicular function was found in LFC compared to CTL; these findings are discussed in our recent research article Zachut et al. (2016) [1]. The present dataset of bovine FF proteome can be used as a reference for any study involving disorders of follicular development in dairy cows or in comparative studies between species. PMID:27182550

  4. Proteome dataset of pre-ovulatory follicular fluids from less fertile dairy cows.

    PubMed

    Zachut, Maya; Sood, Pankaj; Livshitz, Lilya; Kra, Gitit; Levin, Yishai; Moallem, Uzi

    2016-06-01

    This article contains raw and processed data related to research published in Zachut et al. (2016) [1]. Proteomics data from preovulatory follicles in cows was obtained by liquid chromatography-mass spectrometry following protein extraction. Differential expression between controls and less fertile cows (LFC) was quantified using MS1 intensity based label-free. The only previous proteomic analysis of bovine FF detected merely 40 proteins in follicular cysts obtained from the slaughterhouse (Maniwa et al., 2005) [2], and the abundance of proteins in the bovine preovulatory FF remains unknown. Therefore, the objectives were to establish the first dataset of FF proteome in preovulatory follicles of cows, and to examine differentially expressed proteins in FF obtained in-vivo from preovulatory follicles of less fertile cows (also termed "repeat breeder") and control (CTL) cows. The proteome of FF from 10 preovulatory follicles that were aspirated in vivo (estradiol/progesterone>1) was analyzed. This novel dataset contains 219 identified and quantified proteins in FF, consisting mainly of binding proteins, proteases, receptor ligands, enzymes and transporters. In addition, differential abundance of 8 proteins relevant to follicular function was found in LFC compared to CTL; these findings are discussed in our recent research article Zachut et al. (2016) [1]. The present dataset of bovine FF proteome can be used as a reference for any study involving disorders of follicular development in dairy cows or in comparative studies between species.

  5. BCL2 protein expression in follicular lymphomas with t(14;18) chromosomal translocations.

    PubMed

    Masir, Noraidah; Campbell, Lisa J; Goff, Lindsey K; Jones, Margaret; Marafioti, Teresa; Cordell, Jacqueline; Clear, Andrew J; Lister, T Andrew; Mason, David Y; Lee, Abigail M

    2009-03-01

    The t(14;18)(q32;q21) chromosomal translocation induces BCL2 protein overexpression in most follicular lymphomas. However the expression of BCL2 is not always homogeneous and may demonstrate a variable degree of heterogeneity. This study analysed BCL2 protein expression pattern in 33 cases of t(14;18)-positive follicular lymphomas using antibodies against two different epitopes (i.e. the widely used antibody BCL2/124 and an alternative antibody E17). 16/33 (49%) cases demonstrated strong BCL2 expression. In 10/33 (30%) cases, BCL2 expression was heterogeneous and in some of these, its loss appeared to be correlated with cell proliferation, as indicated by Ki67 expression. Double immunofluorescence labelling confirmed an inverse BCL2/Ki67 relationship, where in 24/28 (86%) cases cellular expression of BCL2 and Ki67 was mutually exclusive. In addition, seven BCL2 'pseudo-negative' cases were identified in which immunostaining was negative with antibody BCL2/124, but positive with antibody E17. Genomic DNA sequencing of these 'pseudo-negative' cases demonstrated eleven mutations in four cases and nine of these were missense mutations. It can be concluded that in follicular lymphomas, despite carrying the t(14;18) translocations, BCL2 protein expression may be heterogeneous and loss of BCL2 could be related to cell proliferation. Secondly, mutations in translocated BCL2 genes appear to be common and may cause BCL2 pseudo-negative immunostaining. PMID:19120369

  6. Correlations among antral follicular echotexture, apoptosis and expression of key steroidogenic enzymes in sheep

    PubMed Central

    VANDUZER, Taylor; DUGGAVATHI, Raj; MURAWSKI, Maciej; ZIEBA, Dorota A.; SROKA, Patrycja; BARTLEWSKI, Pawel M.

    2014-01-01

    Nineteen cycling ewes underwent transrectal ultrasonography of ovaries followed by ovariectomies during the growth phase of the first follicular wave of the interovulatory interval or the proestrus/estrus phase of the cycle. Quantitative ultrasonographic characteristics of the antrum and follicular wall in a total of forty-three ovine antral follicles were examined for correlations with the protein expression of three steroidogenic enzymes (cytochrome P450 17α-hydroxylase, CYP17; cytochrome P450 aromatase, CYP19; and 3β-hydroxysteroid dehydrogenase, 3β-HSD) determined by densitometric analysis of immunohistochemical slides, follicular dimensions, granulosa layer thickness and the percentage of apoptotic granulosa cells. Significant correlations were found between echotextural attributes of ovine antral follicles and the percentage of apoptotic granulosa cells, CYP17 expression (theca), CYP19 expression (granulosa) and 3β-HSD expression (theca cells). Computer-aided analyses of ultrasonographic images can be beneficial to the development of assisted reproductive technologies and diagnosis of hormonal imbalances without the need for ovarian biopsies or hormone assays. PMID:25109269

  7. Somatic mutation profiling of follicular thyroid cancer by next generation sequencing.

    PubMed

    Swierniak, Michal; Pfeifer, Aleksandra; Stokowy, Tomasz; Rusinek, Dagmara; Chekan, Mykola; Lange, Dariusz; Krajewska, Jolanta; Oczko-Wojciechowska, Małgorzata; Czarniecka, Agnieszka; Jarzab, Michal; Jarzab, Barbara; Wojtas, Bartosz

    2016-09-15

    The molecular etiology of follicular thyroid tumors is largely unknown, rendering the diagnostics of these tumors challenging. The somatic alterations present in these tumors apart from RAS gene mutations and PAX8/PPARG translocations are not well described. To evaluate the profile of somatic alteration in follicular thyroid tumors, a total of 82 thyroid tissue samples derived from 48 patients were subjected to targeted Illumina HiSeq next generation sequencing of 372 cancer-related genes. New somatic alterations were identified in oncogenes (MDM2, FLI1), transcription factors and repressors (MITF, FLI1, ZNF331), epigenetic enzymes (KMT2A, NSD1, NCOA1, NCOA2), and protein kinases (JAK3, CHEK2, ALK). Single nucleotide and large structural variants were most and least frequently identified, respectively. A novel translocation in DERL/COX6C was detected. Many somatic alterations in non-coding gene regions with high penetrance were observed. Thus, follicular thyroid tumor somatic alterations exhibit complex patterns. Most tumors contained distinct somatic alterations, suggesting previously unreported heterogeneity. PMID:27283500

  8. Follicular and scarring disorders in skin of color: presentation and management.

    PubMed

    Madu, Pamela; Kundu, Roopal V

    2014-08-01

    Skin of color, also known as ethnic skin, is described as skin of individuals of African, Asian, Hispanic, Native-American, Middle Eastern, and Pacific Island backgrounds. Differences in hair morphology, hair grooming, cultural practices, and susceptibility to keloid scarring exist within these populations and have been implicated in hair, scalp, and skin disorders. Acne keloidalis (AK), central centrifugal cicatricial alopecia (CCCA), dissecting cellulitis of the scalp (DCS), pseudofolliculitis barbae (PFB), traction alopecia (TA), and keloids are the most prevalent follicular and scarring disorders in skin of color. They have been associated with disfigurement, permanent hair loss, emotional distress, and decreased quality of life. Hair grooming practices, such as the use of chemical relaxers, heat straightening, and tight braiding and weaving can cause scalp irritation and follicular damage and are linked to the pathogenesis of some of these conditions. Consequently, patient education and behavior modifications are integral to the prevention and management of these disorders. Scarring disorders are also of concern in ethnic populations. Keloid scarring is more prevalent in individuals of African, Asian, and Hispanic descent. The scarring alopecia CCCA is almost exclusively seen in patients of African descent. Therapeutic regimens such as intralesional corticosteroids, surgical excision, and laser therapy can be effective for these follicular and scarring disorders, but carry a risk of dyspigmentation and keloid scarring. Ethnic skin and hair may present unique challenges to the clinician, and knowledge of these differences is essential to providing quality care.

  9. Thyroid Follicular Carcinoma in a Fourteen-year-old Girl with Graves’ Disease

    PubMed Central

    Kojima-Ishii, Kanako; Ihara, Kenji; Ohkubo, Kazuhiro; Matsuo, Terumichi; Toda, Naoko; Yamashita, Hiroyuki; Kono, Shinji; Hara, Toshiro

    2014-01-01

    Abstract Here we present the case of a 14-yr-old girl who developed thyroid follicular carcinoma accompanied by Graves’ disease. She was diagnosed with Graves’ disease at 10 yr of age and soon achieved a euthyroid state after starting treatment. When she was 13 yr of age, her hyperthyroidism and goiter worsened despite medical therapy. Multiple nodules were found in her enlarged thyroid gland by ultrasonography. Her serum Tg level seemed within the normal range. She underwent near-total thyroidectomy for control of thyroid function. Histopathological study demonstrated that multiple oxyphilic follicular neoplasms were surrounded by the thyroid tissue compatible with Graves’ disease. Capsular invasion was identified in one of the nodules, and thus the histological diagnosis was minimally invasive follicular carcinoma. She did not have signs suggesting metastasis, and has had no relapse for 18 mo after the operation. Although some previous studies showed a high prevalence of thyroid cancer with an aggressive nature in adult patients with Graves’ disease, few reports about thyroid cancer accompanied by Graves’ disease are available in children. The present case, however, suggests that careful investigation is needed when we detect thyroid nodules or progressive thyroid enlargement, especially in children with Graves’ disease. PMID:24790388

  10. Granulosa Cell Apoptosis Induced by a Novel FSH Binding Inhibitory Peptide From Human Ovarian Follicular Fluid

    PubMed Central

    Chitnis, Swati S.; Navlakhe, Rajshri M.; Shinde, Gayatri C.; Barve, Sharmila J.; D'Souza, Serena; Mahale, Smita D.; Nandedkar, Tarala D.

    2008-01-01

    Pituitary gonadotropins, follicle-stimulating hormone and luteinizing hormone, are the key regulators of ovarian folliculogenesis; these are known to be directly or indirectly modulated by many intraovarian factors. Our group has identified and studied one such novel peptide from human ovarian follicular fluid. Its partial N-terminal eight amino acid sequence has been deduced, referred to as octapeptide (OP). OP induces follicular atresia in mice and interferes with normal ovarian function in non-human primates, this action being similar to the native peptide. Thus, in this study, an attempt has been made to elucidate the mechanism of action of the synthetic OP by studying the pathway of follicular atresia in mouse ovary. Changes in granulosa cells were studied using various apoptotic markers by flow cytometry and immunohistochemistry. An increase in apoptotic cell population in atretic- and peptide-treated groups was observed compared with normal controls. Interestingly, both these groups exhibited differences in the apoptotic pathway. Results showed that the mitochondrial pathway was predominant in the atretic group, whereas the Fas-FasL pathway was predominant in the peptide-treated groups. The ultrastructural study also showed apoptotic changes in the OP-treated and atretic groups; the pattern of apoptosis differed at the subcellular level. (J Histochem Cytochem 56:961–968, 2008) PMID:18645207

  11. [Combination therapy with rituximab and cladribine for patients with follicular lymphoma].

    PubMed

    Kobayashi, Yutaka; Murotani, Yoshihide; Sawai, Nana; Akaogi, Teruaki; Sako, Masami; Hayashi, Hideo; Matsumoto, Yosuke; Kuroda, Junya; Nomura, Kenichi; Horiike, Shigeo; Shimazaki, Chihiro; Kimura, Shinya; Yoshikawa, Toshikazu; Taniwaki, Masafumi

    2007-10-01

    Treatment strategies for follicular lymphoma have not been established. We report the outcome after combination therapy with rituximab and cladribine (RC) for 8 patients with follicular lymphoma treated between January 2005 and December 2006 in our hospitals. Median patient age was 57 (range 42 approximately 73) years. There were 4 males and 4 females. Only 1 patient had refractory disease, while the others had untreated disease. On the follicular lymphoma international prognostic index, 4 patients were in the low-risk group, 3 in the intermediate-risk group and 1 in the high-risk group. The median follow-up period was 36 (range 22 approximately 90) weeks. The RC protocol consisted of intravenous rituximab at a dose of 375 mg/m (2) on day 1 and cladribine at a dose of 0.1 mg /kg per day for 2-hours on day 1 through 5. The median number of RC courses was 5 (range 3 approximately 8). The median interval between the 2 courses was 7 (range 3 approximately 26) weeks. The overall response rate was 87.5%. Grade 3 neutropenia was observed in 50% patients, although G-CSF was not needed. There was no apparent thrombocytopenia or anemia. Herpes zoster was observed after treatment in 1 patient. RC is considered highly effective and well tolerated.

  12. Contamination of human ovarian follicular fluid and serum by chlorinated organic compounds in three Canadian cities.

    PubMed Central

    Jarrell, J F; Villeneuve, D; Franklin, C; Bartlett, S; Wrixon, W; Kohut, J; Zouves, C G

    1993-01-01

    OBJECTIVES: To determine the extent of contamination of ovarian follicular fluid and serum samples in women undergoing in-vitro fertilization and to study the effect of the contaminants on reproductive outcome. DESIGN: Inception cohort study. PATIENTS: Seventy-four women undergoing in-vitro fertilization at three regional clinics in Halifax, Hamilton, Ont., and Vancouver. MAIN OUTCOME MEASURES: Follicular fluid and serum levels of contaminants, cleavage rates and time to cleavage of first egg. RESULTS: Five chlorinated organic chemicals were frequently found in the two types of samples: alpha-chlordane (ALCH), dichlorochlorophenylethylene (DDE), heptachloroepoxide-oxychlordane (OXCH), hexachlorobenzene (HCB) and polychlorinated biphenyl (PCB). The levels were generally low. Regional differences between the three clinics were present. Samples from the Halifax clinic had the lowest frequency and level of contamination. The source of drinking water (well, bottled or municipal) was an important confounder. The concentrations of the five contaminants did not affect the cleavage rate or the time to cleavage of the first egg. CONCLUSION: Trace amounts of toxic and persistent chlorinated organic chemicals found in the follicular fluid of Canadian women undergoing in-vitro fertilization did not seem to have any adverse biologic effect on the rate of fertilization and the time to cleavage. Reasons for regional differences in the concentrations of contaminants require further study. PMID:8462054

  13. Transpresentation of interleukin-15 by IL-15/IL-15Rα mRNA-engineered human dendritic cells boosts antitumoral natural killer cell activity

    PubMed Central

    Van den Bergh, Johan; Willemen, Yannick; Lion, Eva; Van Acker, Heleen; De Reu, Hans; Anguille, Sébastien; Goossens, Herman; Berneman, Zwi

    2015-01-01

    In cancer immunotherapy, the use of dendritic cell (DC)-based vaccination strategies can improve overall survival, but until now durable clinical responses remain scarce. To date, DC vaccines are designed primarily to induce effective T-cell responses, ignoring the antitumor activity potential of natural killer (NK) cells. Aiming to further improve current DC vaccination outcome, we engineered monocyte-derived DC to produce interleukin (IL)-15 and/or IL-15 receptor alpha (IL-15Rα) using mRNA electroporation. The addition of IL-15Rα to the protocol, enabling IL-15 transpresentation to neighboring NK cells, resulted in significantly better NK-cell activation compared to IL-15 alone. Next to upregulation of NK-cell membrane activation markers, IL-15 transpresentation resulted in increased NK-cell secretion of IFN-γ, granzyme B and perforin. Moreover, IL-15-transpresenting DC/NK cell cocultures from both healthy donors and acute myeloid leukemia (AML) patients in remission showed markedly enhanced cytotoxic activity against NK cell sensitive and resistant tumor cells. Blocking IL-15 transpresentation abrogated NK cell-mediated cytotoxicity against tumor cells, pointing to a pivotal role of IL-15 transpresentation by IL-15Rα to exert its NK cell-activating effects. In conclusion, we report an attractive approach to improve antitumoral NK-cell activity in DC-based vaccine strategies through the use of IL-15/IL-15Rα mRNA-engineered designer DC. PMID:26675759

  14. Dendritic cells mediate the induction of polyfunctional human IL17-producing cells (Th17-1 cells) enriched in the bone marrow of patients with myeloma

    PubMed Central

    Barbuto, Scott; Matthews, Phillip; Kukreja, Anjli; Mazumder, Amitabha; Vesole, David; Jagannath, Sundar; Dhodapkar, Madhav V.

    2008-01-01

    IL17-producing (Th17) cells are a distinct lineage of T helper cells that regulate immunity and inflammation. The role of antigen-presenting cells in the induction of Th17 cells in humans remains to be fully defined. Here, we show that human dendritic cells (DCs) are efficient inducers of Th17 cells in culture, including antigen-specific Th17 cells. Although most freshly isolated circulating human Th17 cells secrete IL17 alone or with IL2, those induced by DCs are polyfunctional and coexpress IL17 and IFNγ (Th17-1 cells). The capacity of DCs to expand Th17-1 cells is enhanced upon DC maturation, and mature DCs are superior to monocytes for the expansion of autologous Th17 cells. In myeloma, where tumors are infiltrated by DCs, Th17 cells are enriched in the bone marrow relative to circulation. Bone marrow from patients with myeloma contains a higher proportion of Th17-1 cells compared with the marrow in preneoplastic gammopathy (monoclonal gammopathy of undetermined significance [MGUS]). Uptake of apoptotic but not necrotic myeloma tumor cells by DCs leads to enhanced induction of Th17-1 cells. These data demonstrate the capacity of DCs to induce expansion of polyfunctional IL17-producing T cells in humans, and suggest a role for DCs in the enrichment of Th17-1 cells in the tumor bed. PMID:18669891

  15. Immunization with HIV Gag targeted to dendritic cells followed by recombinant New York vaccinia virus induces robust T-cell immunity in nonhuman primates

    PubMed Central

    Flynn, Barbara J.; Kastenmüller, Kathrin; Wille-Reece, Ulrike; Tomaras, Georgia D.; Alam, Munir; Lindsay, Ross W.; Salazar, Andres M.; Perdiguero, Beatriz; Gomez, Carmen E.; Wagner, Ralf; Esteban, Mariano; Park, Chae G.; Trumpfheller, Christine; Keler, Tibor; Pantaleo, Giuseppe; Steinman, Ralph M.; Seder, Robert

    2011-01-01

    Protein vaccines, if rendered immunogenic, would facilitate vaccine development against HIV and other pathogens. We compared in nonhuman primates (NHPs) immune responses to HIV Gag p24 within 3G9 antibody to DEC205 (“DEC-HIV Gag p24”), an uptake receptor on dendritic cells, to nontargeted protein, with or without poly ICLC, a synthetic double stranded RNA, as adjuvant. Priming s.c. with 60 μg of both HIV Gag p24 vaccines elicited potent CD4+ T cells secreting IL-2, IFN-γ, and TNF-α, which also proliferated. The responses increased with each of three immunizations and recognized multiple Gag peptides. DEC-HIV Gag p24 showed better cross-priming for CD8+ T cells, whereas the avidity of anti-Gag antibodies was ∼10-fold higher with nontargeted Gag 24 protein. For both protein vaccines, poly ICLC was essential for T- and B-cell immunity. To determine whether adaptive responses could be further enhanced, animals were boosted with New York vaccinia virus (NYVAC)-HIV Gag/Pol/Nef. Gag-specific CD4+ and CD8+ T-cell responses increased markedly after priming with both protein vaccines and poly ICLC. These data reveal qualitative differences in antibody and T-cell responses to DEC-HIV Gag p24 and Gag p24 protein and show that prime boost with protein and adjuvant followed by NYVAC elicits potent cellular immunity. PMID:21467219

  16. Interferon gamma induces retrograde dendritic retraction and inhibits synapse formation.

    PubMed

    Kim, In-Jung; Beck, Hiroko Nagasawa; Lein, Pamela J; Higgins, Dennis

    2002-06-01

    The expression of interferon gamma (IFNgamma) increases after neural injury, and it is sustained in chronic inflammatory conditions such as multiple sclerosis and infection with human immunodeficiency virus. To understand how exposure to this proinflammatory cytokine might affect neural function, we examined its effects on cultures of neurons derived from the central and peripheral nervous systems. IFNgamma inhibits initial dendritic outgrowth in cultures of embryonic rat sympathetic and hippocampal neurons, and this inhibitory effect on process growth is associated with a decrease in the rate of synapse formation. In addition, in older cultures of sympathetic neurons, IFNgamma also selectively induces retraction of existing dendrites, ultimately leading to an 88% decrease in the size of the arbor. Dendritic retraction induced by IFNgamma represents a specific cellular response because it occurs without affecting axonal outgrowth or cell survival, and it is not observed with tumor necrosis factor alpha or other inflammatory cytokines. IFNgamma-induced dendritic retraction is associated with the phosphorylation and nuclear translocation of signal transducer and activator of transcription 1 (STAT1), and expression of a dominant-negative STAT1 construct attenuates the inhibitory effect of IFNgamma. Moreover, retrograde dendritic retraction is observed when distal axons are selectively exposed to IFNgamma. These data imply that IFNgamma-mediated STAT1 activation induces both dendritic atrophy and synaptic loss and that this occurs both at the sites of IFNgamma release and at remote loci. Regressive actions of IFNgamma on dendrites may contribute to the neuropathology of inflammatory diseases.

  17. Axin Regulates Dendritic Spine Morphogenesis through Cdc42-Dependent Signaling

    PubMed Central

    Chen, Yu; Liang, Zhuoyi; Fei, Erkang; Chen, Yuewen; Zhou, Xiaopu; Fang, Weiqun; Fu, Wing-Yu; Fu, Amy K. Y.; Ip, Nancy Y.

    2015-01-01

    During development, scaffold proteins serve as important platforms for orchestrating signaling complexes to transduce extracellular stimuli into intracellular responses that regulate dendritic spine morphology and function. Axin (“axis inhibitor”) is a key scaffold protein in canonical Wnt signaling that interacts with specific synaptic proteins. However, the cellular functions of these protein–protein interactions in dendritic spine morphology and synaptic regulation are unclear. Here, we report that Axin protein is enriched in synaptic fractions, colocalizes with the postsynaptic marker PSD-95 in cultured hippocampal neurons, and interacts with a signaling protein Ca2+/calmodulin-dependent protein kinase II (CaMKII) in synaptosomal fractions. Axin depletion by shRNA in cultured neurons or intact hippocampal CA1 regions significantly reduced dendritic spine density. Intriguingly, the defective dendritic spine morphogenesis in Axin-knockdown neurons could be restored by overexpression of the small Rho-GTPase Cdc42, whose activity is regulated by CaMKII. Moreover, pharmacological stabilization of Axin resulted in increased dendritic spine number and spontaneous neurotransmission, while Axin stabilization in hippocampal neurons reduced the elimination of dendritic spines. Taken together, our findings suggest that Axin promotes dendritic spine stabilization through Cdc42-dependent cytoskeletal reorganization. PMID:26204446

  18. A multiphase solute diffusion model for dendritic alloy solidification

    SciTech Connect

    Wang, C.Y.; Beckermann, C.

    1993-12-01

    A solute diffusion model, aimed at predicting microstructure formation in metal castings, is proposed for dendritic solidification of alloys. The model accounts for the different length scales existing in a dendritic structure. This is accomplished by utilizing a multiphase approach, in which not only the various physical phases but also phases associated with different length scales are considered separately. The macroscopic conservation equations are derived for each phase using the volume averaging technique, with constitutive relations developed for the interfacial transfer terms. It is shown that the multiphase model can rigorously incorporate the growth of dendrite tips and coarsening of dendrite arms. In addition, the distinction of different length scales enables the inclusion of realistic descriptions of the dendrite topology and relations to key metallurgical parameters. Another novel aspect of the model is that a single set of conservation equations for solute diffusion is developed for both equiaxed and columnar dendritic solidification. Finally, illustrative calculations for equiaxed, columnar, and mixed columnar-equiaxed solidification are carried out to provide quantitative comparisons with previous studies, and a variety of fundamental phenomena such as recalescence, dendrite tip undercooling, and columnar-to-equiaxed transition (CET) are predicted.

  19. Dendritic mitochondria reach stable positions during circuit development

    PubMed Central

    Faits, Michelle C; Zhang, Chunmeng; Soto, Florentina; Kerschensteiner, Daniel

    2016-01-01

    Mitochondria move throughout neuronal dendrites and localize to sites of energy demand. The prevailing view of dendritic mitochondria as highly motile organelles whose distribution is continually adjusted by neuronal activity via Ca2+-dependent arrests is based on observations in cultured neurons exposed to artificial stimuli. Here, we analyze the movements of mitochondria in ganglion cell dendrites in the intact retina. We find that whereas during development 30% of mitochondria are motile at any time, as dendrites mature, mitochondria all but stop moving and localize stably to synapses and branch points. Neither spontaneous nor sensory-evoked activity and Ca2+ transients alter motility of dendritic mitochondria; and pathological hyperactivity in a mouse model of retinal degeneration elevates rather than reduces motility. Thus, our findings indicate that dendritic mitochondria reach stable positions during a critical developmental period of high motility, and challenge current views about the role of activity in regulating mitochondrial transport in dendrites. DOI: http://dx.doi.org/10.7554/eLife.11583.001 PMID:26742087

  20. Accelerators, Brakes, and Gears of Actin Dynamics in Dendritic Spines

    PubMed Central

    Pontrello, Crystal G.; Ethell, Iryna M.

    2010-01-01

    Dendritic spines are actin-rich structures that accommodate the postsynaptic sites of most excitatory synapses in the brain. Although dendritic spines form and mature as synaptic connections develop, they remain plastic even in the adult brain, where they can rapidly grow, change, or collapse in response to normal physiological changes in synaptic activity that underlie learning and memory. Pathological stimuli can adversely affect dendritic spine shape and number, and this is seen in neurodegenerative disorders and some forms of mental retardation and autism as well. Many of the molecular signals that control these changes in dendritic spines act through the regulation of filamentous actin (F-actin), some through direct interaction with actin, and others via downstream effectors. For example, cortactin, cofilin, and gelsolin are actin-binding proteins that directly regulate actin dynamics in dendritic spines. Activities of these proteins are precisely regulated by intracellular signaling events that control their phosphorylation state and localization. In this review, we discuss how actin-regulating proteins maintain the balance between F-actin assembly and disassembly that is needed to stabilize mature dendritic spines, and how changes in their activities may lead to rapid remodeling of dendritic spines. PMID:20463852

  1. Input transformation by dendritic spines of pyramidal neurons

    PubMed Central

    Araya, Roberto

    2014-01-01

    In the mammalian brain, most inputs received by a neuron are formed on the dendritic tree. In the neocortex, the dendrites of pyramidal neurons are covered by thousands of tiny protrusions known as dendritic spines, which are the major recipient sites for excitatory synaptic information in the brain. Their peculiar morphology, with a small head connected to the dendritic shaft by a slender neck, has inspired decades of theoretical and more recently experimental work in an attempt to understand how excitatory synaptic inputs are processed, stored and integrated in pyramidal neurons. Advances in electrophysiological, optical and genetic tools are now enabling us to unravel the biophysical and molecular mechanisms controlling spine function in health and disease. Here I highlight relevant findings, challenges and hypotheses on spine function, with an emphasis on the electrical properties of spines and on how these affect the storage and integration of excitatory synaptic inputs in pyramidal neurons. In an attempt to make sense of the published data, I propose that the raison d'etre for dendritic spines lies in their ability to undergo activity-dependent structural and molecular changes that can modify synaptic strength, and hence alter the gain of the linearly integrated sub-threshold depolarizations in pyramidal neuron dendrites before the generation of a dendritic spike. PMID:25520626

  2. Input transformation by dendritic spines of pyramidal neurons.

    PubMed

    Araya, Roberto

    2014-01-01

    In the mammalian brain, most inputs received by a neuron are formed on the dendritic tree. In the neocortex, the dendrites of pyramidal neurons are covered by thousands of tiny protrusions known as dendritic spines, which are the major recipient sites for excitatory synaptic information in the brain. Their peculiar morphology, with a small head connected to the dendritic shaft by a slender neck, has inspired decades of theoretical and more recently experimental work in an attempt to understand how excitatory synaptic inputs are processed, stored and integrated in pyramidal neurons. Advances in electrophysiological, optical and genetic tools are now enabling us to unravel the biophysical and molecular mechanisms controlling spine function in health and disease. Here I highlight relevant findings, challenges and hypotheses on spine function, with an emphasis on the electrical properties of spines and on how these affect the storage and integration of excitatory synaptic inputs in pyramidal neurons. In an attempt to make sense of the published data, I propose that the raison d'etre for dendritic spines lies in their ability to undergo activity-dependent structural and molecular changes that can modify synaptic strength, and hence alter the gain of the linearly integrated sub-threshold depolarizations in pyramidal neuron dendrites before the generation of a dendritic spike.

  3. A critical role of T follicular helper cells in human mucosal anti-influenza response that can be enhanced by immunological adjuvant CpG-DNA.

    PubMed

    Aljurayyan, A N; Sharma, R; Upile, N; Beer, H; Vaughan, C; Xie, C; Achar, P; Ahmed, M S; McNamara, P S; Gordon, S B; Zhang, Q

    2016-08-01

    T Follicular helper cells (TFH) are considered critical for B cell antibody response, and recent efforts have focused on promoting TFH in order to enhance vaccine efficacy. We studied the frequency and function of TFH in nasopharynx-associated lymphoid tissues (NALT) from children and adults, and its role in anti-influenza antibody response following stimulation by a live-attenuated influenza vaccine (LAIV) or an inactivated seasonal virus antigen (sH1N1). We further studied whether CpG-DNA promotes TFH and by which enhances anti-influenza response. We showed NALT from children aged 1.5-10 years contained abundant TFH, suggesting efficient priming of TFH during early childhood. Stimulation by LAIV induced a marked increase in TFH that correlated with a strong production of anti-hemagglutinin (HA) IgA/IgG/IgM antibodies in tonsillar cells. Stimulation by the inactivated sH1N1 antigen induced a small increase in TFH which was markedly enhanced by CpG-DNA, accompanied by enhanced anti-HA antibody responses. In B cell co-culture experiment, anti-HA responses were only seen in the presence of TFH, and addition of plasmacytoid dendritic cell to TFH-B cell co-culture enhanced the TFH-mediated antibody production following CpG-DNA and sH1N1 antigen stimulation. Induction of TFH differentiation from naïve T cells was also shown following the stimulation. Our results support a critical role of TFH in human mucosal anti-influenza antibody response. Use of an adjuvant such as CpG-DNA that has the capacity to promote TFH by which to enhance antigen-induced antibody responses in NALT tissue may have important implications for future vaccination strategies against respiratory pathogens. PMID:27247060

  4. Fractal structures of dendrites in GaSe crystals

    NASA Astrophysics Data System (ADS)

    Kolesnikov, N. N.; Borisenko, E. B.; Borisenko, D. N.; Bozhko, S. I.

    2008-07-01

    Solidification of melts at substantial supercooling is associated with instability on the growth front. This causes growth of dendrites, which form as a branched tree in a crystal. In the layered melt-grown GaSe crystals dendrites are observed, if growth rates are rather high [N.N. Kolesnikov, E.B. Borisenko, D.N. Borisenko, V.K. Gartman, Influence of growth conditions on microstructure and properties of GaSe crystals, J. Crystal Growth 300 (2) (2007) 294-298]. Models based on solution of the thermal diffusion problem are traditionally used to describe dendrite growth. Solution of this problem requires information about several physical parameters, such as diffusion coefficient, heat conductivity coefficient and supercooling at the solid/liquid interface. The study of scale invariance of dendrites formed in a crystal provides a new approach to solution of the dynamic growth problem. The calculated fractal dimensionality of the experimentally observed dendrites in GaSe crystals is D=1.7. It coincides with dimensionality of the clusters obtained through computer simulation in terms of the model of diffusion-limited aggregation (DLA). This result provides a new approach to description of the dynamics of dendrite growth. We have shown that the dendrite growth mechanism in the layered semiconductor crystals can be described by a two-dimensional DLA model. It is shown that probabilistic simulation can be used to show the development of a dendrite in any material. In contrast to the classical theories of dendrite growth, this approach does not require information on physical parameters.

  5. Melanin-producing dendritic cells and histogenesis of malignant melanoma.

    PubMed

    Paul, E; Illig, L

    1976-12-15

    In a total of 70 malignant melanomas we searched for dendritic-branched fluorescent pigment cells. Hereby we found that dendritic-branched tumor cells are especially characteristic in cases of lentigo maligna. In the flat parts of these lesions, these cells are the predominant cell type. Dendrites in the pseudonests or nodular parts of lentigo maligna can only seldom be detected. The prevailing cell type in superficial spreading melanoma and in primary nodular melanoma is the round or oval unbranched tumor cell. In some cases of nodular melanoma, cells with short dendrites could be seen. In superficial spreading melanoma, dendritic tumor cells could be observed particularly in such tumor parts, in which the malignant cells were scattered between the keratinocytes. Melanocytes can evidently produce dendrites between cells of the sebaceous gland. In the marginal parts or in parts of regression of some superficial spreading melanomas, a great area of dendritic tumor cells could also be detected in the basal parts of the epidermis. Altogether, however, in superficial spreading melanoma and in nodular melanoma they occur only rarely. Dendritic-branched cells are also visible in lymph-node metastases of SSM and NM. The fact that the dendritic tumor cells can be observed in all 3 types of tumors (according to Clark and coworkers) gives a rise to a new discussion of the dualistic theory of melanoma-histogenesis of Mishima. Although this theory could not be disproved, up to now on the basis of the present results, an unitarian development of all types of mnelanoma from melanocytes seems to be possible.

  6. Regulatory Dendritic Cells for Immunotherapy in Immunologic Diseases

    PubMed Central

    Gordon, John R.; Ma, Yanna; Churchman, Laura; Gordon, Sara A.; Dawicki, Wojciech

    2013-01-01

    We recognize well the abilities of dendritic cells to activate effector T cell (Teff cell) responses to an array of antigens and think of these cells in this context as pre-eminent antigen-presenting cells, but dendritic cells are also critical to the induction of immunologic tolerance. Herein, we review our knowledge on the different kinds of tolerogenic or regulatory dendritic cells that are present or can be induced in experimental settings and humans, how they operate, and the diseases in which they are effective, from allergic to autoimmune diseases and transplant tolerance. The primary conclusions that arise from these cumulative studies clearly indicate that the agent(s) used to induce the tolerogenic phenotype and the status of the dendritic cell at the time of induction influence not only the phenotype of the dendritic cell, but also that of the regulatory T cell responses that they in turn mobilize. For example, while many, if not most, types of induced regulatory dendritic cells lead CD4+ naïve or Teff cells to adopt a CD25+Foxp3+ Treg phenotype, exposure of Langerhans cells or dermal dendritic cells to vitamin D leads in one case to the downstream induction of CD25+Foxp3+ regulatory T cell responses, while in the other to Foxp3− type 1 regulatory T cells (Tr1) responses. Similarly, exposure of human immature versus semi-mature dendritic cells to IL-10 leads to distinct regulatory T cell outcomes. Thus, it should be possible to shape our dendritic cell immunotherapy approaches for selective induction of different types of T cell tolerance or to simultaneously induce multiple types of regulatory T cell responses. This may prove to be an important option as we target diseases in different anatomic compartments or with divergent pathologies in the clinic. Finally, we provide an overview of the use and potential use of these cells clinically, highlighting their potential as tools in an array of settings. PMID:24550907

  7. Quantifying the Number of Discriminable Coincident Dendritic Input Patterns through Dendritic Tree Morphology

    PubMed Central

    Zippo, Antonio G.; Biella, Gabriele E. M.

    2015-01-01

    Current developments in neuronal physiology are unveiling novel roles for dendrites. Experiments have shown mechanisms of non-linear synaptic NMDA dependent activations, able to discriminate input patterns through the waveforms of the excitatory postsynaptic potentials. Contextually, the synaptic clustering of inputs is the principal cellular strategy to separate groups of common correlated inputs. Dendritic branches appear to work as independent discriminating units of inputs potentially reflecting an extraordinary repertoire of pattern memories. However, it is unclear how these observations could impact our comprehension of the structural correlates of memory at the cellular level. This work investigates the discrimination capabilities of neurons through computational biophysical models to extract a predicting law for the dendritic input discrimination capability (M). By this rule we compared neurons from a neuron reconstruction repository (neuromorpho.org). Comparisons showed that primate neurons were not supported by an equivalent M preeminence and that M is not uniformly distributed among neuron types. Remarkably, neocortical neurons had substantially less memory capacity in comparison to those from non-cortical regions. In conclusion, the proposed rule predicts the inherent neuronal spatial memory gathering potentially relevant anatomical and evolutionary considerations about the brain cytoarchitecture. PMID:26100354

  8. Fundamentals of dendritic solidification. I - Steady-state tip growth. II - Development of sidebranch structure

    NASA Technical Reports Server (NTRS)

    Huang, S.-C.; Glicksman, M. E.

    1981-01-01

    Systematic measurements of dendrite tip radius and growth velocity in succinonitrile reveal that consideration of dendrite tip stability should be incorporated into the heat transfer theory to determine the steady-state dendritic growth condition. The dendritic stability criterion measured is 2 alpha d0/VR squared = 0.0195, where V is the dendritic growth velocity, R is the dendritic tip radius, alpha is the liquid thermal diffusivity, and d0 is a capillary length defined in the text. Several dendritic stability models are reviewed and discussed in comparison to the present experimental results.

  9. Role of Dendritic Cells in Immune Dysfunction

    NASA Technical Reports Server (NTRS)

    Savary, Cherylyn A.

    1998-01-01

    The specific aims of the project were: (1) Application of the NASA bioreactor to enhance cytokine-regulated proliferation and maturation of dendritic cells (DC). (2) Compare the frequency and function of DC in normal donors and immunocompromised cancer patients. (3) Analyze the effectiveness of cytokine therapy and DC-assisted immunotherapy (using bioreactor-expanded DC) in a murine model of experimental fungal disease. Our investigations have provided new insight into DC immunobiology and have led to the development of methodology to evaluate DC in blood of normal donors and patients. Information gained from these studies has broadened our understanding of possible mechanisms involved in the immune dysfunction of space travelers and earth-bound cancer patients, and could contribute to the design of novel therapies to restore/preserve immunity in these individuals. Several new avenues of investigation were also revealed. The results of studies completed during Round 2 are summarized.

  10. Unsteady growth of ammonium chloride dendrites

    NASA Astrophysics Data System (ADS)

    Martyushev, L. M.; Terentiev, P. S.; Soboleva, A. S.

    2016-02-01

    Growth of ammonium chloride dendrites from aqueous solution is experimentally investigated. The growth rate υ and the radius ρ of curvature of branches are measured as a function of the relative supersaturation Δ for steady and unsteady growth conditions. It is shown that the experimental results are quantitatively described by the dependences ρ=a/Δ+b, υ=сΔ2, where the factors for primary branches are a=(1.3±0.2)·10-7 m, b=(2.5±0.4)·10-7 m, and c=(2.2±0.3)·10-4 m/s. The factor c is found to be approximately 7 times smaller for the side branches than that for the primary branches.

  11. Platinum dendritic nanoparticles with magnetic behavior

    SciTech Connect

    Li, Wenxian; Sun, Ziqi; Nevirkovets, Ivan P.; Dou, Shi-Xue; Tian, Dongliang

    2014-07-21

    Magnetic nanoparticles have attracted increasing attention for biomedical applications in magnetic resonance imaging, high frequency magnetic field hyperthermia therapies, and magnetic-field-gradient-targeted drug delivery. In this study, three-dimensional (3D) platinum nanostructures with large surface area that features magnetic behavior have been demonstrated. The well-developed 3D nanodendrites consist of plentiful interconnected nano-arms ∼4 nm in size. The magnetic behavior of the 3D dendritic Pt nanoparticles is contributed by the localization of surface electrons due to strongly bonded oxygen/Pluronic F127 and the local magnetic moment induced by oxygen vacancies on the neighboring Pt and O atoms. The magnetization of the nanoparticles exhibits a mixed paramagnetic and ferromagnetic state, originating from the core and surface, respectively. The 3D nanodendrite structure is suitable for surface modification and high amounts of drug loading if the transition temperature was enhanced to room temperature properly.

  12. Free dendritic growth in viscous melts - Cyclohexanol

    NASA Technical Reports Server (NTRS)

    Singh, N. B.; Glicksman, M. E.

    1989-01-01

    Experiments were carried out to measure the growth speed, V, and dendritic tip radius, R, of highly purified cyclohexanol. The data show that VR-squared = constant over the entire experimentally observed supercooling range, Delta T is between 0.1 and 1 K. The stability parameter estimated from this result indicates that sigma(asterisk) = 0.027, a value in good agreement with the values of sigma(asterisk) found for the cubic plastic crystals succinonitrile pivalic acid. Cyclohexanol differs from other carefully measured plastic crystals in that the viscosity of its melt at the melting point is about 20 times higher, so gravity-induced convection remains weak even at small supercoolings.

  13. Macrophages, dendritic cells, and regression of atherosclerosis.

    PubMed

    Feig, Jonathan E; Feig, Jessica L

    2012-01-01

    Atherosclerosis is the number one cause of death in the Western world. It results from the interaction between modified lipoproteins and cells such as macrophages, dendritic cells (DCs), T cells, and other cellular elements present in the arterial wall. This inflammatory process can ultimately lead to the development of complex lesions, or plaques, that protrude into the arterial lumen. Ultimately, plaque rupture and thrombosis can occur leading to the clinical complications of myocardial infarction or stroke. Although each of the cell types plays roles in the pathogenesis of atherosclerosis, the focus of this review will be primarily on the macrophages and DCs. The role of these two cell types in atherosclerosis is discussed, with a particular emphasis on their involvement in atherosclerosis regression.

  14. Dendritic cell-based immunotherapy in mesothelioma.

    PubMed

    Cornelissen, Robin; Lievense, Lysanne A; Heuvers, Marlies E; Maat, Alexander P; Hendriks, Rudi W; Hoogsteden, Henk C; Hegmans, Joost P; Aerts, Joachim G

    2012-10-01

    Mesothelioma is a rare thoracic malignancy with a dismal prognosis. Current treatment options are scarce and clinical outcomes are rather disappointing. Due to the immunogenic nature of mesothelioma, several studies have investigated immunotherapeutic strategies to improve the prognosis of patients with mesothelioma. In the last decade, progress in knowledge of the modulation of the immune system to attack the tumor has been remarkable, but the optimal strategy for immunotherapy has yet to be unraveled. Because of their potent antigen-presenting capacity, dendritic cells are acknowledged as a promising agent in immunotherapeutic approaches in a number of malignancies. This review gives an update and provides a future perspective in which immunotherapy may improve the outcome of mesothelioma therapy.

  15. Unsteady growth of ammonium chloride dendrites

    NASA Astrophysics Data System (ADS)

    Martyushev, L. M.; Terentiev, P. S.; Soboleva, A. S.

    2016-02-01

    Growth of ammonium chloride dendrites from aqueous solution is experimentally investigated. The growth rate υ and the radius ρ of curvature of branches are measured as a function of the relative supersaturation Δ for steady and unsteady growth conditions. It is shown that the experimental results are quantitatively described by the dependences ρ=a/Δ+b, υ=cΔ2, where the factors for primary branches are a=(1.3±0.2)·10-7 m, b=(2.5±0.4)·10-7 m, and c=(2.2±0.3)·10-4 m/s. The factor c is found to be approximately 7 times smaller for the side branches than that for the primary branches.

  16. Harnessing Human Dendritic Cell Subsets for Medicine

    PubMed Central

    Ueno, Hideki; Schmitt, Nathalie; Klechevsky, Eynav; Pedroza-Gonzales, Alexander; Matsui, Toshimichi; Zurawski, Gerard; Oh, SangKon; Fay, Joseph; Pascual, Virginia; Banchereau, Jacques; Palucka, Karolina

    2010-01-01

    Summary Immunity results from a complex interplay between the antigen-nonspecific innate immune system and the antigen-specific adaptive immune system. The cells and molecules of the innate system employ non-clonal recognition receptors including lectins, Toll-like receptors, NOD-like receptors and helicases. B and T lymphocytes of the adaptive immune system employ clonal receptors recognizing antigens or their derived peptides in a highly specific manner. An essential link between innate and adaptive immunity is provided by dendritic cells (DCs). DCs can induce such contrasting states as immunity and tolerance. The recent years have brought a wealth of information on the biology of DCs revealing the complexity of this cell system. Indeed, DC plasticity and subsets are prominent determinants of the type and quality of elicited immune responses. Here we summarize our recent studies aimed at a better understanding of the DC system to unravel the pathophysiology of human diseases and design novel human vaccines. PMID:20193020

  17. Dendritic cell control of tolerogenic responses

    PubMed Central

    Manicassamy, Santhakumar; Pulendran, Bali

    2011-01-01

    Summary One of the most fundamental problems in immunology is the seemingly schizophrenic ability of the immune system to launch robust immunity against pathogens, while acquiring and maintaining a state of tolerance to the body’s own tissues and the trillions of commensal microorganisms and food antigens that confront it every day. A fundamental role for the innate immune system, particularly dendritic cells (DCs), in orchestrating immunological tolerance has been appreciated, but emerging studies have highlighted the nature of the innate receptors and the signaling pathways that program DCs to a tolerogenic state. Furthermore, several studies have emphasized the major role played by cellular interactions, and the microenvironment in programming tolerogenic DCs. Here we review these studies and suggest that the innate control of tolerogenic responses can be viewed as different hierarchies of organization, in which DCs, their innate receptors and signaling networks, and their interactions with other cells and local microenvironments represent different levels of the hierarchy. PMID:21488899

  18. Regulation of dendritic branching by Cdc42 GAPs

    PubMed Central

    Simó, Sergi; Cooper, Jonathan A.

    2012-01-01

    Nerve cells form elaborate, highly branched dendritic trees that are optimized for the receipt of synaptic signals. Recent work published in this issue of Genes & Development by Rosario and colleagues (pp. 1743–1757) shows that a Cdc42-specific GTPase-activating protein (NOMA-GAP) regulates the branching of dendrites by neurons in the top layers of the mouse cortex. The results raise interesting questions regarding the specification of arbors in different cortical layers and the mechanisms of dendrite branching. PMID:22855828

  19. Communications: Mechanical Deformation of Dendrites by Fluid Flow

    NASA Technical Reports Server (NTRS)

    Pilling, J.; Hellawell, A.

    1996-01-01

    It is generally accepted that liquid agitation during alloy solidification assists in crystal multiplication, as in dendrite fragmentation and the detachment of side arms in the mushy region of a casting. Even without deliberate stirring by electromagnetic or mechanical means, there is often vigorous interdendritic fluid flow promoted by natural thermosolutal convection. In this analysis, we shall estimate the stress at the root of a secondary dendrite arm of aluminum arising from the action of a flow of molten metal past the dendrite arm.

  20. In vivo imaging of dendritic pruning in dentate granule cells.

    PubMed

    Gonçalves, J Tiago; Bloyd, Cooper W; Shtrahman, Matthew; Johnston, Stephen T; Schafer, Simon T; Parylak, Sarah L; Tran, Thanh; Chang, Tina; Gage, Fred H

    2016-06-01

    We longitudinally imaged the developing dendrites of adult-born mouse dentate granule cells (DGCs) in vivo and found that they underwent over-branching and pruning. Exposure to an enriched environment and constraint of dendritic growth by disrupting Wnt signaling led to increased branch addition and accelerated growth, which were, however, counteracted by earlier and more extensive pruning. Our results indicate that pruning is regulated in a homeostatic fashion to oppose excessive branching and promote a similar dendrite structure in DGCs. PMID:27135217