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Sample records for follicular dendritic cell-secreted

  1. Localization and expression pattern of amelotin, odontogenic ameloblast-associated protein and follicular dendritic cell-secreted protein in the junctional epithelium of inflamed gingiva.

    PubMed

    Nakayama, Yohei; Kobayashi, Ryoki; Matsui, Sari; Matsumura, Hiroyoshi; Iwai, Yasunobu; Noda, Keisuke; Yamazaki, Mizuho; Kurita-Ochiai, Tomoko; Yoshimura, Atsutoshi; Shinomura, Tamayuki; Ganss, Bernhard; Ogata, Yorimasa

    2016-11-02

    The purpose of this study is to elucidate the localization of amelotin (AMTN), odontogenic ameloblast-associated protein (ODAM) and follicular dendritic cell-secreted protein (FDC-SP) at the junctional epithelium (JE) in Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans infected mice and inflamed and non-inflamed human gingiva. We performed immunostaining to determine the localization and expression pattern of AMTN, ODAM and FDC-SP. AMTN, ODAM and FDC-SP in A. actinomycetemcomitans infected mice did not change dramatically compared with non-infected mice. AMTN and FDC-SP expressions were observed stronger in P. gingivalis infected mice at early stage. However, at the following stage, the coronal part of the AMTN expression disappeared from the JE, and FDC-SP expression decreased due to severe inflammation by P. gingivalis. ODAM expressed internal and external basal lamina, and the expression increased not only at early stage but also at the following stage in the inflammatory JE induced by P. gingivalis. In the human gingival tissues, AMTN was detected at the surface of the sulcular epithelium and JE in the non-inflamed and inflamed gingiva, and the localization did not change the process of inflammation. ODAM and FDC-SP were more widely detected at the sulcular epithelium and JE in the non-inflamed gingiva. In the inflamed gingiva, localization of ODAM and FDC-SP was spread into the gingival epithelium, compared to AMTN. These studies demonstrated that the expression pattern of AMTN, ODAM and FDC-SP at the JE were changed during inflammation process and these three proteins might play an important role in the resistance to inflammation.

  2. ISOLATION OF CHICKEN FOLLICULAR DENDRITIC CELLS

    USDA-ARS?s Scientific Manuscript database

    The aim of the present study was to isolate chicken follicular dendritic cells (FDC). A combination of methods involving panning, iodixanol density gradient centrifugation, and magnetic cell separation technology made it possible to obtain functional FDC from the cecal tonsils from chickens, which h...

  3. 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

  4. Follicular dendritic cell sarcoma of the abdomen: the imaging findings.

    PubMed

    Kang, Tae Wook; Lee, Soon Jin; Song, Hye Jong

    2010-01-01

    Follicular dendritic cell sarcoma is a rare neoplasm that originates from follicular dendritic cells in lymphoid follicles. This disease usually involves the lymph nodes, and especially the head and neck area. Rarely, extranodal sites may be affected, including tonsil, the oral cavity, liver, spleen and the gastrointestinal tract. We report here on the imaging findings of follicular dendritic cell sarcoma of the abdomen that involved the retroperitoneal lymph nodes and colon. It shows as a well-defined, enhancing homogenous mass with internal necrosis and regional lymphadenopathy.

  5. 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

  6. Splenic Inflammatory Pseudotumor-Like Follicular Dendritic Cell Tumor

    PubMed Central

    Vardas, Konstantinos; Manganas, Dimitrios; Papadimitriou, Georgios; Kalatzis, Vasileios; Kyriakopoulos, Georgios; Chantziara, Maria; Exarhos, Dimitrios; Drakopoulos, Spiros

    2014-01-01

    Inflammatory pseudotumor of the spleen with expression of follicular dendritic cell markers is an extremely rare lesion with only a few cases reported previously. The present study reports on an inflammatory pseudotumor of the spleen 10 × 8 × 7 cm in size that was incidentally found in a 61-year-old man and increased gradually in size during a period of 3 months. Abdominal ultrasonography revealed a well-circumscribed splenic mass, and abdominal computed tomography confirmed the presence of a well-circumscribed isodense lesion in the splenic hilum with inhomogenous enhancement in the early-phase images and no enhancement on delayed-phase contrast-enhanced images. Magnetic resonance imaging of the abdomen showed a well-defined isodense tumor on T1-weighted images with mildly increased signal intensity on T2-weighted images, and this is only the second study that provides MRI findings of this entity. The patient underwent an uncomplicated open splenectomy for definitive histologic diagnosis. Under microscopic examination, the lesion was an admixture of lymphocytes, plasma cells and spindle cells. In situ hybridization analysis for Epstein-Barr virus (EBV) revealed that most of the spindle cells were positive for EBV, and immunochemistry showed the expression of the follicular dendritic cell markers CD21, CD35 and CD23 within the tumor. The diagnosis of inflammatory pseudotumor-like follicular dendritic cell tumor was established. PMID:25076893

  7. Angioimmunoblastic T-Cell Lymphoma: A Questionable Association with Follicular Dendritic Cell Sarcoma

    PubMed Central

    Zekzer, Miriam; Nalbandyan, Karen

    2017-01-01

    An elderly woman presented with generalized lymphadenopathy, several systemic symptoms, and splenomegaly. An inguinal lymph node excision revealed a compound picture. One aspect of the lymph node morphology, including cells with follicular T-helper cell phenotype, was most consistent with angioimmunoblastic T-cell lymphoma. The other component, revealing spindle cells forming whorls with immunostaining for CD21, CD23, and fascin, might be an integral part of this T-cell lymphoma. However, due to the often massive involvement of the nodal tissue by these follicular dendritic cells, these areas were questionably suggestive of involvement by follicular dendritic cell sarcoma. We raise herein the issue of the borderline area between advanced follicular dendritic cell expansion in angioimmunoblastic T-cell lymphoma and a massive follicular dendritic cell proliferation consistent with follicular dendritic cells sarcoma, in the absence of a genomic analysis. PMID:28197348

  8. Imaging Findings of Follicular Dendritic Cell Sarcoma: Report of Four Cases

    PubMed Central

    Long-Hua, Qiu; Qin, Xiao; Jian, Wang; Xiao-Yuan, Feng

    2011-01-01

    Follicular dendritic cell sarcoma is a rare malignant neoplasm and little is known about its radiological features. We present here four cases of follicular dendritic cell sarcomas and we provide the image characteristics of these tumors to help radiologists recognize this entity when making a diagnosis. PMID:21228948

  9. Imaging findings of follicular dendritic cell sarcoma: report of four cases.

    PubMed

    Long-Hua, Qiu; Qin, Xiao; Ya-Jia, Gu; Jian, Wang; Xiao-Yuan, Feng

    2011-01-01

    Follicular dendritic cell sarcoma is a rare malignant neoplasm and little is known about its radiological features. We present here four cases of follicular dendritic cell sarcomas and we provide the image characteristics of these tumors to help radiologists recognize this entity when making a diagnosis.

  10. Follicular Dendritic Cells Retain Infectious HIV in Cycling Endosomes.

    PubMed

    Heesters, Balthasar A; Lindqvist, Madelene; Vagefi, Parsia A; Scully, Eileen P; Schildberg, Frank A; Altfeld, Marcus; Walker, Bruce D; Kaufmann, Daniel E; Carroll, Michael C

    2015-12-01

    Despite the success of antiretroviral therapy (ART), it does not cure Human Immunodeficiency Virus (HIV) and discontinuation results in viral rebound. Follicular dendritic cells (FDC) are in direct contact with CD4+ T cells and they retain intact antigen for prolonged periods. We found that human FDC isolated from patients on ART retain infectious HIV within a non-degradative cycling compartment and transmit infectious virus to uninfected CD4 T cells in vitro. Importantly, treatment of the HIV+ FDC with a soluble complement receptor 2 purges the FDC of HIV virions and prevents viral transmission in vitro. Our results provide an explanation for how FDC can retain infectious HIV for extended periods and suggest a therapeutic strategy to achieve cure in HIV-infected humans.

  11. 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

  12. Inflammatory pseudotumour-like follicular dendritic cell tumour of the spleen

    PubMed Central

    Nishiyama, Raisuke; Baba, Satoshi; Watahiki, Yoichi; Maruo, Hirotoshi

    2015-01-01

    We describe an unusual case of a 73-year-old woman presenting with a solitary splenic mass 8 cm in diameter and an elevation of serum soluble interleukin-2 receptor level. The preoperative diagnosis was primary malignant lymphoma of the spleen. Splenectomy was conducted. Histological analysis confirmed an inflammatory pseudotumour-like follicular dendritic cell tumour that showed different clinicopathological features from those of the classic follicular dendritic cell tumour. Only 33 cases of inflammatory pseudotumour-like follicular dendritic cell tumour have so far been reported. We discuss the incidence, presentation and management of this rare disease. PMID:25766434

  13. Follicular Dendritic Cells Emerge from Ubiquitous Perivascular Precursors

    PubMed Central

    Krautler, Nike Julia; Kana, Veronika; Kranich, Jan; Tian, Yinghua; Perera, Dushan; Lemm, Doreen; Schwarz, Petra; Armulik, Annika; Browning, Jeffrey L.; Tallquist, Michelle; Buch, Thorsten; Oliveira-Martins, José B.; Zhu, Caihong; Hermann, Mario; Wagner, Ulrich; Brink, Robert; Heikenwalder, Mathias; Aguzzi, Adriano

    2013-01-01

    Summary The differentiation of follicular dendritic cells (FDC) is essential to the remarkable microanatomic plasticity of lymphoid follicles. Here we show that FDC arise from ubiquitous perivascular precursors (preFDC) expressing platelet-derived growth factor receptor β (PDGFRβ). PDGFRβ-Cre-driven reporter gene recombination resulted in FDC labeling, whereas conditional ablation of PDGFRβ+-derived cells abolished FDC, indicating that FDC originate from PDGFRβ+ cells. Lymphotoxin-α-overexpressing prion protein (PrP)+ kidneys developed PrP+ FDC after transplantation into PrP mice, confirming that preFDC exist outside lymphoid organs. Adipose tissue-derived PDGFRβ+ stromal-vascular cells responded to FDC maturation factors and, when transplanted into lymphotoxin β receptor (LTβR) kidney capsules, differentiated into Mfge8+CD21/35+ FcγRIIβ+PrP+ FDC capable of trapping immune complexes and recruiting B cells. Spleens of lymphocyte-deficient mice contained perivascular PDGFRβ+ FDC precursors whose expansion required both lymphoid tissue inducer (LTi) cells and lymphotoxin. The ubiquity of preFDC and their strategic location at blood vessels may explain the de novo generation of organized lymphoid tissue at sites of lymphocytic inflammation. PMID:22770220

  14. Hepatic follicular dendritic cell sarcoma without Epstein-Barr virus expression.

    PubMed

    Torres, Ulises; Hawkins, William G; Antonescu, Cristina R; DeMatteo, Ronald P

    2005-11-01

    Follicular dendritic cell sarcoma of the liver is an uncommon pathologic entity, and only 5 cases have been reported previously. Herein, we report the first case, to our knowledge, of hepatic follicular dendritic cell sarcoma without evidence of Epstein-Barr virus infection. The patient is an elderly man who was found to have an incidental liver mass and then developed weight loss and fever. The diagnosis was based on the typical morphologic appearance of spindle cell proliferation associated with a brisk lymphoplasmacytic infiltrate and strong immunoreactivity to CD21 and CD35. Based on our experience and a review of the published reports, we summarize the clinical and pathologic features of hepatic follicular dendritic cell sarcoma and its surgical management.

  15. Follicular dendritic cell sarcoma of mediastinum: a key role of radiotherapy in a multidisciplinary approach.

    PubMed

    Spatola, Corrado; Migliore, Marcello; Emanuele Liardo, Rocco Luca; Bevilacqua, Roberta; Luigi, Raffaele; Vincenzo, Salamone; Tocco, Alessandra; Pagana, Antonio; Militello, Carmelo; Calvo, Damiano; Criscione, Alessandra; Privitera, Giuseppe

    2015-01-01

    Follicular dendritic cell sarcoma is a rare and aggressive tumor and its management is a major clinical challenge. Surgery is considered the mainstay of treatment and no adjuvant approach has demonstrated the ability to reduce the rate of relapses. We report on a case of a man with a 26-year clinical history of mediastinal follicular dendritic cell sarcoma, with several relapses after multiple surgical interventions. The impact of chemotherapy was very small, unlike the radiation therapy that was performed twice, with an interval time of 8 years, through an intensity-modulated technique and an altered fractionation schedule.

  16. [Clinicopathologic study of intraabdominal extranodal follicular dendritic cell sarcoma].

    PubMed

    Tu, Xiao-yu; Sheng, Wei-qi; Lu, Hong-fen; Wang, Jian

    2007-10-01

    To study the clinicopathologic features and immunophenotype of intraabdominal extranodal follicular dendritic cell sarcoma (FDCS) and the relationship with Epstein-Barr virus (EBV). The clinical and histologic features of 4 cases of FDCS were evaluated. Immunohistochemical study was performed using standard EnVision method for CD21, CD23, CD35, S-100 protein, CD68, HLA-DR, vimentin, epithelial membrane antigen, desmin, CD34 and CD117. In-situ hybridization for EBV-encoded RNA (EBER) was carried out in 2 cases. The age of patients ranged from 28 to 63 years (mean=42 years). The male-to-female ratio was 3:1. The clinical presentation was abdominal discomfort, pain or mass. Radiologic examination revealed concurrent lesions in stomach and left lobe of liver in 1 patient, while non-specific intraabdominal masses were detected in the remaining cases (in which the tumor was later found to be located in the appendix, mesentery of jejunum and omentum). Two cases were misdiagnosed as gastrointestinal stromal tumor before operation. Grossly, the tumors appeared as large solid nodules, with a mean diameter of 10.8 cm. Three of the cases showed areas of necrosis. Histologically, there were plump spindle, ovoid to epithelioid cells associated with scattered multinucleated giant cells. The tumor cells were arranged mostly in storiform pattern, whorls, fascicles or solid sheets. Lymphocytic infiltrates with perivascular cuffing were noted in all cases, resulting in a distinctive biphasic pattern. Two tumors showed significant cytologic atypia, with mitotic figures (including atypical mitotic figures) readily demonstrated. The remaining case (occurring in liver) was composed of scattered large atypical cells embedded in a dense inflammatory background, mimicking inflammatory pseudotumor. Immunohistochemical study showed that all cases were positive for CD21, CD23 and vimentin. There was focal expression of CD35, S-100 protein, CD68, HLA-DR and epithelial membrane antigen. The

  17. 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

  18. Cytogenetic abnormalities in follicular dendritic cell sarcoma: report of two cases and literature review.

    PubMed

    Perry, Anamarija M; Nelson, Marilu; Sanger, Warren G; Bridge, Julia A; Greiner, Timothy C

    2013-01-01

    The identification of chromosomal abnormalities in many hematopoietic and mesenchymal neoplasms has contributed significantly to classification systems. Follicular dendritic cell (FDC) sarcoma is an intermediate-grade malignancy with morphological and immunophenotypic features of follicular dendritic cells. Available data on genetic changes in this neoplasm are limited, with only isolated case reports of cytogenetic abnormalities. We reviewed histological, immunophenotypic and cytogenetic findings in two cases of FDC sarcoma. The two cases of FDC sarcoma, were observed in female patients, one was nodal and one extranodal and they exhibited relatively complex karyotypes, characterized by structural abnormalities and loss of multiple chromosomes. One patient had several disease recurrences. At the last follow-up both patients were alive with no residual disease. The cytogenetic findings in these two cases, coupled with the few previously described abnormal karyotypes, suggest that FDC sarcoma is cytogenetically diverse.

  19. Computer Tomography Imaging Findings of Abdominal Follicular Dendritic Cell Sarcoma: A Report of 5 Cases.

    PubMed

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

    2016-01-01

    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.

  20. Follicular cell dendritic sarcoma of cervical nodes in a patient with significant WTC exposure.

    PubMed

    Shemen, Larry; Kaplan, Barry; Sussman, Louis

    2015-01-07

    A patient who worked at the World Trade Center (WTC) site presented with right cervical lymphadenopathy. He underwent right neck dissection. The final pathology showed follicular dendritic cell sarcoma. He was treated with radiation and chemotherapy and remained free of disease initially. He then presented with left cervical lymphadenopathy 2.5 years later and underwent a left neck dissection with similar pathology. A discussion of the disease process and WTC exposure is presented. Clinicians should be cognisant of this disease process and the latency between WTC exposure and the onset of sarcomas. 2015 BMJ Publishing Group Ltd.

  1. Follicular cell dendritic sarcoma of cervical nodes in a patient with significant WTC exposure

    PubMed Central

    Shemen, Larry; Kaplan, Barry; Sussman, Louis

    2015-01-01

    A patient who worked at the World Trade Center (WTC) site presented with right cervical lymphadenopathy. He underwent right neck dissection. The final pathology showed follicular dendritic cell sarcoma. He was treated with radiation and chemotherapy and remained free of disease initially. He then presented with left cervical lymphadenopathy 2.5 years later and underwent a left neck dissection with similar pathology. A discussion of the disease process and WTC exposure is presented. Clinicians should be cognisant of this disease process and the latency between WTC exposure and the onset of sarcomas. PMID:25568274

  2. Follicular dendritic cell sarcoma of the head and neck: case report and literature review.

    PubMed

    Chera, Bhishamjit S; Orlando, Christine; Villaret, Douglas B; Mendenhall, William M

    2008-09-01

    This article presents a case of a patient with follicular dendritic cell sarcoma (FDS), a rare neoplasm usually of the head and neck, and reviews the literature. Literature review. A MEDLINE literature search was performed and the literature was reviewed. Our patient presented with an FDS that had been excised from the upper neck and recurred in a level V node. He was treated with neck dissection and postoperative irradiation and remains disease free 5.25 years after salvage treatment. The literature search yielded 67 case reports on FDS of the head and/or neck. Most patients were treated with surgery (94%). Twenty-eight percent of patients received adjuvant radiotherapy; 18% received adjuvant chemotherapy. Fifty percent of patients were alive with no evidence of disease at last follow-up; 9% died from disease. We currently treat head and neck FDS with wide resection and postoperative radiotherapy.

  3. 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

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

    PubMed

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

    2016-10-11

    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.

  5. (18)F-FDG PET/CT follow-up of follicular dendritic cell sarcoma.

    PubMed

    Albano, D; Bosio, G; Bertagna, F

    Follicular dendritic cell sarcoma (FDCS) is a rare lymphoid neoplasm which occurs mainly in lymph nodes, especially cervical and mediastinal; it can be difficult to diagnose and often is misdiagnosed. Its pathogenesis is still not clear, like its evolution. We report a case of 60-year-old woman with FDCS of left lateral cervical node followed for almost 10 years, after a left selective neck dissection, who underwent five (18)F-FDG PET/CT. This technique has proven to be an useful method for the management of this patient, mainly for the follow up, detection of relapse and therapy response evaluation. Copyright © 2016 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

  6. Dendritic cells and follicular dendritic cells express a novel ligand for CD38 which influences their maturation and antibody responses

    PubMed Central

    Wykes, Michelle N; Beattie, Lynette; MacPherson, Gordon G; Hart, Derek N

    2004-01-01

    CD38 is a cell surface molecule with ADP-ribosyl cyclase activity, which is predominantly expressed on lymphoid and myeloid cells. CD38 has a significant role in B-cell function as some anti-CD38 antibodies can deliver potent growth and differentiation signals, but the ligand that delivers this signal in mice is unknown. We used a chimeric protein of mouse CD38 and human immunogobulin G (IgG) (CD38-Ig) to identify a novel ligand for murine CD38 (CD38L) on networks of follicular dendritic cells (FDCs) as well as dendritic cells (DCs) in the spleen. Flow-cytometry found that all DC subsets expressed cytoplasmic CD38L but only fresh ex vivo CD11c+ CD11b− DCs had cell surface CD38L. Anti-CD38 antibody blocked the binding of CD38-Ig to CD38L, confirming the specificity of detection. CD38-Ig immuno-precipitated ligands of 66 and 130 kDa. Functional studies found that CD38-Ig along with anti-CD40 and anti-major histocompatibility complex (MHC) class II antibody provided maturation signals to DCs in vitro. When CD38-Ig was administered in vivo with antigen, IgG2a responses were significantly reduced, suggesting that B and T cells expressing CD38 may modulate the isotype of antibodies produced through interaction with CD38L on DCs. CD38-Ig also expanded FDC networks when administered in vivo. In conclusion, this study has identified a novel ligand for CD38 which has a role in functional interactions between lymphocytes and DCs or FDCs. PMID:15500618

  7. Isolation of follicular dendritic cells from human tonsils and adenoids. III. Analysis of their Fc receptors.

    PubMed Central

    Heinen, E; Radoux, D; Kinet-Denoel, C; Moeremans, M; De Mey, J; Simar, L J

    1985-01-01

    Follicular dendritic cells (FDC), isolated from human tonsils or adenoids, were tested for their capacity to retain monomeric, aggregated or antigen-bound human antibodies in the absence of serum. FDC retain fluorescein-labelled heat-aggregated human immunoglobulins, but not monomeric ones nor fluorescein-labelled F(ab')2 in monomeric or aggregated form. Ultrastructural observations showed that colloidal gold-labelled monomeric, or antigen-bound, antibodies directed against tetanus toxoid are retained by dendrites and membrane infoldings of FDC but are never located in cytoplasmic vesicles. This retention was inhibited by incubating FDC with unlabelled aggregated or antigen-bound antibodies. When gold-labelled anti-tetanus toxoid antibodies were incubated in the presence of protein-A before the contact with FDC, a strong reduction of their retention occurred. This further suggested the presence of Fc receptors on isolated tonsillar FDC. Endocytosis was not observed in isolated FDC, even after prolonged incubation in presence of labelled immune complexes: their Fc receptors are, thus, not related to a phagocytic activity as they are in macrophages. Simultaneous ultrastructural labelling of Fc and C3b receptors with colloidal gold particles of different sizes did not reveal any clear relations between these two receptors on the surface of FDC. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:3156811

  8. Characteristics, management, and outcomes of patients with follicular dendritic cell sarcoma.

    PubMed

    Jain, Preetesh; Milgrom, Sarah A; Patel, Keyur P; Nastoupil, Loretta; Fayad, Luis; Wang, Michael; Pinnix, Chelsea C; Dabaja, Bouthaina S; Smith, Grace L; Yu, Jun; Hu, Shimin; Bueso Ramos, Carlos E; Kanagal-Shamanna, Rashmi; Medeiros, L Jeffrey; Oki, Yasuhiro; Fowler, Nathan

    2017-04-06

    Dendritic cell sarcomas are rare tumours of antigen presenting cells. Data regarding their biology, management and outcomes are sparse. We analysed 66 patients with follicular dendritic cell sarcoma (FDCS). Six patients also had Castleman disease, 9 had another malignancy and 13 had an autoimmune disease. Fifty-four per cent of patients presented with localized disease and 46% with systemic involvement. The median progression-free (PFS) and overall survival (OS) following frontline therapy was 21 and 50 months, respectively. Survival outcomes were significantly inferior in patients with extranodal, bulky or intra-abdominal disease at presentation. Stage was not associated with survival. Management approaches were heterogeneous. Patients who underwent an upfront gross total resection (GTR) experienced better PFS and OS (both P < 0·0001). In patients who underwent a GTR, consolidative radiotherapy was associated with improved local control (P = 0·03), PFS (P = 0·04) and OS (P = 0·05). In patients with measureable disease, gemcitabine with a taxane yielded an overall response rate of 80%. The pattern of relapse was predominantly locoregional. Salvage rates after recurrence were poor. Studies are underway at our institution to define the genomic profile in FDCS and identify potential novel therapeutic targets.

  9. CD137 Is Expressed in Follicular Dendritic Cell Tumors and in Classical Hodgkin and T-Cell Lymphomas

    PubMed Central

    Anderson, Matthew W.; Zhao, Shuchun; Freud, Aharon G.; Czerwinski, Debra K.; Kohrt, Holbrook; Alizadeh, Ash A.; Houot, Roch; Azambuja, Denize; Biasoli, Irene; Morais, José Carlos; Spector, Nelson; Molina-Kirsch, Hernan F.; Warnke, Roger A.; Levy, Ronald; Natkunam, Yasodha

    2013-01-01

    CD137 (also known as 4-1BB and TNFRSF9) is a member of the tumor necrosis factor receptor superfamily. Originally identified as a costimulatory molecule expressed by activated T cells and NK cells, CD137 is also expressed by follicular dendritic cells, monocytes, mast cells, granulocytes, and endothelial cells. Anti-CD137 immunotherapy has recently shown promise as a treatment for solid tumors and lymphoid malignancies in preclinical models. We defined the expression of CD137 protein in both normal and neoplastic hematolymphoid tissue. CD137 protein is expressed by follicular dendritic cells in the germinal center and scattered paracortical T cells, but not by normal germinal-center B cells, bone marrow progenitor cells, or maturing thymocytes. CD137 protein is expressed by a select group of hematolymphoid tumors, including classical Hodgkin lymphoma, T-cell and NK/T-cell lymphomas, and follicular dendritic cells neoplasms. CD137 is a novel diagnostic marker of these tumors and suggests a possible target for tumor-directed antibody therapy. PMID:22901750

  10. Multi-therapeutic potential of autoantibodies induced by immune complexes trapped on follicular dendritic cells

    PubMed Central

    El Shikh, Mohey Eldin; Kmieciak, Maciej; Manjili, Masoud H; Szakal, Andras K; Pitzalis, Costantino; Tew, John G

    2013-01-01

    Induction of autoantibodies (autoAbs) targeting disease drivers / mediators is emerging as a potential immunotherapeutic strategy. Auto-immune complex (IC)-retaining follicular dendritic cells (FDCs) critically regulate pathogenic autoAb production in autoreactive germinal centers (GCs); however, their ability to induce potentially therapeutic autoAbs has not been explored. We hypothesized that deliberate display of clinically targeted antigens (Ags) in the form of ICs on FDC membranes induces target-specific autoreactive GCs and autoAbs that may be exploited therapeutically. To test our hypothesis, three therapeutically relevant Ags: TNF-α, HER2/neu and IgE, were investigated. Our results indicated that TNF-α-, HER2/neu- and IgE-specific autoAbs associated with strong GC reactions were induced by TNF-α-, HER2/neu- and IgE-IC retention on FDCs. Moreover, the induced anti-TNF-α autoAbs neutralized mouse and human TNF-α with half maximal Inhibitory Concentration (IC50) of 7.1 and 1.6 nM respectively. In addition, we demonstrated that FDC-induced Ab production could be non-specifically inhibited by the IgG-specific Endo-S that accessed the light zones of GCs and interfered with FDC-IC retention. In conclusion, the ability of FDCs to productively present autoAgs raises the potential for a novel immunotherapeutic platform targeting mediators of autoimmune disorders, allergic diseases, and Ab responsive cancers. PMID:23836278

  11. Detection of dendritic cells and related cytokines in follicular fluid of patients with polycystic ovary syndrome.

    PubMed

    Zhang, Tao; Tian, Fuying; Huo, Ran; Tang, Aifa; Zeng, Yong; Duan, Yong-Gang

    2017-09-01

    The presence of dendritic cells (DCs) and associated cytokines in follicular fluid (FF) from patients with polycystic ovary syndrome (PCOS) remains unknown. FF was collected from PCOS patients and patients with severe male factor infertility (control) at the day of transvaginal oocyte retrieval. Phenotypes of DC were detected by flow cytometry, and TNF-α, IL-6, IL-10, and IL-23 were assessed by ELISA. A significant decrease in the percentage of DC was found in patients with PCOS (16.22±5.5%) compared with control (21.27±5.5%, P<.01). E2 on the day of hCG administration was correlated positively with the mean fluorescence intensity of HLA-DR (r=.75, P<.01) and reversely correlated with the concentration of TNF-α in FF (r=-.69, P<.01). The level of TNF-α, IL-6, and IL-10 increased significantly but IL-23 decreased in FF from patients with PCOS. The decrease of DC and disturbance of associated cytokines in FF from PCOS patients indicates a disorder of immunological microenvironment of the ovarian follicle, which might be involved in the dysfunction of folliculogenesis. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. Censoring of self-reactive B cells by follicular dendritic cell-displayed self-antigen.

    PubMed

    Yau, Irene W; Cato, Matthew H; Jellusova, Julia; Hurtado de Mendoza, Tatiana; Brink, Robert; Rickert, Robert C

    2013-08-01

    In the secondary lymphoid organs, intimate contact with follicular dendritic cells (FDCs) is required for B cell retention and Ag-driven selection during the germinal center response. However, selection of self-reactive B cells by Ag on FDCs has not been addressed. To this end, we generated a mouse model to conditionally express a membrane-bound self-antigen on FDCs and to monitor the fate of developing self-reactive B cells. In this article, we show that self-antigen displayed on FDCs mediates effective elimination of self-reactive B cells at the transitional stage. Notwithstanding, some self-reactive B cells persist beyond this checkpoint, showing evidence of Ag experience and intact proximal BCR signaling, but they are short-lived and unable to elicit T cell help. These results implicate FDCs as an important component of peripheral B cell tolerance that prevents the emergence of naive B cells capable of responding to sequestered self-antigens.

  13. 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. © 2016 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.

  14. [Vaginal Follicular dendritic cell sarcoma in patient with previous urinary tract carcinoma. Case Report].

    PubMed

    Zaya, Alejandro Martin; González, Ana Carolina; Sandrone, Silvana S; Sambuelli, Ruben Horacio

    2016-01-01

    follicular dendritic cell sarcoma (FDC sarcoma) is an uncommon neoplasm derived from FDC present in lymphoid follicles. It usually presents in lymph nodes, being extranodal location a very unusual event. A 78 year old female, with prior left nephrectomy for invasive urothelial carcinoma, consulted for genitorragia. At examination, a polypoid vaginal lesion, measuring 3.5 cm in diameter was discovered. It was reported as squamous cell carcinoma in incisional biopsy. A polipectomy was performed. Examination of resected specimen showed a tumor having pushing edges, arranged in a solid pattern with spindle and epithelioid cells, having a syncytial appearance, diffusely sprinkled with numerous lymphocytes and granulocytes. At immunohistochemistry neoplastic cells were positive for vimentin, CD 68, CD 21 and fascine, and focally positive for S-100 and CD45. Occasional scattered neoplastic cells expressed CD30 and CD 23. They were negative for CD3, CD20, myeloperoxidase, AE1 / AE3, EMA, HMB45, Melan A, desmin, Chromogranin, CD1a and CD35. Infiltrating lymphocites were mainly of T cell lineage (CD3 +). We report a case of FDC sarcoma in an unusual location, being to our knowledge, the first one at this site. The fact of having a prior neoplasia posed additional difficulties in differential diagnosis. Histological findings with expression of a specific marker of FDC (in this case CD21) allowed us to establish an accurate diagnosis.

  15. 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

  16. TSLP-activated dendritic cells induce human T follicular helper cell differentiation through OX40-ligand.

    PubMed

    Pattarini, Lucia; Trichot, Coline; Bogiatzi, Sofia; Grandclaudon, Maximilien; Meller, Stephan; Keuylian, Zela; Durand, Melanie; Volpe, Elisabetta; Madonna, Stefania; Cavani, Andrea; Chiricozzi, Andrea; Romanelli, Marco; Hori, Toshiyuki; Hovnanian, Alain; Homey, Bernhard; Soumelis, Vassili

    2017-05-01

    T follicular helper cells (Tfh) are important regulators of humoral responses. Human Tfh polarization pathways have been thus far associated with Th1 and Th17 polarization pathways. How human Tfh cells differentiate in Th2-skewed environments is unknown. We show that thymic stromal lymphopoietin (TSLP)-activated dendritic cells (DCs) promote human Tfh differentiation from naive CD4 T cells. We identified a novel population, distinct from Th2 cells, expressing IL-21 and TNF, suggestive of inflammatory cells. TSLP-induced T cells expressed CXCR5, CXCL13, ICOS, PD1, BCL6, BTLA, and SAP, among other Tfh markers. Functionally, TSLP-DC-polarized T cells induced IgE secretion by memory B cells, and this depended on IL-4Rα. TSLP-activated DCs stimulated circulating memory Tfh cells to produce IL-21 and CXCL13. Mechanistically, TSLP-induced Tfh differentiation depended on OX40-ligand, but not on ICOS-ligand. Our results delineate a pathway of human Tfh differentiation in Th2 environments. © 2017 Pattarini et al.

  17. Rat bone marrow-derived dendritic cells, but not ex vivo dendritic cells, secrete nitric oxide and can inhibit T-cell proliferation

    PubMed Central

    Powell, Timothy J; Jenkins, Chris D; Hattori, Ryuichi; MacPherson, G Gordon

    2003-01-01

    The relationships between different dendritic cell (DC) populations are not clearly established. In particular, it is not known how DC generated in vitro relate to those identified in vivo. Here we have characterized rat bone marrow-derived DC (BMDC) and compared them with DC isolated from spleen (SDC) and pseudo-afferent lymph (LDC). BMDC express typical DC markers and are mostly OX41 positive and CD4 negative. In contrast to ex vivo DC, some BMDC express Fc receptors. FcR+ and FcR− BMDC express similar levels of major histocompatibility complex class II molecules (MHC) and are B7 positive, but some FcR− BMDC express high levels of B7. In contrast to freshly isolated or cultured ex vivo SDC and LDC, both BMDC subpopulations can express inducible nitric oxide synthase (iNOS) and can secrete nitric oxide (NO) in amounts similar to those secreted by peritoneal macrophages. Despite expressing MHC class II and B7, FcR+ BMDC stimulate only a very weak MLR and inhibit stimulation by FcR− BMDC and ex vivo DC. Inhibition is only partially NO dependent. FcR+ BMDC are not macrophages, as judged by adherence and phagocytosis. Both subpopulations are able to present antigen to primed T cells in vitro and are able to prime naïve CD4 T cells in vivo. However, unlike SDC, BMDC are unable to stimulate cytotoxic T-lymphocyte (CTL) responses to a minor histocompatibility antigen. Thus, BMDC show marked differences to ex vivo DC and their relationship to those of in vivo DC populations, to date, is unclear. PMID:12757614

  18. Identification of CXCL13 as a new marker for follicular dendritic cell sarcoma.

    PubMed

    Vermi, W; Lonardi, S; Bosisio, D; Uguccioni, M; Danelon, G; Pileri, S; Fletcher, C; Sozzani, S; Zorzi, F; Arrigoni, G; Doglioni, C; Ponzoni, M; Facchetti, F

    2008-11-01

    The homeostatic chemokine CXCL13 is preferentially produced in B-follicles and is crucial in the lymphoid organ development by attracting B-lymphocytes that express its selective receptor CXCR5. Follicular dendritic cells (FDCs) have been identified as the main cellular source of this chemokine in lymphoid organs. Recently, genome-wide approaches have suggested follicular CD4 T-helper cells (T(H)F) as additional CXCL13 producers in the germinal centre and the neoplastic counterpart of T(H)F (CD4+ tumour T-cells in angioimmunoblastic T-cell lymphoma) retains the capability of producing this chemokine. In contrast, no data are available on CXCL13 expression on FDC sarcoma (FDC-S) cells. By using multiple approaches, we investigated the expression of CXCL13 at mRNA and protein level in reactive and neoplastic FDCs. In reactive lymph nodes and tonsils, CXCL13 protein is mainly expressed by a subset of FDCs in B-cell follicles. CXCL13 is maintained during FDC transformation, since both dysplastic FDCs from 13 cases of Castleman's disease and neoplastic FDCs from ten cases of FDC-S strongly and diffusely express this chemokine. This observation was confirmed at mRNA level by using RT-PCR and in situ hybridization. Of note, no CXCL13 reactivity was observed in a cohort of epithelial and mesenchymal neoplasms potentially mimicking FDC-S. FDC-S are commonly associated with a dense intratumoural inflammatory infiltrate and immunohistochemistry showed that these lymphocytes express the CXCL13 receptor CXCR5 and are mainly of mantle zone B-cell derivation (IgD+ and TCL1+). In conclusion, this study demonstrates that CXCL13 is produced by dysplastic and neoplastic FDCs and can be instrumental in recruiting intratumoural CXCR5+ lymphocytes. In addition to the potential biological relevance of this expression, the use of reagents directed against CXCL13 can be useful to properly identify the origin of spindle cell and epithelioid neoplasms.

  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. Scrapie Affects the Maturation Cycle and Immune Complex Trapping by Follicular Dendritic Cells in Mice

    PubMed Central

    McGovern, Gillian; Mabbott, Neil; Jeffrey, Martin

    2009-01-01

    Transmissible spongiform encephalopathies (TSEs) or prion diseases are infectious neurological disorders of man and animals, characterised by abnormal disease-associated prion protein (PrPd) accumulations in the brain and lymphoreticular system (LRS). Prior to neuroinvasion, TSE agents often accumulate to high levels within the LRS, apparently without affecting immune function. However, our analysis of scrapie-affected sheep shows that PrPd accumulations within the LRS are associated with morphological changes to follicular dendritic cells (FDCs) and tingible body macrophages (TBMs). Here we examined FDCs and TBMs in the mesenteric lymph nodes (MLNs) of scrapie-affected mice by light and electron microscopy. In MLNs from uninfected mice, FDCs could be morphologically categorised into immature, mature and regressing forms. However, in scrapie-affected MLNs this maturation cycle was adversely affected. FDCs characteristically trap and retain immune complexes on their surfaces, which they display to B-lymphocytes. In scrapie-affected MLNs, some FDCs were found where areas of normal and abnormal immune complex retention occurred side by side. The latter co-localised with PrPd plasmalemmal accumulations. Our data suggest this previously unrecognised morphology represents the initial stage of an abnormal FDC maturation cycle. Alterations to the FDCs included PrPd accumulation, abnormal cell membrane ubiquitin and excess immunoglobulin accumulation. Regressing FDCs, in contrast, appeared to lose their membrane-attached PrPd. Together, these data suggest that TSE infection adversely affects the maturation and regression cycle of FDCs, and that PrPd accumulation is causally linked to the abnormal pathology observed. We therefore support the hypothesis that TSEs cause an abnormality in immune function. PMID:19997557

  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. Clusterin in human gut-associated lymphoid tissue, tonsils, and adenoids: localization to M cells and follicular dendritic cells.

    PubMed

    Verbrugghe, Phebe; Kujala, Pekka; Waelput, Wim; Peters, Peter J; Cuvelier, Claude A

    2008-03-01

    The follicle-associated epithelium (FAE) overlying the follicles of mucosa-associated lymphoid tissue is a key player in the initiation of mucosal immune responses. We recently reported strong clusterin expression in the FAE of murine Peyer's patches. In this study, we examined the expression of clusterin in the human gut-associated lymphoid tissue (GALT) and Waldeyer's ring. Immunohistochemistry for clusterin in human Peyer's patches, appendix and colon lymphoid follicles revealed expression in M cells and in follicular dendritic cells (FDCs). Using cryo-immunogold electron microscopy in Peyer's patches, we observed cytosolic immunoreactivity in M cells and labeling in the ER/Golgi biosynthetic pathway in FDCs. In palatine tonsils and adenoids, we demonstrated clusterin expression in germinal centers and in the lymphoepithelium in the crypts where M cells are localized. In conclusion, clusterin is expressed in M cells and follicular dendritic cells at inductive sites of human mucosa-associated lymphoid tissue suggesting a role for this protein in innate immune responses. Moreover, the use of clusterin as a human M cell marker could prove to be a valuable tool in future M cell research.

  3. Follicular dendritic cell tumor of the mediastinum: expression of fractalkine and SDF-1alpha as mast cell chemoattractants.

    PubMed

    Guettier, Catherine; Validire, Pierre; Emilie, Dominique; Tricottet, Viviane; Sebagh, Mylène; Anjo, Aurora; Misset, Jean-Louis; Reynes, Michel

    2006-02-01

    Follicular dendritic cell tumor (FDCT) is a rare tumor mainly located in laterocervical lymph nodes. We report one case of mediastinal FDCT associated with a history of bullous skin disease and clinically obvious immunosuppression. This tumor was characterized by heavy mast cell infiltration. Mast cells were in close relationship with tumor cells as demonstrated by ultrastructural examination and their presence are probably related with the strong expression of mast cell chemoattractants as fraktalkine and stromal cell-derived factor-1alpha by tumor cells. The long follow-up period of more than 17 years allowed to us assess the relatively indolent evolution of this tumor characterized by three slowly growing local recurrences without metastasis.

  4. Cytopathology of a primary follicular dendritic cell sarcoma of the liver of the inflammatory pseudotumor-like type.

    PubMed

    Granados, Rosario; Aramburu, José Antonio; Rodríguez, José María; Nieto, María Antonia

    2008-01-01

    Follicular dendritic cell (FDC) sarcoma is an exceedingly uncommon tumor of lymph nodes and extranodal tissues. The inflammatory pseudotumor (IPT)-like variant of FDC sarcoma of intraabdominal location is considered a separate entity, with different clinical and pathological features than those of the classic FDC tumor. There have been only 12 cytological reports of FDC sarcomas in the literature. Two of them were metastases to the liver and, like our case, had features of IPT. Fine-needle aspiration biopsy (FNAB) and imprint and scrape cytology from the surgically excised tumor here reported revealed spindle tumor cells with moderate pleomorphism, nuclear grooves, prominent nucleoli, and cytoplasmic processes, admixed with inflammatory cells. To the best of our knowledge, this is the first cytology report of a primary hepatic FDC tumor. The cytological findings permit the recognition of this tumor. However, confirmation by inmunohistochemistry (IHQ) is mandatory for a definitive diagnosis.

  5. CNA.42, a new monoclonal antibody directed against a fixative-resistant antigen of follicular dendritic reticulum cells.

    PubMed Central

    Raymond, I.; Al Saati, T.; Tkaczuk, J.; Chittal, S.; Delsol, G.

    1997-01-01

    A new monoclonal antibody (MAb), CNA.42, was generated using the CEM T-cell line. It recognizes a 120-kd formalin-resistant glycosylated antigen that is mainly expressed by follicular dendritic reticulum cells (FDRCs). This antigen is also expressed by a few mononuclear cells in the paracortical area of reactive lymph nodes and by some cortical thymocytes. Two hundred and eighty-nine cases of hematopoietic tumors of various types were tested with this antibody. They showed either intact FDRC networks or FDRC networks dispersed among malignant cells. In follicular lymphomas, the follicular pattern was highlighted by CNA.42 MAb. Expanded FDRC networks were found in angioimmunoblastic T-cell lymphomas. Neoplastic cells were positive in 43.6% (24/55) of T-cell and 4.6% (6/129) of B-cell lymphomas. The highest percentage of cases with positive neoplastic cells was found in anaplastic large-cell lymphomas (62.5%; 15/24). In Hodgkin's disease, FDRC networks, sometimes encasing Hodgkin and Reed-Sternberg (HRS) cells, were found. HRS cells were also stained by this antibody in 23 (21.9%) of the 105 cases examined. A variety of normal nonlymphoid tissues and nonhematopoietic tumors, such as some neurogenic tumors, carcinoma, and occasional sarcomas, were found to be positive. Analysis of the reactivity of CNA.42 antibody with FDRCs of lymphoid tissue from different animal species showed similar reactivity to that observed in humans, suggesting widespread evolutionary conservation of the antigen recognized by this antibody. In daily diagnostic practice, CNA.42 MAb seems to be a suitable FDRC marker and possibly has an auxiliary role in recognizing T-cell lymphomas. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:9403709

  6. Intrinsic features of the CD8α(-) dendritic cell subset in inducing functional T follicular helper cells.

    PubMed

    Shin, Changsik; Han, Jae-A; Choi, Bongseo; Cho, Yoon-Kyoung; Do, Yoonkyung; Ryu, Seongho

    2016-04-01

    T follicular helper (Tfh) cells, a true B cell helper, have a critical role in enhancing humoral immune responses. However, the initial differentiation of Tfh cells by dendritic cells (DCs), the most potent antigen presenting cells, has not been clearly understood, particularly in the knowledge of the two major conventional dendritic cell subsets, CD8α(+) DCs or CD8α(-) DCs. Here we demonstrated that the localization of CD8α(-) DCs in the marginal zone (MZ) bridging channels is closely associated with the induction of CXCR5(+)CCR7(low) Tfh cells. We also showed that the major source of IL-6 for inducing Tfh cells is provided from the activated CD4(+) T cells induced by CD8α(-) DCs, and IL-6 directly secreted from the DC subsets seems minor. CD8α(-) DCs were superior in inducing functional Tfh cells over other antigen presenting cells including B cells. We here observed the unknown intrinsic features of the DC subsets, suggesting the potential of utilizing the CD8α(-) DC subset as therapeutic vaccine for the regulation of humoral immune responses.

  7. 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.

  8. 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

  9. Immunopathological features of palatine tonsil characteristic of IgA nephropathy: IgA1 localization in follicular dendritic cells.

    PubMed

    Kusakari, C; Nose, M; Takasaka, T; Yuasa, R; Kato, M; Miyazono, K; Fujita, T; Kyogoku, M

    1994-01-01

    IgA nephropathy (IgAN) is generally thought to be mediated by the glomerular deposition of circulating immune complexes containing IgA as the major antibody component. Upper respiratory infections and tonsillitis often precede IgAN, and in some cases tonsillectomy is effective for the treatment of IgAN. Thus, the tonsil seems to be a unique organ causing initial and/or progressive events to generate nephritogenic immune complexes in IgAN. In this study we focused on the analysis of immunopathological features of the palatine tonsil characteristic of IgAN patients by using an immunohistochemical technique. The IgA1 subclass was demonstrated in follicular dendritic cells (FDC) of the tonsil of IgAN patients, but not in FDC of non-IgAN controls. On the other hand, IgA2, IgG, IgM and C3 did not show any differences in distribution between the two groups. Moreover, the expression of decay-accelerating factor (DAF), an inhibitor of homologous complement activation, and transforming growth factor-beta 1 (TGF-beta 1), an inducer of antibody-producing cells to IgA class switching, in FDC and interdigitating dendritic cells of the tonsil, respectively, which was also clarified in this study for the first time, was found to be identically distributed in the two groups. These findings may support the idea that IgA1, possibly in an immune complex form, is trapped by FDC and plays an important role in the persistent activation of particular B cell repertoires responsible for the onset and/or progression of IgAN.

  10. Immunopathological features of palatine tonsil characteristic of IgA nephropathy: IgA1 localization in follicular dendritic cells.

    PubMed Central

    Kusakari, C; Nose, M; Takasaka, T; Yuasa, R; Kato, M; Miyazono, K; Fujita, T; Kyogoku, M

    1994-01-01

    IgA nephropathy (IgAN) is generally thought to be mediated by the glomerular deposition of circulating immune complexes containing IgA as the major antibody component. Upper respiratory infections and tonsillitis often precede IgAN, and in some cases tonsillectomy is effective for the treatment of IgAN. Thus, the tonsil seems to be a unique organ causing initial and/or progressive events to generate nephritogenic immune complexes in IgAN. In this study we focused on the analysis of immunopathological features of the palatine tonsil characteristic of IgAN patients by using an immunohistochemical technique. The IgA1 subclass was demonstrated in follicular dendritic cells (FDC) of the tonsil of IgAN patients, but not in FDC of non-IgAN controls. On the other hand, IgA2, IgG, IgM and C3 did not show any differences in distribution between the two groups. Moreover, the expression of decay-accelerating factor (DAF), an inhibitor of homologous complement activation, and transforming growth factor-beta 1 (TGF-beta 1), an inducer of antibody-producing cells to IgA class switching, in FDC and interdigitating dendritic cells of the tonsil, respectively, which was also clarified in this study for the first time, was found to be identically distributed in the two groups. These findings may support the idea that IgA1, possibly in an immune complex form, is trapped by FDC and plays an important role in the persistent activation of particular B cell repertoires responsible for the onset and/or progression of IgAN. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:7507015

  11. Dendritic cell secretion of IL-15 is induced by recombinant huCD40LT and augments the stimulation of antigen-specific cytolytic T cells.

    PubMed

    Kuniyoshi, J S; Kuniyoshi, C J; Lim, A M; Wang, F Y; Bade, E R; Lau, R; Thomas, E K; Weber, J S

    1999-04-10

    Dendritic cells (DC) are professional antigen-presenting cells which stimulate strong proliferative and cytolytic T cell responses. Stimulation of CD40 on dendritic cells by its ligands and anti-CD40 antibodies induces maturation and enhances DC stimulatory ability. In order to understand the mechanism by which ligand:CD40 interactions augment DC function, we assessed the role of T cell stimulatory cytokines IL-12 and IL-15 in the function of DC stimulated with soluble trimeric CD40L, a recombinant fusion protein incorporating three covalently linked extracellular CD40L domains (huCD40LT). Peripheral blood derived DC treated with huCD40LT and/or IFN-gamma were used to stimulate T cell responses in vitro to specific antigens. DC treated with huCD40LT or IFN-gamma/huCD40LT stimulated enhanced T cell proliferation to CASTA, a soluble protein from C. albicans, induced T cells with augmented antigen-specific lysis, and increased the yield of antigen-specific IFN-gamma-producing T cells. IL-15 production by DC was enhanced in cultures treated with huCD40LT and correlated with expansion of antigen-specific cytolytic T cells. Addition of a neutralizing anti-IL-15 monoclonal antibody inhibited the expansion of viral and tumor antigen-specific T cells stimulated by IFN-gamma and huCD40LT-treated DC. In contrast, this enhanced stimulatory ability of DC did not appear to depend on synthesis of IL-12 since huCD40LT treatment stimulated the generation of antigen-specific cytokine producing and cytolytic T cells without increased IL-12 production. Addition of anti-IL-12 monoclonal antibody did not inhibit expansion of these cells. These data suggest that production of IL-15 but not IL-12 is an important factor in the enhanced immunostimulatory ability of huCD40LT-treated DC.

  12. 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.

  13. B lymphocytes induce the formation of follicular dendritic cell clusters in a lymphotoxin alpha-dependent fashion.

    PubMed

    Fu, Y X; Huang, G; Wang, Y; Chaplin, D D

    1998-04-06

    Lymphotoxin (LT)alpha is expressed by activated T cells, especially CD4(+) T helper type 1 cells, and by activated B and natural killer cells, but the functions of this molecule in vivo are incompletely defined. We have previously shown that follicular dendritic cell (FDC) clusters and germinal centers (GCs) are absent from the peripheral lymphoid tissues of LTalpha-deficient (LTalpha-/-) mice. LTalpha-/- mice produce high levels of antigen-specific immunoglobulin (Ig)M, but very low levels of IgG after immunization with sheep red blood cells. We show here that LTalpha-expressing B cells are essential for the recovery of primary, secondary, and memory humoral immune responses in LTalpha-/- mice. It is not necessary for T cells to express LTalpha to support these immune functions. Importantly, LTalpha-expressing B cells alone are essential and sufficient for the formation of FDC clusters. Once these clusters are formed by LTalpha-expressing B cells, then LTalpha-deficient T cells can interact with B cells to generate GCs and productive class-switched antibody responses. Thus, B cells themselves provide an essential signal that induces and maintains the lymphoid microenvironment essential for GC formation and class-switched Ig responses.

  14. Human dendritic cells induce the differentiation of interleukin-21-producing T follicular helper-like cells through interleukin-12.

    PubMed

    Schmitt, Nathalie; Morita, Rimpei; Bourdery, Laure; Bentebibel, Salah Eddine; Zurawski, Sandra M; Banchereau, Jacques; Ueno, Hideki

    2009-07-17

    T follicular helper (Tfh) cells help development of antibody responses via interleukin-21 (IL-21). Here we show that activated human dendritic cells (DCs) induced naive CD4(+) T cells to become IL-21-producing Tfh-like cells through IL-12. CD4(+) T cells primed with IL-12 induced B cells to produce immunoglobulins in a fashion dependent on IL-21 and inducible costimulator (ICOS), thus sharing fundamental characteristics with Tfh cells. The induction of Tfh-like cells by activated DCs was inhibited by neutralizing IL-12. IL-12 induced two different IL-21-producers: IL-21(+)IFN-gamma(+)T-bet(+) Th1 cells and IL-21(+)IFN-gamma(-)T-bet(-) non-Th1 cells, in a manner dependent on signal transducer and activator of transcription 4 (STAT4). IL-12 also regulated IL-21 secretion by memory CD4(+) T cells. Thus, IL-12 produced by activated DCs regulates antibody responses via developing IL-21-producing Tfh-like cells and inducing IL-21 secretion from memory CD4(+) T cells. These data suggest that the developmental pathway of Tfh cells differs between mice and humans, which have considerable implications for vaccine development.

  15. 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. Copyright © 2012 Elsevier Ltd. All rights reserved.

  16. Dendritic Cell-Secreted Lipocalin2 Induces CD8+ T-Cell Apoptosis, Contributes to T-Cell Priming and Leads to a TH1 Phenotype

    PubMed Central

    Floderer, Melanie; Prchal-Murphy, Michaela; Vizzardelli, Caterina

    2014-01-01

    Lipocalin 2 (LCN2), which is highly expressed by dendritic cells (DCs) when treated with dexamethasone (Dex) and lipopolysaccharide (LPS), plays a key role in the defence against bacteria and is also involved in the autocrine apoptosis of T-cells. However, the function of LCN2 when secreted by DCs is unknown: this is a critical gap in our understanding of the regulation of innate and adaptive immune systems. Tolerance, stimulation and suppression are functions of DCs that facilitate the fine-tuning of the immune responses and which are possibly influenced by LCN2 secretion. We therefore examined the role of LCN2 in DC/T-cell interaction. WT or Lcn2−/− bone marrow-derived DCs were stimulated with LPS or LPS+IFN-γ with and without Dex and subsequently co-cultured with T-cells from ovalbumin-specific TCR transgenic (OT-I and OT-II) mice. We found that CD8+ T-cell apoptosis was highly reduced when Lcn2−/− DCs were compared with WT. An in vivo CTL assay, using LPS-treated DCs, showed diminished killing ability in mice that had received Lcn2−/− DCs compared with WT DCs. As a consequence, we analysed T-cell proliferation and found that LCN2 participates in T-cell-priming in a dose-dependent manner and promotes a TH1 microenvironment. DC-secreted LCN2, whose function has previously been unknown, may in fact have an important role in regulating the balance between TH1 and TH2. Our results yield insights into DC-secreted LCN2 activity, which could play a pivotal role in cellular immune therapy and in regulating immune responses. PMID:25010215

  17. 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

  18. 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

  19. Integrin-mediated interactions between B cells and follicular dendritic cells influence germinal center B cell fitness1

    PubMed Central

    Wang, Xiaoming; Rodda, Lauren; Bannard, Oliver; Cyster, Jason G.

    2014-01-01

    Integrin-ligand interactions between germinal center (GC) B cells and antigen-presenting follicular dendritic cells (FDCs) have been suggested to play central roles during GC responses but their in vivo requirement has not been directly tested. Here we show that while integrins αLβ2 and α4β1 are highly expressed and functional on mouse GC B cells, removal of single integrins or their ligands had little effect on B cell participation in the GC response. Combined β2-integrin deficiency and α4-integrin blockade also did not affect the GC response against a particulate antigen. However, the combined integrin deficiency did cause B cells to be outcompeted in splenic GC responses against a soluble protein antigen and in mesenteric lymph node GC responses against gut-derived antigens. Similar findings were made for β2-deficient B cells in mice lacking VCAM1 on FDCs. The reduced fitness of the GC B cells did not appear to be due to decreased antigen acquisition, proliferation rates or pAKT levels. In summary, our findings provide evidence that αLβ2 and α4β1 play overlapping and context-dependent roles in supporting interactions with FDCs that can augment the fitness of responding GC B cells. We also find that mouse GC B cells upregulate αvβ3 and adhere to vitronectin and milk fat globule EGF-factor-8 protein. Integrin β3-deficient B cells contributed in a slightly exaggerated manner to GC responses suggesting this integrin has a regulatory function in GC B cells. PMID:24740506

  20. 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.

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

    PubMed Central

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

    2016-01-01

    Abstract 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

  2. CD21-positive follicular dendritic cells: A possible source of PrPSc in lymph node macrophages of scrapie-infected sheep.

    PubMed

    Herrmann, Lynn M; Cheevers, William P; Davis, William C; Knowles, Donald P; O'Rourke, Katherine I

    2003-04-01

    Natural sheep scrapie is a prion disease characterized by the accumulation of PrP(Sc) in brain and lymphoid tissues. Previous studies suggested that lymph node macrophages and follicular dendritic cells (FDC) accumulate PrP(Sc). In this study, lymph nodes were analyzed for the presence of PrP(Sc) and macrophage or FDC markers using dual immunohistochemistry. A monoclonal antibody (mAb) to the C-terminus of PrP reacted with CD172a+ macrophages and CD21+ FDC processes in secondary follicles. However, a PrP N-terminus-specific mAb reacted with CD21+ FDC processes but not CD172a+ macrophages in secondary follicles. Neither the PrP N-terminus nor C-terminus-specific mAb reacted with CD172a+ macrophages in the medulla. These results indicate that lymph node follicular macrophages acquire PrP(Sc) by phagocytosis of CD21+ FDC processes. The results also suggest that follicular macrophages have proteases that process full-length PrP(Sc) to N-terminally truncated PrP(Sc).

  3. Human immune response to pneumococcal polysaccharides: complement-mediated localization preferentially on CD21-positive splenic marginal zone B cells and follicular dendritic cells.

    PubMed

    Peset Llopis, M J; Harms, G; Hardonk, M J; Timens, W

    1996-04-01

    A functionally intact spleen with a marginal zone, containing B cells with high density of surface C3d-receptors (CD21), is essential for the ability to induce a primary immune response to thymus-independent type 2 (TI-2) antigens. Main representatives of natural TI-2 antigens are capsular pneumococcal polysaccharides (PPSs). In this study the localization of different types of PPS antigen is determined in human spleen tissue. Our findings indicate that a main type of TI-2 antigen, PPS, localizes preferentially in the marginal zone. PPSs show co-localization with C3, presumably C3d, at the surface of strongly CD21+ B cells equipped for rapid activation. This enables a rapid primary humoral response. The other main PPS localization at follicular dendritic cells in germinal centers, relevant for isotype switching of anti-PPS antibodies, does not seem to be dependent on the presence of specific immunoglobulin. This may explain the finding of specific IgG in an early stage after antigenic challenge. It seems likely that complement C3 fragments (likely C3d), bound to PPSs, enable PPS localization at B-cell and follicular dendritic cell surfaces by binding to CD21, the C3d receptor.

  4. TC1(C8orf4) is upregulated by IL-1beta/TNF-alpha and enhances proliferation of human follicular dendritic cells.

    PubMed

    Kim, Youngmi; Kim, Jungtae; Park, Juhee; Bang, Seunghyun; Jung, Yusun; Choe, Jongseon; Song, Kyuyoung; Lee, Inchul

    2006-06-12

    Follicular dendritic cells (FDC) play crucial roles in immune regulation. TNF-alpha has been shown to be essential to the FDC network. However, the molecular regulation of FDC proliferation has not been characterized. Here, we show that TC1(C8orf4), a novel positive regulator of the Wnt/beta-catenin pathway in vertebrates, is upregulated by IL-1beta and TNF-alpha in the human FDC-like line HK. TC1 enhances HK cell proliferation, while TC1-knockdown inhibits the proliferation induced by IL-1beta, suggesting a role of TC1 as a regulator of FDC proliferation. The regulation by pro-inflammatory cytokines suggests that TC1 might be implicated in linking local inflammation to immune response by stimulating FDC.

  5. 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

  6. Protection of germinal centres from complement attack: decay-accelerating factor (DAF) is a constitutive protein on follicular dendritic cells. A study in reactive and neoplastic follicles.

    PubMed

    Lampert, I A; Schofield, J B; Amlot, P; Van Noorden, S

    1993-06-01

    The development of B-cell memory is linked to the presence of germinal centres. This process is dependent on the presence of antigen, usually in the form of immune complexes with antibody, on the surface of the follicular dendritic cells (FDCs) that form a network in the germinal centre. The presence of immune complexes poses a constant danger of activating complement. Decay accelerating factor (DAF, CD55) and the membrane attack complex (MAC) inhibitor (CD59) are two cell proteins whose sole function is to protect cells from the action of complement, the former affecting the earlier components of the complement cascade, and the latter the terminal ones; both are bound to the cell surface via a glycosylphosphatidylinositol link. DAF but not CD59 could be demonstrated on FDCs. DAF is also present on the FDCs in follicular lymphomas despite the absence of complement (C3) in neoplastic follicles. This indicates that DAF is constitutive to FDCs but does not preclude the possibility that its expression is increased when immune complexes are deposited.

  7. Cutting Edge: LL-37-Mediated Formyl Peptide Receptor-2 Signaling in Follicular Dendritic Cells Contributes to B Cell Activation in Peyer's Patch Germinal Centers.

    PubMed

    Kim, Sae-Hae; Kim, Yu Na; Jang, Yong-Suk

    2017-01-15

    Peyer's patches (PPs) are the major mucosal immune-inductive site, and germinal centers (GCs) in PPs determine the quality of the Abs produced. PP GCs are continuously induced by the gut microbiota, and their maintenance contributes to the induction of strong IgA responses to Ags. In this study, we investigated the role of formyl peptide receptor (FPR)-mediated signaling in the maintenance of PP GCs, because FPRs recognize the microbiota and initiate an innate immune response by chemotaxis. We found that follicular dendritic cells (FDCs), a key organizer of B cell follicles and GCs in mucosal immunity, express Fpr2. Additionally, Fpr2-mediated signaling in PP FDCs promoted Cxcl13 and B cell activating factor expression, as well as B cell proliferation and activation. Therefore, we suggest that Fpr2-mediated signaling in FDCs plays a key role in GC maintenance in PPs and results in an Ag-specific IgA response in the gut mucosal immune compartment. Copyright © 2017 by The American Association of Immunologists, Inc.

  8. 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.

  9. 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

  10. Immunohistochemical investigation of cells expressing CD21, membrane IgM, CD32 and a follicular dendritic cell marker in the lymphoid tissues of neonatal calves.

    PubMed

    Chattha, Kuldeep S; Hodgins, Douglas C; DeLay, Josepha; Antoine, Nadine; Shewen, Patricia E

    2010-10-15

    Activation of B lymphocytes in the presence of passive maternal antibodies depends on expression of CD21, membrane IgM and CD32. On colligation with IgM, CD32 inhibits activation whereas CD21 enhances it. Recently, we assessed expression of CD21 and CD32 on IgM(+) cells from lymphoid tissues of newborn calves by flow cytometry, but this approach does not provide information about spatial distribution within lymphoid compartments. Therefore, histologic sections of lymphoid tissues from newborn and 7-month-old calves were examined using an immunoperoxidase technique. In all calves, CD21 and IgM stained cells were collocated in the cortex and paracortex of the retropharyngeal lymph node, in the marginal zone of the spleen and in lymphoid aggregates of palatine tonsils. Most CD32(+) cells were in the mantle zone of lymphoid follicles in 7-month-old calves, whereas only weak staining was observed in newborns. A few CD32(+) cells were also observed in the paracortex at both ages. Absence of CD32(+) cells in the center of follicles suggests that IgM(+)CD32(-) cells observed previously by flow cytometry were from germinal centers. Overall, there were few organized lymphoid aggregates within lymphoid tissues of newborn calves, and follicular dendritic cells were virtually undetectable. Their absence may be an important limitation for neonatal immunization.

  11. 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.

  12. Involvement of miRNAs and Cell-Secreted Vesicles in Mammalian Ovarian Antral Follicle Development.

    PubMed

    da Silveira, Juliano C; de Andrade, Gabriella M; Nogueira, Marcelo F G; Meirelles, Flávio V; Perecin, Felipe

    2015-12-01

    Ovarian follicular development is a controlled series of events culminating with an ovulatory or atretic follicle. MicroRNAs (miRNAs) are small noncoding RNAs involved in translational regulation of genes in different developmental processes. Deletion of Dicer in mice ovaries demonstrated the importance of miRNAs in reproduction, which led to infertility. The miRNAs were thought to act only within host cells; however, these molecules are also present in cell-secreted vesicles. These vesicles are present in body fluids such as milk, serum, and ovarian follicular fluid. Vesicles are secreted in extracellular fluids and travel from donor to target cells, mediating transfer of bioactive material. Herein we discuss the role of hormonal-regulated miRNAs within different ovarian follicular cells as well as cell-secreted vesicles participation in mammalian ovarian follicular fluid. Furthermore, we discuss the possibility of miRNAs transference mediated by cell-secreted vesicles present in ovarian follicular fluid, increasing the versatility of miRNA functions during antral follicle development. © The Author(s) 2015.

  13. CD9 may contribute to the survival of human germinal center B cells by facilitating the interaction with follicular dendritic cells

    PubMed Central

    Yoon, Sun-Ok; Lee, In Yong; Zhang, Xin; Zapata, Mariana C.; Choi, Yong Sung

    2014-01-01

    The germinal center (GC) is a dynamic microenvironment where antigen (Ag)-activated B cells rapidly expand and differentiate, generating plasma cells (PC) that produce high-affinity antibodies. Precise regulation of survival and proliferation of Ag-activated B cells within the GC is crucial for humoral immune responses. The follicular dendritic cells (FDC) are the specialized stromal cells in the GC that prevent apoptosis of GC-B cells. Recently, we reported that human GC-B cells consist of CD9+ and CD9− populations and that it is the CD9+ cells that are committed to the PC lineage. In this study, we investigated the functional role of CD9 on GC-B cells. Tonsillar tissue section staining revealed that in vivo CD9+ GC-B cells localized in the light zone FDC area. Consistent this, in vitro CD9+ GC-B cells survived better than CD9− GC-B cells in the presence of HK cells, an FDC line, in a cell–cell contact-dependent manner. The frozen tonsillar tissue section binding assay showed that CD9+ GC-B cells bound to the GC area of tonsillar tissues significantly more than the CD9− GC-B cells did and that the binding was significantly inhibited by neutralizing anti-integrin β1 antibody. Furthermore, CD9+ cells bound to soluble VCAM-1 more than CD9− cells did, resulting in activation and stabilization of the active epitope of integrin β1. All together, our data suggest that CD9 on GC-B cells contributes to survival by strengthening their binding to FDC through the VLA4/VCAM-1 axis. PMID:24918051

  14. Dendrite

    NASA Technical Reports Server (NTRS)

    2004-01-01

    Researchers have found that as melted metals and alloys (combinations of metals) solidify, they can form with different arrangements of atoms, called microstructures. These microstructures depend on the shape of the interface (boundary) between the melted metal and the solid crystal it is forming. There are generally three shapes that the interface can take: planar, or flat; cellular, which looks like the cells of a beehive; and dendritic, which resembles tiny fir trees. Convection at this interface can affect the interface shape and hide the other phenomena (physical events). To reduce the effects of convection, researchers conduct experiments that examine and control conditions at the interface in microgravity. Microgravity also helps in the study of alloys composed of two metals that do not mix. On Earth, the liquid mixtures of these alloys settle into different layers due to gravity. In microgravity, the liquid metals do not settle, and a solid more uniform mixture of both metals can be formed.

  15. Follicular mucinosis

    PubMed Central

    Lewars, Marie; Levin, Josh; Purcell, Stephen

    2013-01-01

    Follicular mucinosis is an uncommon inflammatory disorder that characteristically presents as follicular papules and/or indurated plaques. The face, neck, and scalp are the most frequently affected sites, although lesions may occur on any site of the body. Histologically, the disorder is characterized by mucin deposition in the follicular epithelium. The condition is frequently divided into primary and secondary forms, with the latter form frequently associated with mycosis fungoides. In this case report, we describe a child with follicular mucinosis of the back and trunk and discuss the clinical variants, histopathological pattern, and treatment options. PMID:24350019

  16. Follicular mucinosis.

    PubMed

    Lewars, Marie; Levin, Josh; Purcell, Stephen

    2013-10-01

    Follicular mucinosis is an uncommon inflammatory disorder that characteristically presents as follicular papules and/or indurated plaques. The face, neck, and scalp are the most frequently affected sites, although lesions may occur on any site of the body. Histologically, the disorder is characterized by mucin deposition in the follicular epithelium. The condition is frequently divided into primary and secondary forms, with the latter form frequently associated with mycosis fungoides. In this case report, we describe a child with follicular mucinosis of the back and trunk and discuss the clinical variants, histopathological pattern, and treatment options.

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

    PubMed

    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

    To explore the expressions of CD11c+HLA-DR+dentritic cells in the follicular fluid of patients with OHSS and their significances. 100 individuals. 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. 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. 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). 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.

  18. Follicular dendritic cells in multicentric Castleman disease present human herpes virus type 8 (HHV8)-latent nuclear antigen 1 (LANA1) in a proportion of cases and is associated with an enhanced T-cell response.

    PubMed

    El-Daly, Hesham; Bower, Mark; Naresh, Kikkeri N

    2010-02-01

    Multicentric Castleman disease (MCD) is a rare human herpes virus type 8 (HHV8)-associated lymphoproliferative disorder that occurs more frequently in patients infected with human immunodeficiency virus (HIV). In tissue samples, HHV8-infected plasmablasts localise to the mantle zones of the lymphoid follicles. We revisited the immunohistological features in 25 lymph node (LN) and three spleen samples of MCD. In five (20%) LN and one (33%) spleen sample, HHV8 latent nuclear antigen 1 (LANA1) staining was also noted on the follicular dendritic cells (FDC). The HHV8-positive FDC subgroup of patients had significantly higher numbers of CD3-positive T cells infiltrating the follicles when compared to the HHV8-negative FDC subgroup (P = 0.047). Furthermore, the numbers of HHV8-positive plasmablasts and serum HHV8 viral copy numbers were lower among the HHV8-positive FDC subgroup when compared to the HHV8-negative FDC subgroup (not statistically significant). Our findings show, for the first time, possible 'presentation' of an HHV8 antigen by FDCs in MCD.

  19. A Rare Case of Epstein-Barr Virus Negative Inflammatory Pseudotumor-like Follicular Dendritic Cell Sarcoma Presenting as a Solitary Colonic Mass in a 53-Year-Old Woman; Case Report and Review of Literature.

    PubMed

    Kazemimood, Rossana; Saei Hamedani, Farid; Sharif, Asma; Gaitonde, Sujata; Wiley, Elizabeth; Giulianotti, Pier Cristoforo; Groth, John Vincent

    2016-06-13

    Follicular dendritic cell (FDC) sarcoma is a rare neoplasm that occurs predominantly in lymph nodes. One third of FDC sarcomas happens in extranodal sites. There are 2 morphologic variants of this tumor: conventional and inflammatory pseudotumor (IPT)-like. IPT-like FDC sarcomas are reported mostly in females and usually involve the spleen and liver. In all cases of IPT-like FDC sarcoma the Epstein-Barr virus (EBV) was positive by in situ hybridization except one instance. We report a case of 53-year-old woman who presented with abdominal discomfort. Colonoscopy identified a sessile polypoid mass. Microscopically, there was a prominent lymphoplasmacytic infiltrate. Interspersed among the reactive lymphoid cells were large, pleomorphic stromal cells with marked atypia, irregular and multilobed nuclei, and hyperchromatic smudged chromatin. Immunohistochemical studies demonstrated the atypical stromal cells to be strongly positive for CD10 and D2-40, but negative for CD21, CD23, Clusterin, and epidermal growth factor receptor. EBV-encoded mRNA was negative. A diagnosis of IPT-like FDC sarcoma was rendered. To our knowledge, this is the second case of EBV-negative IPT-like FDC sarcoma reported so far in the literature.

  20. Activation-induced cytidine deaminase expression in follicular dendritic cell networks and interfollicular large B cells supports functionality of ectopic lymphoid neogenesis in autoimmune sialoadenitis and MALT lymphoma in Sjögren's syndrome.

    PubMed

    Bombardieri, Michele; Barone, Francesca; Humby, Frances; Kelly, Stephen; McGurk, Mark; Morgan, Peter; Challacombe, Stephen; De Vita, Salvatore; Valesini, Guido; Spencer, Jo; Pitzalis, Costantino

    2007-10-01

    Demonstration of ectopic germinal center-like structures (GC-LSs) in chronically inflamed tissues in patients with autoimmune disorders is a relatively common finding. However, to what extent ectopic lymphoid structures behave as true GC and are able to support class switch recombination (CSR) and somatic hypermutation (SHM) of the Ig genes is still debated. In addition, no information is available on whether CSR and SHM can take place in the absence of GCs at extrafollicular sites in an ectopic lymphoid tissue. In this study, we show that in salivary glands (SGs) of Sjögren's syndrome (SS) activation-induced cytidine deaminase (AID), the enzyme responsible for CSR and SHM is invariably expressed within follicular dendritic cell (FDC) networks but is not detectable in SGs in the absence of ectopic GC-LSs, suggesting that FDC networks play an essential role in sustaining the Ag-driven B cell proliferation within SS-SGs. We also show that the recently described population of interfollicular large B cells selectively expresses AID outside ectopic GC in the T cell-rich areas of periductal aggregates. Finally, we report that AID retains its exclusive association with numerous, residual GCs in parotid SS-MALT lymphomas, whereas neoplastic marginal zone-like B cells are consistently AID negative. These results strongly support the notion that ectopic lymphoid structures in SS-SGs express the molecular machinery to support local autoantibody production and B cell expansion and may play a crucial role toward lymphomagenesis.

  1. MicroRNA-100-5p indirectly modulates the expression of Il6, Ptgs1/2 and Tlr4 mRNA in the mouse follicular dendritic cell-like cell line, FL-Y

    PubMed Central

    Aungier, Susan R; Ohmori, Hitoshi; Clinton, Michael; Mabbott, Neil A

    2015-01-01

    Follicular dendritic cells (FDC) are important stromal cells within the B-cell follicles and germinal centres (GC) of secondary lymphoid tissues. FDC trap and retain native antigens on their surfaces in the form of immune complexes that they display to B cells, in order to select those cells with the highest antigen affinity. MicroRNAs are short, non-coding RNAs that are approximately 18–25 nucleotides in length that regulate gene expression at the post-transcriptional level by repressing the translation of target genes. In the current study, in vivo and in vitro systems were used to identify microRNAs that were potentially expressed by FDC. Constitutive lymphotoxin-β receptor (LTβR) stimulation is required to maintain FDC in their differentiated state. We show that the rapid de-differentiation of spleen FDC that accompanied LTβR-blockade, coincided with a significant decrease in the expression of mmu-miR-100-5p, mmu-miR-138-5p and mmu-miR-2137. These microRNAs were shown to be expressed in the FDC-like cell line, FL-YB, and specific inhibition of mmu-miR-100-5p significantly enhanced expression of Il6, Ptgs1/2 and Tlr4 mRNA in this cell line. The expression of Il6, Ptgs1/2 and Tlr4 by FDC play important roles in regulating GC size and promoting high-affinity antibody responses, so it is plausible that mmu-miR-100-5p may help to regulate the expression of these genes during GC reactions. PMID:24944008

  2. 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

  3. Cell-secreted signals shape lymphoma identity.

    PubMed

    Gloghini, Annunziata; Bongarzone, Italia

    2015-10-01

    Sequencing data show that both specific genes and a number of signaling pathways are recurrently mutated in various types of lymphoma. DNA sequencing analyses of lymphoma have identified several aberrations that might affect the interaction between malignant cells and the tumor microenvironment. Microenvironmental functions are essential to lymphoma; they provide survival and proliferation signals and license immune evasion. It is plausible that interventions that aim to destroy tumor-microenvironment interactions may improve responses to therapeutics. Accordingly, the identification of extrinsic factors and their downstream intracellular signaling targets has led to much progress in understanding tumor-microenvironment interactions. Lymphoma cells are differently influenced by cells' interactions with components of their microenvironment; these cell extrinsic factors include soluble and immobilized factors, the extracellular matrix, and signals presented by neighboring cells. Soluble factors, which are often cell-secreted autocrine and paracrine factors, comprise a significant fraction of targetable molecules. To begin to understand how intercellular communication is conducted in lymphoma, a first order of study is deciphering the soluble factors secreted by malignant cells and microenvironmental cells. These soluble factors are shed into the interstitial fluid in lymphoma and can be conveniently explored using mass spectrometry. Protein components can be detected and quantified, thus enabling the routine navigation of the soluble part of the microenvironment. Elucidating functional and signaling states affords a new paradigm for understanding cancer biology and devising new therapies. This review summarizes knowledge in this field and discusses the utility of studying tumor-secreted factors.

  4. 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

  5. Follicular regulatory T cells impair follicular T helper cells in HIV and SIV infection

    PubMed Central

    Miles, Brodie; Miller, Shannon M.; Folkvord, Joy M.; Kimball, Abigail; Chamanian, Mastooreh; Meditz, Amie L.; Arends, Tessa; McCarter, Martin D.; Levy, David N.; Rakasz, Eva G.; Skinner, Pamela J.; Connick, Elizabeth

    2015-01-01

    Human and simian immunodeficiency viruses (HIV and SIV) exploit follicular lymphoid regions by establishing high levels of viral replication and dysregulating humoral immunity. Follicular regulatory T cells (TFR) are a recently characterized subset of lymphocytes that influence the germinal centre response through interactions with follicular helper T cells (TFH). Here, utilizing both human and rhesus macaque models, we show the impact of HIV and SIV infection on TFR number and function. We find that TFR proportionately and numerically expand during infection through mechanisms involving viral entry and replication, TGF-β signalling, low apoptosis rates and the presence of regulatory dendritic cells. Further, TFR exhibit elevated regulatory phenotypes and impair TFH functions during HIV infection. Thus, TFR contribute to inefficient germinal centre responses and inhibit HIV and SIV clearance. PMID:26482032

  6. 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.

  7. Follicular traction urticaria*

    PubMed Central

    Duman, Hatice; Topal, Ilteris Oguz; Kocaturk, Emek

    2016-01-01

    Inducible urticaria is a heterogeneous subgroup of chronic urticarias caused by a wide variety of environmental stimuli, such as exercise, cold, heat, pressure, sunlight, vibration, and water. A new term, follicular traction urticaria, was suggested as an unusual form of inducible urticarias. We report a patient who was diagnosed with follicular traction urticaria.

  8. 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.

  9. 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

  10. Retrospection to discovery of bursal function and recognition of avian dendritic cells; past and present.

    PubMed

    Oláh, Imre; Nagy, Nándor

    2013-11-01

    In 1954 the discovery of bursal function was one of the major contributions to the formation of the T and B cell concept of immunology. In 1978 the avian dendritic cells; bursal secretory dendritic cell (BSDC) and follicular dendritic cell (FDC) in the cecal tonsil were recognized. In 1982 the interdigitating dendritic cell was described in the periarteriolar lymphatic sheath (PALS) of the spleen. This paper is a retrospection of the stories of the discovery of bursal function and recognition of avian dendritic cells and includes the markers which can be used for monitoring and characterizing avian dendritic cells. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. Formation of the ovarian follicular antrum and follicular fluid.

    PubMed

    Rodgers, Raymond J; Irving-Rodgers, Helen F

    2010-06-01

    The formation of the follicular antrum and follicular fluid has received scant attention from researchers, yet both are important processes in follicular development. The central hypothesis on follicular fluid formation suggests that production by granulosa cells of hyaluronan and the chondroitin sulfate proteoglycan versican generates an osmotic gradient. This gradient draws in fluid derived from the thecal vasculature. Inter-alpha-trypsin inhibitor is also present in follicular fluid at least in species with large follicles, and inter-alpha-trypsin inhibitor and versican could additionally bind or cross-link with hyaluronan, resulting in the retention of these molecules within the follicular antrum. Barriers to the movement of fluid across the membrana granulosa are apparently minimal, as even relatively large serum proteins are present in follicular fluid. Despite the relative permeability of the follicular wall, aquaporins are present in granulosa cells and could be actively involved in the transport of water into the follicle. The formation of an antrum also requires movement of granulosa cells relative to each other to allow the fluid to accumulate. This presumably involves remodeling of cell-cell junctions and in species with small follicles may involve death of centrally located granulosa cells. Remodeling of the stroma and thecal layers also accompanies growth and expansion of the antrum and presumably involves similar processes that accompany growth of other glands.

  12. Follicular Lymphoma Presenting Solely as Chronic Follicular Conjunctivitis.

    PubMed

    Duncan, Joshua; Chen, Yingxin; Fuchs, Deborah; Cantu, Carlos; Wang, Mingwu

    2016-03-01

    Conjunctival lymphoma rarely can have atypical clinical presentations. The authors report a case of conjunctival follicular lymphoma that presented solely as bilateral chronic follicular conjunctivitis. This case underscores that the pathological characteristics of conjunctival follicles can only be determined by histopathologic examination. The patient underwent conjunctival scraping and biopsy after clinical history and examination failed to reveal the etiology of his chronic, symptomatic, follicular conjunctivitis. Histopathologic and immunohistochemical testing disclosed a bilateral low-grade conjunctival follicular lymphoma. The patient was treated with radiation therapy and remained in remission clinically 6 months after the treatment. Although rare, conjunctival lymphoma should be included in the differential diagnosis of chronic follicular conjunctivitis. This case is unique and further supports the notion that tissue biopsy may be needed for chronic, symptomatic conjunctivitis of unknown etiology.

  13. Robotic Follicular Unit Graft Selection.

    PubMed

    Bernstein, Robert M; Wolfeld, Michael B

    2016-06-01

    The use of robotic technology to harvest grafts in a follicular unit extraction (FUE) hair transplant procedure has been available since 2011. A new capability of the robotic system is to harvest follicular units based on the number of hairs they contain to increase the hair/wound yield. To assess the benefit of follicular unit graft selection during a robotic FUE procedure. This bilateral controlled study of 24 patients was designed to evaluate the ability of a robotic system to perform follicular unit graft selection. Compared with random follicular unit harvesting (the method performed by current robotic systems), robotic follicular unit graft selection produced more hairs per harvest attempt (2.60 vs 2.22) and more hairs per graft (2.72 vs 2.44). The clinical benefit of follicular unit graft selection (as measured by the increase in hairs per harvest attempt) was 17.0%. The clinical benefit (as measured by the increase in hairs per graft) was 11.4%. Results were statistically significant at p < .01. This study demonstrates the ability of robotic follicular unit graft selection to increase the amount of hairs yielded per donor wounds made in an FUE procedure.

  14. Oral prion disease pathogenesis is impeded in the specific absence of CXCR5-expressing dendritic cells.

    PubMed

    Bradford, Barry M; Reizis, Boris; Mabbott, Neil A

    2017-03-08

    After oral exposure the early replication of certain prion strains upon stromal-derived follicular dendritic cells (FDC) in the Peyer's patches in the small intestine is essential for the efficient spread of disease to the brain. However, little is known of how prions are initially conveyed from the gut lumen to establish infection on FDC. Our previous data suggest that mononuclear phagocytes such as CD11c(+) conventional dendritic cells play an important role in the initial propagation of prions from the gut lumen into Peyer's patches. But whether these cells conveyed orally-acquired prions towards FDC within Peyer's patches was not known. The chemokine CXCL13 is expressed by FDC and follicular stromal cells and modulates the homing of CXCR5-expressing cells towards the FDC-containing B cell follicles. Here, novel compound transgenic mice were created in which CXCR5-deficiency was specifically restricted to CD11c(+) cells. These mice were used to determine whether CXCR5-expressing conventional dendritic cells propagate prions towards FDC after oral exposure. Our data show that in the specific absence of CXCR5-expressing conventional dendritic cells the early accumulation of prions upon FDC in Peyer's patches and the spleen was impaired, and disease susceptibility significantly reduced. These data suggest that CXCR5-expressing conventional dendritic cells play an important role in the efficient propagation of orally-administered prions towards FDC within Peyer's patches in order to establish host infection.IMPORTANCE Many natural prion diseases are acquired by oral consumption of contaminated food or pasture. Once the prions reach the brain they cause extensive neurodegeneration which ultimately leads to death. In order for the prions to efficiently spread from the gut to the brain, they first replicate upon follicular dendritic cells within intestinal Peyer's patches. How the prions are first delivered to follicular dendritic cells to establish infection was

  15. Follicular and percutaneous penetration pathways of topically applied minoxidil foam.

    PubMed

    Blume-Peytavi, Ulrike; Massoudy, Lida; Patzelt, Alexa; Lademann, Jürgen; Dietz, Ekkehart; Rasulev, Utkur; Garcia Bartels, Natalie

    2010-11-01

    In the past, it was assumed that the intercellular route was the only relevant penetration pathway for topically applied substances. Recent results on follicular penetration emphasize that the hair follicles represent a highly relevant and efficient penetration pathway and reservoir for topically applied substances. This study investigates a selective closure technique of hair follicle orifices in vivo assessing interfollicular and follicular absorption rates of topical minoxidil foam in humans. In delimited skin area, single hair orifices or interfollicular skin were blocked with a microdrop of special varnish-wax-mixture in vivo. Minoxidil foam (5%) was topically applied, and transcutaneous absorption was measured by a new surface ionization mass spectrometry technique in serum. Different settings (open, closed or none of both) enabled to clearly distinguish between interfollicular and follicular penetration of the topically applied minoxidil foam. Five minutes after topical application, minoxidil was detected in blood samples when follicles remained open, whereas with closed follicles 30 min were needed. Highest levels were found first when both pathways were open, followed by open follicles and subsequently by closed follicles. These results demonstrate the high importance of the follicular penetration pathway. Hair follicles are surrounded by a dense network of blood capillaries and dendritic cells and have stem cells in their immediate vicinity, making them ideal targets for drug delivery. Copyright © 2010 Elsevier B.V. All rights reserved.

  16. Facial follicular porokeratosis: a case report.

    PubMed

    Wang, Nadia S; Gruson, Lisa M; Kamino, Hideko

    2010-10-01

    Porokeratosis is a disorder of keratinization, characterized clinically by a peripheral keratotic ridge and histologically by the cornoid lamella. We describe a patient with follicular porokeratosis with a distinctive clinical presentation. We believe that follicular porokeratosis is a unique histopathologic variant of porokeratosis, with cornoid lamellae centered in follicular infundibula. Further, this is the only report of follicular porokeratosis involving the face exclusively.

  17. Study of cell secretion using MEMS-based arrays

    NASA Astrophysics Data System (ADS)

    Feng, Xiaojun; Szaro, Ben G.; Castracane, James

    2004-01-01

    This paper focuses on the development of a custom MEMS-based array which will facilitate cell secretion studies by enabling parallel electrochemical detection of secretion events from separate cells with millisecond resolution. Initial prototypes of the microarrays have been fabricated with well-shaped gold electrodes which roughly conform to the shape of a single cell. Amperometric measurements on bovine adrenal chromaffin cells using the prototype microarrays concluded that 80% of the catecholamine secreted from the cells was captured by the well-electrodes. This was a 4-fold increase in detection efficiency over the conventional carbon fiber electrode method. To expand the applicability of this method, additional cell-lines and microarray designs are under investigation. An amphibian fibroblast cell-line (FT cell-line, American Tissue Culture Collection) is being used in our lab. FT cells can take up hormones or other biological compounds from the culture media through a non-specific uptake mechanism which is still under investigation. Microarrays of a new design have been fabricated with patterned gold electrodes on polyimide. A different testing method will be applied to these new microarrays. The FT cells will be cultured directly on top of the microarrays to cover the gold electrodes. Cells will then be loaded with norepinephrine by incubation in media containing 1mM norepinephrine. Rapid elevation of intracellular Ca2+ levels triggers the exocytosis of norepinephrine which then can be detected by the gold electrode. The new polyimide based microarrays have been successfully used to support confluent growth of the FT cells. Loading of the FT cells with norepinephrine and electrochemical detection tests are underway.

  18. Study of cell secretion using MEMS-based arrays

    NASA Astrophysics Data System (ADS)

    Feng, Xiaojun; Szaro, Ben G.; Castracane, James

    2003-12-01

    This paper focuses on the development of a custom MEMS-based array which will facilitate cell secretion studies by enabling parallel electrochemical detection of secretion events from separate cells with millisecond resolution. Initial prototypes of the microarrays have been fabricated with well-shaped gold electrodes which roughly conform to the shape of a single cell. Amperometric measurements on bovine adrenal chromaffin cells using the prototype microarrays concluded that 80% of the catecholamine secreted from the cells was captured by the well-electrodes. This was a 4-fold increase in detection efficiency over the conventional carbon fiber electrode method. To expand the applicability of this method, additional cell-lines and microarray designs are under investigation. An amphibian fibroblast cell-line (FT cell-line, American Tissue Culture Collection) is being used in our lab. FT cells can take up hormones or other biological compounds from the culture media through a non-specific uptake mechanism which is still under investigation. Microarrays of a new design have been fabricated with patterned gold electrodes on polyimide. A different testing method will be applied to these new microarrays. The FT cells will be cultured directly on top of the microarrays to cover the gold electrodes. Cells will then be loaded with norepinephrine by incubation in media containing 1mM norepinephrine. Rapid elevation of intracellular Ca2+ levels triggers the exocytosis of norepinephrine which then can be detected by the gold electrode. The new polyimide based microarrays have been successfully used to support confluent growth of the FT cells. Loading of the FT cells with norepinephrine and electrochemical detection tests are underway.

  19. 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.

  20. IMMUNOGLOBULIN LIGHT CHAIN IMMUNOHISTOCHEMISTRY REVISITED, WITH EMPHASIS ON REACTIVE FOLLICULAR HYPERPLASIA VS. FOLLICULAR LYMPHOMA

    PubMed Central

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

    2009-01-01

    The identification of monotypic light chains is an important adjunct to the diagnosis of B-cell lymphoma, yet is often difficult to reliably perform on formalin-fixed paraffin sections. We have evaluated a new set of monoclonal antibodies to kappa and lambda light chain 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 for the appropriate light chain was seen in each of 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 also seen in 6 additional cases (10%) in which the flow cytometry had been 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. PMID:20042853

  1. Obinutuzumab in follicular lymphoma.

    PubMed

    Martinez-Calle, N; Figueroa-Mora, R; Villar-Fernandez, S; Marcos-Jubilar, M; Panizo, C

    2016-12-01

    The CD20 marker continues to be exploited as a therapeutic target for non-Hodgkin's lymphoma. Obinutuzumab is part of a new generation of anti-CD20 monoclonal antibodies, which are synthesized using molecular engineering technology, resulting in novel target epitopes and unprecedented optimization of antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis. Rituximab is the current gold standard for anti-CD20 therapy, yet despite outstanding results published over the past decade, many patients continue to relapse after anti-CD20 regimens. Obinutuzumab is slowly positioning itself in the treatment of CD20+ B-cell neoplasms. On the basis of favorable results from the phase III GADOLIN trial, obinutuzumab was recently approved by the U.S. Food and Drug Administration in combination with bendamustine followed by obinutuzumab maintenance, for the treatment of follicular lymphoma (FL) patients who relapsed or are refractory to a rituximab-containing regimen. Additional phase III trials are underway to test obinutuzumab as a first-line anti-CD20 agent in FL with good preliminary results (GALLIUM trial); thus, it is likely that obinutuzumab will soon achieve a first-line indication. It is plausible that obinutuzumab will replace rituximab as the gold standard for chemoimmunotherapy in FL, although some safety concerns still need to be resolved. This review will address the preclinical pharmacology and the main aspects of the clinical development of obinutuzumab for the treatment of FL.

  2. Role of ovarian theca and granulosa cell interaction in hormone productionand cell growth during the bovine follicular maturation process.

    PubMed

    Yada, H; Hosokawa, K; Tajima, K; Hasegawa, Y; Kotsuji, F

    1999-12-01

    We have investigated the possible role of theca and granulosa cell interaction in the control of the hormone-producing activity and growth of granulosa and theca cells during bovine ovarian follicular development, using a coculture system in which granulosa and theca cells were grown on opposite sides of a collagen membrane. When follicular cells were isolated from small follicles (3-5 mm), theca cells reduced estradiol, progesterone, and inhibin production by granulosa cells to 14 +/- 5%, 64 +/- 6%, and 27 +/- 4%, respectively, of the production by granulosa cells cultured alone. On the other hand, when the cells were isolated from large follicles (15-18 mm), theca cells increased these levels to 253 +/- 34%, 156 +/- 24%, and 287 +/- 45%, respectively. Theca cells did not affect the growth of granulosa cells. Androstenedione production by theca cells was augmented by granulosa cells to 861 +/- 190% (in small follicles) and 1298 +/- 414% (in large follicles), respectively. The growth of theca cells was also augmented by granulosa cells (small follicle, 210 +/- 43%, and large follicle, 194 +/- 24%, respectively). These results indicate that theca cells secrete factor(s) inhibiting the differentiation of immature while promoting that of matured granulosa cells; they also suggest that granulosa cells secrete factor(s) promoting both the differentiation and growth of theca cells throughout the follicular maturation process.

  3. How T cells earn the follicular rite of passage.

    PubMed

    Vinuesa, Carola G; Cyster, Jason G

    2011-11-23

    The discovery that Bcl-6 was the transcriptional regulator of follicular helper T (Tfh) cells completed the recognition of this population as an effector subset specialized in the provision of help to B cells. Improved reagents and recent models that allow tracking of Bcl-6-expressing T cells have revealed that the decision to become a Tfh cell occurs soon after T cells are primed by dendritic cells and start dividing, before interaction with B cells. The latter are important for sustaining Bcl-6 expression. Bcl-6 coordinates a signaling program that changes expression or function of multiple guidance receptors, leading to Tfh cell localization within germinal centers. This program is not unique to CD4(+) helper T cells; FoxP3(+) regulatory T cells and NKT cells co-opt the follicular differentiation pathway to enter the follicle and become specialized follicular cells. This review will focus on recent insights into the early events that determine Tfh cell differentiation. Copyright © 2011 Elsevier Inc. All rights reserved.

  4. 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

  5. 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.

  6. 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.

  7. Epigenetic dysregulation in follicular lymphoma

    PubMed Central

    Araf, Shamzah; Okosun, Jessica; Koniali, Lola; Fitzgibbon, Jude; Heward, James

    2016-01-01

    The adoption of next-generation sequencing technologies has led to a remarkable shift in our understanding of the genetic landscape of follicular lymphoma. While the disease has been synonymous with the t(14;18), the prevalence of alterations in genes that regulate the epigenome has been established as a pivotal hallmark of these lymphomas. Giant strides are being made in unraveling the biological consequences of these alterations in tumorigenesis opening up new opportunities for directed therapies. PMID:26698557

  8. [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.

  9. [Follicular lymphoma in two brothers].

    PubMed

    Asahi, A; Okamoto, S; Matsushita, H; Hattori, Y; Takayama, N; Ikeda, Y

    2001-05-01

    Two brothers, whose parents had a history of exposure to atomic bomb radiation, developed non-Hodgkin's lymphoma. The younger brother, a 48-year-old man, was diagnosed as having follicular small-cleaved cell lymphoma in October, 1996. He had extranodal lymphoma involvement of the right kidney, bone marrow and skin, in addition to generalized lymphadenopathy. He was treated with intermittent COP chemotherapy, and good control of the lymphoma was obtained. The elder brother, aged 50 years, was diagnosed as having follicular mixed cell lymphoma in May, 1998. He also had extranodal lymphoma involvement of the right parotid gland and bone marrow, as well as generalized lymphadenopathy. After one course of CHOP chemotherapy, he developed paresis of the lower legs and was found to have a mass at the Th5-6 vertebrae by CT scan. After four courses of CHOP chemotherapy followed by ESHAP chemotherapy and radiotherapy, he achieved complete remission, and has since been well. Follicular lymphoma occurring among siblings is rare. Further cytogenetic and molecular studies may provide a better understanding of its etiology.

  10. Follicular helper T cells progressively differentiate to regulate the germinal center response

    PubMed Central

    Licona-Limón, Paula; Esplugues, Enric; Flavell, Richard; Craft, Joe

    2016-01-01

    Germinal center (GC) B cells undergo affinity selection, dependent upon interactions with CD4+ follicular helper T (TFH) cells. We demonstrate that TFH cells progressed through transcriptionally and functionally distinct stages, providing differential signals for GC regulation. They initially localized proximally to mutating B cells, secreted IL-21, induced expression of the transcription factor Bcl-6 and selected high affinity B cell clones. As the GC response evolved, TFH cells extinguished IL-21 and switched to IL-4 production, showed robust CD40 ligand expression and promoted the development of antibody-secreting B cells via upregulation of the transcription factor Blimp-1. Thus, TFH cells in the B cell follicle progressively differentiated through stages of localization, cytokine production and surface ligand expression to fine-tune of the GC reaction. PMID:27573866

  11. Recent Advances in Follicular Lymphoma: Pediatric, Extranodal, and Follicular Lymphoma in Situ.

    PubMed

    Ferry, Judith A

    2010-12-01

    Follicular lymphoma is a relatively common B-cell lymphoma composed of follicle center B lymphocytes. Follicular lymphomas occurring in the pediatric population and in some extranodal sites exhibit particular clinicopathologic features and clinical behavior that are often distinct from adult nodal follicular lymphoma. A type of "in-situ" follicular lymphoma presents as intrafollicular neoplastic cells in a background of architecturally normal lymphoid tissue and may be difficult to recognize in routine sections. Accurate recognition of the morphologic variants and clinicopathologic subtypes of follicular lymphoma is important to avoid confusing them with other lymphomas and reactive processes; in addition, some of these subtypes of follicular lymphoma display unusually indolent clinical behavior that warrant their separation from "conventional" follicular lymphoma. Copyright © 2010 Elsevier Inc. All rights reserved.

  12. 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

  13. Acitretin-induced spiny follicular hyperkeratosis.

    PubMed

    Yanik, Mehmet Emin; Erfan, Gamze; Albayrak, Hulya; Tasolar, Kaan; Albayrak, Sule; Gelincik, Ibrahim; Kulac, Mustafa

    2015-08-12

    Spiny follicular hyperkeratosis (SFH) is follicular flesh-colored hyperkeratotic spicules that are linked to different situations including drug reactions. Previously suspected drugs are BRAF inhibitors and cyclosporine. We described a 51-year-old psoriasis patient with SFH who had been using acitretin.

  14. Acitretin-induced spiny follicular hyperkeratosis.

    PubMed

    Yanik, Mehmet Emin; Erfan, Gamze; Albayrak, Hulya; Tasolar, Kaan; Albayrak, Sule; Gelincik, Ibrahim; Kulac, Mustafa

    2016-01-01

    Spiny follicular hyperkeratosis (SFH) is follicular flesh-colored hyperkeratotic spicules that are linked to different situations including drug reactions. Previously suspected drugs are BRAF inhibitors and cyclosporine. We described a 51-year-old psoriasis patient with SFH who had been using acitretin.

  15. Association between follicular tracheitis and gastroesophageal reflux.

    PubMed

    Duval, Melanie; Meier, Jeremy; Asfour, Fadi; Jackson, Daniel; Grimmer, J Fredrik; Muntz, Harlan R; Park, Albert H

    2016-03-01

    Follicular tracheitis (also known as tracheal cobblestoning) is an entity that is poorly described and of unclear significance. The objective of this study was to better define follicular tracheitis and determine the association between the clinical finding of follicular tracheitis on bronchoscopy and objective evidence of gastroesophageal reflux disease. Retrospective chart review of children with recurrent croup having undergone a rigid bronchoscopy and an investigation for gastroesophageal reflux between 2001 and 2013. 117 children with recurrent croup children age 6-144 months were included in the study. Follicular tracheitis was noted on 41% of all bronchoscopies. Fifty-nine percent of all children who underwent bronchoscopy were diagnosed with gastroesophageal reflux on at least one investigation. Forty-nine of 117 children underwent a pH probe study, and 51% were found to have evidence of reflux on this study. Nine children were diagnosed with eosinophilic esophagitis. Three patients underwent a biopsy of the follicular tracheitis lesions, which revealed chronic inflammation. There was no evidence of an association between findings of follicular tracheitis and a positive test for gastroesophageal reflux (p=0.52) or a positive pH probe study (p=0.64). There was no association between follicular tracheitis and subglottic stenosis (p=0.33) or an history of asthma and/or atopy (p=0.19). In children with recurrent croup, follicular tracheitis remains an unspecific finding associated with an inflammatory disorder of unknown etiology. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  16. Endothelial cell-derived microparticles induce plasmacytoid dendritic cell maturation: potential implications in inflammatory diseases

    PubMed Central

    Angelot, Fanny; Seillès, Estelle; Biichlé, Sabeha; Berda, Yael; Gaugler, Béatrice; Plumas, Joel; Chaperot, Laurence; Dignat-George, Françoise; Tiberghien, Pierre; Saas, Philippe; Garnache-Ottou, Francine

    2009-01-01

    Background Increased circulating endothelial microparticles, resulting from vascular endothelium dysfunction, and plasmacytoid dendritic cell activation are both encountered in common inflammatory disorders. The aim of our study was to determine whether interactions between endothelial microparticles and plasmacytoid dendritic cells could contribute to such pathologies. Design and Methods Microparticles generated from endothelial cell lines, platelets or activated T cells were incubated with human plasmacytoid dendritic cells sorted from healthy donor blood or with monocyte-derived dendritic cells. Dendritic cell maturation was evaluated by flow cytometry, cytokine secretion as well as naive T-cell activation and polarization. Labeled microparticles were also used to study cellular interactions. Results Endothelial microparticles induced plasmacytoid dendritic cell maturation. In contrast, conventional dendritic cells were resistant to endothelial microparticle-induced maturation. In addition to upregulation of co-stimulatory molecules, endothelial microparticle-matured plasmacytoid dendritic cells secreted inflammatory cytokines (interleukins 6 and 8, but no interferon-α) and also induced allogeneic naive CD4+ T cells to proliferate and to produce type 1 cytokines such as interferon-γ and tumor necrosis factor-α. Endothelial microparticle endocytosis by plasmacytoid dendritic cells appeared to be required for plasmacytoid dendritic cell maturation. Importantly, the ability of endothelial microparticles to induce plasmacytoid dendritic cells to mature was specific as microparticles derived from activated T cells or platelets (the major source of circulating microparticules in healthy subjects) did not induce such plasmacytoid dendritic cell maturation. Conclusions Our data show that endothelial microparticles specifically induce plasmacytoid dendritic cell maturation and production of inflammatory cytokines. This novel activation pathway may be implicated in

  17. 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.

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

    ClinicalTrials.gov

    2016-12-20

    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

  19. Duodenal follicular lymphoma: Comprehensive gene expression analysis with insights into pathogenesis

    PubMed Central

    Takata, Katsuyoshi; Tanino, Motohiko; Ennishi, Daisuke; Tari, Akira; Sato, Yasuharu; Okada, Hiroyuki; Maeda, Yoshinobu; Goto, Naoe; Araki, Hiroshi; Harada, Mai; Ando, Midori; Iwamuro, Masaya; Tanimoto, Mitsune; Yamamoto, Kazuhide; Gascoyne, Randy D; Yoshino, Tadashi

    2014-01-01

    Follicular lymphoma (FL) of the gastrointestinal tract, particularly duodenal follicular lymphoma (DFL), is a rare variant of FL with indolent clinical behavior, and this disease is included in the 2008 World Health Organization classification system. In contrast to nodal follicular lymphoma (NFL), DFL occurs most frequently in the second part of the duodenum, lacks follicular dendritic cell meshworks and has memory B-cell characteristics. However, its molecular pathogenesis is still unclear. In the present study, we examined 10 DFL, 18 NFL and 10 gastric MALT lymphoma samples using gene expression analysis. Quantitative RT-PCR experiments and immunohistochemical analysis for 72 formalin-fixed, paraffin-embedded tissues from an independent series, including 32 DFL, 19 gastric MALT lymphoma and 27 NFL samples, were performed for validation of microarray data. Gene expression profiles of the three lymphoma types were compared using 2918 differentially expressed genes (DEG) and results suggested that DFL shares characteristics of MALT lymphoma. Among these DEG, CCL20 and MAdCAM-1 were upregulated in DFL and MALT but downregulated in NFL. In contrast, protocadherin gamma subfamily genes were upregulated in DFL and NFL. Quantitative RT-PCR and immunohistochemical studies demonstrated concordant results. Double immunofluorescence studies revealed that CCL20 and CCR6 were co-expressed in both DFL and MALT. We hypothesize that increased expression of CCL20 and MAdCAM-1 and co-expression of CCL20 and CCR6 may play an important role in tumorigenesis. PMID:24602001

  20. Rituximab and Oblimersen in Treating Patients With Stage II, Stage III, or Stage IV Follicular Non-Hodgkin's Lymphoma

    ClinicalTrials.gov

    2013-01-04

    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

  1. Punctate follicular porokeratosis: clinical and pathologic features.

    PubMed

    Trikha, Ritika; Wile, Anna; King, Joy; Ward, Kimberley H M; Brodell, Robert T

    2015-11-01

    Porokeratosis is a disorder of keratinization characterized by an abnormal cornoid lamella surrounding an annular, scaly plaque with an atrophic center. A histologic variant of this condition has been proposed, termed follicular porokeratosis, in cases where follicular involvement was contiguous with an annular cornoid lamella. There has been only 1 report of punctate follicular porokeratosis, in which cornoid lamellae originated exclusively from hair follicles with no associated annular plaque. The authors present the second case of punctate follicular porokeratosis, further supporting the contention that this entity is a unique form of porokeratosis rather than a histologic variant. A 56-year-old African American female presented to the dermatology clinic with a 3-month history of keratotic lesions localized on the right posterior shoulder. Examination revealed an area of perifollicular keratotic papules, each surrounded by an erythematous rim. Histopathology revealed a cornoid lamella originating within a hair follicle, with the parakeratotic column protruding through the follicular orifice. The static nature of the condition along with exclusive involvement of hair follicles supports the notion of punctate follicular porokeratosis as a distinct clinical entity. The diagnosis of this condition relies heavily on proper histopathologic sampling revealing punctate follicular cornoid lamellae.

  2. 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.

  3. 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.

  4. Follicular Bronchiolitis: A Literature Review

    PubMed Central

    Okafor, Ndubuisi C.; Ramirez, Jose F.; Smolley, Laurence

    2015-01-01

    Follicular bronchiolitis (FB) also known as hyperplasia of the bronchial associated lymphoid tissue (BALT), or bronchiolar nodular lymphoid hyperplasia, is an entity characterized by the development of lymphoid follicles with germinal centers in the walls of small airways. FB is thought to be caused by antigenic stimulation of BALT, followed by a polyclonal lymphoid hyperplasia. It is currently classified as one of the reactive pulmonary lymphoid disorders in a group known as the lymphoproliferative pulmonary diseases (LPDs). FB is a pathological diagnosis that can be seen in several clinical settings, including connective tissue diseases, immunodeficiency states, autoimmune diseases, infections, obstructive airway diseases, as well as several types of interstitial lung diseases (ILDs). Its characteristics need to be carefully identified and differentiated from other closely related diseases in the group of LPDs due to significant differences in treatment and prognosis. PMID:26500941

  5. Novel Drugs in Follicular Lymphoma

    PubMed Central

    Anastasia, Antonella; Rossi, Giuseppe

    2016-01-01

    Follicular lymphoma(FL) is the most common indolent non-Hodgkin lymphoma and constitutes 15% to 30% of lymphoma diagnoses. The natural history of the disease is characterized by recurrent relapses and progressively shorter remissions with a median survival of 10yrs. The impossibility of achieving a definite cure, have prompted investigations into the possible role of more active and less toxic strategies with innovative therapeutic agents. Recently Casulo et al. demonstrated that approximately 20% of patients with FL relapse within two years after achieving remission with R-CHOP and have a poor prognosis. It is conceivable that this particularly chemoresistant population would benefit from specifically targeting the biologic and genetic factors that likely contribute to their poor prognosis. Evolving strategies for difficult to treat FL patients have recently considered immunomodulatory agents, new monoclonal antibodies as well as drugs targeting selective intracellular pathways. The importance of targeting the microenvironment together with the malignant FL cell has been particularly underscored. We review the most promising approaches, such as combining anti-CD20 antibodies with immunomodulatory drugs (Lenalidomide), mAbs directed against other surface antigens such as CD22 and CD23 (Epratuzumab, Lumiliximab), immunomodulatory antibodies such as PD-1, or inhibitors of key steps in the B-cell receptor pathway signaling such as PI3K inhibitors (Idelalisib, Duvelisib). Another highly attractive approach is the application of the bi-specific T-cell engaging (BiTE) antibody blinatumomab which targets both CD19 and CD3 antigens. Moreover, we highlight the potential of these therapies, taking into account their toxicity. Of course, we must wait for Phase III trials results to confirm the benefit of these new treatment strategies toward a new era of chemotherapy-free treatment for follicular lymphoma. PMID:27872741

  6. Clinicopathological features of neuroblastic tumors with opsoclonus-myoclonus-ataxia syndrome: Follicular structure predicts a better neurological outcome.

    PubMed

    Fukushima, Hiroko; Inoue, Takeshi; Takama, Yuichi; Ishii, Naomi; Okuno, Takahiro; Kobayashi, Yasutsugu; Yoneda, Akihiro; Nakamura, Tetsuro; Kuki, Ichiro; Hara, Junichi

    2017-10-01

    Neuroblastic tumors (NT) with opsoclonus-myoclonus syndrome (OMS) display characteristic histological features, such as lymphocytic infiltration with lymphoid follicles, indicating an underlying immune response. We retrospectively assessed NT patients from 2001 to 2016. Five cases of NT with OMS and 76 cases of NT without OMS were histopathologically reviewed in this study. The grade of lymphocytic infiltration was evaluated. The number of follicles was counted and the presence or absence of lymphoid follicles was recorded for each case. We also confirmed the presence or absence of follicular dendritic cells (FDCs). We investigated the relationship between the histopathological and clinical findings of NT with OMS. Lymphocytic infiltration was observed in all cases; however, the precise follicular structure was occasionally unclear. Patients with clear follicular structures displayed germinal centers including tingible body macrophages and FDCs. All patients without neurological sequelae demonstrated a clear follicular structure with a FDC meshwork pattern. The interval between OMS onset and the detection and initial treatment of NT was typically longer in patients with neurological sequelae compared to those without neurological sequelae. Early detection and treatment of NT with OMS at the phase of a clear follicular formation with multiple FDC may provide favorable neurological outcomes. © 2017 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.

  7. 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

  8. Dendritic spikes veto inhibition.

    PubMed

    Stuart, Greg J

    2012-09-06

    How inhibition regulates dendritic excitability is critical to an understanding of the way neurons integrate the many thousands of synaptic inputs they receive. In this issue of Neuron, Müller et al. (2012) show that inhibition blocks the generation of weak dendritic spikes, leaving strong dendritic spikes intact. Copyright © 2012 Elsevier Inc. All rights reserved.

  9. [Multiple familial follicular hamartoma (author's transl)].

    PubMed

    Delacrétaz, J; Balsiger, F

    1979-01-01

    Multiple cystic and proliferative follicular lesions localized on the face and the genitalia of several members of an Italian family are described. Transmission seems to be autosomal dominant, with weak penetration and variable expressivity.

  10. Primary conjunctival follicular lymphoma mimicking chronic conjunctivitis.

    PubMed

    Labrador Velandia, S; García Lagarto, E; Saornil, M A; García Álvarez, C; Cuello, R; Diezhandino, P

    2016-02-01

    The case is presented of a 43 year-old male patient with chronic follicular conjunctivitis, negative bacterial serology, and refractory to local treatment. The incisional biopsy performed showed to be consistent with reactive lymphoid hyperplasia. A year later, a new incisional biopsy showed follicular lymphoma, with no systemic involvement, and he was treated with local radiotherapy. When a chronic follicular conjunctivitis is refractory to treatment, it is essential to perform an incisional biopsy to establish the histopathological diagnosis that can range from chronic inflammation, reactive lymphoid hyperplasia to lymphoma. Follicular lymphoma is rare among conjunctival lymphomas, and the staging is indispensable for the correct therapeutic approach. Copyright © 2014 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

  11. Tumor of follicular infundibulum with unique features*

    PubMed Central

    Haddad, Natalie; de Oliveira Filho, Jayme; Reis, Mariana Junqueira Lacerda; Michalany, Alexandre Ozores; Nasser, Kassila da Rosa; Corbett, Ana Maria França

    2014-01-01

    Tumor of the follicular infundibulum is a rare benign cutaneous adnexal neoplasm with variable clinical presentation. In most cases the diagnosis is made with the help of histopathology, due to lack of a characteristic clinical presentation. The most common form is a solitary lesion, but it can be multiple or eruptive, then called infundibulomatose. This case report illustrates a patient with multiple lesions of tumor of the follicular infundibulum with bizarre aspect and atypical location. PMID:25387502

  12. Microbubble Array Diffusion Assay for the Detection of Cell Secreting Factors

    PubMed Central

    Bobo, Bryan; Phalen, Dana; Rebhahn, Jonathan; Piepenbrink, Michael S.; Zheng, Bo; Mosmann, Tim R.; Kobie, James J.; DeLouise, Lisa

    2014-01-01

    The therapeutic potential of monoclonal antibodies (mAbs) makes them an ideal tool in both clinical and research applications due to their ability to recognize and bind specific epitopes with high affinity and selectivity. While mAbs offer significant therapeutic potential, their utility is overshadowed by the cost associated with their production, which often relies on the ability to identify minority antigen specific cells out of a heterogeneous population. To address concerns with suboptimal methods for screening cells, we have developed a cell sorting array comprised of nanoliter spherical cell culture compartments, termed microbubble (MB) wells. We demonstrate a proof-of-concept system for the detection of cell secreted factors from both immortalized cell lines and primary B cell samples. Exploiting the unique ability of the MB well architecture to accumulate cell secreted factors as well as affinity capture coatings, we demonstrate on chip detection and recovery of antibody secreting cells for sequencing of immunoglobin genes. Furthermore, rapid image capture and analysis capabilities were developed for the processing of large MB arrays, thus facilitating the ability to conduct high-throughput screening of heterogeneous cell samples faster and more efficiently than ever before. The proof-of-concept assays presented herein lay the groundwork for the progression of MB well arrays as an advanced on chip cell sorting technology. PMID:25079889

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

    PubMed Central

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

    2014-01-01

    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. PMID:24803956

  14. 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

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. Pancreatic tumor cell secreted CCN1/Cyr61 promotes endothelial cell migration and aberrant neovascularization.

    PubMed

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

    2014-05-16

    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.

  20. 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.

  1. Effects of breed on follicular dynamics and oestradiol secretion during the follicular phase in sheep.

    PubMed

    Gonzalez-Añover, P; Encinas, T; Veiga-Lopez, A; Ammoun, I; Contreras, I; Ros, J M; Ariznavarreta, C; Tresguerres, J A F; Gonzalez-Bulnes, A

    2007-02-01

    Current study evaluates effects from breed and management background on follicular dynamics and endocrine output during the follicular phase of sheep oestrous cycle. Follicular phases were synchronized with three cloprostenol doses, 10 days apart, in three groups of 10 females of different non-prolific Spanish breeds (Manchega, Rubia del Molar and Negra de Colmenar). Development of all follicles reaching antral diameters >or=2 mm was assessed by daily transrectal ultrasonographies, whereas follicular function was evaluated by measurement of plasma oestradiol concentrations. All the ovulatory follicles were present at induced luteolysis in Manchega sheep, while a 93.7% were detected in Rubia del Molar and Negra de Colmenar ewes. The mean size of these ovulatory follicles was similar between breeds at 0 h, but their growth rates were higher in Manchega ewes, reaching a larger size at oestrous detection than in Negra de Colmenar and Rubia del Molar sheep (p < 0.05). Conversely, the oestradiol levels increased with time in Rubia del Molar and Negra de Colmenar (p < 0.05); whilst remained stable in Manchega females. However, the patterns of follicular turnover were similar between breeds. These results indicate that, though differences in follicular size and size distribution, patterns of follicular turnover in sheep are affected neither by the breed nor by the background of management and selection.

  2. Inflammation and Human Ovarian Follicular Dynamics

    PubMed Central

    Boots, Christina E.

    2016-01-01

    Inflammation is a biologic process that mediates tissue effects including vasodilation, hyperemia, edema, collagenolysis and cell proliferation through complex immunologic pathways. In regards to the ovary, inflammation has key physiologic roles in ovarian folliculogenesis and ovulation. On the other hand inflammatory processes are subject to underlying pathology and if pushed, pro-inflammatory conditions may have a negative impact on ovarian follicular dynamics. Obesity and polycystic ovary syndrome (PCOS) serve as examples of conditions associated with chronic endogenous production of low-grade pro-inflammatory cytokines. Both conditions negatively impact ovarian folliculogenesis and ovulation. The pages that follow summarize the role of inflammation in normal ovarian follicular dynamics and evidence for its role in mediating the negative effects of obesity and PCOS on ovarian follicular dynamics. The review concludes with a summary supporting a role for lifestyle factors that favorably impact inflammatory process involved in obesity and PCOS to improve ovarian function. PMID:26132931

  3. An analysis of follicular punches, mechanics, and dynamics in follicular unit extraction.

    PubMed

    Cole, John P

    2013-08-01

    Success in follicular unit extraction requires an understanding of forces, fluid dynamics, instrumentation, and individual patient variation. Sharp punches require a lower axial and tangential force to dissect follicular groups. The angle of hair emergence and the size of a punch influence the wound size and the depth of an incision. A procedure must be individualized based on surface follicular group characteristics; hair splay; and strength of attachment between the outer root sheath, inner root sheath, and adipose with regard to hair follicles. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. Meningioma with metastasis from follicular carcinoma thyroid.

    PubMed

    Chaturvedi, Sujata; Gupta, Sanjeev; Kumari, Rima

    2010-01-01

    A 45-year-old female presented with loss of vision in the left eye, numbness on left half of face and left-sided hemicrania for two months. On the basis of radiological investigations, provisional diagnosis of basal meningioma was made. Tissue sent for histopathological evaluation revealed a dual tumor-meningioma with metastasis from follicular carcinoma, thyroid. To the best of authors' knowledge, this is the first report of a tumor metastasizing to another tumor, where a follicular carcinoma thyroid metastasized to meningioma.

  5. Etiology and differential diagnosis of non-trachomatous follicular conjunctivitis

    PubMed Central

    Thygeson, P.

    1957-01-01

    The author points out that while previously only follicular conjunctivitis of the inclusion or swimming-pool type, and of the Béal type, was classified as “acute follicular conjunctivitis”, it is now necessary to enlarge this group to include at least four other clinical or etiological entities: epidemic keratoconjunctivitis, acute herpetic keratoconjunctivitis, Newcastle disease conjunctivitis, and pharyngoconjunctival fever. The author then defines and describes chronic follicular conjunctivitis, toxic follicular conjunctivitis (molluscum contagiosum) and folliculosis. Imagesp1001-a PMID:13472441

  6. 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.

  7. Enhanced Eradication of Lymphoma by Tumor-Specific Cytotoxic T Cells Secreting an Engineered Tumor-Specific Immunotoxin

    DTIC Science & Technology

    2008-06-01

    particularly in hairy cell leukemia , were offset by an unfavorable toxicity profile. The current project will use the anti- tumor activity of CD22-PEA...Tumor-Specific Cytotoxic T Cells Secreting an Engineered Tumor-Specific Immunotoxin PRINCIPAL INVESTIGATOR: Yotnda Patricia, Ph.D...CONTRACTING ORGANIZATION: Baylor College of Medicine Cell and Gene Center Houston, TX 77030 REPORT DATE: June 2008 TYPE OF

  8. Follicular vitiligo: A report of 8 cases.

    PubMed

    Gan, Emily Yiping; Cario-André, Muriel; Pain, Catherine; Goussot, Jean-Francois; Taïeb, Alain; Seneschal, Julien; Ezzedine, Khaled

    2016-06-01

    Follicular vitiligo, a recently proposed new subtype of vitiligo, has primary involvement of the hair follicle melanocytic reservoir. We sought to characterize follicular vitiligo through a case series of 8 patients. Patients with features of follicular vitiligo who were seen at the vitiligo clinic in the National Center for Rare Skin Disorders in Bordeaux, France, were recruited. A retrospective review of case records and clinical photographs was carried out. There were 8 male patients with a mean age of 48 years. All patients reported significant whitening of their body and, in some, scalp hairs before cutaneous depigmentation. Examination revealed classic generalized depigmented lesions of vitiligo and an impressive presence of leukotrichia, not only in the vitiliginous areas, but also in areas with clinically normal-appearing skin. Punch biopsy specimen of the leukotrichia and vitiligo lesions demonstrated loss of melanocytes and precursors in the basal epidermis and hair follicle. This was a cross-sectional study based on a single-center experience. Follicular vitiligo is a distinct entity within the spectrum of vitiligo. This entity may serve as the missing link between alopecia areata and vitiligo, with probable physiopathological similarities between these conditions. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  9. 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

  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. Transplanted stem cell-secreted vascular endothelial growth factor effects poststroke recovery, inflammation, and vascular repair.

    PubMed

    Horie, Nobutaka; Pereira, Marta P; Niizuma, Kuniyasu; Sun, Guohua; Keren-Gill, Hadar; Encarnacion, Angelo; Shamloo, Mehrdad; Hamilton, Scott A; Jiang, Kewen; Huhn, Stephen; Palmer, Theo D; Bliss, Tonya M; Steinberg, Gary K

    2011-02-01

    Cell transplantation offers a novel therapeutic strategy for stroke; however, how transplanted cells function in vivo is poorly understood. We show for the first time that after subacute transplantation into the ischemic brain of human central nervous system stem cells grown as neurospheres (hCNS-SCns), the stem cell-secreted factor, human vascular endothelial growth factor (hVEGF), is necessary for cell-induced functional recovery. We correlate this functional recovery to hVEGF-induced effects on the host brain including multiple facets of vascular repair and its unexpected suppression of the inflammatory response. We found that transplanted hCNS-SCns affected multiple parameters in the brain with different kinetics: early improvement in blood-brain barrier integrity and suppression of inflammation was followed by a delayed spatiotemporal regulated increase in neovascularization. These events coincided with a bimodal pattern of functional recovery, with, an early recovery independent of neovascularization, and a delayed hVEGF-dependent recovery coincident with neovascularization. Therefore, cell transplantation therapy offers an exciting multimodal strategy for brain repair in stroke and potentially other disorders with a vascular or inflammatory component. Copyright © 2011 AlphaMed Press.

  12. Cell-secreted matrices perpetuate the bone-forming phenotype of differentiated mesenchymal stem cells

    PubMed Central

    Hoch, Allison I.; Mittal, Vaishali; Mitra, Debika; Vollmer, Nina; Zikry, Christopher A.; Leach, J. Kent

    2015-01-01

    Prior to transplantation, mesenchymal stem/stromal cells (MSCs) can be induced toward the osteoblastic phenotype using a cocktail of soluble supplements. However, there is little evidence of differentiated MSCs directly participating in bone formation, suggesting that MSCs may either die or revert in phenotype upon transplantation. Cell-secreted decellularized extracellular matrices (DMs) are a promising platform to confer bioactivity and direct cell fate through the presentation of a complex and physiologically relevant milieu. Therefore, we examined the capacity of biomimetic DMs to preserve the mineral-producing phenotype upon withdrawal of the induction stimulus. Regardless of induction duration, ranging up to 6 weeks, MSCs exhibited up to a 5-fold reduction in osteogenic markers within 24 hours following stimulus withdrawal. We show that seeding osteogenically induced MSCs on DMs yields up to 2-fold more calcium deposition than tissue culture plastic, and this improvement is at least partially mediated by increasing actin cytoskeletal tension via the ROCK II pathway. MSCs on DMs also secreted 25% more vascular endothelial growth factor (VEGF), a crucial endogenous proangiogenic factor that is abrogated during MSC osteogenic differentiation. The deployment of DMs into a subcutaneous ectopic site enhanced the persistence of MSCs 5-fold, vessel density 3-fold, and bone formation 2-fold more than MSCs delivered without DMs. These results underscore the need for deploying MSCs using biomaterial platforms such as DMs to preserve the in vitro-acquired mineral-producing phenotype and accelerate the process of bone repair. PMID:26457835

  13. Transplanted stem cell-secreted VEGF effects post-stroke recovery, inflammation, and vascular repair

    PubMed Central

    Horie, Nobutaka; Pereira, Marta P.; Niizuma, Kuniyasu; Sun, Guohua; Keren-Gill, Hadar; Encarnacion, Angelo; Shamloo, Mehrdad; Hamilton, Scott A.; Jiang, Kewen; Huhn, Stephen; Palmer, Theo D.; Bliss, Tonya M.; Steinberg, Gary K.

    2012-01-01

    Cell transplantation offers a novel therapeutic strategy for stroke; however, how transplanted cells function in vivo is poorly understood. We show for the first time that after sub-acute transplantation into the ischemic brain of human central nervous system stem cells grown as neurospheres (hCNS-SCns), the stem cell-secreted factor, human VEGF (hVEGF), is necessary for cell-induced functional recovery. We correlate this functional recovery to hVEGF-induced effects on the host brain including multiple facets of vascular repair, and its unexpected suppression of the inflammatory response. We found that transplanted hCNS-SCns affected multiple parameters in the brain with different kinetics: early improvement in blood-brain barrier (BBB) integrity and suppression of inflammation was followed by a delayed spatio-temporal regulated increase in neovascularization. These events coincided with a bi-modal pattern of functional recovery: an early recovery independent of neovascularization, and a delayed hVEGF-dependent recovery coincident with neovascularization. Therefore, cell transplantation therapy offers an exciting multi-modal strategy for brain repair in stroke and potentially other disorders with a vascular or inflammatory component. PMID:21732485

  14. Early life allergen-induced mucus overproduction requires augmented neural stimulation of pulmonary neuroendocrine cell secretion.

    PubMed

    Barrios, Juliana; Patel, Kruti R; Aven, Linh; Achey, Rebecca; Minns, Martin S; Lee, Yoonjoo; Trinkaus-Randall, Vickery E; Ai, Xingbin

    2017-09-01

    Pulmonary neuroendocrine cells (PNECs) are the only innervated airway epithelial cells. To what extent neural innervation regulates PNEC secretion and function is unknown. Here, we discover that neurotrophin 4 (NT4) plays an essential role in mucus overproduction after early life allergen exposure by orchestrating PNEC innervation and secretion of GABA. We found that PNECs were the only cellular source of GABA in airways. In addition, PNECs expressed NT4 as a target-derived mechanism underlying PNEC innervation during development. Early life allergen exposure elevated the level of NT4 and caused PNEC hyperinnervation and nodose neuron hyperactivity. Associated with aberrant PNEC innervation, the authors discovered that GABA hypersecretion was required for the induction of mucin Muc5ac expression. In contrast, NT4(-/-) mice were protected from allergen-induced mucus overproduction and changes along the nerve-PNEC axis without any defects in inflammation. Last, GABA installation restored mucus overproduction in NT4(-/-) mice after early life allergen exposure. Together, our findings provide the first evidence for NT4-dependent neural regulation of PNEC secretion of GABA in a neonatal disease model. Targeting the nerve-PNEC axis may be a valid treatment strategy for mucus overproduction in airway diseases, such as childhood asthma.-Barrios, J., Patel, K. R., Aven, L., Achey, R., Minns, M. S., Lee, Y., Trinkaus-Randall, V. E., Ai, X. Early life allergen-induced mucus overproduction requires augmented neural stimulation of pulmonary neuroendocrine cell secretion. © FASEB.

  15. 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.

  16. Full restoration of Brucella-infected dendritic cell functionality through Vγ9Vδ2 T helper type 1 crosstalk.

    PubMed

    Ni, Ming; Martire, Delphine; Scotet, Emmanuel; Bonneville, Marc; Sanchez, Francoise; Lafont, Virginie

    2012-01-01

    Vγ9Vδ2 T cells play an important role in the immune response to infectious agents but the mechanisms contributing to this immune process remain to be better characterized. Following their activation, Vγ9Vδ2 T cells develop cytotoxic activity against infected cells, secrete large amounts of cytokines and influence the function of other effectors of immunity, notably cells playing a key role in the initiation of the adaptive immune response such as dendritic cells. Brucella infection dramatically impairs dendritic cell maturation and their capacity to present antigens to T cells. Herein, we investigated whether V T cells have the ability to restore the full functional capacities of Brucella-infected dendritic cells. Using an in vitro multicellular infection model, we showed that: 1/Brucella-infected dendritic cells activate Vγ9Vδ2 T cells through contact-dependent mechanisms, 2/activated Vγ9Vδ2 T cells induce full differentiation into IL-12 producing cells of Brucella-infected dendritic cells with functional antigen presentation activity. Furthermore, phosphoantigen-activated Vγ9Vδ2 T cells also play a role in triggering the maturation process of dendritic cells already infected for 24 h. This suggests that activated Vγ9Vδ2 T cells could be used to modulate the outcome of infectious diseases by promoting an adjuvant effect in dendritic cell-based cellular therapies.

  17. Dendrite Model Explained

    NASA Technical Reports Server (NTRS)

    2000-01-01

    Angie Jackman, a NASA project manager in microgravity research, explains a model of a dendrite to a visitor to the NASA exhibit at AirVenture 2000 sponsored by the Experimental Aircraft Association in Oshkosh, WI. The model depicts microscopic dendrites that grow as molten metals solidify. NASA sponsored three experiments aboard the Space Shuttle that used the microgravity environment to study the formation of large (1 to 4 mm) dendrites without Earth's gravity disrupting their growth. Three advanced follow-on experiments, managed by Jackman, are being developed for the International Space Station (ISS).

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

    ClinicalTrials.gov

    2017-10-04

    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

  19. Microorganisms within Human Follicular Fluid: Effects on IVF

    PubMed Central

    Pelzer, Elise S.; Allan, John A.; Waterhouse, Mary A.; Ross, Tara; Beagley, Kenneth W.; Knox, Christine L.

    2013-01-01

    Our previous study reported microorganisms in human follicular fluid. The objective of this study was to test human follicular fluid for the presence of microorganisms and to correlate these findings with the in vitro fertilization (IVF) outcomes. In this study, 263 paired follicular fluids and vaginal swabs were collected from women undergoing IVF cycles, with various causes for infertility, and were cultured to detect microorganisms. The cause of infertility and the IVF outcomes for each woman were correlated with the microorganisms detected within follicular fluid collected at the time of trans-vaginal oocyte retrieval. Microorganisms isolated from follicular fluids were classified as: (1) ‘colonizers’ if microorganisms were detected within the follicular fluid, but not within the vaginal swab (at the time of oocyte retrieval); or (2) ‘contaminants’ if microorganisms detected in the vagina at the time of oocyte retrieval were also detected within the follicular fluid. The presence of Lactobacillus spp. in ovarian follicular fluids was associated with embryo maturation and transfer. This study revealed microorganisms in follicular fluid itself and that the presence of particular microorganisms has an adverse affect on IVF outcomes as seen by an overall decrease in embryo transfer rates and pregnancy rates in both fertile and infertile women, and live birth rates in women with idiopathic infertility. Follicular fluid microorganisms are a potential cause of adverse pregnancy outcomes in IVF in both infertile women and in fertile women with infertile male partners. PMID:23554970

  20. Microorganisms within human follicular fluid: effects on IVF.

    PubMed

    Pelzer, Elise S; Allan, John A; Waterhouse, Mary A; Ross, Tara; Beagley, Kenneth W; Knox, Christine L

    2013-01-01

    Our previous study reported microorganisms in human follicular fluid. The objective of this study was to test human follicular fluid for the presence of microorganisms and to correlate these findings with the in vitro fertilization (IVF) outcomes. In this study, 263 paired follicular fluids and vaginal swabs were collected from women undergoing IVF cycles, with various causes for infertility, and were cultured to detect microorganisms. The cause of infertility and the IVF outcomes for each woman were correlated with the microorganisms detected within follicular fluid collected at the time of trans-vaginal oocyte retrieval. Microorganisms isolated from follicular fluids were classified as: (1) 'colonizers' if microorganisms were detected within the follicular fluid, but not within the vaginal swab (at the time of oocyte retrieval); or (2) 'contaminants' if microorganisms detected in the vagina at the time of oocyte retrieval were also detected within the follicular fluid. The presence of Lactobacillus spp. in ovarian follicular fluids was associated with embryo maturation and transfer. This study revealed microorganisms in follicular fluid itself and that the presence of particular microorganisms has an adverse affect on IVF outcomes as seen by an overall decrease in embryo transfer rates and pregnancy rates in both fertile and infertile women, and live birth rates in women with idiopathic infertility. Follicular fluid microorganisms are a potential cause of adverse pregnancy outcomes in IVF in both infertile women and in fertile women with infertile male partners.

  1. Dendritic Growth Investigators

    NASA Technical Reports Server (NTRS)

    2000-01-01

    Representatives of NASA materials science experiments supported the NASA exhibit at the Rernselaer Polytechnic Institute's Space Week activities, April 5 through 11, 1999. From left to right are: Angie Jackman, project manager at NASA's Marshall Space Flight Center for dendritic growth experiments; Dr. Martin Glicksman of Rennselaer Polytechnic Instutute, Troy, NY, principal investigator on the Isothermal Dendritic Growth Experiment (IDGE) that flew three times on the Space Shuttle; and Dr. Matthew Koss of College of the Holy Cross in Worcester, MA, a co-investigator on the IDGE and now principal investigator on the Transient Dendritic Solidification Experiment being developed for the International Space Station (ISS). The image at far left is a dendrite grown in Glicksman's IDGE tests aboard the Shuttle. Glicksman is also principal investigator for the Evolution of Local Microstructures: Spatial Instabilities of Coarsening Clusters.

  2. Multi-scale modelling of ovarian follicular development: From follicular morphogenesis to selection for ovulation.

    PubMed

    Monniaux, Danielle; Michel, Philippe; Postel, Marie; Clément, Frédérique

    2016-06-01

    In this review, we present multi-scale mathematical models of ovarian follicular development that are based on the embedding of physiological mechanisms into the cell scale. During basal follicular development, follicular growth operates through an increase in the oocyte size concomitant with the proliferation of its surrounding granulosa cells. We have developed a spatio-temporal model of follicular morphogenesis explaining how the interactions between the oocyte and granulosa cells need to be properly balanced to shape the follicle. During terminal follicular development, the ovulatory follicle is selected amongst a cohort of simultaneously growing follicles. To address this process of follicle selection, we have developed a model giving a continuous and deterministic description of follicle development, adapted to high numbers of cells and based on the dynamical and hormonally regulated repartition of granulosa cells into different cell states, namely proliferation, differentiation and apoptosis. This model takes into account the hormonal feedback loop involving the growing ovarian follicles and the pituitary gland, and enables the exploration of mechanisms regulating the number of ovulations at each ovarian cycle. Both models are useful for addressing ovarian physio-pathological situations. Moreover, they can be proposed as generic modelling environments to study various developmental processes and cell interaction mechanisms.

  3. Elastic Staining in Differentiating Between Follicular Streamers and Follicular Scars in Horizontal Scalp Biopsy Sections.

    PubMed

    Tan, Timothy; Guitart, Joan; Gerami, Pedram; Yazdan, Pedram

    2017-08-09

    Accurate identification of follicular streamers versus follicular scars on horizontal scalp biopsy sections is important to differentiate between cicatricial and noncicatricial alopecias. However, distinguishing between them can be difficult especially in nonoptimal specimens. The utility of elastic Verhoeff-Van Gieson (EVG) stain in cicatricial alopecias has been described on vertical sections, but its evaluation on horizontal sections has not been performed. Sixty-four cicatricial alopecias (25 lichen planopilaris, 29 central centrifugal cicatricial alopecias, and 10 discoid lupus erythematosus) and 53 noncicatricial alopecias (34 androgenic alopecia, 8 telogen effluvium, and 11 alopecia areata) were identified, and EVG staining was performed on horizontal sections. In follicular streamers, EVG highlighted an intact elastic network composed of delicate and thin elastic fibers circumferentially surrounding the angiofibrotic streamer without elastic network attenuation, loss, clumping, thickening, or recoil. In follicular scars, EVG demonstrated central attenuation and loss of the elastic network with peripheral clumping and recoil of elastic fibers. In cases where distinguishing between follicular streamers and scars is difficult, EVG may be a helpful adjunctive tool in this regard and aid in allowing better discrimination between cicatricial and noncicatricial alopecias.

  4. Immunotherapy with Rituximab in Follicular Lymphomas

    PubMed Central

    SAGUNA, Carmen; MUT, Ileana Delia; LUPU, Anca Roxana; TEVET, Mihaela; BUMBEA, Horia; DRAGAN, Cornel

    2011-01-01

    ABSTRACT Background: Non-Hodgkin Lymphomas (NHL) represent a recent and fascinating domain of hemato-oncology, in which remarkable progress has been made. The conventional treatments of indolent lymphomas do not extend the survival rate, nor do they cure. Recent directions are centered on using several new drugs that are capable of overcoming the mechanisms that are resistant to recovery. The initiation of immunotherapy (Rituximab in 1997) seems to have changed the natural evolution of follicular lymphomas (FL). It is possible that resistance to healing in follicular lymphomas may be neutralized with Rituximab by suppressing STAT-1 positive macrophages that are present in the cellular microenvironment.Thereinafter, the re-evaluation of recent models of prognostic and therapeutic paradigmas that were used in FL became compulsory. The purpose of the paper is to compare the evolution of patients with follicular lymphoma and the period of response, according to the treatments. Material and method: The study group consisted of the 71 patients diagnosed with follicular lymphoma, out of a total of 767 malignant lymphatic proliferations with B cells, for a period of 7 years (2002-2008), at the Hematology Department, Hospital Coltea, Bucharest and Hematology Department, Universitary Hospital, Bucharest Results and conclusions: Combining chemotherapy with Rituximab had better results compared to the same chemotherapy, administered alone, both in induction and in case of relapse. The overall response rate in our study group was 74.7%, out of which 42.3% complete remissions. The overall response rate was 84.61% in the Rituximab group, compared to 68.88% in patients without Rituximab. PMID:22205891

  5. Immunotherapy with rituximab in follicular lymphomas.

    PubMed

    Saguna, Carmen; Mut, Ileana Delia; Lupu, Anca Roxana; Tevet, Mihaela; Bumbea, Horia; Dragan, Cornel

    2011-04-01

    Non-Hodgkin Lymphomas (NHL) represent a recent and fascinating domain of hemato-oncology, in which remarkable progress has been made. The conventional treatments of indolent lymphomas do not extend the survival rate, nor do they cure. Recent directions are centered on using several new drugs that are capable of overcoming the mechanisms that are resistant to recovery. The initiation of immunotherapy (Rituximab in 1997) seems to have changed the natural evolution of follicular lymphomas (FL). It is possible that resistance to healing in follicular lymphomas may be neutralized with Rituximab by suppressing STAT-1 positive macrophages that are present in the cellular microenvironment.Thereinafter, the re-evaluation of recent models of prognostic and therapeutic paradigmas that were used in FL became compulsory.The purpose of the paper is to compare the evolution of patients with follicular lymphoma and the period of response, according to the treatments. The study group consisted of the 71 patients diagnosed with follicular lymphoma, out of a total of 767 malignant lymphatic proliferations with B cells, for a period of 7 years (2002-2008), at the Hematology Department, Hospital Coltea, Bucharest and Hematology Department, Universitary Hospital, BucharestResults and conclusions: Combining chemotherapy with Rituximab had better results compared to the same chemotherapy, administered alone, both in induction and in case of relapse. The overall response rate in our study group was 74.7%, out of which 42.3% complete remissions. The overall response rate was 84.61% in the Rituximab group, compared to 68.88% in patients without Rituximab.

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

    DOE PAGES

    Ho, Melissa E.; Quek, Sue -Ing; True, Lawrence D.; ...

    2016-02-15

    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. Normal organs express AGR2 and might also secrete AGR2, which would impact on the utility of AGR2 as a cancer biomarker. Uniform AGR2 expression is found in the normal bladder urothelium. Little AGR2 is, however, 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. The blood proteomes also contain no significantmore » peptide counts for AGR2 suggesting that little urothelial secretion into capillaries of the lamina propria. Expression is lost in urothelial carcinoma, but 25% primary tumors retained 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 urine, which matched the frequency of AGR2-positive urothelial carcinoma. Since cancer cells secrete AGR2 while normal cells do not, its measurement in body fluids could be used to indicate tumor presence. In addition to secretion, AGR2 is also localized to the cell surface. Thus, secretion/cell surface localization of AGR2 is pecific to cancer while expression itself is not. Lastly, since AGR2 is found in many solid tumor types, this tumor-associated antigen constitutes a highly promising therapeutic target.« less

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

    SciTech Connect

    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.

    2016-02-15

    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. Normal organs express AGR2 and might also secrete AGR2, which would impact on the utility of AGR2 as a cancer biomarker. Uniform AGR2 expression is found in the normal bladder urothelium. Little AGR2 is, however, 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. The blood proteomes also contain no significant peptide counts for AGR2 suggesting that little urothelial secretion into capillaries of the lamina propria. Expression is lost in urothelial carcinoma, but 25% primary tumors retained 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 urine, which matched the frequency of AGR2-positive urothelial carcinoma. Since cancer cells secrete AGR2 while normal cells do not, its measurement in body fluids could be used to indicate tumor presence. In addition to secretion, AGR2 is also localized to the cell surface. Thus, secretion/cell surface localization of AGR2 is pecific to cancer while expression itself is not. Lastly, since AGR2 is found in many solid tumor types, this tumor-associated antigen constitutes a highly promising therapeutic target.

  8. Dog mastocytoma cells secrete a 92-kD gelatinase activated extracellularly by mast cell chymase.

    PubMed Central

    Fang, K C; Raymond, W W; Lazarus, S C; Caughey, G H

    1996-01-01

    Gelatinolytic metalloproteinases implicated in connective tissue remodeling and tumor invasion are secreted from several types of cells in the form of inactive zymogens. In this report, characterization of gelatinase activity secreted by the BR line of dog mastocytoma cells reveals a phorbol-inducible, approximately 92-kD, Ca2+ - and Zn2+ -dependent proenzyme cleaved over time to smaller, active forms. Incubation of cells with the general serine protease inhibitor, PMSF, prevented proenzyme cleavage and permitted its purification free of activation products. The NH2-terminal 13 amino acids of the purified mastocytoma progelatinase are 50-67% identical to those of human, mouse, and rabbit 92-kD progelatinase (gelatinase B; matrix metalloproteinase-9). Degranulation of mastocytoma cells using ionophore A23187 greatly accelerated proenzyme cleavage, suggesting that a serine protease present in secretory granules hydrolyzed the progelatinase to active fragments. To identify the activating protease, cells were coincubated with ionophore and a panel of selective serine protease inhibitors. Soybean trypsin inhibitor and succinyl-L-Ala-Ala-Pro-Phe-chloromethylketone, which inhibit mast cell chymase, prevented progelatinase activation. Inhibitors of tryptase and dog mast cell protease (dMCP)-3, i.e., aprotinin or bis(5-amidino-2-benzimidazolyl) methane (BABIM), did not. In further experiments using highly purified enzymes, mastocytoma cell chymase activated 92-kD progelatinase in the absence of other enzymes or cofactors; tryptase and dMCP-3, however, had no effect. These data demonstrate that dog mastocytoma cells secrete a metalloproteinase related to progelatinase B that is directly activated outside of the cell by exocytosed chymase, and provide the first demonstration of a cell that activates a matrix metalloproteinase it secretes by cosecreting an activating enzyme. In mastocytomas, this pathway may facilitate tumor invasion of surrounding tissues, and in normal mast

  9. 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

  10. Memory B cells contribute to rapid Bcl6 expression by memory follicular helper T cells.

    PubMed

    Ise, Wataru; Inoue, Takeshi; McLachlan, James B; Kometani, Kohei; Kubo, Masato; Okada, Takaharu; Kurosaki, Tomohiro

    2014-08-12

    In primary humoral responses, B-cell lymphoma 6 (Bcl6) is a master regulator of follicular helper T (TFH) cell differentiation; however, its activation mechanisms and role in memory responses remain unclear. Here we demonstrate that survival of CXCR5(+) TFH memory cells, and thus subsequent recall antibody response, require Bcl6 expression. Furthermore, we show that, upon rechallenge with soluble antigen Bcl6 in memory TFH cells is rapidly induced in a dendritic cell-independent manner and that peptide:class II complexes (pMHC) on cognate memory B cells significantly contribute to this induction. Given the previous evidence that antigen-specific B cells residing in the follicles acquire antigens within minutes of injection, our results suggest that memory B cells present antigens to the cognate TFH memory cells, thereby contributing to rapid Bcl6 reexpression and differentiation of the TFH memory cells during humoral memory responses.

  11. Extracellular Vesicles from Bovine Follicular Fluid Support Cumulus Expansion.

    PubMed

    Hung, Wei-Ting; Hong, Xioman; Christenson, Lane K; McGinnis, Lynda K

    2015-11-01

    Expansion of the cumulus complex surrounding the oocyte is critical for ovulation of a fertilizable egg. The ovulation-inducing surge of luteinizing hormone leads to an increased expression of genes such as prostaglandin-endoperoxide synthase 2 (Ptgs2), pentraxin-related protein 3 (Ptx3), and tumor necrosis factor alpha-induced protein 6 (Tnfaip6) that support cumulus expansion. Factors released by mural granulosa and cumulus granulosa cells into the follicular fluid induce paracrine signaling within the follicular compartment. The follicular fluid that separates these distinct granulosa cell types is an enriched fluid containing numerous proteins, nucleic acids, and other macromolecules. Extracellular vesicles (EVs) are also present; however, no physiologically relevant functions of follicular EVs have yet been demonstrated. In our study, the effect of follicular EVs on cumulus-oocyte complex (COC) expansion and relevant gene expression was assayed. Follicular EVs were isolated using ultracentrifugation from follicular fluid of small (3-5 mm) and large (>9 mm) antral bovine follicles, then characterized by nanoparticle tracking analysis, electron microscopy, and Western blot analysis. To test for bioactivity, mouse and bovine COCs were cultured with follicular EVs. Cumulus expansion and Ptgs2, Ptx3, and Tnfaip6 gene expression were measured following COC maturation culture. The results demonstrated that follicular EVs can support both measurable cumulus expansion and increased gene expression.

  12. Extracellular Vesicles from Bovine Follicular Fluid Support Cumulus Expansion1

    PubMed Central

    Hung, Wei-Ting; Hong, Xioman; Christenson, Lane K.; McGinnis, Lynda K.

    2015-01-01

    Expansion of the cumulus complex surrounding the oocyte is critical for ovulation of a fertilizable egg. The ovulation-inducing surge of luteinizing hormone leads to an increased expression of genes such as prostaglandin-endoperoxide synthase 2 (Ptgs2), pentraxin-related protein 3 (Ptx3), and tumor necrosis factor alpha-induced protein 6 (Tnfaip6) that support cumulus expansion. Factors released by mural granulosa and cumulus granulosa cells into the follicular fluid induce paracrine signaling within the follicular compartment. The follicular fluid that separates these distinct granulosa cell types is an enriched fluid containing numerous proteins, nucleic acids, and other macromolecules. Extracellular vesicles (EVs) are also present; however, no physiologically relevant functions of follicular EVs have yet been demonstrated. In our study, the effect of follicular EVs on cumulus-oocyte complex (COC) expansion and relevant gene expression was assayed. Follicular EVs were isolated using ultracentrifugation from follicular fluid of small (3–5 mm) and large (>9 mm) antral bovine follicles, then characterized by nanoparticle tracking analysis, electron microscopy, and Western blot analysis. To test for bioactivity, mouse and bovine COCs were cultured with follicular EVs. Cumulus expansion and Ptgs2, Ptx3, and Tnfaip6 gene expression were measured following COC maturation culture. The results demonstrated that follicular EVs can support both measurable cumulus expansion and increased gene expression. PMID:26423123

  13. New insights into the immunopathogenesis of systemic lupus erythematosus: the role of T follicular helper cells.

    PubMed

    Ma, Huijuan; Wan, Suigui; Xia, Changqing

    2014-01-01

    To review the development of T follicular helper (TFH) cells and their role in systemic lupus erythematosus (SLE) pathogenesis, the effect of dendritic cells (DCs) on TFH cells in SLE, as well as the potential use of TFH cells as a new therapeutic target in clinical practice. The data used in this review were retrieved mainly from the PubMed database (1989-2013). The terms used in the literature search were "T follicular helper cells," "systemic lupus erythematosus," and "dendritic cells." Relevant publications about the TFH cells development, the interaction between the TFH cells and the DCs, and the clinical applications of TFH cells were identified, retrieved, and reviewed. TFH cells, a novel distinct CD4+ T cell subset, are specialized in providing help to B cells in the formation of germinal centers (GCs) and long-term protective humoral immune responses. The development of TFH cells from naïve CD4+ T cell is a multistep process. As the pivot of immunoregulation, DCs are indispensable for TFH cells generation. In addition to receptor-ligand interactions between TFH cells and DCs, the cytokines secreted by DCs are also necessary for TFH cell generation. TFH cell dysregulation has been implicated in the development of SLE. More evidence from animal models of SLE and SLE patients suggests that TFH cells are necessary for pathogenic autoantibody production. Therefore, therapeutically targeting TFH cells can be a promising approach to treat antibody-mediated autoimmune diseases including SLE. TFH cells play a critical role in the pathogenesis of SLE, making them attractive therapeutic targets in clinical practice.

  14. 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.

  15. Active properties of neuronal dendrites.

    PubMed

    Johnston, D; Magee, J C; Colbert, C M; Cristie, B R

    1996-01-01

    Dendrites of neurons in the central nervous system are the principal sites for excitatory synaptic input. Although little is known about their function, two disparate perspectives have arisen to describe the activity patterns inherent to these diverse tree-like structures. Dendrites are thus considered either passive or active in their role in integrating synaptic inputs. This review follows the history of dendritic research from before the turn of the century to the present, with a primary focus on the hippocampus. A number of recent techniques, including high-speed fluorescence imaging and dendritic patch clamping, have provided new information and perspectives about the active properties of dendrites. The results support previous notions about the dendritic propagation of action potentials and also indicate which types of voltage-gated sodium and calcium channels are expressed and functionally active in dendrites. Possible roles for the active properties of dendrites in synaptic plasticity and integration are also discussed.

  16. 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.

  17. Hormonal composition of follicular fluid from abnormal follicular structures in mares.

    PubMed

    Beltman, M E; Walsh, S W; Canty, M J; Duffy, P; Crowe, M A

    2014-12-01

    The objective was to characterise the hormonal composition of follicular fluid from mares with distinct anovulatory-cystic follicles. Follicular fluid was aspirated from six mares that presented with cystic follicles and from pre-ovulatory follicles of five normal mares (controls). Differences in progesterone, oestradiol, testosterone, IGF-I and IGF binding were analysed using Fisher's exact test. There were greater (P < 0.03) follicular fluid oestradiol concentrations in normal follicles and the testosterone concentration of the cystic fluid was greater (P < 0.05) than that of the normal fluid. There also was a greater (P < 0.03) percentage of IGF-I binding and lower (P < 0.02) IGF-I concentrations in the fluid collected from the cystic structures compared with the fluid from normal follicles. Despite the limited number of animals, the fact that fluid aspirated from cystic follicles had higher testosterone and lower oestradiol concentrations could be of diagnostic value when a practitioner wants to distinguish between a cystic and non-cystic persistent follicle. The research reported here also indicates a likely role for the IGF system in the pathogenesis of the development and maintenance of anovulatory follicular structures in mare ovaries.

  18. 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

  19. Dendritic Release of Neurotransmitters.

    PubMed

    Ludwig, Mike; Apps, David; Menzies, John; Patel, Jyoti C; Rice, Margaret E

    2016-12-06

    Release of neuroactive substances by exocytosis from dendrites is surprisingly widespread and is not confined to a particular class of transmitters: it occurs in multiple brain regions, and includes a range of neuropeptides, classical neurotransmitters, and signaling molecules, such as nitric oxide, carbon monoxide, ATP, and arachidonic acid. This review is focused on hypothalamic neuroendocrine cells that release vasopressin and oxytocin and midbrain neurons that release dopamine. For these two model systems, the stimuli, mechanisms, and physiological functions of dendritic release have been explored in greater detail than is yet available for other neurons and neuroactive substances. © 2017 American Physiological Society. Compr Physiol 7:235-252, 2017.

  20. 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.

  1. 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.

  2. [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.

  3. Follicular Lymphoma: The Management of Elderly Patient

    PubMed Central

    Castellino, Alessia; Santambrogio, Elisa; Nicolosi, Maura; Botto, Barbara; Boccomini, Carola; Vitolo, Umberto

    2017-01-01

    Follicular lymphoma (FL) is the most common indolent non-Hodgkin lymphoma, which typically affects mature adults and elderly, whose median age at diagnosis is 65 years. The natural history of FL appears to have been favorably impacted by the introduction of Rituximab. Randomized clinical trials demonstrated that the addition of rituximab to standard chemotherapy induction has improved the overall survival and new strategies of chemo-immunotherapy, such as Bendamustine combined with Rituximab, showed optimal results on response and reduced hematological toxicity, becoming one of the standard treatments, particularly in elderly patients. Moreover, maintenance therapy with Rituximab demonstrated improvement of progression-free survival. Despite these exciting results, FL is still an incurable disease. It remains a critical unmet clinical need finding new prognostic factors to identify poor outcome patients better, to reduce the risk of transformation and to explore new treatment strategies, especially for patients not candidate to intensive chemotherapy regimens, such as elderly patients. Some progress were already reached with novel agents, but larger and more validated studies are needed. Elderly patients are the largest portion of patients with FL and represent a subgroup with higher treatment difficulties, because of comorbidities and smaller spectrum for treatment choice. Further studies, focused on elderly follicular lymphoma patients, with their peculiar characteristics, are needed to define the best-tailored treatment at diagnosis and at the time of relapse in this setting. PMID:28105297

  4. Mixed Medullary-follicular-derived carcinomas of the thyroid gland.

    PubMed

    Sadow, Peter M; Hunt, Jennifer L

    2010-07-01

    Tumors of the thyroid are subclassified based on the cell of origin and commonly include follicular-derived tumors and C-cell-derived tumors. The most common follicular-derived tumors are papillary carcinoma and follicular carcinoma, whereas the malignant C-cell-derived tumor is medullary thyroid carcinoma. Rare cases in the literature describe patients who have follicular-derived and C-cell-derived tumors in the same thyroid gland. These can be synchronous but anatomically separate carcinomas, or they can show some mixing of the 2 components. The mixture may be at an interface, as in collision tumors, or can be throughout the entire lesion, as in true mixed medullary-follicular-derived carcinomas. The clinical, histologic, and molecular features of these mixed tumors and the classification guidelines are reviewed.

  5. 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.

  6. Molecular mechanisms of dendrite morphogenesis

    PubMed Central

    Arikkath, Jyothi

    2012-01-01

    Dendrites are key integrators of synaptic information in neurons and play vital roles in neuronal plasticity. Hence, it is necessary that dendrite arborization is precisely controlled and coordinated with synaptic activity to ensure appropriate functional neural network integrity. In the past several years, it has become increasingly clear that several cell intrinsic and extrinsic mechanisms contribute to dendritic arborization. In this review, we will discuss some of the molecular mechanisms that regulate dendrite morphogenesis, particularly in cortical and hippocampal pyramidal neurons and some of the implications of aberrant dendritic morphology for human disease. Finally, we will discuss the current challenges and future directions in the field. PMID:23293584

  7. 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

  8. Relationship between endogenous progesterone and follicular dynamics in lactating dairy cows with ovarian follicular cysts.

    PubMed

    Hatler, T B; Hayes, S H; Laranja da Fonseca, L F; Silvia, W J

    2003-07-01

    Two experiments were conducted to examine circulating concentrations of progesterone (P4) in cows with ovarian follicular cysts (OFCs) and to relate differing levels of P4 to subsequent follicular events. In experiment 1, peripheral concentrations of P4 were determined in cows diagnosed with OFCs. Nonpregnant, lactating Holstein and Jersey cows (n = 32) were diagnosed as having OFCs by rectal palpation. Ovarian follicular cysts were then examined by transrectal ultrasonography to confirm the presence of OFCs (follicle diameter, >/=17 mm; absence of luteal tissue). At confirmation, a blood sample was collected for quantification of P4. The concentration of P4 at confirmation was classified as low (<0.1 ng/ml), intermediate (0.1-1.0 ng/ml), or high (1.0-2.0 ng/ml). More OFCs were associated with intermediate (66%) than with either low (28%) or high (6%) concentrations of P4. In experiment 2, the fate of follicles (diameter, >/=10 mm) that formed in the presence of an OFC was determined and related to circulating concentrations of P4 during follicular development. Follicles (n = 59) that formed in the presence of an OFC ovulated (n = 19), formed a cyst (n = 30), or underwent normal growth and regression (NGR; n = 10). Endogenous P4 in the 7-day period during follicular development was classified as low (if P4 dropped to <0.1 ng/ml for 1 day or longer), intermediate (if P4 averaged between 0.1 and 1.0 ng/ml and never dropped to <0.1 ng/ml), or high (if P4 averaged >1.0 ng/ml and never dropped to <0.1 ng/ml). In the presence of intermediate P4, 75% of observed follicles formed cysts, compared with 10% that ovulated and 15% that experienced NGR. In the presence of low P4, 53%, 41%, and 6% of follicles ovulated, formed a follicular cyst, or experienced NGR, respectively. Thus, an association between intermediate P4 and the formation of OFCs was established.

  9. 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

  10. 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

  11. Avian Follicular and Interdigitating Dendritic Cells: Isolation and Morphologic, Phenotypic, and Functional Analyses

    USDA-ARS?s Scientific Manuscript database

    An antiserum against Eimeria tenella sporozoites was used to localize and isolate Ag-binding cells in intestinal cecal tonsils of parasite-infected chickens. Based on their tissue localization, ultrastructural features, and expression of surface markers, two subpopulations of cells were isolated, C...

  12. 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.

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

    PubMed

    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

    2016-04-21

    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.

  14. 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

  15. 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.

  16. T follicular helper and T follicular regulatory cells have different TCR specificity

    PubMed Central

    Maceiras, Ana Raquel; Almeida, Silvia Cristina Paiva; Mariotti-Ferrandiz, Encarnita; Chaara, Wahiba; Jebbawi, Fadi; Six, Adrien; Hori, Shohei; Klatzmann, David; Faro, Jose; Graca, Luis

    2017-01-01

    Immunization leads to the formation of germinal centres (GCs) that contain both T follicular helper (Tfh) and T follicular regulatory (Tfr) cells. Whether T-cell receptor (TCR) specificity defines the differential functions of Tfh and Tfr cells is unclear. Here we show that antigen-specific T cells after immunization are preferentially recruited to the GC to become Tfh cells, but not Tfr cells. Tfh cells, but not Tfr cells, also proliferate efficiently on restimulation with the same immunizing antigen in vitro. Ex vivo TCR repertoire analysis shows that immunization induces oligoclonal expansion of Tfh cells. By contrast, the Tfr pool has a TCR repertoire that more closely resembles that of regulatory T (Treg) cells. Our data thus indicate that the GC Tfh and Tfr pools are generated from distinct TCR repertoires, with Tfh cells expressing antigen-responsive TCRs to promote antibody responses, and Tfr cells expressing potentially autoreactive TCRs to suppress autoimmunity. PMID:28429709

  17. Dendritic Spikes in Sensory Perception.

    PubMed

    Manita, Satoshi; Miyakawa, Hiroyoshi; Kitamura, Kazuo; Murayama, Masanori

    2017-01-01

    What is the function of dendritic spikes? One might argue that they provide conditions for neuronal plasticity or that they are essential for neural computation. However, despite a long history of dendritic research, the physiological relevance of dendritic spikes in brain function remains unknown. This could stem from the fact that most studies on dendrites have been performed in vitro. Fortunately, the emergence of novel techniques such as improved two-photon microscopy, genetically encoded calcium indicators (GECIs), and optogenetic tools has provided the means for vital breakthroughs in in vivo dendritic research. These technologies enable the investigation of the functions of dendritic spikes in behaving animals, and thus, help uncover the causal relationship between dendritic spikes, and sensory information processing and synaptic plasticity. Understanding the roles of dendritic spikes in brain function would provide mechanistic insight into the relationship between the brain and the mind. In this review article, we summarize the results of studies on dendritic spikes from a historical perspective and discuss the recent advances in our understanding of the role of dendritic spikes in sensory perception.

  18. Dendritic Spikes in Sensory Perception

    PubMed Central

    Manita, Satoshi; Miyakawa, Hiroyoshi; Kitamura, Kazuo; Murayama, Masanori

    2017-01-01

    What is the function of dendritic spikes? One might argue that they provide conditions for neuronal plasticity or that they are essential for neural computation. However, despite a long history of dendritic research, the physiological relevance of dendritic spikes in brain function remains unknown. This could stem from the fact that most studies on dendrites have been performed in vitro. Fortunately, the emergence of novel techniques such as improved two-photon microscopy, genetically encoded calcium indicators (GECIs), and optogenetic tools has provided the means for vital breakthroughs in in vivo dendritic research. These technologies enable the investigation of the functions of dendritic spikes in behaving animals, and thus, help uncover the causal relationship between dendritic spikes, and sensory information processing and synaptic plasticity. Understanding the roles of dendritic spikes in brain function would provide mechanistic insight into the relationship between the brain and the mind. In this review article, we summarize the results of studies on dendritic spikes from a historical perspective and discuss the recent advances in our understanding of the role of dendritic spikes in sensory perception. PMID:28261060

  19. [Follicular bronchiolitis associated with rheumatoid arthritis].

    PubMed

    Morita, S; Sato, A; Hayakawa, H; Chida, K; Sato, J; Todate, A; Tsukamoto, K; Toyoshima, M; Imokawa, S; Iwata, M

    1996-08-01

    A 52-year-old man with an 8-year history of rheumatoid arthritis was admitted to the hospital because of coughing and purulent sputum. A chest X-ray film obtained on admission showed small nodular shadows without overinflation in both lower lung fields, and a high-resolution CT scan showed many micronodular shadows in the centrilobular regions. Follicular bronchiolitis was diagnosed from the results of an open-lung biopsy, and prednisolone therapy was started at a dosage of 40 mg/day. Sinusitis developed 4 years later. Five years after the start of steroid therapy, dilation of bronchi and thickening of bronchial walls appeared on a CT scan, which also showed areas of low attenuation that were presumed to be bronchiolitis obliterans. These findings suggest that the pattern of airway disease can vary during the course of rheumatoid arthritis.

  20. T follicular helper cell diversity and plasticity.

    PubMed

    Cannons, Jennifer L; Lu, Kristina T; Schwartzberg, Pamela L

    2013-05-01

    CD4(+) T helper (Th) cells play an instrumental role in orchestrating adaptive immune responses to invading pathogens through their ability to differentiate into specialized effector subsets. Part of this customized response requires the development of T follicular helper (Tfh) cells, which provide help to B cells for the generation of germinal centers (GCs) and long-term protective humoral responses. Although initially viewed as terminally differentiated, we now recognize that Th cell subsets, including Tfh cells, display substantial flexibility and overlap in their characteristics. In this review, we highlight advances in our understanding of Tfh cell development, cytokine production, and the potential plasticity that allows Tfh cells to possess characteristics of other effector Th cell populations. Published by Elsevier Ltd.

  1. Initial management strategies for follicular lymphoma

    PubMed Central

    Chen, Qiushi; Ayer, Turgay; Nastoupil, Loretta J; Seward, Miray; Zhang, Hongzheng; Sinha, Rajni; Flowers, Christopher R

    2013-01-01

    SUMMARY Follicular lymphoma (FL) can vary markedly in its initial presentation, and no single standard approach for its initial management has been adopted. Available options for the initial management of FL include watchful waiting, radiation, single-agent rituximab and combination of rituximab and chemotherapy with strategies segregated for patients who have low and high tumor burden disease based on established criteria. However, marked debate occurs regarding the role of watchful waiting in the modern era for low tumor burden, asymptomatic patients, the optimal timing of rituximab, the selection of chemotherapy regimen to partner with rituximab in high tumor burden patients, and strategies for the management of relapsed disease. We provide an evidence-based discussion on these and other issues regarding the management of FL, and propose a mathematical modeling approach for addressing some of these questions. PMID:23476737

  2. 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

  3. 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

  4. 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.

  5. Dendritic Materials Systems

    DTIC Science & Technology

    2003-09-22

    2-hydroxyethyl)-e-caprolactone,” Macromolecules, 32, 6881-4, (1999). Yu, D.; Vladimirov, N.; Fréchet, J.M.J. “ MALDI - TOF in the Characterization of...Mat Sci. Eng., (1999). Yu, D.; Vladimirov, N.; Fréchet, J. M. J. “ MALDI - TOF Mass Spectrometry in the Characterization of Dendritic-Linear Block and...with long endgroups capable of chain entanglements providing uniform continuous films. We found that the surface properties of polyetherimide ( PEI

  6. Human dendritic cell subsets

    PubMed Central

    Collin, Matthew; McGovern, Naomi; Haniffa, Muzlifah

    2013-01-01

    Summary Dendritic cells are highly adapted to their role of presenting antigen and directing immune responses. Developmental studies indicate that DCs originate independently from monocytes and tissue macrophages. Emerging evidence also suggests that distinct subsets of DCs have intrinsic differences that lead to functional specialisation in the generation of immunity. Comparative studies are now allowing many of these properties to be more fully understood in the context of human immunology. PMID:23621371

  7. 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.

  8. 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.

  9. 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.

  10. Follicular Psoriasis: Differentiation from Pityriasis Rubra Pilaris-An Illustrative Case and Review of the Literature.

    PubMed

    Nguyen, Cuong V; Farah, Ronda S; Maguiness, Sheilagh M; Miller, Daniel D

    2017-01-01

    The follicular presentation of psoriasis is a well-described but uncommon variant. In some cases, follicular psoriasis may clinically and histopathologically mimic pityriasis rubra pilaris. There are several reports discussing the resemblance of widespread follicular psoriasis in children to pityriasis rubra pilaris. We describe a case of follicular psoriasis in a 16-year-old black girl with acrally distributed follicular hyperkeratotic papules with associated keratoderma of her plantar surfaces resembling pityriasis rubra pilaris. © 2016 Wiley Periodicals, Inc.

  11. 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.

  12. Follicular penetration of topically applied caffeine via a shampoo formulation.

    PubMed

    Otberg, N; Teichmann, A; Rasuljev, U; Sinkgraven, R; Sterry, W; Lademann, J

    2007-01-01

    Follicular drug delivery is the prerequisite for an effective treatment of androgenetic alopecia or other reasons of premature hair loss. The follicular penetration of caffeine, applied topically in a shampoo formulation for 2 min, was measured with highly sensitive surface ionization in combination with mass spectroscopy, a selective method for the detection of very small quantities of transcutaneously absorbed substances in the blood. An experimental protocol, developed to selectively block the follicular pathway within the test area, was used. Based on this principle, a clear distinction between interfollicular and follicular penetration of topically applied caffeine was feasible. After 2 min, caffeine penetrated via the hair follicles and stratum corneum. It was found that the penetration via hair follicles was faster and higher compared with the interfollicular route and that hair follicles are the only pathway for fast caffeine absorption during the first 20 min after application. Copyright 2007 S. Karger AG, Basel.

  13. 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.

  14. Follicular thyroglobulin induces cathepsin H expression and activity in thyrocytes.

    PubMed

    Oda, Kenzaburo; Luo, Yuqian; Yoshihara, Aya; Ishido, Yuko; Sekihata, Kengo; Usukura, Kensei; Sue, Mariko; Hiroi, Naoki; Hirose, Takahisa; Suzuki, Koichi

    2017-01-29

    Thyroglobulin (Tg) stored in thyroid follicles exerts a potent negative-feedback effect on each step of pre-hormone biosynthesis, including Tg gene transcription and iodine uptake and organification, by suppressing the expression of specific transcription factors that regulate these steps. Pre-hormones are stored in the follicular colloid before being reabsorbed. Following lysosomal proteolysis of its precursor, thyroid hormone (TH) is released from thyroid follicles. Although the suppressive effects of follicular Tg on each step of pre-hormone biosynthesis have been extensively characterized, whether follicular Tg accumulation also affects hormone reabsorption, proteolysis, and secretion is unclear. In this study we explored whether follicular Tg can regulate the expression and function of the lysosomal endopeptidases cathepsins. We found that in the rat thyroid cell line FRTL-5 follicular Tg induced cathepsin H mRNA and protein expression, as well as cathepsin H enzyme activity. Double immunofluorescence staining showed that Tg endocytosis promoted cathepsin H translocalization into lysosomes where it co-localized with internalized Tg. These results suggest that cathepsin H is an active participant in lysosome-mediated pre-hormone degradation, and that follicular Tg stimulates mobilization of pre-hormones by activating cathepsin H-associated proteolysis pathways. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Clinical parameters predictive of malignancy of thyroid follicular neoplasms

    SciTech Connect

    Davis, N.L.; Gordon, M.; Germann, E.; Robins, R.E.; McGregor, G.I. )

    1991-05-01

    Needle aspiration biopsy is commonly employed in the evaluation of thyroid nodules. Unfortunately, the cytologic finding of a 'follicular neoplasm' does not distinguish between a thyroid adenoma and a follicular cancer. The purpose of this study was to identify clinical parameters that characterize patients with an increased risk of having a thyroid follicular cancer who preoperatively have a 'follicular neoplasm' identified by needle aspiration biopsy. A total of 395 patients initially treated at Vancouver General Hospital and the British Columbia Cancer Agency between the years of 1965 and 1985 were identified and their data were entered into a computer database. Patients with thyroid adenomas were compared to patients with follicular cancer using the chi-square test and Student's t-test. Statistically significant parameters that distinguished patients at risk of having a thyroid cancer (p less than 0.05) included age greater than 50 years, nodule size greater than 3 cm, and a history of neck irradiation. Sex, family history of goiter or neoplasm, alcohol and tobacco use, and use of exogenous estrogen were not significant parameters. Patients can be identified preoperatively to be at an increased risk of having a follicular cancer and accordingly appropriate surgical resection can be planned.

  16. Follicular porokeratosis: distinct clinical entity or histologic variant?

    PubMed

    Pongpudpunth, M; Farber, J; Mahalingam, M

    2009-11-01

    Various clinical subtypes of porokeratosis, clinically characterized by annular plaques with a normal or atrophic center and a distinctive keratotic ridge, are described based on the age of onset, size, number and distribution of the lesions. Follicular involvement, identified by follicular localization of cornoid lamellae, is uncommon and has only been reported in association with other subtypes such as disseminated superficial actinic porokeratosis and porokeratosis of Mibelli. We present a case of follicular porokeratosis in a 40-year-old male who presented initially with scaly red "papules" in a follicular distribution on the upper extremity. Microscopic examination of a punch biopsy specimen revealed parakeratosis confined to the follicle and mild interface change. A repeat biopsy performed in 2008 revealed identical histologic features. In terms of etiopathogenesis, a clone of cells at the base of the follicle demonstrating abnormal keratinization is not a novel concept and has been demonstrated in other porokeratotic dermatoses. However, the presence of lesions that are solely follicular based, in terms of clinical presentation and histologic findings, and static over a 3-year period favors the concept that follicular porokeratosis is a distinct clinical entity and not merely a histologic variant of the porokeratotic dermatoses described in the literature thus far.

  17. Serum allotypes in ovarian follicular fluids of pigs.

    PubMed

    Matousek, J; Hojný, J; Janik, A

    1986-01-01

    Sera and ovarian follicular fluids of 158 sows were tested with 27 allotype reagents. Immunodiffusion in agar gel (microtest) and haemagglutination inhibition were used as detection methods. Out of eight 'individual' (Lpb 1,-2,-3,-4,-5,-6,-7,-9) and four 'common' (Lpb 12,-13,-14,-16) specificities of serum beta-lipoproteins (LDL), 11 were present in sera, but none in follicular fluids. On the other hand, Lpr 1 and Lpr (x) allotypes of the VHDL + VLDL beta-lipoprotein system were detected both in sera and in follicular fluids. Of four antigens of the Gp system (Gp A,-a, -B,-b), only the 'dominant' characters, Gp A and Gp B, occurred in the follicular fluid. The typing of polymorphic IgG immunoglobulins (IgG-a or IgG-b system) showed that B1 or A2, B2 or A1 and B3 or A(x) allotypes could be detected both in serum and follicular fluid. Among allotypes that were not yet genetically classified, only the P3 specificity was not found in the population tested. The G1 allotype (preliminarily described as an alpha-globulin) was present in sera only, and the remaining allotypes, G9, P1, P16 and P23 (alpha- or beta-globulins) were present both in sera and follicular fluids. The mechanism of the transmission of serum proteins into ovarian follicles and their possible importance is discussed.

  18. Supplementation with small-extracellular vesicles from ovarian follicular fluid during in vitro production modulates bovine embryo development

    PubMed Central

    Andrade, Gabriella M.; del Collado, Maite; Sampaio, Rafael V.; Sangalli, Juliano R.; Silva, Luciano A.; Pinaffi, Fábio V. L.; Jardim, Izabelle B.; Cesar, Marcelo C.; Nogueira, Marcelo F. G.; Cesar, Aline S. M.; Coutinho, Luiz L.; Pereira, Rinaldo W.; Perecin, Felipe; Meirelles, Flávio V.

    2017-01-01

    Pregnancy success results from the interaction of multiple factors, among them are folliculogenesis and early embryonic development. Failure during these different processes can lead to difficulties in conception. Alternatives to overcome these problems are based on assisted reproductive techniques. Extracellular vesicles are cell-secreted vesicles present in different body fluids and contain bioactive materials, such as messenger RNA, microRNAs (miRNAs), and proteins. Thus, our hypothesis is that extracellular vesicles from follicular fluid from 3–6 mm ovarian follicles can modulate bovine embryo development in vitro. To test our hypothesis follicular fluid from bovine ovaries was aspirated and small-extracellular vesicles (<200 nm) were isolated for further analysis. Additionally, small-extracellular vesicles (EVs) were utilized for functional experiments investigating their role in modulating messenger RNA, microRNA as well as global DNA methylation and hydroxymethylation levels of bovine blastocysts. EVs from 3–6 mm follicles were used for RNA-seq and miRNA analysis. Functional annotation analysis of the EVs transcripts revealed messages related to chromatin remodeling and transcriptional regulation. EVs treatment during oocyte maturation and embryo development causes changes in blastocyst rates, as well as changes in the transcription levels of genes related to embryonic metabolism and development. Supplementation with EVs from 3–6 mm follicles during oocyte maturation and early embryo development (until the 4-cell stage) increased the levels of bta-miR-631 (enriched in EVs from 3–6 mm follicles) in embryos. Interestingly, the addition of EVs from 3–6 mm follicles induced changes in global DNA methylation and hydroxymethylation levels compared to embryos produced by the standard in vitro production system. Our results indicate that the supplementation of culture media with EVs isolated from the follicular fluid of 3–6 mm follicles during oocyte

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

    ClinicalTrials.gov

    2017-02-17

    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. Development of T follicular helper cells and their role in disease and immune system.

    PubMed

    Eivazi, Sadegh; Bagheri, Salman; Hashemzadeh, Mohammad Sadegh; Ghalavand, Majdedin; Qamsari, Elmira Safaie; Dorostkar, Ruhollah; Yasemi, Maryam

    2016-12-01

    The T follicular helper cells (TFH) are a subset of CD4+ T cells specialized to regulate antibody responses. The production of these cells is associated with the dendritic cells (DCs) and B cells. TFH cells help B cells form germinal centers (GC) differentiate into memory and plasma cells (antibody-secreting cells) as humoral responses. In addition, there is strong evidence that TFH cells play a pivotal role in the development of long-lived humoral immunity. Molecular factors such as transcription factors, surface receptors, cytokine and micro RNAs are involved in the formation of TFH cells. Such TFH cells are diagnosed by transcription factor (BCL-6), surface marker expression (including CXCR5, PD-1, ICOS and CD40L) and a unique cytokine production pattern (such as IL-21 and IL-6). Memory TFH cells, accompanied by memory B cells, are known to be formed during antibody responses. It is now clear that the precise control of TFH cells is critically important for both inducing the optimal affinity maturation of antibody responses and preventing self-reactivity. Exclusive controls of TFH cell function and production are essential for human health. However, it is important to note that excessive activities may lead to autoimmune diseases, while reduced activity often results in immunodeficiency. It has also been shown that TFH cells are associated with cancers such as angioimmunoblastic T-cell lymphoma (AITL), follicular T-cell lymphoma (FTCL) and nonspecific Peripheral T-cell lymphomas (PTCLs). The biology of TFH cells, including their differentiation and transcriptional regulation will be described in the present review. Some of The developments of these cells in immunodeficiency diseases, autoimmunity and cancer will also be taken into account.

  1. Developing dendrites demonstrate unexpected specificity.

    PubMed

    Chalupa, Leo M

    2006-11-22

    Our knowledge of how developing dendrites attain their mature state is still rudimentary. In this issue of Neuron, Mumm et al. rely on time-lapsed analysis of ingrowing dendrites of retinal ganglion cells in transgenic zebrafish to show that this process is much more specific than has been suspected.

  2. Human dendritic cells and macrophages. In situ immunophenotypic definition of subsets that exhibit specific morphologic and microenvironmental characteristics.

    PubMed Central

    Wood, G. S.; Turner, R. R.; Shiurba, R. A.; Eng, L.; Warnke, R. A.

    1985-01-01

    Using a panel of monoclonal antibodies and antisera in situ, the authors have defined subsets of human dendritic cells and macrophages that exhibit specific morphologic and microenvironmental characteristics. All subsets contained cells that reacted with antibodies directed against HLA-A,B,C, HLA-Dr, leukocyte common, Leu-M3, and Leu-3(T4) antigens. R4/23 and anti-S100 defined three major subsets. R4/23+, S100- cells constituted the B-cell-related follicular dendritic cells, which were identified only within the germinal center/mantle microenvironment of lymphoid follicles. R4/23-, S100+ cells constituted the T-cell-related dendritic cell subset. Anti-Leu-6(T6) further subdivided this group into Leu-6(T6)- interdigitating cells within the T-cell microenvironments of lymphoid organs and Leu-6(T6)+ Langerhans cells found predominantly in epithelial microenvironments, especially the skin. R4/23-, S100- cells constituted the nondendritic tissue macrophage subset which was widely distributed, primarily outside of dendritic-cell microenvironments. These data indicate that although dendritic cells and macrophages share several common antigenic features, morphologically and microenvironmentally distinct subsets express distinct immunologic phenotypes. Such data may provide insight into the ontogeny and function of these subsets and constitute a basis for the comparison of normal dendritic cells and macrophages to various histiocytic proliferative disorders. Images Figure 1 Figure 2 p78-c Figure 3 Figure 4 Figure 5 PMID:3985124

  3. Follicular adenomatoid odontogenic tumor: immunohistochemical study.

    PubMed

    Vera Sempere, Francisco José; Artes Martínez, María Jose; Vera Sirera, Beatriz; Bonet Marco, Jaime

    2006-07-01

    Adenomatoid odontogenic tumor (AOT) is an uncommon benign odontogenic lesion that affects young patients, with female predominance, mainly in second decade, showing a radiolucent unilocular image associated with an unerupted tooth, usually a canine. In spite of previous and confusing denominations, such as adenoameloblastoma or adenomatoid ameloblastic tumor, AOT is a benign tumor with a very low rate of recurrence, that show a peculiar morphological picture (basaloid appearance with glandular-like structures, calcifying areas, and amiloid-like material) that allow its histopathological recognition. We present a clinicopathological analysis of a case of follicular AOT affecting the mandible in a 9 years-old female patient associated with unerupted lower left canine. Immunohistochemical study showed some data previously unrecognised. All cellular types that composed AOT showed nuclear positivity for p63 indicating a basal characterization in the different cellular components. According to its benign character and low potential for recurrence, AOT revealed a scant proliferative activity (2-3% nuclei showed Ki-67 positivity) limited to some epithelial nodules (AE1-3 +) of fusiform appearance. Absence of reactivity for hormonal receptors (RE and RPg) excluded a possible hormonodependence in AOT that could explain the observed female predominance.

  4. Exploring Risk Factors for Follicular Lymphoma

    PubMed Central

    Ambinder, Alexander J.; Shenoy, Pareen J.; Malik, Neha; Maggioncalda, Alison; Nastoupil, Loretta J.; Flowers, Christopher R.

    2012-01-01

    Follicular lymphoma (FL) is an indolent malignancy of germinal center B cells with varied incidence across racial groups and geographic regions. Improvements in the classification of non-Hodgkin lymphoma subtypes provide an opportunity to explore associations between environmental exposures and FL incidence. Our paper found that aspects of Western lifestyle including sedentary lifestyle, obesity, and diets high in meat and milk are associated with an increased risk of FL. Diets rich in fruits and vegetables, polyunsaturated fatty acids, vitamin D, and certain antioxidants are inversely associated with FL risk. A medical history of Sjogren's syndrome, influenza vaccination, and heart disease may be associated with FL incidence. Associations between FL and exposure to pesticides, industrial solvents, hair dyes, and alcohol/tobacco were inconsistent. Genetic risk factors include variants at the 6p21.32 region of the MHC II locus, polymorphisms of the DNA repair gene XRCC3, and UV exposure in individuals with certain polymorphisms of the vitamin D receptor. Increasing our understanding of risk factors for FL must involve integrating epidemiological studies of genetics and exposures to allow for the examination of risk factors and interactions between genes and environment. PMID:23028387

  5. Follicular ovarian cysts in stillbirths and neonates.

    PubMed Central

    deSa, D J

    1975-01-01

    A review of the histology of 332 ovaries from stillbirths and neonatal deaths within the first 28 days of life showed that follicular cysts, lined by granulosa epithelium and having a diameter greater than 1 mm on a microscopical section, were present in 113 infants. In 48 cases multiple cysts were present, while in 65 only a single cyst satisfying the criteria was found. There was an excess number of infants of low birthweight score among those with multiple cysts and the results were highly significant. Cysts, whether single or multiple in distribution, were commoner with increasing gestation, and possibly occurred more commonly in the infants of diabetic mothers and in infants where pregnancy had been complicated by rhesus isoimmunization. The nature of the changes seen in the granulosa lining and theca internal layer surrounding the cysts suggested that these cysts were not some degenerative phenomenon but occured in response to stimulation. It is suggested that homologous changes may occur in the testis of the dysmature male. The possible significance of these findings with regard to hormonal imbalance in the growth-retarded infant is considered, and the need for closer attention to endocrine function in these infants stressed. Images FIG. 1. FIG. 2. FIG. 3. FIG. 4. PMID:1124943

  6. Treatment of follicular lymphoma: current status.

    PubMed

    Tilly, Hervé; Zelenetz, Andrew

    2008-01-01

    With the recent proliferation of treatment options for patients with follicular lymphoma (FL), median survival has been shown to have improved, from 84 months between 1983 and 1989 to 93 months between 1993 and 1999. Nevertheless, relapse is common in this patient group, and treatment options that extend the duration of remission without increased toxicity are still required. Rituximab has made a major contribution to the treatment of patients with FL, improving outcomes and making new treatment schedules possible. It is now a standard practice to administer rituximab with first-line combination chemotherapy in patients with FL. In addition, a number of current trials are examining the potential role of rituximab maintenance therapy in improving outcomes in FL. However, at present it is not clear which schedules or combinations are the most effective, and further randomised controlled trials of treatment strategies incorporating rituximab are needed to provide the evidence that will allow clinicians to maximise the potential of this drug. Second-line options for the treatment of FL include allogeneic stem cell transplantation, radioimmunotherapy targeted to CD20 and, in selected patients, autologous stem cell transplantation. New treatment approaches for FL currently being investigated in the second-line setting include the proteasome inhibitor, bortezomib and novel anti-CD20 monoclonal antibodies.

  7. Eradication of Helicobacter pylori in follicular and nonfollicular gastritis.

    PubMed

    Mehmet, Sokmen; Ozdal, Ersoy; Kamil, Ozdil; Beşir, Kesici; Huseyin, Demirsoy; Nihat, Akbayir; Cigdem, Ersoy Yazici; Nusret, Erdogan

    2009-01-01

    Effective eradication therapy of Helicobacter pylori (Hp) in non-follicular type gastritis is commonly demonstrated by many studies. In contrast, some other studies show that the eradication of Hp is low in follicular type gastritis. However, the subject concerning the comparison of the results of triple-drug Hp eradication treatment between follicular and nonfollicular type gastritis is still unclear because of the paucity of studies. The aim of this study was to compare the results of Hp eradication therapy between follicular and non-follicular type gastritis. Two age- and sex-matched groups, consisting of 21 patients with follicular type and 23 patients with nonfollicular type gastritis associated with Hp (histopathologically diagnosed after endoscopic procedure), were enrolled into our study. Triple-drug Hp eradication therapy [lansoprazole (L) 30 mg bid, amoxicillin (A) 1000 g bid and clarithromycin (C) 500 mg bid] was given to all patients in both groups for two weeks. Control for the eradication of Hp was performed by endoscopic biopsy (3 months after treatment) in the follicular group and by urea-breath test (1 month after treatment) in the nonfollicular group. Eradication of the follicles in follicular type gastritis was also observed in the control endoscopic biopsies. For the statistical analysis, SPSS 11 for Windows was used and paired-samples t-test was performed. p<0.05 was considered as significant. In total, 66 patients were enrolled into the study. All were histopathologically diagnosed as having Hp-associated gastritis (31 follicular and 35 nonfollicular) and started on triple-drug Hp eradication therapy. Only 44 of these patients (21 follicular gastritis and 23 nonfollicular gastritis) completed 2 weeks of treatment. The other 22 patients were not able to complete the treatment because of not taking the drugs properly or of the side-effects of the drugs. Patient compliance ratio to the treatment was 67.7%. The ratios for Hp eradication in

  8. Diagnostic role of 18F-fluorodeoxyglucose positron emission tomography for follicular lymphoma with gastrointestinal involvement

    PubMed Central

    Iwamuro, Masaya; Okada, Hiroyuki; Takata, Katsuyoshi; Shinagawa, Katsuji; Fujiki, Shigeatsu; Shiode, Junji; Imagawa, Atsushi; Araki, Masashi; Morito, Toshiaki; Nishimura, Mamoru; Mizuno, Motowo; Inaba, Tomoki; Suzuki, Seiyu; Kawai, Yoshinari; Yoshino, Tadashi; Kawahara, Yoshiro; Takaki, Akinobu; Yamamoto, Kazuhide

    2012-01-01

    AIM: To investigate the capacity for 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) to evaluate patients with gastrointestinal lesions of follicular lymphoma. METHODS: This retrospective case series consisted of 41 patients with follicular lymphoma and gastrointestinal involvement who underwent 18F-FDG-PET and endoscopic evaluations at ten different institutions between November 1996 and October 2011. Data for endoscopic, radiological, and biological examinations performed were retrospectively reviewed from clinical records. A semi-quantitative analysis of 18F-FDG uptake was performed for each involved area by calculating the maximum standardized uptake value (SUVmax). Based on the positivity of 18F-FDG uptake in the gastrointestinal lesions analyzed, patients were subdivided into two groups. To identify potential predictive factors for 18F-FDG positivity, these two groups were compared with respect to gender, age at diagnosis of lymphoma, histopathological grade, pattern of follicular dendritic cells, mitotic rate, clinical stage, soluble interleukin-2 receptor levels detected by 18F-FDG-PET, lactate dehydrogenase (LDH) levels, hemoglobin levels, bone marrow involvement, detectability of gastrointestinal lesions by computed tomography (CT) scanning, and follicular lymphoma international prognostic index (FLIPI) risk. RESULTS: Involvement of follicular lymphoma in the stomach, duodenum, jejunum, ileum, cecum, colon, and rectum was identified in 1, 34, 6, 3, 2, 3, and 6 patients, respectively. No patient had esophageal involvement. In total, 19/41 (46.3%) patients exhibited true-positive 18F-FDG uptake in the lesions present in their gastrointestinal tract. In contrast, false-negative 18F-FDG uptake was detected in 24 patients (58.5%), while false-positive 18F-FDG uptake was detected in 5 patients (12.2%). In the former case, 2/19 patients had both 18F-FDG-positive lesions and 18F-FDG-negative lesions in the gastrointestinal tract. In patients

  9. FSH-stimulated follicular secretions enhance oocyte maturation in pigs.

    PubMed

    Ding, J; Foxcroft, G R

    1994-01-01

    Follicular secretions can support cytoplasmic maturation in vitro in the pig. The effects of follicular secretions stimulated in vitro by different combinations of gonadotropins and over different culture periods on cytoplasmic maturation of the pig oocyte were studied. In Experiment 1, follicular shells (including theca and mural granulosa cells) from 5 to 7-mm follicles were cultured in vitro under the stimulation of different combinations of gonadotropins for 48 h, and then the obtained conditioned media were used for oocyte maturation. Oocytes cultured in conditioned medium harvested after treatment of follicular shells with 2.5 mug/ml FSH (FSH-stimulated conditioned medium) yielded a higher percentage of male pronuclear formation than those matured in conditioned medium harvested after culture of follicular shells with a combination of hormones (2.5mug/ml FSH, 2.5 mug/ml LH and 20 ng/ml PRL, FSH-LH-PRL-stimulated conditioned medium; 54.1 vs 28.5%; P=0.001). Addition of the combination of FSH, LH and PRL during the period of oocyte maturation marginally improved male pronuclear formation rates (41.3 vs 55.6%; P=0.06). In Experment 2, follicular shells were cultured under the stimulation of FSH only. Conditioned media were harvested after the first 24 h and the second 24 h of culture. The rates of male pronuclear formation in oocytes matured in these 2 conditioned media did not differ (P=0.65), but were higher than those of oocytes matured in fresh control medium (P<0.03). It is concluded that factors secreted by follicular cells stimulated by FSH alone provide better support for full oocyte maturation in the pig than by combined FSH, LH and PRL treatment.

  10. Phase II study of a TLR-9 agonist (1018 ISS) with rituximab in patients with relapsed or refractory follicular lymphoma.

    PubMed

    Friedberg, Jonathan W; Kelly, Jennifer L; Neuberg, Donna; Peterson, Derick R; Kutok, Jeffery L; Salloum, Rabih; Brenn, Thomas; Fisher, David C; Ronan, Elizabeth; Dalton, Virginia; Rich, Lynn; Marquis, Diana; Sims, Paul; Rothberg, Paul G; Liesveld, Jane; Fisher, Richard I; Coffman, Robert; Mosmann, Tim; Freedman, Arnold S

    2009-08-01

    Toll-like receptor-9 (TLR-9) agonists have pleotropic effects on both the innate and adaptive immune systems, including increased antigen expression, enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) and T helper cell type 1 shift in the immune response. We combined a TLR-9 agonist (1018 ISS, 0.2 mg/kg sc weekly x 4 beginning day 8) with standard rituximab (375 mg/m(2) weekly x 4) in patients (n = 23) with relapsed/refractory, histologically confirmed follicular lymphoma, and evaluated immunological changes following the combination. Treatment was well-tolerated with no significant adverse events attributable to therapy. Clinical responses were observed in 48% of patients; the overall median progression-free survival was 9 months. Biologically relevant increases in ADCC and circulating CD-3 positive T cells were observed in 35% and 39% of patients, respectively. Forty-five percent of patients had increased T cells and dendritic cells in skin biopsies of 1018 ISS injection sites 24 h post-therapy. Pre- and post-biopsies of tumour tissue demonstrated an infiltration of CD8(+) T cells and macrophages following treatment. This group of patients had favourable clinical outcome despite adverse prognostic factors. This study is the first to histologically confirm perturbation of the local immune microenvironment following systemic biological therapy of follicular lymphoma.

  11. Phase II study of a TLR-9 agonist (1018 ISS) with rituximab in patients with relapsed or refractory follicular lymphoma

    PubMed Central

    Friedberg, Jonathan W; Kelly, Jennifer L; Neuberg, Donna; Peterson, Derick R.; Kutok, Jeffery L; Salloum, Rabih; Brenn, Thomas; Fisher, David C; Ronan, Elizabeth; Dalton, Virginia; Rich, Lynn; Marquis, Diana; Sims, Paul; Rothberg, Paul G.; Liesveld, Jane; Fisher, Richard I; Coffman, Robert; Mosmann, Tim; Freedman, Arnold S

    2009-01-01

    Summary Toll-Like Receptor-9 (TLR-9) agonists have pleotropic effects on both the innate and adaptive immune systems, including increased antigen expression, enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) and T helper cell type 1 shift in the immune response. We combined a TLR-9 agonist (1018 ISS, 0.2 mg/kg sc weekly × 4 beginning day 8) with standard rituximab (375mg/m2 weekly × 4) in patients (n=23) with relapsed/refractory, histologically confirmed follicular lymphoma, and evaluated immunological changes following the combination. Treatment was well-tolerated with no significant adverse events attributable to therapy. Clinical responses were observed in 48% of patients; the overall median progression-free survival was 9 months. Biologically relevant increases in ADCC and circulating CD-3 positive T cells were observed in 35% and 39% of patients, respectively. 45% of patients had increased T cells and dendritic cells in skin biopsies of 1018 ISS injection sites 24 h post-therapy. Pre-and post-biopsies of tumour tissue demonstrated an infiltration of CD8+ T cells and macrophages following treatment. This group of patients had favourable clinical outcome despite adverse prognostic factors. This study is the first to histologically confirm perturbation of the local immune microenvironment following systemic biological therapy of follicular lymphoma. PMID:19519691

  12. 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.

  13. 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

  14. Equiaxed Dendritic Solidification Experiment (EDSE)

    NASA Technical Reports Server (NTRS)

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

    1999-01-01

    The objective of the research is to quantitatively determine and understand the fundamental mechanisms that control the microstructural evolution during solidification of an assemblage of equiaxed dendritic crystals. A microgravity experiment will be conducted to obtain benchmark data on the transient growth and interaction of up to four equiaxed crystals of a pure and transparent metal analog (succinonitrile, SCN) under strictly diffusion dominated conditions. Of interest in the experiment are the transient evolution of the primary and secondary dendrite tip speeds, the dendrite morphology (i.e., tip radii, branch spacings, etc.) and solid fraction, the tip selection criterion, and the temperature field in the melt for a range of initial supercoolings and, thus, interaction "strengths" between the crystals. The experiment thus extends the microgravity measurements of Glicksman and coworkers for steady growth of a single dendrite [Isothermal Dendritic Growth Experiment (IDGE), first flown on USMP-2] to a case where growth transients are introduced due to thermal interactions between neighboring dendrites - a situation more close to actual casting conditions. Corresponding earth-based experiments will be conducted to ascertain the influence of melt convection. The experiments are supported by a variety of analytical models and numerical simulations. The data will primarily be used to develop and test theories of transient dendritic growth and the solidification of multiple interacting equiaxed crystals in a supercooled melt.

  15. Equiaxed Dendritic Solidification Experiment (EDSE)

    NASA Technical Reports Server (NTRS)

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

    2001-01-01

    The objective of the research is to quantitatively determine and understand the fundamental mechanisms that control the microstructural evolution during equiaxed dendritic solidification. A microgravity experiment will be conducted to obtain benchmark data on the transient growth and interaction of up to four equiaxed crystals of a pure and transparent metal analog (succinonitrile, SCN) under strictly diffusion-dominated conditions. Of interest in the experiment are the transient evolution of the primary and secondary dendrite tip speeds, the dendrite morphology and solid fraction, the tip selection criterion, and the temperature field in the melt for a range of interaction "strengths" between the crystals. The experiment extends the microgravity measurements of Glicksman and co-workers isothermal dendritic growth experiment (IDGE) for steady growth of a single dendrite to a case where growth transients are introduced due to thermal interactions between neighboring dendrites - a situation closer to actual casting conditions. Corresponding Earth-based experiments will be conducted to ascertain the influence of melt convection. The experiments are supported by a variety of analytical models and numerical simulations. The data will be used to develop and test theories of transient dendritic growth and the solidification of multiple interacting equiaxed crystals in a supercooled melt.

  16. 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.

  17. 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.

  18. Clonally related Histiocytic/dendritic cell sarcoma and chronic lymphocytic leukemia/small lymphocytic lymphoma: A study of 7 cases

    PubMed Central

    Shao, Haipeng; Xi, Liqiang; Raffeld, Mark; Feldman, Andrew L.; Ketterling, Rhett P.; Knudson, Ryan; Rodriguez-Canales, Jaime; Hanson, Jeffrey; Pittaluga, Stefania; Jaffe, Elaine S

    2011-01-01

    Histiocytic and interdigitating dendritic cell sarcomas are rare tumors originating from bone marrow derived myeloid stem cells. Recent studies have shown evidence of cross-lineage transdifferentiation of B-cells in follicular lymphoma to histiocytic and dendritic cell sarcomas. In this study, we report the morphologic, molecular and cytogenetic analysis of 7 cases of chronic lymphocytic leukemia/small lymphocytic lymphoma associated with histiocytic and dendritic cell sarcomas. All seven patients were elderly males (median age, 71 years). The B-cell neoplasms preceded the development of the histiocytic and dendritic cell sarcomas in 6 of 7 patients, and one patient had both tumors diagnosed at the same time. The tumors included 4 interdigitating dendritic cell sarcomas; 1 Langerhans cell sarcoma, 1 histiocytic sarcoma, and 1 immature neoplasm with evidence of histiocytic origin. Laser-capture microdissection and PCR analysis showed identical clonal immunoglobulin gene rearrangements in the two phenotypically distinct components in all cases. There was a preferential usage of IGHV4-39 by the V-D-J gene rearrangement. By FISH analysis two cases showed deletion 17p in both components, while 4 cases had normal cytogenetic findings by FISH in the CLL/SLL cells, but acquired cytogenetic abnormalities in the corresponding histiocytic and dendritic tumors. Chromosome 17p abnormalities were the most common cytogenetic abnormality detected in the sarcomas, seen in 5 of 6 cases studied. Compared with the CLL/SLL cells, the histiocytic/dendritic cells were largely negative for PAX5, but showed strong expression of PU.1 and variable and weak expression of CEBPβ. Our study provides evidence for transdifferentiation of CLL/SLL B-cells to tumors of dendritic and less often histiocytic lineage, and suggests that secondary genetic events may play a role in this phenomenon. PMID:21666687

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

    ClinicalTrials.gov

    2017-02-02

    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

  20. Treatment of follicular NHL: The old and the new

    PubMed Central

    Friedberg, Jonathan W.

    2008-01-01

    Despite remaining an incurable disease, overall survival improvements have been noted in patients with advanced stage follicular lymphoma. The Follicular Lymphoma International Prognostic Index (FLIPI) is a robust prognostic index in this disease, and continues to provide prognostic information in the rituximab era. Rituximab has significantly changed the management of follicular lymphoma, and the most dramatic impact of rituximab is observed in combination with cytotoxic chemotherapy. However, resistance to rituximab remains a problem, and standard therapy in the rituximab-refractory setting includes radioimmunotherapy, autologous stem cell transplantation, and allogeneic stem cell transplantation. In addition, several novel agents show encouraging activity in FL, including bendamustine, lenalidomide, bortezomib and other proteasome inhibitors, and BCL2 inhibitors. PMID:18760706

  1. T follicular regulatory cells in mice and men.

    PubMed

    Maceiras, Ana Raquel; Fonseca, Valter R; Agua-Doce, Ana; Graca, Luis

    2017-09-01

    It has long been known that CD4 T cells are necessary to provide help to B cells, triggering a germinal centre (GC) reaction where affinity maturation and isotype switching occur. However, the nature of the dedicated CD4 helper T cells, known as T follicular helper (Tfh), was only recently described. Here, we review the biology and function of the recently described T follicular regulatory (Tfr) cells, another CD4 T-cell population also found within GCs but with regulatory function and characteristics. Tfr cells have been identified in mice and humans as simultaneously presenting characteristics of T follicular cells (namely CXCR5 expression) and regulatory T cells (including Foxp3 expression). These Tfr cells have been implicated in the regulation of the magnitude of the GC reaction, as well as in protection from immune-mediated pathology. © 2017 John Wiley & Sons Ltd.

  2. Noninvasive follicular thyroid neoplasm with papillary-like nuclear features.

    PubMed

    Ghuzlan, Abir A; Ramos, Helton E; Schlumberger, Martin

    2017-10-01

    The purpose of this review is to present an overview regarding the renaming of encapsulated follicular variant of papillary thyroid cancer as 'noninvasive follicular thyroid neoplasm with papillary-like nuclear features'. A recent retrospective study has shown the excellent clinical outcomes of noninvasive encapsulated follicular variant of papillary thyroid cancer, for which the diagnosis is based on a thorough examination of all tumor tissue and its capsule to exclude any vascular or capsular invasion. Given the extremely low malignant potential of this entity, the term cancer was eliminated from its name, as this tumor requires less aggressive follow-up and treatment. The low-risk tumor was previously treated conservatively prior to its renaming. However, elimination of the term cancer from its name may decrease the psychological and social consequences of its diagnosis.

  3. Follicular atresia in the prepubertal spiny mouse (Acomys cahirinus) ovary.

    PubMed

    Hułas-Stasiak, Monika; Gawron, Antoni

    2011-10-01

    This study was designed to determine follicular atresia in the newborn and the prepubertal spiny mouse. We analyzed the processes of follicle loss using classical markers of apoptosis (TUNEL reaction, active caspase-3) and autophagy (Lamp1). Numerous small clear vacuoles and autophagosomes as well as strong Lamp1 staining were observed in dying oocytes of all follicle types, especially of the primordial and primary ones. Active caspase 3 and the TUNEL reaction were detected only in the granulosa cells of large secondary and antral follicles. The expression of apoptosis and autophagy markers was also changing during the prepubertal period. Western blot analysis indicated that at the moment of birth, females undergo an increased rate of follicular atresia mediated by autophagy, while apoptosis is the dominant form of ovarian atresia in consecutive postnatal days. On the basis of these observations, we concluded that apoptosis and autophagy are involved in follicular atresia and these processes are cell and developmental stage-specific.

  4. Extracellular vesicles in human follicular fluid do not promote coagulation.

    PubMed

    Franz, Cordula; Böing, Anita N; Montag, Markus; Strowitzki, Thomas; Markert, Udo R; Mastenbroek, Sebastiaan; Nieuwland, Rienk; Toth, Bettina

    2016-11-01

    Body fluids contain extracellular vesicles expressing tissue factor on their surface and serve as an additional trigger for coagulation. During the menstrual cycle ovarian tissue restoration is mandatory and it is unknown whether follicular fluid might provide procoagulant substances. Within an observational study, follicular fluid from women undergoing IVF/intracytoplasmic sperm injection (ICSI) was analysed by fluorescence-activated cell sorting (FACS), electron microscopy, resistive pulse sensing (RPS), nanoparticle-tracking analysis (NTA) and fibrin generation tests (FGT). The presence of extracellular vesicles, especially CD9-positive extracellular vesicles in follicular fluid, was proven. However, clotting tests revealed no procoagulant properties of the detected extracellular vesicles. Copyright © 2016 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

  5. Immunoblastic follicular lymphoma: a very unusual transformation of low-grade follicular lymphoma.

    PubMed

    Gheith, Shereen; Cornfield, Dennis; Chen, Weiyi; Singh-Kahlon, Pal; Ahmed, Basil

    2014-11-01

    A 73-year-old man, in clinical remission 17 years after radiation therapy for a localized low-grade follicular lymphoma (FL), developed extensive lymphadenopathy, ascites, and splenomegaly with splenic masses. Axillary lymph node biopsy showed FL composed of nodules of centrocytes side by side with nodules of immunoblasts rather than centroblasts. Immunophenotyping revealed conventional FL markers (BCL-2, BCL-6, and CD10) as well as MUM-1 in the immunoblastic component, suggesting postgerminal center differentiation. Fluorescence in situ hybridization showed t(14;18) in both centrocytic and immunoblastic components and a copy gain of BCL-6 predominantly in the immunoblastic component. Areas of centrocytic and of immunoblastic nodules were macrodissected separately and underwent molecular evaluation for immunoglobulin heavy chain gene rearrangement. Identical base-pair peaks were found, attesting to their clonal identity. This case represents a very unusual example of transformation of a low-grade FL to a nodular immunoblastic FL.

  6. Folliculitis, follicular mucinosis, and papular mucinosis as a presentation of chronic myelomonocytic leukemia.

    PubMed

    Rashid, Rashid; Hymes, Sharon

    2009-05-15

    Leukemias and Lymphomas can present in indolent and surprisingly unusual manners. Although uncommon, follicular lesions such as eosinophilic folliculitis have been reported in association with leukemia. However, follicular and papular mucinosis are novel associations for chronic myelomonocytic leukemia.

  7. 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

  8. Dendritic oligoguanidines as intracellular translocators.

    PubMed

    Chung, Hyun-Ho; Harms, Guido; Seong, Churl Min; Choi, Byung Hyune; Min, Changhee; Taulane, Joseph P; Goodman, Murray

    2004-01-01

    A series of polyguanidylated dendritic structures that can be used as molecular translocators have been designed and synthesized based on nonpeptide units. The dendritic oligoguanidines conjugated with fluorescein or with a green fluorescent protein (GFP) mutant as cargos were isolated and characterized. Quantification and time-course analyses of the cellular uptake of the conjugates using HeLa S3 and human cervical carcinoma cells reveal that the polyguanidylated dendrimers have comparable translocation efficiency to the Tat(49-57) peptide. Furthermore, the deconvolution microscopy image analysis shows that they are located inside the cells. These results clearly show that nonlinear, branched dendritic oligoguanidines are capable of translocation through the cell membrane. This work also demonstrates the potential of these nonpeptidic dendritic oligoguanidines as carriers for intracellular delivery of small molecule drugs, bioactive peptides, and proteins. Copyright 2004 Wiley Periodicals, Inc. Biopolymers (Pept Sci), 2004

  9. 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

  10. Can dendritic cells see light?

    NASA Astrophysics Data System (ADS)

    Chen, Aaron C.-H.; Huang, Ying-Ying; Sharma, Sulbha K.; Hamblin, Michael R.

    2010-02-01

    There are many reports showing that low-level light/laser therapy (LLLT) can enhance wound healing, upregulate cell proliferation and has anti-apoptotic effects by activating intracellular protective genes. In the field of immune response study, it is not known with any certainty whether light/laser is proinflammatory or anti-inflammatory. Increasingly in recent times dendritic cells have been found to play an important role in inflammation and the immunological response. In this study, we try to look at the impact of low level near infrared light (810-nm) on murine bone-marrow derived dendritic cells. Changes in surface markers, including MHC II, CD80 and CD11c and the secretion of interleukins induced by light may provide additional evidence to reveal the mystery of how light affects the maturation of dendritic cells as well how these light-induced mature dendritic cells would affect the activation of adaptive immune response.

  11. Glycosylation of surface Ig creates a functional bridge between human follicular lymphoma and microenvironmental lectins.

    PubMed

    Coelho, Vania; Krysov, Sergey; Ghaemmaghami, Amir M; Emara, Mohamed; Potter, Kathleen N; Johnson, Peter; Packham, Graham; Martinez-Pomares, Luisa; Stevenson, Freda K

    2010-10-26

    Surface Ig (sIg) of follicular lymphoma (FL) is vital for tumor cell survival. We found previously that the Ig in FL is unusual, because the variable region genes carry sequence motifs for N-glycan addition. These are introduced by somatic mutation and are tumor specific. Unexpectedly, added glycans terminate at high mannose, suggesting a potentially important interaction of FL cells with mannose-binding lectins of the innate immune system. We have now identified mannosylated IgM at the surface of primary lymphoma cells. Recombinant lectin domains of the mannose receptor (MR) or DC-SIGN bind mannosylated Igs in vitro and bind to FL cells, signaling sIgM-associated increases in intracellular Ca(2+). Lectins also bind to normal B cells but fail to signal. In contrast, anti-Ig signaled similarly in both FL and normal B cells. Mannosylation patterns were mimicked by FL Ig-derived single-chain Fvs (scFv), providing probes for potential receptors. Mannosylated scFv bound specifically to the lectin domains of the MR and DC-SIGN and blocked signaling. Mannosylated scFv also bound to DC-SIGN on the surface of dendritic cells. This unique lymphoma-specific interaction of sIg with lectins of innate immunity reveals a potential route for microenvironmental support of tumor cells, mediated via the key B-cell receptor.

  12. Glycosylation of surface Ig creates a functional bridge between human follicular lymphoma and microenvironmental lectins

    PubMed Central

    Coelho, Vania; Krysov, Sergey; Ghaemmaghami, Amir M.; Emara, Mohamed; Potter, Kathleen N.; Johnson, Peter; Packham, Graham; Martinez-Pomares, Luisa; Stevenson, Freda K.

    2010-01-01

    Surface Ig (sIg) of follicular lymphoma (FL) is vital for tumor cell survival. We found previously that the Ig in FL is unusual, because the variable region genes carry sequence motifs for N-glycan addition. These are introduced by somatic mutation and are tumor specific. Unexpectedly, added glycans terminate at high mannose, suggesting a potentially important interaction of FL cells with mannose-binding lectins of the innate immune system. We have now identified mannosylated IgM at the surface of primary lymphoma cells. Recombinant lectin domains of the mannose receptor (MR) or DC-SIGN bind mannosylated Igs in vitro and bind to FL cells, signaling sIgM-associated increases in intracellular Ca2+. Lectins also bind to normal B cells but fail to signal. In contrast, anti-Ig signaled similarly in both FL and normal B cells. Mannosylation patterns were mimicked by FL Ig-derived single-chain Fvs (scFv), providing probes for potential receptors. Mannosylated scFv bound specifically to the lectin domains of the MR and DC-SIGN and blocked signaling. Mannosylated scFv also bound to DC-SIGN on the surface of dendritic cells. This unique lymphoma-specific interaction of sIg with lectins of innate immunity reveals a potential route for microenvironmental support of tumor cells, mediated via the key B-cell receptor. PMID:20937880

  13. Pituitary follicular cells produce basic fibroblast growth factor

    SciTech Connect

    Ferrara, N.; Schweigerer, L.; Neufeld, G.; Mitchell, R.; Gospodarowicz, D.

    1987-08-01

    Cultured monolayers of bovine pituitary follicular cells, which transport ions, contain high amounts of mitogenic activity for endothelial cells which, on the basis of gene expression analysis, heparin-Sepharose elution profile, bioassay, immunoblotting, radioimmunoassay, and radioreceptor assay, has been identified as basic fibroblast growth factor (bFGF). These data indicate that follicular cells may be a major source of bFGF in the pituitary gland. Considering that bFGF has been proposed to play a role in paracrine regulation of pituitary hormone secretion, the data also suggest that these cells may exert important local regulatory functions.

  14. Mixed medullary and follicular carcinoma of the thyroid.

    PubMed

    Pfaltz, M; Hedinger, C E; Mühlethaler, J P

    1983-01-01

    We report a case of medullary carcinoma of the thyroid which on light microscopy showed not only the well known arrangement of cells in sheets and nests but also unequivocal follicular structures. These follicular structures are present both in the primary tumor and in lymph node metastases. Immunohistochemical investigations revealed that the cells lining the follicles produce thyroglobulin, whereas the remaining tumor tissue is positive for calcitonin and carcinoembrionic antigen. This case represents a medullary carcinoma of the thyroid with an atypical pattern consisting of both thyroglobulin and calcitonin producing cells.

  15. Follicular lymphoma presenting as mumps, with persistent cervical lymphadenopathy.

    PubMed

    Cole, A S; Trotter, M I; O'Connell, J

    2007-05-01

    We report a case of follicular lymphoma in a healthy individual, which presented as saliva- and serum-proven mumps. The patient presented with a sore throat and parotid and submandibular lymphadenopathy. Fine needle aspiration, undertaken three weeks following presentation, revealed no malignant cells. An excision biopsy of a level two node was performed due to persistent lymphadenopathy, five weeks following presentation. As far as we are aware, this is the first reported case of follicular lymphoma presenting as mumps. This case highlights the importance of follow up in patients in whom lymphadenopathy is persistent despite the proven diagnosis of mumps.

  16. 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.

  17. Uterine Epithelial Cell Regulation of DC-SIGN Expression Inhibits Transmitted/Founder HIV-1 Trans Infection by Immature Dendritic Cells

    PubMed Central

    Ochiel, Daniel O.; Ochsenbauer, Christina; Kappes, John C.; Ghosh, Mimi; Fahey, John V.; Wira, Charles R.

    2010-01-01

    Background Sexual transmission accounts for the majority of HIV-1 infections. In over 75% of cases, infection is initiated by a single variant (transmitted/founder virus). However, the determinants of virus selection during transmission are unknown. Host cell-cell interactions in the mucosa may be critical in regulating susceptibility to infection. We hypothesized in this study that specific immune modulators secreted by uterine epithelial cells modulate susceptibility of dendritic cells (DC) to infection with HIV-1. Methodology/Principal Findings Here we report that uterine epithelial cell secretions (i.e. conditioned medium, CM) decreased DC-SIGN expression on immature dendritic cells via a transforming growth factor beta (TGF-β) mechanism. Further, CM inhibited dendritic cell-mediated trans infection of HIV-1 expressing envelope proteins of prototypic reference. Similarly, CM inhibited trans infection of HIV-1 constructs expressing envelopes of transmitted/founder viruses, variants that are selected during sexual transmission. In contrast, whereas recombinant TGF- β1 inhibited trans infection of prototypic reference HIV-1 by dendritic cells, TGF-β1 had a minimal effect on trans infection of transmitted/founder variants irrespective of the reporter system used to measure trans infection. Conclusions/Significance Our results provide the first direct evidence for uterine epithelial cell regulation of dendritic cell transmission of infection with reference and transmitted/founder HIV-1 variants. These findings have immediate implications for designing strategies to prevent sexual transmission of HIV-1. PMID:21179465

  18. The Isothermal Dendritic Growth Experiment

    NASA Technical Reports Server (NTRS)

    Glicksman, M. E.; Koss, M. B.; Malarik, D. C.

    1998-01-01

    The growth of dendrites is one of the commonly observed forms of solidification encountered when metals and alloys freeze under low thermal gradients, as occurs in most casting and welding processes. In engineering alloys, the details of the dendritic morphology directly relates to important material responses and properties. Of more generic interest, dendritic growth is also an archetypical problem in morphogenesis, where a complex pattern evolves from simple starting conditions. Thus, the physical understanding and mathematical description of how dendritic patterns emerge during the growth process are of interest to both scientists and engineers. The Isothermal Dendritic Growth Experiment (IDGE) is a basic science experiment designed to measure, for a fundamental test of theory, the kinetics and morphology of dendritic growth without complications induced by gravity-driven convection. The IDGE, a collaboration between Rensselaer Polytechnic Institute, in Troy NY, and NASA's Lewis Research Center (LeRC) was developed over a ten year period from a ground-based research program into a space flight experiment. Important to the success of this flight experiment was provision of in situ near-real-time teleoperations during the spaceflight experiment.

  19. An Innovative Scalp-Dyeing Technique with Gentian Violet Solution During Follicular Unit Extraction for White-Haired Follicular Units

    PubMed Central

    Moon, Min Seon

    2017-01-01

    There exist some restrictions and difficulties in performing follicular unit extraction (FUE) in white-haired patients, for several reasons. In this paper, we introduce a novel technique for visualizing white hair during the punching procedure and graft preparation in FUE for white-haired patients. In white-haired older male patients, we dyed the surrounding scalp skin purple with a gentian violet solution-stained toothpick. Our method has several advantages: surgeons can easily focus on the center of the follicular unit and rapidly perform punching, they can recognize the condition of the harvested follicular units during FUE, and the hair transplant team can secure a clear view for trimming and loading into the implanter. We suggest that scalp dyeing in difficult FUE procedures, especially in patients with white hair, may be a simple method that provides a good visualization for donor site harvesting and for microdissection. PMID:28352608

  20. Reconsideration of macrophage and dendritic cell classification.

    PubMed

    Kadowaki, Takeshi; Shimada, Misato; Inagawa, Hiroyuki; Kohchi, Chie; Hirashima, Mitsuomi; Soma, Gen-Ichiro

    2012-06-01

    It is well known that the activation of innate immune cells, especially antigen-presenting cells such as macrophages and dendritic cells, can ameliorate or exacerbate various diseases, including cancer. Currently, the macrophages and dendritic cells are categorized into several groups by their cell surface and intracellular molecules. However, the detailed classification of the differences between macrophages and dendritic cells has still not been established. Here, we summarized and reviewed the previous studies on the classification of macrophages and dendritic cells. In addition, the previous classification of monocytes, macrophages and dendritic cells is discussed based on our findings of macrophage activation, which has both conventional and plasmacytoid dendritic cell phenotype.

  1. Follicular atrophoderma with multiple basal cell carcinomas (Bazex).

    PubMed

    Gould, D J; Barker, D J

    1978-10-01

    Five patients from a single family are reported who have an inherited condition of which the main features are follicular atrophoderma, abnormalities of scalp hair and multiple basal cell carcinomas. Thes abnormalities are consistent with the syndrome described by Bazex et al. (1964). The pattern of inheritance of this condition is discussed.

  2. SPARC preserves follicular epithelium integrity in insect ovaries.

    PubMed

    Irles, Paula; Ramos, Saray; Piulachs, Maria-Dolors

    2017-02-15

    The importance of juvenile hormone regulating insect oogenesis suggests looking for genes whose expression is regulated by this hormone. SPARC is a calcium-binding glycoprotein that forms part of the extracellular membranes, which in vertebrates participates in bones mineralization or regulating cell proliferation in some cancer types. This large number of functions described for SPARC in different species might be related to the significant differences in its structure observed when comparing different species-groups. Indeed, these structural differences allow characterizing the different clades. In the cockroach Blattella germanica, a SPARC homolog emerged from ovarian transcriptomes that were constructed to find genes responding to juvenile hormone. In insects, SPARC functions have been studied in oogenesis and in embryo development of Drosophila melanogaster. In the present work, using RNAi approaches, novel functions for SPARC in the B. germanica panoistic ovaries are described. We found that depletion of SPARC does not allow to the follicular cells to complete mitosis, resulting in giant follicular cells nuclei and in a great alteration of the ovarian follicle cytoskeleton. The SPARC contribution to B. germanica oogenesis occurs stabilizing the follicular cell program and helping to maintain the nuclear divisions. Moreover, SPARC is necessary to maintain the cytoskeleton of the follicular cells. Any modification of these key processes disables females for oviposition.

  3. Multiple perianal infundibular follicular cysts in a dog.

    PubMed

    Park, Jin-Kyu; Hong, Il-Hwa; Ki, Mi-Ran; Hong, Kyung-Sook; Ji, Ae-Ri; Do, Sun-Hee; Jeong, Kyu-Shik

    2010-06-01

    This case report describes a 7-year-old male cocker spaniel dog with multiple perianal infundibular follicular cysts. Clinically the dog had moderate anal sacculitis, peri-anal pruritus causing it to 'scoot' and lick the area. On examination of the perianal area, there were over 100 firm, well circumscribed papules, ranged from 0.2 to 0.5 cm in diameter with a central pore, and were found in the perianal region. Alopecia was present in the perianal region. The skin tissue in the perianal region resected surgically was submitted for histological examination. Microscopically, the tissue revealed multiple dilated cysts filled with keratins and the papules corresponded to infundibular follicular cysts. The affected dog showed moderate anal sacculitis. Anal sacculitis commonly causes repeated scooting or licking the area around the anus. Therefore, the multiple follicular cysts in the present case appear to be primarily a sequela to chronic external trauma to the perianal area, probably in response to anal sacculitis. To the best of the authors' knowledge, the present report is the first documented case of multiple perianal infundibular follicular cysts in a dog.

  4. Comparative Proteomic Analysis of Yak Follicular Fluid during Estrus.

    PubMed

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

    2016-09-01

    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.

  5. Follicular variant papillary thyroid carcinoma with a twist

    PubMed Central

    Nwaeze, Obinna; Obidike, Stephen; Mullen, Dorinda; Aftab, Fuad

    2015-01-01

    Background We report an adnexal lesion, which turned out to be a metastasis to the scalp from a left sided follicular variant papillary thyroid cancer. The patient has had history of right multi-nodular goiter 10 years prior to presentation. Case presentation A 75-year old lady presented with a cutaneous lesion about 1 year post left total thyroidectomy for FVPTC. She underwent surgical excision of the lesion and histology revealed it to be metastases from a thyroid carcinoma. Discussion Cutaneous metastases from thyroid carcinomas are relatively uncommon in clinical practice. A worldwide literature review reveals that follicular carcinoma has a greater preponderance than papillary carcinoma for cutaneous metastasis and that the majority of skin metastases from either papillary or follicular thyroid cancer are localized to the head and neck, with the scalp as the commonest site. Conclusion Skin metastasis from papillary and follicular thyroid carcinoma is an uncommon occurrence and these lesions should be differentiated from primary skin tumors. They are very important to recognize as early recognition can lead to accurate and prompt diagnosis leading to timely treatment. The scalp has been found to be the commonest site of cutaneous metastasis that may appear benign. PMID:25651538

  6. Cutaneous metastasis from follicular carcinoma of the thyroid gland.

    PubMed

    Caron, P; Moreau-Cabarrot, A; Gorguet, B; Bazex, J

    1993-01-01

    A 65-year-old man with a history of malignant melanoma presented a reddish nodule on the left temporal region of the scalp. Histologic features and immunoperoxidase staining on the skin biopsy specimen confirmed the diagnosis of metastatic thyroid follicular carcinoma. The patient presented recurrences of metastatic skin nodules, lung and bone metastases, and died after a 3-year follow-up.

  7. 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.

  8. 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. © 2015 S. Karger AG, Basel.

  9. Follicular lymphoma: first-line treatment without chemotherapy for follicular lymphoma.

    PubMed

    Reagan, Patrick M; Friedberg, Jonathan W

    2015-07-01

    Opinion statement: The optimal initial treatment of follicular lymphoma (FL) is not known, and initial management of patients varies considerably between providers and institutions. The assertion that patients with low tumor burden can be observed for a period of time is being challenged owing to the safety and tolerability of novel therapeutics and the movement of the field away from traditional chemotherapy agents. Single agent rituximab has become increasingly popular as initial management of patients with low tumor burden disease, and there is evidence that prolonged treatment with rituximab can improve progression-free survival (PFS) when compared to induction with rituximab or observation. Radioimmunotherapy (RIT) has similarly shown efficacy in low tumor burden disease. Novel agents such as lenalidomide, idelalisib, and ibrutinib are being studied in the first-line setting. Importantly, none of these strategies have demonstrated an improved overall survival in a randomized study versus observation. It is the opinion of the authors that endpoints such as PFS alone, while important, should not drive changes in management with limited resources. Composite endpoints including quality of life are more informative on the true impact of treatments on patients with follicular lymphoma. Providers should encourage all patients to be treated in the context of an appropriate clinical trial when possible. If a patient is not a clinical trial candidate, we typically treat patients with advanced stage and high tumor burden with chemoimmunotherapy. The decision to give maintenance rituximab is individualized to the patient, as there is no overall survival benefit. In patients with early stage disease, we favor consideration of radiation therapy if the patient is a candidate. Our initial recommendation to patients with advanced stage, low tumor burden disease, is close observation or "watch and wait." We have observed that most patients become comfortable over time with an

  10. [Follicular cell (papillary and follicular) thyroid carcinoma, genetic inheritance, and molecular diagnostic markers].

    PubMed

    Kazubskaia, T P; Kozlova, V M; Kondrat'eva, T T; Pavlovskaia, A I; Marakhonov, A V; Baranova, A V; Ivanova, N I; Stepanova, A A; Poliakov, A V; Belev, N F; Brzhezovskiĭ, V Zh

    2014-01-01

    To determine the genetic forms of follicular cell thyroid carcinoma (FCTC) (papillary and follicular thyroid carcinoma (PTC and FTC)), to identify criteria to individually predict the development of the same disease for relatives, and to assess the role of molecular markers in the diagnosis, prognosis, and treatment of this disease. One hundred and ninety adult patients aged 20 to 84 years with histologically verified PTC and FTC and 20 children (12 patients with PTC and 8 with benign thyroid tumors) aged 2 to 16 years were examined. To assess the role of the BRAF gene as a molecular marker for thyroid carcinoma, DNA was isolated from the thyroid tumor tissue of 29 patients, which had been obtained by fine-needle aspiration biopsy (FNAB) and scraping and swabbing the cytological specimen previously showing an area containing tumor cells. A BRAF c.1799T>A (p.V600E) mutation in the FNAB specimens was tested by allele-specific ligation, followed by PCR amplification. The examinees' families were found to have a segregation of benign thyroid tumor and nontumor diseases (13.6%). Neoplasias of different sites were observed in 15% of the patients' relatives. Multiple primary tumors were detected in 6.1% of the patients and in 25% of the examined children (3/12). PTC was ascertained to accumulate as two clinical forms in the families. One form belongs to familial PTC (FPTC) in which two or three generations of relatives in the family are afflicted by only PTC and have a more severe phenotype of the disease. The other includes an association of FPTC with papillary kidney cancer. Furthermore, FPTC and PTC may be a component of multitumor syndromes, such as multiple endocrine neoplasia type 1, Cowden syndrome, and familial adenomatous polyposis. The familial hereditary forms of FCTC were generally revealed in 4.2% of the patients. BRAF v600E mutations were found in only 3 patients with Stages II and III PTC and were not in all the 12 children with PTC. The found clinical

  11. Homophilic Dscam interactions control complex dendrite morphogenesis

    PubMed Central

    Hughes, Michael E.; Bortnick, Rachel; Tsubouchi, Asako; Bäumer, Philipp; Kondo, Masahiro; Uemura, Tadashi; Schmucker, Dietmar

    2007-01-01

    Summary The morphogenesis of complex dendritic fields requires highly specific patterning and dendrite-dendrite recognition mechanisms. Alternative splicing of the Drosophila cell surface receptor Dscam results in up to 38,016 different receptor isoforms and in vitro binding studies suggested that sequence variability in immunoglobulin-like ecto-domains determines the specificity of strictly homophilic interactions. We report that diverse Dscam receptors play an important role in controlling cell-intrinsic aspects of dendrite guidance. We examined the function of Dscam during morphogenesis of dendrite arborization neurons (“da” neurons) and found that loss of Dscam in single neurons causes abnormal dendritic fasciculation and a strong increase in self-crossing of dendritic branches of da neurons. Restriction of dendritic fields of neighboring class III neurons appeared intact in Dscam deficient neurons suggesting that dendritic self-avoidance but not hetero-neuronal tiling may depend on Dscam function. Over-expression of the same Dscam isoforms in two da neurons with normally overlapping dendritic fields forced a spatial segregation of the two dendritic fields. Taken together, our results suggest that dendritic branches of all four classes of da neurons use isoform-specific homophilic interactions of Dscam to ensure minimal overlap of dendrites. The large pool of Dscam’s extracellular recognition domains may allow the same ‘core’ repulsion mechanism to be used in every da neuron without interfering with hetero-neuronal interactions. PMID:17481395

  12. [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.

  13. Coding and decoding with dendrites.

    PubMed

    Papoutsi, Athanasia; Kastellakis, George; Psarrou, Maria; Anastasakis, Stelios; Poirazi, Panayiota

    2014-02-01

    Since the discovery of complex, voltage dependent mechanisms in the dendrites of multiple neuron types, great effort has been devoted in search of a direct link between dendritic properties and specific neuronal functions. Over the last few years, new experimental techniques have allowed the visualization and probing of dendritic anatomy, plasticity and integrative schemes with unprecedented detail. This vast amount of information has caused a paradigm shift in the study of memory, one of the most important pursuits in Neuroscience, and calls for the development of novel theories and models that will unify the available data according to some basic principles. Traditional models of memory considered neural cells as the fundamental processing units in the brain. Recent studies however are proposing new theories in which memory is not only formed by modifying the synaptic connections between neurons, but also by modifications of intrinsic and anatomical dendritic properties as well as fine tuning of the wiring diagram. In this review paper we present previous studies along with recent findings from our group that support a key role of dendrites in information processing, including the encoding and decoding of new memories, both at the single cell and the network level. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. Follicular lymphoma grade 3B is a distinct neoplasm according to cytogenetic and immunohistochemical profiles

    PubMed Central

    Horn, Heike; Schmelter, Christopher; Leich, Ellen; Salaverria, Itziar; Katzenberger, Tiemo; Ott, M. Michaela; Kalla, Jörg; Romero, Monica; Siebert, Reiner; Rosenwald, Andreas; Ott, German

    2011-01-01

    Background According to the current World Health Organization Classification of Lymphoid Tumours, follicular lymphoma is subclassified into three grades according to the number of centroblasts. Follicular lymphoma grade 3 can be further divided into types A and B. Almost all available genetic data on grade 3B follicular lymphomas have been generated from tumors with an additional diffuse large B-cell lymphoma component. The purely follicular type of follicular lymphoma grade 3B is a rare neoplasm. Design and Methods We performed a detailed immunohistochemical (CD10, IRF4/MUM1, BCL2, Ig light chains) and genetic (translocations of BCL2, BCL6, MYC, IRF4) characterization of the largest series of purely follicular cases of grade 3B follicular lymphoma available to date, comprising 23 tumor samples. We also included 25 typical grade 1 or 2 follicular lymphomas, 9 follicular lymphomas with large centrocytes and/or high proliferation indices (FL/LCC), 12 cases of follicular lymphoma grade 3A, 16 cases of diffuse large B-cell lymphoma/follicular lymphoma grade 3B and 15 follicular lymphomas in which a straightforward distinction between grades 3A and 3B was not possible. Results Translocations affecting BCL2 and BCL6 genes are rare in grade 3B follicular lymphomas (2/23, 9% and 4/23, 17%) when compared with grade 1 or 2 follicular lymphomas (22/25, 88%, P<0.001 and 0/25, P<0.05), FL/LCC (7/9, 78%, P<0.001 and 2/9, 22%), grade 3A follicular lymphomas (7/12, 58%, P<0.01 and 2/12, 17%), unclassified grade 3 follicular lymphomas (6/15, 40% and 2/15, 13%) and diffuse large B-cell lymphoma/follicular lymphoma grade 3B (2/16, 13% and 8/16, 50%, P<0.05). MYC translocations were detected occasionally in FL/LCC, follicular lymphoma grade 3B, and diffuse large B-cell lymphoma/follicular lymphoma grade 3B (13%–22%), but not in grade 1, 2 or 3A follicular lymphomas (P<0.05 when compared with follicular lymphoma grade 3B). Both follicular lymphoma grade 3B and diffuse large B

  15. 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.

  16. Dissecting the gray zone between follicular lymphoma and marginal zone lymphoma using morphological and genetic features.

    PubMed

    Krijgsman, Oscar; Gonzalez, Patricia; Ponz, Olga Balagué; Roemer, Margaretha G M; Slot, Stefanie; Broeks, Annegien; Braaf, Linde; Kerkhoven, Ron M; Bot, Freek; van Groningen, Krijn; Beijert, Max; Ylstra, Bauke; de Jong, Daphne

    2013-12-01

    Nodal marginal zone lymphoma is a poorly defined entity in the World Health Organization classification, based largely on criteria of exclusion and the diagnosis often remains subjective. Follicular lymphoma lacking t(14;18) has similar characteristics which results in a major potential diagnostic overlap which this study aims to dissect. Four subgroups of lymphoma samples (n=56) were analyzed with high-resolution array comparative genome hybridization: nodal marginal zone lymphoma, t(14;18)-negative follicular lymphoma, localized t(14:18)-positive follicular lymphoma and disseminated t(14;18)-positive follicular lymphoma. Gains on chromosomes 7, 8 and 12 were observed in all subgroups. The mean number of aberrations was higher in disseminated t(14;18)-positive follicular lymphoma than in localized t(14:18)-positive follicular lymphoma (P<0.01) and the majority of alterations in localized t(14:18)-positive follicular lymphoma were also found in disseminated t(14;18)-positive follicular lymphoma. Nodal marginal zone lymphoma was marked by 3q gains with amplifications of four genes. A different overall pattern of aberrations was seen in t(14;18)-negative follicular lymphoma compared to t(14;18)-positive follicular lymphoma. t(14;18)-negative follicular lymphoma is characterized by specific (focal) gains on chromosome 3, as observed in nodal marginal zone lymphoma. Our results support the notion that localized t(14:18)-positive follicular lymphoma represents an early phase of disseminated t(14;18)-positive follicular lymphoma. t(14;18)-negative follicular lymphoma bears aberrations that are more like those in nodal marginal zone lymphoma, suggesting a relation between these groups.

  17. 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.

  18. 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

  19. Induction of protective immunity against Eimeria tenella, Eimeria maxima, and Eimeria acervulina infections using dendritic cell-derived exosomes.

    PubMed

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

    2012-05-01

    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 T(h)1 cytokines, T(h)2 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 T(h)1 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 T(h)2 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.

  20. An Inverse Approach for Elucidating Dendritic Function

    PubMed Central

    Torben-Nielsen, Benjamin; Stiefel, Klaus M.

    2010-01-01

    We outline an inverse approach for investigating dendritic function–structure relationships by optimizing dendritic trees for a priori chosen computational functions. The inverse approach can be applied in two different ways. First, we can use it as a “hypothesis generator” in which we optimize dendrites for a function of general interest. The optimization yields an artificial dendrite that is subsequently compared to real neurons. This comparison potentially allows us to propose hypotheses about the function of real neurons. In this way, we investigated dendrites that optimally perform input-order detection. Second, we can use it as a “function confirmation” by optimizing dendrites for functions hypothesized to be performed by classes of neurons. If the optimized, artificial, dendrites resemble the dendrites of real neurons the artificial dendrites corroborate the hypothesized function of the real neuron. Moreover, properties of the artificial dendrites can lead to predictions about yet unmeasured properties. In this way, we investigated wide-field motion integration performed by the VS cells of the fly visual system. In outlining the inverse approach and two applications, we also elaborate on the nature of dendritic function. We furthermore discuss the role of optimality in assigning functions to dendrites and point out interesting future directions. PMID:21258425

  1. An inverse approach for elucidating dendritic function.

    PubMed

    Torben-Nielsen, Benjamin; Stiefel, Klaus M

    2010-01-01

    We outline an inverse approach for investigating dendritic function-structure relationships by optimizing dendritic trees for a priori chosen computational functions. The inverse approach can be applied in two different ways. First, we can use it as a "hypothesis generator" in which we optimize dendrites for a function of general interest. The optimization yields an artificial dendrite that is subsequently compared to real neurons. This comparison potentially allows us to propose hypotheses about the function of real neurons. In this way, we investigated dendrites that optimally perform input-order detection. Second, we can use it as a "function confirmation" by optimizing dendrites for functions hypothesized to be performed by classes of neurons. If the optimized, artificial, dendrites resemble the dendrites of real neurons the artificial dendrites corroborate the hypothesized function of the real neuron. Moreover, properties of the artificial dendrites can lead to predictions about yet unmeasured properties. In this way, we investigated wide-field motion integration performed by the VS cells of the fly visual system. In outlining the inverse approach and two applications, we also elaborate on the nature of dendritic function. We furthermore discuss the role of optimality in assigning functions to dendrites and point out interesting future directions.

  2. 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. Dendrite irritator control for the EDSE in the Microgravity Development Lab (MDL).

  3. Follicular density and ratios in scarring and nonscarring alopecia.

    PubMed

    Horenstein, Marcelo G; Bacheler, Christian J

    2013-12-01

    Follicular counts from transverse sectioning of scalp biopsies have not been statistically scrutinized across disease entities in a standardized fashion. We applied uniform histological criteria and strict statistical measures to compare nonscarring and scarring alopecia. We studied 700 consecutive cases including 355 nonscarring alopecia [136 telogen effluvium, 115 alopecia areata (AA), 95 androgenetic alopecia, and 9 trichotillosis] and 345 scarring alopecia [238 central centrifugal cicatricial alopecia, 29 traction alopecia, 26 lichen planopilaris, 21 end-stage alopecia, 20 lupus erythematosus, 11 folliculitis decalvans]. We counted follicular units, anagen, catagen/telogen, and vellus-like follicles at the central follicular unit level. We calculated follicular density per square centimeter, anagen percentage, telogen percentage, anagen to telogen ratio, and terminal to vellus ratio (TVR). The following achieved statistical significance (P < 0.05): follicular density was 249.4 ± 4.6 in nonscarring alopecia versus 120.1 ± 3.8 in scarring alopecia, follicular density of telogen effluvium was 273.5 ± 7.0 (36.5 ± 12.5 above nonscarring alopecia mean), TVR of androgenetic alopecia was 1.6 ± 0.1 (3.6 ± 0.5 below nonscarring alopecia mean), TVR of AA was 3.2 ± 0.4 (1.5 ± 0.6 below nonscarring alopecia mean), anagen percentage of AA was 26.8 ± 1.8 (26.3 ± 3.0 below nonscarring alopecia mean), anagen to telogen ratio of AA was 1.6 ± 0.4 (3.9 ± 0.7 below nonscarring alopecia mean), and telogen percentage of AA was 59.0 ± 2.3 (31.0 ± 3.5 above nonscarring alopecia mean). There exists a great overlap of densities and ratios across the various disorders due to the limited nature of the punch biopsy sample, variations in scalp anatomy, disease biology and duration, patient gender, and age, etc. Our data provide a bell curve distribution that helps analyze hair counts in the clinicopathologic context.

  4. Immunohistochemical detection of dendritic cell markers in cattle.

    PubMed

    Romero-Palomo, F; Risalde, M A; Molina, V; Sánchez-Cordón, P J; Pedrera, M; Gómez-Villamandos, J C

    2013-11-01

    Dendritic cells (DCs) are "professional" antigen-presenting cells with a critical role in the regulation of innate and adaptive immune responses and thus have been considered of great interest in the study of a variety of infectious diseases. The objective of this investigation was to characterize the in vivo distribution of DCs in bovine tissues by using potential DC markers to establish a basis for the study of DCs in diseased tissues. Markers evaluated included MHCII, CD208, CD1b, CD205, CNA.42, and S100 protein, the latter 2 being expressed by follicular dendritic cells whose origin and role are different from the rest of hematopoietic DCs. Paraffin wax-embedded tissues from 6 healthy Friesian calves were subjected to the avidin-biotin-peroxidase method, and the most appropriate fixatives, dilutions, and antigen retrieval pretreatments were studied for each of the primary antibodies. The most significant results included the localization of CD208-positive cells not only in the T zone of lymphoid organs but also within lymphoid follicles; CD1b-positive cells were mainly found in thymus and interfollicular areas of some lymph nodes; cells stained with anti-CD205 antibody were scarce, and their location was mainly in nonlymphoid tissues; and CNA.42- and S100 protein-positive cells localized in primary lymphoid follicles and light zones of germinal centers, although showing differences in the staining pattern. Furthermore, MHCII was established as one of the most sensitive markers for any DC of hematopoietic origin. These results increase our understanding of DC immunolabeling and will help in future DC studies of both healthy and diseased tissues.

  5. 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

  6. 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

  7. New drugs for follicular lymphoma in older adults.

    PubMed

    Schmitt, Anna; Soubeyran, Pierre

    2014-06-01

    Follicular lymphoma is essentially a disease of the elderly, and the aging of the population in developed countries will increase patient numbers in coming years. Significant achievements have been made for treatment, but better understanding of the disease and major progress in biology now facilitate the development of many new drugs, which may have improved toxicity profiles making them appropriate for treatment of older adults. However, the increasing number of treatment possibilities, can also increase the toxicity risks, and unexpected toxicities specific to older adults may be encountered. Consequently, specific studies of older patients should be considered, using appropriate evaluation tools such as comprehensive geriatric assessment. This review will described the development of these new drugs, in the context of the treatment of older-adults with follicular lymphoma.

  8. Follicular bronchiolitis: A rare cause of persistent atelectasis in children.

    PubMed

    Dias, Ângela; Jardim, Joana; Nunes, Teresa; Souto Moura, Conceição; Vaz, Luísa

    2013-01-01

    Although atelectasis is common in children, its persistence or refractoriness to treatment should lead prompt evaluation to identify causal mechanism. We describe the case of a child presenting in first year of life with persistent left upper lobe atelectasis, recurrent wheezing and respiratory infections refractory to medical therapy, submitted to partial lobectomy when he was 3 years old age. Histopathological examination revealed follicular bronchiolitis. Systemic underlying diseases were excluded. Clinical improvement was initially achieved using inhaled corticosteroids, but oral therapy was needed due to clinical relapse, with favorable response. Follicular bronchiolitis, a rare pulmonary primary lymphoid lesion, consists of numerous reactive lymphoid follicles in a peribonchiolar distribution. Its precise cause is unknown, particularly in children, in which few cases have been reported. Treatment usually includes steroids and prognosis is generally good.

  9. Intrinsic and extrinsic mechanisms of dendritic morphogenesis.

    PubMed

    Dong, Xintong; Shen, Kang; Bülow, Hannes E

    2015-01-01

    The complex, branched morphology of dendrites is a cardinal feature of neurons and has been used as a criterion for cell type identification since the beginning of neurobiology. Regulated dendritic outgrowth and branching during development form the basis of receptive fields for neurons and are essential for the wiring of the nervous system. The cellular and molecular mechanisms of dendritic morphogenesis have been an intensely studied area. In this review, we summarize the major experimental systems that have contributed to our understandings of dendritic development as well as the intrinsic and extrinsic mechanisms that instruct the neurons to form cell type-specific dendritic arbors.

  10. Regulation of dendrite morphogenesis by extrinsic cues.

    PubMed

    Valnegri, Pamela; Puram, Sidharth V; Bonni, Azad

    2015-07-01

    Dendrites play a central role in the integration and flow of information in the nervous system. The morphogenesis and maturation of dendrites is hence an essential step in the establishment of neuronal connectivity. Recent studies have uncovered crucial functions for extrinsic cues in the development of dendrites. We review the contribution of secreted polypeptide growth factors, contact-mediated proteins, and neuronal activity in distinct phases of dendrite development. We also highlight how extrinsic cues influence local and global intracellular mechanisms of dendrite morphogenesis. Finally, we discuss how these studies have advanced our understanding of neuronal connectivity and have shed light on the pathogenesis of neurodevelopmental disorders.

  11. Bone marrow-derived dendritic cells.

    PubMed

    Roney, Kelly

    2013-01-01

    While much is understood about dendritic cells and their role in the immune system, the study of these cells is critical to gain a more complete understanding of their function. Dendritic cell isolation from mouse body tissues can be difficult and the number of cells isolated small. This protocol describes the growth of large number of dendritic cells from the culture of mouse bone marrow cells. The dendritic cells grown in culture facilitate experiments that may require large number of dendritic cells without great expense or use of large number of mice.

  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. Pattern selection in dendritic solidification

    NASA Technical Reports Server (NTRS)

    Ben-Jacob, E.; Goldenfeld, N.; Kotliar, B. G.; Langer, J. S.

    1984-01-01

    It is shown that the dynamically selected velocity and tip radius of dendrites in the boundary-layer model of solidification have the special values which permit the existence of steady-state needle-crystal solutions. This result, in conjunction with considerations of stability, provides new insight concerning the validity of the marginal-stability hypothesis.

  14. Mandibular metastasis of follicular thyroid carcinoma. Case report.

    PubMed

    Ostrosky, Alejandro; Mareso, Eduardo Arístides; Klurfan, Federico Juan; Gonzalez, Maximiliano Jorge

    2003-01-01

    Thyroid carcinoma mandibular metastasis are not very frequent and the cases described in literature are few. Due to its bloodstream dissemination, most of them are a consequence of the follicular variant of thyroid carcinomas. A case is presented and a review of the clinicopathologic characteristics of the lesion is made, so the oral and maxilofacial surgeon can recognize it, make a correct differential diagnosis with other mandibular radioluciencies and in consequence, carry out an adequate treatment.

  15. Spontaneous thyroid follicular adenoma in a laboratory mouse (Mus musculus).

    PubMed

    Onyekaba, C O

    1986-10-01

    Spontaneous thyroid micro-follicular adenoma was found in an 18-month-old nursing Swiss albino mouse. The lesion was first noted as a tiny bulge at the base of the neck. The tumor was solid, and within two months, had grown such an enormous size that movement, feeding and suckling of the litter were greatly hampered. The litter of seven mice later died due to improper nursing while their mother remained generally unaffected by the mass.

  16. The History of the Follicular Variant of Papillary Thyroid Carcinoma.

    PubMed

    Tallini, Giovanni; Tuttle, R Michael; Ghossein, Ronald A

    2017-01-01

    This review provides historical context to recent developments in the classification of the follicular variant of papillary thyroid carcinoma (FVPTC). The evolution of the diagnostic criteria for papillary thyroid carcinoma is described, clarifying the role of molecular analysis and the impact on patient management. A PubMed search using the terms "follicular variant" and "papillary thyroid carcinoma" covering the years 1960 to 2016 was performed. Additional references were identified through review of the citations of the retrieved articles. The encapsulated/well-demarcated, noninvasive form of FVPTC that occurs annually in 45,000 patients worldwide was thought for 30 years to be a carcinoma. Many studies have shown almost no recurrence in these noninvasive tumors, even in patients treated by surgery alone without radioactive iodine therapy. The categorization of the tumor as outright cancer has led to aggressive forms of treatment, with their side effects, financial costs, and the psychological and social impacts of a cancer diagnosis. Recently, the encapsulated/well-demarcated, noninvasive FVPTC was renamed as noninvasive follicular thyroid neoplasm with papillary-like nuclear features. The new terminology lacks the carcinoma label, enabling clinicians to avoid aggressive therapy. By understanding the history of FVPTC, future classification of tumors will be greatly improved.

  17. Nutritional and lactational effects on follicular development in the pig.

    PubMed

    Quesnel, H

    2009-01-01

    In sows, follicular development is inhibited during lactation, and weaning the piglets allows recruitment and selection of follicles that will undergo preovulatory maturation and ovulate. Lactation inhibits GnRH secretion, and in turn LH secretion, through neuroendocrine stimuli induced by suckling. Pituitary response to GnRH and the sensitivity of the hypothalamo-pituitary unit to oestradiol positive feedback are also reduced. The impact of lactation on the reproductive axis is further complicated by the physiological and metabolic adaptations that are developed for milk production and that depend on nutrient intake, nutrient needs and body reserves. A strongly catabolic state during lactation amplifies the inhibition of LH secretion, thereby inducing a delay of oestrus and ovulation after weaning. Nevertheless, post-weaning ovulation is less delayed nowadays than in the 1970's or 80's. Nutritional deficiency has also deleterious effects on embryo survival, which are likely related to alterations in follicular growth and maturation. The physiological mechanisms by which information on the metabolic changes is transmitted to the hypothalamus-pituitary-ovary axis are not fully understood in the sow. Glucose, insulin and leptin are the most likely signals informing the hypothalamus of the metabolic state, yet their roles have not been definitely established. At the ovarian level, folliculogenesis is likely to be altered by the reduction in insulin and IGF-I concentrations induced by nutritional deficiency. More knowledge is needed at the intrafollicular level to better understand nutritional effects on follicular development, and also on occyte quality and embryo development.

  18. Selenium supplementation modulates apoptotic processes in thyroid follicular cells.

    PubMed

    Nettore, Immacolata C; De Nisco, Emma; Desiderio, Silvio; Passaro, Carmela; Maione, Luigi; Negri, Mariarosaria; Albano, Luigi; Pivonello, Rosario; Pivonello, Claudia; Portella, Giuseppe; Ungaro, Paola; Colao, Annamaria; Macchia, Paolo E

    2017-03-02

    Selenium (Se) is an essential micronutrient modulating several physiopathological processes in the human body. The aim of the study is to characterize the molecular effects determined by Se-supplementation in thyroid follicular cells, using as model the well-differentiated rat thyroid follicular cell line FRTL5. Experiments have been performed to evaluate the effects of Se on cell growth, mortality and proliferation and on modulation of pro- and antiapoptotic pathways. The results indicate that Se-supplementation improves FRTL5 growth rate. Furthermore, Se reduces the proportion of cell death and modulates both proapoptotic (p53 and Bim) and antiapoptotic (NF-kB and Bcl2) mRNA levels. In addition, incubation with high doses of Na-Se might prevent the ER-stress apoptosis induced by tunicamycin, as assessed by membrane integrity maintenance, reduction in caspase 3/7 activities, and reduction in Casp-3 and PARP cleavage. Taken together, these results provide molecular evidences indicating the role of Se supplementation on cell death and apoptosis modulation in thyroid follicular cells. These observations may be useful to understand the effects of this micronutrient on the physiopathology of the thyroid gland. © 2017 The Authors BioFactors published by Wiley Periodicals, Inc. on behalf of International Union of Biochemistry and Molecular Biology, 2017.

  19. Molecular and cellular mechanisms of dendritic morphogenesis

    PubMed Central

    Gao, Fen-Biao

    2008-01-01

    Summary Dendrites exhibit unique cell-type specific branching patterns and targeting specificity that are critically important for neuronal function and connectivity. Recent evidence indicates that highly complex transcriptional regulatory networks dictate various aspects of dendritic outgrowth, branching, and routing. In addition to other intrinsic molecular pathways such as membrane protein trafficking, interactions between neighboring dendritic branches also contribute to the final specification of dendritic morphology. Nonredundant coverage by dendrites of same type of neurons, known as tiling, requires the actions of the Tricornered/Furry (Sax-1/Sax-2) signaling pathway. However, the dendrites of a neuron do not cross over each other, a process called self-avoidance that is mediated by Down’s syndrome cell adhesion molecule (Dscam). Those exciting findings have enhanced significantly our understanding of dendritic morphogenesis and revealed the magnitude of complexity in the underlying molecular regulatory networks. PMID:17933513

  20. CD10 down expression in follicular lymphoma correlates with gastrointestinal lesion involving the stomach and large intestine.

    PubMed

    Ohnishi, Nobuhiko; Takata, Katsuyoshi; Miyata-Takata, Tomoko; Sato, Yasuharu; Tari, Akira; Gion, Yuka; Noujima-Harada, Mai; Taniguchi, Kohei; Tabata, Tetsuya; Nagakita, Keina; Omote, Shizuma; Takahata, Hiroyuki; Iwamuro, Masaya; Okada, Hiroyuki; Maeda, Yoshinobu; Yanai, Hiroyuki; Yoshino, Tadashi

    2016-11-01

    Follicular lymphoma (FL) shows co-expression of B-cell lymphoma 2 (BCL2) and CD10, whereas downexpression of CD10 is occasionally experienced in gastrointestinal (GI) FL with unknown significance. Gastrointestinal FL is a rare variant of FL, and its similarity with mucosa-associated lymphoid tissue lymphoma was reported. We investigated the clinicopathological and genetic features of CD10 downexpressed (CD10(down) ) GI-FL. The diagnosis of CD10(down) FL was carried out with a combination of pathological and molecular analyses. The incidence of CD10(down) GI-FL was shown in 35/172 (20.3%) cases, which was more frequent than nodal FL (3.5%, P < 0.001). The difference was additionally significant between GI-FL and nodal FL when the analysis was confined to primary GI-FL (55.2% vs 3.5%, P < 0.001). Compared to CD10(+) GI-FL, CD10(down) GI-FL significantly involved the stomach or large intestine (P = 0.015), and additionally showed the downexpression of BCL6 (P < 0.001). The follicular dendritic cell meshwork often showed a duodenal pattern in the CD10(down) group (P = 0.12). Furthermore, a lymphoepithelial lesion was observed in 5/12 (40%) gastric FL cases, which indicated caution in the differentiation of mucosa-associated lymphoid tissue lymphoma. Molecular analyses were undertaken in seven cases of CD10(down) GI-FL, and an identical clone was found between CD10(down) follicles and CD10(+) BCL2(+) neoplastic follicles. In the diagnosis of cases with CD10(down) BCL2(+) follicles, careful examination with molecular studies should be carried out. © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  1. Evidence that dendritic mitochondria negatively regulate dendritic branching in pyramidal neurons in the neocortex.

    PubMed

    Kimura, Toshiya; Murakami, Fujio

    2014-05-14

    The precise branching patterns of dendritic arbors have a profound impact on information processing in individual neurons and the brain. These patterns are established by positive and negative regulation of the dendritic branching. Although the mechanisms for positive regulation have been extensively investigated, little is known about those for negative regulation. Here, we present evidence that mitochondria located in developing dendrites are involved in the negative regulation of dendritic branching. We visualized mitochondria in pyramidal neurons of the mouse neocortex during dendritic morphogenesis using in utero electroporation of a mitochondria-targeted fluorescent construct. We altered the mitochondrial distribution in vivo by overexpressing Mfn1, a mitochondrial shaping protein, or the Miro-binding domain of TRAK2 (TRAK2-MBD), a truncated form of a motor-adaptor protein. We found that dendritic mitochondria were preferentially targeted to the proximal portion of dendrites only during dendritic morphogenesis. Overexpression of Mfn1 or TRAK2-MBD depleted mitochondria from the dendrites, an effect that was accompanied by increased branching of the proximal portion of the dendrites. This dendritic abnormality cannot be accounted for by changes in the distribution of membrane trafficking organelles since the overexpression of Mfn1 did not alter the distributions of the endoplasmic reticulum, Golgi, or endosomes. Additionally, neither did these constructs impair neuronal viability or mitochondrial function. Therefore, our results suggest that dendritic mitochondria play a critical role in the establishment of the precise branching pattern of dendritic arbors by negatively affecting dendritic branching.

  2. Pembrolizumab and Combination Chemotherapy in Treating Patients With Previously Untreated Diffuse Large B-cell Lymphoma or Grade 3b Follicular Lymphoma

    ClinicalTrials.gov

    2017-07-20

    Composite Lymphoma; Grade 3b Follicular Lymphoma; Stage I Diffuse Large B-Cell Lymphoma; Stage I Follicular Lymphoma; Stage II Diffuse Large B-Cell Lymphoma; Stage II Follicular Lymphoma; Stage III Diffuse Large B-Cell Lymphoma; Stage III Follicular Lymphoma; Stage IV Diffuse Large B-Cell Lymphoma; Stage IV Follicular Lymphoma

  3. IMMUNOHISTOCHEMICAL ANALYSIS FOR CD21, CD35, CALDESMON AND S100 PROTEIN ON DENDRITIC CELLS TYPES IN ORAL LYMPHOMAS

    PubMed Central

    Mesquita, Ricardo Alves; de Araújo, Vera Cavalcanti; Paes, Roberto Antônio Pinto; Nunes, Fábio Daumas; de Sousa, Suzana Cantanhede Orsini Machado

    2009-01-01

    Objective: Follicular dendritic cells (FDCs) and interdigitating dendritic cells (IDCs) are dendritic cells found in lymphoid follicles, reactive follicles and in lymphomas. The goal of this study was to evaluate the presence and distribution of FDCs and IDCs in oral lymphomas. Material and Methods: Immunohistochemistry reactions were applied to 50 oral lymphomas using the antibodies anti-CD21, anti-CD35 and anti-caldesmon to FDCs, and anti-S100 protein to IDCs. Caldesmon+/FDCs and S100+/IDCs were quantified in Imagelab® software. Results: FDCs revealed by CD21 and CD35 were positively stained in two cases of diffuse large B-cell lymphoma, one MALT lymphoma, and in one case of mantle cell lymphoma. FDCs were immunopositive to caldesmon in all cases, as well as IDCs to S100 protein. Burkitt lymphoma presented a lower amount of caldesmon+/FDCs and S100+/IDCs than diffuse large B-cell lymphoma and plasmablastic lymphoma of the oral mucosa type. Conclusions: The microenvironment determined by neoplastic lymphoid cells in oral lymphomas is responsible by the development and expression of dendritic cells types. PMID:19466261

  4. Follicular morphological characteristics may be associated with invasion in follicular thyroid neoplasms with papillary-like nuclear features.

    PubMed

    Can, Nuray; Celik, Mehmet; Sezer, Yavuz Atakan; Ozyilmaz, Filiz; Ayturk, Semra; Tastekin, Ebru; Sut, Necdet; Gurkan, Hakan; Ustun, Funda; Bulbul, Buket Yilmaz; Guldiken, Sibel; Puyan, Fulya Oz

    2017-08-20

    The newly proposed nomenclature and diagnostic criteria for encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC), the noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), could improve the consistency and accuracy of diagnosing this entity. Diagnosis of NIFTP requires evaluation of the complete tumor border or capsule. The presence of tumor invasion in follicular thyroid neoplasms with papillary-like nuclear features has been recently discussed by many authors. In this study, we examined the predictive value and association of follicular morphological characteristics with the tumor invasion. In addition, we analyzed the association between tumor encapsulation and molecular profile in EFVPTC/NIFTP cases. A total of 106 cases of FVPTC were included in the study. The tumors were grouped based on the presence of tumor capsule and characteristics of tumor border, as 1) completely encapsulated tumors without invasion, 2) encapsulated tumors with invasion, 3) infiltrative tumors without a capsule. Clinicopathological features, histomorphological features [nuclear criteria, minor diagnostic features, follicles oriented perpendicular to tumor border/capsule (FOPBC)] and molecular alterations in BRAF, NRAS, and KRAS genes were evaluated. FOPBC were significantly more frequently seen in encapsulated tumors with invasion (p = 0.008). The nuclear features were not associated with the presence of encapsulation and characteristics of tumor border. BRAF mutation was more frequent in infiltrative tumors, while NRAS mutation was more frequent in encapsulated tumors, but the results were not statistically significant (p = 0.917). In conclusion, FOPBC histomorphological feature may be associated with tumor invasion in EFVPTC/NIFTP. Additionally, BRAF/KRAS/NRAS mutation analysis may prevent inadequate treatment in these patients.

  5. Characterization of ovarian follicular dynamics in dromedary camels (Camelus dromedarius).

    PubMed

    Manjunatha, B M; Pratap, N; Al-Bulushi, Samir; Hago, B E

    2012-09-15

    Ovarian follicular dynamics was monitored by transrectal ultrasonography, for a period of 60 to 90 days, and its correlation with plasma estradiol-17β (E2) and progesterone (P4) were studied in seventeen, multiparous, non-lactating, 12 to 20-year-old dromedary camels. The average number of follicles recruited (12.77 ± 0.93) in each wave between animals varied (P < 0.001). The number of follicles recruited during different follicular waves was highly repeatable (0.95) within individual animals. The growth and mature phase periods of the dominant follicle (DF) were 6.10 ± 0.15 and 10.20 ± 0.47 days, respectively with a linear growth rate of 1.17 ± 0.02 mm/day between Day 0 and 10 of the follicular wave. There was an inverse relationship between the diameter of the largest DF and number of follicles (r = -0.95, P < 0.001). The DF development did not regularly alternate between the ovaries and the incidence of codominance was 45%. The mean maximum diameter of DF during its mature phase was 27.30 ± 0.78 mm and oversized follicle was 38.43 ± 1.41 mm. In 73.3% waves, the DF continued its growth for a period of 10.64 ± 1.53 days even after losing its dominance and developed into oversized follicle. The duration of the regression phase of DF and oversized follicle were 24.71 ± 3.79 and 18.50 ± 2.23 days. The mean duration of a complete follicular wave was 47.11 ± 2.94 days with an interwave interval (IWI) of 16.36 ± 0.37 days. The IWI within an individual was repeatable (0.88) and between the animals was variable (P < 0.001). Plasma E2 concentration profiles showed a wave like pattern. The peak plasma E2 concentrations were attained approximately 12 days after beginning of the growth phase, when the largest DF grew to a diameter of 18.7 mm. Plasma concentration of P4 was below 1.0 ng/mL in 85% of waves and above 1.0 ng/mL in 15% of the waves for a period of 3 to 6 days in the absence of spontaneous ovulation. It is concluded that ovarian follicular development

  6. Characterization of intratumoral follicular helper T cells in follicular lymphoma: role in the survival of malignant B cells

    PubMed Central

    Amé-Thomas, Patricia; Le Priol, Jérôme; Yssel, Hans; Caron, Gersende; Pangault, Céline; Jean, Rachel; Martin, Nadine; Marafioti, Teresa; Gaulard, Philippe; Lamy, Thierry; Fest, Thierry; Semana, Gilbert; Tarte, Karin

    2012-01-01

    Accumulating evidences indicate that the cellular and molecular microenvironment of follicular lymphoma (FL) plays a key role in both lymphomagenesis and patient outcome. Malignant FL B cells are found admixed to specific stromal and immune cell subsets, in particular CD4pos T cells displaying phenotypic features of follicular helper T cells (TFH). The goal of our study was to functionally characterize intratumoral CD4pos T cells. We showed that CXCR5hiICOShiCD4pos T cells sorted from FL biopsies comprise at least two separate cell populations with distinct genetic and functional features: i) CD25pos follicular regulatory T cells (TFR), and ii) CD25neg TFH displaying a FL-B cell supportive activity without regulatory functions. Furthermore, despite their strong similarities with tonsil-derived TFH, purified FL-derived TFH displayed a specific gene expression profile including an overexpression of several genes potentially involved directly or indirectly in lymphomagenesis, in particular TNF, LTA, IL4, or CD40LG. Interestingly, we further demonstrated that these two last signals efficiently rescued malignant B cells from spontaneous and Rituximab-induced apoptosis. Altogether, our study demonstrates that tumor-infiltrating CD4pos T cells are more heterogeneous than previously presumed, and underlines for the first time the crucial role of TFH in the complex set of cellular interactions within FL microenvironment. PMID:22015774

  7. Dendritic cell analysis in primary immunodeficiency

    PubMed Central

    Bigley, Venetia; Barge, Dawn; Collin, Matthew

    2016-01-01

    Purpose of review Dendritic cells are specialized antigen-presenting cells which link innate and adaptive immunity, through recognition and presentation of antigen to T cells. Although the importance of dendritic cells has been demonstrated in many animal models, their contribution to human immunity remains relatively unexplored in vivo. Given their central role in infection, autoimmunity, and malignancy, dendritic cell deficiency or dysfunction would be expected to have clinical consequences. Recent findings Human dendritic cell deficiency disorders, related to GATA binding protein 2 (GATA2) and interferon regulatory factor 8 (IRF8) mutations, have highlighted the importance of dendritic cells and monocytes in primary immunodeficiency diseases and begun to shed light on their nonredundant roles in host defense and immune regulation in vivo. The contribution of dendritic cell and monocyte dysfunction to the pathogenesis of primary immunodeficiency disease phenotypes is becoming increasingly apparent. However, dendritic cell analysis is not yet a routine part of primary immunodeficiency disease workup. Summary Widespread uptake of dendritic cell/monocyte screening in clinical practice will facilitate the discovery of novel dendritic cell and monocyte disorders as well as advancing our understanding of human dendritic cell biology in health and disease. PMID:27755182

  8. Black-hair follicular dysplasia in a New Zealand Huntaway Dog.

    PubMed

    Munday, J S; French, A F; McKerchar, G R K

    2009-06-01

    A 6-year-old intact male New Zealand Huntaway dog had slowly progressive alopecia that was first observed at 12 weeks of age. Patchy alopecia was confined to the black-haired areas of the body, and was most evident on the head and dorsum of the body; tan-haired areas of skin appeared normal. Histological examination of black-haired skin revealed distended melanocytes and large aggregates of melanin within, and surrounding, the hair follicles and the epidermis. Macrophages distended with melanin were also visible within the peri-follicular and superficial dermis, and follicular lumina were often plugged by keratin that contained aggregates of melanin. The follicles were dysplastic and few hair shafts were visible emerging from follicular infundibula within the sections. The clinical and histological findings were consistent with black-hair follicular dysplasia (BHFD). This is the first report of BHFD in a dog in New Zealand, and is the first report in a Huntaway. The most significant effect of BHFD is a predisposition to follicular plugging and secondary bacterial skin infections. Due to the hereditary nature of the follicular dysplasias, breeding from affected dogs should be discouraged. Histological examination of the skin is required to differentiate between the different follicular dysplasias as well as differentiating between follicular dysplasia and follicular atrophy due to endocrinopathy.

  9. Differential diagnosis of follicular cancer and follicular adenoma using an expert system based on a set of qualitative signs of cell atypia.

    PubMed

    Kirillov, Vladimir; Emeliyanova, Olga

    2011-10-01

    To determine the efficiency of the developed expert system based on a set of qualitative signs of cell atypia and their weighting coefficients in the differential diagnosis of follicular cancer and follicular adenoma of the thyroid gland. Sixty cytologic preparations of patients with histologic diagnosis of a follicular cancer and follicular adenoma were investigated. Weighting coefficients for each sign of atypia for both forms of pathology have been calculated with the help of the deduced equation. This allowed creating an expert system by which the function of transforming qualitative signs of cell atypia to a quantitative form was realized. "Strength reserve" according to the diagnostic index value, coincidence of the verified diagnosis with the histologic conclusion, and its invariability for all 12 iterations testified to the reliability of an expert system. Preliminary trials showed the efficiency of an expert system for differentiating the nature of a thyroid follicular tumor to be 97.5%. The developed expert system allows high efficiency in making a differential diagnosis of thyroid follicular cancer and follicular adenoma.

  10. 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.

  11. Lipid dynamics at dendritic spines

    PubMed Central

    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. PMID:25152717

  12. 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.

  13. Dendritic Spine Pathology in Schizophrenia

    PubMed Central

    Glausier, Jill R.; Lewis, David A.

    2012-01-01

    Schizophrenia is a neurodevelopmental disorder whose clinical features include impairments in perception, cognition and motivation. These impairments reflect alterations in neuronal circuitry within and across multiple brain regions that are due, at least in part, to deficits in dendritic spines, the site of most excitatory synaptic connections. Dendritic spine alterations have been identified in multiple brain regions in schizophrenia, but are best characterized in layer 3 of the neocortex, where pyramidal cell spine density is lower. These spine deficits appear to arise during development, and thus are likely the result of disturbances in the molecular mechanisms that underlie spine formation, pruning, and/or maintenance. Each of these mechanisms may provide insight into novel therapeutic targets for preventing or repairing the alterations in neural circuitry that mediate the debilitating symptoms of schizophrenia. PMID:22546337

  14. Dendritic cells in Graves' disease.

    PubMed

    Purnamasari, Dyah; Soewondo, Pradana; Djauzi, Samsuridjal

    2015-01-01

    Dendritic cells are major antigen-presenting cells (APC) that stimulate naive T cells, which induce adaptive immune responses. Graves' disease (GD) is an autoimmune disease characterized by the presence of autoantibodies against Thyroid Stimulating Hormone Receptor (TSHR). The autoantibodies bind with TSHR and stimulate thyroid hormone production. Dendritic cells are still the major APC in GD immune response although thyrocytes in GD can also express Major Histocompatibility Class (MHC) class II molecule. Studies about DC in GD have been conducted by isolating intra-thyroid DC or DC in peripheral circulation. Results of DC studies in GD are still controversial. Changes in number and profile of DC are found, which indicate altered immune response activity and defects of regulator T cell (Treg) in GD.

  15. Dendritic cell-based immunotherapy for the treatment of hematological malignancies.

    PubMed

    Büchler, Tomas; Michalek, Jaroslav; Kovarova, Lucie; Musilova, Romana; Hajek, Roman

    2003-04-01

    Dendritic cells (DCs) are professional antigen-presenting cells and are frequently used in current immunotherapy protocols. The administration of DCs loaded with tumor-associated proteins or peptides results in the induction of immune responses against different types of malignant cells. Methods for large-scale generation of DCs in a sufficient quality and quantity have permitted their use in clinical experiments. DC-based vaccines have already shown promise in follicular non-Hodgkin's lymphoma, and to some extent, in other hematological malignancies. Several strategies have been developed to boost their potency as a new and relatively non-toxic treatment modality. Our review focuses on clinical trials using DCs in the treatment of hematologic malignancies and on recent studies of the immunophenotype, development, and maturation of DCs may have an important impact on designing DC-based antitumor vaccines.

  16. Cell-intrinsic drivers of dendrite morphogenesis.

    PubMed

    Puram, Sidharth V; Bonni, Azad

    2013-12-01

    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.

  17. 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.

  18. Active Dendrites Enhance Neuronal Dynamic Range

    PubMed Central

    Gollo, Leonardo L.; Kinouchi, Osame; Copelli, Mauro

    2009-01-01

    Since the first experimental evidences of active conductances in dendrites, most neurons have been shown to exhibit dendritic excitability through the expression of a variety of voltage-gated ion channels. However, despite experimental and theoretical efforts undertaken in the past decades, the role of this excitability for some kind of dendritic computation has remained elusive. Here we show that, owing to very general properties of excitable media, the average output of a model of an active dendritic tree is a highly non-linear function of its afferent rate, attaining extremely large dynamic ranges (above 50 dB). Moreover, the model yields double-sigmoid response functions as experimentally observed in retinal ganglion cells. We claim that enhancement of dynamic range is the primary functional role of active dendritic conductances. We predict that neurons with larger dendritic trees should have larger dynamic range and that blocking of active conductances should lead to a decrease in dynamic range. PMID:19521531

  19. 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.

  20. Dendritic Ion Channel Trafficking and Plasticity

    PubMed Central

    Shah, Mala M.; Hammond, Rebecca S.; Hoffman, Dax

    2010-01-01

    Dendrites, the elaborate processes emerging from neuronal cell bodies, receive most excitatory synaptic inputs. Voltage- and calcium-gated ion channels are abundant in dendrites and modify the shape, propagation and integration of synaptic signals. These ion channels also determine intrinsic dendritic excitability and are therfore important for the induction and manifestation of Hebbian and non-Hebbian plasticity. Revealingly, dendritic channels have distinct expression patterns and biophysical properties from those present in other neuronal compartments. Recent evidence suggests that dendritic ion channels are locally regulated, perhaps contributing to different forms of plasticity. In this review, we will discuss the implications of regulating dendritic ion channel function and trafficking in the context of plasticity and information processing. PMID:20363038

  1. 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.

  2. 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).

  3. Do alterations in follicular fluid proteases contribute to human infertility?

    PubMed

    Cookingham, Lisa Marii; Van Voorhis, Bradley J; Ascoli, Mario

    2015-05-01

    Cathepsin L and ADAMTS-1 are known to play critical roles in follicular rupture, ovulation, and fertility in mice. Similar studies in humans are limited; however, both are known to increase during the periovulatory period. No studies have examined either protease in the follicular fluid of women with unexplained infertility or infertility related to advanced maternal age (AMA). We sought to determine if alterations in cathepsin L and/or ADAMTS-1 existed in these infertile populations. Patients undergoing in vitro fertilization (IVF) for unexplained infertility or AMA-related infertility were prospectively recruited for the study; patients with tubal or male factor infertility were recruited as controls. Follicular fluid was collected to determine gene expression (via quantitative polymerase chain reaction), enzyme concentrations (via enzyme-linked immunosorbent assays), and enzymatic activities (via fluorogenic enzyme cleavage assay or Western blot analysis) of cathepsin L and ADAMTS-1. The analysis included a total of 42 patients (14 per group). We found no statistically significant difference in gene expression, enzyme concentration, or enzymatic activity of cathepsin L or ADAMTS-1 in unexplained infertility or AMA-related infertility as compared to controls. We also found no statistically significant difference in expression or concentration with advancing age. Cathepsin L and ADAMTS-1 are not altered in women with unexplained infertility or AMA-related infertility undergoing IVF, and they do not decline with advancing age. It is possible that differences exist in natural cycles, contributing to infertility; however, our findings do not support a role for protease alterations as a common cause of infertility.

  4. 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

  5. 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.

  6. Single-Hair Follicular Unit Transplant for Stable Vitiligo

    PubMed Central

    Kumaresan, Muthuvel

    2011-01-01

    Follicular unit transplant (FUT) is one of the surgical procedures which has been recently used to repigment a stable vitiligo patch. Single-hair FUT was done for a 30-year-old male with stable vitiligo patch on the upper lip. Repigmentation was noted in 4 weeks and complete pigmentation seen at 8 weeks. No recurrence was noted at the end of 6-month follow-up with excellent colour match. This case is presented to highlight the effectiveness of FUT in focal vitligo patch with leukotrichia. PMID:21572681

  7. Congenital systematized basaloid follicular hamartoma with microphthalmia and hemimegalencephaly.

    PubMed

    Boccaletti, Valeria; Accorsi, Patrizia; Pinelli, Lorenzo; Ungari, Marco; Giordano, Lucio; Neri, Iria; De Panfilis, Giuseppe

    2011-01-01

    The lines of Blaschko are a cutaneous pattern of mosaicism present in a variety of skin disorders. Developmental abnormalities affecting other tissues derived from the embryonic ectoderm and mesoderm are sometimes associated. Here, we describe a 5-year-old boy with basaloid follicular hamartoma affecting the left side of the body in linear multiple bands, following Blaschko lines. Lesions were predominantly hypopigmented macules and streaks, but among these, we could observe brownish atrophic patches and brown papules. Furthermore, ipsilateral hemimegaloencephaly and microphthalmia were present. These findings suggest a neurocutaneous condition recently described by Happle and Tinschert. Its nosologic classification will be discussed. © 2010 Wiley Periodicals, Inc.

  8. Follicular and oocyte development in gilts of different age.

    PubMed

    Brüssow, K P; Rátky, J; Torner, H; Egerszegi, I; Schneider, F; Solti, L; Tuchscherer, A

    2002-01-01

    The aim of the present study was to estimate follicular and oocyte development of the same gilts in three phases of their reproductive life--prepuberal gilt (6 months old), cycling gilt (9.5 months old) and primiparous sow. Follicular development was induced by injections of 1000 IU PMSG followed by 500 IU hCG 72 h later. Cumulus-oocyte-complexes (COCs) were recovered from preovulatory follicles of the left ovary, and follicular fluid (FF) from the right ovary always 34 h after hCG by endoscopy. Altogether, 19 gilts were used in the prepuberal (P) and cycling (C) trials and 12 of them in the primiparous trial (S). Altogether 168, 190 and 82 follicles were aspirated from the left ovary and 106, 125 and 42 COCs recovered (recovery rate 60.5 +/- 26.9, 62.7 +/- 20.9 and 52.9 +/- 21.8%). The average number of follicles was higher in C compared to P (19.7 +/- 6.8 vs. 15.7 +/- 6.8, p = 0.06) and to S (14.2 +/- 4.0, p < 0.05), respectively. More uniform expanded COCs were aspirated from prepuberal and cycling gilts as compared to sows (89.7 and 78.4% vs. 46.3%, p < 0.05). Furthermore, the meiotic configuration in oocytes differed (p < 0.05) between these groups (55.5 and 61.7% vs. 0% Telo 1/Meta 2). Concentrations of progesterone in FF decreased (p < 0.05) from 590.0 +/- 333.6 (P) to 249.1 +/- 72.6 (C) and 161.4 +/- 75.2 ng/ml (S). FF concentrations of oestradiol-17 beta were different between gilts and sows (9.3 +/- 2.9, 21.9 +/- 10.6 and 94.0 +/- 15.9 pg/ml, p < 0.05). The progesterone/oestradiol ratio was 72.1, 15.2 and 4.7. Results indicate a different follicular and oocyte development during the investigated lifetime periods. Cycling gilts should preferably be used in IVF and breeding programs. The lower reproductive potential of primiparous sows is taken into consideration at breeding. Prediction of lifetime performance based on individual ovarian reaction of prepuberal gilts is unsuitable.

  9. Intravital imaging of dendritic spine plasticity

    PubMed Central

    Sau Wan Lai, Cora

    2014-01-01

    Abstract Dendritic spines are the postsynaptic part of most excitatory synapses in the mammalian brain. Recent works have suggested that the structural and functional plasticity of dendritic spines have been associated with information coding and memories. Advances in imaging and labeling techniques enable the study of dendritic spine dynamics in vivo. This perspective focuses on intravital imaging studies of dendritic spine plasticity in the neocortex. I will introduce imaging tools for studying spine dynamics and will further review current findings on spine structure and function under various physiological and pathological conditions. PMID:28243511

  10. 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.

  11. 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.

  12. Orientations of dendritic growth during solidification

    NASA Astrophysics Data System (ADS)

    Lee, Dong Nyung

    2017-02-01

    Dendrites are crystalline forms which grow far from the limit of stability of the plane front and adopt an orientation which is as close as possible to the heat flux direction. Dendritic growth orientations for cubic metals, bct Sn, and hcp Zn, can be controlled by thermal conductivity, Young's modulus, and surface energy. The control factors have been elaborated. Since the dendrite is a single crystal, its properties such as thermal conductivity that influences the heat flux direction, the minimum Young's modulus direction that influences the strain energy minimization, and the minimum surface energy plane that influences the crystal/liquid interface energy minimization have been proved to control the dendritic growth direction. The dendritic growth directions of cubic metals are determined by the minimum Young's modulus direction and/or axis direction of symmetry of the minimum crystal surface energy plane. The dendritic growth direction of bct Sn is determined by its maximum thermal conductivity direction and the minimum surface energy plane normal direction. The primary dendritic growth direction of hcp Zn is determined by its maximum thermal conductivity direction and the minimum surface energy plane normal direction and the secondary dendrite arm direction of hcp Zn is normal to the primary dendritic growth direction.

  13. Orientations of dendritic growth during solidification

    NASA Astrophysics Data System (ADS)

    Lee, Dong Nyung

    2017-03-01

    Dendrites are crystalline forms which grow far from the limit of stability of the plane front and adopt an orientation which is as close as possible to the heat flux direction. Dendritic growth orientations for cubic metals, bct Sn, and hcp Zn, can be controlled by thermal conductivity, Young's modulus, and surface energy. The control factors have been elaborated. Since the dendrite is a single crystal, its properties such as thermal conductivity that influences the heat flux direction, the minimum Young's modulus direction that influences the strain energy minimization, and the minimum surface energy plane that influences the crystal/liquid interface energy minimization have been proved to control the dendritic growth direction. The dendritic growth directions of cubic metals are determined by the minimum Young's modulus direction and/or axis direction of symmetry of the minimum crystal surface energy plane. The dendritic growth direction of bct Sn is determined by its maximum thermal conductivity direction and the minimum surface energy plane normal direction. The primary dendritic growth direction of hcp Zn is determined by its maximum thermal conductivity direction and the minimum surface energy plane normal direction and the secondary dendrite arm direction of hcp Zn is normal to the primary dendritic growth direction.

  14. 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.

  15. The renal microenvironment modifies dendritic cell phenotype.

    PubMed

    Chessa, Federica; Mathow, Daniel; Wang, Shijun; Hielscher, Thomas; Atzberger, Ann; Porubsky, Stefan; Gretz, Norbert; Burgdorf, Sven; Gröne, Hermann-Josef; Popovic, Zoran V

    2016-01-01

    Renal dendritic cells are a major component of the renal mononuclear phagocytic system. In the renal interstitium, these cells are exposed to an osmotic gradient, mainly sodium, whose concentration progressively increases towards inner medulla. Renal allograft rejection affects predominantly the cortex, suggesting a protective role of the renal medullary micromilieu. Whether osmolar variations can modulate the function of renal dendritic cells is currently undefined. Considering the central role of dendritic cells in promoting allorejection, we tested whether the biophysical micromilieu, particularly the interstitial osmotic gradient, influences their alloreactivity. There was a progressive depletion of leukocytes towards the medulla of homeostatic kidney. Only macrophages opposed this tendency. Flow cytometry of homeostatic and post-transplant medullary dendritic cells revealed a switch towards a macrophage-like phenotype. Similarly, bone marrow-derived dendritic cells developed ex vivo in sodium chloride-enriched medium acquired a M2-like signature. Microarray analysis of allotransplant dendritic cells posed a medullary downregulation of genes mainly involved in alloantigen recognition. Gene expression profiles of both medullary dendritic cells and bone marrow-derived dendritic cells matured in hyperosmolar medium had an overlap with the macrophage M2 signature. Thus, the medullary environment inhibits an alloimmune response by modulating the phenotype and function of dendritic cells.

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

    USDA-ARS?s Scientific Manuscript database

    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...

  17. Follicular steroid hormones as markers of oocyte quality and oocyte development potential.

    PubMed

    Carpintero, Nayara López; Suárez, Onica Armijo; Mangas, Carmen Cuadrado; Varea, Carolina González; Rioja, Rubén Gómez

    2014-07-01

    Various components of follicular fluid are suggested as biochemical predictors of oocyte quality. Previous studies of follicular steroid hormone levels have shown disparate results when related with fertilization outcomes. The objective of the study was to relate the levels of steroid hormones of each individual follicle with oocyte maturation, fertilization results, embryo quality, and pregnancy rates. Prospective cohort study in a university hospital. In 31 patients, who underwent intracytoplasmic sperm injection, it was performed an ultrasound guided aspiration of follicular fluid of the first two mature follicles from each ovary. Follicular levels of estradiol, progesterone, testosterone, and dehydroepiandrosterone sulfate were measured by chemiluminescent immunoassay. Generalized estimating equation model. In follicular fluids with mature oocyte presence, in normal as well as in failed fertilization, there was a positive correlation between follicular testosterone and progesterone (r = 0.794, P = 0.0001 and r = 0.829, P = 0.0001). Progesterone levels were higher in cases of normal fertilization compared to failed fertilization (P = 0.003). B quality embryos came from oocytes immersed in follicular fluids with higher estradiol values and higher estradiol/progesterone and estradiol/testosterone ratios than those of C quality (P = 0.01; P = 0.0009; P = 0.001). Estradiol levels were higher in patients who achieved pregnancy (P = 0.02). The analysis of follicular hormone composition could be considered as an additional tool in oocyte selection.

  18. Follicular steroid hormones as markers of oocyte quality and oocyte development potential

    PubMed Central

    Carpintero, Nayara López; Suárez, Onica Armijo; Mangas, Carmen Cuadrado; Varea, Carolina González; Rioja, Rubén Gómez

    2014-01-01

    CONTEXT: Various components of follicular fluid are suggested as biochemical predictors of oocyte quality. Previous studies of follicular steroid hormone levels have shown disparate results when related with fertilization outcomes. AIM: The objective of the study was to relate the levels of steroid hormones of each individual follicle with oocyte maturation, fertilization results, embryo quality, and pregnancy rates. SETTINGS AND DESIGN: Prospective cohort study in a university hospital. METHODS: In 31 patients, who underwent intracytoplasmic sperm injection, it was performed an ultrasound guided aspiration of follicular fluid of the first two mature follicles from each ovary. Follicular levels of estradiol, progesterone, testosterone, and dehydroepiandrosterone sulfate were measured by chemiluminescent immunoassay. STATISTICAL ANALYSIS: Generalized estimating equation model. RESULTS: In follicular fluids with mature oocyte presence, in normal as well as in failed fertilization, there was a positive correlation between follicular testosterone and progesterone (r = 0.794, P = 0.0001 and r = 0.829, P = 0.0001). Progesterone levels were higher in cases of normal fertilization compared to failed fertilization (P = 0.003). B quality embryos came from oocytes immersed in follicular fluids with higher estradiol values and higher estradiol/progesterone and estradiol/testosterone ratios than those of C quality (P = 0.01; P = 0.0009; P = 0.001). Estradiol levels were higher in patients who achieved pregnancy (P = 0.02). CONCLUSION: The analysis of follicular hormone composition could be considered as an additional tool in oocyte selection. PMID:25395744

  19. The effect of follicular wave on fertility characteristics in beef cattle

    USDA-ARS?s Scientific Manuscript database

    Adequate fertility of beef cattle in the US is a major economic concern. The use of luminogenic substrates to ascertain steroid metabolism in beef females bred to the dominant follicle of the first follicular wave versus the dominant follicle of the second follicular wave in this study further provi...

  20. Recombinant rabies virus expressing IL-21 enhances immunogenicity through activation of T follicular helper cells and germinal centre B cells.

    PubMed

    Zhang, Yajing; Zhou, Ming; Wang, Zhao; Yang, Jie; Li, Mingming; Wang, Kunlun; Cui, Min; Chen, Huanchun; Fu, Zhen F; Zhao, Ling

    2016-12-01

    Previous studies have demonstrated that the lack of interleukin-21 (IL-21) signalling could affect specific antibody induction after rabies vaccination. Here, to further investigate the over-expression of IL-21 on the immunogenicity of rabies virus (RABV), a recombinant RABV expressing murine IL-21, designated LBNSE-IL21, was constructed and evaluated in a mouse model. It was found that in mice immunized with LBNSE-IL21, there was a substantial increase in the number of T follicular helper cells and germinal centre B cells but no enhancement of dendritic cell activation. Furthermore, significantly higher rabies virus-neutralizing antibody (VNA) titres were produced in mice immunized with LBNSE-IL21 than in mice immunized with the parent virus LBNSE in the first six weeks, resulting in higher protection. Together, these results suggest that LBNSE-IL21 can induce a rapid and robust VNA titre, and it has the potential to be developed as a promising rabies vaccine.

  1. 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

  2. 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

  3. Follicular thyroid carcinoma presenting as bilateral cheek masses.

    PubMed

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

    2013-03-01

    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.

  4. [Early transformation from follicular lymphoma to Burkitt lymphoma].

    PubMed

    Takahashi, Takeshi; Hara, Takeshi; Yoshikawa, Takeshi; Shimomura, Yoriko; Tsurumi, Hisashi; Yamada, Tetsuya; Tomita, Eiichi; Moriwaki, Hisataka

    2005-09-01

    We report a rare case of follicular lymphoma which rapidly showed transformation to the Burkitt type of lymphoma after a treatment consisting of chemotherapy and irradiation. A 51-year-old male visited our hospital in August 2000 because of bilateral neck lymphadenopathy. He was diagnosed as having follicular lymphoma (grade 2) (clinical stage IIIA) with complex karyotypic abnormalities involving t(14 ; 18)(q32 ; q21) and CD20 expression. Initially he was followed as an outpatient without chemotherapy. Six months later, he was admitted because of hydronephrosis due to an intrapelvic tumor. He underwent chemotherapy with 4 courses of CHOP regimen following irradiation therapy and a partial response was obtained. Four months after initiation of the treatment, his disease recurred with numb chin syndrome. Bone marrow aspiration revealed bone marrow involvement by lymphoma cells which had a Burkitt-like appearance. A cytogenetic study using bone marrow blood showed complex abnormalities involving t(8 ; 22)(q24 ; q11) in addition to t(14 ; 18). In spite of salvage chemotherapy, the patient died in September 2001.

  5. Pros and cons of rituximab maintenance in follicular lymphoma.

    PubMed

    Zhang, Lu; Ghielmini, Michele; Cheson, Bruce D; Ujjani, Chaitra

    2017-07-01

    Follicular lymphoma (FL) is the most prevalent indolent non-Hodgkin lymphoma. Most patients present with advanced disease and are incurable with current therapy. The approval of rituximab has revolutionized the treatment of follicular lymphoma when administered in the induction setting for high-tumor burden disease, but the use of rituximab as a maintenance therapy (MR) continues to be a point of controversy. In this article, we review the main data and arguments in favor and against MR in FL. In summary, most studies have demonstrated a significant benefit in progression-free or event-free survival in this notoriously recurrent disease; however, long-term outcomes could not consistently demonstrate to be improved with this intervention. In a meta-analysis of randomized trials overall survival (OS) showed a tendency to improvement when given to patients in relapse, but no single study reached a significant OS advantage. The risk of high-grade transformation does not seem to be reduced in prospective trials. On the other hand, MR clearly increases toxicity without an improvement in quality of life. Finally, MR is expensive, and it is not proven that the delayed relapse time can compensate for these costs. In conclusion, despite the proven increase in progression-free survival, MR can't be recommended as a standard for the treatment of FL. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Pax8 controls thyroid follicular polarity through cadherin-16

    PubMed Central

    Koumarianou, Petrina; Goméz-López, Gonzalo

    2017-01-01

    ABSTRACT Organization of epithelial cells during follicular lumen formation is crucial for thyroid morphogenesis and function of the thyroid gland; however, the molecular mechanisms underlying this are poorly understood. To investigate this process, we established three-dimensional (3D) epithelial culture model systems using Fischer rat thyroid (FRT) cells or murine primary thyrocytes that developed polarized spherical structures with a central lumen, mimicking thyroid follicles. Using microarray-based differential expression analysis of FRT cells grown under 2D or 3D conditions, followed by RNA-mediated interference (RNAi) and morphogenetic analysis, we identified a key role for the thyroid transcription factor Pax8 and its target cadherin-16 (Cdh16) in the generation of polarized follicle-like structures. Silencing Pax8 expression inhibited the acquisition of apical–basal membrane polarity and impaired lumen formation. Both laminin and β1-integrin (Itgb1) expression was reduced, and cell cytoskeleton polarized distribution was altered. Silencing Cdh16 expression also led to the formation of defective structures characterized by very low laminin expression at the follicle–matrix interface, downregulation of Itgb1, and unpolarized distribution of cell cytoskeleton. Our results demonstrate that Pax8 controls apical–basal follicular polarization and follicle formation through Cdh16. PMID:27780871

  7. Transcriptomes of bovine ovarian follicular and luteal cells.

    PubMed

    Romereim, Sarah M; Summers, Adam F; Pohlmeier, William E; Zhang, Pan; Hou, Xiaoying; Talbott, Heather A; Cushman, Robert A; Wood, Jennifer R; Davis, John S; Cupp, Andrea S

    2017-02-01

    Affymetrix Bovine GeneChip® Gene 1.0 ST Array RNA expression analysis was performed on four somatic ovarian cell types: the granulosa cells (GCs) and theca cells (TCs) of the dominant follicle and the large luteal cells (LLCs) and small luteal cells (SLCs) of the corpus luteum. The normalized linear microarray data was deposited to the NCBI GEO repository (GSE83524). Subsequent ANOVA determined genes that were enriched (≥2 fold more) or decreased (≤-2 fold less) in one cell type compared to all three other cell types, and these analyzed and filtered datasets are presented as tables. Genes that were shared in enriched expression in both follicular cell types (GCs and TCs) or in both luteal cells types (LLCs and SLCs) are also reported in tables. The standard deviation of the analyzed array data in relation to the log of the expression values is shown as a figure. These data have been further analyzed and interpreted in the companion article "Gene expression profiling of ovarian follicular and luteal cells provides insight into cellular identities and functions" (Romereim et al., 2017) [1].

  8. Changes in follicular cells architecture during vitellogenin transport in the ovary of social Hymenoptera.

    PubMed

    Ronnau, Milton; Azevedo, Dihego Oliveira; Fialho, Maria do Carmo Queiroz; Gonçlaves, Wagner Gonzaga; Zanuncio, José Cola; Serrão, José Eduardo

    2016-05-01

    Vitellogenins are the major yolk proteins, synthesized in the fat body, released into the hemolymph and captured by the developing oocytes, but the mechanisms by which these proteins cross the follicular cell layer are still poorly understood. This study describes the actin distribution in follicular cells during vitellogenin transport to the oocyte in social Hymenoptera represented by bees Apis mellifera and Melipona quadrifasciata, the wasp Mischocyttarus cassununga and the ant Pachycondyla curvinodis. In oocytic chambers of vitellogenic follicles, vitellogenin was found within the follicular cells, perivitelline space and oocyte, indicating a transcellular route from the hemolymph to the perivitelline space. The cortical actin cytoskeleton in follicular cells underwent reorganization during transport of vitellogenin across this epithelium suggesting that in the ovary of social hymenopterans, vitellogenin delivery to oocytes requires a dynamic cytoskeletal rearrangement of actin filaments in the follicular cells.

  9. Follicular mucinosis: an important differential diagnosis of leprosy in an endemic area*

    PubMed Central

    Westphal, Danielle Cristine; Pennini, Silmara Navarro; de Souza, Petra Pereira; Maquiné, Gustavo Ávila; Schettini, Antônio Pedro Mendes; Santos, Mônica

    2015-01-01

    Primary follicular mucinosis is a rare dermatosis characterized by the accumulation of mucin in the follicular epithelium and sebaceous glands. Clinically, it is characterized by the presence of papules or well-circumscribed and infiltrated plaques. In this paper, we report the case of a female patient, seven years old, evolving for three months with an asymptomatic, erythematous and infiltrated plaque located in the chin region. The research of thermal, pain and tactile sensitivity was inconclusive. Histological findings confirmed the diagnosis of follicular mucinosis. There was regression of the lesion with the use of medium potency topical corticosteroids for 20 days. The pathogenesis of follicular mucinosis remains unknown, being in some cases associated with lymphoproliferative disorders. In endemic areas of leprosy, isolated and infiltrated follicular mucinosis lesions should be further differentiated from leprosy. PMID:26312699

  10. Biochemical and steroid concentrations in follicular fluid and blood plasma in different follicular waves of the estrous cycle from normal and superovulated beef cows.

    PubMed

    Aller, J F; Callejas, S S; Alberio, R H

    2013-11-30

    The objectives of the current study were to (i) define the changes in size and number of follicles populations, (ii) determine the follicular fluid (FF) biochemical and steroid concentrations collected from different-sized follicles (5-9 and ≥ 10 mm) and (iii) compare between biochemical and hormonal concentrations of FF with those in blood plasma in relation to the first two follicular waves of the estrous cycle (days 4 and 13) from normal and cows primed for superovulation. After estrus, cows (n=20) were assigned randomly to each of four treatment groups. Group 1: ovariectomy on day 4 (day 0 = ovulation). Group 2: FSH treatment and ovariectomy on day 4. Group 3: dominant follicle ablation (DFA) on day 8 and ovariectomy on day 13. Group 4: DFA on day 8, FSH treatment and ovariectomy on day 13. Blood samples were collected and FF was aspirated and pooled per follicle class within cow to determine glucose, urea, triglycerides, cholesterol, total protein, albumin, lactate dehydrogenase, alkaline phosphatase, gamma-glutamyl transpeptidase, aspartate aminotransferase, creatin phosphokinase, estradiol-17β and progesterone concentrations. Follicular class×follicular wave interaction was detected for albumin and lactate dehydrogenase. Results showed that FF concentrations of cholesterol increased from medium to large follicles and decreased for urea and aspartate aminotransferase. Tryglycerides and total protein were greater in the second than in the first follicular wave. FSH treatment decreased FF alkaline phosphatase, E2 and P4 concentrations. Quantitative differences between these fluids are discussed with respect to follicular development.

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

    PubMed Central

    Li, Tun; Jan, Lily Yeh; Jan, Yuh Nung

    2016-01-01

    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

  12. 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.

  13. High frequency of clonal IG and T-cell receptor gene rearrangements in histiocytic and dendritic cell neoplasms

    PubMed Central

    Huang, Wenting; Qiu, Tian; Zeng, Linshu; Zheng, Bo; Ying, Jianming; Feng, Xiaoli

    2016-01-01

    The 2008 World Health Organization (WHO) diagnostic criteria of histiocytic and dendritic cell neoplasms from hematopoietic and lymphoid tissues no longer required the absence of clonal B-cell/T-cell receptor gene rearrangements. It is true that the clonal B-cell/T-cell receptor gene rearrangements have been identified in rare cases of histiocytic and dendritic cell neoplasms, such as those with or following lymphoma/leukemia or in some sporadic histiocytic/dendritic cell sarcomas, but the clonal features of such group of tumor are still not clear. Here we investigated the clonal status of 33 samples including Langerhans cell histiocytosis (LCH), Langerhans cell sarcoma (LCS), follicular dendritic cell sarcoma (FDCS), interdigitating dendritic cell sarcoma (IDCS) and histiocytic sarcoma (HS). Among them, twenty-eight cases were sporadic without current or past lymphoma/leukemia. Three cases were found with a past history of T-cell lymphoma, one case was followed by extraosseous plasmacytoma, and one case was found with diffuse large B-cell lymphoma (DLBCL). Our results showed that there was a high frequency of clonal IG and T-cell receptor gene rearrangements in these cases. Notably, 4 cases of LCH and 2 cases of FDCS showed both B and T cell receptor gene rearrangements concurrently. One case of FDCS synchronous with DLBCL showed identical clonal IGH in both tumor populations and clonal TCRβ in FDCS alone. No matter if the presence of clonal receptor gene rearrangements was associated with the tumor origin or tumorigenesis, it might serve as a novel tumor marker for developing target therapy. PMID:27823979

  14. Study on follicular characteristics, hormonal and biochemical profile in norgestomet+PMSG treated acyclic buffaloes

    PubMed Central

    Jerome, A.; Srivastava, S. K.; Sharma, R. K.

    2016-01-01

    This research was conducted to study the follicular dynamics, hormonal, biochemical profile and fertility response in acyclic and norgestomet+PMSG treated acyclic buffaloes in summer. The study animals were divided into two groups: group I [control (n=8): no treatment] and II [treatment group (n=15)]. In group II, seven animals were used for follicular biochemical and hormonal profile and eight animals for fertility studies following Crestar® (Intervet, France) treatment (day 0: Crestar® insertion; day 8: 500 IU PMSG; day 9: Crestar® removal; day 11 AI). Follicular fluid stradiol (E2) and progesterone (P4) in acyclic and pre-ovulatory follicle in study groups was significantly (P<0.01) higher than peripheral level. Peripheral E2 concentration, during pre-ovulatory period in group II was higher (P<0.05) than group I. Significant correlation between serum and follicular E2 was deduced (r=0.888; P<0.01) as significant difference in serum cholesterol content was shown between groups. Lower follicular total protein (P<0.05) in acyclic animals and higher follicular glucose (P<0.05) in treated group were concluded. Significant correlation (r=-0.770; P<0.05) was observed between follicular cholesterol and triglycerides. Follicular characteristics, post PMSG administration, differed significantly (0.83 ± 0.20 vs 1.32 ± 0.12; P<0.01) in all buffaloes exhibiting estrus, out of which four conceived. In conclusion, follicular hormonal and biochemical profile exhibits alteration in protein and glucose level between summer acyclic and treated buffaloes. However, peripheral E2 along with fertility response showed significant difference (P<0.01) between the study groups with significant correlation in E2, cholesterol and triglycerides between peripheral and follicular compartment. PMID:28224008

  15. Generation of T-follicular helper cells in vitro: requirement for BCR cross-linking and cognate B- and T-cell interaction.

    PubMed

    Kolenbrander, Anne; Grewe, Bastian; Nemazee, David; Überla, Klaus; Temchura, Vladimir

    2017-09-07

    The minimal requirements for in vitro modeling of the natural CD4(+) T-cell differentiation into T follicular helper (TFH) cells are still under investigation. We co-cultured wild type and TCR-transgenic CD4(+) T-cells from naïve mice with dendritic cells and BCR-transgenic B-cells in the presence of HIV-derived virus-like particles containing matched B- and T-cell epitopes. This co-culturing induced co-expression of TFH-master regulator transcription factor BCL-6 and CXCR5 in up to 10% of the wild type and up to 40% of the TCR-transgenic CD4(+) T-cells. Phenotypic markers, production of IL-21 and isotype switching of the B-cells to IgG1 further indicated a helper function of the induced TFH-cells in vitro. Dendritic cells supported the generation of functional TFH-cells, but were unable to induce them without cognate B-cells. Thus, our study presents a robust experimental system for efficient generation of functionally active TFH-cells in vitro and confirms the importance of cognate B- and T-cell cross-talk for the TFH differentiation process. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  16. Dendritic Growth in Undercooled Melts

    NASA Technical Reports Server (NTRS)

    Glicksman, M. E.

    1985-01-01

    The kinetic and morphological behavior of systems solidifying at small undercooling were investigated with emphasis on the role of convective and diffusive transport and the influence of gravity. A data base was established for pure succinonitrile which permits a comprehensive check on diffusional dendrite growth theory and the development of scaling laws to extend the theory to other material systems. A departure from diffusional-controlled growth was observed which becomes more significant at smaller undercoolings. A shuttle experiment is prepared to test the theory at the low undercoolings where convective effects begin to dominate.

  17. [Disseminated interdigitating dendritic cell sarcoma].

    PubMed

    Santarelli, Ignacio M; Veltri, Mariano; Manzella, Diego J; Avagnina, María Alejandra; Pereyra, Pablo M; Chavín, Hernán C

    2017-01-01

    A 70 year-old woman was admitted to our hospital with a 3-month history of abdominal pain, weight loss and night sweats. On physical examination, she presented with a 5 cm diameter abdominal mass extended from epigastrium to the left flank, and at least three bilateral supraclavicular adenopathies. A disseminated interdigitating dendritic cell sarcoma was diagnosed through a biopsy of the abdominal mass. After that, a CHOP regime (cyclophosphamide, doxorubicin, vincristine and prednisone) was iniciated. She died after completion of the first cycle of treatment, six months after diagnosis.

  18. Lung dendritic cells and the inflammatory response.

    PubMed

    Grayson, Mitchell H

    2006-05-01

    To discuss the role of conventional and plasmacytoid dendritic cells in inducing and modulating immune responses in the lung. The primary literature and selected review articles studying the role of dendritic cells in both rodent and human lungs as identified via a PubMed/MEDLINE search using the keywords dendritic cell, antigen-presenting cell, viral airway disease, asthma, allergy, and atopy. The author's knowledge of the field was used to identify studies that were relevant to the stated objective. Dendritic cells are well positioned in the respiratory tract and other mucosal surfaces to respond to any foreign protein. These cells are crucial to the initiation of the adaptive immune response through induction of antigen specific T-cell responses. These cells also play an important role in the regulation of developing and ongoing immune responses, an area that is currently under intense investigation. This review discusses the various subsets of human and rodent dendritic cells and the pathways involved in antigen processing and subsequent immune regulation by dendritic cells in the lung using both viral and nonviral allergenic protein exposure as examples. Conventional and plasmacytoid dendritic cells are uniquely situated in the immune cascade to not only initiate but also modulate immune responses. Therapeutic interventions in allergic and asthmatic diseases will likely be developed to take advantage of this exclusive position of the dendritic cell.

  19. ‘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

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

    PubMed Central

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

    2015-01-01

    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). PMID:26236782

  1. Cell-free DNA in human follicular fluid as a biomarker of embryo quality.

    PubMed

    Scalici, E; Traver, S; Molinari, N; Mullet, T; Monforte, M; Vintejoux, E; Hamamah, S

    2014-12-01

    Could cell-free DNA (cfDNA) quantification in individual human follicular fluid (FF) samples become a new non-invasive predictive biomarker for in vitro fertilization (IVF) outcomes? CfDNA level in human follicular fluid samples was significantly correlated with embryo quality and could be used as an innovative non-invasive biomarker to improve IVF outcomes. CfDNA fragments, resulting from apoptotic or necrotic events, are present in the bloodstream and their quantification is already used as a biomarker for gynaecological and pregnancy disorders. Follicular fluid is important for oocyte development and contains plasma components and factors secreted by granulosa cells during folliculogenesis. CfDNA presence in follicular fluid and its potential use as an IVF outcome biomarker have never been investigated. One hundred individual follicular fluid samples were collected from 43 female patients undergoing conventional IVF (n = 26) or ICSI (n = 17). CfDNA level was quantified in each individual follicular fluid sample. At oocyte collection day, follicles were aspirated individually. Only blood-free follicular fluid samples were included in the study. Follicle size was calculated based on the follicular fluid volume. Each corresponding cumulus-oocyte complex was isolated for IVF or ICSI procedures. Follicular fluid cfDNA was measured by quantitative PCR with ALU-specific primers. Human follicular fluid samples from individual follicles contain measurable amounts of cfDNA (mean ± SD, 1.62 ± 2.08 ng/µl). CfDNA level was significantly higher in small follicles (8-12 mm in diameter) than in large ones (>18 mm) (mean ± SD, 2.54 ± 0.78 ng/µl versus 0.71 ± 0.44 ng/µl, respectively, P = 0.007). Moreover, cfDNA concentration was significantly and negatively correlated with follicle size (r = -0.34; P = 0.003). A weak significant negative correlation between DNA integrity and 17β-estradiol level in follicular fluid samples at oocyte collection day was observed (r = -0

  2. Convection and diffusion effects during dendritic solidification

    NASA Technical Reports Server (NTRS)

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

    1979-01-01

    A report is presented of the first quantitative measurements of dendritic growth at supercooling levels where convection instead of diffusion is the controlling heat transfer mechanism. Precautions similar to that used in an investigation conducted by Glicksman et al. (1976) were taken to insure 'free' dendritic growth conditions. Dendritic growth velocity was measured as a function of growth orientation at seventeen supercoolings which ranged from 0.043 C to 2 C. Selected but representative measurements of velocity versus orientation angle are shown in a graph. The relative growth velocity of a downward growing dendrite is found to be greater than that of a diffusion-limited dendrite. This result is consistent with that expected from the enhanced heat transfer arising from natural convection.

  3. Isolation and generation of human dendritic cells.

    PubMed

    Nair, Smita; Archer, Gerald E; Tedder, Thomas F

    2012-11-01

    Dendritic cells are highly specialized antigen-presenting cells (APC), which may be isolated or generated from human blood mononuclear cells. Although mature blood dendritic cells normally represent ∼0.2% of human blood mononuclear cells, their frequency can be greatly increased using the cell enrichment methods described in this unit. More highly purified dendritic cell preparations can be obtained from these populations by sorting of fluorescence-labeled cells. Alternatively, dendritic cells can be generated from monocytes by culture with the appropriate cytokines, as described here. In addition, a negative selection approach is provided that may be employed to generate cell preparations that have been depleted of dendritic cells to be used for comparison in functional studies.

  4. Acute primary canine herpesvirus-1 dendritic ulcerative keratitis in an adult dog.

    PubMed

    Gervais, Kristen J; Pirie, Christopher G; Ledbetter, Eric C; Pizzirani, Stefano

    2012-03-01

    We present a report of dendritic ulcerative keratitis in a 4-year old locally immunosuppressed dog suspected to result from acute primary canine herpesvirus-1 (CHV-1) infection. The dog was presented for evaluation of mild blepharospasm and conjunctival hyperemia in the right eye (OD) shortly after attending a public boarding facility. For approximately 3 months, the dog had been receiving topical prednisolone acetate 1.0% and tacrolimus 0.02% in both eyes (OU) q12h for treatment of follicular conjunctivitis. Ophthalmic examination revealed three regions of corneal fluorescein retention OD. The lesions had a dendritic pattern, were approximately 2-3 mm in length, and were located at the dorsomedial, lateral, and ventromedial aspects of the cornea. No additional abnormalities were noted on complete ophthalmic and physical examinations. CHV-1 was identified in conjunctival samples OD by polymerase chain reaction, and paired CHV-1 serum virus neutralization antibody titers were positive and consistent with acute infection. Topical prednisolone acetate and tacrolimus were discontinued. The dog was treated with cidofovir 0.5% OU q12h for a period of 4 weeks, with resolution of corneal disease noted within 1 week of treatment. In conjunction with previous studies, this case report supports a central role for alterations in host immune status in the pathogenesis and clinical manifestations of CHV-1 ocular disease in dogs.

  5. Active dendrites, potassium channels and synaptic plasticity.

    PubMed Central

    Johnston, Daniel; Christie, Brian R; Frick, Andreas; Gray, Richard; Hoffman, Dax A; Schexnayder, Lalania K; Watanabe, Shigeo; Yuan, Li-Lian

    2003-01-01

    The dendrites of CA1 pyramidal neurons in the hippocampus express numerous types of voltage-gated ion channel, but the distributions or densities of many of these channels are very non-uniform. Sodium channels in the dendrites are responsible for action potential (AP) propagation from the axon into the dendrites (back-propagation); calcium channels are responsible for local changes in dendritic calcium concentrations following back-propagating APs and synaptic potentials; and potassium channels help regulate overall dendritic excitability. Several lines of evidence are presented here to suggest that back-propagating APs, when coincident with excitatory synaptic input, can lead to the induction of either long-term depression (LTD) or long-term potentiation (LTP). The induction of LTD or LTP is correlated with the magnitude of the rise in intracellular calcium. When brief bursts of synaptic potentials are paired with postsynaptic APs in a theta-burst pairing paradigm, the induction of LTP is dependent on the invasion of the AP into the dendritic tree. The amplitude of the AP in the dendrites is dependent, in part, on the activity of a transient, A-type potassium channel that is expressed at high density in the dendrites and correlates with the induction of the LTP. Furthermore, during the expression phase of the LTP, there are local changes in dendritic excitability that may result from modulation of the functioning of this transient potassium channel. The results support the view that the active properties of dendrites play important roles in synaptic integration and synaptic plasticity of these neurons. PMID:12740112

  6. Comparative analysis of rosacea and cutaneous lupus erythematosus: histopathologic features, T-cell subsets, and plasmacytoid dendritic cells.

    PubMed

    Brown, Theodore T; Choi, Eun-Young K; Thomas, Dafydd G; Hristov, Alexandra C; Chan, May P

    2014-07-01

    Distinction of rosacea and cutaneous lupus erythematosus (LE) can be challenging because of significant clinical and histologic overlap. A controlled study comparing these conditions is lacking. We compared the histologic features, T-cell subsets, and plasmacytoid dendritic cells in rosacea and LE. Biopsy specimens of rosacea (n = 27) and facial LE (n = 30) were retrospectively reviewed and reacted with Alcian blue and periodic acid-Schiff stains, and CD4, CD8, CD25, and CD123 immunostains. LE demonstrates a lower CD4:CD8 ratio (1.74 vs 2.80, P = .0064), fewer CD4(+)CD25(+) regulatory T cells (13% vs 31%, P < .0001), and more CD123(+) plasmacytoid dendritic cells (18% vs 6%, P = .0137) than rosacea. The plasmacytoid dendritic cells in LE are more likely to form clusters (P = .0137) and comprise at least 20% of the infiltrate (P = .0340). Also associated with LE are follicular plugging (P = .0039), perineural lymphocytic infiltrate (P = .0211), abundant mucin deposition (P = .0031), and conspicuous basement membrane thickening (P = .0073), whereas Demodex infestation (P = .0064) and sebaceous hyperplasia (P = .0029) are significantly associated with rosacea. Although statistically significant, the immunophenotypic differences are rather small and limited for routine use. The infiltrates in rosacea and LE differ immunophenotypically, and may aid in their distinction in addition to conventional histologic examination. Copyright © 2014 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

  7. 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

  8. Fine-needle aspiration of follicular lesions of the thyroid. Diagnosis and follow-Up

    PubMed Central

    Deveci, M Salih; Deveci, Güzin; LiVolsi, Virginia A; Baloch, Zubair W

    2006-01-01

    The differential diagnosis of a follicular lesion/neoplasm in thyroid FNA specimens includes hyperplastic/adenomatoid nodule, follicular adenoma and carcinoma, and follicular variant of papillary thyroid carcinoma. In our laboratory we separate follicular lesions of thyroid into hyperplastic/adenomatoid nodule (HN), follicular neoplasm (FON) and follicular derived neoplasm with focal nuclear features suspicious for papillary thyroid carcinoma (FDN). This study reports our experience with 339 cases diagnosed as FON and 120 as FDN. All cases were evaluated for histologic diagnosis, age, sex and size of the nodule. Histopathologic follow-up was available in all cases. The malignancy rate was 22% (74/359) and 72% (86/120) for cases diagnosed as FON and FDN, respectively. In the FON category almost half of the malignant cases were papillary carcinoma. The risk of malignancy was higher in patients younger than 40 yr (53% vs. 30%) than in patients 40 year or more years old and greater in males (41% vs. 33%) than females. No statistically significant relationship was noted between the sizes of the nodules and benign vs. malignant diagnosis. According to this study it is important to divide follicular patterned lesions of thyroid into FON and FDN in the cytology specimens due to significantly different risk of malignancy (22% vs. 72%). In addition, clinical features, including gender and age can be part of the decision analysis in selecting patients for surgery. PMID:16603062

  9. 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

  10. Detection and Classification of Thyroid Follicular Lesions Based on Nuclear Structure from Histopathology Images

    PubMed Central

    Wang, Wei; Ozolek, John A.; Rohde, Gustavo K.

    2010-01-01

    Follicular lesions of the thyroid are traditionally difficult and tedious challenges in diagnostic surgical pathology in part due to lack of obvious discriminatory cytological and microarchitectural features. We describe a computerized method to detect and classify follicular adenoma of the thyroid, follicular carcinoma of the thyroid, and normal thyroid based on the nuclear chromatin distribution from digital images of tissue obtained by routine histological methods. Our method is based on determining whether a set of nuclei, obtained from histological images using automated image segmentation, is most similar to sets of nuclei obtained from normal or diseased tissues. This comparison is performed utilizing numerical features, a support vector machine, and a simple voting strategy. We also describe novel methods to identify unique and defining chromatin patterns pertaining to each class. Unlike previous attempts in detecting and classifying these thyroid lesions using computational imaging, our results show that our method can automatically classify the data pertaining to 10 different human cases with 100% accuracy after blind cross validation using at most 43 nuclei randomly selected from each patient. We conclude that nuclear structure alone contains enough information to automatically classify the normal thyroid, follicular carcinoma, and follicular adenoma, as long as groups of nuclei (instead of individual ones) are used. We also conclude that the distribution of nuclear size and chromatin concentration (how tightly packed it is) seem to be discriminating features between nuclei of follicular adenoma, follicular carcinoma, and normal thyroid. PMID:20099247

  11. Application of artificial neural network for classification of thyroid follicular tumors.

    PubMed

    Shapiro, Naum A; Poloz, Tatiana L; Shkurupij, Viycheslav A; Tarkov, Mikhail S; Poloz, Vadim V; Demin, Alexander V

    2007-04-01

    To analyze smears of 197 thyroid follicular tumors (adenoma and carcinoma). Several types of artificial neural networks (ANN) of various designs were used for diagnosis of thyroid follicular tumors. The typical complex of cytologic features, some nuclear morphometric parameters (area, perimeter, shape factor) and density features of chromatin texture (mean value and SD of gray levels) were defined for each tumor. The ANN was trained by means of cytologic features characteristic for a thyroid follicular adenoma and a follicular carcinoma. At subsequent testing, the correct cytologic diagnosis was established in 93% (25 of 27) of cases. The morphometry increased the accuracy of diagnosis for follicular tumors in up to 97% (75 of 78) of cases. ANN correctly distinguished an adenoma or a carcinoma in 87% (73 of 84) of cases when using color microscopic images of tumors. The usage of ANN has raised sensitivity of cytologic diagnosis of follicular tumors to 90%, compared with a usual cytologic method (sensitivity of 56%). The automatic classification of thyroid follicular tumors by means of ANN is prospective.

  12. 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.

  13. Recommendations for Clinical Trial Development in Follicular Lymphoma.

    PubMed

    Maddocks, Kami; Barr, Paul M; Cheson, Bruce D; Little, Richard F; Baizer, Lawrence; Kahl, Brad S; Leonard, John P; Fowler, Nathan; Gordon, Leo I; Link, Brian K; Friedberg, Jonathan W; Ansell, Stephen M

    2017-03-01

    Follicular lymphoma (FL) is the second most common lymphoid malignancy, representing 20% to 25% of all cases of non-Hodgkin's lymphoma (NHL), and the most common of the indolent NHLs. FL is considered incurable in the majority of patients with the current standard therapeutic approaches, although outcomes have improved in the last few decades with our current therapies, with a median overall survival that now exceeds 18 years. While the majority of patients with FL have improved outcomes with our current therapeutic approaches, there are patients with high-risk disease features that have inferior outcomes to these therapies. There is an urgent need to integrate novel therapeutic agents into the treatment regimens for these patients to improve outcomes with continued evaluation of biomarkers indicative of prognosis and effects of these regimens on quality of life.

  14. Expression of the bcl-2 gene product in follicular lymphoma.

    PubMed Central

    Gaulard, P.; d'Agay, M. F.; Peuchmaur, M.; Brousse, N.; Gisselbrecht, C.; Solal-Celigny, P.; Diebold, J.; Mason, D. Y.

    1992-01-01

    Expression of bcl-2 protein was analyzed in 140 cases of follicular lymphoma by immunohistologic staining of paraffin-embedded tissue; 85% of cases were positive, the frequency being related to histologic grade (100% for the small-cleaved cell type, 86% for the mixed cell type, and 76% for the large cell group). There was striking heterogeneity of bcl-2 content in a number of cases and the smaller neoplastic cells (i.e., centrocytes) were usually the most strongly labeled. In most cases, bcl-2 protein staining was much weaker in normal lymphoid cells than in the neoplastic cells. In several cases, staining for bcl-2 revealed patterns of neoplastic cell spread into adjacent tissue (e.g., normal follicles, lymphoid sinuses), and bcl-2 protein expression tended to be highest in these migratory cells. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 PMID:1374590

  15. Rare Intradural Cervical Nerve Root Metastasis of Follicular Thyroid Carcinoma

    PubMed Central

    Milosavljevic, Elena; Hanna, George; Gospodarev, Vadim; Raghavan, Ravi; Ghostine, Samer

    2016-01-01

    Intradural extramedullary nerve root metastasis is extremely unusual with only a handful of cases reported, and it presents most commonly in the thoracic and lumbosacral regions. We report the first case of metastasis to a ventral cervical nerve root in a patient with low-grade follicular thyroid carcinoma thought to be in remission for several years. Histopathology demonstrated malignant transformation and invasion of the nerve root. This case underscores that any history of malignancy regardless of staging, grading, or remission status should raise the suspicion of metastasis as it can mimic other spine and nerve sheath tumors and represent malignant transformation. Gross total resection can be safely achieved with intraoperative neuromonitoring and result in improved function; however, treatment is likely palliative. PMID:28018768

  16. Development and function of follicular helper T cells.

    PubMed

    Ise, Wataru

    2015-01-01

    Most currently available vaccines rely on the induction of long-lasting protective humoral immune responses by memory B cells and plasma cells. Antibody responses against most antigens require interactions between antigen-specific B cells and CD4(+) T cells. Follicular helper T cells (TFH cells) are specialized subset of T cells that provide help to B cells and are essential for germinal center formation, affinity maturation, and the development of high-affinity antibodies. TFH-cell differentiation is a multistage process involving B-cell lymphoma 6 and other transcription factors, cytokines, and costimulation through inducible costimulator (ICOS) and several other molecules. This article reviews recent advances in our understanding of TFH cell biology, including their differentiation, transcriptional regulation, and function.

  17. Evolution of the rat oocyte nucleolus during follicular growth.

    PubMed

    Antoine, N; Lepoint, A; Baeckeland, E; Goessens, G

    1987-01-01

    The ultrastructural evolution of the nucleolus was followed during follicular growth by means of a silver staining procedure. The oocyte nucleolus in the primordial and primary follicles consists of strands of dense fibrillar silver-stained component and aggregates of granules which are devoid of silver grains. Small fibrillar centres are also recognized and appear to have less silver stainability. At the secondary follicle stage, a new nucleolar component appears in the reticulated oocyte nucleolus. This component is devoid of silver grains. During follicle growth, at the antral follicle stage, this new component seems to fuse and the nucleolus becomes constituted of a compact homogeneous mass which exhibits a vacuole at the end of the oocyte maturation. The results obtained suggest that this nucleolar mass is essentially made of proteins and particularly of acidic proteins.

  18. T follicular helper cell differentiation, function, and roles in disease

    PubMed Central

    Crotty, Shane

    2014-01-01

    Summary Follicular helper T (Tfh) cells are specialized providers of T cell help to B cells, and are essential for germinal center formation, affinity maturation, and the development of most high affinity antibodies and memory B cells. Tfh cell differentiation is a multi-stage, multi-factorial process involving B cell lymphoma 6 (Bcl6) and other transcription factors. This article reviews understanding of Tfh cell biology, including their differentiation, migration, transcriptional regulation, and B cell help functions. Tfh cells are critical components of many protective immune responses against pathogens. As such, there is strong interest in harnessing Tfh cells to improve vaccination strategies. Tfh cells also have roles in a range of other diseases, particularly autoimmune diseases. Overall, there have been dramatic advances in this young field, but there is much to be learned about Tfh cell biology in the interest of applying that knowledge to biomedical needs. PMID:25367570

  19. Epidemiology, pathology and treatment of non-follicular indolent lymphomas.

    PubMed

    Landgren, Ola; Tilly, Hervé

    2008-01-01

    Non-follicular indolent subtypes of non-Hodgkin lymphoma (NHL), which include chronic lymphocytic leukemia, small lymphocytic lymphoma (SLL) and marginal zone lymphomas (MZL), are a diverse group of disorders with different presenting features, behaviour patterns and treatment outcomes. Current knowledge of these subtypes is largely based on retrospective analyses. A precise diagnosis can be difficult to achieve, and specific diagnostic criteria are needed to more precisely define some of the rarer indolent tumors, such as nodal and splenic MZLs. Although some subtypes of NHL have a prolonged indolent course, with a good prognosis (e.g. SLL), others (e.g. nodal and splenic MZLs) can rapidly evolve into more aggressive subtypes. In asymptomatic patients, treatment may be deferred until the disease progresses and the patient becomes symptomatic. Universally accepted therapeutic guidelines do not exist, however, and carefully designed, prospective clinical studies are needed to further assess optimal therapeutic approaches for these indolent NHLs.

  20. Eyelash transplantation using leg hair by follicular unit extraction.

    PubMed

    Umar, Sanusi

    2015-03-01

    Fine hairs of the head and nape areas have been used as donor sources in eyelash transplantation but are straight, coarse, and grow rapidly, requiring frequent eyelash maintenance. This is the first reported case of eyelash transplantation by follicular unit extraction using leg hair as a donor source; findings were compared with that of another patient who underwent a similar procedure with donor hairs from the nape area. Although both patients reported marked improvement in fullness of eyelashes within 3 months postsurgery, the transplanted leg hair eyelashes required less frequent trimming (every 5-6 weeks) compared with nape hair eyelashes (every 2-3 weeks). Additionally, in leg hair eyelashes, the need for perming to sustain a natural looking eyelash curl was eliminated. Eyelash transplantation using leg donor hair in hirsute women may result in good cosmetic outcomes and require less maintenance compared with nape donor hair.

  1. Eyelash Transplantation Using Leg Hair by Follicular Unit Extraction

    PubMed Central

    2015-01-01

    Summary: Fine hairs of the head and nape areas have been used as donor sources in eyelash transplantation but are straight, coarse, and grow rapidly, requiring frequent eyelash maintenance. This is the first reported case of eyelash transplantation by follicular unit extraction using leg hair as a donor source; findings were compared with that of another patient who underwent a similar procedure with donor hairs from the nape area. Although both patients reported marked improvement in fullness of eyelashes within 3 months postsurgery, the transplanted leg hair eyelashes required less frequent trimming (every 5–6 weeks) compared with nape hair eyelashes (every 2–3 weeks). Additionally, in leg hair eyelashes, the need for perming to sustain a natural looking eyelash curl was eliminated. Eyelash transplantation using leg donor hair in hirsute women may result in good cosmetic outcomes and require less maintenance compared with nape donor hair. PMID:25878935

  2. 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

  3. Scalp Surgery: Quantitative Analysis of Follicular Unit Growth

    PubMed Central

    Caruana, Giorgia

    2015-01-01

    Background: Over the years, different kinds of hair transplantation have been compared in an attempt to overcome male pattern alopecia and, at the same time, maximize both the survival and growth rate of grafted hair. In this study, we have assessed the survival and growth rate of follicular units (FU) in an in vitro model, as compared with that of conventional hair micrografts, to experimentally evaluate and elaborate on the differences between these 2 approaches in hair transplantation procedures. Methods: Group A (control; n = 100 follicles) was composed of hair micrografts, whereas FUs were assigned to Group B (experimental; n = 100 follicles, n = 35 FUs). Each group was cultured for a period of 10 days; the total stretch of follicles was measured soon after the harvest and 10 days later. The Kruskal-Wallis one-way analysis of variance on ranks test was used to perform statistical analysis. Results: The growth rate of follicles from Group A (mean 10-day shaft growth rate = 0.30 mm) proved to be statistically different compared with that of Group B (mean 10-day shaft growth rate = 0.23 mm). Conversely, our data did not show any significant difference between the survival rate of hair grafts from these 2 groups. Conclusions: Our data highlighted a reduced FU shaft growth compared with that of hair micrografts, corroborating, to a certain extent, the hypothesis that a significant amount of adipose tissue surrounding the follicle included in the graft may result in an inadequate nourishment supply to follicular cells. PMID:26579345

  4. Life expectancy of young adults with follicular lymphoma.

    PubMed

    Conconi, A; Lobetti-Bodoni, C; Montoto, S; Lopez-Guillermo, A; Coutinho, R; Matthews, J; Franceschetti, S; Bertoni, F; Moccia, A; Rancoita, P M V; Gribben, J; Cavalli, F; Gaidano, G; Lister, T A; Montserrat, E; Ghielmini, M; Zucca, E

    2015-11-01

    This study was aimed at investigating the clinical features and outcomes of follicular lymphoma (FL) patients younger than 40 years, which have not been extensively investigated yet. One hundred and fifty-five patients younger than 40 years were retrospectively studied from a series of 1002 FL patients diagnosed in four different European Oncology Centres (Barcelona, Spain; Bellinzona, Switzerland; London, UK; Novara, Italy) from 1985 to 2010. Patients younger than 40 had a lower incidence of elevated LDH, high beta2-microglobulin, and a high-risk Follicular Lymphoma International Prognostic Index (FLIPI) score, whereas bone marrow involvement and bulky and disseminated lymphadenopathy were more frequent. At a median follow-up of 10 years, younger patients, in comparison with those older than 40, had significantly better overall (OS), cause-specific survival (CSS), and progression-free survival (PFS), with 10-year OS rate of 81% versus 51% (P < 0.0001), 10-year CSS rate of 82% versus 60% (P < 0.0001), and 10-year PFS of 39% versus 24% (P = 0.0098). However, there were no significant CSS and PFS differences in comparison with the patients aged 40-60. In multivariate analysis, having the lymphoma diagnosed in the last two decades and a favourable FLIPI score were associated with a significantly longer PFS and CSS in younger patients, whereas only FLIPI retained statistical significance for OS. In our series, FL patients younger than 40 have a median OS of 24 years and their outcome seems to be improving over time. However, they still have a significantly shorter life expectancy than that of an age-matched general healthy population. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  5. Probe dendritic functions through poking and peeking

    NASA Astrophysics Data System (ADS)

    Xiong, Wenhui; Zhou, Zhishang; Zeng, Shaoqun; Chen, Wei R.

    2003-12-01

    Several photonic approaches have been utilized to study functional dynamics of olfactory bulb dendrites, which plays a critical role in odor discrimination and recognition. Firstly, with infrared differential interference contrast (DIC) video microscopy, we can visualize living nerve cells in an olfactory bulb slice preparation and target glass electrodes to different dendritic locations for direct electrical measurement. This furnishes a high temporal resolution of signal recording from dendrites. Secondly, by using a cooled CCD camera and loading calcium-sensitive dyes into neurons, we have explored the spatial distribution and propagation of spike signals within complex dendritic trees. Thirdly, two-photon microscope enables us to analyze active properties of very tiny dendritic structures such as dendritic spines. Lastly, by using UV light pulse to release calcium ions from caged compounds, we have examined the mechanisms for signal communication between two dendrites with reciprocal synaptic connections. Our research highlights an important contribution of optical imaging methods to functional dissection of neuronal circuitry in the brain.

  6. Dendritic potassium channels in hippocampal pyramidal neurons

    PubMed Central

    Johnston, Daniel; Hoffman, Dax A; Magee, Jeffrey C; Poolos, Nicholas P; Watanabe, Shigeo; Colbert, Costa M; Migliore, Michele

    2000-01-01

    Potassium channels located in the dendrites of hippocampal CA1 pyramidal neurons control the shape and amplitude of back-propagating action potentials, the amplitude of excitatory postsynaptic potentials and dendritic excitability. Non-uniform gradients in the distribution of potassium channels in the dendrites make the dendritic electrical properties markedly different from those found in the soma. For example, the influence of a fast, calcium-dependent potassium current on action potential repolarization is progressively reduced in the first 150 μm of the apical dendrites, so that action potentials recorded farther than 200 μm from the soma have no fast after-hyperpolarization and are wider than those in the soma. The peak amplitude of back-propagating action potentials is also progressively reduced in the dendrites because of the increasing density of a transient potassium channel with distance from the soma. The activation of this channel can be reduced by the activity of a number of protein kinases as well as by prior depolarization. The depolarization from excitatory postsynaptic potentials (EPSPs) can inactivate these A-type K+ channels and thus lead to an increase in the amplitude of dendritic action potentials, provided the EPSP and the action potentials occur within the appropriate time window. This time window could be in the order of 15 ms and may play a role in long-term potentiation induced by pairing EPSPs and back-propagating action potentials. PMID:10811726

  7. Dendritic potassium channels in hippocampal pyramidal neurons.

    PubMed

    Johnston, D; Hoffman, D A; Magee, J C; Poolos, N P; Watanabe, S; Colbert, C M; Migliore, M

    2000-05-15

    Potassium channels located in the dendrites of hippocampal CA1 pyramidal neurons control the shape and amplitude of back-propagating action potentials, the amplitude of excitatory postsynaptic potentials and dendritic excitability. Non-uniform gradients in the distribution of potassium channels in the dendrites make the dendritic electrical properties markedly different from those found in the soma. For example, the influence of a fast, calcium-dependent potassium current on action potential repolarization is progressively reduced in the first 150 micrometer of the apical dendrites, so that action potentials recorded farther than 200 micrometer from the soma have no fast after-hyperpolarization and are wider than those in the soma. The peak amplitude of back-propagating action potentials is also progressively reduced in the dendrites because of the increasing density of a transient potassium channel with distance from the soma. The activation of this channel can be reduced by the activity of a number of protein kinases as well as by prior depolarization. The depolarization from excitatory postsynaptic potentials (EPSPs) can inactivate these A-type K+ channels and thus lead to an increase in the amplitude of dendritic action potentials, provided the EPSP and the action potentials occur within the appropriate time window. This time window could be in the order of 15 ms and may play a role in long-term potentiation induced by pairing EPSPs and back-propagating action potentials.

  8. Endocrine-disrupting chemicals in human follicular fluid impair in vitro oocyte developmental competence.

    PubMed

    Petro, Evi M L; Leroy, Jo L M R; Covaci, Adrian; Fransen, Erik; De Neubourg, Diane; Dirtu, Alin C; De Pauw, Ingrid; Bols, Peter E J

    2012-04-01

    Increased global industrial activity has exposed humans to a wide variety of chemical substances some of which, called 'endocrine-disrupting chemicals' (EDCs) or 'endocrine disruptors', can disrupt the endocrine system in the body. The ovarian follicle is a very fragile micro-environment where interactions between hormones, growth factors, the oocyte and its surrounding somatic cells are essential to generate a fully competent oocyte. In vitro experiments suggest that EDCs can disturb this finely tuned balance, but very scarse in vivo data are available to confirm this assumption. Therefore, we have investigated if the presence of EDCs in human follicular fluid is a risk factor for the developmental competence of an in vivo exposed oocyte. Furthermore, because of the limited access to human follicular fluid, we verified if follicular fluid contamination can be predicted based on EDC levels in serum. Follicular fluid (n = 40) and serum (n = 20) samples from women undergoing assisted reproductive technology (ART) were analyzed by means of gas chromatography combined with mass spectrometry to examine the presence of different EDCs, such as polychlorinated biphenyls, polybrominated diphenyl ethers and organochlorine pesticides. Statistical models were used to investigate the relation between the characteristics and ART results of the patients and the contamination status of their follicular fluid and to assess the capacity of serum samples to predict follicular fluid contamination. Chlorinated biphenyl 153 (72 ± 44 and 201 ± 106 pg/ml) and p,p'-DDE (392 ± 348 and 622 ± 406 pg/ml) were the compounds found in the highest concentrations in follicular fluid and serum samples, respectively. A new variable principal component 1, representing the overall contamination status of the follicular fluid samples, is strongly associated with fertilization rate (P < 0.00001) and the proportion of high-quality embryos relative to the amount of retrieved oocytes (P < 0.05), even

  9. Frontal bone metastasis from an occult follicular thyroid carcinoma: Diagnosed by FNAC

    PubMed Central

    Kalra, Rajnish; Pawar, Richa; Hasija, Sonia; Chandna, Abha; Sankla, Manoj; Malhotra, Chanchal

    2017-01-01

    Metastatic deposits in skull bones from follicular thyroid carcinoma is rare, and metastatic disease in skull being the presenting symptom without obvious thyroid lesion (occult primary) is even rarer. A 60-year-old female patient presented with a mass in the frontal region of the skull. Fine needle aspiration cytology was done which revealed an adenocarcinoma with repeated follicular pattern, reminiscent of follicular neoplasm of thyroid, which on immunocytochemistry revealed positivity for thyroglobulin. Patient was investigated further for primary thyroid malignancy, and imaging revealed a nodule in the left lobe of thyroid. Neuroimaging showed osteolytic lesion involving the cranium. PMID:28182063

  10. Follicular Dowling Degos disease: a rare variant of an evolving dermatosis.

    PubMed

    Singh, Saurabh; Khandpur, Sujay; Verma, Parul; Singh, Manoj

    2013-01-01

    Dowling Degos disease is a rare, reticulate pigmentary disorder with variable phenotypic expression that manifests as hyperpigmented macules and reticulate pigmentary anomaly of the flexures. Many variants of this condition and its overlap with other reticulate pigmentary disorders have been reported in the literature. We present here two cases of DDD with follicular localization, both clinically and histologically. It was associated with ichthyosis vulgaris in one case. Follicular DDD is an uncommon variant of this evolving dermatosis. Our report supports the possible role for disordered follicular keratinisation in its pathogenesis.

  11. 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

  12. Neural image processing by dendritic networks.

    PubMed

    Cuntz, Hermann; Haag, Jürgen; Borst, Alexander

    2003-09-16

    Convolution is one of the most common operations in image processing. Based on experimental findings on motion-sensitive visual interneurons of the fly, we show by realistic compartmental modeling that a dendritic network can implement this operation. In a first step, dendritic electrical coupling between two cells spatially blurs the original motion input. The blurred motion image is then passed onto a third cell via inhibitory dendritic synapses resulting in a sharpening of the signal. This enhancement of motion contrast may be the central element of figure-ground discrimination based on relative motion in the fly.

  13. Fractional Cable Models for Spiny Neuronal Dendrites

    NASA Astrophysics Data System (ADS)

    Henry, B. I.; Langlands, T. A. M.; Wearne, S. L.

    2008-03-01

    Cable equations with fractional order temporal operators are introduced to model electrotonic properties of spiny neuronal dendrites. These equations are derived from Nernst-Planck equations with fractional order operators to model the anomalous subdiffusion that arises from trapping properties of dendritic spines. The fractional cable models predict that postsynaptic potentials propagating along dendrites with larger spine densities can arrive at the soma faster and be sustained at higher levels over longer times. Calibration and validation of the models should provide new insight into the functional implications of altered neuronal spine densities, a hallmark of normal aging and many neurodegenerative disorders.

  14. Solidification under microgravity conditions - Dendritic growth

    NASA Technical Reports Server (NTRS)

    Glicksman, M. E.; Hahn, R. C.; Lograsso, T. A.; Rubinstein, E. R.; Winsa, E.

    1987-01-01

    The experimental approach and apparatus of a zero-gravity active crystal growth experiment to test dendritic growth theory at low supercoolings are discussed. The experiment consists of 20 experimental cycles. Estimates have been made as to how low gravitational accelerations would have to be reduced to observe convection-free dendritic growth at supercoolings from 0.01-1.0 K. The experiment requires temperature control of + or - 2 mK and photographic resolution of a few microns with a depth of field of + or - 6 mm. The thermostatic bath and temperature control system, photographic system, growth chamber, and dendrite detection system are described in detail.

  15. Tumor Targeting, Trifunctional Dendritic Wedge

    PubMed Central

    2015-01-01

    We report in vitro and in vivo evaluation of a newly designed trifunctional theranostic agent for targeting solid tumors. This agent combines a dendritic wedge with high boron content for boron neutron capture therapy or boron MRI, a monomethine cyanine dye for visible-light fluorescent imaging, and an integrin ligand for efficient tumor targeting. We report photophysical properties of the new agent, its cellular uptake and in vitro targeting properties. Using live animal imaging and intravital microscopy (IVM) techniques, we observed a rapid accumulation of the agent and its retention for a prolonged period of time (up to 7 days) in fully established animal models of human melanoma and murine mammary adenocarcinoma. This macromolecular theranostic agent can be used for targeted delivery of high boron load into solid tumors for future applications in boron neutron capture therapy. PMID:25350602

  16. Dendritic Cell-Targeted Vaccines

    PubMed Central

    Cohn, Lillian; Delamarre, Lélia

    2014-01-01

    Despite significant effort, the development of effective vaccines inducing strong and durable T-cell responses against intracellular pathogens and cancer cells has remained a challenge. The initiation of effector CD8+ T-cell responses requires the presentation of peptides derived from internalized antigen on class I major histocompatibility complex molecules by dendritic cells (DCs) in a process called cross-presentation. A current strategy to enhance the effectiveness of vaccination is to deliver antigens directly to DCs. This is done via selective targeting of antigen using monoclonal antibodies directed against endocytic receptors on the surface of the DCs. In this review, we will discuss considerations relevant to the design of such vaccines: the existence of DC subsets with specialized functions, the impact of the antigen intracellular trafficking on cross-presentation, and the influence of maturation signals received by DCs on the outcome of the immune response. PMID:24910635

  17. [Exosomes derived from dendritic cells].

    PubMed

    Amigorena, S

    2001-01-01

    Dendritic cells (DC) are potent antigen presenting cells and the only ones capable of inducing primary cytotoxic immune responses both in vivo and vitro. DCs secrete a 60-80 nm membrane vesicle population of endocytic origin, called exosomes. The protein composition of exosomes was analyzed using a systematic proteomic approach. Besides MHC and costimulatory molecules, exosomes bear several adhesion proteins, probably involved in their specific targeting. Exosomes also accumulate several cytosolic factors, most likely involved in exoxome's biogenesis in late endosomes. Like DCs, exosomes induce potent anti tumor immune responses in vivo. Indeed, a single injection of DC-derived exosomes sensitized with tumor peptides induced the eradication of established mouse tumors. Tumor-specific cytotoxic T lymphocytes were found in the spleen of exosome treated mice, and depletion of CD8+ T cells in vivo inhibited the anti tumor effect of exosomes. These results strongly support the implementation of human DC-derived exosomes for cancer immunotherapy.

  18. Neurotensin promotes the dendrite elongation and the dendritic spine maturation of the cerebral cortex in vitro.

    PubMed

    Gandou, Chihiro; Ohtani, Akiko; Senzaki, Kouji; Shiga, Takashi

    2010-03-01

    We examined roles of neurotensin in the dendrite formation and the maturation of dendritic spines in the rat cerebral cortex. Embryonic day (E) 18 cortical neurons were cultured for 2 or 4 days in the presence of neurotensin. The chronic treatment of cortical neurons with neurotensin for 4 days increased the dendritic length of non-GABAergic neurons. In addition, the acute treatment of cortical neurons for 24h at 3 days in vitro also increased the dendritic length of non-GABAergic neurons similarly but more strongly than the chronic treatment. In contrast, the acute treatment for 4h had no effects on the dendrite formation. Next, we examined the effects of neurotensin on the maturation of dendritic spines. E16 cortical neurons were cultured for 10 or 14 days in a basal medium and then treated with neurotensin for 24h. At 11 days in vitro, neurotensin increased the postsynaptic density (PSD) 95-positive dendritic protrusions (filopodia, puncta and spines) together with the increase of spine density and the decrease of puncta density. At 15 days in vitro, neurotensin decreased the puncta density. In addition, the immunohistochemical localization of neurotensin type 1 and type 3 receptors in cultured neurons suggested the differential contribution of the receptors in these effects. These findings suggest that neurotensin promotes the dendrite outgrowth and the maturation of dendritic spines of cultured cortical neurons, although further studies are needed to conclude that these roles of neurotensin are also the case in vivo.

  19. 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

  20. Dendritic ion channelopathy in acquired epilepsy

    PubMed Central

    Poolos, Nicholas P.; Johnston, Daniel

    2012-01-01

    Summary Ion channel dysfunction or “channelopathy” is a proven cause of epilepsy in the relatively uncommon genetic epilepsies with Mendelian inheritance. But numerous examples of acquired channelopathy in experimental animal models of epilepsy following brain injury have also been demonstrated. Our understanding of channelopathy has grown due to advances in electrophysiology techniques that have allowed the study of ion channels in the dendrites of pyramidal neurons in cortex and hippocampus. The apical dendrites of pyramidal neurons comprise the vast majority of neuronal surface membrane area, and thus the majority of the neuronal ion channel population. Investigation of dendritic ion channels has demonstrated remarkable plasticity in ion channel localization and biophysical properties in epilepsy, many of which produce hyperexcitability and may contribute to the development and maintenance of the epileptic state. Here we review recent advances in dendritic physiology and cell biology, and their relevance to epilepsy. PMID:23216577

  1. 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

  2. Podosomes of dendritic cells facilitate antigen sampling

    PubMed Central

    Reinieren-Beeren, Inge; Cambi, Alessandra; Figdor, Carl G.; van den Bogaart, Geert

    2014-01-01

    Summary Dendritic cells sample the environment for antigens and play an important role in establishing the link between innate and acquired immunity. Dendritic cells contain mechanosensitive adhesive structures called podosomes that consist of an actin-rich core surrounded by integrins, adaptor proteins and actin network filaments. They facilitate cell migration via localized degradation of extracellular matrix. Here we show that podosomes of human dendritic cells locate to spots of low physical resistance in the substrate (soft spots) where they can evolve into protrusive structures. Pathogen recognition receptors locate to these protrusive structures where they can trigger localized antigen uptake, processing and presentation to activate T-cells. Our data demonstrate a novel role in antigen sampling for podosomes of dendritic cells. PMID:24424029

  3. Podosomes of dendritic cells facilitate antigen sampling.

    PubMed

    Baranov, Maksim V; Ter Beest, Martin; Reinieren-Beeren, Inge; Cambi, Alessandra; Figdor, Carl G; van den Bogaart, Geert

    2014-03-01

    Dendritic cells sample the environment for antigens and play an important role in establishing the link between innate and acquired immunity. Dendritic cells contain mechanosensitive adhesive structures called podosomes that consist of an actin-rich core surrounded by integrins, adaptor proteins and actin network filaments. They facilitate cell migration via localized degradation of extracellular matrix. Here, we show that podosomes of human dendritic cells locate to spots of low physical resistance in the substrate (soft spots) where they can evolve into protrusive structures. Pathogen recognition receptors locate to these protrusive structures where they can trigger localized antigen uptake, processing and presentation to activate T-cells. Our data demonstrate a novel role in antigen sampling for the podosomes of dendritic cells.

  4. 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

  5. Treatment of follicular non-Hodgkin's lymphoma: the old and the new.

    PubMed

    Friedberg, Jonathan W

    2008-07-01

    Despite remaining an incurable disease, overall survival improvements have been noted in patients with advanced-stage follicular lymphoma. The Follicular Lymphoma International Prognostic Index (FLIPI) is a robust prognostic index in this disease, and continues to provide prognostic information in the rituximab era. Rituximab has significantly changed the management of follicular lymphoma, and the most dramatic impact of rituximab is observed in combination with cytotoxic chemotherapy. However, resistance to rituximab remains a problem, and standard therapy in the rituximab-refractory setting includes radioimmunotherapy, autologous stem cell transplantation, and allogeneic stem cell transplantation. In addition, several novel agents show encouraging activity in follicular lymphoma, including bendamustine, lenalidomide, bortezomib, and other proteasome inhibitors, and BCL2 inhibitors.

  6. Diagnosis of follicular lymphoma of the gastrointestinal tract: A better initial diagnostic workup

    PubMed Central

    Iwamuro, Masaya; Kondo, Eisei; Takata, Katsuyoshi; Yoshino, Tadashi; Okada, Hiroyuki

    2016-01-01

    Due to an increasing incidence and more frequent recognition by endoscopists, gastrointestinal follicular lymphoma has been established as a variant of follicular lymphoma. However, due to its rarity, there are no established guidelines on the optimal diagnostic strategy for patients with primary gastrointestinal follicular lymphoma or secondary gastrointestinal involvement of systemic follicular lymphoma. This review offers an overview and pitfalls to avoid during the initial diagnostic workup of this disease entity. Previously reported case reports, case series, and retrospective studies are reviewed and focus on the disease’s endoscopic and histological features, the roles of computed tomography and positron emission tomography scanning, the clinical utility of the soluble interleukin-2 receptor, and the possible pathogenesis. PMID:26819532

  7. Follicular regulatory T cells control humoral autoimmunity via NFAT2-regulated CXCR5 expression.

    PubMed

    Vaeth, Martin; Müller, Gerd; Stauss, Dennis; Dietz, Lena; Klein-Hessling, Stefan; Serfling, Edgar; Lipp, Martin; Berberich, Ingolf; Berberich-Siebelt, Friederike

    2014-03-10

    Maturation of high-affinity B lymphocytes is precisely controlled during the germinal center reaction. This is dependent on CD4(+)CXCR5(+) follicular helper T cells (TFH) and inhibited by CD4(+)CXCR5(+)Foxp3(+) follicular regulatory T cells (TFR). Because NFAT2 was found to be highly expressed and activated in follicular T cells, we addressed its function herein. Unexpectedly, ablation of NFAT2 in T cells caused an augmented GC reaction upon immunization. Consistently, however, TFR cells were clearly reduced in the follicular T cell population due to impaired homing to B cell follicles. This was TFR-intrinsic because only in these cells NFAT2 was essential to up-regulate CXCR5. The physiological relevance for humoral (auto-)immunity was corroborated by exacerbated lupuslike disease in the presence of NFAT2-deficient TFR cells.

  8. Extreme signet ring cell change in a large B-cell lymphoma of follicular origin.

    PubMed

    Bogusz, Agata Monika; Tierno, Bethany; Brown, Daniel; Pihan, German

    2013-08-01

    We report a large B-cell lymphoma of follicular origin with extreme signet ring cell differentiation. Initially classified as follicular lymphoma on a fine needle core biopsy, the presence of cohesive sheets of extrafollicular signet ring cells triggered an excisional biopsy for further characterization. The excised lymph node revealed focal follicular hyperplasia, follicular lymphoma, and a neoplasm composed of vague nodules and sheets of large atypical cells, all of which virtually exhibited large clear intracytoplasmic vacuoles with peripheral displacement of nuclei. The tumor cells were negative for mucin and lacked immunoreactivity with pancytokeratin, but were strongly immunoreactive with CD20, BCL-2, BCL-6, and CD10 antibodies. Electron microscopy studies revealed electron-lucent vacuoles with no particular internal structure. This case is unique in that extreme signet ring cell differentiation somewhat obscured the true cytological identity of the interfollicular lymphoma and suggested alternative diagnoses.

  9. Porokeratosis with follicular involvement: report of three cases and review of literatures.

    PubMed

    Zhao, Mengjie; Sanusi, Tutyana; Zhao, Yun; Huang, Changzheng; Chen, Siyuan

    2015-01-01

    Porokeratosis is characterized clinically by annular plaques with a distinct peripheral keratotic ridge and histologically by the cornoid lamella. Porokeratosis with follicular involvement is rarely reported. To provide the basis of that follicular porokeratosis is a clinical variant or not. Biopsy was taken from three patients who were diagnosed porokeratosis. Routine stain was made and reviewed the literatures about well-documented cases of porokeratosis with follicular involvement. Porokeratosis with follicular involvement may have some clinical features: asymptomatic, erythematous, brownish or skin-color, less than 1 cm in the areas excluding palm and plantar, which commonly involved on middle-age. But there have still not enough proof as an independent clinical variant.

  10. Porokeratosis with follicular involvement: report of three cases and review of literatures

    PubMed Central

    Zhao, Mengjie; Sanusi, Tutyana; Zhao, Yun; Huang, Changzheng; Chen, Siyuan

    2015-01-01

    Porokeratosis is characterized clinically by annular plaques with a distinct peripheral keratotic ridge and histologically by the cornoid lamella. Porokeratosis with follicular involvement is rarely reported. To provide the basis of that follicular porokeratosis is a clinical variant or not. Biopsy was taken from three patients who were diagnosed porokeratosis. Routine stain was made and reviewed the literatures about well-documented cases of porokeratosis with follicular involvement. Porokeratosis with follicular involvement may have some clinical features: asymptomatic, erythematous, brownish or skin-color, less than 1 cm in the areas excluding palm and plantar, which commonly involved on middle-age. But there have still not enough proof as an independent clinical variant. PMID:26097620

  11. 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.

  12. 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. This image shows the overview for the EDSE in the Microgravity Development Lab (MDL).

  13. Characteristics of ovarian follicular dynamics throughout the estrous cycle of Egyptian buffaloes.

    PubMed

    Barkawi, A H; Hafez, Y M; Ibrahim, S A; Ashour, G; El-Asheeri, Amal K; Ghanem, N

    2009-02-01

    Data of 56 normal and 9 abnormal estrous cycles were collected from 9 Egyptian buffaloes (Bublus bublis) to describe the follicular growth wave pattern. Heat was checked twice daily while, ovaries were scanned daily to monitor the patterns of follicular waves. Day of ovulation was determined when the largest follicle was replaced by corpus haemorrhgicum (CH). Number of waves/cycle, day of emergence of the follicular wave, characteristics of the dominant follicle and corpus luteum (CL) growth features were monitored. Buffaloes displayed mainly two types of follicular waves; two (46.4%) and three (53.6%). In cycles of three wave pattern, time of emergence of the 1st wave post-heat was longer (P<0.05) and number of recruited follicles/wave were larger (P<0.05) compared to the corresponding values of the two wave pattern. Number of recruited follicles in early follicular waves (1st or the 2nd) had larger number (P<0.05) compared to the subsequent ones. Follicles that reached ovulation in both types of estrous cycle had shorter life-span (P<0.05) than the previous ones. Life-span of CH, growing and regressed CL were 3.6+/-0.6, 11.2+/-0.8 and 4.4+/-0.5 days, respectively with no difference in both types of follicular wave. Three types of ovarian disorders were observed. Follicular waves and CL growth features showed unique pattern for each individual. These results demonstrate that buffaloes display two main types of follicular waves with dominance of three wave type.

  14. Follicular keratosis of the chin treated with 1.24R-dihydroxyvitamin D3 ointment.

    PubMed

    Yanagihara, Makoto; Takeda, Kiminobu; Tanabe, Hiroshi; Abe, Shinya; Ishizaki, Hiroshi

    2007-01-01

    In follicular keratosis of the chin, keratotic follicular papules occur on the chin and jaw due to localized prolonged pressure and friction on the naked skin. We present one patient with this disorder. The dermatoscopic examination revealed many well-demarcated yellow spindle bodies in the patchy lesion. Therapy with 1.24R-dihydroxyvitamin D3 ointment was effective during the treatment but had no residual positive effect.

  15. The effect of follicle size and homogeneity of follicular development on the morphokinetics of human embryos.

    PubMed

    Kahraman, Semra; Cetinkaya, Caroline Pirkevi; Cetinkaya, Murat; Yelke, Hakan; Colakoglu, Yesim Kumtepe; Aygun, Melih; Montag, Markus

    2017-07-01

    Our aim was to investigate follicular size (large, ≥17 mm and small, <17 mm) at the time of OPU and homogeneity of follicular development (homogenous development: follicles being present in a homogenous spread of all sizes; heterogeneous: a predominance of small and large follicles) by analysing the morphokinetics of embryo development. In this prospective cohort study, 2526 COCs belonging to 187 patients were cultured to day 5. Embryos were evaluated morphokinetically. Four subgroups were defined: large follicles from heterogeneous cycles (LHet) and homogenous cycles (LHom) and small follicles from heterogeneous cycles (SHet) and homogenous cycles (SHom). Rates of fertilization, blastocyst formation and top and good quality blastocysts were found to be significantly higher in embryos from the LHom group (p < 0.001; p < 0.001; p < 0.001). Small follicles from both homogenous and heterogeneous cycles had significantly lower blastocyst formation and top and good quality blastocyst rates (p < 0.001; p < 0.001). Embryos from SHet had significantly more direct cleavages (p = 0.011). Time to reach blastocyst was shorter in SHom than LHet and LHom (p = 0.002; p = 0.027, respectively). However, once the blastocyst stage was achieved, implantation rates were not significantly different between subgroups, the highest rate being observed in the LHom group. Multivariable analysis revealed that homogeneity of follicular development and follicular size had a significant effect on blastocyst development and quality (p = 0.049; p < 0.001, respectively). Follicular dynamics, illustrated by follicular size and homogeneity of follicular development, influence early human embryo development. Patterns of follicular growth have an impact on embryo quality and viability which is reflected in morphokinetic variables.

  16. 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

  17. Fast Kalman filtering on quasilinear dendritic trees.

    PubMed

    Paninski, Liam

    2010-04-01

    Optimal filtering of noisy voltage signals on dendritic trees is a key problem in computational cellular neuroscience. However, the state variable in this problem-the vector of voltages at every compartment-is very high-dimensional: realistic multicompartmental models often have on the order of N = 10(4) compartments. Standard implementations of the Kalman filter require O(N (3)) time and O(N (2)) space, and are therefore impractical. Here we take advantage of three special features of the dendritic filtering problem to construct an efficient filter: (1) dendritic dynamics are governed by a cable equation on a tree, which may be solved using sparse matrix methods in O(N) time; and current methods for observing dendritic voltage (2) provide low SNR observations and (3) only image a relatively small number of compartments at a time. The idea is to approximate the Kalman equations in terms of a low-rank perturbation of the steady-state (zero-SNR) solution, which may be obtained in O(N) time using methods that exploit the sparse tree structure of dendritic dynamics. The resulting methods give a very good approximation to the exact Kalman solution, but only require O(N) time and space. We illustrate the method with applications to real and simulated dendritic branching structures, and describe how to extend the techniques to incorporate spatially subsampled, temporally filtered, and nonlinearly transformed observations.

  18. Ovarian Follicular Dynamics, Ovarian Follicular Growth, Oocyte Yield, In vitro Embryo Production and Repeated Oocyte Pick Up in Thai Native Heifers Undergoing Superstimulation.

    PubMed

    Chasombat, J; Nagai, T; Parnpai, R; Vongpralub, T

    2013-04-01

    The objective of this study was to compare the effectiveness of the protocols for superstimulation of follicular growth in Thai native heifers. Heifers (n = 20) were randomly divided into four groups of five heifers/group. Heifers were given a single dose by i.m. administration of 100 mg Follicle Stimulating Hormone dissolved in polyvinylpyrrolidone (FSHp) at 24 h. Ovum pick up (OPU) occurred at 72 h (F24O72 protocol; Group 1) or 96 h (F24O96 protocol; Group 2), and at 36 h and OPU at 72 h (F36O72 protocol; Group 3) or 96 h (F36O96 protocol; Group 4) after follicular ablation. The dynamics of ovarian follicular growth were monitored by twice-daily ultrasonographic examinations. Blood sample collections were performed every 12 h after initiation of treatment for assessment of FSH, E2 and P4 profiles. All heifers were subjected to eight repeated sequential sessions of OPU. The follicular deviation commenced 24±5.32 h after follicular ablation in all groups. The circulatory FSH surged quickly from 24 to 36 h (>0.8 ng/ml) after follicular ablation and circulatory estrogen levels steadily increased from 36 h until OPU in all groups. At the end of the OPU sessions, the mean number of aspirated follicles/heifer/session in F36O72 protocol (Group 3) and F36O96 protocol (Group 4) were higher than in the two other groups (p<0.05). The number of cumulus-oocyte complexes (COCs), cleaved and day 8 blastocysts rates in the F36O72 protocol (Group 3) were higher than in the other groups (p<0.05). It can be concluded that a single dose i.m. administration of 100 mg FSHp at 36 h and OPU at 72 h after follicular ablation (F36O72 protocol; Group 3) was the most effective protocol for superstimulation of follicular growth for repeated OPU and subsequent in vitro embryo production in Thai native heifers.

  19. Ovarian Follicular Dynamics, Ovarian Follicular Growth, Oocyte Yield, In vitro Embryo Production and Repeated Oocyte Pick Up in Thai Native Heifers Undergoing Superstimulation

    PubMed Central

    Chasombat, J.; Nagai, T.; Parnpai, R.; Vongpralub, T.

    2013-01-01

    The objective of this study was to compare the effectiveness of the protocols for superstimulation of follicular growth in Thai native heifers. Heifers (n = 20) were randomly divided into four groups of five heifers/group. Heifers were given a single dose by i.m. administration of 100 mg Follicle Stimulating Hormone dissolved in polyvinylpyrrolidone (FSHp) at 24 h. Ovum pick up (OPU) occurred at 72 h (F24O72 protocol; Group 1) or 96 h (F24O96 protocol; Group 2), and at 36 h and OPU at 72 h (F36O72 protocol; Group 3) or 96 h (F36O96 protocol; Group 4) after follicular ablation. The dynamics of ovarian follicular growth were monitored by twice-daily ultrasonographic examinations. Blood sample collections were performed every 12 h after initiation of treatment for assessment of FSH, E2 and P4 profiles. All heifers were subjected to eight repeated sequential sessions of OPU. The follicular deviation commenced 24±5.32 h after follicular ablation in all groups. The circulatory FSH surged quickly from 24 to 36 h (>0.8 ng/ml) after follicular ablation and circulatory estrogen levels steadily increased from 36 h until OPU in all groups. At the end of the OPU sessions, the mean number of aspirated follicles/heifer/session in F36O72 protocol (Group 3) and F36O96 protocol (Group 4) were higher than in the two other groups (p<0.05). The number of cumulus-oocyte complexes (COCs), cleaved and day 8 blastocysts rates in the F36O72 protocol (Group 3) were higher than in the other groups (p<0.05). It can be concluded that a single dose i.m. administration of 100 mg FSHp at 36 h and OPU at 72 h after follicular ablation (F36O72 protocol; Group 3) was the most effective protocol for superstimulation of follicular growth for repeated OPU and subsequent in vitro embryo production in Thai native heifers. PMID:25049814

  20. 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.

  1. MicroRNA Mediating Networks in Granulosa Cells Associated with Ovarian Follicular Development

    PubMed Central

    Zhang, Baoyun; Chen, Long; Feng, Guangde; Xiang, Wei; Zhang, Ke; Chu, Mingxing

    2017-01-01

    Ovaries, which provide a place for follicular development and oocyte maturation, are important organs in female mammals. Follicular development is complicated physiological progress mediated by various regulatory factors including microRNAs (miRNAs). To demonstrate the role of miRNAs in follicular development, this study analyzed the expression patterns of miRNAs in granulosa cells through investigating three previous datasets generated by Illumina miRNA deep sequencing. Furthermore, via bioinformatic analyses, we dissected the associated functional networks of the observed significant miRNAs, in terms of interacting with signal pathways and transcription factors. During the growth and selection of dominant follicles, 15 dysregulated miRNAs and 139 associated pathways were screened out. In comparison of different styles of follicles, 7 commonly abundant miRNAs and 195 pathways, as well as 10 differentially expressed miRNAs and 117 pathways in dominant follicles in comparison with subordinate follicles, were collected. Furthermore, SMAD2 was identified as a hub factor in regulating follicular development. The regulation of miR-26a/b on smad2 messenger RNA has been further testified by real time PCR. In conclusion, we established functional networks which play critical roles in follicular development including pivotal miRNAs, pathways, and transcription factors, which contributed to the further investigation about miRNAs associated with mammalian follicular development. PMID:28316977

  2. An intra-thoracic follicular carcinoma of thyroid: An uncommon presentation.

    PubMed

    Kant, Surya; Srivastava, Anand; Kumar, Rahul; Verma, Ajay Kumar; Mishra, Anand Kumar; Husain, Nuzhat

    2017-01-01

    Follicular carcinoma of thyroid is the second most common type of carcinoma of thyroid, and it may metastasize to bone, lung, brain, and skin. However, the initial presentation of follicular carcinoma of the thyroid as a large intrathoracic mass without any symptoms of thyroid gland enlargement and dysfunction is very rare. We hereby report a case of a 50-year-old male who presented with chief complaints of chest and low back pain. Preliminary evaluation led to the provisional diagnosis of left-sided intrathoracic mass with vertebral metastasis which was suspected to be a case of bronchogenic carcinoma with distant metastasis. Surprisingly, transthoracic biopsy and histopathology revealed metastasis from follicular carcinoma of thyroid. This prompted us for a retrograde evaluation for a primary thyroid malignancy for which an ultrasound and contrast enhanced computed tomography (CECT) of the neck was done which confirmed the presence of a solitary thyroid nodule. Ultrasonography-guided fine-needle aspiration cytology of the nodule revealed follicular carcinoma of thyroid. Histopathological evaluation subsequent to total thyroidectomy revealed follicular carcinoma thyroid, further confirming the diagnosis. The patient was then referred to Department of Nuclear Medicine and Radiotherapy for radionuclide ablation and chemotherapy. We chose to report this case because of its rare presentation as a large intrathoracic mass and the retrograde diagnosis of follicular carcinoma of thyroid. To the best of our knowledge, this is the first report of such a rare case.

  3. Reactive oxygen species level in follicular fluid--embryo quality marker in IVF?

    PubMed

    Das, S; Chattopadhyay, R; Ghosh, S; Ghosh, S; Goswami, S K; Chakravarty, B N; Chaudhury, K

    2006-09-01

    The impact of oxidative stress in female reproduction is not clear. Contradictory reports on the effect of various oxidative stress markers on follicular fluid, oocytes and embryo quality and fertilization potential exist. The objectives of this study were to examine reactive oxygen species (ROS) levels in follicular fluid of women undergoing IVF and to relate these levels to embryo formation and quality. A total of 208 follicular fluid samples were obtained from 78 women undergoing controlled ovarian stimulation and analysed for ROS and lipid peroxidation (LPO). These samples were divided into groups I and II which represented follicular fluid containing grade III and grade II oocytes, respectively. These groups were further subdivided into groups IA, IB, IIA and IIB according to embryo quality. Subgroups IA and IIA consisted of follicular fluid samples corresponding to grade I/II embryo formation. Subgroups IB and IIB represented fertilization failure/pro-nucleolus (PN) arrest/grade III embryos. No significant correlation was observed in ROS levels on comparing groups I and II (P > 0.05). However, ROS levels were observed to be significantly different on comparing groups IA and IB (P < or = 0.01) and groups IIA and IIB (P < or = 0.05). LPO levels further supported our results. ROS levels in follicular fluid appear to play a significant role in embryo formation and quality.

  4. An intra-thoracic follicular carcinoma of thyroid: An uncommon presentation

    PubMed Central

    Kant, Surya; Srivastava, Anand; Kumar, Rahul; Verma, Ajay Kumar; Mishra, Anand Kumar; Husain, Nuzhat

    2017-01-01

    Follicular carcinoma of thyroid is the second most common type of carcinoma of thyroid, and it may metastasize to bone, lung, brain, and skin. However, the initial presentation of follicular carcinoma of the thyroid as a large intrathoracic mass without any symptoms of thyroid gland enlargement and dysfunction is very rare. We hereby report a case of a 50-year-old male who presented with chief complaints of chest and low back pain. Preliminary evaluation led to the provisional diagnosis of left-sided intrathoracic mass with vertebral metastasis which was suspected to be a case of bronchogenic carcinoma with distant metastasis. Surprisingly, transthoracic biopsy and histopathology revealed metastasis from follicular carcinoma of thyroid. This prompted us for a retrograde evaluation for a primary thyroid malignancy for which an ultrasound and contrast enhanced computed tomography (CECT) of the neck was done which confirmed the presence of a solitary thyroid nodule. Ultrasonography-guided fine-needle aspiration cytology of the nodule revealed follicular carcinoma of thyroid. Histopathological evaluation subsequent to total thyroidectomy revealed follicular carcinoma thyroid, further confirming the diagnosis. The patient was then referred to Department of Nuclear Medicine and Radiotherapy for radionuclide ablation and chemotherapy. We chose to report this case because of its rare presentation as a large intrathoracic mass and the retrograde diagnosis of follicular carcinoma of thyroid. To the best of our knowledge, this is the first report of such a rare case. PMID:28360474

  5. Developmental programming: Impact of prenatal testosterone treatment and postnatal obesity on ovarian follicular dynamics.

    PubMed

    Padmanabhan, V; Smith, P; Veiga-Lopez, A

    2012-08-01

    Prenatal testosterone (T) excess leads to reproductive dysfunctions in sheep with obesity exaggerating such defects. Developmental studies found ovarian reserve is similar in control and prenatal T sheep at fetal day 140, with prenatal T females showing increased follicular recruitment and persistence at 10 months of age (postpubertal). This study tested if prenatal T sheep show accelerated depletion prepubertally and if depletion of ovarian reserve would explain loss of cyclicity in prenatal T females and its amplification by postnatal obesity. Stereological examinations were performed at 5 (prepubertal, control and prenatal T) and 21 months (control, prenatal T and prenatal T obese, following estrus synchronization) of age. Obesity was induced by overfeeding from weaning. At 5 months, prenatal T females had 46% less primordial follicles than controls (P < 0.01), supportive of increased follicular depletion. Depletion rate was slower and a higher percentage of growing follicles was present in 21 month than 5 month old prenatal T females (P < 0.01). Postnatal obesity did not exaggerate the impact of prenatal T on follicular recruitment indicating that compounding effects of obesity on loss of cyclicity females is not due to depletion of ovarian reserve. Assessment of follicular dynamics across several time points during the reproductive life span (this and earlier study combined) provides evidence supportive of a shift in follicular dynamics in prenatal T females from one of accelerated follicular depletion initiated prior to puberty to stockpiling of growing follicles after puberty, a time point critical in the development of the polycystic ovary syndrome phenotype.

  6. [Follicular bronchiolitis: report of 3 cases and literature review].

    PubMed

    Dai, J; Cai, H R; Li, Y; Meng, F Q; Wu, J Q

    2017-06-12

    Objective: To improve understanding of the characteristics of follicular bronchiolitis(FB). Methods: The clinical data of 3 patients with FB confirmed by thoracoscopic lung biopsy were retrospectively analyzed. A literature search was performed with "follicular bronchiolitis" as the key word in China Knowledge Resource Integrated Database, Wanfang and PubMed, Ovid Database. The time interval was from January 1947 to December 2015. Related articles of FB were retrieved and the clinical, radiographic characteristics and prognosis were analyzed. Results: Among the 3 patients, 1 was male and 2 were female, aging 32-55 years. Two patients were asymptomatic, and 1 patient presented with fever, cough and dyspnea. Two patients showed normal pulmonary ventilatory function with decreased diffusive function, and 1 patient showed normal pulmonary function. The predominant HRCT findings were bilateral multiple small nodules and cystic opacities, patchy ground-glass opacities, reticular opacities and traction bronchiectasis. The pathological examination by thoracoscopic biopsy revealed bronchiolar and peribronchiolar lymphoid follicles. All patients were treated with corticosteroids, with 2 patients receiving immunosuppressants. Follow-up HRCT after 1-2 months showed no improvement, and further follow-up HRCT after 2-4 years revealed no change in 2 patients while the other patient had increased pulmonary nodules and cystic opacities. Seventeen articles concerning FB with complete records were included in the literature review. A total of 64 patients were reported in these articles. The typical images were bilateral multiple small nodules and ground-glass opacities, reticular opacities, and cystic opacities. The majority of patients improved after treatment of corticosteroids and (or) immunosuppressants. But our 3 cases showed no improvement. Conclusions: FB is a rare small airway disease which has non-specific clinical manifestations and pulmonary function. The most common

  7. Nomenclature Revision for Encapsulated Follicular Variant of Papillary Thyroid Carcinoma

    PubMed Central

    Nikiforov, Yuri E.; Seethala, Raja R.; Tallini, Giovanni; Baloch, Zubair W.; Basolo, Fulvio; Thompson, Lester D. R.; Barletta, Justine A.; Wenig, Bruce M.; Ghuzlan, Abir Al; Kakudo, Kennichi; Giordano, Thomas J.; Alves, Venancio A.; Khanafshar, Elham; Asa, Sylvia L.; El-Naggar, Adel K.; Gooding, William E.; Hodak, Steven P.; Lloyd, Ricardo V.; Maytal, Guy; Mete, Ozgur; Nikiforova, Marina N.; Nosé, Vania; Papotti, Mauro; Poller, David N.; Sadow, Peter M.; Tischler, Arthur S.; Tuttle, R. Michael; Wall, Kathryn B.; LiVolsi, Virginia A.; Randolph, Gregory W.; Ghossein, Ronald A.

    2017-01-01

    IMPORTANCE Although growing evidence points to highly indolent behavior of encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC), most patients with EFVPTC are treated as having conventional thyroid cancer. OBJECTIVE To evaluate clinical outcomes, refine diagnostic criteria, and develop a nomenclature that appropriately reflects the biological and clinical characteristics of EFVPTC. DESIGN, SETTING, AND PARTICIPANTS International, multidisciplinary, retrospective study of patients with thyroid nodules diagnosed as EFVPTC, including 109 patients with noninvasive EFVPTC observed for 10 to 26 years and 101 patients with invasive EFVPTC observed for 1 to 18 years. Review of digitized histologic slides collected at 13 sites in 5 countries by 24 thyroid pathologists from 7 countries. A series of teleconferences and a face-to-face conference were used to establish consensus diagnostic criteria and develop new nomenclature. MAIN OUTCOMES AND MEASURES Frequency of adverse outcomes, including death from disease, distant or locoregional metastases, and structural or biochemical recurrence, in patients with noninvasive and invasive EFVPTC diagnosed on the basis of a set of reproducible histopathologic criteria. RESULTS Consensus diagnostic criteria for EFVPTC were developed by 24 thyroid pathologists. All of the 109 patients with noninvasive EFVPTC (67 treated with only lobectomy, none received radioactive iodine ablation) were alive with no evidence of disease at final follow-up (median [range], 13 [10–26] years). An adverse event was seen in 12 of 101 (12%) of the cases of invasive EFVPTC, including 5 patients developing distant metastases, 2 of whom died of disease. Based on the outcome information for noninvasive EFVPTC, the name “noninvasive follicular thyroid neoplasm with papillary-like nuclear features” (NIFTP) was adopted. A simplified diagnostic nuclear scoring scheme was developed and validated, yielding a sensitivity of 98.6% (95% CI, 96.3%

  8. 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.

  9. 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

  10. Cell-secreted Flavins Bound to Membrane Cytochromes Dictate Electron Transfer Reactions to Surfaces with Diverse Charge and pH

    PubMed Central

    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

  11. 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

  12. Hydroxypropyl-β-cyclodextrin spikes local inflammation that induces Th2 cell and T follicular helper cell responses to the coadministered antigen.

    PubMed

    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; Ishii, Ken J

    2015-03-15

    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. Copyright © 2015 by The American Association of Immunologists, Inc.

  13. 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.

  14. [Melanoma immunotherapy: dendritic cell vaccines].

    PubMed

    Lozada-Requena, Ivan; Núñez, César; Aguilar, José Luis

    2015-01-01

    This is a narrative review that shows accessible information to the scientific community about melanoma and immunotherapy. Dendritic cells have the ability to participate in innate and adaptive immunity, but are not unfamiliar to the immune evasion of tumors. Knowing the biology and role has led to generate in vitro several prospects of autologous cell vaccines against diverse types of cancer in humans and animal models. However, given the low efficiency they have shown, we must implement strategies to enhance their natural capacity either through the coexpression of key molecules to activate or reactivate the immune system, in combination with biosimilars or chemotherapeutic drugs. The action of natural products as alternative or adjuvant immunostimulant should not be ruled out. All types of immunotherapy should measure the impact of myeloid suppressor cells, which can attack the immune system and help tumor progression, respectively. This can reduce the activity of cellular vaccines and/or their combinations, that could be the difference between success or not of the immunotherapy. Although for melanoma there exist biosimilars approved by the Food and Drug Administration (FDA), not all have the expected success. Therefore it is necessary to evaluate other strategies including cellular vaccines loaded with tumor antigenic peptides expressed exclusively or antigens from tumor extracts and their respective adjuvants.

  15. Dendritic cells in hematological malignancies.

    PubMed

    Galati, Domenico; Corazzelli, Gaetano; De Filippi, Rosaria; Pinto, Antonio

    2016-12-01

    Dendritic cells (DCs) are bone-marrow-derived immune cells accounted for a crucial role in initiating and modulating the adaptive immune response and supporting the innate immune response independently from T cells. While functioning as the most effective antigen-presenting cells within the immune system, DCs can otherwise induce tolerance in central and peripheral lymphoid organs acting therefore as suppressors rather than stimulators of the immune response. Within mechanisms regulating antitumor immunity, DCs can capture antigens from viable or damaged tumor cells and present the processed peptides to T-cells to prompt the generation and maintenance of an effective tumor-specific T-cell response. Upon a complex cross-talk with other cellular components of the tumor microenvironment, DCs can, on the other hand, exert a potent antigen-dependent and -independent tolerogenic function by favoring the process of tumor immune evasion. Due to this dual-role in balancing antitumor immunity and tolerance, possibly linked to distinct developmental stages and functional subsets, several studies have addressed the regulatory significance of DCs in different types of malignancies. This review summarizes the most significant pieces of evidence highlighting the critical relevance of bone marrow-derived DCs within the immune pathways regulating pathogenesis and progression of hemopoietic tumors. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  16. 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.

  17. 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.

  18. The bottleneck: mitochondrial imperatives in oogenesis and ovarian follicular fate.

    PubMed

    Jansen, R P; de Boer, K

    1998-10-25

    Molecular geneticists and ovarian physiologists today face the challenge of defining and reconciling two major biological imperatives that each center on oogenesis, folliculogenesis and competition between ovarian follicles: (1), defining how the mitochondrial genome--important in both aging and a number of serious mitochondrial diseases--is refreshed and purified as it passes, via the oocyte's cytoplasm, from one generation to the next; and (2), endeavouring to discover what cytoplasmic factor(s) it is that permits some eggs but not others to produce viable embryos and ongoing pregnancies. We review here in detail the passage of mitochondria through the female germ cell line. For mitochondria, the processes of oogenesis, follicle formation and loss constitute a restriction/amplification/constraint event of the kind predicted by L. Chao for purification and refinement of a haploid genome. We argue that maintaining the integrity of mitochondrial inheritance is such a strong evolutionary imperative that we should expect at least some features of ovarian follicular formation, function and loss to be primarily adapted to this specific purpose. We predict, moreover, that to prevent accumulation of mild mitochondrial genomes in the population there is a need for physiological female sterility prior to total depletion of ovarian oocytes, a phenomenon for which there is empirical evidence and which we term the oöpause.

  19. Immunophenotypic and genotypic characterization of progression in follicular lymphomas.

    PubMed

    Natkunam, Yasodha; Soslow, Robert; Matolcsy, Andras; Dolezal, Milana; Bhargava, Vivek; Knowles, Daniel M; Warnke, Roger

    2004-06-01

    Progression of follicular lymphomas (FLs) is often accompanied by a spectrum of histologic changes and an aggressive clinical course. Although molecular alterations have been implicated in this event, the underlying factors are largely unknown. We studied the expression of selected tumor suppressor genes (P53 and retinoblastoma [RB]), oncogenes (MYC and BCL2), and a transferrin-receptor related protein (Trump) in sequential biopsies in 16 patients. Eleven patients progressed from grade I or II FL to aggressive B-cell lymphomas with diffuse morphology, whereas 5 patients presented with diffuse aggressive lymphomas and recurred with indolent lymphomas. Immunoreactivity for P53 correlated with higher histologic grade in lymphomas progressing from indolent to aggressive; however, only 1 patient who presented with aggressive lymphoma demonstrated a P53 gene mutation. Neither P53 immunoreactivity nor genotypic alterations correlated with presentation with an aggressive histology and relapse with FL. Growth fraction, as assessed by Ki-67 staining, and Trump expression correlated with histologic grade. Immunoreactivity for RB, BCL2, and MYC was seldom associated with progression. Eight of 9 cases tested exhibited identical immunoglobulin heavy and light chain rearrangements or identical BCL2 gene rearrangements in the sequential lymphomas. We conclude that P53 and Trump protein expression and proliferation activity correlate with histologic grade, but not with recurrence or progression of FL. Our results further indicate that progression of FL to diffuse aggressive lymphomas and presentation of an aggressive B-cell lymphoma followed by FL are clonally related.

  20. Inherited genetic variation and overall survival following follicular lymphoma

    PubMed Central

    Gibson, Todd M.; Wang, Sophia S.; Cerhan, James R.; Maurer, Matthew J.; Hartge, Patricia; Habermann, Thomas M.; Davis, Scott; Cozen, Wendy; Lynch, Charles F.; Severson, Richard K.; Rothman, Nathaniel; Chanock, Stephen J.; Morton, Lindsay M.

    2012-01-01

    Follicular lymphoma (FL) has variable progression and survival, and improved identification of patients at high risk for progression would aid in identifying patients most likely to benefit from alternative therapy. In a sample of 244 FL cases identified during a population-based case-control study of non-Hodgkin lymphoma (NHL), we examined 6,679 tag SNPs in 488 gene regions for associations with overall FL survival. Over a median follow-up of 89 months with 65 deaths in this preliminary study, we identified 5 gene regions (BMP7, GALNT12, DUSP2, GADD45B, and ADAM17) that were associated with overall survival from FL. Results did not meet the criteria for statistical significance after adjustment for multiple hypothesis testing. These results, which support a role for host factors in determining the variable progression of FL, serve as an initial examination that can inform future studies of genetic variation and FL survival. However, they require replication in independent populations, as well as assessment in rituximab-treated patients. PMID:22473939

  1. T follicular helper cell programming by cytokine-mediated events.

    PubMed

    Read, Kaitlin A; Powell, Michael D; Oestreich, Kenneth J

    2016-11-01

    CD4(+) T cells, or T helper cells, are critical mediators and coordinators of adaptive immunity. Unique effector T helper cell populations have been identified that perform distinct functions in response to pathogenic infection. The T follicular helper (Tfh) cells are one such subset, which has been identified as the primary T-cell population responsible for interacting with B cells to promote effective antibody-mediated immune responses. Since their initial description at the turn of the century, and subsequent classification as a distinct T helper cell subset, there has been substantial interest in elucidating the regulatory mechanisms that govern Tfh cell formation. The collective insight from this body of work has demonstrated that Tfh cell differentiation is a complex and multistage process regulated by a litany of cell-intrinsic and cell-extrinsic factors. As with the development of the other recognized T helper cell subsets, specific cytokines exercise prominent roles in both the positive and negative regulation of Tfh cell development. However, the exact composition of, and stage-specific requirements for, these environmental factors in the governance of Tfh cell differentiation remain incompletely understood. In this review, we summarize what is known regarding the role of cytokines in both the promotion and inhibition of Tfh cell differentiation and function. © 2016 John Wiley & Sons Ltd.

  2. Systemic follicular lymphoma with massive intestinal involvement with leukemic manifestation.

    PubMed

    Ono, Yuichiro; Aoki, Kazunari; Kato, Aiko; Arima, Hiroshi; Takiuchi, Yohko; Nagano, Seiji; Tabata, Sumie; Yanagita, Sohshi; Matsushita, Akiko; Maruoka, Hayato; Imai, Yukihiro; Ishikawa, Takayuki; Takahashi, Takayuki

    2011-01-01

    A 30-year-old man was referred to our hospital with leukocytosis and fecal occult blood. His white blood cell count was 30.2 × 10(9)/L with 79% small- to medium-sized lymphocytes. Surface antigen analysis revealed that these lymphocytes were positive for CD19, CD20, CD10, and CD23, but negative for CD5. The lymphocytes infiltrated the bone marrow. On endoscopic examination of the duodenum and jejunum, many small polypoid lesions were observed. A histologic picture of a biopsied lesion showed diffuse infiltration of small- to medium-sized lymphocytes in the submucosal region. On immunohistochemistry, these lymphocytes were positive for CD20, BCL2, and CD10 (weakly). Polymerase chain reaction analysis of cells from peripheral blood, bone marrow, and intestinal lesion showed a fusion product of BCL2 and immunoglobulin heavy chain (IGH) genes. The fused BCL2/IGH gene was also demonstrated by fluorescence in situ hybridization in the same cell sources. Computed tomography scanning showed marked wall thickening throughout the small intestine and enlarged mesenteric lymph nodes. A diagnosis of follicular lymphoma with massive intestinal involvement in a leukemic state was made. After 6 courses of rituximab-combined CHOP chemotherapy, complete remission was obtained.

  3. Emerging concepts in T follicular helper cell responses to malaria.

    PubMed

    Hansen, Diana S; Obeng-Adjei, Nyamekye; Ly, Ann; Ioannidis, Lisa J; Crompton, Peter D

    2017-02-01

    Antibody responses to malaria and candidate malaria vaccines are short-lived in children, leaving them susceptible to repeated malaria episodes. Because T follicular helper (TFH) cells provide critical help to B cells to generate long-lived antibody responses, they have become the focus of recent studies of Plasmodium-infected mice and humans. The emerging data converge on common themes, namely, that malaria-induced TH1 cytokines are associated with the activation of (i) T-like memory TFH cells with impaired B cell helper function, and (ii) pre-TFH cells that acquire Th1-like features (T-bet expression, IFN-γ production), which impede their differentiation into fully functional TFH cells, thus resulting in germinal center dysfunction and suboptimal antibody responses. Deeper knowledge of TFH cells in malaria could illuminate strategies to improve vaccines through modulating TFH cell responses. This review summarizes emerging concepts in TFH cell responses to malaria. Copyright © 2016. Published by Elsevier Ltd.

  4. 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.

  5. Autologous and allogeneic hematopoietic stem cell transplantation in follicular lymphoma.

    PubMed

    Bhatt, V R; Armitage, J O

    2016-01-01

    High-dose chemotherapy and autologous stem cell transplantation (ASCT) improve survival in follicular lymphoma; however, relapse remains the most common cause of death. The lower risk of relapse with allogeneic SCT (alloSCT) is offset by a high transplant-related mortality (TRM). English articles indexed in the MEDLINE database were reviewed to discuss the role of graft purging, rituximab maintenance after ASCT, reduced-intensity conditioning (RIC) alloSCT, T-cell depletion, donor lymphocyte infusion (DLI) and alternate donor sources. Optimal salvage consolidation strategy may utilize ASCT following non-total body irradiation-based conditioning regimen in second remission. Rituximab maintenance after ASCT may improve molecular remission but is not yet shown to improve overall survival. RIC alloSCT permits its use in older and less-fit patients. Studies with T-cell depleted graft failed to reduce TRM despite a decline in graft-versus-host disease; however, these studies did demonstrate a therapeutic role of DLI in post-transplant relapses. In recent years, haploidentical and umbilical cord blood donors have emerged as alternative donor sources, with outcomes comparable to matched unrelated donor SCT. In the future, incorporation of novel therapeutic agents, improved risk-adapted treatment strategies, and advancement of transplant techniques may provide a better chance of survival.

  6. Computer-aided classification of centroblast cells in follicular lymphoma.

    PubMed

    Belkacem-Boussaid, Kamel; Pennell, Michael; Lozanski, Gerard; Shana'ah, Arwa; Gurcan, Metin

    2010-10-01

    To distinguish centroblast cells from non-centroblast cells using a novel automated method in follicular lymphoma cases and measure its performance on cases obtained by a consensus of six pathologists. Geometric and color texture features were used in the training and testing of the supervised quadratic discriminant analysis classifier. The technique was trained and tested on a data set composed of 218 centroblast images and 218 non-centroblast images. Computer performance was tested by measuring sensitivity and specificity among cells classified as centroblast and non-centroblast by consensus of six board-certified hematopathologists. Automated classification distinguished centroblast from non-centroblast cells with a classification accuracy of 82.56% and sensitivity and specificity of 86.67% and 86.96%, respectively, when the approach was tested. The novelty of our approach is the identification of the centroblast cells with prior information and the introduction of the principal component analysis in the spectral domain to extract texture color features.

  7. Endocrine and paracrine controls of canine follicular development and function.

    PubMed

    Songsasen, N; Nagashima, J; Thongkittidilok, C

    2017-04-01

    Canid reproduction is unique among other mammals in that females experience long and variable periods of ovarian inactivity. While the domestic dog exhibits a non-seasonal, largely sporadic monoestrus occurring once or twice a year, most wild canids, such as the gray wolf (Canis lupus) and red wolf (Canis rufus), are seasonal breeders with onset apparently dependent on species, latitudinal location and/or variety of environment factors. Neuroendocrine controls of ovarian functions have been mostly studied in the dog, but less so in their wild counterparts, due to difficulties in regular blood sampling. Yet, development of non-invasive hormone monitoring has advanced the understanding of reproductive cycle in wild canids. Recent advances in in vitro follicle culture technology also have begun to provide insights into paracrine controls of canid ovarian folliculogenesis. This review highlights current knowledge on canid reproduction with emphasis on endocrine and paracrine controls of follicular development. We also discuss future research priorities, including advancing the understanding of anoestrous termination and role of paracrine factors in canine folliculogenesis. © 2017 Blackwell Verlag GmbH.

  8. Follicular lymphomas and their transformation: Past and current research.

    PubMed

    Mendez, Miriam; Torrente, Maria; Provencio, Mariano

    2017-06-01

    Follicular lymphoma (FL) is the second most common type of non-Hodgkin lymphoma (NHL). Histological transformation (HT) refers to the evolution of a clinically indolent NHL to a clinically aggressive one, defined as those lymphomas in which survival is limited to a few months when untreated. Areas covered: HT is associated with rapid progression of lymphadenopathy, infiltration of extranodal sites, development of systemic symptoms, and elevated serum level of lactate dehydrogenase (LDH). It is frequently related to a poor prognosis, and the median survival after transformation is less than 2 years. Transformation to diffuse large B cell lymphoma (DLBCL) in patients with FL occurs at an annual rate of approximately 3% for the first 15 years, after which the risk of HT falls for reasons that remain unclear. Expert commentary: Although it has long been assumed that transformation reflects the emergence of an aggressive subclone of cells from the primary FL, recent studies suggest that FL transformation might also arise by divergent evolution from a more immature common progenitor cell. Studies on genomic changes and DNA sequencing have shed some light onto the process of transformation. Nowadays, we know that HT is a complex process where several molecular pathways are involved.

  9. 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

  10. [What's new in follicular thyroid cancer management in 2014?].

    PubMed

    Abeillon-du Payrat, J; Caron, P; Borson-Chazot, F

    2014-10-01

    The American Thyroid Association has presented new guidelines for the management of thyroid cancer. These guidelines tend to appreciate more accurately the individual risk of patients, to adapt accordingly the treatment and the follow up. The initial risk stratification has been completed, especially precising the risk of N1 patients, follicular thyroid cancers, and the prognostic impact of molecular markers. Indications, doses and modalities of radioiodine (RAI) have been reevaluated, restricting its utilization in order to avoid overtreatment of low risk patients. Moreover the response to initial treatment allows to restratify the risk of the patients, and to adapt the monitoring and the thyroid hormone therapy management. The risk of suppressive thyroid hormone therapy has also to be considered. Concerning advanced thyroid cancer, prognosis is mainly depending on its RAI sensitivity. The systemic treatment of progressive, threatening refractory cancers is nowadays based on targeted therapy. However none of these treatments has demonstrated an improvement in overall survival, and side effects are frequent. Fagin et al presented promising results concerning short term treatment with selective inhibitors of the MAPK pathway, able to partially restore RAI sensitivity of refractory lesions in murine models, and recently in human patients.

  11. Follicular lymphoma (FL): Immunological tolerance theory in FL.

    PubMed

    García-Muñoz, Ricardo; Panizo, Carlos

    2017-02-01

    The ultimate cause of follicular lymphoma (FL) remains unknown. Remarkably, almost nothing is known about immunological tolerance mechanisms that might contribute to FL development. Immunological tolerance mechanisms, like other stimuli, also induce persistent changes of B cell receptors that induce genetic instability and molecular aberrations promoting the development of a neoplasm. Using the same method as Burnet, we provide a new perspective taking advantage of the comparison of a normal linear B cell differentiation process and FL development within the framework of clonal selection theory. We propose that FL is a malignancy of cells that acquire both translocation t(14;18) and self-BCR, inducing them to proliferate and mature, resistant to negative selection. Additional genetic damage induced by non-apoptotic tolerance mechanisms, such as receptor editing, may transform a self-reactive B cell with t(14;18) into an FL. The result of tolerogenic mechanisms and genetic aberrations is the survival of FL B cell clones with similar markers and homogenous gene expression signatures despite the different stages of maturation at which the molecular damage occurs. To antagonize further growth advantage due to self-antigen recognition and chronic activation of tolerance mechanisms in the apoptosis-resistant background of FL B cells, inhibitors of BCR signaling may be promising therapeutic options.

  12. Exclusive facial porokeratosis: histopathologically showing follicular cornoid lamellae.

    PubMed

    Lee, Yoonhee; Choi, Eung Ho

    2011-11-01

    Porokeratosis is a heterogeneous group of disorders that are mostly inherited in an autosomal dominant fashion. It has a wide variety of clinical manifestations with a characteristic histological finding of cornoid lamella. Porokeratosis usually affects the trunk or the extremities. Exclusive facial lesions are rare, although 15% of patients with disseminated, superficial, actinic porokeratosis do have facial lesions. Herein, we discuss the case of a 25-year-old woman who noticed the appearance of well-defined, brownish, macular lesions located on both cheeks. She had no other symptoms. A skin examination showed well-demarcated, multiple, brownish macules with raised hyperkeratotic borders on both cheeks and a half-palm-sized, arcuate-shaped lesion formed by grouped macules on the right cheek. No other parts of the body were affected. Histopathological examination of a biopsy specimen obtained from the hyperkeratotic margin gave a diagnosis of porokeratosis with follicular involvement of the cornoid lamellae. Topical pimecrolimus was applied twice a day to the lesions, although little improvement was achieved after 2 months. © 2011 Japanese Dermatological Association.

  13. The bHLH-PAS protein Spineless is necessary for the diversification of dendrite morphology of Drosophila dendritic arborization neurons

    PubMed Central

    Kim, Michael D.; Jan, Lily Yeh; Jan, Yuh Nung

    2006-01-01

    Dendrites exhibit a wide range of morphological diversity, and their arborization patterns are critical determinants of proper neural connectivity. How different neurons acquire their distinct dendritic branching patterns during development is not well understood. Here we report that Spineless (Ss), the Drosophila homolog of the mammalian aryl hydrocarbon (dioxin) receptor (Ahr), regulates dendrite diversity in the dendritic arborization (da) sensory neurons. In loss-of-function ss mutants, class I and II da neurons, which are normally characterized by their simple dendrite morphologies, elaborate more complex arbors, whereas the normally complex class III and IV da neurons develop simpler dendritic arbors. Consequently, different classes of da neurons elaborate dendrites with similar morphologies. In its control of dendritic diversity among da neurons, ss likely acts independently of its known cofactor tango and through a regulatory program distinct from those involving cut and abrupt. These findings suggest that one evolutionarily conserved role for Ahr in neuronal development concerns the diversification of dendrite morphology. PMID:17015425

  14. Molecules and mechanisms of dendrite development in Drosophila.

    PubMed

    Corty, Megan M; Matthews, Benjamin J; Grueber, Wesley B

    2009-04-01

    Neurons are one of the most morphologically diverse cell types, in large part owing to their intricate dendrite branching patterns. Dendrites are structures that are specialized to receive and process inputs in neurons, thus their specific morphologies reflect neural connectivity and influence information flow through circuits. Recent studies in Drosophila on the molecular basis of dendrite diversity, dendritic guidance, the cell biology of dendritic branch patterning and territory formation have identified numerous intrinsic and extrinsic cues that shape diverse features of dendrites. As we discuss in this review, many of the mechanisms that are being elucidated show conservation in diverse systems.

  15. Dendritic spine dysgenesis in neuropathic pain.

    PubMed

    Tan, Andrew M; Waxman, Stephen G

    2015-08-05

    Neuropathic pain is a significant unmet medical need in patients with variety of injury or disease insults to the nervous system. Neuropathic pain often presents as a painful sensation described as electrical, burning, or tingling. Currently available treatments have limited effectiveness and narrow therapeutic windows for safety. More powerful analgesics, e.g., opioids, carry a high risk for chemical dependence. Thus, a major challenge for pain research is the elucidation of the mechanisms that underlie neuropathic pain and developing targeted strategies to alleviate pathological pain. The mechanistic link between dendritic spine structure and circuit function could explain why neuropathic pain is difficult to treat, since nociceptive processing pathways are adversely "hard-wired" through the reorganization of dendritic spines. Several studies in animal models of neuropathic pain have begun to reveal the functional contribution of dendritic spine dysgenesis in neuropathic pain. Previous reports have demonstrated three primary changes in dendritic spine structure on nociceptive dorsal horn neurons following injury or disease, which accompany chronic intractable pain: (I) increased density of dendritic spines, particularly mature mushroom-spine spines, (II) redistribution of spines toward dendritic branch locations close to the cell body, and (III) enlargement of the spine head diameter, which generally presents as a mushroom-shaped spine. Given the important functional implications of spine distribution, density, and shape for synaptic and neuronal function, the study of dendritic spine abnormality may provide a new perspective for investigating pain, and the identification of specific molecular players that regulate spine morphology may guide the development of more effective and long-lasting therapies.

  16. Characterization of chicken epidermal dendritic cells

    PubMed Central

    Igyártó, Botond-Zoltán; Lackó, Erzsébet; Oláh, Imre; Magyar, Attila

    2006-01-01

    It has been known for 15 years that the chicken epidermis contains ATPase+ and major histocompatibility complex class II-positive (MHCII+) dendritic cells. These cells were designated as Langerhans cells but neither their detailed phenotype nor their function was further investigated. In the present paper we demonstrate a complete overlapping of ATPase, CD45 and vimentin staining in all dendritic cells of the chicken epidermis. The CD45+ ATPase+ vimentin+ dendritic cells could be divided into three subpopulations: an MHCII+ CD3– KUL01+ and 68.1+ (monocyte-macrophage subpopulation markers) subpopulation, an MHCII– CD3– KUL01– and 68.1– subpopulation and an MHCII– CD3+ KUL01– and 68.1– subpopulation. The first population could be designated as chicken Langerhans cells. The last population represents CD4– CD8– T-cell receptor-αβ– and -γδ– natural killer cells with cytoplasmic CD3 positivity. The epidermal dendritic cells have a low proliferation rate as assessed by bromodeoxyuridine incorporation. Both in vivo and in vitro experiments showed that dendritic cells could be mobilized from the epidermis. Hapten treatment of epidermis resulted in the decrease of the frequency of epidermal dendritic cells and hapten-loaded dendritic cells appeared in the dermis or in in vitro culture of isolated epidermis. Hapten-positive cells were also found in the so-called dermal lymphoid nodules. We suggest that these dermal nodules are responsible for some regional immunological functions similar to the mammalian lymph nodes. PMID:16889640

  17. Human spleen contains phenotypic subsets of macrophages and dendritic cells that occupy discrete microanatomic locations.

    PubMed Central

    Buckley, P. J.; Smith, M. R.; Braverman, M. F.; Dickson, S. A.

    1987-01-01

    Macrophages (M phi s) are an important component of the immune response and mediate numerous other functions. Phenotypic and functional subsets of circulating monocytes have been described, but few similar studies have analyzed M phi s in human tissues. By use of immunohistochemical techniques and a large number of monoclonal antibodies, the presence and distribution of phenotypic subpopulations of M phi s and dendritic cells in human spleen were assessed. The results of this study show that different subsets of M phi s and dendritic cells are present in the spleen and that some of these occupy discrete microanatomic locations. In the red pulp (RP) certain groups of antigens are expressed by different proportions of uniformly distributed M phi s in the cords. On the other hand, some antigens are present on M phi s that form clusters of variable size within the red pulp. M phi s in the splenic marginal zone (MZ) share some antigens with red pulp M phi s, but in addition express CR3, Mo-2, 61D3, and 63D3. These antigens are found on only a few RP M phi s. MZ cells expressing one antigen shared with RP M phi s (Leu-3a,b) and one present largely on the MZ cells (63D3) form clusters around small vessels; these structures resemble the so-called splenic ellipsoids that may play a role in the trapping of circulating antigens. Phagocytic M phi s (tingible body M phi s) of the white pulp follicular germinal centers were also shown to differ from RP and MZ cels with respect to the expression of the antigens detected by anti-FcR, Leu-M3, Mo-2, 25F9, and anti-CR3. The unique topographical and surface antigenic features of dendritic cells were confirmed by this study. Furthermore, these cells were found to share a number of antigens with RP, MZ, and white pulp M phi s, which suggests that they may be derived from a common progenitor. The presence of phenotypic subpopulations and variation in distribution among human splenic phagocytic cells and dendritic cells may be indicative

  18. Follicular neoplasms of the thyroid: importance of clinical and cytological correlation.

    PubMed

    Granados-García, Martín; Cortés-Flores, Ana Olivia; del Carmen González-Ramírez, Imelda; Cano-Valdez, Ana María; Flores-Hernández, Lorena; Aguilar-Ponce, José Luis

    2010-01-01

    Thyroid cancer presents as nodules. Thyroid nodules are frequent, but only 5-30% are malignant. Fine needle aspiration biopsy (FNAB) is useful for initial evaluation; nevertheless, malignancy is uncertain when follicular neoplasm is reported. Some factors can be associated with malignancy. Therefore, we analyzed our follicular neoplasms in order to identify those factors associated with a higher risk of malignancy. We analyzed the clinical files of consecutive patients with cytological diagnoses of follicular neoplasm. From 1,005 cases of thyroid nodules, 121 were follicular neoplasms according to cytology. Of these, 75 were surgically treated. Definitive report showed 45 benign (60%) and 30 malignant (40%) cases. Benign cases included 29 goiters, 11 follicular adenomas, and 5 cases of thyroiditis. Malignant cases were comprised of 12 papillary carcinomas, 4 follicular carcinomas, 3 papillary carcinomas-follicular variant, 1 lymphoma, 1 teratoma, 5 medullary carcinomas, 2 insular carcinomas, 1 anaplastic carcinoma and 1 metastatic breast carcinoma. Tumor size of benign lesions was 3.43 ± 2.04 cm, and 4.67 ± 2.78 (p = 0.049) for malignant lesions. Age was 46.95 ± 15.39 years for benign lesions and 48.67 ± 17.28 for malignant lesions (p = 0.66). Fifty percent of males showed malignancy vs. 37.7% of females (p < 0.005). Our results suggest that size and gender, but not age, are associated with cytological pattern. Ultrasonographic characteristics may be useful discriminating patients with a higher risk of malignancy. FNAB is a useful tool for initial evaluation of thyroid nodules, but clinical evaluation can enhance predictive value.

  19. Comparison of computed tomography features between follicular neoplasm and nodular hyperplasia.

    PubMed

    Lee, Kwang Hwi; Kim, Dong Wook; Baek, Jin Wook; Lee, Yoo Jin; Choo, Hye Jung; Cho, Young Jun; Lee, Sun Joo; Park, Young Mi; Jung, Soo Jin; Baek, Hye Jin

    2016-10-03

    To date, appropriate management for Bethesda IV thyroid nodules is controversial, and no specific features of follicular neoplasm and nodular hyperplasia on ultrasonography, computed tomography (CT), or other imaging modalities have been reported. This study aimed to compare CT features of follicular neoplasm and nodular hyperplasia and to determine the specific CT features that could be used to distinguish follicular neoplasm from nodular hyperplasia. In 122 patients who underwent preoperative CT of the neck and thyroid surgery, 59 follicular neoplasms and 65 nodular hyperplasias were included. In each case, non-enhanced and contrast-enhanced CT images were obtained, and a single radiologist retrospectively analyzed CT images, including degree and pattern of attenuation, nodular configuration, margin, shape, pattern of calcification, degree and pattern of nodular enhancement, and CT halo sign. A univariate and multivariate logistic regression analyses were used to evaluate the predictive power of each variable and CT features with a high predictive power, respectively. According to the univariate analysis, iso-attenuation, intraglandular configuration, smooth margin, ovoid shape, decreased enhancement, and absence of CT halo sign were more frequently observed in nodular hyperplasia (p < 0.05), whereas low attenuation, expansile configuration, lobulated margin, taller-than-wide shape, increased enhancement, and presence of computed tomography halo sign were more frequently observed in follicular neoplasm (p < 0.05). Multivariate analysis revealed significant differences in configuration (OR: 2.73, 1.13-6.57), degree of enhancement (OR: 2.14, 1.21-3.78), and presence of CT halo sign (OR: 7.97, 2.74-23.37) between follicular neoplasm and nodular hyperplasia (p < 0.05). Neck CT may be helpful for distinguishing follicular neoplasm from nodular hyperplasia. Rretrospectively registered.

  20. Genomic imbalances during transformation from follicular lymphoma to diffuse large B-cell lymphoma.

    PubMed

    Berglund, Mattias; Enblad, Gunilla; Thunberg, Ulf; Amini, Rose-Marie; Sundström, Christer; Roos, Göran; Erlanson, Martin; Rosenquist, Richard; Larsson, Catharina; Lagercrantz, Svetlana

    2007-01-01

    Follicular lymphoma is commonly transformed to a more aggressive diffuse large B-cell lymphoma (DLBCL). In order to provide molecular characterization of this histological and clinical transformation, comparative genomic hybridization was applied to 23 follicular lymphoma and 35 transformed DLBCL tumors from a total of 30 patients. The results were also compared with our published findings in de novo DLBCL. Copy number changes were detected in 70% of follicular lymphoma and in 97% of transformed DLBCL. In follicular lymphoma, the most common alterations were +18q21 (33%), +Xq25-26 (28%), +1q31-32 (23%), and -17p (23%), whereas transformed DLBCL most frequently exhibited +Xq25-26 (36%), +12q15 (29%), +7pter-q22 (25%), +8q21 (21%), and -6q16-21(25%). Transformed DLBCL showed significantly more alterations as compared to follicular lymphoma (P=0.0001), and the alterations -6q16-21 and +7pter-q22 were only found in transformed DLBCL but not in follicular lymphoma (P=0.02). Alterations involving +13q22 were significantly less frequent, whereas -4q13-21 was more common in transformed as compared to de novo DLBCL (P=0.01 and P=0.02, respectively). Clinical progression from follicular lymphoma to transformed DLBCL is on the genetic level associated with acquisition of increasing number of genomic copy number changes, with non-random involvement of specific target regions. The findings support diverse genetic background between transformed and de novo DLBCL.

  1. Follicular mucinosis presenting as an acneiform eruption: a follow-up study.

    PubMed

    Brau-Javier, Cristina N; Santos-Arroyo, Aileen E; De Sanctis-González, Ivette M; Sánchez, Jorge L

    2013-12-01

    It has been proposed by many authors that follicular mucinosis is directly associated with mycosis fungoides (MF). Follicular mucinosis may be classified into 3 main clinical variants: a benign idiopathic form in children and young adults, which includes an acneiform presentation; an idiopathic form in older patients with a benign course; and a third variant that occurs in adults and is associated with MF. Our goal was to study the relationship between the acneiform variant of follicular mucinosis and MF. Eight patients previously diagnosed with the acneiform variant of follicular mucinosis were identified. Biopsy specimens were reviewed to evaluate the histopathologic attributes that characterize the disease and the infiltrate's immunohistochemistry. Also, patient follow-up was assessed to evaluate the clinical course of the disease. Median age of onset of disease was 29.5 years; 95% of lesions were located in the head and neck region. Biopsy specimens showed a moderate to dense perivascular, perifollicular, and interstitial infiltrate of lymphocytes with mucinous deposits within the follicular epithelium. On immunohistochemistry, the infiltrate showed prominent leukocyte common antigen (LCA) positivity and a CD3-positive and CD4-positive infiltrate with rare CD20-positive cells. None of the study patients showed evidence of MF after a mean follow-up of 3 years. The benign course of disease demonstrated in the study patients suggests that the acneiform variant of follicular mucinosis probably represents a subpopulation of the benign idiopathic form of the disease. However, given that histopathologically this variant cannot be distinguished from the lymphoma-associated variant of follicular mucinosis, longitudinal evaluation is still warranted in these patients.

  2. The Isothermal Dendritic Growth Experiment (IDGE)

    NASA Technical Reports Server (NTRS)

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

    2001-01-01

    Dendritic solidification is one of the simplest examples of pattern formation where a structureless melt evolves into a ramified crystalline microstructure; it is a common mode of solidification in many materials, but especially so in metals and alloys. There is considerable engineering interest in dendrites because of the role dendrites play in the determination of microstructure, and thereby in influencing the physical properties of cast metals and alloys. Dendritic solidification provides important examples of non-equilibrium physics, pattern formation dynamics, and models for computational condensed matter and material physics. Current theories of dendritic growth generally couple diffusion effects in the melt with the physics introduced by the interface. Unfortunately, in terrestrial based experiments, convective effects in the melt alter the growth process in such a manner as to prevent definitive analysis of convective, diffusive or interfacial effects. Thus, the effective elimination of convection in the melt by operating experiments on orbit were required to produce high-fidelity data needed for achieving further progress. This simple fact comprised the scientific justification for the IDGE.

  3. Nerve Conduction Through Dendrites via Proton Hopping.

    PubMed

    Kier, Lemont B

    2017-01-01

    In our previous studies of nerve conduction conducted by proton hopping, we have considered the axon, soma, synapse and the nodes of Ranvier. The role of proton hopping described the passage of information through each of these units of a typical nerve system. The synapse projects information from the axon to the dendrite and their associated spines. We have invoked the passage of protons via a hopping mechanism to illustrate the continuum of the impulse through the system, via the soma following the dendrites. This is proposed to be a continuum invoked by the proton hopping method. With the proposal of the activity through the dendrites, via proton hopping, a complete model of the nerve function is invoked. At each step to the way, a water pathway is present and is invoked in the proposed model as the carrier of the message via proton hopping. The importance of the dendrites is evident by the presence of a vast number of spines, each possessing the possibility to carry unique messages through the nervous system. With this model of the role of dendrites, functioning with the presence of proton hopping, a complete model of the nerve system is presented. The validity of this model will be available for further studies and models to assess it's validity. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  4. Dendritic spine abnormalities in mental retardation.

    PubMed

    von Bohlen Und Halbach, Oliver

    2010-12-01

    Abnormalities in dendritic spine morphologies are often associated with mental retardation. Since dendritic spines are thought to represent a morphological correlate of neuronal plasticity, altered spine morphologies may underlie or contribute to cognitive deficits seen in mental retardation. Signaling cascades that are important for cytoskeletal regulation may have an impact upon spine morphologies. The Rho GTPase signaling pathway has been shown to be involved in the regulation of the cytoskeleton and to play fundamental roles in the structural plasticity of dendritic spines. Moreover, alterations in the Rho GTPase signaling pathway have been shown to contribute to mental retardation. Recently, different mental retardation-associated genes have been identified that encode modulators of the Rho GTPases. Disturbances in these genes can lead to mental retardation and-on the morphological level-to alterations in dendritic spines. Thus, getting more insight into the Rho GTPase signaling pathways, and the molecules involved, would not only help in understanding the basic mechanisms by which the morphologies of dendritic spines are modulated but may also allow the development of therapeutic strategies to counteract some aspects of mental retardation.

  5. Anti-ICOS Monoclonal Antibody MEDI-570 in Treating Patients With Relapsed or Refractory Peripheral T-cell Lymphoma Follicular Variant or Angioimmunoblastic T-cell Lymphoma

    ClinicalTrials.gov

    2017-09-28

    Follicular Variant Peripheral T-Cell Lymphoma; Grade 1 Follicular Lymphoma; Grade 2 Follicular Lymphoma; Grade 3a Follicular Lymphoma; Recurrent Angioimmunoblastic T-cell Lymphoma; Recurrent Follicular Lymphoma; Recurrent Mature T- and NK-Cell Non-Hodgkin Lymphoma; Recurrent Mycosis Fungoides; Recurrent Primary Cutaneous T-Cell Non-Hodgkin Lymphoma; Refractory Angioimmunoblastic T-cell Lymphoma; Refractory Follicular Lymphoma; Refractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Stage IB Mycosis Fungoides; Stage II Mycosis Fungoides; Stage III Cutaneous T-Cell Non-Hodgkin Lymphoma; Stage III Mycosis Fungoides; Stage IV Cutaneous T-Cell Non-Hodgkin Lymphoma; Stage IV Mycosis Fungoides

  6. 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.

  7. Genes regulating dendritic outgrowth, branching, and routing in Drosophila

    PubMed Central

    Gao, Fen-Biao; Brenman, Jay E.; Jan, Lily Yeh; Jan, Yuh Nung

    1999-01-01

    Signaling between neurons requires highly specialized subcellular structures, including dendrites and axons. Dendrites exhibit diverse morphologies yet little is known about the mechanisms controlling dendrite formation in vivo. We have developed methods to visualize the stereotyped dendritic morphogenesis in living Drosophila embryos. Dendrite development is altered in prospero mutants and in transgenic embryos expressing a constitutively active form of the small GTPase cdc42. From a genetic screen, we have identified several genes that control different aspects of dendrite development including dendritic outgrowth, branching, and routing. These genes include kakapo, a large cytoskeletal protein related to plectin and dystrophin; flamingo, a seven-transmembrane protein containing cadherin-like repeats; enabled, a substrate of the tyrosine kinase Abl; and nine potentially novel loci. These findings begin to reveal the molecular mechanisms controlling dendritic morphogenesis. PMID:10521399

  8. Genes regulating dendritic outgrowth, branching, and routing in Drosophila.

    PubMed

    Gao, F B; Brenman, J E; Jan, L Y; Jan, Y N

    1999-10-01

    Signaling between neurons requires highly specialized subcellular structures, including dendrites and axons. Dendrites exhibit diverse morphologies yet little is known about the mechanisms controlling dendrite formation in vivo. We have developed methods to visualize the stereotyped dendritic morphogenesis in living Drosophila embryos. Dendrite development is altered in prospero mutants and in transgenic embryos expressing a constitutively active form of the small GTPase cdc42. From a genetic screen, we have identified several genes that control different aspects of dendrite development including dendritic outgrowth, branching, and routing. These genes include kakapo, a large cytoskeletal protein related to plectin and dystrophin; flamingo, a seven-transmembrane protein containing cadherin-like repeats; enabled, a substrate of the tyrosine kinase Abl; and nine potentially novel loci. These findings begin to reveal the molecular mechanisms controlling dendritic morphogenesis.

  9. Kidney tubular-cell secretion of osteoblast growth factor is increased by kaempferol: a scientific basis for "the kidney controlling the bone" theory of Chinese medicine.

    PubMed

    Long, Mian; Li, Shun-xiang; Xiao, Jiang-feng; Wang, Jian; Lozanoff, Scott; Zhang, Zhi-guang; Luft, Benjamin J; Johnson, Francis

    2014-09-01

    To study, at the cytological level, the basic concept of Chinese medicine that "the Kidney (Shen) controls the bone". Kaempferol was isolated form Rhizoma Drynariae (Gu Sui Bu, GSB) and at several concentrations was incubated with opossum kidney (OK) cells, osteoblasts (MC3T3 E1) and human fibroblasts (HF) at cell concentrations of 2×10(4)/mL. Opossum kidney cell-conditioned culture media with kaempferol at 70 nmol/L (70kaeOKM) and without kaempferol (0OKM) were used to stimulate MC3T3 E1 and HF proliferation. The bone morphological protein receptors I and II (BMPR I and II) in OK cells were identified by immune-fluorescence staining and Western blot analysis. Kaempferol was found to increase OK cell growth (P<0.05), but alone did not promote MC3T3 E1 or HF cell proliferation. However, although OKM by itself increased MC3T3 E1 growth by 198% (P<0.01), the 70kaeOKM further increased the growth of these cells by an additional 127% (P<0.01). It indicates that the kidney cell generates a previously unknown osteoblast growth factor (OGF) and kaempferol increases kidney cell secretion of OGF. Neither of these media had any significant effect on HF growth. Kaempferol also was found to increase the level of the BMPR II in OK cells. This lends strong support to the original idea that the Kidney has a significant influence over bone-formation, as suggested by some long-standing Chinese medical beliefs, kaempferol may also serve to stimulate kidney repair and indirectly stimulate bone formation.

  10. Reduced Purkinje cell dendritic arborization and loss of dendritic spines in essential tremor.

    PubMed

    Louis, Elan D; Lee, Michelle; Babij, Rachel; Ma, Karen; Cortés, Etty; Vonsattel, Jean-Paul G; Faust, Phyllis L

    2014-12-01

    Based on accumulating post-mortem evidence of abnormalities in Purkinje cell biology in essential tremor, we hypothesized that regressive changes in dendritic morphology would be apparent in the Purkinje cell population in essential tremor cases versus age-matched controls. Cerebellar cortical tissue from 27 cases with essential tremor and 27 age-matched control subjects was processed by the Golgi-Kopsch method. Purkinje cell dendritic anatomy was quantified using a Neurolucida microscopic system interfaced with a motorized stage. In all measures, essential tremor cases demonstrated significant reductions in dendritic complexity compared with controls. Median values in essential tremor cases versus controls were: 5712.1 versus 10 403.2 µm (total dendrite length, P=0.01), 465.9 versus 592.5 µm (branch length, P=0.01), 22.5 versus 29.0 (maximum branch order, P=0.001), and 165.3 versus 311.7 (number of terminations, P=0.008). Furthermore, the dendritic spine density was reduced in essential tremor cases (medians=0.82 versus 1.02 µm(-1), P=0.03). Our demonstration of regressive changes in Purkinje cell dendritic architecture and spines in essential tremor relative to control brains provides additional evidence of a pervasive abnormality of Purkinje cell biology in this disease, which affects multiple neuronal cellular compartments including their axon, cell body, dendrites and spines.

  11. Nak regulates localization of clathrin sites in higher-order dendrites to promote local dendrite growth.

    PubMed

    Yang, Wei-Kang; Peng, Yu-Huei; Li, Hsun; Lin, Hsiu-Chen; Lin, Yu-Ching; Lai, Tzu-Ting; Suo, Hsien; Wang, Chien-Hsiang; Lin, Wei-Hsiang; Ou, Chan-Yen; Zhou, Xin; Pi, Haiwei; Chang, Henry C; Chien, Cheng-Ting

    2011-10-20

    During development, dendrites arborize in a field several hundred folds of their soma size, a process regulated by intrinsic transcription program and cell adhesion molecule (CAM)-mediated interaction. However, underlying cellular machineries that govern distal higher-order dendrite extension remain largely unknown. Here, we show that Nak, a clathrin adaptor-associated kinase, promotes higher-order dendrite growth through endocytosis. In nak mutants, both the number and length of higher-order dendrites are reduced, which are phenocopied by disruptions of clathrin-mediated endocytosis. Nak interacts genetically with components of the endocytic pathway, colocalizes with clathrin puncta, and is required for dendritic localization of clathrin puncta. More importantly, these Nak-containing clathrin structures preferentially localize to branching points and dendritic tips that are undergoing active growth. We present evidence that the Drosophila L1-CAM homolog Neuroglian is a relevant cargo of Nak-dependent internalization, suggesting that localized clathrin-mediated endocytosis of CAMs facilitates the extension of nearby higher-order dendrites. Copyright © 2011 Elsevier Inc. All rights reserved.

  12. 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.

  13. Prolonged hypothyroidism severely reduces ovarian follicular reserve in adult rats.

    PubMed

    Meng, Li; Rijntjes, Eddy; Swarts, Hans J M; Keijer, Jaap; Teerds, Katja J

    2017-03-16

    There is substantial evidence both in humans and in animals that a prolonged reduction in plasma thyroid hormone concentration leads to reproductive problems, including disturbed folliculogenesis, impaired ovulation and fertilization rates, miscarriage and pregnancy complications. The objective of the present study is to examine the consequences of chronic hypothyroidism, induced in adulthood, for the size of the ovarian follicle pool. In order to investigate this, adult female rats were provided either a control or an iodide deficient diet in combination with perchlorate supplementation to inhibit iodide uptake by the thyroid. Sixteen weeks later animals were sacrificed. Blood was collected for hormone analyses and ovaries were evaluated histologically. At the time of sacrifice, plasma thyroid-stimulating hormone concentrations were 20- to 40-fold increased, thyroxine concentrations were negligible while tri-iothyronin concentrations were decreased by 40% in the hypothyroid group, confirming that the animals were hypothyroid. Primordial, primary and preantral follicle numbers were significantly lower in the hypothyroid ovaries compared to the euthyroid controls, while a downward trend in antral follicle and corpora lutea numbers was observed. Surprisingly the percentage of atretic follicles was not significantly different between the two groups, suggesting that the reduced preantral and antral follicle numbers were presumably not the consequence of increased degeneration of these follicle types in the hypothyroid group. Plasma anti-Müllerian hormone (AMH) levels showed a significant correlation with the growing follicle population represented by the total ovarian number of primary, preantral and antral follicles, suggesting that also under hypothyroid conditions AMH can serve as a surrogate marker to assess the growing ovarian follicle population. The induction of a chronic hypothyroid condition in adult female rats negatively affects the ovarian follicular

  14. 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

  15. Active Idiotypic Vaccination Versus Control Immunotherapy for Follicular Lymphoma

    PubMed Central

    Levy, Ronald; Ganjoo, Kristen N.; Leonard, John P.; Vose, Julie M.; Flinn, Ian W.; Ambinder, Richard F.; Connors, Joseph M.; Berinstein, Neil L.; Belch, Andrew R.; Bartlett, Nancy L.; Nichols, Craig; Emmanouilides, Christos E.; Timmerman, John M.; Gregory, Stephanie A.; Link, Brian K.; Inwards, David J.; Freedman, Arnold S.; Matous, Jeffrey V.; Robertson, Michael J.; Kunkel, Lori A.; Ingolia, Diane E.; Gentles, Andrew J.; Liu, Chih Long; Tibshirani, Robert; Alizadeh, Ash A.; Denney, Dan W.

    2014-01-01

    Purpose Idiotypes (Ids), the unique portions of tumor immunoglobulins, can serve as targets for passive and active immunotherapies for lymphoma. We performed a multicenter, randomized trial comparing a specific vaccine (MyVax), comprising Id chemically coupled to keyhole limpet hemocyanin (KLH) plus granulocyte macrophage colony-stimulating factor (GM-CSF) to a control immunotherapy with KLH plus GM-CSF. Patients and Methods Patients with previously untreated advanced-stage follicular lymphoma (FL) received eight cycles of chemotherapy with cyclophosphamide, vincristine, and prednisone. Those achieving sustained partial or complete remission (n = 287 [44%]) were randomly assigned at a ratio of 2:1 to receive one injection per month for 7 months of MyVax or control immunotherapy. Anti-Id antibody responses (humoral immune responses [IRs]) were measured before each immunization. The primary end point was progression-free survival (PFS). Secondary end points included IR and time to subsequent antilymphoma therapy. Results At a median follow-up of 58 months, no significant difference was observed in either PFS or time to next therapy between the two arms. In the MyVax group (n = 195), anti-Id IRs were observed in 41% of patients, with a median PFS of 40 months, significantly exceeding the median PFS observed in patients without such Id-induced IRs and in those receiving control immunotherapy. Conclusion This trial failed to demonstrate clinical benefit of specific immunotherapy. The subset of vaccinated patients mounting specific anti-Id responses had superior outcomes. Whether this reflects a therapeutic benefit or is a marker for more favorable underlying prognosis requires further study. PMID:24799467

  16. Follicular bronchiolitis as phenotype associated with CD25 deficiency.

    PubMed

    Bezrodnik, L; Caldirola, M S; Seminario, A G; Moreira, I; Gaillard, M I

    2014-02-01

    Regulatory T cells [Tregs ; CD4(+) CD25(+) forkhead box protein 3 (FoxP3(+) )] are subsets of T cells involved in the maintenance of peripheral self-tolerance by actively suppressing the activation and expansion of autoreactive T cells. Signalling through the interleukin-2 receptor (IL-2R) contributes to T cell tolerance by controlling three important aspects of regulatory T cell (Treg ) biology. CD25 is the α-chain of the IL-2R that, in concert with the β-chain and γ-chain, constitutes the complete IL-2R. CD25 contributes only to IL-2 binding affinity but not to the recruitment of signalling molecules. However, its importance in the development of a normal immune response is emphasized by the finding that a truncation mutant of CD25 results in an immunodeficiency in humans characterized by an increased susceptibility to viral, bacterial and fungal infections. In 1997, Sharfe et al. described an infant with severe bacterial, viral and fungal infections. Counts of autologous T lymphocytes were moderately low, T cells displayed a weak proliferative response to mitogens in vitro and the patient displayed no rejection of an allogeneic skin graft. However, unlike children with severe combined immunodeficiency (SCID), besides not having circulating T cells, the patient also developed peripheral lymphocytic proliferation and autoimmune primary biliary cirrhosis. We present the first female Argentine patient with mutation in CD25 associated with chronic and severe inflammatory lung disease (follicular bronchiolitis with lymphocyte hyperplasia), eczema and infections. She has no expression of CD25 on CD4(+) T cells and an extremely low amount of Tregs . The molecular study confirmed homozygous missense mutation in the alpha subunit of the IL-2 receptor (CD25αR) (c. 122 a > c; p. Y41S). © 2013 British Society for Immunology.

  17. Proteomic analysis of preovulatory follicular fluid reveals differentially abundant proteins in less fertile dairy cows.

    PubMed

    Zachut, Maya; Sood, Pankaj; Levin, Yishai; Moallem, Uzi

    2016-04-29

    The follicular fluid (FF) proteome can provide an indication of follicular quality. High-yielding dairy cows suffer from low fertility, which could be related to follicular function. However, the proteome of preovulatory follicles has never been described in cows. Our objectives were to: 1) define the bovine preovulatory FF proteome, and 2) examine differentially abundant proteins in FF of controls (CTL, n=10) and less fertile cows (LFC; failed to conceive following ≥6 inseminations, n=8). Follicles ≥7mm in diameter were aspirated in vivo, and estradiol (E2) and progesterone (P4) were examined. The FF from 10 preovulatory follicles (E2/P4>1) was analyzed; E2 was higher and follicle diameter tended to be larger in LFC. As aspirations were conducted at a fixed time, this suggests accelerated follicular growth in LFC. The 219 identified and quantified proteins consisted mainly of binding proteins, proteases, receptor ligands, enzymes and transporters. Differential abundance of 8 relevant proteins was found in LFC compared to CTL: SERPINA1, TIMP2, ITIH1, HSPG2, C8A, COL1A2, F2, and IL1RAP. These proteins could influence follicular function-e.g., decreased SERPINA1 may be related to accelerated follicular growth-and therefore, further examination of their roles in the etiology of LFC is warranted. High yielding dairy cows suffer from infertility that leads to major economic losses worldwide. In Israel, about 30% of dairy cows fail to conceive following ≥4 inseminations. The etiology of this low fertility is multifactorial and remains a serious challenge. Follicular fluid proteome can provide indication to follicular quality, yet the proteome of pre-ovulatory follicles has not been described in cows. This work examined the differential abundance of proteins in less fertile dairy cows compared to controls, and found 8 relevant novel proteins that could influence follicular function. The role of these proteins in the etiology of less fertile cows should be further

  18. The path integral for dendritic trees.

    PubMed

    Abbott, L F; Farhi, E; Gutmann, S

    1991-01-01

    We construct the path integral for determining the potential on any dendritic tree described by a linear cable equation. This is done by generalizing Brownian motion from a line to a tree. We also construct the path integral for dendritic structures with spatially-varying and/or time-dependent membrane conductivities due, for example, to synaptic inputs. The path integral allows novel computational techniques to be applied to cable problems. Our analysis leads ultimately to an exact expression for the Green's function on a dendritic tree of arbitrary geometry expressed in terms of a set of simple diagrammatic rules. These rules providing a fast and efficient method for solving complex cable problems.

  19. Dendritic inhomogeneity of stainless maraging steels

    SciTech Connect

    Krasnikova, S.I.; Drobot, A.V.; Shmelev, A.Y.; Vukelich, S.B.

    1986-03-01

    The authors investigated dendritic inhomogeneity in industrial ingots 630 mm (steel I) in diameter and 500 mm (steel II) in diameter. The variation in the degree of dendritic inhomogeneity was investigated over the height of the ingots and across the sections on an MS-46 microprobe. It was established that the elements can be placed in the following order in accordance with the degree of reduction in the liquation factor: titanium, molybdenum, nickel, chromium, and cobalt. Titanium and molybdenum exhibit forward liquation in both steels, and chromium in steel II. The distribution of nickel and chromium in the steel I ingots and cobalt in the steel II ingots is unconventional. Dendritic inhomogeneity, which must be considered in assigning the heat treatment for finished articles, develops during the crystallization of stainless maraging steels.

  20. Measuring dendritic distribution of membrane proteins.

    PubMed

    Ballou, Edmund W; Smith, W Bryan; Anelli, Roberta; Heckman, C J

    2006-09-30

    Neurons perform much of their integrative work in the dendritic tree, and spinal motoneurons have the largest tree of any cell. Electrical excitability is strongly influenced by dendrite membrane properties, which are difficult to measure directly. We describe a method to measure the distribution of ion channel membrane densities along dendritic trajectories. The method combines standard immunohistochemistry with reconstruction procedures for both large-scale and small-scale optical microscopy. Software written for Matlab then extracts the colocalization of the target ion channel with the target dye injected cell, and calculates the relative channel density per square micron of cell surface area, as a function of distance from the cell body. The technique can be used to quantify the localization and distribution of any immunoreactive moiety, and the software provides a flexible vehicle for sensitivity analysis, to validate heuristics for selecting thresholds.

  1. 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.

  2. 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

  3. Microorganisms inhabiting follicular contents of facial acne are not only Propionibacterium but also Malassezia spp.

    PubMed

    Akaza, Narifumi; Akamatsu, Hirohiko; Numata, Shigeki; Yamada, Shunji; Yagami, Akiko; Nakata, Satoru; Matsunaga, Kayoko

    2016-08-01

    To clarify the relationship between major cutaneous microorganisms (Propionibacterium, Staphylococcus and Malassezia spp.) and acne vulgaris (acne), we examined the microbiota quantitatively in the follicular contents of inflammatory acne and on the facial skin of patients with acne. Fifteen Japanese untreated acne outpatients were studied. The follicular contents from inflammatory acne lesions of the face were collected using a comedo extractor. The skin surface samples were obtained by the swab method from 10 cm(2) of facial skin. The microbiota was analyzed using polymerase chain reaction. The microbiota in follicular contents was similar to that on the skin surface, namely, there were large populations of Propionibacterium spp., Staphylococcus spp. and Malassezia spp. Moreover, the number of Malassezia spp. on the skin surface was correlated with that of inflammatory acne and that in follicular contents. This study clarified that there are large populations of Propionibacterium spp., Staphylococcus spp. and Malassezia spp. in follicular contents. These results suggest the possibility that not only Propionibacterium acnes but also other cutaneous resident microorganisms are related to acne. Particularly, we considered that Malassezia spp. is closely related.

  4. 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. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Keratosis Pilaris Revisited: Is It More Than Just a Follicular Keratosis?

    PubMed Central

    Thomas, Mary; Khopkar, Uday Sharadchandra

    2012-01-01

    Background: Keratosis pilaris (KP) is characterized by keratinous plugs in the follicular orifices and varying degrees of perifollicular erythema. The most accepted theory of its pathogenesis proposes defective keratinization of the follicular epithelium resulting in a keratotic infundibular plug. We decided to test this hypothesis by doing dermoscopy of patients diagnosed clinically as keratosis pilaris. Materials and Methods: Patients with a clinical diagnosis of KP seen between September 2011 and December 2011 were included in the study. A clinical history was obtained and examination and dermoscopic evaluation were performed on the lesions of KP. Results: The age of the patients ranged from 6-38 years. Sixteen patients had history of atopy. Nine had concomitant ichthyosis vulgaris. All the 25 patients were found to have coiled hair shafts within the affected follicular infundibula. The hair shafts were extracted with the help of a sterile needle and were found to retain their coiled nature. Perifollicular erythema was seen in 11 patients; perifollicular scaling in 9. Conclusion: Based on our observations and previously documented histological data of KP, we infer that KP may not be a disorder of keratinization, but caused by the circular hair shaft which ruptures the follicular epithelium leading to inflammation and abnormal follicular keratinization. PMID:23766609

  6. 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

  7. Follicular growth and atresia in mammalian ovaries: regulation by survival and death of granulosa cells.

    PubMed

    Matsuda, Fuko; Inoue, Naoko; Manabe, Noboru; Ohkura, Satoshi

    2012-01-01

    The mammalian ovary is an extremely dynamic organ in which a large majority of follicles are effectively eliminated throughout their reproductive life. Due to the numerous efforts of researchers, mechanisms regulating follicular growth and atresia in mammalian ovaries have been clarified, not only their systemic regulation by hormones (gonadotropins) but also their intraovarian regulation by gonadal steroids, growth factors, cytokines and intracellular proteins. Granulosa cells in particular have been demonstrated to play a major role in deciding the fate of follicles, serving molecules that are essential for follicular growth and maintenance as well as killing themselves by an apoptotic process that results in follicular atresia. In this review, we discuss the factors that govern follicular growth and atresia, with a special focus on their regulation by granulosa cells. First, ovarian folliculogenesis in adult life is outlined. Then, we explain about the regulation of follicular growth and atresia by granulosa cells, in which hormones, growth factors and cytokines, death ligand-receptor system and B cell lymphoma/leukemia 2 (BCL2) family members (mitochondria-mediated apoptosis) are further discussed.

  8. MicroRNAs: New Insight in Modulating Follicular Atresia: A Review.

    PubMed

    Worku, Tesfaye; Rehman, Zia Ur; Talpur, Hira Sajjad; Bhattarai, Dinesh; Ullah, Farman; Malobi, Ngabu; Kebede, Tesfaye; Yang, Liguo

    2017-02-09

    Our understanding of the post-transcriptional mechanisms involved in follicular atresia is limited; however, an important development has been made in understanding the biological regulatory networks responsible for mediating follicular atresia. MicroRNAs have come to be seen as a key regulatory actor in determining cell fate in a wide range of tissues in normal and pathological processes. Profiling studies of miRNAs during follicular atresia and development have identified several putative miRNAs enriched in apoptosis signaling pathways. Subsequent in vitro and/or in vivo studies of granulosa cells have elucidated the functional role of some miRNAs along with their molecular pathways. In particular, the regulatory roles of some miRNAs have been consistently observed during studies of follicular cellular apoptosis. Continued work should gradually lead to better understanding of the role of miRNAs in this field. Ultimately, we expect this understanding will have substantial benefits for fertility management at both the in vivo or/and in vitro levels. The stable nature of miRNA holds remarkable promise in clinical use as a diagnostic tool and in reproductive medicine to solve the ever-increasing fertility problem. In this review, we summarize current knowledge of the involvement of miRNAs in follicular atresia, discuss the challenges for further work and pinpoint areas for future research.

  9. MicroRNAs: New Insight in Modulating Follicular Atresia: A Review

    PubMed Central

    Worku, Tesfaye; Rehman, Zia Ur; Talpur, Hira Sajjad; Bhattarai, Dinesh; Ullah, Farman; Malobi, Ngabu; Kebede, Tesfaye; Yang, Liguo

    2017-01-01

    Our understanding of the post-transcriptional mechanisms involved in follicular atresia is limited; however, an important development has been made in understanding the biological regulatory networks responsible for mediating follicular atresia. MicroRNAs have come to be seen as a key regulatory actor in determining cell fate in a wide range of tissues in normal and pathological processes. Profiling studies of miRNAs during follicular atresia and development have identified several putative miRNAs enriched in apoptosis signaling pathways. Subsequent in vitro and/or in vivo studies of granulosa cells have elucidated the functional role of some miRNAs along with their molecular pathways. In particular, the regulatory roles of some miRNAs have been consistently observed during studies of follicular cellular apoptosis. Continued work should gradually lead to better understanding of the role of miRNAs in this field. Ultimately, we expect this understanding will have substantial benefits for fertility management at both the in vivo or/and in vitro levels. The stable nature of miRNA holds remarkable promise in clinical use as a diagnostic tool and in reproductive medicine to solve the ever-increasing fertility problem. In this review, we summarize current knowledge of the involvement of miRNAs in follicular atresia, discuss the challenges for further work and pinpoint areas for future research. PMID:28208755

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

    PubMed

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

    2015-03-01

    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. 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. 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.

  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.

  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. Blastic/blastoid transformation of follicular lymphoma: immunohistologic and molecular analyses of five cases.

    PubMed

    Natkunam, Y; Warnke, R A; Zehnder, J L; Jones, C D; Milatovich-Cherry, A; Cornbleet, P J

    2000-04-01

    Progression of follicular lymphoma to a higher-grade malignancy frequently heralds a poor prognosis. Clinical transformation is variably accompanied by a spectrum of histologic changes characterized by alteration in growth and cytology. Although several cytogenetic events and potential oncogenes have been documented in this progression, the underlying molecular mechanisms are largely unknown. We present five patients with an unusual histologic transformation of follicular lymphoma manifested by blastic/blastoid morphology. This transformation is histologically distinct from other types of transformation of follicular lymphoma. All five cases exhibited the t(14;18) translocation and expressed the BCL-2 protein. In addition, two of the five patients showed increased levels of the p53 protein within neoplastic cells implicating a possible role for this oncogene in blastic/blastoid transformation. The lack of BCL-1 and myeloid antigens by immunohistochemistry and flow cytometry studies served to distinguish blastic/blastoid transformation of follicular lymphoma from its morphologic mimics. This distinction is clinically important because lymphoblastic and myeloid leukemias require significantly different therapeutic modalities and show better prognosis. Moreover, the lack of Epstein-Barr virus-specific mRNA suggests that this virus is unlikely to participate in blastic/blastoid transformation of follicular lymphoma.

  14. 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.

  15. 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.

  16. 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

  17. 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.

  18. On dendritic growth in undercooled melts

    NASA Technical Reports Server (NTRS)

    Ohsaka, K.; Trinh, E. H.

    1988-01-01

    The role of gravity-dependent convection in the steady-state growth of dendrites in undercooled melts is investigated theoretically. The model described by Huang and Glicksman (1981) is extended and refined, using the concept of a thermal diffusion boundary layer (Burton et al., 1987) to characterize the dendritic interface. Theoretical predictions are presented in graphs and shown to be in good general agreement with published experimental data on succinonitrile. The need for careful space experiments to clarify the role of nongravity-dependent convection is indicated.

  19. The multifaceted biology of plasmacytoid dendritic cells

    PubMed Central

    Swiecki, Melissa; Colonna, Marco

    2015-01-01

    Plasmacytoid dendritic cells (pDCs) are a unique dendritic cell subset that specializes in the production of type I interferons (IFNs). pDCs promote antiviral immune responses and have been implicated in the pathogenesis of autoimmune diseases characterized by a type I IFN signature. However, pDCs can also induce tolerogenic immune responses. Here, we review recent progress from the field of pDC biology, focusing on: the molecular mechanisms that regulate pDC development and functions; the pathways involved in their sensing of pathogens and endogenous nucleic acids; the function of pDCs at mucosal sites; and their roles in infections, autoimmunity and cancer. PMID:26160613

  20. Regulation of dendrite growth and maintenance by exocytosis.

    PubMed

    Peng, Yun; Lee, Jiae; Rowland, Kimberly; Wen, Yuhui; Hua, Hope; Carlson, Nicole; Lavania, Shweta; Parrish, Jay Z; Kim, Michael D

    2015-12-01

    Dendrites lengthen by several orders of magnitude during neuronal development, but how membrane is allocated in dendrites to facilitate this growth remains unclear. Here, we report that Ras opposite (Rop), the Drosophila ortholog of the key exocytosis regulator Munc18-1 (also known as STXBP1), is an essential factor mediating dendrite growth. Neurons with depleted Rop function exhibit reduced terminal dendrite outgrowth followed by primary dendrite degeneration, suggestive of differential requirements for exocytosis in the growth and maintenance of different dendritic compartments. Rop promotes dendrite growth together with the exocyst, an octameric protein complex involved in tethering vesicles to the plasma membrane, with Rop-exocyst complexes and exocytosis predominating in primary dendrites over terminal dendrites. By contrast, membrane-associated proteins readily diffuse from primary dendrites into terminals, but not in the reverse direction, suggesting that diffusion, rather than targeted exocytosis, supplies membranous material for terminal dendritic growth, revealing key differences in the distribution of materials to these expanding dendritic compartments.