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Sample records for langerhans cells preferentially

  1. Langerhans Cell Histiocytosis—Patient Version

    Science.gov (United States)

    Langerhans cell histiocytosis is a rare blood cancer that forms when a type of white blood cell called Langerhans cells becomes abnormal and grows in different parts of the body. LCH is most common in young children but can occur at any age. Start here to find information on Langerhans cell histiocytosis treatment.

  2. The Langerhans cell

    International Nuclear Information System (INIS)

    Wolff, K.; Stingl, G.

    1983-01-01

    Langerhans cells are the bone-marrow-derived immune cells of the epidermis; they express Ia antigens and receptors for the Fc portion of IgG and complement components and are required for epidermal-cell-induced antigen-specific, syngeneic and allogeneic T-cell activitation and the generation of epidermal-cell-induced cytotoxic T cells. Their presence within the epidermis and functional integrity determine whether topical application of haptens leads to specific sensitization or unresponsiveness, and in skin grafts of only I region disparate donors, they represent the cells responsible for the critical allosensitizing signal. UV radiation abrogates most of Langerhans cell functions in vitro; under certain conditions in vivo, it prevents contact sensitization favoring the development of specific unresponsiveness. UV radiation abrogates antigen-presenting capacities of epidermal cells by interfering both with the processing of antigen by Langerhans cells and the production of the epidermal-cell-derived thymocyte activating factor required for optimal T-cell responses

  3. EXPRESSION OF CELLULAR ADHESION MOLECULES IN LANGERHANS CELL HISTIOCYTOSIS AND NORMAL LANGERHANS CELLS

    NARCIS (Netherlands)

    DEGRAAF, JH; TAMMINGA, RYJ; KAMPS, WA; TIMENS, W

    1995-01-01

    Langerhans cell histiocytosis (LCH) is characterized by lesions with an accumulation and/or proliferation of Langerhans cells (LCs). Little is known of the etiology and pathogenesis of LCH. Although the relation between the LCH cell and normal LCs is currently uncertain, the localizations of the LCH

  4. The presence of cytokines in Langerhans' cell histiocytosis

    NARCIS (Netherlands)

    deGraaf, JH; Tamminga, RYJ; DamMeiring, A; Kamps, WA; Timens, W

    1996-01-01

    Langerhans' cell histiocytosis (LCH) is characterized by an accumulation and/or proliferation of cells with a Langerhans' cell (LC) phenotype. The aetiology and pathogenesis of LCH are unknown; it is suggested that LCH is caused by an immunological dysregulation. Production of cytokines is a central

  5. Liver involvement in Langerhans' cell histiocytosis. Case report.

    Science.gov (United States)

    Dina, Ion; Copaescu, Catalin; Herlea, Vlad; Wrba, Fritz; Iacobescu, Claudia

    2006-03-01

    Langerhans'cell histiocytosis (Histiocytosis X) is a rare disease of unknown cause characterized by oligoclonal proliferation of Langerhans cells. It occurs mostly in children and young adults and involves one or more body systems such as bone, hypothalamus, posterior pituitary gland, lymph nodes, liver or various soft tissues. The diagnosis is always made by a histological approach. We report a case of Langerhans'cell histiocytosis in a young patient with clinical signs of diabetes insipidus and hepatic involvement in whom the immunohistochemical analysis of the liver tissue led to the definitive diagnosis.

  6. A Rare Disease in Adult: Langerhans Cell Histiocytosis

    Science.gov (United States)

    Berber, Ilhami; Erkurt, Mehmet Ali; Kuku, Irfan; Koroglu, Mustafa; Kaya, Emin; Unlu, Serkan

    2013-01-01

    Langerhans cell histiocytosis is a rare histiocytic disorder and has been diagnosed in all age groups, but is most common in children. This disease is very rare in adults. We presented a patient who was 62 years old man diagnosed langerhans cell histiocytosis. PMID:29147350

  7. Number of Langerhans cells is decreased in premalignant keratosis and skin cancers.

    Science.gov (United States)

    Shevchuk, Z; Filip, A; Shevchuk, V; Kashuba, E

    2014-03-01

    It was shown earlier that a number of CD207 positive Langerhans cells was lower in basal cell carcinomas than in the normal epidermis. Moreover, benign skin lesions presented a higher number of Langerhans cells when they were compared to malignant tumors. To count Langerhans cells, assessing expression levels of CD1A and CD207 markers in actinic keratosis, basal and squamous cell carcinomas, compared with the normal skin. Comparison of Langerhans cells might give a valuable prognostic marker for skin cancer. Immunohistochemistry and methods of statistics were used. Expression of CD1A and CD207 markers was assessed in tumor samples of actinic keratosis, cutaneous basal and squamous cell carcinomas, in comparison with the normal skin. In each cohort there were 40 patients (and 11 healthy individuals). We have shown that the number of Langerhans cells is considerably lower in cutaneous basal and squamous cell carcinomas, compared with their number in the normal skin (p keratosis, basal and squamous cell carcinoma. This may suggest an alteration of Langerhans cells phenotype in skin neoplastic diseases, making the number of Langerhans cells a valuable prognostic factor for skin tumors.

  8. Pulmonary langerhans cell histiocytosis

    Directory of Open Access Journals (Sweden)

    Suri Harpreet S

    2012-03-01

    Full Text Available Abstract Pulmonary Langerhans Cell Histiocytosis (PLCH is a relatively uncommon lung disease that generally, but not invariably, occurs in cigarette smokers. The pathologic hallmark of PLCH is the accumulation of Langerhans and other inflammatory cells in small airways, resulting in the formation of nodular inflammatory lesions. While the overwhelming majority of patients are smokers, mechanisms by which smoking induces this disease are not known, but likely involve a combination of events resulting in enhanced recruitment and activation of Langerhans cells in small airways. Bronchiolar inflammation may be accompanied by variable lung interstitial and vascular involvement. While cellular inflammation is prominent in early disease, more advanced stages are characterized by cystic lung destruction, cicatricial scarring of airways, and pulmonary vascular remodeling. Pulmonary function is frequently abnormal at presentation. Imaging of the chest with high resolution chest CT scanning may show characteristic nodular and cystic abnormalities. Lung biopsy is necessary for a definitive diagnosis, although may not be required in instances were imaging findings are highly characteristic. There is no general consensus regarding the role of immunosuppressive therapy in smokers with PLCH. All smokers must be counseled on the importance of smoking cessation, which may result in regression of disease and obviate the need for systemic immunosuppressive therapy. The prognosis for most patients is relatively good, particularly if longitudinal lung function testing shows stability. Complications like pneumothoraces and secondary pulmonary hypertension may shorten life expectancy. Patients with progressive disease may require lung transplantation.

  9. Langerhans Cell Histiocytosis Involving Maxilla and Mandible

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    M. Guna Shekhar

    2009-06-01

    Full Text Available Langerhans cell histiocytosis is a relatively rare unique disease process characterized by an abnormal proliferation of immature dendritic cells usually affecting children and young adults. Jaws are involved in less than 10% of children with the disease while mandibular involvement in young children is uncommon and bilateral affection is very rare. The purpose of this report is to describe a unique and very rare case of simultaneous and bilateral occurrence of Langerhans cell histiocytosis in both the jaws of a four-year-old boy.

  10. Fibered Confocal Fluorescence Microscopy for the Noninvasive Imaging of Langerhans Cells in Macaques.

    Science.gov (United States)

    Todorova, Biliana; Salabert, Nina; Tricot, Sabine; Boisgard, Raphaël; Rathaux, Mélanie; Le Grand, Roger; Chapon, Catherine

    2017-01-01

    We developed a new approach to visualize skin Langerhans cells by in vivo fluorescence imaging in nonhuman primates. Macaques were intradermally injected with a monoclonal, fluorescently labeled antibody against HLA-DR molecule and were imaged for up to 5 days by fibered confocal microscopy (FCFM). The network of skin Langerhans cells was visualized by in vivo fibered confocal fluorescence microscopy. Quantification of Langerhans cells revealed no changes to cell density with time. Ex vivo experiments confirmed that injected fluorescent HLA-DR antibody specifically targeted Langerhans cells in the epidermis. This study demonstrates the feasibility of single-cell, in vivo imaging as a noninvasive technique to track Langerhans cells in nontransgenic animals.

  11. Paediatric neuroradiological aspects of Langerhans cell histiocytosis

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    Demaerel, Philippe [University Hospital K.U.Leuven, Department of Radiology, Leuven (Belgium); Gool, Stefaan van [University Hospital K.U.Leuven, Paediatric Haemato-oncology/Neuro-oncology, Leuven (Belgium)

    2008-01-15

    Langerhans cell histiocytosis, previously known as histiocytosis X, is a complex disease consisting of three entities that are all characterized by a proliferation of the Langerhans cell. The clinical course is variable and ranges from a solitary lytic bone or skin lesion with complete remission to a multisystem disorder with possible lethal outcome. The clinical suspicion can be increased based on radiological findings that are important criteria in defining the extent of the disease involvement. A biopsy is often necessary for establishing the final diagnosis. The lytic craniofacial bone lesions are the most common craniospinal abnormality in Langerhans cell histiocytosis. Abnormalities in the hypothalamic-pituitary region are the most frequent manifestations, often accompanied with diabetes insipidus as the presenting symptom. A range of different central nervous system abnormalities can be recognized. It is important to be able to recognize the extensive spectrum of neuroradiological abnormalities in order to arrive at the diagnosis. Neuroimaging plays an even more important role in assessing the response to treatment or possible relapse. (orig.)

  12. Langerhans cell sarcoma following marginal zone lymphoma: expanding the knowledge on mature B cell plasticity.

    Science.gov (United States)

    Ambrosio, Maria Raffaella; De Falco, Giulia; Rocca, Bruno Jim; Barone, Aurora; Amato, Teresa; Bellan, Cristiana; Lazzi, Stefano; Leoncini, Lorenzo

    2015-10-01

    The concept of unidirectional differentiation of the haematopoietic stem cell has been challenged after recent findings that human B cell progenitors and even mature B cells can be reprogrammed into histiocytic/dendritic cells by altering expression of lineage-associated transcription factors. The conversion of mature B cell lymphomas to Langerhans cell neoplasms is not well documented. Three previous reports have described clonally related follicular lymphoma and Langerhans cell tumours, whereas no case has been published of clonally related marginal zone lymphoma and Langerhans cell sarcoma. We describe the case of a 77-year-old patient who developed a Langerhans cell sarcoma and 6 years later a nodal marginal zone lymphoma. Mutation status examination showed 100 % gene identity to the germline sequence, suggesting direct trans-differentiation or dedifferentiation of the nodal marginal zone lymphoma to the Langerhans cell sarcoma rather than a common progenitor. We found inactivation of paired box 5 (PAX-5) in the lymphoma cells by methylation, along with duplication of part of the long arm of chromosomes 16 and 17 in the sarcoma cells. The absence of PAX-5 could have triggered B cells to differentiate into macrophages and dendritic cells. On the other hand, chromosomal imbalances might have activated genes involved in myeloid lineage maturation, transcription activation and oncogenesis. We hypothesize that this occurred because of previous therapies for nodal marginal zone lymphoma. Better understanding of this phenomenon may help in unravelling the molecular interplay between transcription factors during haematopoietic lineage commitment and may expand the spectrum of clonally related mature B cell neoplasms and Langerhans cell tumours.

  13. High expression of markers of apoptosis in Langerhans cell histiocytosis

    DEFF Research Database (Denmark)

    Petersen, Bodil Laub; Lundegaard, Pia Rengtved; Bank, M I

    2003-01-01

    53 and the number of cells in apoptosis detected with TUNEL. Langerhans cell histiocytosis cells showed strong expression of p53 and in some cases co-expression of Fas and Fas-L. The expression of Fas-L was significantly higher in infiltrates from patients with single-system disease. The actual...... number of pathological Langerhans cells in apoptosis as estimated by TUNEL was low. CONCLUSIONS: The low number of TUNEL-reactive cells can be explained by the rapid turnover of apoptotic cells in the tissue, not leaving the apoptotic cells long enough in the tissue to be detected. The co......-expression of Fas and Fas-L in some Langerhans cells can lead to an autocrine apoptotic shortcut, mediating the death of the double-positive cells. Our findings suggest that apoptosis mediated through the Fas/Fas-L pathway may contribute to the spontaneous regression of lesions in single-system disease. A delicate...

  14. [Langerhans cell histiocytosis in adults].

    Science.gov (United States)

    Néel, A; Artifoni, M; Donadieu, J; Lorillon, G; Hamidou, M; Tazi, A

    2015-10-01

    Langerhans cell histiocytosis (LCH) is a rare disease characterized by the infiltration of one or more organs by Langerhans cell-like dendritic cells, most often organized in granulomas. The disease has been initially described in children. The clinical picture of LCH is highly variable. Bone, skin, pituitary gland, lung, central nervous system, lymphoid organs are the main organs involved whereas liver and intestinal tract localizations are less frequently encountered. LCH course ranges from a fulminant multisystem disease to spontaneous resolution. Several randomized controlled trials have enable pediatricians to refine the management of children with LCH. Adult LCH has some specific features and poses distinct therapeutic challenges, knowing that data on these patients are limited. Herein, we will provide an overview of current knowledge regarding adult LCH and its management. We will also discuss recent advances in the understanding of the disease, (i.e. the role of BRAF oncogene) that opens the way toward targeted therapies. Copyright © 2015 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  15. Thoracolumbar Langerhans cell histiocytosis in a toddler

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    Zhi Gang Lan

    2018-01-01

    Full Text Available Introduction: Langerhans cell histiocytosis (LCH is a rare uni or multisystem disorder associated with extreme production of immunoreactive Langerhans cells. Although this disorder has been reported in all age groups, spinal involvement especially thoracolumbar spine is seldom reported in toddlers. Case presentation: We present a one (1 year, four (4 months female child with a history of recurrent fever, irritability and severe anemia of one (1 month duration. CT-scan and MRI revealed a collapsed twelfth thoracic vertebra (T12 body height greater than 95% with a huge intradural soft tissue mass. T12 cortectomy via posterior thoracolumbar approach was used to decompress the soft tissue part followed by interbody fusion with titanium cage filled with autologous iliac crest bone graft, fixation using plates and screws. Conclusion: We are of the view that surgical decompression of spinal LHC lesions with interbody fusion with titanium cage filled with autologous iliac crest bone graft and fixation using plates and screws is very crucial in relieving neurological deficits. However, the patient will need repeated surgeries as she advances with age in a timely manner to avert any neurological deficit that may occur. Keywords: Langerhans cell histiocytosis (LCH, Letterer-Siwe disease, Hand-Schüller-Christian disease, Eosinophilic granuloma

  16. Langerhans' cell histiocytosis presenting with an intracranial epidural hematoma

    International Nuclear Information System (INIS)

    Lee, K.-W.; McLeary, M.S.; Zuppan, C.W.; Won, D.J.

    2000-01-01

    An 8-year-old boy developed vomiting and severe headache following minor head trauma. A CT scan of the head demonstrated a lytic lesion of the skull and adjacent epidural hematoma. Surgical evacuation and removal of the skull lesion and hematoma were carried out, and pathologic evaluation resulted in a diagnosis of Langerhans' cell histiocytosis (LCH). Epidural involvement of Langerhans' cell histiocytosis is very rare, and we report the first case of LCH presenting as an intracranial epidural hematoma. (orig.)

  17. Langerhans Cells: the 'Yin and Yang' of HIV Restriction and Transmission.

    Science.gov (United States)

    Mayr, Luzia; Su, Bin; Moog, Christiane

    2017-03-01

    Langerhans cells are specialized sentinels present in the epidermis expressing Langerin, a specific C-type lectin receptor involved in HIV capture and destruction. Recently, the specific mechanism leading to this HIV restriction was discovered. Nevertheless, Langerhans cells can be infected and the way HIV escapes this restriction needs to be unraveled. Copyright © 2017. Published by Elsevier Ltd.

  18. Langerhans' cell histiocytosis presenting with an intracranial epidural hematoma

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    Lee, K.-W. [Department of Pediatrics, Loma Linda Children' s Hospital and University Medical Center, Loma Linda, CA (United States); McLeary, M.S. [Div. of Pediatric Radiology, Loma Linda Children' s Hospital and University Medical Center, Loma Linda, CA (United States); Zuppan, C.W. [Dept. of Pathology, Loma Linda Children' s Hospital and University Medical Center, Loma Linda, CA (United States); Won, D.J. [Div. of Pediatric Neurosurgery, Loma Linda University Children' s Hospital, Loma Linda, CA (United States)

    2000-05-01

    An 8-year-old boy developed vomiting and severe headache following minor head trauma. A CT scan of the head demonstrated a lytic lesion of the skull and adjacent epidural hematoma. Surgical evacuation and removal of the skull lesion and hematoma were carried out, and pathologic evaluation resulted in a diagnosis of Langerhans' cell histiocytosis (LCH). Epidural involvement of Langerhans' cell histiocytosis is very rare, and we report the first case of LCH presenting as an intracranial epidural hematoma. (orig.)

  19. Pituitary and pulmonary abnormalities in an adult patient with Langerhans cell histiocytosis

    International Nuclear Information System (INIS)

    Perez, Adrian; Castro, Ricardo; Pantuso, Silvina

    2003-01-01

    Pulmonary histiocytosis is an uncommon interstitial lung disease, which is infrequent in adults and is part of a spectrum of disorders characterized by monoclonal proliferation and infiltration of organs by Langerhans cells. Histiocytosis X affects only the lungs in more than 85% of the cases. We report a case of a 21-years-old male patient with Diabetes Insipidus (DI) and respiratory symptoms due to a spontaneous pneumothorax with favorable clinical evolution. High-resolution CT demonstrated bilateral nodular and cystic pulmonary lesions. MRI revealed a nodular widening of the pituitary stalk. An endoscopic trans bronchial biopsy was negative for Langerhans cells. After thoracoscopy with surgical biopsy of the lung the diagnosis of Langerhans' cell histiocytosis was confirmed. (author)

  20. The ELAM-1 ligand sialosyl-Le(X) is present on Langerhans cells isolated from stratified epithelium

    DEFF Research Database (Denmark)

    Nylander, K; Larsen, J K; Larsen, J

    1992-01-01

    In this study we show the expression of the newly identified carbohydrate ligand, sialosyl-Le(X) on Langerhans cells. The receptor for sialosyl-Le(X) is the endothelial leukocyte adhesion molecule-1 (ELAM-1) present on activated endothelial cells. Using flow cytometry, Langerhans cells were selec...... at investigating the importance of adhesion between sialosyl Le(X) and ELAM-1 in epithelial recruitment of Langerhans cells....

  1. LANGERHANS CELL HISTIOCYTOSIS - EXPRESSION OF LEUKOCYTE CELLULAR ADHESION MOLECULES SUGGESTS ABNORMAL HOMING AND DIFFERENTIATION

    NARCIS (Netherlands)

    DEGRAAF, JH; TAMMINGA, RYJ; KAMPS, WA; TIMENS, W

    Langerhans' cell histiocytosis (LCH) is characterized by an accumulation of cells with a Langerhans' cell (LC) phenotype. Most patients present with solitary skin or bone lesions, but multi-organ lesions may appear Twenty-two LCH-tissue sections from 13 children and adolescents, with lesions at

  2. Unusual location of central nervous system langerhans cell histiocytosis: case report

    International Nuclear Information System (INIS)

    Kim, E. Yup; Lee, Jae Kyu; Kim, Chan Kyo; Lee, Chang Hyun; Kang, Chang Ho; Chung, Phil Wook

    2003-01-01

    Langerhans cell histiocytosis of the central nervous system (CNS) usually involves the hypothalamic-pituitary axis, and T1-weighted MR images normally demonstrate infundibular thickening and/or a mass lesion in the hypothalamus and the absence of a posterior pituitary 'bright spot'. We recently encountered a case of CNS langerhans cell histiocytosis with no posterior pituitary 'bright spot' and with lesions involving the cerebellum and basal ganglia but not the hypothalamic-pituitary axis

  3. Langerhans cell histiocytosis revisited: Case report with review

    Directory of Open Access Journals (Sweden)

    Y Pavan Kumar

    2015-01-01

    Full Text Available Langerhans cell histiocytosis (LCH is a group of idiopathic disorders characterized by proliferation of bone marrow derived Langerhans cells and mature eosinophils. Their clinical features simulate common oral findings such as gingival enlargement, oral ulcers, and mobility of teeth, along with nonspecific radiographic features; hence, diagnosing such lesions becomes difficult for the oral physicians. These lesions are commonly seen in childhood; however, we are reporting a case of LCH in 29-year-old adult male. A provisional diagnosis of giant cell granuloma was considered based on history and examination, although the lesion was histologically proven to be LCH and was confirmed with immunohistochemical staining of S100 protein and CD1a antigen. The purpose of this paper is to enhance the understanding of diverse, nonpathognomical oral presentation of LCH that is easily misdiagnosed and overlooked by dentist.

  4. Langerhans cells are required for UVR-induced immunosuppression

    NARCIS (Netherlands)

    Schwarz, Agatha; Noordegraaf, Madelon; Maeda, Akira; Torii, Kan; Clausen, Björn E.; Schwarz, Thomas

    2010-01-01

    Painting of haptens onto UVR-exposed skin does not result in sensitization but induces regulatory T cells (Treg). This was explained by UVR-mediated depletion of Langerhans cells (LCs). Furthermore, migration of UVR-damaged but still viable LCs into lymph nodes appears to be essential to induce

  5. Unusual location of central nervous system langerhans cell histiocytosis: case report

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    Kim, E. Yup; Lee, Jae Kyu; Kim, Chan Kyo; Lee, Chang Hyun; Kang, Chang Ho; Chung, Phil Wook [Armed Forces Capital Hospital, Seongnam (Korea, Republic of)

    2003-03-01

    Langerhans cell histiocytosis of the central nervous system (CNS) usually involves the hypothalamic-pituitary axis, and T1-weighted MR images normally demonstrate infundibular thickening and/or a mass lesion in the hypothalamus and the absence of a posterior pituitary 'bright spot'. We recently encountered a case of CNS langerhans cell histiocytosis with no posterior pituitary 'bright spot' and with lesions involving the cerebellum and basal ganglia but not the hypothalamic-pituitary axis.

  6. Burn injury suppresses human dermal dendritic cell and Langerhans cell function

    NARCIS (Netherlands)

    van den Berg, Linda M.; de Jong, Marein A. W. P.; Witte, Lot de; Ulrich, Magda M. W.; Geijtenbeek, Teunis B. H.

    2011-01-01

    Human skin contains epidermal Langerhans cells (LCs) and dermal dendritic cells (DCs) that are key players in induction of adaptive immunity upon infection. After major burn injury, suppressed adaptive immunity has been observed in patients. Here we demonstrate that burn injury affects adaptive

  7. [Pulmonary Langerhans' cell histiocytosis (PLCH) revealed by pneumothorax: about a case].

    Science.gov (United States)

    Sajiai, Hafsa; Rachidi, Mariam; Serhane, Hind; Aitbatahar, Salma; Amro, Lamyae

    2016-01-01

    Langerhans cell histiocytosis is a rare disease of unknown etiology characterized by the infiltration of Langerhans cells in one or more organs. It has a polymorphic clinical presentation. We report the case of Mr R.Y, age 22, with 8 pack year history of smoking, admitted to hospital with complete spontaneous right-sided pneumothorax. Chest drainage was performed with good evolution. Control chest CT scan showed multiple diffuse cyst formations, predominant in the upper lobes. Lab and imaging tests were performed in order to detect systemic histiocytosis with negative results. Patient's evolution was marked by pneumothorax recurrence; pleurodesis and lung biopsy were performed which confirmed the diagnosis. The diagnosis of Langerhans cell histiocytosis should be evoked in front of pneumothorax associated with lung cystic. The diagnosis is easy in front of a suggestive clinical and radiological picture. Nevertheless, therapeutic options are limited and pneumothorax recurrence is common.

  8. Low dose ultraviolet B-irradiated Langerhans cells preferentially activate CD4+ cells of the T helper 2 subset

    International Nuclear Information System (INIS)

    Simon, J.C.; Cruz, P.D. Jr.; Bergstresser, P.R.; Tigelaar, R.E.

    1990-01-01

    UVB radiation distorts the Ag-presenting function of epidermal Langerhans cells (LC); this has been shown for the presentation of soluble Ag to primed T cells in vitro and for the initiation of delayed-type hypersensitivity in vivo, such as contact hypersensitivity (CH). Previous work has also demonstrated UVB-induced suppression of CH to be mediated ultimately by T cells. Two subsets of CD4+ Th cells, Th1 and Th2, have been identified, based on their cytokine production and functional activities. In particular, Th1 mediate delayed-type hypersensitivity, whereas Th2 do not. To investigate whether the perturbation of LC function induced by UVB radiation leads to a differential activation of these subsets of CD4+ cells, we examined the capacity of unirradiated and irradiated (200 J/m2) APC from adult BALB/c mice to present keyhole limpet hemocyanin to Ag-specific, H2d-restricted Th1 and Th2 cell lines. Four sources of APC were utilized: epidermal cells (EC), flow microfluorometry-purified Ia+ EC (LC), flow microfluorometry-purified Ia- EC, and splenic adherent cells (SAC). Unirradiated EC, LC, and SAC, but not Ia-EC, presented keyhole limpet hemocyanin to both Th1 and Th2. Irradiated EC and LC lost their ability to stimulate Th1, but retained fully their capacity to stimulate Th2. On the other hand, irradiated SAC were unable to induce proliferation of either Th1 or Th2. These findings indicate that suppression of CH mediated by UVB-irradiated LC may result from an alteration of the ratio and/or activity of Th1 and Th2 cells normally generated during the induction of such responses

  9. [Neuroimaging of Langerhans cell histiocytosis in the central nervous system of children].

    Science.gov (United States)

    De La Hoz Polo, M; Rebollo Polo, M; Fons Estupiña, C; Muchart López, J; Cruz Martinez, O

    2015-01-01

    Langerhans cell histiocytosis (LCH) is a rare disease characterized by the accumulation within tissues of anomalous dendritic cells similar to Langerhans cells. The clinical presentation varies, ranging from the appearance of a single bone lesion to multisystemic involvement. Central nervous system (CNS) involvement, manifesting as diabetes insipidus secondary to pituitary involvement, has been known since the original description of the disease. Two types of CNS lesions are currently differentiated. The first, pseudotumoral lesions with infiltration by Langerhans cells, most commonly manifests as pituitary infiltration. The second, described more recently, consists of neurodegenerative lesions of the CNS associated with neurologic deterioration. This second type of lesion constitutes a complication of the disease; however, there is no consensus about the cause of this complication. Our objective was to describe the radiologic manifestations of LCH in the CNS in pediatric patients. Copyright © 2013 SERAM. Published by Elsevier España, S.L.U. All rights reserved.

  10. Somatic activating ARAF mutations in Langerhans cell histiocytosis

    NARCIS (Netherlands)

    Nelson, David S.; Quispel, Willemijn; Badalian-Very, Gayane; van Halteren, Astrid G. S.; van den Bos, Cor; Bovée, Judith V. M. G.; Tian, Sara Y.; van Hummelen, Paul; Ducar, Matthew; MacConaill, Laura E.; Egeler, R. Maarten; Rollins, Barrett J.

    2014-01-01

    The extracellular signal-regulated kinase (ERK) signaling pathway is activated in Langerhans cell histiocytosis (LCH) histiocytes, but only 60% of cases carry somatic activating mutations of BRAF. To identify other genetic causes of ERK pathway activation, we performed whole exome sequencing on

  11. Estudo quantitativo das células de Langerhans em carcinomas basocelulares com maior e menor potencial de agressividade local Quantitative study of Langerhans cells in basal cell carcinoma with higher or lower potential of local aggressiveness

    Directory of Open Access Journals (Sweden)

    Itamar Santos

    2010-04-01

    Full Text Available FUNDAMENTOS - O carcinoma basocelular localiza-se principalmente em áreas expostas ao sol, apresentando formas clínicas e histológicas diferentes, algumas com grande e outras com pequena agressividade local. Células de Langerhans participam ativamente do sistema imune da pele. OBJETIVO - Avaliar quantitativamente as células de Langerhans sobrepostas aos carcinomas basocelulares de maior e menor potencial de agressividade local, assim como nas respectivas epidermes sãs adjacentes. MÉTODOS - Dois grupos com 14 preparações histológicas cada. No primeiro, carcinoma basocelular de menor potencial de agressividade local e, no segundo, carcinoma basocelular de maior potencial. Empregou-se a imunoistoquímica com proteína S100 para identificação das células de Langerhans. Utilizando microscópio óptico em aumento de 400 vezes e a grade morfométrica de Weibel, foram contadas as células de Langerhans presentes em sete campos, obtendo-se a média em cada lâmina. Foi utilizado teste estatístico de Wilcoxon para análise estatística. RESULTADOS - No grupo de menor potencial de agressividade local, na epiderme sã adjacente houve aumento significativo no número de células de Langerhans comparado ao da epiderme sobreposta ao carcinoma basocelular (p d 0,05. No grupo de maior potencial de agressividade local, não houve diferença com significado estatístico (p > 0,05. CONCLUSÃO - O maior número de células de Langerhans na epiderme sã vizinha à lesão tumoral de menor potencial de agressividade local poderia representar uma maior resistência imunológica da epiderme, limitando a agressividade da neoplasia.BACKGROUNDS - Basal cell carcinoma affects areas of the body that have been exposed to the sun, and this disorder has different clinical and histopathologic presentations. Some of these forms have a higher potential of local aggressiveness, while others have a lower potential. Langerhans cells actively participate in the skin

  12. Langerhans cells and subsets of lymphocytes in the nasal mucosa

    DEFF Research Database (Denmark)

    Hellquist-Dahl, B; Olsen, K E; Irander, K

    1991-01-01

    Langerhans cells and different lymphocytes were studied in the nasal mucosa of 39 woodwork teachers and a control group of 14 healthy subjects. Ten of the woodwork teachers were sensitized as determined by skin prick test. A panel of different monoclonal antibodies was applied on the frozen nasal...... mucosal specimens. Intraepithelial CD1-positive dendritic cells were found in all specimens. However, there was no difference between the number of these Langerhans cells found in the study group and the number found in the controls. In every specimen the intraepithelial lymphocyte population...... was dominated by T lymphocytes, and there were relatively few B cells. Similarly the ratio between CD4- and CD8-positive lymphocytes in the study group and the controls was the same. In all specimens there was a dominance of T suppressor/cytotoxic cells compared with T helper/inducer cells. The study confirms...

  13. Acute leukemia in association with Langerhans cell histiocytosis

    NARCIS (Netherlands)

    R.M. Egeler (Maarten); J.P. Neglia (J.); M. Aricò (Maurizio); B.E. Favara (B.); A. Heitger (A.); M.E. Nesbit (M.)

    1994-01-01

    textabstractLangerhans cell histiocytosis (LCH) and malignancy occurring in the same individual is unusual and has generally been the subject of isolated case reports. To better define the occurrence of these events a registry of cases with synchronous or asynchronous LCH and malignancy was

  14. Langerhans cell histiocytosis of bone in an adult: A case report

    Directory of Open Access Journals (Sweden)

    Zachary Christopher, MD

    2018-04-01

    Full Text Available Langerhans cell histiocytosis (LCH may clinically manifest in a variety of ways due to its ability to involve nearly every organ system. LCH may present as a single bone lesion, skin rash, or as invasive disseminated disease and occurs typically in the pediatric and adolescent population, affecting both males and females. Independent of its clinical presentation and severity, LCH lesions share the common histology of CD1a+/CD207+ dendritic cells along with an inflammatory infiltrate, and, based upon improved scientific understanding, is now classified as a myeloproliferative neoplasm. We present a case report of an adult diagnosed with LCH of the pelvis. Keywords: Langerhans cell histiocytosis, Adults, Pelvis

  15. Polyclonal T-cells express CD1a in Langerhans cell histiocytosis (LCH lesions.

    Directory of Open Access Journals (Sweden)

    Jennifer A West

    Full Text Available Langerhans cell histiocytosis (LCH is a complex and poorly understood disorder that has characteristics of both inflammatory and neoplastic disease. By using eight-colour flow cytometry, we have identified a previously unreported population of CD1a(+/CD3(+ T-cells in LCH lesions. The expression of CD1a is regarded as a hallmark of this disease; however, it has always been presumed that it was only expressed by pathogenic Langerhans cells (LCs. We have now detected CD1a expression by a range of T-cell subsets within all of the LCH lesions that were examined, establishing that CD1a expression in these lesions is no longer restricted to pathogenic LCs. The presence of CD1a(+ T-cells in all of the LCH lesions that we have studied to date warrants further investigation into their biological function to determine whether these cells are important in the pathogenesis of LCH.

  16. Quantitative studies of the fate of epidermal Langerhans cells after X-irradiation of guinea-pig and mouse footpad skin

    Energy Technology Data Exchange (ETDEWEB)

    Cole, S.; Fairweather, J.M.; Townsend, K.M.S.

    1987-01-01

    Langerhans cell numbers, morphology and distribution were observed in cross sections of footpad epidermis from 1 to 28 days after exposure of the hind feed of CBA/H mice or albino guinea-pigs to a single absorbed dose of 20 Gy of X-rays. In mice, the number of Langerhans cells reactive with anti-macrophage F4/80 monoclonal antibody steadily declined by approximately 85% within 10 days after irradiation. Remaining Langerhans cells were exceptionally dendritic. Very few Birbeck granule-containing cells were found in murine popliteal lymph nodes before or after irradiation but damaged cells were present in superficial strata of irradiated epidermis. The morphology and number of epidermal F4/80-positive cells approached normal by 15 days after irradiation. In guinea-pigs, gradual suprabasal movement and loss of rounded, ATPase-positive Langerhans cells from the epidermis were detectable from 5 to 20 days after irradiation but the magnitude of the cell loss and redistribution was partially obscured by the simultaneous appearance of clusters of replacement Langerhans cells in the basal layer and by keratinocyte hyperplasia.

  17. TNP-specific Lyt-2+ cytolytic T cell clones preferentially respond to TNP-conjugated epidermal cells

    International Nuclear Information System (INIS)

    Shimada, S.; Katz, S.I.

    1985-01-01

    A most effective method for the induction of hapten-specific allergic contact sensitivity (CS) is via epicutaneous application of the hapten. Another effective method is by the administration of haptenated epidermal cells (EC) subcutaneously. The latter method induces more intense and longer lasting CS than does the subcutaneous administration of haptenated spleen cells (SC). Thus, there may be something unique about EC which, when haptenated, allows them to generate effector cells more effectively than do SC. The authors therefore, attempted to generate T cell clones that were both hapten- and epidermal-specific. Four days after painting mice with 7% trinitrochlorobenzene, draining lymph node cells were obtained and T cells were purified. These cells were co-cultured with trinitrophenylated (TNP) Langerhans cell-enriched EC. After 4 days, cells were harvested and rested on non-TNP-conjugated EC. The cells were restimulated and rested three times, and were then cloned by limiting dilution with added interleukin 2, which was then continually added. Proliferation of T cells was assessed by [ 3 H]-thymidine incorporation. Cytotoxicity assays utilized TNP-conjugated concanavalin A SC blasts or EC as targets. Clones A-2 and E-4 are Thy-1+, Lyt-2+, and L3T4-, and TNP-specific. In contrast to noncloned TNP-specific T cells, the clones proliferate preferentially in response to TNP-EC rather than TNP-SC. Also in contrast to noncloned T cells, the clones were preferentially cytotoxic for TNP-EC; compared to TNP-SC, there was an eight- to 32-fold increase in killing when TNP-EC were used as targets. Clones A-2 and E-4 therefore exhibit hapten and epidermal specificity

  18. Conventional radiology in the bony compromise of Langerhans cells Histiocytosis

    International Nuclear Information System (INIS)

    Morales, Nilson; Gonzalez, Claudia Patricia; Melendez, Patricia; Terselich, Gretty

    1999-01-01

    We present a descriptive study of 47 patients who attended the National Cancer Institute in Bogota, Colombia with pathological diagnosis of Langerhans cell histiocytosis. We reviewed the most frequent conventional x-ray findings

  19. Skull Base Langerhans Cell Histiocytosis with Diabetes Insipidus and Panhypopituitarism- A Rare Clinical Entity

    Directory of Open Access Journals (Sweden)

    Anirban Ghosh

    2017-12-01

    Case Report A 16 year old male presented with diminished vision, bilateral ptosis, left sided lateral rectus palsy, hypoesthesia of trigeminal nerve with nasal obstruction for last 5 months. There was polypoidal, bleeding mass in both nasal cavities. Contrast enhanced CT Scan showed a large homogenous mass arising from sphenoid extending into cavernous sinus and the suprasellar region. Endoscopic nasal biopsy revealed abundant Langerhans cell histiocytes, macrophages, neutrophils. Chemotherapy and radiotherapy were administered. But within 2 months the patient presented with Cushingoid features and further diminution of vision. Detailed work-up revealed Hypogonadotrophic hypogonadism and diabetes insipidus. Debulking of the tumour was done and left optic nerve decompression was done. PET scan was performed and showed large, well defined mass with increased FDG uptake in the skull base with suprasellar extension, reaching upto petrous temporal bone and causing bony erosion of ethmoid and sphenoid sinuses. Patient was then advised adjuvant chemotherapy.   Discussion Langerhans cell histiocytosis is a rare group of disorders characterised by abnormal clonal proliferation and accumulation of abnormal dendritic cells. Involvement of base of skull is even rarer. Though diabetes insipidus has been reported in Langerhans cell histiocytosis involving pituitary, panhypopituitarism is rare. These combinations of extensive Langerhans cell histiocytosis of base skull with clinical features of Diabetes insipidus and panhypopituitarism makes this case a rare clinical entity.

  20. Ontogeny and function of murine epidermal Langerhans cells.

    Science.gov (United States)

    Kaplan, Daniel H

    2017-09-19

    Langerhans cells (LCs) are epidermis-resident antigen-presenting cells that share a common ontogeny with macrophages but function as dendritic cells (DCs). Their development, recruitment and retention in the epidermis is orchestrated by interactions with keratinocytes through multiple mechanisms. LC and dermal DC subsets often show functional redundancy, but LCs are required for specific types of adaptive immune responses when antigen is concentrated in the epidermis. This Review will focus on those developmental and functional properties that are unique to LCs.

  1. Langerhans cell scarcoma in two young children: Imaging findings on initial presentation and recurrence

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Woong Do; Im, Soo Ah; Chung, Nak Gyun; Park, Gyeong Sin [Seoul St. Mary' s Hospital, Callege of Medicine, The Catholic University of Korea, Seoul (Korea, Republic of)

    2013-06-15

    Langerhans cell sarcoma (LCS) is a neoplastic proliferation of Langerhans cells with malignant cytological features and multi-organ involvement that typically has a poor prognosis. We experienced 2 cases of LCS in children less than 2 years of age and report them based primarily on CT and MR findings. Both children had findings of hepatosplenomegaly with low-attenuation nodular lesions, had multiple lymphadenopathy, and had shown recurrent lesions invading the skull during follow-up after chemotherapy.

  2. Melanotic paraganglioma arising in the temporal horn following Langerhans cell histiocytosis

    International Nuclear Information System (INIS)

    Yoo, Jeong Hyun; Rivera, Andreana; Naeini, Ramin M.; Yedururi, Sireesha; Megahead, Hatem; Bayindir, Petek; Fuller, Gregory N.; Suh, Jeong Soo; Adesina, Adekunle M.; Hunter, Jill V.

    2008-01-01

    Intracerebral paragangliomas are rare because of the lack of paraganglial cells in the cerebral tissue. We report a rare case of melanotic paraganglioma arising from the temporal horn of the lateral ventricle in a patient with prior Langerhans cell histiocytosis (LCH) treated with chemotherapy and radiation. (orig.)

  3. Enrichment of unlabeled human Langerhans cells from epidermal cell suspensions by discontinuous density gradient centrifugation

    NARCIS (Netherlands)

    Teunissen, M. B.; Wormmeester, J.; Kapsenberg, M. L.; Bos, J. D.

    1988-01-01

    In this report we introduce an alternative procedure for enrichment of human epidermal Langerhans cells (LC) from epidermal cell suspensions of normal skin. By means of discontinuous Ficoll-Metrizoate density gradient centrifugation, a fraction containing high numbers of viable, more than 80% pure

  4. Intracranial non-Langerhans cell histiocytosis presenting as an isolated intraparenchymal lesion

    Energy Technology Data Exchange (ETDEWEB)

    Rajaram, Smitha; Shackley, Fiona; Raghavan, Ashok [Western Bank, Sheffield Children' s Hospital, Sheffield (United Kingdom); Wharton, Stephen B. [University of Sheffield, Department of Neurosciences, Sheffield (United Kingdom); Connolly, Daniel J.A. [Western Bank, Sheffield Children' s Hospital, Sheffield (United Kingdom); University of Sheffield, Academic Radiology, Sheffield (United Kingdom)

    2010-12-15

    Non-Langerhans cell histiocytosis in the absence of cutaneous or other organ involvement is very rare. A Caucasian boy age 3 years 11 months presented with episodes of recurrent right-side seizures over 2 weeks. Brain CT and MR imaging showed a single enhancing left frontal lobe lesion. Stereotactic biopsy was performed and histological examination showed diffuse infiltrate of macrophages with foamy cytoplasm. Four months later there was recurrence of seizure activity despite anti-epileptic medication and a repeat MR scan showed a persistent enhancing lesion in the left frontal lobe. Histological examination of the resection specimen resembled juvenile xanthogranuloma (JXG) involving the central nervous system. In the absence of skin lesions a diagnosis of non-Langerhans cell histiocytosis was made. The child made a full recovery following surgery with resolution of his symptoms. (orig.)

  5. Isolated thymic Langerhans cell histiocytosis discovered on F-18 fluorodeoxyglucose positron emission tomography/computed tomography (F-18 FDG PET/CT).

    Science.gov (United States)

    Turpin, Sophie; Carret, Anne-Sophie; Dubois, Josée; Buteau, Chantal; Patey, Natalie

    2015-11-01

    The thymic infiltration in young patients with multisystemic Langerhans cell histiocytosis and its radiologic features are well known. However, isolated thymic disease has seldom been reported in the literature. We report the case of a 10-month-old child admitted for fever of unknown origin. Whole-body F-18 fluorodeoxyglucose positron emission tomography/computed tomography (F-18 FDG PET/CT) was performed to identify a focus of infection. It demonstrated an unusual aspect of the thymus, which led to further investigation and revealed isolated infiltration of the thymus by Langerhans cell histiocytosis. The patient was treated accordingly and is now disease free. As evaluation of Langerhans cell histiocytosis patients with F-18 FDG PET/CT is becoming more frequent, it is important to be aware of the scintigraphical characteristics of thymic Langerhans cell histiocytosis.

  6. Isolated thymic Langerhans cell histiocytosis discovered on F-18 fluorodeoxyglucose positron emission tomography/computed tomography (F-18 FDG PET/CT)

    Energy Technology Data Exchange (ETDEWEB)

    Turpin, Sophie [CHU Sainte-Justine, Nuclear Medicine, Montreal (Canada); Carret, Anne-Sophie [CHU Sainte-Justine, Hemato-Oncology, Montreal (Canada); Dubois, Josee [CHU Sainte-Justine, Radiology, Montreal (Canada); Buteau, Chantal [CHU Sainte-Justine, Infectious Diseases, Montreal (Canada); Patey, Natalie [CHU Sainte-Justine, Pathology, Montreal (Canada)

    2015-11-15

    The thymic infiltration in young patients with multisystemic Langerhans cell histiocytosis and its radiologic features are well known. However, isolated thymic disease has seldom been reported in the literature. We report the case of a 10-month-old child admitted for fever of unknown origin. Whole-body F-18 fluorodeoxyglucose positron emission tomography/computed tomography (F-18 FDG PET/CT) was performed to identify a focus of infection. It demonstrated an unusual aspect of the thymus, which led to further investigation and revealed isolated infiltration of the thymus by Langerhans cell histiocytosis. The patient was treated accordingly and is now disease free. As evaluation of Langerhans cell histiocytosis patients with F-18 FDG PET/CT is becoming more frequent, it is important to be aware of the scintigraphical characteristics of thymic Langerhans cell histiocytosis. (orig.)

  7. Murine epidermal Langerhans cells and langerin-expressing dermal dendritic cells are unrelated and exhibit distinct functions

    NARCIS (Netherlands)

    Nagao, Keisuke; Ginhoux, Florent; Leitner, Wolfgang W.; Motegi, Sei-Ichiro; Bennett, Clare L.; Clausen, Björn E.; Merad, Miriam; Udey, Mark C.

    2009-01-01

    A new langerin(+) DC subset has recently been identified in murine dermis (langerin(+) dDC), but the lineage and functional relationships between these cells and langerin(+) epidermal Langerhans cells (LC) are incompletely characterized. Selective expression of the cell adhesion molecule EpCAM by LC

  8. High-resolution computed tomography findings in pulmonary Langerhans cell histiocytosis

    Energy Technology Data Exchange (ETDEWEB)

    Rodrigues, Rosana Souza [Universidade Federal do Rio de Janeiro (HUCFF/UFRJ), RJ (Brazil). Hospital Universitario Clementino Fraga Filho. Unit of Radiology; Capone, Domenico; Ferreira Neto, Armando Leao [Universidade do Estado do Rio de Janeiro (UERJ), Rio de Janeiro, RJ (Brazil)

    2011-07-15

    Objective: The present study was aimed at characterizing main lung changes observed in pulmonary Langerhans cell histiocytosis by means of high-resolution computed tomography. Materials and Methods: High-resolution computed tomography findings in eight patients with proven disease diagnosed by open lung biopsy, immunohistochemistry studies and/or extrapulmonary manifestations were retrospectively evaluated. Results: Small rounded, thin-walled cystic lesions were observed in the lung of all the patients. Nodules with predominantly peripheral distribution over the lung parenchyma were observed in 75% of the patients. The lesions were diffusely distributed, predominantly in the upper and middle lung fields in all of the cases, but involvement of costophrenic angles was observed in 25% of the patients. Conclusion: Comparative analysis of high-resolution computed tomography and chest radiography findings demonstrated that thinwalled cysts and small nodules cannot be satisfactorily evaluated by conventional radiography. Because of its capacity to detect and characterize lung cysts and nodules, high-resolution computed tomography increases the probability of diagnosing pulmonary Langerhans cell histiocytosis. (author)

  9. A case of congenital solitary Langerhans cell histiocytoma.

    LENUS (Irish Health Repository)

    Ricciardo, Bernadette

    2012-02-01

    A newborn baby boy was referred to the Paediatric Dermatology Unit with a solitary asymptomatic nodule overlying his right nasolabial fold. Complete physical examination, full blood count, serum chemistry, liver function tests and baseline imaging were unremarkable. Histopathological examination showed an atypical dermal infiltrate of mononuclear cells that stained positive with CD1a and S100. A diagnosis of congenital solitary Langerhans cell histiocytoma was made. The lesion completely resolved by 4 months of age. The baby is now 15 months old and repeat systemic evaluation has remained normal.

  10. Button sequestrum in a case of localized Langerhans' cell histiocytosis of the ilium: case report

    International Nuclear Information System (INIS)

    Tordeur, M.; Wybier, M.; Laporte, J.L.; Grenier, P.; Laredo, J.D.

    2000-01-01

    Langerhans' cell histiocytosis (LCH) is characterized by a proliferation of cells exhibiting the same immunohistochemical and ultra-structural characteristics as Langerhans' cells of the epidermis. Eosinophilic granuloma, chronic polyostotic disease (Hand-Schuller-Christian disease) and multisystemic disease (Letterer-Siwe disease) all belong to the spectrum LCH. Osseous lesions are the most common findings. the radiological appearance of skeletal LCH depends on the site and on disease activity. Button sequestrum has been described as uncommon in LCH of the skull and exceedingly rare in LCH at other sites. We report a case of localized LCH of the ilium with a button sequestrum. (author)

  11. Langerhans cell histiocytosis with involvement of the pons: case report

    International Nuclear Information System (INIS)

    Vourtsi, A.; Papadopoulos, A.; Moulopoulos, L.A.; Vlahos, L.; Xenellis, J.

    1998-01-01

    Central nervous system involvement is uncommon in Langerhans cell histiocytosis. The suprasellar region is more frequently affected. There have been few reports of involvement of the brain parenchyma shown on CT or MRI. We present a case of involvement of the pons, showing marked contrast enhancement on MRI. (orig.)

  12. Rho-family GTPase Cdc42 controls migration of Langerhans cells in vivo

    DEFF Research Database (Denmark)

    Luckashenak, Nancy; Wähe, Anna; Breit, Katharina

    2013-01-01

    Epidermal Langerhans cells (LCs) of the skin represent the prototype migratory dendritic cell (DC) subtype. In the skin, they take up Ag, migrate to the draining lymph nodes, and contribute to Ag transport and immunity. Different depletion models for LCs have revealed contrasting roles and contri...

  13. CT and MR findings of langerhans cell histiocytois involving the spleen: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Pyun, Hae Wook; Kim, Mee Eun; Kim, Jang Ho [Fatima Hospital, Taegu (Korea, Republic of)

    2002-02-01

    Langerhans cell histiocytosis (LCH) is systemic disease resulting from the proliferation and dissemination of abnormal histiocytic cells of the Langerhans cell system. Common sites of involvement include the skin, bone, bone marrow, lung, lymph nodes and central nervous system, and the condition manifests in variety of ways. We present the CT and MR findings of a case of LCH involving the spleen, an organ invloved relatively rarely. Post-contrast CT revealed multiple hypodense nodules. T1-weighted MR images of the spleen depicted no definitive lesion, but T2-weighted images showed abnormal low signals scattered throughout this organ. In addition, post-contrast, fat-saturated T1-weighted MR images lesions showed multiple, low-signal-intensity lesions.

  14. MUTZ-3 derived Langerhans cells in human skin equivalents show differential migration and phenotypic plasticity after allergen or irritant exposure

    NARCIS (Netherlands)

    Kosten, I.J.; Spiekstra, S.W.; de Gruijl, T.D.; Gibbs, S.

    2015-01-01

    After allergen or irritant exposure, Langerhans cells (LC) undergo phenotypic changes and exit the epidermis. In this study we describe the unique ability of MUTZ-3 derived Langerhans cells (MUTZ-LC) to display similar phenotypic plasticity as their primary counterparts when incorporated into a

  15. In situ behavior of human Langerhans cells in skin organ culture

    NARCIS (Netherlands)

    Rambukkana, A.; Bos, J. D.; Irik, D.; Menko, W. J.; Kapsenberg, M. L.; Das, P. K.

    1995-01-01

    Epidermal Langerhans cells (ELC) play a critical role in the initiation of cutaneous immune responses. ELC are characterized by the expression of major histocompatibility complex (MHC) class II Ag and a number of adhesion/costimulatory molecules. Evidence suggests that cytokines induced within the

  16. Multifocal Langerhans cell sarcoma involving epidermis: a case report and review

    Directory of Open Access Journals (Sweden)

    Wang Changsong

    2012-08-01

    Full Text Available Abstract Objective To study the clinico-pathological characteristics of Langerhans cell sarcoma (LCS which involving epidermis. Methods A case of primary multifocal LCS was analyzed in histopathology and immunophenotype. Results A 41-year-old man with multifocal cutaneous LCS involving the inguina and waist was reported. Clinical and pathology data were available. Neoplastic cells with markedly malignant cytological features were observed. Tumor cells exhibited irregular shape with abundant and eosinophilic red staining cytoplasm; large, irregular-shaped, showing lobulated or dented nucleus and some cells with a longitudinal nuclear groove and prominent nucleoli. The tumor cells expressed CD1a, Langerin (CD207, S-100 protein, CD68 and vimentin, and did not express pan-T or B cell markers and epithelial markers. The patient died less than 1 year after diagnosis due to local recurrence and metastasis to the lung, despite the administration of local radiation and chemotherapy. Conclusions LCS is a tumor with markedly malignant cytological features that originates from Langerhans cells. Primary multifocal neoplasms involving epidermis is even rare. Accurate diagnosis is based on the histopathological and immunohistochemical of the tumor cells. Virtual slide The virtual slide(s for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1182345104754765.

  17. Liver involvement in Langerhans cell histiocytosis

    International Nuclear Information System (INIS)

    Wong, Adelaine; Ortiz-Neira, Clara L.; Abou Reslan, Walid; Kaura, Deepak; Sharon, Raphael; Anderson, Ronald; Pinto-Rojas, Alfredo

    2006-01-01

    Liver involvement in Langerhans cell histiocytosis (LCH) typically presents with hepatomegaly and other signs of liver dysfunction. We present an 11-month-old child having only minimally elevated liver enzymes as an indication of liver involvement. Using sonography as the initial diagnostic tool followed by MRI, LCH of the liver was revealed. A review of sonographic, CT, MRI and MR cholangiopancreatography findings in liver LCH is presented. We recommend that physicians consider sonography and MRI screening for liver involvement in patients with newly diagnosed LCH, as periportal involvement may be present with little or no liver function abnormality present, as in this patient. (orig.)

  18. Multisystem Langerhans cell histiocytosis coexisting with metastasizing adenocarcinoma of the lung: A case report

    Directory of Open Access Journals (Sweden)

    Lovrenski Aleksandra

    2013-01-01

    Full Text Available Introduction. Langerhans cell histiocytosis (LCH is an uncommon disease of unknown etiology characterized by uncontrolled proliferation and infiltration of various organs by Langerhans cells. Case report. We presented a 54-year-old man, heavy smoker, with dyspnea, cough, hemoptysis, headache and ataxia, who died shortly after admission to our hospital. On the autopsy, tumor was found in the posterior segment of the right upper pulmonary lobe as well as a right-sided occipitoparietal lesion which penetrated into the right ventricle resulting in internal and external hematocephalus. Histologically and immunohistohemically, the diagnosis of primary lung adenocarcinoma with brain metastasis was made (tumor cells showed positivity for CK7 and TTF-1 which confirmed the diagnosis. In the lung parenchyma around the tumor, as well as in brain tissue around the metastatic adenocarcinoma histiocytic lesions were found. Light microscopic examination of the other organs also showed histiocytic lesions involving the pituitary gland, hypothalamus, spleen and mediastinal lymph nodes. Immunohistochemical studies revealed CD68, S-100 and CD1a immunoreactivity within the histiocytes upon which the diagnosis of Langerhans' cells histiocytosis was made. Conclusion. The multisystem form of LCH with extensive organ involvement was an incidental finding, while metastatic lung adenocarcinoma to the brain that led to hematocephalus was the cause of death.

  19. Langerhans cell histiocytosis with involvement of the pons: case report

    Energy Technology Data Exchange (ETDEWEB)

    Vourtsi, A. [Xatzopoulou, Athens (Greece)]|[Department of Radiology, University of Athens Medical School, Athens (Greece); Papadopoulos, A.; Moulopoulos, L.A.; Vlahos, L. [Department of Radiology, University of Athens Medical School, Athens (Greece); Xenellis, J. [Department of Otorhinolaryngology, University of Athens Medical School, Athens (Greece)

    1998-03-01

    Central nervous system involvement is uncommon in Langerhans cell histiocytosis. The suprasellar region is more frequently affected. There have been few reports of involvement of the brain parenchyma shown on CT or MRI. We present a case of involvement of the pons, showing marked contrast enhancement on MRI. (orig.) With 2 figs., 17 refs.

  20. Langerhans cells favor skin flora tolerance through limited presentation of bacterial antigens and induction of regulatory T cells

    NARCIS (Netherlands)

    van der Aar, Angelic M. G.; Picavet, Daisy I.; Muller, Femke J.; de Boer, Leonie; van Capel, Toni M. M.; Zaat, Sebastian A. J.; Bos, Jan D.; Janssen, Hans; George, Thaddeus C.; Kapsenberg, Martien L.; van Ham, S. Marieke; Teunissen, Marcel B. M.; de Jong, Esther C.

    2013-01-01

    The mechanisms preventing detrimental T-cell responses against commensal skin bacteria remain elusive. Using monocyte-derived and skin-derived dendritic cells (DCs), we demonstrate that epidermal Langerhans cells (LCs), the DCs in the most superficial layer of the skin, have a poor capacity to

  1. Histiocitose das células de Langerhans na região anogenital Langerhans cell histiocytosis of the anogenital region

    Directory of Open Access Journals (Sweden)

    M. S. Neto

    1998-12-01

    Full Text Available A Histiocitose das células de Langerhans (HCL acometendo o trato genital tem uma incidência rara com apenas 48 casos relatados na literatura1-5 . Considerando somente as lesões da região anogenital, esse número cai para dois casos descritos1,2. Reportamos o 3º caso de HCL anogenital em uma paciente de 31 anos, branca, cuja comprovação diagnóstica foi feita através de microscopia eletrônica. O tratamento realizado foi quimioterapia sistêmica e excisão cirúrgica local.The Langerhans cell histiocytosis (LCH of the genital tract is rare, with only 48 cases related in the literature1-5. There were reported only 2 cases in the anogenital region1,2. We reported the third case of LCH in the anogenital region; patient was female, 31 years-old, caucasian and the diagnosis was confirmed by electron microscopic magnification. The treatment was local surgical excision and systemic chemotherapy.

  2. Persistent pulmonary interstitial emphysema in a case of Langerhans cell histiocytosis

    International Nuclear Information System (INIS)

    Abbey, Pooja; Narula, Mahender K.; Anand, Rama; Chandra, Jagdish

    2014-01-01

    We present the case of a 10-month-old boy with multisystem Langerhans cell histiocytosis showing thin-walled lung cysts along with computed tomography (CT) evidence of persistent pulmonary interstitial emphysema (PPIE), in the absence of pneumothorax or pneumomediastinum. Follow-up CT performed after 6 months demonstrated complete resolution of interstitial emphysema

  3. Inducible ablation of mouse Langerhans cells diminishes but fails to abrogate contact hypersensitivity

    NARCIS (Netherlands)

    Bennett, Clare L.; van Rijn, Erwin; Jung, Steffen; Inaba, Kayo; Steinman, Ralph M.; Kapsenberg, Martien L.; Clausen, Björn E.

    2005-01-01

    Langerhans cells (LC) form a unique subset of dendritic cells ( DC) in the epidermis but so far their in vivo functions in skin immunity and tolerance could not be determined, in particular in relation to dermal DC ( dDC). Here, we exploit a novel diphtheria toxin (DT) receptor (DTR)/ DT- based

  4. Langerhans Cell Histiocytosis: A Diagnostic Challenge in the Oral Cavity

    Directory of Open Access Journals (Sweden)

    Mehmet Ali Altay

    2017-01-01

    Full Text Available Background. Langerhans cell histiocytosis (LCH is a rare disorder of the reticuloendothelial system with unknown etiology. This report aims to present a case of LCH with diffuse involvement of the oral cavity and to raise awareness of the distinguishing features of this diagnostically challenging entity. Case Report. A 26-year-old male patient presented with complaints of teeth mobility, intense pain, and difficulty in chewing. Intraoral and radiological examinations revealed generalized gingival hyperplasia and severe teeth mobility with widespread alveolar bone loss. Periodontal therapy was performed with no significant improvement. An incisional biopsy revealed Langerhans cells and positive reaction to S-100 and CD1, and the patient was diagnosed with LCH. The patient underwent systemic chemotherapy with vinca alkaloids and corticosteroids. Regression of gingival lesions, as well as significant decrease in mobility of the remaining teeth and severity of pain, was achieved during 12 months of follow-up. Conclusion. The rarity and variable system involvement of LCH necessitate a multidisciplinary approach be carried out for accurate diagnosis, effective treatment, and an uneventful follow-up. Awareness of oral manifestations of LCH may aid clinicians greatly in reducing morbidity and mortality associated with this debilitating condition.

  5. Comparative Ultrastructure of Langerhans-Like Cells in Spleens of Ray-Finned Fishes (Actinopterygii)

    Czech Academy of Sciences Publication Activity Database

    Lovy, J.; Wright, G. M.; Speare, D. J.; Tyml, Tomáš; Dyková, Iva

    2010-01-01

    Roč. 271, č. 10 (2010), s. 1229-1239 ISSN 0362-2525 R&D Projects: GA MŠk LC522 Institutional research plan: CEZ:AV0Z60220518 Keywords : fish * cyprinidae * halibut * dendritic cells * Langerhans cell * Birbeck granules * ultrastructure Subject RIV: GJ - Animal Vermins ; Diseases, Veterinary Medicine Impact factor: 1.773, year: 2010

  6. Langerhans cells from human oral epithelium are more effective at stimulating allogeneic T cells in vitro than Langerhans cells from skin.

    Science.gov (United States)

    Hasséus, B; Jontell, M; Bergenholtz, G; Dahlgren, U I

    2004-06-01

    This report is focused on the functional capacity of Langerhans cells (LC) in the epithelium of skin and oral mucosa, which both meet different antigenic challenges. The capacity of LC from human oral and skin epithelium to provide co-stimulatory signals to T cells in vitro was compared. LC in a crude suspension of oral epithelial cells had a significantly enhanced T cell co-stimulatory capacity compared to skin epithelial cells. This applied both to cultures with concanavalin A (con-A)-stimulated syngeneic T cells and to a mixed epithelial cell lymphocyte reaction involving allogeneic T cells. The co-stimulatory capacity of oral and skin epithelial cells was reduced by >70% if monoclonal antibodies against HLA-DR, -DP and -DQ were added to the cultures with allogeneic T cells, indicating the involvement of HLA class II expressing LC. Immunohistochemistry revealed that 6% of the epithelial cells were CD1a + LC in sections from both oral and skin epithelium. Interleukin (IL)-8 production was higher in cultures of oral epithelial cells and con-A stimulated T cells than in corresponding cultures with skin epithelial cells as accessory cells. The results suggest that LC in human oral epithelium are more efficient at stimulating T cells than those of skin.

  7. Histiocitose das células de Langerhans: experiência de 16 anos Langerhans cell histiocytosis: a 16-year experience

    Directory of Open Access Journals (Sweden)

    Márcia Kanadani Campos

    2007-02-01

    Full Text Available OBJETIVOS: Descrever a apresentação clínica da histiocitose das células de Langerhans e comparar sua evolução de acordo com a idade, estadiamento e resposta ao tratamento. MÉTODOS: Análise retrospectiva dos dados referentes a 33 crianças com histiocitose das células de Langerhans acompanhadas no Hospital das Clínicas da Universidade Federal de Minas Gerais no período de 1988 a 2004. RESULTADOS: A idade ao diagnóstico variou de 2 meses a 16 anos (mediana: 2,5 anos. Dezessete crianças eram do sexo masculino. O tempo de seguimento variou de 21 dias a 16,2 anos (mediana: 3,4 anos. As manifestações clínicas mais comuns ao diagnóstico foram lesões osteolíticas, linfadenomegalia e lesões cutâneas. A sobrevida global para todo o grupo foi de 86,1% aos 16 anos (IC95% 66,6-94,6. Os óbitos ocorreram em pacientes com doença multissistêmica e disfunção orgânica ao diagnóstico. Os pacientes que apresentaram resposta "melhor" à sexta semana de tratamento apresentaram uma probabilidade estimada de sobrevida global significativamente maior em relação aos que apresentaram progressão da doença. A sobrevida global foi significativamente maior para os pacientes com doença em um único sistema. A probabilidade de sobrevida livre de eventos para todo o grupo foi de 30,9% aos 16 anos (IC95% 15,6-47,5, sendo significativamente maior para os portadores de doença em um único sistema. A idade não se associou com a sobrevida livre de eventos. A seqüela mais comum foi o diabetes insipidus. Não foram observados casos de neoplasias secundárias. CONCLUSÃO: A histiocitose das células de Langerhans apresenta uma grande variedade de manifestações clínicas, com alta taxa de recidivas e baixa taxa de mortalidade.OBJECTIVES: To describe the clinical course of Langerhans cell histiocytosis and to compare its outcome according to age, staging of the disease and treatment response. METHODS: Retrospective analysis of data on 33 children with

  8. Histiocitosis de células de Langerhans localizada en hueso malar: Presentación de un caso Localized langerhans cell histiocytosis of the zygomatic bone: A case report

    Directory of Open Access Journals (Sweden)

    María Loreto Castellón Zirpel

    2011-09-01

    Full Text Available La histiocitosis de células de Langerhans localizada (HCLL, conocida como granuloma eosinófilo, representa entre el 50 y el 60% de todos los casos de histiocitosis de células de Langerhans. El tratamiento clásico para la HCLL ha sido el curetaje o la resección de las lesiones óseas. Hay publicaciones de casos tratados con inyección intralesional de corticosteroides, combinado con curetaje. Se presenta un caso clínico de un paciente de tres años de edad con diagnóstico de HCLL que compromete en su extensión el hueso malar, tratado con infiltraciones de corticosteroides y posterior curetaje de la lesión. A un año de realizado el tratamiento, el paciente se encuentra asintomático y con una regeneración ósea del hueso malar, evidenciable en la tomografía axial computarizada.Localized Langerhans cell histiocytosis (LLCH, also known as eosinophilic granuloma, represents 50 to 60% of all cases of Langerhans cell histiocytosis. The standard treatment for LLCH has been lesion curettage or resection. Cases treated with intralesional corticosteroid injections combined with curettage have been described. We report the case of a three-year-old patient diagnosed of LLCH with extensive zygomatic bone involvement, who was treated with corticosteroid infiltrations and subsequent curettage of the lesion. One year after treatment, the patient is asymptomatic with zygomatic reossification evidenced on computed tomography.

  9. Pulmonary Langerhans Cell Histiocytosis with Lytic Bone Involvement in an Adult Smoker: Regression following Smoking Cessation

    Directory of Open Access Journals (Sweden)

    B. Routy

    2015-01-01

    Full Text Available Langerhans cell histiocytosis (LCH is a rare myeloid neoplasm characterized by the proliferation and dissemination of histiocytes. These in turn may cause symptoms ranging from isolated, infiltrative lesions to severe multisystem disease. Pulmonary Langerhans cell histiocytosis (PLCH presents as a localized polyclonal proliferation of Langerhans cells in the lungs causing bilateral cysts and fibrosis. In adults, this rare condition is considered a reactive process associated with cigarette smoking. Recently, clonal proliferation has been reported with the presence of BRAF V600E oncogenic mutation in a subset of PLCH patients. Spontaneous resolution was described; however, based on case series, smoking cessation remains the most effective way to achieve complete remission and prevent long term complications related to tobacco. Herein, we report the case of an adult woman with biopsy-proven PLCH presenting with thoracic (T8 vertebral bone destruction. Both the lung and the bone diseases regressed following smoking cessation, representing a rare case of synchronous disseminated PCLH with bone localization. This observation underscores the contribution of cigarette smoking as a systemic trigger of both pulmonary and extrapulmonary bone lesions. A review of similar cases in the literature is also presented.

  10. Primary cerebral non-Langerhans cell histiocytosis: MRI and differential diagnosis

    Energy Technology Data Exchange (ETDEWEB)

    Ernemann, U.; Skalej, M.; Voigt, K. [Department of Neuroradiology, University Hospital Tuebingen, Hoppe-Seyler-Strasse 3, 72076 Tuebingen (Germany); Hermisson, M.; Platten, M. [Department of Neurology, University Hospital Tuebingen, Hoppe-Seyler-Strasse 3, 72076 Tuebingen (Germany); Jaffe, R. [Pathology Department, Children' s Hospital of Pittsburgh, 3705 Fifth Avenue, Pittsburgh, PA 15213 (United States)

    2002-09-01

    We report a young woman with primary cerebral non-Langerhans cell histiocytosis of the juvenile xanthogranuloma family. The clinical course was complicated by extensive infiltration of cranial nerves and meninges and epi- and intramedullary spinal dissemination. Whereas the cutaneous form of juvenile xanthogranuloma is usually benign and self-limited, central nervous system involvement is associated with high morbidity and mortality and might therefore be considered a separate clinical entity. (orig.)

  11. New insights in lymphangioleiomyomatosis and pulmonary Langerhans cell histiocytosis

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    Olga Torre

    2017-09-01

    Full Text Available Lymphangioleiomyomatosis (LAM and pulmonary Langerhans cell histiocytosis (PLCH are rare diseases that lead to progressive cystic destruction of the lungs. Despite their distinctive characteristics, these diseases share several features. Patients affected by LAM or PLCH have similar radiological cystic patterns, a similar age of onset, and the possibility of extrapulmonary involvement. In this review, the recent advances in the understanding of the molecular pathogenesis, as well as the current and most promising biomarkers and therapeutic approaches, are described.

  12. Human papillomavirus-exposed Langerhans cells are activated by stabilized Poly-I:C

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    Diane M. Da Silva

    2015-12-01

    Full Text Available Human papillomaviruses (HPV establish persistent infections because of evolved immune evasion mechanisms, particularly HPV-mediated suppression of the immune functions of Langerhans cells (LC, the antigen presenting cells of the epithelium. Polyinosinic-polycytidilic acid (Poly-I:C is broadly immunostimulatory with the ability to enhance APC expression of costimulatory molecules and inflammatory cytokines resulting in T cell activation. Here we investigated the activation of primary human LC derived from peripheral blood monocytes after exposure to HPV16 virus like particles followed by treatment with stabilized Poly-I:C compounds (s-Poly-I:C, and their subsequent induction of HPV16-specific T cells. Our results indicate that HPV16 particles alone were incapable of inducing LC activation as demonstrated by the lack of costimulatory molecules, inflammatory cytokines, chemokine-directed migration, and HPV16-specific CD8+ T cells in vitro. Conversely, s-Poly-I:C caused significant upregulation of costimulatory molecules and induction of chemokine-directed migration of LC that were pre-exposed to HPV16. In HLA-A*0201-positive donors, s-Poly-I:C treatment was able to induce CD8+ T cell immune responses against HPV16-derived peptides. Thus, s-Poly-I:C compounds are attractive for translation into therapeutics in which they could potentially mediate clearance of persistent HPV infection. Keywords: Papillomavirus, HPV16, Langerhans cells, Immune escape

  13. A rare case of langerhans cell histiocytosis of the gastrointestinal tract

    Institute of Scientific and Technical Information of China (English)

    Uday Shankar; Monika Prasad; Om P Chaurasia

    2012-01-01

    Langerhans cell histiocytosis (LCH) is a group of idiopathic disorders characterized by the proliferation of specialized,bone marrow-derived langerhans cells and mature eosinophils.The clinical spectrum ranges from an acute,fulminant,disseminated disease called LettererSiwe disease to solitary or few,indolent and chronic lesions of the bone or other organs called eosinophilic granuloma.Involvement of the gastrointestinal tract is very rare in LCH.We present the case of a 53-year-old woman referred by her primary care physician for a screening colonoscopy.A single sessile polyp,measuring 4 mm in size,was found in the rectum.Histopathological examination revealed that the lesion was relatively well circumscribed and comprised mainly a mixture of polygonal cells with moderate-to-abundant pink slightly granular cytoplasm.The nuclei within these cells had frequent grooves and were occasionally folded.Immunohistochemical staining was positive for CD-1a which confirmed the diagnosis of LCH.On further workup,there was no evidence of involvement of any other organ.On follow up colonoscopy one year later,there was no evidence of disease recurrence.Review of the published literature revealed that LCH presenting as solitary colonic polyp is rare.However,with the increasing rates of screening colonoscopy,more colonic polyps may be identified as LCH on histopathology.This underscores the importance of recognizing this rare condition and ensuring proper follow-up to rule out systemic disease.

  14. Langerhans cell histiocytosis involving central nervous system: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Moon, Won Jin; Park, Dong Woo; Lee, Seung Ro; Hahm, Chang Kok; Ju, Kyung Bin [Hanyang University College of Medicine, Seoul (Korea, Republic of); Kim, Sung Tae [Ulsan University College of Medicine, Seoul (Korea, Republic of)

    1997-01-01

    Langerhans cell histiocytosis(LCH) is a systemic disorder characterized by idiopathic proliferation of histiocytes in the reticuloendothelial system; CNS involvement outside the hypothalamus or pituitary gland is uncommon. We present a case of LCH involving the brainstem, cerebellum, and temporal lobes, and also showing hypothalamic involvement. The lesions were isointense or hypointense on T1WI and hyperintense on T2WI, and showed multifocal enhancing nodules on post-contrast CT and Gd-enhanced MRI.

  15. T cell ignorance is bliss: T cells are not tolerized by Langerhans cells presenting human papillomavirus antigens in the absence of costimulation

    Directory of Open Access Journals (Sweden)

    Andrew W. Woodham

    2016-12-01

    Full Text Available Human papillomavirus type 16 (HPV16 infections are intra-epithelial, and thus, HPV16 is known to interact with Langerhans cells (LCs, the resident epithelial antigen-presenting cells (APCs. The current paradigm for APC-mediated induction of T cell anergy is through delivery of T cell receptor signals via peptides on MHC molecules (signal 1, but without costimulation (signal 2. We previously demonstrated that LCs exposed to HPV16 in vitro present HPV antigens to T cells without costimulation, but it remained uncertain if such T cells would remain ignorant, become anergic, or in the case of CD4+ T cells, differentiate into Tregs. Here we demonstrate that Tregs were not induced by LCs presenting only signal 1, and through a series of in vitro immunizations show that CD8+ T cells receiving signal 1+2 from LCs weeks after consistently receiving signal 1 are capable of robust effector functions. Importantly, this indicates that T cells are not tolerized but instead remain ignorant to HPV, and are activated given the proper signals. Keywords: T cell anergy, T cell ignorance, Immune tolerance, Human papillomavirus, HPV16, Langerhans cells

  16. Need for a cooperative study: Pulmonary Langerhans cell histiocytosis and its management in adults

    NARCIS (Netherlands)

    McClain, Kenneth L.; Gonzalez, Jorge Mario; Jonkers, Rene; de Juli, Emanuela; Egeler, Maarten

    2002-01-01

    BACKGROUND: Pulmonary involvement with Langerhans cell histiocytosis (LCH, formerly known as histiocytosis-X) presents as an interstitial process in children and adults either with or without symptoms. In contrast to other manifestations of LCH, most patients with pulmonary disease are adults.

  17. Langerhans Cell Histiocytosis in Childhood: Review, Symptoms in the Oral Cavity, Differential Diagnosis and Report of One Case

    Directory of Open Access Journals (Sweden)

    Mohammad Shooriabi

    2016-08-01

    Full Text Available Background Langerhans cell histiocytosis (LCH is a rare disease in which monoclonal migration and proliferation of specific dendritic cells is seen. The disease primarily affects the bones and skin, but there is a possibility that involves other organs or appears as a multi-systemic disease. Case Report In oral examination of a nine-month girl, two deep wounds with a yellow membrane with approximate size of 1 × 1 cm on both sides of mandibular alveolar ridge were seen. The edges of the wounds were swollen and proliferated and redder than the surrounding mucosa. At the touch the edges of the wound were not indurated. The wound were created from the third-month and the size of wounds had become slightly larger within 6 months. According to the chronic wound and being non-responsive to various systemic and local treatments, incisional biopsy was taken from the wounds. Langerhans cell histiocytosis was confirmedhistologically and immune histochemically. Conclusion Mouth ulcers may be the only symptoms of Langerhans cell histiocytosis. Therefore, the role of dentist could be important in diagnosis of this disease.

  18. Genetics Home Reference: Langerhans cell histiocytosis

    Science.gov (United States)

    ... as viral infections and environmental toxins, may also influence the development of this complex disorder. Learn more about the ... occur? How can gene mutations affect health and development? More about Mutations and ... in people with no history of the disorder in their family. A few families with multiple cases of Langerhans ...

  19. Hepatic involvement of Langerhans cell histiocytosis in children - imaging findings of computed tomography, magnetic resonance imaging and magnetic resonance cholangiopancreatography

    International Nuclear Information System (INIS)

    Shi, Yingyan; Qiao, Zhongwei; Gong, Ying; Yang, Haowei; Li, Guoping; Pa, Mier; Xia, Chunmei

    2014-01-01

    Langerhans cell histiocytosis is a rare disease that occurs mainly in children, and hepatic involvement is generally a poor prognostic factor. To describe CT and MRI findings of hepatic involvement of Langerhans cell histiocytosis in children, especially the abnormal bile duct manifestation on magnetic resonance cholangiopancreatography (MRCP). Thirteen children (seven boys, six girls; mean age 28.9 months) were diagnosed with disseminated Langerhans cell histiocytosis. They underwent CT (n = 5) or MRI (n = 4), or CT and MRI examinations (n = 4) to evaluate the liver involvement. Periportal abnormalities presented as band-like or nodular lesions on CT and MRI in all 13 children. The hepatic parenchymal lesions were found in the peripheral regions of the liver in seven children, including multiple nodules on MRI (n = 6), and cystic-like lesions on CT and MRI (n = 3). In 11 of the 13 children the dilatations of the bile ducts were observed on CT and MRI. Eight of the 13 children underwent MR cholangiopancreatography, which demonstrated stenoses or segmental stenoses with slight dilatation of the central bile ducts, including the common hepatic duct and its first-order branches. The peripheral bile ducts in these children showed segmental dilatations and stenoses. Stenosis of the central bile ducts revealed by MR cholangiopancreatography was the most significant finding of liver involvement in Langerhans cell histiocytosis in children. (orig.)

  20. Hepatic involvement of Langerhans cell histiocytosis in children - imaging findings of computed tomography, magnetic resonance imaging and magnetic resonance cholangiopancreatography

    Energy Technology Data Exchange (ETDEWEB)

    Shi, Yingyan; Qiao, Zhongwei; Gong, Ying; Yang, Haowei; Li, Guoping; Pa, Mier [Children' s Hospital of Fudan University, Department of Radiology, Shanghai (China); Xia, Chunmei [Shanghai Medical College of Fudan University, Physiology and Pathophysiology Department, Shanghai (China)

    2014-06-15

    Langerhans cell histiocytosis is a rare disease that occurs mainly in children, and hepatic involvement is generally a poor prognostic factor. To describe CT and MRI findings of hepatic involvement of Langerhans cell histiocytosis in children, especially the abnormal bile duct manifestation on magnetic resonance cholangiopancreatography (MRCP). Thirteen children (seven boys, six girls; mean age 28.9 months) were diagnosed with disseminated Langerhans cell histiocytosis. They underwent CT (n = 5) or MRI (n = 4), or CT and MRI examinations (n = 4) to evaluate the liver involvement. Periportal abnormalities presented as band-like or nodular lesions on CT and MRI in all 13 children. The hepatic parenchymal lesions were found in the peripheral regions of the liver in seven children, including multiple nodules on MRI (n = 6), and cystic-like lesions on CT and MRI (n = 3). In 11 of the 13 children the dilatations of the bile ducts were observed on CT and MRI. Eight of the 13 children underwent MR cholangiopancreatography, which demonstrated stenoses or segmental stenoses with slight dilatation of the central bile ducts, including the common hepatic duct and its first-order branches. The peripheral bile ducts in these children showed segmental dilatations and stenoses. Stenosis of the central bile ducts revealed by MR cholangiopancreatography was the most significant finding of liver involvement in Langerhans cell histiocytosis in children. (orig.)

  1. MAP2K1 and MAP3K1 mutations in langerhans cell histiocytosis

    NARCIS (Netherlands)

    Nelson, David S.; van Halteren, Astrid; Quispel, Willemijn T.; van den Bos, Cor; Bovée, Judith V. M. G.; Patel, Bhumi; Badalian-Very, Gayane; van Hummelen, Paul; Ducar, Matthew; Lin, Ling; MacConaill, Laura E.; Egeler, R. Maarten; Rollins, Barrett J.

    2015-01-01

    Langerhans cell histiocytosis (LCH) is now understood to be a neoplastic disease in which over 50% of cases have somatic activating mutations of BRAF. However, the extracellular signal-related (ERK) pathway is activated in all cases including those with wild type BRAF alleles. Here, we applied a

  2. Cerebellar and basal ganglion involvement in Langerhans cell histiocytosis

    Energy Technology Data Exchange (ETDEWEB)

    Saatci, I.; Baskan, O.; Haliloglu, M.; Aydingoz, U. [Department of Radiology, Hacettepe University Hospital, Sihhiye 06100, Ankara (Turkey)

    1999-06-01

    Langerhans cell histiocytosis (LCH) is a disease of unknown cause characterised by proliferation of histiocytic granulomas in tissues; the primary cerebral manifestation is diabetes insipidus caused by hypothalamic infiltration. We present a patient in whom, except for the absence of high signal on T 1 weighting in the posterior pituitary, consistent with central diabetes insipidus, MRI showed no evidence of hypothalamic involvement by histiocytosis, despite the long duration of the disease. However, there was bilateral, symmetrical involvement of the cerebellum and globus pallidus in addition to a calvarial lesion. High signal in the cerebellar white matter on T 2-weighted images may represent demyelination, gliosis and cell loss, as previously reported on pathologic examination. (orig.) With 5 figs., 22 refs.

  3. A case report of orbital Langerhans cell histiocytosis presenting as a orbital cellulitis.

    Science.gov (United States)

    Albert-Fort, M; González-Candial, M

    2018-04-08

    A 10-year-old girl was seen with a 3-week history of right upper lid swelling and with no other symptoms or fever. There was no recent history of sinusitis, trauma, or previous infection involving the periorbital area, or response to oral antibiotic treatment. Orbital computed tomography showed a lesion involving the upper margin of the orbit, and bone destruction at the orbital roof. Biopsy performed revealed the presence of Langerhans cell Histiocytosis. The lesion was surgically debulked and corticosteroids were used intra-operatively. The lesion responded to treatment. The orbital involvement of Langerhans cell histiocytosis, despite its low incidence, should be considered in the examination of acute peri-orbital swelling. It usually presents as an osteolytic lesion, and it is confirmed with a histological examination and immunohistochemical techniques for CD1a and S100. An interdisciplinary approach is recommended to rule out multifocal or multisystemic diseases, as well as to develop an appropriate treatment strategy. Copyright © 2018 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

  4. Effect of UV-irradiation on immunological and histochemical markers of Langerhans cells in normal appearing skin of psoriatic patients

    International Nuclear Information System (INIS)

    Tjernlund, U.; Juhlin, L.

    1982-01-01

    A total of 12 patients with moderately severe psoriasis was treated with psoralen baths and/or ultraviolet radiation. Punch biopsies were taken for mimunological markers and shave biopsies for ATPase detection. As immunological marker immunosorbent purified antibodies against Ia antigens and monoclonal antigens against thymocyte antigens were used. The study showed that in the clinical relevant situation PUVA treatment had a more profound effect on the immunological markers of epidermal Langerhans cells than had light treatment without psoralens. With UV treatment without psoralens the ATPase activity of the Langerhans cells seemed to be more influenced than the immunological markers. (orig.)

  5. Partial hypopituitarism and Langerhans cell histiocytosis

    Science.gov (United States)

    Balaguruswamy, S; Chattington, P D

    2011-01-01

    A case of multisystem Langerhans cell histiocytosis with pituitary involvement nearly 20 years after initial presentation. A 48-year-old man had histiocytosis X 22 years ago initially involving the groin; subsequently his external auditory meatus, scalp, gum, mandibular bone, perineum and axilla were involved and treated. The pituitary gland was involved 4 years ago. A thyrotropin-releasing hormone test showed delayed response suggestive of hypothalamic disease. Prolactin levels were normal. A gonadotropin-releasing hormone test showed impaired testosterone and gonadotrophin response in keeping with pituitary disease. A glucagon stimulation test showed an impaired growth hormone response but a normal cortisol increase. MRI pituitary showed an empty sella. There was no evidence of diabetes insipidus. Bone mineral densitometry was normal. He has partial hypopituitarism needing thyroxine and testosterone replacement. He also developed type 2 diabetes mellitus 9 years ago. He is closely monitored for any development of diabetes insipidus and the need for growth hormone supplementation. PMID:22715201

  6. Magnetic resonance imaging of thickened pituitary stalk proceeding to langerhans cell histiocytosis in a child

    International Nuclear Information System (INIS)

    Halefoglu, A.M.

    2006-01-01

    Magnetic resonance imaging has shown isolated pituitary stalk thickening in certain cases of idiopathic or secondary central diabetes insipidus (Dl) due to infiltrative processes. We present a 4-year-old boy who was initially diagnosed as having central Dl. The MRI showed isolated pituitary stalk thickening with prominent homogeneous contrast enhancement. The remaining findings on MRI were within normal limits. The patient's personal and family history and laboratory and clinical findings were unremarkable; therefore, he was initially diagnosed as having idiopathic Dl. Since central Dl and isolated pituitary stalk thickening may be considered to be the first manifestations of Langerhans cell histiocytosis, we decided to follow up the patient. After 5 months, following the initial diagnosis, on skeletal X-ray survey, the patient did indeed develop multiple lytic skull lesions which, on biopsy, were histologically typical bone lesions of Langerhans cell histiocytosis. Copyright (2006) Blackwell Science Pty Ltd

  7. Changes of Langerhans cells during skin ageing

    Directory of Open Access Journals (Sweden)

    Barbara Zegarska

    2017-05-01

    Full Text Available Introduction : During the process of skin ageing, changes occur in all skin layers and all cells, including the Langerhans cells. Aim: To assess whether any quantitative difference in the number of CD1a+ LC cells/mm 2 and HLA-DR+ LC cells/mm 2 as well as in their morphological features can be observed during the course of different types of skin ageing. Material and methods: The study was conducted in a group of 60 women, which was divided into three independent groups: group I with symptoms of menopausal skin ageing, group II with symptoms of photoageing, group III with symptoms of chronological ageing. Skin biopsy samples were taken from the pre-auricular region from all of the participants. The number of CD1a+ LC cells/mm 2 and HLA-DR+ LC cells/mm 2 as well as their morphological features were evaluated. Results : The frequency of CD1a+ LC and HLA-DR+ LC in all the studied groups was diverse. In groups I and III, the LC with large cell bodies and long, multi-branched processes were the majority. In group II, the LC had small cell bodies and their processes were mainly short and unbranched. Conclusions : The obtained results indicate the presence of quantitative and morphological changes of the CD1a+ LC and HLA-DR+ LC during the course of different types of skin ageing.

  8. Perianal Ulcer and Diabetes Insipidus: A Rare Presentation of Langerhans Cell Histiocytosis in an Adult Male

    Directory of Open Access Journals (Sweden)

    Ng Chong Beng

    2017-07-01

    Full Text Available Langerhans cell histiocytosis (LCH, previously known as Histiocystosis X, is a rare idiopathic disease caused by a build-up of langerhan cells in the body. LCH has a heterogenous form of clinical presentation and presents with varying degree of severity. The severity often depends on the disease burden. LCH can manifest as a unifocal disease, multifocal-unisystem or multifocal-multisystem disease with the latter being more fatal than the rest. Risk organ involvement confers a grim prognosis. Perianal lesions are extremely rare skin manifestation of LCH with only few cases reported in the past. Vinca-alkaloids and steroid therapy have been shown to be effective in a large percentage of those presenting with LCH. This case report highlights the diagnosis and management of LCH presenting as a painful perianal ulcer in the background of newly diagnosed diabetes insipidus.

  9. Effect of glucocorticoids and gamma radiation on epidermal Langerhans cells

    International Nuclear Information System (INIS)

    Belsito, D.V.; Baer, R.L.; Thorbecke, G.J.; Gigli, I.

    1984-01-01

    The effect of 750 rads of gamma radiation on the rate of return of epidermal Langerhans cells (LC) following suppressive doses of topical glucorticoids was studied in guinea pigs. Gamma radiation alone had no effect on the LC as assessed by staining for cell membrane ATPase activity and Ia antigen. It did, however, delay the expected return of Ia but not ATPase surface markers on the LC after perturbation with glucocorticoids. The delayed return of surface Ia antigen is possibly related to a radiation-induced defect in the production of a required lymphokine and/or in intracellular Ia transport. Although our data do not rule out a cytolytic effect of steroids on the LC, they do strongly suggest that, at least in part, glucocorticoids act on the LC by altering cell surface characteristics

  10. Health-related quality of life, cognitive functioning and behaviour problems in children with Langerhans cell histiocytosis

    NARCIS (Netherlands)

    Vrijmoet-Wiersma, C. M. Jantien; Kooloos, Vicky M.; Koopman, Hendrik M.; Kolk, Annemarie M.; van der Laan, Ingrid; Grootenhuis, Martha A.; Egeler, R. Maarten

    2009-01-01

    BACKGROUND: This study was designed to evaluate generic and disease-specific health-related quality of life (HRQoL), cognitive functioning and behaviour problems of children with Langerhans Cell Histiocytosis (LCH). Furthermore, we investigated which medical determinants and social demographic

  11. Immunological aspects of the investigation in the effect of external UV-irradiation and UV-irradiated bioliquids of the Langerhans cell

    International Nuclear Information System (INIS)

    Volyanskij, Yu.L.; Marchuk, L.M.; Telepneva, L.G.

    1989-01-01

    The origin and role of the Langerhans cell are considered in the immune response of the organism, as well as in a number of human diseases. It is noted that the antigen-presenting function of this macrophage suffers when taking glucocorticosteroid preparations, at AIDS and large doses of ultraviolet radiation. Therefore, the investigation of the effect of UV-irradiated blood reinfusion on the Langerhans cell will help to determine the possibilities of UV-irradiated blood therapy in treating a wide range of diseases, including AIDS, in the transplantation of organs and tissues. 163 refs.; 2 figs

  12. Paul Langerhans: a prilgrim "traveling" from functional histology to marine biology.

    Science.gov (United States)

    Raica, Marius; Cimpean, Anca Maria

    2017-06-01

    The nineteenth century was the time of a real revolution in science and medicine. A lot of seminal discoveries in medicine and biology were done in this time, and many of them were coincident with the introduction of the compound microscope by Hermann van Deijl and the standard histological technique by Paul Ehrlich. The main tissue types and individual cells were characterized and originally classified more than hundred years ago, although less attention was paid to their basic functions. This was mainly due to the modality of tissue specimen processing that allowed particularly detailed descriptive studies. Even so, we can notice some attempts to correlate the structure with the function. The German scientist Paul Langerhans, well-known for the discovery of Langerhans islets of the pancreas and Langerhans cells from the epidermis, tried to change the conventional fate of morphological studies introducing in his works functional hypothesis based on traditional microscopic observations even from the beginning of his scientific career. Paul Langerhans was a complex personality of the second half of the nineteenth century, not only in medicine, but also in other fields of biology. In the present review, presented is the life and research activity of Paul Langerhans, not only because of the importance of his discoveries, but also for perspectives that were opened by these findings in unexpected fields of medicine and biology.

  13. Langerhans' cell histiocytosis: pathology, imaging and treatment of skeletal involvement

    Energy Technology Data Exchange (ETDEWEB)

    Azouz, E. Michel [University of Miami, Pediatric Radiology Section, Department of Radiology, Miami, FL (United States); Saigal, Gaurav [McGill University, Department of Medical Imaging, Quebec (Canada); Rodriguez, Maria M. [University of Miami, Department of Pathology, Miami, FL (United States); Podda, Antonello [University of Miami, Division of Pediatric Hematology/Oncology, Miami, FL (United States)

    2005-02-01

    Langerhans' cell histiocytosis (LCH) is manifested in a variety of ways, the most common being the eosinophilic granuloma, a localized, often solitary bone lesion that occurs predominantly in the pediatric age group. The hallmark of LCH is the proliferation and accumulation of a specific histiocyte: the Langerhans' cell. In bone this may cause pain and adjacent soft-tissue swelling, but some lesions are asymptomatic. LCH can involve any bone, but most lesions occur in the skull (especially the calvarium and temporal bones), the pelvis, spine, mandible, ribs, and tubular bones. Imaging diagnosis of the disease in bone is first based on the plain radiographic appearance, which is usually a central destructive, aggressive-looking lesion. In the skull, the lesions develop in the diploic space, are lytic, and their edges may be beveled, scalloped or confluent (geographic), or show a ''button sequestrum.'' Vertebral body involvement usually causes collapse, resulting in vertebra plana. With significant recent improvements in the quality of gamma cameras, imaging techniques, and in studying children, bone scintigraphy at diagnosis and on follow-up usually reveals the sites of active disease, especially when the involvement is polyostotic. CT and MR imaging are very useful in providing detailed cross-sectional anatomic detail of the involved bone, including the bone marrow and the adjacent soft tissues. CT is better suited for demonstrating bone detail and MR imaging for bone marrow and soft-tissue involvement. (orig.)

  14. Relationship between the ability of sunscreens containing 2-ethylhexyl-4'-methoxycinnamate to protect against UVR-induced inflammation, depletion of epidermal Langerhans (Ia+) cells and suppression of alloactivating capacity of murine skin in vivo.

    Science.gov (United States)

    Walker, S L; Morris, J; Chu, A C; Young, A R

    1994-01-01

    The UVB sunscreen 2-ethylhexyl-4'-methoxycinnamate was evaluated in hairless albino mouse skin for its ability to inhibit UVR-induced (i) oedema, (ii) epidermal Langerhans cell (Ia+) depletion and (iii) suppression of the alloactivating capacity of epidermal cells (mixed epidermal cell-lymphocyte reaction, MECLR). The sunscreen, prepared at 9% in ethanol or a cosmetic lotion, was applied prior to UVB/UVA irradiation. In some experiments there was a second application halfway through the irradiation. Single applications in both vehicles gave varying degrees of protection from oedema and Langerhans cell depletion but afforded no protection from suppression of MECLR. When the sunscreens were applied twice there was improved protection from oedema and Langerhans cell depletion and complete protection was afforded from suppression of MECLR. There was a clear linear relationship between Langerhans cell numbers and oedema with and without sunscreen application. The relationship between Langerhans cell numbers and MECLR was more complex. These data confirm published discrepancies between protection from oedema (a model for human erythema) and endpoints with immunological significance, but show that 2-ethylhexyl-4'-methoxycinnamate can afford complete immunoprotection, although protection is dependent on the application rate and vehicle.

  15. CT manifestations of pulmonary Langerhans cell histiocytosis

    International Nuclear Information System (INIS)

    Qiang Jun; Yu Wei; Gao Wanqin; Song Haiqiao; Ma Yingjian

    2010-01-01

    Objective: To analyzes the CT manifestations of pulmonary Langerhans cell histiocytosis (PLCH). Methods: CT features of 11 patients with PLCH proved pathologically were analyzed retrospectively. Results: The main findings in 11 PLCHs were cysts and nodules. Two cases only had cysts, and 1 only had nodules, which most had cavitations. The other 8 cases showed cysts and nodules with 4 cases mainly manifested with cysts and nine mainly manifested with nodules. Two cases had pulmonary interstitial changes. One case only had cysts in the left upper lung field and 10 cases had lesions not only in the upper and middle but in the lower lung field, which 2 cases had more lesions in the lower and costo-phrenic angle field and 8 cases had less lesions in the costo-phrenic angle field. Three of these 8 cases had more lesions in the superior lobe and apical segment of lower lobe. Conclusion: CT manifestations of PLCH are helpful for the early diagnosis. (authors)

  16. Human Langerhans Cells with Pro-inflammatory Features Relocate within Psoriasis Lesions

    Science.gov (United States)

    Eidsmo, Liv; Martini, Elisa

    2018-01-01

    Psoriasis is a common skin disease that presents with well-demarcated patches of inflammation. Recurrent disease in fixed areas of the skin indicates a localized disease memory that is preserved in resolved lesions. In line with such concept, the involvement of tissue-resident immune cells in psoriasis pathology is increasingly appreciated. Langerhans cells (LCs) are perfectly placed to steer resident T cells and local tissue responses in psoriasis. Here, we present an overview of the current knowledge of LCs in human psoriasis, including findings that highlight pro-inflammatory features of LCs in psoriasis lesions. We also review the literature on conflicting data regarding LC localization and functionality in psoriasis. Our review highlights that further studies are needed to elucidate the molecular mechanisms that drive LCs functionality in inflammatory diseases. PMID:29520279

  17. Circulating and in situ lymphocyte subsets and Langerhans cells in patients with compositae oleoresin dermatitis and increased ultraviolet A sensitivity during treatment with azathioprine

    International Nuclear Information System (INIS)

    Baadsgaard, O.

    1986-01-01

    Circulating and in situ lymphocyte subsets and Langerhans cells in four patients with compositae oleoresin dermatitis and increased ultraviolet A sensitivity before and during treatment with azathioprine were estimated. It was found that the number of Leu 6+ Langerhans cells decreased during therapy. This decrease was accompanied by a reduction in the number of Leu 2a+, Leu 3a+, Leu 4+, DR+, and Leu M2+ cells in the blood and a reduction in the number of Leu 2a+, Leu 3a+, Leu 4+, and DR+ cells in the skin. Concomitantly with the changes in the number of immunocompetent cells, the eczema cleared

  18. Topical grape seed proanthocyandin extract reduces sunburn cells and mutant p53 positive epidermal cell formation, and prevents depletion of Langerhans cells in an acute sunburn model.

    Science.gov (United States)

    Yuan, Xiao-Ying; Liu, Wei; Hao, Jian-Chun; Gu, Wei-Jie; Zhao, Yan-Shuang

    2012-01-01

    The purpose of this study was to investigate whether grape seed proanthocyanidin extract (GSPE) can provide photoprotection against ultraviolet (UV) irradiation. Study has shown that GSPE is a natural oxidant, and is used in many fields such as ischemia-reperfusion injury, chronic pancreatitis, and even cancer. However, the effect of GSPE on UV irradiation is as yet unknown. Cutaneous areas on the backs of normal volunteers were untreated or treated with GSPE solutions or vehicles 30 min before exposure to two minimal erythema doses (MED) of solar simulated radiation. Cutaneous areas at different sites were examined histologically for the number of sunburn cells, or immunohistochemically for Langerhans cells and mutant p53 epidermal cells. On histological and immunohistochemical examination, skin treated with GSPE before UV radiation showed fewer sunburn cells and mutant p53-positive epidermal cells and more Langerhans cells compared with skin treated with 2-MED UV radiation only (p<0.001, p<0.001, and p<0.01, respectively). GSPE may be a possible preventive agent for photoprotection.

  19. The molecular fingerprint of human papillomavirus infection and its effect on the Langerhans cell population in squamous cell carcinomas of the genital skin

    Directory of Open Access Journals (Sweden)

    Jose M Rios-Yuil

    2014-01-01

    Full Text Available Background: Information is scarce about the presence of molecular alterations related to human papillomavirus (HPV infection in squamous cell carcinomas of the genital skin and about the effect of this infection in the number of Langerhans cells present in these tumors. Aims: To determine the presence of HPV in genital skin squamous cell carcinomas and to see the relationship between HPV infection and changes in the expression of Ki-67 antigen (Ki-67, p53 protein (p53, retinoblastoma protein (pRb and E-cadherin and to alterations in Langerhans cell density, if any. Methods: A descriptive, comparative, retrospective and cross-sectional study was performed with all the cases diagnosed as squamous cell carcinomas of the genital skin at the Dermatopathology Service from 2001 to 2011. The diagnosis was verified by histopathological examination. The presence of HPV was examined using chromogenic in situ hybridization, and protein expression was studied via immunohistochemical analysis. Results: The 34 cases studied were verified as squamous cell carcinomas and 44.1% were HPV positive. The degree of expression of pRb was 17.50% ±14.11% (mean ± SD in HPV-positive cases and 29.74% ±20.38% in HPV-negative cases (P = 0.0236. The degree of expression of Ki-67 was 47.67% ±30.64% in HPV-positive cases and 29.87% ±15.95% in HPV-negative cases (P = 0.0273. Conclusion: HPV infection was related to lower pRb expression and higher Ki-67 expression in comparison with HPV negative samples. We could not find a relationship between HPV infection and the degree of expression of p53 and E-cadherin or with Langerhans cell density.

  20. Human Epidermal Langerhans Cells Maintain Immune Homeostasis in Skin by Activating Skin Resident Regulatory T Cells

    Science.gov (United States)

    Seneschal, Julien; Clark, Rachael A.; Gehad, Ahmed; Baecher-Allan, Clare M.; Kupper, Thomas S.

    2013-01-01

    Recent discoveries indicate that the skin of a normal individual contains 10-20 billion resident memory T cells ( which include various T helper, T cytotoxic, and T regulatory subsets, that are poised to respond to environmental antigens. Using only autologous human tissues, we report that both in vitro and in vivo, resting epidermal Langerhan cells (LC) selectively and specifically induced the activation and proliferation of skin resident regulatory T cells (Treg), a minor subset of skin resident memory T cells. In the presence of foreign pathogen, however, the same LC activated and induced proliferation of effector memory T (Tem) cells and limited Treg cells activation. These underappreciated properties of LC: namely maintenance of tolerance in normal skin, and activation of protective skin resident memory T cells upon infectious challenge, help clarify the role of LC in skin. PMID:22560445

  1. Functional analysis of HPV-like particle-activated Langerhans cells in vitro.

    Science.gov (United States)

    Yan, Lisa; Woodham, Andrew W; Da Silva, Diane M; Kast, W Martin

    2015-01-01

    Langerhans cells (LCs) are antigen-presenting cells responsible for initiating an immune response against human papillomaviruses (HPVs) entering the epithelial layer in vivo as they are the first immune cell that HPV comes into contact with. LCs become activated in response to foreign antigens, which causes internal signaling resulting in the increased expression of co-stimulatory molecules and the secretion of inflammatory cytokines. Functionally activated LCs are then capable of migrating to the lymph nodes where they interact with antigen-specific T cells and initiate an adaptive T-cell response in vivo. However, HPV has evolved in a manner that suppresses LC function, and thus the induction of antigen-specific T cells is hindered. While many methods exist to monitor the activity of LCs in vitro, the migration and induction of cytotoxic T cells is ultimately indicative of a functional immune response. Here, methods in analyzing functional migration and induction of antigen-specific T cells after stimulation of LCs with HPV virus-like particles in vitro are described.

  2. Pulmonary langerhans cell histiocytosis in adults: high-resolution CT - pathology comparisons and evolutional changes at CT

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hyo Jin; Lee, Ho Yun; Kim, Tae Sung [Sungkyunkwan University School of Medicine, Department of Radiology and Center for Imaging Science, Samsung Medical Center, Seoul (Korea, Republic of); Lee, Kyung Soo [Sungkyunkwan University School of Medicine, Department of Radiology and Center for Imaging Science, Samsung Medical Center, Seoul (Korea, Republic of); Samsung Medical Center, Department of Radiology, Seoul (Korea, Republic of); Johkoh, Takeshi [Kinki Central Hospital of Mutual Aid Association of Public School Teachers, Department of Radiology, Hyoko (Japan); Tomiyama, Noriyuki [Osaka University Graduate School of Medicine, Department of Radiology, Osaka (Japan); Han, Joungho [Sungkyunkwan University School of Medicine, Department of Pathology, Samsung Medical Center, Seoul (Korea, Republic of)

    2011-07-15

    To compare high-resolution (HR) CT and histopathological findings and to evaluate serial CT findings in pulmonary Langerhans cell histiocytosis (PLCH). We reviewed CT of lung lesions in 27 adults (M:F = 20:7, mean age, 41 {+-} 12.3 years) with PLCH. After evaluating lung abnormalities including nodules, micronodules, thick-walled, thin-walled, and bizarre-shaped cysts and reticulation, observers compared CT findings obtained at lung biopsy sites with histopathological findings. The final CT was compared with the initial CT to determine disease extent changes. The most frequently observed patterns of lung abnormalities were micronodules (n = 24, 89%), thick-walled (n = 22, 82%), and thin-walled (n = 22, 82%) cysts. Even thin-walled and bizarre cysts harboured active inflammatory Langerhans cell sheets and eosinophils in their walls. In thin-walled cysts, we noted pericystic inflammatory cell infiltrations along the alveolar walls, as well as pericystic emphysema. Thin-walled or bizarre cysts demonstrated a tendency to coalesce with surrounding cysts via their cystic wall destruction. Fourteen (52%) patients showed improvement and nine (33%) showed progressing disease. More than half of patients with pulmonary PLCH show improvement at follow-up CT. Even thin-walled cysts harbour active inflammatory cells on histopathology and exhibit improvement at follow-up CT. (orig.)

  3. Radiotherapy for management of Langerhans' cell histiocytosis. Two case reports and a literature review

    International Nuclear Information System (INIS)

    Heyd, R.; Strassmann, G.; Martin, T.; Zamboglou, N.; Donnerstag, F.

    2000-01-01

    The use of radiotherapy in the treatment of Langerhans' cell histiocytosis was first reported in the literature in 1930 and has been proven as effective in numerous studies. We present the results of two female adults with eosinophilic granuloma of bone who underwent conventionally fractionated radiation therapy with total doses of 7x1.8 Gy and 7x2.0 Gy in four different sites. After observation periods raging from three months to six years local control of the disease was achieved in all treated locations. A review of 18 previously published studies include a total of 310 sites of eosinophilic granuloma of bone in 216 patients. It was demonstrated in 13 studies that the patients had complete relief of symptoms. An average of 94.3% had local control of the symptoms. Furthermore, in 12 studies for a total of 344 cases with involvement of other organs local control was reported in an average of 64.8% (range: 14.3-100%). Based on our own observations and on the literature review we conclude that low dose radiation therapy plays an important role in the management of localised Langerhans' cell histiocytosis. In order to minimise the risk of radiation induced neoplasms an accurate and precise radiation technique is required. (orig.) [de

  4. CT findings of orbital langerhans cell histiocytosis

    International Nuclear Information System (INIS)

    Yi, Gina; Yoon, Hye Kyung; Han, Bokyung Kim; Kim, Kyeong Ah; Choo, In Wook

    2000-01-01

    To evaluate the CT findings in patients with Langerhans cell histiocytosis (LCH) involving the orbit. Orbital CT scans of six children with pathologically proven LCH were retrospectively analyzed. Follow-up CT (n=3D5) and MR (n=3D1) imaging findings were also reviewed. Initial CT scans revealed varying degree of bone destruction with soft-tissue masses, and on nonenhanced images the mean attenuation value was 44 Hounsfield units (HU). All masses showed mild to moderate enhancement with a mean attenuation value of 74 HU. The bony margins abutting onto soft tissue masses were irregular but clearly demarcated. No evidence of calcification or periosteal reaction was noted. Suprasellar mass and rib involvement was noted in one patient and hepatosplenomegaly in two. Follow-up CT and MR images showed that the soft tissue masses were almost completely resolved, with bone remodeling and reossification. A soft tissue mass with irregular but clearly demarcated bone destruction is thought to be a characteristic finding of LCH involving the orbit. Follow-up images after treatment showed bone remodeling and reossification. (author)

  5. Mechanisms of pancreatic islet cell destruction. Dose-dependent cytotoxic effect of soluble blood mononuclear cell mediators on isolated islets of Langerhans

    DEFF Research Database (Denmark)

    Mandrup-Poulsen, T; Bendtzen, K; Nerup, J

    1986-01-01

    Supernatants of peripheral blood mononuclear cells from healthy human donors stimulated with recall antigen (purified protein derivative of tuberculin) or lectin (phytohaemagglutinin) markedly inhibited the insulin release from isolated human and rat islets of Langerhans, and decreased rat islet...... reconstituted with tuberculin or phytohaemagglutinin did not impair islet function. Electron microscopy demonstrated that supernatants were cytotoxic to islet cells. The cytotoxic mononuclear cell mediator(s) was non-dialysable, sensitive to heating to 56 degrees C, labile even when stored at -70 degrees C...

  6. Monostotic Langerhans' cell histiocytosis in a child with central diabetes insipidus.

    Science.gov (United States)

    Soares, Eduardo Costa Studart; Quidute, Ana Rosa Pinto; Costa, Fábio Wildson Gurgel; Gurgel, Maria Helane Costa; Alves, Ana Paula Negreiros Nunes; Fonteles, Cristiane Sá Roriz

    2012-01-01

    Langerhans'cell histiocytosis (LCH) comprises a rare group of reticuloendothelial system disorders that can produce focal or systemic manifestations. Diabetes insipidus is considered to be an important indicator of serious underlying diseases in children, including LCH. We report the case of a young patient with monostotic LCH confined to the mandibular ramus, who was diagnosed with the disease after presenting symptoms of central diabetes insipidus and was satisfactorily treated with multi-agent chemotherapy. Additionally, we discuss the clinical, radiographic, histological and immunohistochemical findings, as well as the multidisciplinary approach of this important disease, which should receive attention by dental practitioners, especially when it occurs in children.

  7. p53 expression in biopsies from children with Langerhans cell histiocytosis

    DEFF Research Database (Denmark)

    Bank, Micha I; Lundegaard, Pia Rengtved; Carstensen, Henrik

    2002-01-01

    based on CD1a positivity. The slides were stained with p53 antibody and semiquantitatively evaluated using a grading system from 1 to 5 as an estimate for 0% to 20%, 20% to 40%, 40% to 60%, 60% to 80%, and 80% to 100% p53-positive for pathologic Langerhans cells (pLC), respectively. RESULTS: The p53...... protein was expressed in various degrees in pLC in all lesions. The degree of p53 expression could not be correlated to either clinical manifestation or outcome. CONCLUSIONS: An increased expression of p53 in pLC indicates an altered DNA repair control with or without abnormal control of apoptosis....

  8. Molecular analysis of human papillomavirus virus-like particle activated Langerhans cells in vitro.

    Science.gov (United States)

    Woodham, Andrew W; Raff, Adam B; Da Silva, Diane M; Kast, W Martin

    2015-01-01

    Langerhans cells (LC) are the resident antigen-presenting cells in human epithelium, and are therefore responsible for initiating immune responses against human papillomaviruses (HPV) entering the epithelial and mucosal layers in vivo. Upon proper pathogenic stimulation, LC become activated causing an internal signaling cascade that results in the up-regulation of co-stimulatory molecules and the release of inflammatory cytokines. Activated LC then migrate to lymph nodes where they interact with antigen-specific T cells and initiate an adaptive T-cell response. However, HPV manipulates LC in a suppressive manner that alters these normal maturation responses. Here, in vitro LC activation assays for the detection of phosphorylated signaling intermediates, the up-regulation of activation-associated surface markers, and the release of inflammatory cytokines in response to HPV particles are described.

  9. Diagnósticos diferenciales de la histiocitosis a células de Langerhans The differential diagnostics of Langerhans cell histiocytosis

    Directory of Open Access Journals (Sweden)

    C. N. Chirino

    2007-06-01

    Full Text Available La histiocitosis a células de Langerhans (HCL debe diferenciarse de las siguientes entidades: eritema tóxico neonatorum (ETN, dermatitis seborreica (DS, foliculitis pustulosa eosinofílica (FPE, incontinencia pigmenti (IP, mastocitosis/urticaria pigmentosa (M/UP, acrodermatitis enteropática (ADE, síndrome de Wiskott-Aldrich (WAS, acropustulosis infantil (API. Además se deben considerar la enfermedad de Rosai- Dorfman (ERD, xantomas diseminados, melanosis pustulosa neonatal (MPN, candidiasis congénita, listeriosis neonatal, herpes simple perinatal y la varicela neonatal. Debido a que los métodos auxiliares de laboratorio no siempre están disponibles o los resultados laboratoriales algunas veces son extemporáneos, y puesto que el médico práctico a menudo necesita tomar decisiones precozmente, es que la epidemiología resulta útil, pues brinda el marco adecuado para ordenar y jerarquizar las sospechas diagnósticas frente a un caso concreto, con un paciente determinado, en un momento específico.The differential diagnostics of Langerhans cell histiocytosis should include the following disorders: erythema toxicum neonatorum, seborrheic dermatitis, eosinophilic pustular folliculitis, incontinentia pigmenti, mastocytosis / urticaria pigmentosa, acrodermatitis enteropathica, Wiskott-Aldrich syndrome, infantile acropustulosis, Rosai- Dorfman disease, xanthoma disseminatum, neonatal pustular melanosis, congenital candidiasis, perinatal listeriosis, perinatal herpes simplex, neonatal varicella. Since the auxiliary methods of lab are not always available, or lab results are sometimes extemporaneous, the physicians often needs to make quick decisions. The epidemiology is useful because it offers the appropriate mark to prioritize the diagnostic in specific cases

  10. The rapid evolution of CT findings in pulmonary langerhans cell histiocytosis: a case report

    International Nuclear Information System (INIS)

    Kang, Tae Wook; Lee, Kyung Soo; Cho, Eun Yoon

    2007-01-01

    Imaging findings of pulmonary Langerhans cell histiocytosis (PLCH) demonstrate evolving changes over time, and the radiological transitions shown by imaging tools may allow a prediction of histopathological activity in PLCH. However, there are no reports describing how rapidly CT findings change with time. We describe a case of PLCH that showed a rapid evolutional change of the pulmonary lesions in a 48-year-old man, in which the nodular lesions showed cystic changes within two-month follow-up periods on chest CT scans

  11. Langerhans-cell histiocytosis of the cervical spine in an adult patient: Case report and review of the literature.

    Science.gov (United States)

    Vielgut, Ines; Liegl-Atzwanger, Bernadette; Bratschitsch, Gerhard; Leithner, Andreas; Radl, Roman

    2017-06-01

    Langerhans-cell histiocytosis (LCH) is a rare, benign bone tumor, usually occurring in children and younger adults under 20 years old. Only a few cases of solitary bone lesions of the adult spine are reported in literature, therapeutic guidelines or treatment regimens for lesions of the adult spine are not established yet to our knowledge.

  12. Management and Outcome of Patients With Langerhans Cell Histiocytosis and Single-Bone CNS-Risk Lesions: A Multi-Institutional Retrospective Study

    NARCIS (Netherlands)

    Chellapandian, Deepak; Shaikh, Furqan; van den Bos, Cor; Somers, Gino R.; Astigarraga, Itziar; Jubran, Rima; Degar, Barbara; Carret, Anne-Sophie; Mandel, Karen; Belletrutti, Mark; Dix, David; Visser, Johannes; Abuhadra, Nour; Chang, Tiffany; Rollins, Barret; Whitlock, James; Weitzman, Sheila; Abla, Oussama

    2015-01-01

    Children with Langerhans cell histiocytosis (LCH) and single-bone CNS-risk lesions have been reported to be at increased risk of diabetes insipidus (DI), central nervous system neurodegeneration (CNS-ND), and recurrence of disease. However, it is unknown whether the addition of chemotherapy or

  13. BRAF V600E-Positive Multisite Langerhans Cell Histiocytosis in a Preterm Neonate

    Directory of Open Access Journals (Sweden)

    Sara V. Bates

    2013-10-01

    Full Text Available Hemorrhagic pustules with a “blueberry muffin” appearance accompanied by respiratory failure in a neonate present a challenging differential diagnosis that includes infections and neoplasms. We present a case of multiorgan, multisite Langerhans cell histiocytosis (LCH, positive for the oncogenic BRAF V600E mutation, in a preterm neonate. Infants with LCH pose a diagnostic challenge due to their heterogeneous presentations. This case is unusual in that the newborn presented with severe multiorgan involvement. Due to the rare incidence, wide spectrum of clinical manifestations, and high mortality rate, clinicians must maintain a high index of suspicion for LCH.

  14. Cytotoxicity of human pI 7 interleukin-1 for pancreatic islets of Langerhans

    DEFF Research Database (Denmark)

    Bendtzen, K; Mandrup-Poulsen, T; Nerup, J

    1986-01-01

    Activated mononuclear cells appear to be important effector cells in autoimmune beta cell destruction leading to insulin-dependent (type 1) diabetes mellitus. Conditioned medium from activated mononuclear cells (from human blood) is cytotoxic to isolated rat and human islets of Langerhans. This c...

  15. GM-CSF Monocyte-Derived Cells and Langerhans Cells As Part of the Dendritic Cell Family

    Directory of Open Access Journals (Sweden)

    Manfred B. Lutz

    2017-10-01

    Full Text Available Dendritic cells (DCs and macrophages (Mph share many characteristics as components of the innate immune system. The criteria to classify the multitude of subsets within the mononuclear phagocyte system are currently phenotype, ontogeny, transcription patterns, epigenetic adaptations, and function. More recently, ontogenetic, transcriptional, and proteomic research approaches uncovered major developmental differences between Flt3L-dependent conventional DCs as compared with Mphs and monocyte-derived DCs (MoDCs, the latter mainly generated in vitro from murine bone marrow-derived DCs (BM-DCs or human CD14+ peripheral blood monocytes. Conversely, in vitro GM-CSF-dependent monocyte-derived Mphs largely resemble MoDCs whereas tissue-resident Mphs show a common embryonic origin from yolk sac and fetal liver with Langerhans cells (LCs. The novel ontogenetic findings opened discussions on the terminology of DCs versus Mphs. Here, we bring forward arguments to facilitate definitions of BM-DCs, MoDCs, and LCs. We propose a group model of terminology for all DC subsets that attempts to encompass both ontogeny and function.

  16. Binding of [125I] Concanavalin A to isolated Langerhans islets of rats

    International Nuclear Information System (INIS)

    Prey, N.

    1983-01-01

    Langerhans islets of rats were isolated using Lacy's collagenase technique and were incubated in vitro. The binding of iodine-labelled Concanavalin A to isolated Langerhans islets was investigated. We were unable to decide whether multiple Concanavalin A binding sites are located on the cell membrane, or whether the Concanavalin A binding sites are negatively influenced via a allosteric protein. Although the secretion mechanism induced by sulfony urea is not influenced by Concanavalin A, enhanced binding of Concanavalin A indicates that the region of identification cannot be identical for glucose and sulfonyl urea. (orig./MG) [de

  17. MUTZ-3 derived Langerhans cells in human skin equivalents show differential migration and phenotypic plasticity after allergen or irritant exposure

    Energy Technology Data Exchange (ETDEWEB)

    Kosten, Ilona J.; Spiekstra, Sander W. [Department of Dermatology, VU University Medical Center, Amsterdam (Netherlands); Gruijl, Tanja D. de [Department of Dermatology Medical Oncology, VU University Medical Center, Amsterdam (Netherlands); Gibbs, Susan, E-mail: s.gibbs@acta.nl [Department of Dermatology, VU University Medical Center, Amsterdam (Netherlands); Department of Oral Cell Biology, Academic Center for Dentistry (ACTA), Amsterdam (Netherlands)

    2015-08-15

    After allergen or irritant exposure, Langerhans cells (LC) undergo phenotypic changes and exit the epidermis. In this study we describe the unique ability of MUTZ-3 derived Langerhans cells (MUTZ-LC) to display similar phenotypic plasticity as their primary counterparts when incorporated into a physiologically relevant full-thickness skin equivalent model (SE-LC). We describe differences and similarities in the mechanisms regulating LC migration and plasticity upon allergen or irritant exposure. The skin equivalent consisted of a reconstructed epidermis containing primary differentiated keratinocytes and CD1a{sup +} MUTZ-LC on a primary fibroblast-populated dermis. Skin equivalents were exposed to a panel of allergens and irritants. Topical exposure to sub-toxic concentrations of allergens (nickel sulfate, resorcinol, cinnamaldehyde) and irritants (Triton X-100, SDS, Tween 80) resulted in LC migration out of the epidermis and into the dermis. Neutralizing antibody to CXCL12 blocked allergen-induced migration, whereas anti-CCL5 blocked irritant-induced migration. In contrast to allergen exposure, irritant exposure resulted in cells within the dermis becoming CD1a{sup −}/CD14{sup +}/CD68{sup +} which is characteristic of a phenotypic switch of MUTZ-LC to a macrophage-like cell in the dermis. This phenotypic switch was blocked with anti-IL-10. Mechanisms previously identified as being involved in LC activation and migration in native human skin could thus be reproduced in the in vitro constructed skin equivalent model containing functional LC. This model therefore provides a unique and relevant research tool to study human LC biology in situ under controlled in vitro conditions, and will provide a powerful tool for hazard identification, testing novel therapeutics and identifying new drug targets. - Highlights: • MUTZ-3 derived Langerhans cells integrated into skin equivalents are fully functional. • Anti-CXCL12 blocks allergen-induced MUTZ-LC migration.

  18. Langerhans cell histiocytosis or tuberculosis on a medieval child (Oppidum de la Granède, Millau, France - 10th-11th centuries AD).

    Science.gov (United States)

    Colombo, Antony; Saint-Pierre, Christophe; Naji, Stephan; Panuel, Michel; Coqueugniot, Hélène; Dutour, Olivier

    2015-06-01

    In 2008, a skeleton of a 1 - 2.5-year-old child radiocarbon dated from the 10th - 11th century AD was discovered on the oppidum of La Granède (Millau, France). It presents multiple cranial osteolytic lesions having punched-out or geographical map-like aspects associated with sequestrum and costal osteitis. A multi 3D digital approach (CT, μCT and virtual reconstruction) enabled us to refine the description and identify the diploic origin of the lytic process. Furthermore, precise observation of the extent of the lesions and associated reorganization of the skeletal micro-structure were possible. From these convergent pieces of evidence, the differential diagnosis led to three possibilities: Langerhans cell histiocytosis, tuberculosis, or Langerhans cell histiocytosis and tuberculosis. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Splenomegaly unresponsive to standard and salvage chemotherapy in Langerhans cell histiocytosis: a case of extramedullary hematopoiesis.

    Science.gov (United States)

    Christiansen, Ellen C; Ellwein, Marcine; Neglia, Joseph P

    2012-06-01

    Langerhans cell histiocytosis (LCH) is a proliferative disorder of dendritic cells which has evaded efforts to clearly define pathogenesis, diagnostic criteria, and therapeutic response markers. Strides have been made at classification with the recent development of a quantified score of disease severity. Splenic involvement is an indicator of poor prognosis, with spleen size its surrogate marker in evaluation and scoring. We describe a case of pediatric LCH with progressive splenomegaly despite treatment, which when examined at splenectomy revealed no LCH involvement but extramedullary hematopoiesis. These findings thus challenge our understanding of splenomegaly as a marker of disease. Copyright © 2011 Wiley Periodicals, Inc.

  20. LANGERHANS CELL HISTIOCYTOSIS OF THE SCAPULA - DIAGNOSIS & TREATMENT OPTIONS

    Directory of Open Access Journals (Sweden)

    ROHIT PANDEY

    Full Text Available ABSTRACT Langerhans cell histiocytosis (LCH is characterised by an abnormal histiocytic accumulation in tissues such as the lung, spleen, bone marrow, skin, central nervous system, liver and lymph nodes, causing focal or systemic effects. No specific clinical & radiographic presentation of LCH is described in literature. This poses a diagnostic dilemma for surgeons. The scapula is the site of 3% of bone tumours, while for LCH it is the least common site. In a 10-year-old boy with isolated lesion of the scapula with no other systemic involvement, and no specific finding in MRI or CT scan of scapula, diagnosis was confirmed on biopsy. Division into single and multi-system disease is paramount in treatment, given that it is a single system disease. The patient improved clinically on follow-up of 2 years. The scapula is one of the rarest site of LCH, and because various lesions mimic each other, a biopsy is always required, with immunohistochemistry for CD68 & S-100. This was only a single system disease, so conservative management was performed, and the patent improved clinically.

  1. Radiological signs of childhood Langerhans cell histiocytosis

    International Nuclear Information System (INIS)

    Mas, F.; Menor, F.; Moreno, A.; Vallcanera, A.; Esteban, M.J.; Muro, D.; Cortina, H.

    1997-01-01

    To describe the most prominent radiological sings of Langerhans cell histiocytosis (LCH) in childhood and review the general aspects of greatest interest to the general radiologist. The clinical and radiological histories of 40 children diagnosed on the basis of biopsy and/or cytology as having LCH in our center over a 16-year period were reviewed. Bone involvement was observed in 95% of patients; flat bones were affected in 95% of the cases, most frequently the cranium. Radiological changes in temporal bone were viewed in 15% of cases. There were long-bone lesions in 21% of the patients, involving, metaphyseal-diaphyseal bones in every case; multiple epiphyseal dysplasia was found in one and a purely cortical lesion in another. Vertebral involvement was detected in 18% of patients. Clinical evidence of diabetes insipidus (DI) was present in 22.5% of cases, while there were clinical or radiological signs of lung involvement in 15%. Bone involvement is the most common association reported in childhood LCH and is usually the reason for medical consultation. The flat bones, especially the cranium, are those most often affected. Diagnosis and follow-up studies are mainly based on plain radiography. DI due to hypothalamic infiltration in usually associated with normal CT scan. Lung involvement, uncommon in pediatric patients, is the major clinical and radiological difference with respect to the adult form. (Author) 33 refs

  2. Human papillomavirus-exposed Langerhans cells are activated by stabilized Poly-I:C.

    Science.gov (United States)

    Da Silva, Diane M; Woodham, Andrew W; Rijkee, Laurie K; Skeate, Joseph G; Taylor, Julia R; Koopman, Maaike E; Brand, Heike E; Wong, Michael K; McKee, Greg M; Salazar, Andres M; Kast, W Martin

    2015-12-01

    Human papillomaviruses (HPV) establish persistent infections because of evolved immune evasion mechanisms, particularly HPV-mediated suppression of the immune functions of Langerhans cells (LC), the antigen presenting cells of the epithelium. Polyinosinic-polycytidilic acid (Poly-I:C) is broadly immunostimulatory with the ability to enhance APC expression of costimulatory molecules and inflammatory cytokines resulting in T cell activation. Here we investigated the activation of primary human LC derived from peripheral blood monocytes after exposure to HPV16 virus like particles followed by treatment with stabilized Poly-I:C compounds (s-Poly-I:C), and their subsequent induction of HPV16-specific T cells. Our results indicate that HPV16 particles alone were incapable of inducing LC activation as demonstrated by the lack of costimulatory molecules, inflammatory cytokines, chemokine-directed migration, and HPV16-specific CD8 + T cells in vitro . Conversely, s-Poly-I:C caused significant upregulation of costimulatory molecules and induction of chemokine-directed migration of LC that were pre-exposed to HPV16. In HLA-A*0201-positive donors, s-Poly-I:C treatment was able to induce CD8 + T cell immune responses against HPV16-derived peptides. Thus, s-Poly-I:C compounds are attractive for translation into therapeutics in which they could potentially mediate clearance of persistent HPV infection.

  3. Primary Langerhans cell histiocytosis (LCH in the adult cervical spine: A case report and review of the literature

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    Sang-Deok Kim, M.D.

    2017-03-01

    Full Text Available Langerhans cell histiocytosis (LCH of the spine is a common benign disease in children and adolescents that rarely affects adults. Main management of single lesion (unifocal vertebral LCH is conservative method, unless there is neurological deficit due to mass effect, surgery must be considered. This is an interesting and rare case report of the patient with LCH at C5 vertebral body who underwent fusion surgery.

  4. Immunohistochemical detection of the apoptosis-related proteins FADD, FLICE, and FLIP in Langerhans cell histiocytosis

    DEFF Research Database (Denmark)

    Bank, Micha I; Gudbrand, Charlotte; Lundegaard, Pia Rengtved

    2005-01-01

    -apoptotic)-in lesions from LCH patients. Immunohistochemistry was performed on paraffin-embedded tissue specimens from 43 children with LCH. The infiltrates were scored according to the amount of positive pathologic Langerhans cells (pLCs). In all investigated specimens, the majority of the pLCs expressed FADD, active...... FLICE, and FLIP. The clinical outcome of the disease could not be correlated to the expression of the investigated proteins. This study shows a high expression of the apoptosis-related proteins FADD, active FLICE, and FLIP in pLCs. The authors previously showed that pLCs express Fas and Fas ligand...

  5. Long-term in vivo polychlorinated biphenyl 126 exposure induces oxidative stress and alters proteomic profile on islets of Langerhans

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    Loiola, Rodrigo Azevedo; Dos Anjos, Fabyana Maria; Shimada, Ana Lúcia; Cruz, Wesley Soares; Drewes, Carine Cristiane; Rodrigues, Stephen Fernandes; Cardozo, Karina Helena Morais; Carvalho, Valdemir Melechco; Pinto, Ernani; Farsky, Sandra Helena

    2016-06-01

    It has been recently proposed that exposure to polychlorinated biphenyls (PCBs) is a risk factor to type 2 diabetes mellitus (DM2). We investigated this hypothesis using long-term in vivo PCB126 exposure to rats addressing metabolic, cellular and proteomic parameters. Male Wistar rats were exposed to PCB126 (0.1, 1 or 10 μg/kg of body weight/day; for 15 days) or vehicle by intranasal instillation. Systemic alterations were quantified by body weight, insulin and glucose tolerance, and blood biochemical profile. Pancreatic toxicity was measured by inflammatory parameters, cell viability and cycle, free radical generation, and proteomic profile on islets of Langerhans. In vivo PCB126 exposure enhanced the body weight gain, impaired insulin sensitivity, reduced adipose tissue deposit, and elevated serum triglycerides, cholesterol, and insulin levels. Inflammatory parameters in the pancreas and cell morphology, viability and cycle were not altered in islets of Langerhans. Nevertheless, in vivo PCB126 exposure increased free radical generation and modified the expression of proteins related to oxidative stress on islets of Langerhans, which are indicative of early β-cell failure. Data herein obtained show that long-term in vivo PCB126 exposure through intranasal route induced alterations on islets of Langerhans related to early end points of DM2.

  6. Langerhans cell precursors acquire RANK/CD265 in prenatal human skin.

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    Schöppl, Alice; Botta, Albert; Prior, Marion; Akgün, Johnnie; Schuster, Christopher; Elbe-Bürger, Adelheid

    2015-01-01

    The skin is the first barrier against foreign pathogens and the prenatal formation of a strong network of various innate and adaptive cells is required to protect the newborn from perinatal infections. While many studies about the immune system in healthy and diseased adult human skin exist, our knowledge about the cutaneous prenatal/developing immune system and especially about the phenotype and function of antigen-presenting cells such as epidermal Langerhans cells (LCs) in human skin is still scarce. It has been shown previously that LCs in healthy adult human skin express receptor activator of NF-κB (RANK), an important molecule prolonging their survival. In this study, we investigated at which developmental stage LCs acquire this important molecule. Immunofluorescence double-labeling of cryostat sections revealed that LC precursors in prenatal human skin either do not yet [10-11 weeks of estimated gestational age (EGA)] or only faintly (13-15 weeks EGA) express RANK. LCs express RANK at levels comparable to adult LCs by the end of the second trimester. Comparable with adult skin, dermal antigen-presenting cells at no gestational age express this marker. These findings indicate that epidermal leukocytes gradually acquire RANK during gestation - a phenomenon previously observed also for other markers on LCs in prenatal human skin. Copyright © 2015 The Authors. Published by Elsevier GmbH.. All rights reserved.

  7. Langerhans cells in lichen planus and lichenoid mucositis an immunohistochemical study

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    M Devi

    2014-01-01

    Full Text Available Aim: The aim of this study is to identify and evaluate Langerhans cell (LC in lichen planus (LP, lichenoid mucositis (LM and normal mucosa (NM using CD1a monoclonal antibody immunohistochemically. Materials and Methods: A total of 15 cases of oral lichen planus and 15 cases of LM were selected based on clinical examination and confirmed by histopathological analysis. The biopsies from the 10 patients were taken from normal buccal mucosa as control. Paraffin blocks of tissue were made, which are used for routine hematoxylin and eosin staining and immunohistochemical staining using biotin streptavidin methods (CD1a monoclonal antibody. Analysis of CD1a expression was performed by evaluating the labeling index (LI for each slide. Results: The mean CD1a LI for LP was significantly higher than that of LM and NM in the basal and supra basal layer. The mean CD1a positive cells in the connective tissues for LP were higher than that of LM and NM. Conclusion: This study clearly demonstrates a statistically significant increase in number of LC in LP than in LM, indicating the possible different immunopathogenic mechanisms.

  8. Real-time visualization of macromolecule uptake by epidermal Langerhans cells in living animals.

    Science.gov (United States)

    Frugé, Rachel E; Krout, Colleen; Lu, Ran; Matsushima, Hironori; Takashima, Akira

    2012-03-01

    As a skin-resident member of the dendritic cell family, Langerhans cells (LCs) are generally regarded to function as professional antigen-presenting cells. Here we report a simple method to visualize the endocytotic activity of LCs in living animals. BALB/c mice received subcutaneous injection of FITC-conjugated dextran (DX) probes into the ear skin and were then examined under confocal microscopy. Large numbers of FITC(+) epidermal cells became detectable 12-24 hours after injection as background fluorescence signals began to disappear. Most (>90%) of the FITC(+) epidermal cells expressed Langerin, and >95% of Langerin(+) epidermal cells exhibited significant FITC signals. To assess intracellular localization, Alexa Fluor 546-conjugated DX probes were locally injected into IAβ-enhanced green fluorescent protein (EGFP) knock-in mice and Langerin-EGFP-diphtheria toxin receptor mice--three dimensional rotation images showed close association of most of the internalized DX probes with major histocompatibility complex (MHC) class II molecules, but not with Langerin molecules. These observations support the current view that LCs constantly sample surrounding materials, including harmful and innocuous antigens, at the environmental interface. Our data also validate the potential utility of the newly developed imaging approach to monitor LC function in wild-type animals.

  9. Effects of pimecrolimus versus triamcinolone on Langerhans cells after UV exposure.

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    Martires, Kathryn J; Domingo, Diana S; Hsia, Andrew; Fu, Pingfu; Cooper, Kevin D; Baron, Elma D

    2011-03-01

    Pimecrolimus is a topical immunomodulator for atopic dermatitis. Concerns regarding malignancy risk resulted in its black box warning in 2006. The purpose of this study is to determine the effects of pimecrolimus on Langerhans cells (LC), mediators of the cutaneous immunity UV-irradiated skin. A RCT was conducted investigating pimecrolimus 1% cream vs triamcinolone 0.1% cream on UV-irradiated epidermal LC on 20 healthy volunteers. Punch biopsies were stained with antibodies to CD1a, HLADR and CD83. Triamcinolone caused more depletion in UV-irradiated CD1a(+) epidermis relative to pimecrolimus treatment. (P=0.030). Using HLA-DR as a pan-marker for APCs, pimecrolimus caused marginally less depletion than triamcinolone (P=0.013). Using anti-CD83 as a maturation marker, UV-irradiated skin treated with pimecrolimus showed more mature LC than skin treated with triamcinolone (P=0.00090). UV-induced changes in LC are minimally affected by pimecrolimus, compared with triamcinolone. © 2010 John Wiley & Sons A/S.

  10. An unusual case of adult-onset multi-systemic Langerhans cell histiocytosis with perianal and incident thyroid involvement

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    Ozen Oz Gul

    2017-02-01

    Full Text Available Langerhans cell histiocytosis (LCH is a rare sporadic disease characterized by histiocytic neoplastic infiltration of various organ systems and a wide spectrum of clinical manifestations, ranging from benign and self-limiting to lethal. Herein, we report a rare case of adult-onset multi-systemic LCH in a 36-year-old male patient with an initial perianal presentation and incidental finding of subsequent thyroid gland involvement in the follow-up period. The patient with a history of perianal LCH treated with surgical excision and local radiotherapy was referred to our Endocrinology Department upon detection of hypermetabolic nodular lesions in the left lateral lobe of thyroid gland on positron emission tomography–computed tomography (PET/CT scan in the nineth month of follow-up. Current evaluation revealed euthyroid status, a hypoechoic solid lesion of 13 × 9 mm in size with irregular borders in the left thyroid lobe on thyroid USG and cytologic assessment of thyroid nodule. The patient was diagnosed with suspected, oncocytic lesion, Hashimoto thyroiditis or LCH. The patient underwent total thyroidectomy and pathological assessment confirmed the diagnosis of Langerhans cell histiocytosis. Assessments in the sixth month of postoperative follow-up revealed euthyroid status with no thyroid tissue remnants or pathological lymph node on thyroid USG. In view of the multifocal lesions indicating multi-system disease, a systemic chemotherapy protocol with combination of prednisone (PRED and vinblastine (VBL has been planned by the hematology department.

  11. Preferential radiosensitization of G1 checkpoint--deficient cells by methylxanthines

    International Nuclear Information System (INIS)

    Russell, Kenneth J.; Wiens, Linda W.; Demers, G. William; Galloway, Denise A.; Le, Tiep; Rice, Glenn C.; Bianco, James A.; Singer, Jack W.; Groudine, Mark

    1996-01-01

    Purpose: To develop a checkpoint-based strategy for preferential radiosensitization of human tumors with deficient and/or mutant p53. Methods and Materials: A549 human lung adenocarcinoma cell lines differing in their expression of the p53 tumor suppressor gene were produced by transduction with the E6 oncogene from human papilloma virus type 16. The cells expressing E6 (E6+) lack a G1 arrest in response to ionizing radiation, are deficient in p53 and p21 expression, and exhibit a fivefold greater clonogenic survival following 10 Gy radiation. Results: Postirradiation incubation with millimolar concentrations of the methylxanthine pentoxifylline (PTX) results in preferential radiosensitization of the E6+ cells compared to the LXSN+ vector transduced controls. There is a threefold sensitization of the LXSN+ cells and a 15-fold sensitization of the E6+ cells, which results in equal clonogenic survival of the two lines. Flow cytometry reveals PTX abrogation of the radiation induced G2 arrest for both cell lines. PTX also prolongs G1 transit for both cell lines. Preliminary results are presented using a novel methylxanthine, lisofylline (LSF), which has similar cell cycle effects on G1 and G2 and achieves differential radiosensitization at micromolar concentrations that are sustainable in humans. Conclusions: This checkpoint-based strategy is a promising approach for achieving preferential radiosensitization of p53- tumors relative to p53+ normal tissues

  12. Histopathology and immune histochemistry of red tattoo reactions. Interface dermatitis is the lead pathology, with increase in T-lymphocytes and Langerhans cells suggesting an allergic pathomechanism.

    Science.gov (United States)

    Høgsberg, T; Thomsen, B M; Serup, J

    2015-11-01

    The majority of tattoo reactions are affiliated to red pigmented areas and often suspected to be allergic in nature. A sizeable series of biopsies of such reactions has not previously been performed. The aim of this study was to type and grade epidermal and dermal changes in tattoo reactions to red/red nuances by microscopy and immunochemistry relevant for the assessment of a possible allergic pathomechanism. Skin biopsies were taken from red tattoo reactions, graded by conventional microscopy and stained for T and B-lymphocytes, Langerhans cells, macrophages and tumour necrosis factor (TNF)-α. The study included 19 biopsies from 19 patients. The culprit colours were red/pink (n = 15) and purple/bordeaux (n = 4). Interface dermatitis was clearly the lead pathology found in 78% of samples, overlapped with granulomatous (in 32%) and pseudolymphomatous reaction patterns (in 32%). Epidermal hyperkeratosis (in 89%) was common as was leakage of red pigment across the dermo-epidermal junction, with transepidermal elimination (in 28%). The dermal cellular infiltration was dominated by T-lymphocytes (in 100%), Langerhans cells (in 95%) and macrophages (in 100%). TNF-α was common. The predominant histological pattern of chronic tattoo reactions in red/red nuances is interface dermatitis. T-lymphocytes and Langerhans cells are increased suggesting an allergic pathomechanism. TNF-α may contribute to reactions. In many cases, overlapping reactive patterns were identified. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Whole-body MRI in children with Langerhans cell histiocytosis for the evaluation of the skeletal system

    International Nuclear Information System (INIS)

    Steinborn, M.; Woertler, K.; Rummeny, E.J.; Nathrath, M.; Schoeniger, M.; Hahn, H.

    2008-01-01

    Purpose: the usefulness of whole-body MRI (WB-MRI) for the detection of skeletal lesions in patients with Langerhans cell histiocytosis should be documented on the basis of case presentations. Materials and methods: in six patients with histologically proven Langerhans cell histiocytosis, 14 WB-MRI examinations were performed to evaluate the skeletal system within disease staging (6 primary, 8 follow-up examinations). The examinations were performed on a 1.5 Tesla, 32-channel whole-body scanner. The examination protocol consisted of T1-weighted and STIR sequences in coronal and sagittal orientation. For comparison, radiographs of the initial skeletal lesions and those that were additionally detected on WB-MRI were available. Results: in 4 patients no additional skeletal lesions were found on WB-MRI besides the initial lesion leading to the diagnosis of unifocal single system disease. In 2 patients WB-MRI was able to identify additional skeletal lesions. In a 5 1/2 year-old boy with the primary lesion located in the cervical spine, a second lesion was detected in the lumbar spine on the initial scan and in the skull and proximal femur during follow-up examination. In a 12 year-old girl with a primary lesion of the thoracic spine, WB-MRI diagnosed additional lesions in the pelvic bone and the tibia. In both patients the diagnosis of multifocal skeletal involvement led to chemotherapy. During follow-up examination, the healing response under therapy could be demonstrated. Comparison with conventional imaging showed that especially lesions located in the spine or the pelvis were not detectable on radiographs even when knowing the MR results. (orig.)

  14. Spared pre-irradiated area in pustular lesions induced by icotinib showing decreased expressions of CD1a+ langerhans cells and FGFR2

    International Nuclear Information System (INIS)

    Zhao Qiong; Wang Yi Na; Wang Bo

    2013-01-01

    Icotinib hydrochloride, a novel inhibitor of epidermal growth factor receptor tyrosine kinase, has been approved by the State Food and Drug Administration for the treatment of advanced non-small-cell lung cancer. Up to date, cutaneous response to icotinib is largely unknown. Here we report an uncommon lesional phenomenon in a 56-year-old Chinese male with non-small-cell lung cancer, who received icotinib as a second-line treatment. Characteristic papulopustular rash on the chest and back was observed 4 days later. Interestingly, the rash completely spares a pre-irradiated area. The immunohistochemical study in the lesional skin area and spared skin area revealed a significant decrease in CD1a + Langerhans cells, Ki-67 as well as FGFR2 in the spared area than in the lesional area. Thus, the present case indicated that loss of the basal layer of proliferative cells and antigen-presenting cells (Langerhans cell), as well as the down-regulation of FGFR2 signaling in the pre-irradiated skin area, may join forces in inhibiting icotinib-associated cutaneous reactions. To our knowledge, this is the first report of both lesional area and lesion-spared area in a Chinese male receiving treatment with a new epidermal growth factor receptor-tyrosine kinase inhibitor (icotinib). The immunohistochemical reactions described here also provide new insight into the pathogenesis of epidermal growth factor receptor-tyrosine kinase inhibitor-related skin toxicities, and the role that other tyrosine kinase receptors (including FGFR) played in non-small-cell lung cancer. (author)

  15. Spared pre-irradiated area in pustular lesions induced by icotinib showing decreased expressions of CD1a+ langerhans cells and FGFR2.

    Science.gov (United States)

    Zhao, Qiong; Wang, Yi Na; Wang, Bo

    2013-02-01

    Icotinib hydrochloride, a novel inhibitor of epidermal growth factor receptor tyrosine kinase, has been approved by the State Food and Drug Administration for the treatment of advanced non-small-cell lung cancer. Up to date, cutaneous response to icotinib is largely unknown. Here we report an uncommon lesional phenomenon in a 56-year-old Chinese male with non-small-cell lung cancer, who received icotinib as a second-line treatment. Characteristic papulopustular rash on the chest and back was observed 4 days later. Interestingly, the rash completely spares a pre-irradiated area. The immunohistochemical study in the lesional skin area and spared skin area revealed a significant decrease in CD1a(+) Langerhans cells, Ki-67 as well as FGFR2 in the spared area than in the lesional area. Thus, the present case indicated that loss of the basal layer of proliferative cells and antigen-presenting cells (Langerhans cell), as well as the down-regulation of FGFR2 signaling in the pre-irradiated skin area, may join forces in inhibiting icotinib-associated cutaneous reactions. To our knowledge, this is the first report of both lesional area and lesion-spared area in a Chinese male receiving treatment with a new epidermal growth factor receptor-tyrosine kinase inhibitor (icotinib). The immunohistochemical reactions described here also provide new insight into the pathogenesis of epidermal growth factor receptor-tyrosine kinase inhibitor-related skin toxicities, and the role that other tyrosine kinase receptors (including FGFR) played in non-small-cell lung cancer.

  16. The Beta Cell in Its Cluster: Stochastic Graphs of Beta Cell Connectivity in the Islets of Langerhans.

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    Deborah A Striegel

    2015-08-01

    Full Text Available Pancreatic islets of Langerhans consist of endocrine cells, primarily α, β and δ cells, which secrete glucagon, insulin, and somatostatin, respectively, to regulate plasma glucose. β cells form irregular locally connected clusters within islets that act in concert to secrete insulin upon glucose stimulation. Due to the central functional significance of this local connectivity in the placement of β cells in an islet, it is important to characterize it quantitatively. However, quantification of the seemingly stochastic cytoarchitecture of β cells in an islet requires mathematical methods that can capture topological connectivity in the entire β-cell population in an islet. Graph theory provides such a framework. Using large-scale imaging data for thousands of islets containing hundreds of thousands of cells in human organ donor pancreata, we show that quantitative graph characteristics differ between control and type 2 diabetic islets. Further insight into the processes that shape and maintain this architecture is obtained by formulating a stochastic theory of β-cell rearrangement in whole islets, just as the normal equilibrium distribution of the Ornstein-Uhlenbeck process can be viewed as the result of the interplay between a random walk and a linear restoring force. Requiring that rearrangements maintain the observed quantitative topological graph characteristics strongly constrained possible processes. Our results suggest that β-cell rearrangement is dependent on its connectivity in order to maintain an optimal cluster size in both normal and T2D islets.

  17. The Beta Cell in Its Cluster: Stochastic Graphs of Beta Cell Connectivity in the Islets of Langerhans.

    Science.gov (United States)

    Striegel, Deborah A; Hara, Manami; Periwal, Vipul

    2015-08-01

    Pancreatic islets of Langerhans consist of endocrine cells, primarily α, β and δ cells, which secrete glucagon, insulin, and somatostatin, respectively, to regulate plasma glucose. β cells form irregular locally connected clusters within islets that act in concert to secrete insulin upon glucose stimulation. Due to the central functional significance of this local connectivity in the placement of β cells in an islet, it is important to characterize it quantitatively. However, quantification of the seemingly stochastic cytoarchitecture of β cells in an islet requires mathematical methods that can capture topological connectivity in the entire β-cell population in an islet. Graph theory provides such a framework. Using large-scale imaging data for thousands of islets containing hundreds of thousands of cells in human organ donor pancreata, we show that quantitative graph characteristics differ between control and type 2 diabetic islets. Further insight into the processes that shape and maintain this architecture is obtained by formulating a stochastic theory of β-cell rearrangement in whole islets, just as the normal equilibrium distribution of the Ornstein-Uhlenbeck process can be viewed as the result of the interplay between a random walk and a linear restoring force. Requiring that rearrangements maintain the observed quantitative topological graph characteristics strongly constrained possible processes. Our results suggest that β-cell rearrangement is dependent on its connectivity in order to maintain an optimal cluster size in both normal and T2D islets.

  18. Altered TNF-Alpha, Glucose, Insulin and Amino Acids in Islets Langerhans Cultured in a Microgravity Model System

    Science.gov (United States)

    Tobin, Brian W.; Leeper-Woodford, Sandra K.; Hashemi, Brian B.; Smith, Scott M.; Sams, Clarence F.

    2001-01-01

    The present studies were designed to determine effects of a microgravity model system upon lipopolysaccharide (LPS) stimulated tumor necrosis factor alpha (TNF-alpha) activity and indices of insulin and fuel homeostasis of pancreatic islets of Langerhans. Islets (1726+/-1 17,150 u IEU) from Wistar Furth rats were treated as: 1) HARV (High Aspect Ratio Vessel cell culture) , 2) HARV plus LPS, 3) static culture, 4) static culture plus LPS. TNF-alpha (L929 cytotoxicity assay) was significantly increased in LPS-induced HARV and static cultures, yet the increase was more pronounced in the static culture group (palpha production of pancreatic islets of Langerhans, favoring a lesser TNF activity in the HARV. These alterations in fuel homeostasis may be promulgated by gravity averaged cell culture methods or by three dimensional cell assembly.

  19. Examination of tetrachlorosalicylanilide (TCSA) photoallergy using in vitro photohapten-modified Langerhans cell-enriched epidermal cells

    International Nuclear Information System (INIS)

    Gerberick, G.F.; Ryan, C.A.; Von Bargen, E.C.; Stuard, S.B.; Ridder, G.M.

    1991-01-01

    Lymphocytes from BALB/c mice photosensitized in vivo to tetrachlorosalicylanilide (TCSA) were investigated to determine whether they could be stimulated to proliferate when cultured with Langerhans cell-enriched cultured epidermal cells (LC-EC) photohapten-modified in vitro with TCSA + UVA radiation. Cultured LC-EC were photohapten-modified in vitro by irradiation in TCSA-containing medium using a 1000-watt solar simulator equipped with filters to deliver primarily UVA radiation (320-400 nm). Lymphocytes from TCSA-photosensitized mice were incubated with LC-EC that had been treated in vitro with 0.1 mM TCSA and 2 J/cm2 UVA radiation (TCSA + UVA). Responder lymphocytes demonstrated a significant increase in their blastogenesis response compared to lymphocytes that were incubated with LC-EC irradiated with UVA prior to treatment with TCSA (UVA/TCSA) or with LC-EC that had received no treatment. Lymphocytes from naive mice or mice photosensitized with musk ambrette (MA) demonstrated a significantly lower response to LC-EC modified with TCSA + UVA, indicating the specificity of the response. Maximum blastogenesis response was achieved when LC-EC were treated with 0.1 mM TCSA and a UVA radiation dose of at least 0.5 J/cm2. Epidermal cells depleted of LC by treatment with anti-Ia antibody plus complement or by an adherence procedure were unable to stimulate this blastogenesis response. Epidermal cells treated in vitro with TCSA + UVA demonstrated enhanced fluorescence compared to control cells. The fluorescence observed was not restricted to any specific epidermal cell type; however, fluorescence microscopy studies revealed that dendritic Ia-positive cells, presumably LC, were also TCSA fluorescent

  20. Preferentially Cytotoxic Constituents of Andrographis paniculata and their Preferential Cytotoxicity against Human Pancreatic Cancer Cell Lines.

    Science.gov (United States)

    Lee, Sullim; Morita, Hiroyuki; Tezuka, Yasuhiro

    2015-07-01

    In the course of our search for anticancer agents based on a novel anti-austerity strategy, we found that the 70% EtOH extract of the crude drug Andrographis Herba (aerial parts of Andrographis paniculata), used in Japanese Kampo medicines, killed PANC-1 human pancreatic cancer cells preferentially in nutrient-deprived medium (NDM). Phytochemical investigation of the 70% EtOH extract led to the isolation of 21 known compounds consisting of six labdane-type diterpenes (11, 15, 17-19, 21), six flavones (5, 7, 10, 12, 14, 20), three flavanones (2, 6, 16), two sterols (3, 8), a fatty acid (1), a phthalate (4), a triterpene (9), and a monoterpene (13). Among them, 14-deoxy-11,12-didehydroandrographolide (17) displayed the most potent preferential cytotoxicity against PANC-1 and PSN-1 cells with PC50 values of 10.0 μM and 9.27 μM, respectively. Microscopical observation, double staining with ethidium bromide (EB) and acridine orange (AO), and flow cytometry with propidium iodide/annexin V double staining indicated that 14-deoxy-11,12-didehydroandrographolide (17) triggered apoptosis-like cell death in NDM with an amino acids and/or serum-sensitive mode.

  1. Simulated Microgravity Reduces TNF-Alpha Activity, Suppresses Glucose Uptake and Enhances Arginine Flux in Pancreatic Islets of Langerhans

    Science.gov (United States)

    Tobin, Brian W.; Leeper-Woodford, Sandra K.; Hashemi, Brian B.; Smith, Scott M.; Sams, Clarence F.; Paloski, W. H. (Technical Monitor)

    2000-01-01

    The present studies were designed to determine effects of microgravity upon lipopolysaccharide (LPS) stimulated tumor necrosis factor alpha (TNF - alpha) activity and indices of insulin and fuel homeostasis of pancreatic islets of Langerhans. Islets (1726+/-117,150 u IEU) from Wistar Furth rats were treated as: 1) HARV (High Aspect Ratio Vessel cell culture) , 2) HARV plus LPS 3) static culture, 4) static culture plus LPS TNF-alpha (L929 cytotoxicity assay) was significantly increased in LPS-induced HARV and static cultures, yet the increase was more pronounced in the static culture group (palpha production of pancreatic islets of Langerhans, favoring a lesser TNF activity in the HARV paradigm. These alterations in fuel homeostasis may be promulgated by gravity averaged cell culture methods or by three dimensional cell assembly.

  2. Immunostimulatory Activity of the Cytokine-Based Biologic, IRX-2, on Human Papillomavirus-Exposed Langerhans Cells.

    Science.gov (United States)

    Da Silva, Diane M; Woodham, Andrew W; Naylor, Paul H; Egan, James E; Berinstein, Neil L; Kast, W Martin

    2016-05-01

    Langerhans cells (LCs) are the antigen-presenting cells of the epithelial layer and are responsible for initiating immune responses against skin and mucosa-invading viruses. Human papillomavirus (HPV)-mediated suppression of LC function is a crucial mechanism of HPV immune evasion, which can lead to persistent infection and development of several human cancers, including cervical, anal, and head and neck cancers. The cell-derived cytokine-based biologic, IRX-2, consists of multiple well-defined cytokines and is broadly active on various immune cell subsets. In this study, we investigated primary human LC activation after exposure to HPV16, followed by treatment with IRX-2 in vitro, and evaluated their subsequent ability to induce HPV16-specific T cells. In contrast to its activity on dendritic cells, HPV16 alone is not sufficient to induce phenotypic and functional activation of LCs. However, IRX-2 induces a significant upregulation of antigen presentation and costimulatory molecules, T helper 1 (Th1)-associated cytokine release, and chemokine-directed migration of LCs pre-exposed to HPV16. Furthermore, LCs treated with IRX-2 after HPV16 exposure induced CD8(+) T-cell responses against specific HLA-A*0201-binding HPV16 T-cell epitopes. The present study suggests that IRX-2 is an attractive immunomodulator for assisting the immune response in eradication of HPV-infected cells, thereby potentially preventing HPV-induced cancers.

  3. A Rare Case of Erdheim-Chester Disease and Langerhans Cell Histiocytosis Overlap Syndrome

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    Shahzaib Nabi

    2015-01-01

    Full Text Available A 48-year-old woman with a past medical history of seizures and end-stage renal disease secondary to obstructive uropathy from retroperitoneal fibrosis presented to the emergency department with seizures and altered mental status. A Glasgow Coma Scale of 4 prompted intubation, and she was subsequently admitted to the intensive care unit. Magnetic resonance imaging of the brain performed to elucidate the aetiology of her seizure showed a dural-based mass within the left temporoparietal lobe as well as mass lesions within the orbits. Further imaging showed extensive retroperitoneal fibrosis extending to the mediastinum with involvement of aorta and posterior pleural space. Imaging of the long bones showed bilateral sclerosis and cortical thickening of the diaphyses. Imaging of the maxillofacial structures showed osseous destructive lesions involving the mandible. These clinical and radiological features were consistent with a diagnosis of Erdheim-Chester disease; however, the patient’s skin biopsy was consistent with Langerhans cell histiocytosis.

  4. Preferential transfer of certain plasma membrane proteins onto T and B cells by trogocytosis.

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    Sandrine Daubeuf

    2010-01-01

    Full Text Available T and B cells capture antigens via membrane fragments of antigen presenting cells (APC in a process termed trogocytosis. Whether (and how a preferential transfer of some APC components occurs during trogocytosis is still largely unknown. We analyzed the transfer onto murine T and B cells of a large panel of fluorescent proteins with different intra-cellular localizations in the APC or various types of anchors in the plasma membrane (PM. Only the latter were transferred by trogocytosis, albeit with different efficiencies. Unexpectedly, proteins anchored to the PM's cytoplasmic face, or recruited to it via interaction with phosphinositides, were more efficiently transferred than those facing the outside of the cell. For proteins spanning the PM's whole width, transfer efficiency was found to vary quite substantially, with tetraspanins, CD4 and FcRgamma found among the most efficiently transferred proteins. We exploited our findings to set immunodiagnostic assays based on the capture of preferentially transferred components onto T or B cells. The preferential transfer documented here should prove useful in deciphering the cellular structures involved in trogocytosis.

  5. Granulomatosis de células de Langerhans: Presentación de un caso

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    . Caridad Nazco Ríos

    1998-12-01

    Full Text Available Se reporta un inusual caso de granulomatosis de células de Langerhans localizado en maxilares en un paciente de 30 meses de edad, quien presentaba además de las lesiones líticas óseas, lesiones de aspecto tumoral en encía palatina y lingual de ambas arcadas dentarias. El examen óseo no arrojaba compromiso de otros huesos. El diagnóstico histológico fue corroborado por el Centro Nacional de Referencia en Anatomía Patológica.A unusual case of Langerhans´ cells is reported, located in maxillae of a 30 months old patients, who, apart from bone lithic injuries, showed injuries of tumoral type in lingual and palatine gingiva of both dental archs. According to bone examination, there weren´t involvement of other bones. Histologic diagnosis was corroborated by National Reference Center in Pathologic Anatomy.

  6. The role of bone scintigraphy in Langerhans' cell histiocytosis; a case report; Interet de la scintigraphie osseuse dans l'histiocytose langerhansienne: a propos d'un cas

    Energy Technology Data Exchange (ETDEWEB)

    Razzouk, M.; Carrier, P.; Darcourt, J. [Centre TEP, Hopital de l' Archet-1, Service Universitaire de Medecine Nucleaire, 06 - Nice (France); Razzouk, M.; Carrier, P.; Darcourt, J. [Federation interhospitaliere, CHU, CAL universitaire de Nice, 06 - Nice (France); Deville, A. [Hopital de l' Archet, Service d' Hemato-Oncologie Pediatrique, 06 - Nice (France); Cadet, G. [Centre Hospitalier intercommunal de Grasse, Service de Pediatrie, 06 - Grasse (France)

    2008-09-15

    We present one case of bone-Langerhans cell histiocytosis in a three-year-old male child presenting osseous lesions in the skull and the femur, which are very frequent localizations in histiocytosis. Bone scintigraphy is useful for both initial staging and follow-up associated with other imaging modalities. (authors)

  7. An Aggressive Form of Langerhan Cell Histiocytosis in an Adult: Therapeutic Challenges

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    Karan Seegobin

    2017-01-01

    Full Text Available Langerhans cell histiocytosis (LCH is rare in adults. Regular follow-up is mandatory due to reoccurrence. A 35-year-old male with an incidental left iliac bone lesion was diagnosed with LCH. He later became symptomatic with hip pain and spread of the disease. Despite excision of the symptomatic iliac lesion, he had progression while on cytarabine and nivolumab, evidenced by increased bone pain and involvement of other bones on imaging. He underwent excision of the jaw lesion followed by vinblastine; he was pain free and had stable disease on PET imaging after 3 months. LCH is an uncommon neoplasia. Treatment is reserved for symptomatic patients while asymptomatic patients are observed. Follow-up is imperative due to the risk of reoccurrence. Despite surgical treatment together with one of the front-line agents for refractory disease, in this case cytarabine, he still had progression of the disease. Furthermore, the trial of nivolumab was of no benefit. This case highlights good response to vinblastine which is previously reported to have good success. No trials are published, and the optimal strategy has yet to be defined. LCH with multiple bony involvement can be aggressive and therapeutically challenging.

  8. Células de Langerhans no epitélio da prega vocal humana: estudo imunoistoquímico Langerhans cells in human vocal folds mucosa: immunohistochemical study

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    João Aragão Ximenes Filho

    2004-10-01

    Full Text Available Células de Langerhans (CL são um tipo de células dendríticas que têm funções que envolvem apresentação de antígeno e a estimulação de resposta T dependente. Elas representam aproximadamente 4% das células do epitélio laríngeo. OBJETIVO: Identificar a presença de CL no epitélio das pregas vocais, comparar suas subpopulações, bem com comparar a capacidade de quatro marcadores imunoistoquímicos. FORMA DE ESTUDO: Experimental. CASUÍSTICA E MÉTODO: Seis cadáveres, 3 homens e 3 mulheres foram estudados. Foram analisadas amostras de pele e das pregas vocais coradas e imunomarcadas para vimentina, proteína S-100, CD-68 e fascina. Após análise histológica, foi realizado o teste t de Student e análise de variância no estudo estatístico. RESULTADOS E CONCLUSÕES: Foi possível identificar a presença de CL no epitélio das pregas vocais de humanos não fumantes de ambos os sexos. A fascina, a vimentina o CD-68 mostraram-se bons marcadores das CL, enquanto a proteína S-100 teve estatisticamente menor poder de marcação tanto na prega vocal (p=0,01 como na pele (p=0,02. Foi possível identificar três diferentes subpopulações de CL presentes tanto na prega vocal como na pele destes indivíduos, contudo apenas na pele observarmos maior quantidade estatisticamente significante na camada basal do epitélio.Langerhans Cells (LC are a type of dendritic cells that have functions which involves antigen presentation and the stimulation of a T cell response. They represent about 4% of the laryngeal epithelial cells. AIM: The aim of this study was to identify the presence of LC in the epithelium of the vocal folds, to compare their subpopulations, as well as to compare the capacity of four immunohistochemistry markers. STUDY DESIGN: Experimental. MATERIAL AND METHOD: Six cadavers, 3 men and 3 women, were studied. Analysis of vocal folds and skin paraffin blocks stained with commercially available polyclonal S-100, vimentin, CD-68 and

  9. Candidate Microbicides Block HIV-1 Infection of Human Immature Langerhans Cells within Epithelial Tissue Explants

    Science.gov (United States)

    Kawamura, Tatsuyoshi; Cohen, Sandra S.; Borris, Debra L.; Aquilino, Elisabeth A.; Glushakova, Svetlana; Margolis, Leonid B.; Orenstein, Jan M.; Offord, Robin E.; Neurath, A. Robert; Blauvelt, Andrew

    2000-01-01

    Initial biologic events that underlie sexual transmission of HIV-1 are poorly understood. To model these events, we exposed human immature Langerhans cells (LCs) within epithelial tissue explants to two primary and two laboratory-adapted HIV-1 isolates. We detected HIV-1Ba-L infection in single LCs that spontaneously emigrated from explants by flow cytometry (median of infected LCs = 0.52%, range = 0.08–4.77%). HIV-1–infected LCs downregulated surface CD4 and CD83, whereas MHC class II, CD80, and CD86 were unchanged. For all HIV-1 strains tested, emigrated LCs were critical in establishing high levels of infection (0.1–1 μg HIV-1 p24 per milliliter) in cocultured autologous or allogeneic T cells. HIV-1Ba-L (an R5 HIV-1 strain) more efficiently infected LC–T cell cocultures when compared with HIV-1IIIB (an X4 HIV-1 strain). Interestingly, pretreatment of explants with either aminooxypentane-RANTES (regulated upon activation, normal T cell expressed and secreted) or cellulose acetate phthalate (potential microbicides) blocked HIV-1 infection of LCs and subsequent T cell infection in a dose-dependent manner. In summary, we document HIV-1 infection in single LCs after exposure to virus within epithelial tissue, demonstrate that relatively low numbers of these cells are capable of inducing high levels of infection in cocultured T cells, and provide a useful explant model for testing of agents designed to block sexual transmission of HIV-1. PMID:11085750

  10. Brain tumor initiating cells adapt to restricted nutrition through preferential glucose uptake.

    Science.gov (United States)

    Flavahan, William A; Wu, Qiulian; Hitomi, Masahiro; Rahim, Nasiha; Kim, Youngmi; Sloan, Andrew E; Weil, Robert J; Nakano, Ichiro; Sarkaria, Jann N; Stringer, Brett W; Day, Bryan W; Li, Meizhang; Lathia, Justin D; Rich, Jeremy N; Hjelmeland, Anita B

    2013-10-01

    Like all cancers, brain tumors require a continuous source of energy and molecular resources for new cell production. In normal brain, glucose is an essential neuronal fuel, but the blood-brain barrier limits its delivery. We now report that nutrient restriction contributes to tumor progression by enriching for brain tumor initiating cells (BTICs) owing to preferential BTIC survival and to adaptation of non-BTICs through acquisition of BTIC features. BTICs outcompete for glucose uptake by co-opting the high affinity neuronal glucose transporter, type 3 (Glut3, SLC2A3). BTICs preferentially express Glut3, and targeting Glut3 inhibits BTIC growth and tumorigenic potential. Glut3, but not Glut1, correlates with poor survival in brain tumors and other cancers; thus, tumor initiating cells may extract nutrients with high affinity. As altered metabolism represents a cancer hallmark, metabolic reprogramming may maintain the tumor hierarchy and portend poor prognosis.

  11. Metformin kills and radiosensitizes cancer cells and preferentially kills cancer stem cells

    Science.gov (United States)

    Song, Chang W.; Lee, Hyemi; Dings, Ruud P. M.; Williams, Brent; Powers, John; Santos, Troy Dos; Choi, Bo-Hwa; Park, Heon Joo

    2012-01-01

    The anti-cancer effects of metformin, the most widely used drug for type 2 diabetes, alone or in combination with ionizing radiation were studied with MCF-7 human breast cancer cells and FSaII mouse fibrosarcoma cells. Clinically achievable concentrations of metformin caused significant clonogenic death in cancer cells. Importantly, metformin was preferentially cytotoxic to cancer stem cells relative to non-cancer stem cells. Metformin increased the radiosensitivity of cancer cells in vitro, and significantly enhanced the radiation-induced growth delay of FSaII tumors (s.c.) in the legs of C3H mice. Both metformin and ionizing radiation activated AMPK leading to inactivation of mTOR and suppression of its downstream effectors such as S6K1 and 4EBP1, a crucial signaling pathway for proliferation and survival of cancer cells, in vitro as well as in the in vivo tumors. Conclusion: Metformin kills and radiosensitizes cancer cells and eradicates radioresistant cancer stem cells by activating AMPK and suppressing mTOR. PMID:22500211

  12. Neurotransmitters and Neuropeptides: New Players in the Control of Islet of Langerhans' Cell Mass and Function.

    Science.gov (United States)

    Di Cairano, Eliana S; Moretti, Stefania; Marciani, Paola; Sacchi, Vellea Franca; Castagna, Michela; Davalli, Alberto; Folli, Franco; Perego, Carla

    2016-04-01

    Islets of Langerhans control whole body glucose homeostasis, as they respond, releasing hormones, to changes in nutrient concentrations in the blood stream. The regulation of hormone secretion has been the focus of attention for a long time because it is related to many metabolic disorders, including diabetes mellitus. Endocrine cells of the islet use a sophisticate system of endocrine, paracrine and autocrine signals to synchronize their activities. These signals provide a fast and accurate control not only for hormone release but also for cell differentiation and survival, key aspects in islet physiology and pathology. Among the different categories of paracrine/autocrine signals, this review highlights the role of neurotransmitters and neuropeptides. In a manner similar to neurons, endocrine cells synthesize, accumulate, release neurotransmitters in the islet milieu, and possess receptors able to decode these signals. In this review, we provide a comprehensive description of neurotransmitter/neuropetide signaling pathways present within the islet. Then, we focus on evidence supporting the concept that neurotransmitters/neuropeptides and their receptors are interesting new targets to preserve β-cell function and mass. A greater understanding of how this network of signals works in physiological and pathological conditions would advance our knowledge of islet biology and physiology and uncover potentially new areas of pharmacological intervention. J. Cell. Physiol. 231: 756-767, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  13. Langerhans Cell Histiocytosis of the Cranial Base: Is Low-Dose Radiotherapy Effective?

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    Andreas Meyer

    2012-01-01

    Full Text Available Introduction. Langerhans cell histiocytosis (LCH is a rare disease of unknown etiology with different clinical features. A standardised treatment has not been established so far. Case Report. We report a case of a 28-year-old patient who initially presented with hypesthesia of the fifth cranial nerve and pain of the left ear. Diagnosis showed a tumour localised in the cranial base with a maximum diameter of 4.1 cm. The diagnosis of LCH was confirmed histologically by biopsy. Diagnostic workup verified the cranial lesion as the sole manifestation of LCH. A total dose of 9 Gy (single dose 1.8 Gy was delivered. The symptoms dissolved completely within 6 months after radiation; repeated CT and MRI scans revealed a reduction in size of the lesion and a remineralisation of the bone. After a followup of 13 years the patient remains free of symptoms without relapse or any side effects from therapy. Discussion. Due to the indolent course of the disease with a high rate of spontaneous remissions the choice of treatment strongly depends on the individual clinical situation. In the presented case low-dose radiotherapy was sufficient to obtain long-term local control in a region with critical structures and tissues.

  14. A Historical Perspective on the Identification of Cell Types in Pancreatic Islets of Langerhans by Staining and Histochemical Techniques.

    Science.gov (United States)

    Baskin, Denis G

    2015-08-01

    Before the middle of the previous century, cell types of the pancreatic islets of Langerhans were identified primarily on the basis of their color reactions with histological dyes. At that time, the chemical basis for the staining properties of islet cells in relation to the identity, chemistry and structure of their hormones was not fully understood. Nevertheless, the definitive islet cell types that secrete glucagon, insulin, and somatostatin (A, B, and D cells, respectively) could reliably be differentiated from each other with staining protocols that involved variations of one or more tinctorial techniques, such as the Mallory-Heidenhain azan trichrome, chromium hematoxylin and phloxine, aldehyde fuchsin, and silver impregnation methods, which were popularly used until supplanted by immunohistochemical techniques. Before antibody-based staining methods, the most bona fide histochemical techniques for the identification of islet B cells were based on the detection of sulfhydryl and disulfide groups of insulin. The application of the classical islet tinctorial staining methods for pathophysiological studies and physiological experiments was fundamental to our understanding of islet architecture and the physiological roles of A and B cells in glucose regulation and diabetes. © The Author(s) 2015.

  15. Dendritic cell neoplasms: an overview.

    Science.gov (United States)

    Kairouz, Sebastien; Hashash, Jana; Kabbara, Wadih; McHayleh, Wassim; Tabbara, Imad A

    2007-10-01

    Dendritic cell neoplasms are rare tumors that are being recognized with increasing frequency. They were previously classified as lymphomas, sarcomas, or histiocytic neoplasms. The World Health Organization (WHO) classifies dendritic cell neoplasms into five groups: Langerhans' cell histiocytosis, Langerhans' cell sarcoma, Interdigitating dendritic cell sarcoma/tumor, Follicular dendritic cell sarcoma/tumor, and Dendritic cell sarcoma, not specified otherwise (Jaffe, World Health Organization classification of tumors 2001; 273-289). Recently, Pileri et al. provided a comprehensive immunohistochemical classification of histiocytic and dendritic cell tumors (Pileri et al., Histopathology 2002;59:161-167). In this article, a concise overview regarding the pathological, clinical, and therapeutic aspects of follicular dendritic, interdigitating dendritic, and Langerhans' cell tumors is presented.

  16. The natural history of skin-limited Langerhans cell histiocytosis: a single-institution experience.

    Science.gov (United States)

    Ehrhardt, Matthew J; Humphrey, Stephen R; Kelly, Michael E; Chiu, Yvonne E; Galbraith, Sheila S

    2014-11-01

    Prior reports of Langerhans cell histiocytosis (LCH) suggest that isolated skin involvement is rare and often progresses to systemic disease. More rapid access to pediatric subspecialty care has likely led to more frequent representation of this condition. The purpose of this study is to characterize the natural history of skin-limited LCH in an era of increased access to pediatric subspecialty care. A retrospective chart review was performed on all patients newly diagnosed with LCH between 2001 and 2012 at the Children's Hospital of Wisconsin. Extensive review of laboratory, physical examination, and imaging reports was performed and data collected for patients with biopsy-proven skin LCH. Sixteen individuals with skin-limited LCH were identified. The median age at onset of skin eruption was birth (range, birth to 6 mo), and median duration of follow-up was 19.5 months (range, 2 wk to 10 y) from diagnosis. One patient (6%) developed pituitary disease and 1 patient (6%) had refractory skin involvement. All others experienced complete resolution. For patients without progressive or refractory disease, resolution of skin findings occurred within 7 months from onset. Progression of skin-limited to multisystem LCH likely may be less frequent than previously described.

  17. Chronic low-dose UVA irradiation induces local suppression of contact hypersensitivity, Langerhans cell depletion and suppressor cell activation in C3H/HeJ mice

    International Nuclear Information System (INIS)

    Bestak, Rosa; Halliday, G.M.

    1996-01-01

    It has previously been demonstrated that chronic low-dose solar-simulated UV radiation could induce both local and systemic immunosuppression as well as tolerance to a topically applied hapten. In this study, we have used a chronic low-dose UV-irradiation protocol to investigate the effects of UVA on the skin immune system of C3H/HeJ mice. Irradiation with UVA+B significantly suppressed the local and systemic primary contact hypersensitivity (CHS) response to the hapten 2,4,6-trinitrochlorobenzene. Furthermore, UVA+B reduced Langerhans cell (LC) and dendritic epidermal T cell (DETC) densities in chronically UV-irradiated mice. Ultraviolet A irradiation induced local, but not systemic, immunosuppression and reduced LC (32%) but not DETC from the epidermis compared to the shaved control animals. Treatment of mice with both UVA+B and UVA radiation also induced an impaired secondary CHS response, and this tolerance was transferable with spleen cells. (Author)

  18. Non-calcifying and Langerhans cell-rich variant of calcifying epithelial odontogenic tumor

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    Hung-Pin Lin

    2016-06-01

    Full Text Available This study reported the clinicopathological features, treatment and prognosis of nine cases of noncalcifying and Langerhans cell (LC-rich calcifying epithelial odontogenic tumor (CEOT collected from the English literature. Of the nine cases, seven were intraosseous and two were extraosseous. All nine tumors were found in Asian patients. The age of the nine patients ranged from 20 years to 58 years with a mean age of 41 years. There were five female and four male patients. The seven intraosseous cases included six in the anterior and premolar region of the maxilla and one in the posterior region and ascending ramus of the mandible. The two extraosseous cases were located at the upper lateral incisor and premolar gingivae, respectively. Of the seven intraosseous cases, five showed unilocular and two multilocular radiolucency without foci of calcification. Six of the seven intraosseous cases showed resorption of the tooth roots in the tumor-involved region. Histologically, noncalcifying and LC-rich CEOTs were composed of small nests and thin strands of tumor epithelial cells with a relatively high number of LCs among them. This was the reason why we classed these nine cases as noncalcifying and LC-rich CEOTs. Two extraosseous cases received total excision of the gingival mass. For the seven intraosseous cases, four accepted partial maxillectomy or mandibulectomy, two received total excision or enucleation, and one underwent curettage. The six cases with the follow-up information available showed no tumor recurrence after a follow-up period of 6 months to 10 years.

  19. BISPHOSPHONATES IN LANGERHANS CELL HISTIOCYTOSIS: AN INTERNATIONAL RETROSPECTIVE CASE SERIES

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    Deepak Chellapandian

    2016-07-01

    Full Text Available Background: Bone is the most common organ of involvement in patients with Langerhans cell histiocytosis (LCH, which is often painful and associated with significant morbidity from pathological fractures. Current first-line treatments include chemotherapy and steroids that are effective but often associated with adverse effects, whereas the disease may reactivate despite an initial response to first-line agents. Bisphosphonates are osteoclast inhibitors that have shown to be helpful in treating bone lesions of LCH. To date, there are no large international studies to describe their role in treating bone lesions of LCH. Method: We conducted a multicenter retrospective review of 13 patients with histologically proven LCH, who had received bisphosphonates either at diagnosis or at disease reactivation. Results: Ten patients (77% had a single system bone disease, and 3 (23% had bone lesions as part of multisystem disease. Median follow-up time post-bisphosphonate therapy was 4.6 years (range, 0.8 to 8.2 years. Treatment with bisphosphonates was associated with significant pain relief in almost all patients. Twelve  (92% achieved resolution of active bone lesions, and 10 out of them had no active disease for a median of 3.5 years (range, 0.8 to 5 years. One patient did not respond. No major adverse effects were reported in this series.  Conclusion: Bisphosphonates are well-tolerated drugs that can significantly improve bone pain and induce remission in active bone LCH. Future prospective studies evaluating the role of bisphosphonates in LCH are warranted.

  20. Early Diagnosis and Monitoring of Neurodegenerative Langerhans Cell Histiocytosis.

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    Elena Sieni

    Full Text Available Neurodegenerative Langerhans Cell Histiocytosis (ND-LCH is a rare, unpredictable consequence that may devastate the quality of life of patients cured from LCH. We prospectively applied a multidisciplinary diagnostic work-up to early identify and follow-up patients with ND-LCH, with the ultimate goal of better determining the appropriate time for starting therapy.We studied 27 children and young adults with either ND-LCH verified by structural magnetic resonance imaging (MRI (group 1 or specific risk factors for (diabetes insipidus, craniofacial bone lesions, but no evidence of, neurodegenerative MRI changes (group 2. All patients underwent clinical, neurophysiological and MRI studies.Seventeen patients had MRI alterations typical for ND-LCH. Nine showed neurological impairment but only three were symptomatic; 11 had abnormal somatosensory evoked potentials (SEPs, and five had abnormal brainstem auditory evoked potentials (BAEPs. MR spectroscopy (MRS showed reduced cerebellar NAA/Cr ratio in nine patients. SEPs showed sensitivity, specificity, positive predictive value (PPV and negative predictive value (NPV for predicting ND-LCH of 70.6% (95%CI, 44.0%-89.7%, 100% (69.2%-100%, 100% (73.5%-100%, and 66.7% (38.4%-88.2%, respectively. Repeated investigations in group 1 revealed increasingly abnormal EP parameters, or neurological examination, or both, in nine of fifteen patients while MRI remained unchanged in all but one patient.A targeted MRI study should be performed in all patients with risk factors for ND-LCH for early identification of demyelination. The combined use of SEPs and careful neurological evaluation may represent a valuable, low-cost, well-tolerated and easily available methodology to monitor patients from pre-symptomatic to symptomatic stages. We suggest a multidisciplinary protocol including clinical, MRS, and neurophysiological investigations to identify a population target for future therapeutic trials.

  1. Central diabetes insipidus as a very late relapse limited to the pituitary stalk in Langerhans cell histiocytosis.

    Science.gov (United States)

    Nakagawa, Shunsuke; Shinkoda, Yuichi; Hazeki, Daisuke; Imamura, Mari; Okamoto, Yasuhiro; Kawakami, Kiyoshi; Kawano, Yoshifumi

    2016-07-01

    Central diabetes insipidus (CDI) and relapse are frequently seen in multifocal Langerhans cell histiocytosis (LCH). We present two females with multifocal LCH who developed CDI 9 and 5 years after the initial diagnosis, respectively, as a relapse limited to the pituitary stalk. Combination chemotherapy with cytarabine reduced the mass in the pituitary stalk. Although CDI did not improve, there has been no anterior pituitary hormone deficiency (APHD), neurodegenerative disease in the central nervous system (ND-CNS) or additional relapse for 2 years after therapy. It was difficult to predict the development of CDI in these cases. CDI might develop very late in patients with multifocal LCH, and therefore strict follow-up is necessary, especially with regard to symptoms of CDI such as polydipsia and polyuria. For new-onset CDI with LCH, chemotherapy with cytarabine might be useful for preventing APHD and ND-CNS.

  2. Expression of natural antimicrobial peptide β-defensin-2 and Langerhans cell accumulation in epidermis from human non-healing leg ulcers

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    Urszula Wojewodzka

    2011-08-01

    Full Text Available Chronic wounds like venous calf and diabetic foot ulcers are frequently contaminated and colonized by bacteria and it remains unclear whether there is sufficient expression of defensins and recruitment of epidermal Langerhans cells in the margin of ulcer compared to normal skin. The aim of this study was to examine immunohistochemically the expression of β-defensin-2 (hBD2, GM-CSF, VEGF growth factors and accumulation of CD1a+ Langerhans cells (LC in epidermis from chronic skin ulcers and to compare it to normal skin from the corresponding areas. Studies were carried out in 10 patients with diabetic foot, 10 patients with varicous ulcers of the calf and 10 patients undergoing orthopedic surgery (normal skin for control. Biopsy specimens were immunostained using specific primary antibodies, LSAB+ kit based on biotin-avidinperoxidase complex technique and DAB chromogen. Results were expressed as a mean staining intensity. Statistical analysis of staining showed significantly higher staining of hBD2 in both normal and ulcerated epidermis from foot sole skin compared to calf skin (normal and ulcerated, p<0.05. Chronic ulcers showed the same expression of hBD2 as normal skin. There was significantly lower accumulation of CD1a+ LC in normal epidermis from foot sole skin compared to normal calf skin (p<0.05. Accumulation of CD1a+ LC and GM-CSF upregulation at the border area of diabetic foot ulcer and reduction of LC concentration at the margin of venous calf ulcer compared to normal skin were observed. It seems that normal calf and sole epidermis is, unlike in the mechanisms of innate immunity, influenced by the different keratinocyte turnover and bacterial flora colonizing these regions. Insufficient upregulation of hBD2 in both diabetic foot and venous calf ulcers may suggest the pathological role of this protein in the chronicity of ulcers.

  3. Langerhans cell homeostasis and activation is altered in hyperplastic human papillomavirus type 16 E7 expressing epidermis.

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    Nor Malia Abd Warif

    Full Text Available It has previously been shown that expression of human papillomavirus type 16 (HPV E7 in epidermis causes hyperplasia and chronic inflammation, characteristics of pre-malignant lesions. Importantly, E7-expressing epidermis is strongly immune suppressed and is not rejected when transplanted onto immune competent mice. Professional antigen presenting cells are considered essential for initiation of the adaptive immune response that results in graft rejection. Langerhans cells (LC are the only antigen presenting cells located in normal epidermis and altered phenotype and function of these cells may contribute to the immune suppressive microenvironment. Here, we show that LC are atypically activated as a direct result of E7 expression in the epidermis, and independent of the presence of lymphocytes. The number of LC was significantly increased and the LC are functionally impaired, both in migration and in antigen uptake. However when the LC were extracted from K14E7 skin and matured in vitro they were functionally competent to present and cross-present antigen, and to activate T cells. The ability of the LC to present and cross-present antigen following maturation supports retention of full functional capacity when removed from the hyperplastic skin microenvironment. As such, opportunities are afforded for the development of therapies to restore normal LC function in hyperplastic skin.

  4. Experimental evidence for the origin of ductal-type adenocarcinoma from the islets of Langerhans.

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    Pour, P. M.; Weide, L.; Liu, G.; Kazakoff, K.; Scheetz, M.; Toshkov, I.; Ikematsu, Y.; Fienhold, M. A.; Sanger, W.

    1997-01-01

    To investigate the role of the islets of Langerhans in pancreatic carcinogenesis, freshly isolated islets from male Syrian hamsters were transplanted into the right submandibular glands of 50 female hamsters that were or were not pre-treated with streptozotocin. Thyroid gland fragments, cellulose powder, and immortal hamster pancreatic ductal cells were injected into the left submandibular gland of the same hamsters. All recipient hamsters were then treated with the potent pancreatic carcinog...

  5. Histiocitosis de Células de Langerhans

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    Lis Arocho

    2017-07-01

    Full Text Available Histiocitosis de células de Langerhans (HCL es una singular enfermedad idiopática, la cual se caracteriza por proliferación clónica de células de Langerhans. HCL puede presentarse como una simple lesión osteolitica o puede afectar múltiples sistemas en el cuerpo. Oralmente se puede preceder manifestaciones sistémicas o simular desordenes infecciosos/inflamatorios. El reporte de este caso presenta a un varón de 3 años de edad referido a la clínica del programa Postdoctoral de Odontopediatria en la Universidad de Puerto Rico para evaluar una posible enfermedad periodontal en los segundos molares deciduos. En la evaluación clínica se observó inflamación extraoral bilateral en los lados izquierdo y derecho del rostro obliterando los ángulos mandibulares. La piel suprayacente estaba intacta y sin sintomatología. En la evaluación intraoral mostró inflamación localizada en la mucosa suprayacente de los molares deciduos en ambos lados con cierto grado de movilidad. Este caso ejemplifica la necesidad tanto de pediatras como odontopediatras de estar conscientes que HCL puede simular lesiones periodontales.

  6. [Factors causing damage and destruction of beta-cells of the islets of Langerhans in the pancreas].

    Science.gov (United States)

    Anděl, Michal; Němcová, Vlasta; Pavlíková, Nela; Urbanová, Jana; Cecháková, Marie; Havlová, Andrea; Straková, Radka; Večeřová, Livia; Mandys, Václav; Kovář, Jan; Heneberg, Petr; Trnka, Jan; Polák, Jan

    2014-09-01

    Insulin secretion in patients with manifested diabetes mellitus tends to disappear months to decades after the diagnosis, which is a clear sign of a gradual loss of pancreatic islet beta-cells. In our sample of 30 type 2 diabetic patients, whose disease manifested between 30 and 45 years of age, about a half have retained or even increased insulin secretion 30 years later, while the other half exhibit a much diminished or lost insulin secretion. Factors that can damage or destroy beta-cells can be divided into the following groups: Metabolic factors: hyperglycemia and glucotoxicity, lipotoxicity, hypoxia, reactive oxygen species; Pharmacological factors: antimicrobial medication pentamidine, SSRI antidepressants; Factors related to impaired insulin secretion: MODY type diabetes; Environmental toxic factors: rat poison Vacor, streptozotocin, polychlorinated and polybrominated hydrocarbons; Disorders of the exocrine pancreas: tumor infiltration, fibrous infiltration, chronic pancreatitis, cystic fibrosis; Infections, inflammation, autoimmunity, viral factors: Coxsackie viruses, H1N1 influenza, enteroviruses. We are currently working on finding other factors leading to beta-cell damage, studying their effect on apoptosis and necrosis and looking for possible protective factors to prevent this damage. We our increasing knowledge about the mechanisms of beta-cell damage and destruction we come ever closer to suggest measures for their prevention. In this review we offer a brief and simplified summary of some of the findings related to this area.Key words: pancreatic islet beta-cells of Langerhans - factors damaging or destroying beta-cells - insulin secretion.

  7. Human cytomegalovirus alters localization of MHC class II and dendrite morphology in mature Langerhans cells.

    Science.gov (United States)

    Lee, Andrew W; Hertel, Laura; Louie, Ryan K; Burster, Timo; Lacaille, Vashti; Pashine, Achal; Abate, Davide A; Mocarski, Edward S; Mellins, Elizabeth D

    2006-09-15

    Hemopoietic stem cell-derived mature Langerhans-type dendritic cells (LC) are susceptible to productive infection by human CMV (HCMV). To investigate the impact of infection on this cell type, we examined HLA-DR biosynthesis and trafficking in mature LC cultures exposed to HCMV. We found decreased surface HLA-DR levels in viral Ag-positive as well as in Ag-negative mature LC. Inhibition of HLA-DR was independent of expression of unique short US2-US11 region gene products by HCMV. Indeed, exposure to UV-inactivated virus, but not to conditioned medium from infected cells, was sufficient to reduce HLA-DR on mature LC, implicating particle binding/penetration in this effect. Reduced surface levels reflected an altered distribution of HLA-DR because total cellular HLA-DR was not diminished. Accumulation of HLA-DR was not explained by altered cathepsin S activity. Mature, peptide-loaded HLA-DR molecules were retained within cells, as assessed by the proportion of SDS-stable HLA-DR dimers. A block in egress was implicated, as endocytosis of surface HLA-DR was not increased. Immunofluorescence microscopy corroborated the intracellular retention of HLA-DR and revealed markedly fewer HLA-DR-positive dendritic projections in infected mature LC. Unexpectedly, light microscopic analyses showed a dramatic loss of the dendrites themselves and immunofluorescence revealed that cytoskeletal elements crucial for the formation and maintenance of dendrites are disrupted in viral Ag-positive cells. Consistent with these dendrite effects, HCMV-infected mature LC exhibit markedly reduced chemotaxis in response to lymphoid chemokines. Thus, HCMV impedes MHC class II molecule trafficking, dendritic projections, and migration of mature LC. These changes likely contribute to the reduced activation of CD4+ T cells by HCMV-infected mature LC.

  8. ATPase and morphologic changes induced by UVB on Langerhans cells in guinea pigs

    International Nuclear Information System (INIS)

    Hanau, D.; Fabre, M.; Lepoittevin, J.P.; Stampf, J.L.; Grosshans, E.; Benezra, C.

    1985-01-01

    The authors have devised, in guinea pigs, an improved ATPase technique which enables one to proceed from light to electron microscope study while preserving, on the ultrastructural level, the various membranous structures, in particular the Langerhans cell (LC) granules. Using this method, they have been able to confirm the action of acute, low-dose UVB on the surface enzymatic marker, ATPase. Moreover, this study has shown that the ATPase-negative LC contain abnormal LC granules or, more often, are deficient in LC granules. In a previous work, the authors have shown that, after epicutaneous application of a hapten, one successively observes an extensive adsorptive pinocytosis process, the disappearance of the membranous ATPase system, and the appearance of LC granules in the cytoplasm. Therefore, the authors may suppose that, after UVB irradiation, the disappearance of the ATPase system and/or the possible alteration of the adsorptive pinocytosis process interrupts or alters the formation of LC granules. These successive events might play a vital role in the formation of the hapten--carrier protein-Ia antigen complex. In their absence in a large number of LC, following UV irradiation, epicutaneous application of a hapten would lead to the development of a state of immune tolerance

  9. Radiographic skeletal survey and radionuclide bone scan in Langerhans cell histiocytosis of bone

    International Nuclear Information System (INIS)

    Nieuwenhuyse, J.P. van; Clapuyt, P.; Malghem, J.; Everarts, P.; Melin, J.; Pauwels, S.; Brichard, B.; Ninane, J.; Vermylen, C.; Cornu, G.

    1996-01-01

    Background. The lack of a consensus in the literature on the imaging strategy in Langerhans cell histiocytosis (LCH) bone lesions in childhood. Objective. To evaluate the relative value of radionuclide bone scan (RBS) and radiographic skeletal survey (RSS) in the detection of LCH bone lesions, both in the initial work-up of the disease and during the follow-up period. Materials and methods. Ten children with bone lesions evaluated by means of RSS and RBS in a retrospective study (1984-1993). Results. Fifty radiologically and/or scintigraphically abnormal foci were detected: 27 anomalies in the initial work-up (12 by both RSS and RBS, 8 by RSS only and 7 by RBS only) and 23 additional anomalies during follow-up (10 by both RSS and RBS, 10 by RSS only and 3 by RBS only). RSS+/RBS- lesions (n = 18) are more frequently encountered in the skull (P = 0.038), and more frequently lack radiologic signs of osteoblastic activity (P = 0.020), than RSS+/RBS+ lesions (n = 22). RSS-/RBS+ abnormalities (n = 10) were most frequently insignificant. Conclusion. In the initial work-up both RSS and RBS should be carried out, while in the follow-up only RSS should be performed. (orig.). With 2 figs., 4 tabs

  10. Distribution and infection of Langerhans cells in the skin of HIV-infected healthy subjects and AIDS patients.

    Science.gov (United States)

    Müller, H; Weier, S; Kojouharoff, G; Grez, M; Berger, S; Kappus, R; Shah, P M; Stutte, H J; Schmidts, H L

    1993-01-01

    The in situ content of cells of the reticuloendothelial system and lymphatic cells was examined in the skin of eight symptom-free HIV-positive individuals, three AIDS patients and eleven healthy immunocompetent volunteers. The epidermis was obtained in vivo by the suction blister technique. The numbers of CD68+, CD3+, CD8+, CD25-(IL2R)+ and HLA-DR+ intraepidermal cells proved to be independent of the number of CD4+ peripheral blood lymphocytes. At the same time, the intraepidermal concentrations of these cells were generally low in symptom-free HIV-infected individuals. The strong inverse correlation between the number of epidermal Langerhans cells (LC) and the severity of immunodeficiency was quantitatively confirmed; an increase in LC in symptom-free HIV-infected individuals was found. Thus, the reduction in these cells which was observed in the epidermis of AIDS patients began at a significantly elevated level. In contrast to results from other studies, in AIDS patients, in the present study, the concentration of epidermal LC did not differ significantly from that of healthy immunocompetent volunteers. The immunohistochemical technique can be as effective as in situ hybridization for the detection of HIV in the skin. Our results suggest that the viral load of the skin is rather low in HIV-infected subjects. HIV was demonstrated in one cell of one AIDS case by in situ techniques and this result was confirmed by a polymerase chain reaction examination using the same amount of tissue as for the in situ techniques.(ABSTRACT TRUNCATED AT 250 WORDS)

  11. Maturational steps of bone marrow-derived dendritic murine epidermal cells. Phenotypic and functional studies on Langerhans cells and Thy-1+ dendritic epidermal cells in the perinatal period.

    Science.gov (United States)

    Elbe, A; Tschachler, E; Steiner, G; Binder, A; Wolff, K; Stingl, G

    1989-10-15

    The adult murine epidermis harbors two separate CD45+ bone marrow (BM)-derived dendritic cell systems, i.e., Ia+, ADPase+, Thy-1-, CD3- Langerhans cells (LC) and Ia-, ADPase-, Thy-1+, CD3+ dendritic epidermal T cells (DETC). To clarify whether the maturation of these cells from their ill-defined precursors is already accomplished before their entry into the epidermis or, alternatively, whether a specific epidermal milieu is required for the expression of their antigenic determinants, we studied the ontogeny of CD45+ epidermal cells (EC). In the fetal life, there exists a considerable number of CD45+, Ia-, ADPase+ dendritic epidermal cells. When cultured, these cells become Ia+ and, in parallel, acquire the potential of stimulating allogeneic T cell proliferation. These results imply that CD45+, Ia-, ADPase+ fetal dendritic epidermal cells are immature LC precursors and suggest that the epidermis plays a decisive role in LC maturation. The day 17 fetal epidermis also contains a small population of CD45+, Thy-1+, ADPase-, CD3- round cells. Over the course of 2 to 3 wk, they are slowly replaced by an ever increasing number of round and, finally, dendritic CD45+, Thy-1+, CD3+ EC. Thus, CD45+, Thy-1+, ADPase-, CD3- fetal EC may either be DETC precursors or, alternatively, may represent a distinctive cell system of unknown maturation potential. According to this latter theory, these cells would be eventually outnumbered by newly immigrating CD45+, Thy-1+, CD3+ T cells--the actual DETC.

  12. Langerhans cell-like dendritic cells stimulated with an adjuvant direct the development of Th1 and Th2 cells in vivo.

    Science.gov (United States)

    Matsui, K; Mori, A; Ikeda, R

    2015-10-01

    It is well known that Langerhans cells (LCs) work as the primary orchestrators in the polarization of immune responses towards a T helper type 1 (Th1) or Th2 milieu. In this study, we attempted to generate LCs from murine bone marrow cells and elicit a Th1- or Th2-prone immune response through the LCs after stimulation with Th1 or Th2 adjuvant. LCs were generated from murine bone marrow cells using granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-4 and transforming growth factor (TGF)-β, and were obtained as I-A(d) positive cells. Mice were primed with Th1/Th2 adjuvant- and ovalbumin (OVA)-pulsed LCs and then given a booster injection of OVA 2 days later via the hind footpad. Five days after the OVA injection, the cytokine response in the draining popliteal lymph nodes was investigated by reverse transcription-polymerase chain reaction (RT-PCR) flow cytometry and enzyme-linked immunosorbent assay (ELISA). The generated LCs expressed typical LC surface markers, E-cadherin and Langerin, and were classified accordingly as LC-like dendritic cells (LDCs). Administration of Th1 adjuvant, cytosine-phosphate-guanosine (CpG)-DNA- and OVA-pulsed LDCs into the hind footpads of mice induced a Th1-prone immune response, as represented by up-regulation of IFN-γ production and down-regulation of IL-4 production in the lymph node cells. Conversely, Th2 adjuvant, histamine-pulsed LDCs induced a Th2-prone immune response, as represented by up-regulation of IL-4 production and down-regulation of IFN-γ production. These results suggest that LDCs may be used as a substitute for LCs and have the ability to induce the development of Th1 and Th2 cells in vivo. Our experimental system would therefore be useful for screening of inhibitors of Th1/Th2 differentiation in order to control allergic disease. © 2015 British Society for Immunology.

  13. Immunohistochemical analysis of Langerhans cells in chronic gingivitis using anti-CD1a antibody

    Directory of Open Access Journals (Sweden)

    Shweta Jaitley

    2014-01-01

    Full Text Available Background: The Langerhans cells (LCs are dendritic cells (DCs which belong to the group of antigen presenting cells (APCs. Their function is to recognize the antigen, capture it, and present it to the T lymphocytes; thus initiating an early immune response. The antigen presenting functional LCs may play an important part in initiation and development of gingivitis. The aim of this study was to analyze the density, intraepithelial distribution, and morphology of LCs in gingival epithelium among different age groups with chronic gingivitis and to compare it with that of normal gingiva. Materials and Methods: Immunohistochemistry (IHC was performed to study LCs in normal gingival epithelium (n = 10 and gingival epithelium in chronic gingivitis (n = 30 using anti-CD1a antibody. Mann Whitney U test was performed to compare the density of LCs in normal gingiva with chronic gingivitis. The distribution of LCs in various layers of the epithelium within the three age groups was analyzed using Kruskal-Wallis test. P value less than 0.05 was considered as significant. Results: The density of LCs in chronic gingivitis was significantly higher then that of normal gingiva. Comparing different age groups, the younger individuals had more number of LCs which were located in the superficial layers of gingival epithelium. In chronic gingivitis, higher number of LCs were located in deeper layers when compared with that of normal gingiva. Three morphological types of CD1a positive LCs were observed in normal gingiva, out of which the density of LCs with branched dendritic processes was highest in normal gingiva. Conclusion: The LCs showed variable number, location, and morphology which indicated their adaptation for function in chronic gingivitis.

  14. Cyclic mechanical stretch contributes to network development of osteocyte-like cells with morphological change and autophagy promotion but without preferential cell alignment in rat.

    Science.gov (United States)

    Inaba, Nao; Kuroshima, Shinichiro; Uto, Yusuke; Sasaki, Muneteru; Sawase, Takashi

    2017-09-01

    Osteocytes play important roles in controlling bone quality as well as preferential alignment of biological apatite c -axis/collagen fibers. However, the relationship between osteocytes and mechanical stress remains unclear due to the difficulty of three-dimensional (3D) culture of osteocytes in vitro . The aim of this study was to investigate the effect of cyclic mechanical stretch on 3D-cultured osteocyte-like cells. Osteocyte-like cells were established using rat calvarial osteoblasts cultured in a 3D culture system. Cyclic mechanical stretch (8% amplitude at a rate of 2 cycles min -1 ) was applied for 24, 48 and 96 consecutive hours. Morphology, cell number and preferential cell alignment were evaluated. Apoptosis- and autophagy-related gene expression levels were measured using quantitative PCR. 3D-cultured osteoblasts became osteocyte-like cells that expressed osteocyte-specific genes such as Dmp1 , Cx43 , Sost , Fgf23 and RANKL , with morphological changes similar to osteocytes. Cell number was significantly decreased in a time-dependent manner under non-loaded conditions, whereas cyclic mechanical stretch significantly prevented decreased cell numbers with increased expression of anti-apoptosis-related genes. Moreover, cyclic mechanical stretch significantly decreased cell size and ellipticity with increased expression of autophagy-related genes, LC3b and atg7 . Interestingly, preferential cell alignment did not occur, irrespective of mechanical stretch. These findings suggest that an anti-apoptotic effect contributes to network development of osteocyte-like cells under loaded condition. Spherical change of osteocyte-like cells induced by mechanical stretch may be associated with autophagy upregulation. Preferential alignment of osteocytes induced by mechanical load in vivo may be partially predetermined before osteoblasts differentiate into osteocytes and embed into bone matrix.

  15. Preferential killing of cancer cells and activated human T cells using ZnO nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Hanley, Cory; Layne, Janet; Feris, Kevin; Wingett, Denise [Department of Biological Sciences, Boise State University, Boise, ID 83725 (United States); Punnoose, Alex; Reddy, K M; Coombs, Isaac; Coombs, Andrew [Department of Physics, Boise State University, Boise, ID 83725 (United States)], E-mail: denisewingett@boisestate.edu

    2008-07-23

    Nanoparticles are increasingly being recognized for their potential utility in biological applications including nanomedicine. Here we examine the response of normal human cells to ZnO nanoparticles under different signaling environments and compare it to the response of cancerous cells. ZnO nanoparticles exhibit a strong preferential ability to kill cancerous T cells ({approx}28-35 x) compared to normal cells. Interestingly, the activation state of the cell contributes toward nanoparticle toxicity, as resting T cells display a relative resistance while cells stimulated through the T cell receptor and CD28 costimulatory pathway show greater toxicity in direct relation to the level of activation. Mechanisms of toxicity appear to involve the generation of reactive oxygen species, with cancerous T cells producing higher inducible levels than normal T cells. In addition, nanoparticles were found to induce apoptosis and the inhibition of reactive oxygen species was found to be protective against nanoparticle induced cell death. The novel findings of cell selective toxicity, towards potential disease causing cells, indicate a potential utility of ZnO nanoparticles in the treatment of cancer and/or autoimmunity.

  16. Preferential killing of cancer cells and activated human T cells using ZnO nanoparticles

    International Nuclear Information System (INIS)

    Hanley, Cory; Layne, Janet; Feris, Kevin; Wingett, Denise; Punnoose, Alex; Reddy, K M; Coombs, Isaac; Coombs, Andrew

    2008-01-01

    Nanoparticles are increasingly being recognized for their potential utility in biological applications including nanomedicine. Here we examine the response of normal human cells to ZnO nanoparticles under different signaling environments and compare it to the response of cancerous cells. ZnO nanoparticles exhibit a strong preferential ability to kill cancerous T cells (∼28-35 x) compared to normal cells. Interestingly, the activation state of the cell contributes toward nanoparticle toxicity, as resting T cells display a relative resistance while cells stimulated through the T cell receptor and CD28 costimulatory pathway show greater toxicity in direct relation to the level of activation. Mechanisms of toxicity appear to involve the generation of reactive oxygen species, with cancerous T cells producing higher inducible levels than normal T cells. In addition, nanoparticles were found to induce apoptosis and the inhibition of reactive oxygen species was found to be protective against nanoparticle induced cell death. The novel findings of cell selective toxicity, towards potential disease causing cells, indicate a potential utility of ZnO nanoparticles in the treatment of cancer and/or autoimmunity

  17. Successful treatment with cladribine of Erdheim-Chester disease with orbital and central nervous system involvement developing after treatment of langerhans cell histiocytosis

    Directory of Open Access Journals (Sweden)

    Perić Predrag

    2016-01-01

    Full Text Available Introduction. Erdheim-Chester disease (ECD is a rare, systemic form of non-Langerhans cell histiocytosis of the juvenile xantho-granuloma family with characteristic bilateral symmetrical long bone osteosclerosis, associated with xanthogranulomatous extras-keletal organ involvement. In ECD, central nervous system (CNS and orbital lesions are frequent, and more than half of ECD patients carry the V600E mutation of the proto-oncogene BRAF. The synchronous or metachronous development of ECD and Langerhans cell histiocytosis (LCH in the same patients is rare, and the possible connection between them is still obscure. Cladribine is a purine substrate analogue that is toxic to lymphocytes and monocytes with good hematoencephalic penetration. Case report. We presented a 23-year-old man successfully treated with cladribine due to BRAF V600E-mutation-negative ECD with bilateral orbital and CNS involvement. ECD developed metachronously, 6 years after chemotherapy for multisystem LCH with complete disease remission and remaining central diabetes insipidus. During ECD treatment, the patient received 5 single-agent chemotherapy courses of cladribine (5 mg/m2 for 5 consecutive days every 4 weeks, with a reduction in dose to 4 mg/m2 in a fifth course, delayed due to severe neutropenia and thoracic dermatomal herpes zoster infection following the fourth course. Radiologic signs of systemic and CNS disease started to resolve 3 months after the end of chemotherapy, and CNS lesions completely resolved within 2 years after the treatment. After 12-year follow-up, there was no recurrence or appearance of new systemic or CNS xanthogranu-lomatous lesions or second malignancies. Conclusion. In accordance with our findings and recommendations provided by other authors, cladribine can be considered an effective alternative treatment for ECD, especially with CNS involvement and BRAF V600E-mutation-negative status, when interferon-α as the first-line therapy fails.

  18. 18-F-FDG PET/CT in Localizing Additional CNS Lesion in a Case of Langerhans Cell Histiocytosis: Determining Accurate Extent of the Disease.

    Science.gov (United States)

    Shamim, Shamim Ahmed; Tripathy, Sarthak; Mukherjee, Anirban; Bal, Chandrasekhar; Tripathi, Madhavi

    2017-01-01

    Central nervous system involvement is a rare manifestation of Langerhans cell histiocytosis (LCH), with bone and skin lesions being more frequent. MR remains the investigation of choice for localizing brain lesions. However, due to poor sensitivity of MRI in detecting osseous and pulmonary lesions, it is not used routinely in staging purposes until and unless indicated. We hereby discuss a case of 6-year-old boy of LCH who was referred for 18-F-FDG PET/CT for staging and knowing the extent of the disease, but a lesion in hypothalamus was picked up incidentally on FDG PET-CT study that was confirmed by MRI.

  19. Affinity-purified human interleukin I is cytotoxic to isolated islets of Langerhans

    DEFF Research Database (Denmark)

    Mandrup-Poulsen, T; Bendtzen, K; Nerup, J

    1986-01-01

    Addition of highly purified human Interleukin-1 to the culture medium of isolated rat islets of Langerhans for 6 days led to 88% inhibition of glucose-induced insulin-release, reduction of islet contents of insulin and glucagon to 31% and 8% respectively, and disintegration of the islets. These e......Addition of highly purified human Interleukin-1 to the culture medium of isolated rat islets of Langerhans for 6 days led to 88% inhibition of glucose-induced insulin-release, reduction of islet contents of insulin and glucagon to 31% and 8% respectively, and disintegration of the islets...

  20. Analysis of the BRAFV600E mutation in 19 cases of Langerhans cell histiocytosis in Japan.

    Science.gov (United States)

    Sasaki, Yuya; Guo, Ying; Arakawa, Fumiko; Miyoshi, Hiroaki; Yoshida, Noriaki; Koga, Yuhki; Nakashima, Kazutaka; Kurita, Daisuke; Niino, Daisuke; Seto, Masao; Ohshima, Koichi

    2017-09-01

    Langerhans cell histiocytosis (LCH) is a rare disease characterized by clonal proliferation of CD1a- and CD207 (langerin)-positive dendritic cells. Mutated BRAF (p.V600E) is observed in histiocyte-related diseases and dendritic cell-related diseases, including LCH. BRAFV600E is observed in some LCH cases and is thought to be involved in maintaining MAPK activation. We retrospectively analyzed BRAFV600E in 19 patients diagnosed with LCH. In our study, direct sequencing for exon 15, a mutation hotspot, demonstrated that 4 out of the 19 patients (21%) harbored a GTG > GAG (valine > glutamic acid) base substitution, which encodes BRAFV600E. The clinical impact of BRAFV600E in such diseases is unclear. The frequency of BRAFV600E in our LCH patients from Japan was lower than that reported in the United States and in Germany. However, reports from Asia tend to show a lower rate of the BRAFV600E mutation. These results imply the possibility of different genetic backgrounds in the pathogenesis of LCH across various ethnicities. We also performed an immunohistochemical analysis to detect BRAFV600E using the mutation-specific monoclonal antibody. However, immunohistochemical analysis failed to detect any mutated protein in any of the 4 BRAFV600E-positive cases. This implies that at present, BRAFV600E should be assessed by direct sequencing. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  1. Total pleurectomy as the surgical treatment for recurrent secondary spontaneous pneumothorax in a child with severe pulmonary Langerhans cells histiocytosis.

    Science.gov (United States)

    Abdul Aziz, Dayang Anita; Abdul Rahman, Nur Afdzillah; Tang, Swee Fong; Abdul Latif, Hasniah; Zaki, Faizah Mohd; Annuar, Zulfiqar Mohd; Alias, Hamidah; Abdul Latiff, Zarina

    2011-12-01

    Pulmonary Langerhans cell histiocytosis (LCH) in children is more extensive and is a rare cause of spontaneous secondary pneumothorax (SSP) which tends to be recurrent and refractory to conventional treatment. Its occurrence in paediatric patients posed great challenge to the choice of surgical management. Surgery in the form of pleurodesis is only considered if SSP does not improve after chemotherapy and after considering all relevant risk and benefits of surgery to patients. Chemical pleurodesis will not give the expected effect to eradicate SSP in this patient. Therefore mechanical pleurodesis is the treatment of choice. There are various techniques to perform mechanical pleurodesis; from pleural abrasion to pleurectomy. In the authors' experience, bilateral total pleurectomy provided the best outcome for this 9-year-old patient with persistent respiratory distress from SSP due to extensive pulmonary LCH.

  2. Dihydroartemisinin induces apoptosis preferentially via a Bim-mediated intrinsic pathway in hepatocarcinoma cells.

    Science.gov (United States)

    Qin, Guiqi; Zhao, ChuBiao; Zhang, Lili; Liu, Hongyu; Quan, Yingyao; Chai, Liuying; Wu, Shengnan; Wang, Xiaoping; Chen, Tongsheng

    2015-08-01

    This report is designed to dissect the detail molecular mechanism by which dihydroartemisinin (DHA), a derivative of artemisinin, induces apoptosis in human hepatocellular carcinoma (HCC) cells. DHA induced a loss of the mitochondrial transmemberane potential (ΔΨm), release of cytochrome c, activation of caspases, and externalization of phosphatidylserine indicative of apoptosis induction. Compared with the modest inhibitory effects of silencing Bax, silencing Bak largely prevented DHA-induced ΔΨm collapse and apoptosis though DHA induced a commensurable activation of Bax and Bak, demonstrating a key role of the Bak-mediated intrinsic apoptosis pathway. DHA did not induce Bid cleavage and translocation from cytoplasm to mitochondria and had little effects on the expressions of Puma and Noxa, but did increase Bim and Bak expressions and decrease Mcl-1 expression. Furthermore, the cytotoxicity of DHA was remarkably reduced by silencing Bim, and modestly but significantly reduced by silencing Puma or Noxa. Silencing Bim or Noxa preferentially reduced DHA-induced Bak activation, while silencing Puma preferentially reduced DHA-induced Bax activation, demonstrating that Bim and to a lesser extent Noxa act as upstream mediators to trigger the Bak-mediated intrinsic apoptosis pathway. In addition, silencing Mcl-1 enhanced DHA-induced Bak activation and apoptosis. Taken together, our data demonstrate a crucial role of Bim in preferentially regulating the Bak/Mcl-1 rheostat to mediate DHA-induced apoptosis in HCC cells.

  3. Langerhans cells from women with cervical precancerous lesions become functionally responsive against human papillomavirus after activation with stabilized Poly-I:C.

    Science.gov (United States)

    Da Silva, Diane M; Woodham, Andrew W; Skeate, Joseph G; Rijkee, Laurie K; Taylor, Julia R; Brand, Heike E; Muderspach, Laila I; Roman, Lynda D; Yessaian, Annie A; Pham, Huyen Q; Matsuo, Koji; Lin, Yvonne G; McKee, Greg M; Salazar, Andres M; Kast, W Martin

    2015-12-01

    Human papillomavirus (HPV)-mediated suppression of Langerhans cell (LC) function can lead to persistent infection and development of cervical intraepithelial neoplasia (CIN). Women with HPV-induced high-grade CIN2/3 have not mounted an effective immune response against HPV, yet it is unknown if LC-mediated T cell activation from such women is functionally impaired against HPV. We investigated the functional activation of in vitro generated LC and their ability to induce HPV16-specific T cells from CIN2/3 patients after exposure to HPV16 followed by treatment with stabilized Poly-I:C (s-Poly-I:C). LC from patients exposed to HPV16 demonstrated a lack of costimulatory molecule expression, inflammatory cytokine secretion, and chemokine-directed migration. Conversely, s-Poly-I:C caused significant phenotypic and functional activation of HPV16-exposed LC, which resulted in de novo generation of HPV16-specific CD8(+) T cells. Our results highlight that LC of women with a history of persistent HPV infection can present HPV antigens and are capable of inducing an adaptive T cell immune response when given the proper stimulus, suggesting that s-Poly-I:C compounds may be attractive immunomodulators for LC-mediated clearance of persistent HPV infection. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Increased Number of Langerhans Cells in the Epidermis of Diabetic Foot Ulcers Correlates with Healing Outcome

    Science.gov (United States)

    Stojadinovic, Olivera; Yin, Natalie; Lehmann, Janin; Pastar, Irena; Kirsner, Robert S.; Tomic-Canic, Marjana

    2015-01-01

    Langerhans cells (LCs) are a specialized subset of epidermal dendritic cells. They represent one of the first cells of immunological barrier and play an important role during the inflammatory phase of acute wound healing. Despite considerable progress in our understanding of the immunopathology of diabetes mellitus and its associated co-morbidities such as diabetic foot ulcers (DFUs), considerable gaps in our knowledge exist. In this study, we utilized the human ex vivo wound model and confirmed the increased epidermal LCs at wound edges during early phases of wound healing. Next, we aimed to determine differences in quantity of LCs between normal human and diabetic foot skin and to learn if the presence of LCs correlates with the healing outcome in DFUs. We utilized immunofluorescence to detect CD207+ LCs in specimens from normal and diabetic foot skin and DFU wound edges. Specimens from DFUs were collected at the initial visit and 4 weeks at the time when the healing outcome was determined. DFUs that decreased in size by >50% were considered to be healing, while DFUs with a size reduction of healing. Quantitative assessment of LCs showed a higher number of LCs in healing when compared to non–healing DFU’s. Our findings provide evidence that LCs are present in higher number in diabetic feet than normal foot skin. Healing DFUs show a higher number of LCs compared to non-healing DFUs. These findings indicate that the epidermal immune barrier plays an important role in the DFU healing outcome and may offer new therapeutic avenues targeting LC in non-healing DFUs. PMID:24277309

  5. The value of bone scintigraphy in diagnosing of langerhans cells histiocytosis

    International Nuclear Information System (INIS)

    Shao Hong; Shi Meihua; Wu Jinchuan

    2004-01-01

    Purpose: To investigate the clinical value of bone scintigraphy in the diagnosis of Langerhans cells histiocytosis (LCH). Methods: Whole-body bone scintigraphy was performed in 23 patients, 16 males and 7 females, average age was 4.5+1.4, with histologic diagnosis of LCH. The clinical presentation varied from local mass (10 cases), tenderness (12 cases), othemorrhea (1 case), limb fatigue (3 cases), restriction of spinal activity (2 cases) to irregular fever, cough and rash (4 cases). 99Tcm-MDP was injected intravenously , the dose modified as age, according to the formula of [ adult dosage x [(age+l)/(age+7)] ] , and sedation was given to the young children who could not cooperate well. After 3 hours of administration whole-body bone scan was performed. Images were acquired using GE Millennium SPR, with a high-resolution low-energy collimator, 8 min/m sweep speed, matrix 1024 x 256, zoom 1. Results: 19 of 23 patients (82.6%) showed positive in their bone scan. 8 cases with cranial abnormal uptake, some of them exhibited peripheral high and central low uptake; clavicle, rib and pelvis involvements were 3 respectively; 2 cases in upper limb, 4 in lower limb, most lesions of limb were located in the diaphysis; spinal abnormal uptakes were seen in 5 patients, and 1 child had photon deficient area in the lower of sternium. Among 19 positive scintigram, single bone lesion was shown in 9 patients (47.3%), the most common lesion located in cranium (5 cases). Conclusion: Some characters of bone scintigraphy in LCH are useful in the diagnosis of this disease, and accompanied with comprehensive sensation of clinical manifestation of LCH, the diagnostic accuracy will be promoted. (authors)

  6. Influence of High Aspect Ratio Vessel Cell Culture on TNF-Alpha, Insulin Secretion and Glucose Homeostasis in Pancreatic Islets of Langerhans from Wistar Furth Rats

    Science.gov (United States)

    Tobin, Brian W.a; Leeper-Woodford, Sandra K.

    1999-01-01

    The present studies were carried out to determine the influence of a ground based microgravity paradigm, utilizing the High Aspect Ratio Vessel (HARV) cell culture upon lipopolysaccharide (LPS) stimulated tumor necrosis factor alpha (TNF-alpha) production of pancreatic islets of Langerhans. An additional aim was to elucidate alterations in insulin secretion and glucose utilization using the HARV low shear, gravity averaged vector, cell culture technique. Islets were isolated (1726 +/- 117, 150 micron islet equivalent units) from Wistar Furth rats and assigned to four treatment groups: 1) HARV, 2) HARV plus LPS, 3) static culture, 4) static culture plus LPS. Following 48 hours of culture, insulin concentration was increased in both HARV and static cultures (palpha (L929 cytotoxicity assay) and was measured at selected time points for 48 hours. TNF-alpha was significantly increased in LPS-induced HARV and static cultures, yet the increase was more pronounced in the static culture group (palpha is associated with a decreased insulin secretion is intriguing, both as it relates to in-flight investigations, and as it may provide insight into the pathophysiology of Type I and Type 11 diabetes. Glucose concentration in islet medium was lesser throughout the experiment in static cultures, suggesting a decreased reliance upon glucose as a metabolic substrate in the islets cultured in HARVS. In conclusion, the present studies demonstrate alterations in LPS induced TNF-alpha production of pancreatic islets of Langerhans, favoring a lesser TNF production in the microgravity HARV paradigm. Additionally, alterations in fuel homeostasis may be promulgated by HARV culture. The clinical and physiological significance of these observations remains to be determined.

  7. Radiologic findings of adult pelvis and appendicular skeletal Langerhans cell histiocytosis in nine patients

    International Nuclear Information System (INIS)

    Song, You Seon; Lee, In Sook; Kim, Do Kyung; Yi, Jae Hyuck; Cho, Kil Ho; Song, Jong Woon

    2011-01-01

    The purpose of this article was to evaluate the radiologic findings of adult pelvis and appendicular skeletal Langerhans cell histiocytosis (LCH), emphasizing the CT and MR findings. The images of nine patients with pathologically proven LCH (five men and four women; mean age, 37.11 years) were retrospectively reviewed. Imaging analysis was confined to the long and flat bones. CT scans were performed in five patients and MR imaging was performed in eight. Images were assessed for the following features on CT and MRI: the location and number of lesions; the presence of cortical destruction, endosteal scalloping, and a periosteal reaction on CT or MRI; the margin of soft tissue masses, the presence of bone marrow edema, and a ''budding'' appearance on MRI; and the presence of sclerotic margins or septations on CT. The involved skeletal sites were the pelvis (seven), femurs (five), humeri (two), tibias (two), fibula (one), clavicle (one), scapula (one), and sternum (one). Endosteal scalloping, a periosteal reaction, and a budding appearance were common on MRI or CT images. Although cortical destruction and the soft tissue lesion formation were rare, soft tissue masses had well-defined margins. Endosteal scalloping and a budding appearance with a periosteal reaction on CT and MRI may be helpful signs for differentiation of LCH from malignant tumors in adults. (orig.)

  8. Adult Multisystem Langerhans Cell Histiocytosis Presenting with Central Diabetes Insipidus Successfully Treated with Chemotherapy

    Directory of Open Access Journals (Sweden)

    Jung-Eun Choi

    2014-09-01

    Full Text Available We report the rare case of an adult who was diagnosed with recurrent multisystem Langerhans cell histiocytosis (LCH involving the pituitary stalk and lung who present with central diabetes insipidus and was successfully treated with systemic steroids and chemotherapy. A 49-year-old man visited our hospital due to symptoms of polydipsia and polyuria that started 1 month prior. Two years prior to presentation, he underwent excision of right 6th and 7th rib lesions for the osteolytic lesion and chest pain, which were later confirmed to be LCH on pathology. After admission, the water deprivation test was done and the result indicated that he had central diabetes insipidus. Sella magnetic resonance imaging showed a mass on the pituitary stalk with loss of normal bright spot at the posterior lobe of the pituitary. Multiple patchy infiltrations were detected in both lung fields by computed tomography (CT. He was diagnosed with recurrent LCH and was subsequently treated with inhaled desmopressin, systemic steroids, vinblastine, and mercaptopurine. The pituitary mass disappeared after two months and both lungs were clear on chest CT after 11 months. Although clinical remission in multisystem LCH in adults is reportedly rare, our case of adult-onset multisystem LCH was treated successfully with systemic chemotherapy using prednisolone, vinblastine, and 6-mercaptopurine, which was well tolerated.

  9. IL-1beta induced protein changes in diabetes prone BB rat islets of Langerhans identified by proteome analysis

    DEFF Research Database (Denmark)

    Sparre, T; Bjerre-Christensen, Ulla; Mose Larsen, P

    2002-01-01

    of 82 out of 1 815 protein spots detected by two dimensional gel electrophoresis in IL-1beta exposed diabetes prone Bio Breeding (BB-DP) rat islets of Langerhans in vitro. The aim of this study was to identify the proteins in these 82 spots by mass spectrometry and compare these changes with those seen......Type I (insulin-dependent) diabetes mellitus is characterized by selective destruction of the insulin producing beta cells. Interleukin-1beta (IL-1beta) modulates the beta-cell function, protein synthesis, energy production and causes apoptosis. We have previously shown changes in the expression...

  10. Evolving radiological features of hypothalamo-pituitary lesions in adult patients with Langerhans cell histiocytosis (LCH)

    International Nuclear Information System (INIS)

    Makras, P.; Samara, C.; Antoniou, M.; Nikolakopoulou, Z.; Zetos, A.; Papadogias, D.; Piaditis, G.; Kaltsas, G.A.; Toloumis, G.; Andreakos, E.; Kontogeorgos, G.

    2006-01-01

    Langerhans cell histiocytosis (LCH) is a rare, systemic disease caused by monoclonal expansion of dendritic cells that shows a particular predilection for the hypothalamic-pituitary system (HPS). We studied the function (anterior and posterior pituitary hormonal secretion) and morphology using magnetic resonance imaging (MRI) of the HPS in 17 adult patients (seven males, median age 35 years, range 18-59 years) with multisystem LCH. We also evaluated the evolution of structural HPS abnormalities in relation to pituitary function and response to treatment in 12 of these patients during a median follow-up period of 3.75 years (range 1.5-10 years). Of the 17 patients, 14 (82%) had abnormal HPS imaging, and 12 (70%) had more than one area involved. Lack of the bright spot of the posterior pituitary lobe was typically found in all patients with the diagnosis of diabetes insipidus (DI). Eight patients (47%) had infundibular enlargement, six (35%) pituitary infiltration, four (24%) partially or completely empty sella, three (18%) hypothalamic involvement, and two (12%) infundibular atrophy. DI was found in 16 patients (94%) and anterior pituitary hormonal deficiency (APHD) in 10 patients (59%); two patients had single (12%) and 8 (47%) multiple APHD. During the follow-up period there was improvement of the initially demonstrated HPS pathology in seven (47%) patients, and five (33%) of them had received at least one form of treatment. APHD and DI persisted in all patients except in one in whom established gonadotrophin deficiency recovered. In summary, DI and APHD are very common in patients with multisystem LCH and are almost always associated with abnormal HPS imaging. (orig.)

  11. Suppression of Langerhans cell activation is conserved amongst human papillomavirus α and β genotypes, but not a µ genotype.

    Science.gov (United States)

    Da Silva, Diane M; Movius, Carly A; Raff, Adam B; Brand, Heike E; Skeate, Joseph G; Wong, Michael K; Kast, W Martin

    2014-03-01

    Human papillomavirus (HPV) has evolved mechanisms that allow it to evade the human immune system. Studies have shown HPV-mediated suppression of activation of Langerhans cells (LC) is a key mechanism through which HPV16 evades initial immune surveillance. However, it has not been established whether high- and low-risk mucosal and cutaneous HPV genotypes share a common mechanism of immune suppression. Here, we demonstrate that LC exposed to capsids of HPV types 18, 31, 45, 11, (alpha-papillomaviruses) and HPV5 (beta-papillomavirus) similarly suppress LC activation, including lack of costimulatory molecule expression, lack of cytokine and chemokine secretion, lack of migration, and deregulated cellular signaling. In contrast, HPV1 (mu-papillomavirus) induced costimulatory molecule and cytokine upregulation, but LC migration and cellular signaling was suppressed. These results suggest that alpha and beta HPV genotypes, and partially a mu genotype, share a conserved mechanism of immune escape that enables these viruses to remain undetected in the absence of other inflammatory events. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Alotransplante de ilhotas de Langerhans no fígado de ratos submetidos a manipulação tímica com células não-parenquimatosas Allogenic islet transplantation on the rat liver after allogenic nonparenchymal cells injection in the thymus

    Directory of Open Access Journals (Sweden)

    Eleazar Chaib

    2006-12-01

    éticos, antes do alotransplante de ilhotas de Langerhans no fígado, ao contrário de inibir a reação do receptor contra o enxerto, prolongando a sobrevida média das ilhotas e, possivelmente, levando ao estado de tolerância imunológica, induziu ao processo de rejeição aguda precoce.BACKGROUD: The major indication for pancreas or islet transplantation is diabetes mellitus type I. This process has to supply the insulin necessity keeping glucose under control AIM: We studied allogenic islet transplantation on the rat liver, Wistar (RT1u to Lewis (RT1¹ as a recipient. Control group (n = 8 and nonparenchymal cell group (n = 8 respectively with injection of Hanks solution and nonparenchymal cells in the thymus before islet transplantation. MATERIAL AND METHODS: With the method of isolation and purification of the islets we obtained both in the control group 3.637 ± 783,3 islets with purity of 85 ± 3,52% and nonparenchymal cell group 3.270 ± 770 islets with purity of 84,25 ± 2,76%. The nonparenchymal cells were retrieved from the liver and we obtained 2 x 106 cells. Diabetes was induced by i.v. streptozotocin RESULTS: Control group the transplantation of 3.637 ± 783,3 islets in the rat liver normalized glucose test, 7,21 ± 0,57 mmol/L in the 2nd postoperative day. Acute rejection came in the 6th postoperative day with significantly increase of glucose test in nonparenchymal cell group, the transplantation of 3.270 ± 770 islets in the rat liver, almost normalized the glucose test was 17,95 ± 5,33 mmol/L in the 2nd postoperative day. From the 4th postoperative day to 10th postoperative day. The glucose test increase significantly showing an early acute rejection CONCLUSION: The injection of nonparenchymal cells in the thymus before allogenic islet transplantation in the rat liver lead to an early acute rejection.

  13. Central nervous system imaging in childhood Langerhans cell histiocytosis – a reference center analysis

    International Nuclear Information System (INIS)

    Porto, Luciana; Schöning, Stefan; Hattingen, Elke; Sörensen, Jan; Jurcoane, Alina; Lehrnbecher, Thomas

    2015-01-01

    The aim of our study was (1) to describe central nervous system (CNS) manifestations in children with Langerhans cell histiocytosis (LCH) based on images sent to a reference center and meeting minimum requirements and (2) to assess the inter-rater agreement of CNS-MRI results, which represents the overall reproducibility of this investigation. We retrospectively reviewed brain MRI examinations in children with LCH, for which MRI minimum requirements were met. Abnormalities were rated by two experienced neuroradiologists, and the inter-rater agreement was assessed. Out of a total of 94 imaging studies, only 31 MRIs met the minimum criteria, which included T2w, FLAIR, T1w images before/after contrast in at least two different section planes, and thin post contrast sagittal slices T1w through the sella. The most common changes were osseous abnormalities, followed by solid enlargement of the pineal gland, thickened enhancing stalk and signal changes of the dentate nucleus. Whereas inter-rater agreement in assessing most of the CNS lesions was relatively high (κ > 0.61), the application of minimum criteria often did not allow to evaluate the posterior pituitary. The diversity of radiological protocols from different institutions leads to difficulties in the diagnosis of CNS abnormalities in children with LCH. Although the inter-rater agreement between neuroradiologists was high, not all the LCH manifestations could be completely ruled out when using the minimum criteria. Brain MRIs should therefore follow LCH guideline protocols and include T1 pre-gadolinium sagittal images, and be centrally reviewed in order to improve the comparison of clinical trials

  14. Pancreatic islet cell tumor

    Science.gov (United States)

    ... cell tumors; Islet of Langerhans tumor; Neuroendocrine tumors; Peptic ulcer - islet cell tumor; Hypoglycemia - islet cell tumor ... stomach acid. Symptoms may include: Abdominal pain Diarrhea ... and small bowel Vomiting blood (occasionally) Glucagonomas make ...

  15. B cells in the spotlight: innocent bystanders or major players in the pathogenesis of type 1 diabetes.

    Science.gov (United States)

    Silveira, Pablo A; Grey, Shane T

    2006-01-01

    It has long been established that type 1 diabetes (T1D) is a T cell-mediated autoimmune disease, with CD4+ and CD8+ T cells being largely responsible for the destruction of beta cells within the pancreatic islets of Langerhans. Although autoantibodies specific for islet cell proteins are regularly detected in individuals with T1D and can be utilized as effective markers for predicting the onset of disease, they are not believed to be directly pathogenic to beta cells. Thus, activation of autoantibody-secreting B cells has long been regarded as a secondary consequence of the ongoing self-reactive T cell response. However, recently, studies in the nonobese diabetic mouse model of disease have demonstrated that B cells are an important component in the development of T1D by virtue of their ability to act as the preferential antigen presenting cell population required for efficient expansion of diabetogenic CD4+ T cells. Furthermore, autoantibodies might also be responsible for mediating early beta cell pathogenesis in this model.

  16. Src Kinase becomes preferentially associated with the VEGFR, KDR/Flk-1, following VEGF stimulation of vascular endothelial cells

    Directory of Open Access Journals (Sweden)

    Wang Jing

    2002-12-01

    Full Text Available Abstract Background The cytoplasmic tyrosine kinase, Src, has been found to play a crucial role in VEGF (vascular endothelial growth factor – dependent vascular permeability involved in angiogenesis. The two main VEGFRs present on vascular endothelial cells are KDR/Flk-1 (kinase insert domain-containing receptor/fetal liver kinase-1 and Flt-1 (Fms-like tyrosine kinase-1. However, to date, it has not been determined which VEGF receptor (VEGFR is involved in binding to and activating Src kinase following VEGF stimulation of the receptors. Results In this report, we demonstrate that Src preferentially associates with KDR/Flk-1 rather than Flt-1 in human umbilical vein endothelial cells (HUVECs, and that VEGF stimulation resulted in an increase of Src activity associated with activated KDR/Flk-1. These findings were determined through immunoprecipitation-kinase experiments and coimmunoprecipitation studies, and were further confirmed by GST-pull-down assays and Far Western studies. However, Fyn and Yes, unlike Src, were found to associate preferentially with Flt-1. Conclusions Thus, Src preferentially associates with KDR/Flk-1, rather than with Flt-1, upon VEGF stimulation in endothelial cells. Our findings further highlight the potential significance of upregulated KDR/Flk-1-associated Src activity in the process of angiogenesis, and help to elucidate more clearly the specific roles and mechanisms involving Src family tyrosine kinase in VEGF-stimulated signal transduction events.

  17. Calcitonin Gene-Related Peptide Induces HIV-1 Proteasomal Degradation in Mucosal Langerhans Cells.

    Science.gov (United States)

    Bomsel, Morgane; Ganor, Yonatan

    2017-12-01

    The neuroimmune dialogue between peripheral neurons and Langerhans cells (LCs) within mucosal epithelia protects against incoming pathogens. LCs rapidly internalize human immunodeficiency virus type 1 (HIV-1) upon its sexual transmission and then trans -infect CD4 + T cells. We recently found that the neuropeptide calcitonin gene-related peptide (CGRP), secreted mucosally from peripheral neurons, inhibits LC-mediated HIV-1 trans -infection. In this study, we investigated the mechanism of CGRP-induced inhibition, focusing on HIV-1 degradation in LCs and its interplay with trans -infection. We first show that HIV-1 degradation occurs in endolysosomes in untreated LCs, and functionally blocking such degradation with lysosomotropic agents results in increased trans -infection. We demonstrate that CGRP acts via its cognate receptor and at a viral postentry step to induce faster HIV-1 degradation, but without affecting the kinetics of endolysosomal degradation. We reveal that unexpectedly, CGRP shifts HIV-1 degradation from endolysosomes toward the proteasome, providing the first evidence for functional HIV-1 proteasomal degradation in LCs. Such efficient proteasomal degradation significantly inhibits the first phase of trans -infection, and proteasomal, but not endolysosomal, inhibitors abrogate CGRP-induced inhibition. Together, our results establish that CGRP controls the HIV-1 degradation mode in LCs. The presence of endogenous CGRP within innervated mucosal tissues, especially during the sexual response, to which CGRP contributes, suggests that HIV-1 proteasomal degradation predominates in vivo Hence, proteasomal, rather than endolysosomal, HIV-1 degradation in LCs should be enhanced clinically to effectively restrict HIV-1 trans -infection. IMPORTANCE During sexual transmission, HIV-1 is internalized and degraded in LCs, the resident antigen-presenting cells in mucosal epithelia. Yet during trans -infection, infectious virions escaping degradation are transferred

  18. The effect of chronic low-dose UVB radiation on Langerhans cells, sunburn cells, urocanic acid isomers, contact hypersensitivity and serum immunoglobulins in mice

    International Nuclear Information System (INIS)

    El-Ghorr, A.A.; Norval, M.; Lappin, M.B.

    1995-01-01

    C3H mice were irradiated three times a week for up to 6 weeks with either 500 J/m 2 or 1000 J/m 2 broadband UVB (270-350 nm) or 3000 J/m 2 narrowband UVB (311-312 nm; TL01 source). Each dose was suberythemal to the mouse strain used. The number of Langerhans cells (LC) in the epidermis was reduced by over 50% after 2 weeks of irradiation with the UVB source and by 20% following TL01 irradiation. Continued irradiation for up to 6 weeks resulted in no further decrease in LC numbers in the case of the UVB source but a steady decline to 40% in the case of the TL01 source. Sunburn cells were detected following irradiation with both sources but the numbers were very low in comparison with acute exposure. Ultraviolet-B exposure resulted in doubling of the thickness of the epidermis throughout the 6 weeks of irradiation while TL01 exposure did not alter epidermal thickness. Conversion of trans- to cis-urocanic acid (UCA) was observed with both UVB and TL01 sources. The percentage of cis-UCA started to return to normal after 4 weeks of TL01 exposure despite continued irradiation. As observed following a single exposure, the contact hypersensitivity (CH) response was significantly reduced following 6 weeks of UVB irradiation but was unaffected by TL01 exposure, indicating no correlation between cis-UCA levels and CH response. (author)

  19. Hydroxychloroquine preferentially induces apoptosis of CD45RO+ effector T cells by inhibiting autophagy: A possible mechanism for therapeutic modulation of T cells

    OpenAIRE

    van Loosdregt, Jorg; Spreafico, Roberto; Rossetti, Maura; Prakken, Berent J; Lotz, Martin; Albani, Salvatore

    2013-01-01

    Although hydroxychloroquine is used for treatment of numerous autoimmune disorders the mechanism is unclear. We here demonstrate that hydroxychloroquine preferentially induces apoptosis of CD45RO+ memory and effector T cells by inhibiting the survival pathway of autophagy.

  20. Quantification of oral palatine Langerhans cells in HIV/AIDS associated oral Kaposi sarcoma with and without oral candidiasis.

    Science.gov (United States)

    Jivan, Vibha; Meer, Shabnum

    2016-01-01

    Langerhans cells (LCs) are effective antigen-presenting cells that function as "custodians" of mucosa, modifying the immune system to pathogen entry, and tolerance to self-antigen and commensal microbes. A reduction in number of LCs in human immunodeficiency virus (HIV)-positive individuals may predispose to local mucosal infections. To quantitatively determine the number of oral mucosal LCs in HIV/acquired immunodeficiency syndrome HIV/acquired immunodeficiency syndrome (AIDS) associated oral Kaposi sarcoma (KS) with/without oral candidiasis (OC) and to define in situ interrelationships between the cells, OC, and HIV infection. Thirty-two periodic acid-Schiff. (PAS) stained histologic sections of palatal HIV/AIDS associated KS with intact oral epithelium were examined for Candida and divided into two groups: . (1) KS coinfected with Candida and. (2) KS noninfected with Candida. Sections were immunohistochemically stained with CD1a. The standard length of surface epithelium was measured and number of positively stained LCs counted per unit length. Control cases included non-Candida infected palatal mucosa overlying pleomorphic adenoma. (PA) and oral mucosa infected with Candida in otherwise healthy individuals. LC number per unit length of surface epithelium was statistically significantly greatest in uninfected PA mucosa and lowest in KS coinfected with Candida (P = 0.0001). A statistically significant difference was also noted between uninfected PA mucosa and non-Candida infected KS (P = 0.0014), in KS coinfected with Candida and non-infected KS (P = 0.0035), between OC and PA (P = 0.0001), and OC and KS coinfected with Candida (P = 0.0247). LC numbers are significantly reduced in oral tissues of HIV/AIDS infected patients by Candida infection when compared to oral tissues without.

  1. From normal to abnormal MR findings within three weeks in a solitary pelvic Langerhans histiocytosis

    International Nuclear Information System (INIS)

    Hung, Po-Cheng; Wang, Huei-Shyong; Jaing, Tang-Her; Huang, Tsung-Jen; Pang, Leou-Chuan

    2003-01-01

    We present a histologically proven case of pelvic Langerhans histiocytosis (eosinophilic granuloma) which showed abnormality on MR imaging 3 weeks after a normal MR examination mimicking an infection. (orig.)

  2. Th17 Cells and Activated Dendritic Cells Are Increased in Vitiligo Lesions

    Science.gov (United States)

    Fuentes-Duculan, Judilyn; Moussai, Dariush; Gulati, Nicholas; Sullivan-Whalen, Mary; Gilleaudeau, Patricia; Cohen, Jules A.; Krueger, James G.

    2011-01-01

    Background Vitiligo is a common skin disorder, characterized by progressive skin de-pigmentation due to the loss of cutaneous melanocytes. The exact cause of melanocyte loss remains unclear, but a large number of observations have pointed to the important role of cellular immunity in vitiligo pathogenesis. Methodology/Principal Findings In this study, we characterized T cell and inflammation-related dermal dendritic cell (DC) subsets in pigmented non-lesional, leading edge and depigmented lesional vitiligo skin. By immunohistochemistry staining, we observed enhanced populations of CD11c+ myeloid dermal DCs and CD207+ Langerhans cells in leading edge vitiligo biopsies. DC-LAMP+ and CD1c+ sub-populations of dermal DCs expanded significantly in leading edge and lesional vitiligo skin. We also detected elevated tissue mRNA levels of IL-17A in leading edge skin biopsies of vitiligo patients, as well as IL-17A positive T cells by immunohistochemistry and immunofluorescence. Langerhans cells with activated inflammasomes were also noted in lesional vitiligo skin, along with increased IL-1ß mRNA, which suggest the potential of Langerhans cells to drive Th17 activation in vitiligo. Conclusions/Significance These studies provided direct tissue evidence that implicates active Th17 cells in vitiligo skin lesions. We characterized new cellular immune elements, in the active margins of vitiligo lesions (e.g. populations of epidermal and dermal dendritic cells subsets), which could potentially drive the inflammatory responses. PMID:21541348

  3. Alteration in murine epidermal Langerhans cell population by various UV irradiations: quantitative and morphologic studies on the effects of various wavelengths of monochromatic radiation on Ia-bearing cells

    International Nuclear Information System (INIS)

    Obata, M.; Tagami, H.

    1985-01-01

    The present study was undertaken in order to clarify the exact mode of the Langerhans cell (LC) depleting process caused by UV irradiation. Following irradiation with a single dose of various wavelengths of monochromatic UV radiation (UVR), the number of Ia-positive cells were studied in mouse epidermal sheets quantitatively, particularly with regard to dose-response relationships, action spectrum, and time course change. In addition, morphologic alterations of these cells were studied using electron- and immunoelectron microscopy (EM and IEM). The authors obtained the following results after a single dose of UVB radiation (200 mJ/cm2 of 300 nm) or PUVA (1% of 8-methoxypsoralen (8-MOP) 20 microliter and 1 J/cm2 of 360 nm): (1) EM and IEM showed that while some LCs simply lost their Ia marker without any structural alterations, the majority of the LCs disappeared due to actual cell damage. (2) During an ''injury phase,'' the initial 48 h, and a ''recovery phase,'' lasting from 4-14 days after irradiation, enlargement of the size of remaining Ia-positive LCs occurred. The degree of enlargement was closely related to the degree of reduction in number, suggesting a process compensating for the loss of the LC population. (3) It was found that the recovery rate of LCs after irradiation damage was slower than that of keratinocytes, indicating different cell kinetics between these distinct cell populations in the epidermis, i.e., restoration of LCs after irradiation seems to be achieved at least partially through a repopulation process originating in the bone marrow

  4. Mycobacterium leprae-Infected Macrophages Preferentially Primed Regulatory T Cell Responses and Was Associated with Lepromatous Leprosy.

    Directory of Open Access Journals (Sweden)

    Degang Yang

    2016-01-01

    Full Text Available The persistence of Mycobacterium leprae (M. leprae infection is largely dependent on the types of host immune responses being induced. Macrophage, a crucial modulator of innate and adaptive immune responses, could be directly infected by M. leprae. We therefore postulated that M. leprae-infected macrophages might have altered immune functions.Here, we treated monocyte-derived macrophages with live or killed M. leprae, and examined their activation status and antigen presentation. We found that macrophages treated with live M. leprae showed committed M2-like function, with decreased interleukin 1 beta (IL-1beta, IL-6, tumor necrosis factor alpha (TNF-alpha and MHC class II molecule expression and elevated IL-10 and CD163 expression. When incubating with naive T cells, macrophages treated with live M. leprae preferentially primed regulatory T (Treg cell responses with elevated FoxP3 and IL-10 expression, while interferon gamma (IFN-gamma expression and CD8+ T cell cytotoxicity were reduced. Chromium release assay also found that live M. leprae-treated macrophages were more resistant to CD8+ T cell-mediated cytotoxicity than sonicated M. leprae-treated monocytes. Ex vivo studies showed that the phenotype and function of monocytes and macrophages had clear differences between L-lep and T-lep patients, consistent with the in vitro findings.Together, our data demonstrate that M. leprae could utilize infected macrophages by two mechanisms: firstly, M. leprae-infected macrophages preferentially primed Treg but not Th1 or cytotoxic T cell responses; secondly, M. leprae-infected macrophages were more effective at evading CD8+ T cell-mediated cytotoxicity.

  5. Mycobacterium leprae-Infected Macrophages Preferentially Primed Regulatory T Cell Responses and Was Associated with Lepromatous Leprosy.

    Science.gov (United States)

    Yang, Degang; Shui, Tiejun; Miranda, Jake W; Gilson, Danny J; Song, Zhengyu; Chen, Jia; Shi, Chao; Zhu, Jianyu; Yang, Jun; Jing, Zhichun

    2016-01-01

    The persistence of Mycobacterium leprae (M. leprae) infection is largely dependent on the types of host immune responses being induced. Macrophage, a crucial modulator of innate and adaptive immune responses, could be directly infected by M. leprae. We therefore postulated that M. leprae-infected macrophages might have altered immune functions. Here, we treated monocyte-derived macrophages with live or killed M. leprae, and examined their activation status and antigen presentation. We found that macrophages treated with live M. leprae showed committed M2-like function, with decreased interleukin 1 beta (IL-1beta), IL-6, tumor necrosis factor alpha (TNF-alpha) and MHC class II molecule expression and elevated IL-10 and CD163 expression. When incubating with naive T cells, macrophages treated with live M. leprae preferentially primed regulatory T (Treg) cell responses with elevated FoxP3 and IL-10 expression, while interferon gamma (IFN-gamma) expression and CD8+ T cell cytotoxicity were reduced. Chromium release assay also found that live M. leprae-treated macrophages were more resistant to CD8+ T cell-mediated cytotoxicity than sonicated M. leprae-treated monocytes. Ex vivo studies showed that the phenotype and function of monocytes and macrophages had clear differences between L-lep and T-lep patients, consistent with the in vitro findings. Together, our data demonstrate that M. leprae could utilize infected macrophages by two mechanisms: firstly, M. leprae-infected macrophages preferentially primed Treg but not Th1 or cytotoxic T cell responses; secondly, M. leprae-infected macrophages were more effective at evading CD8+ T cell-mediated cytotoxicity.

  6. Motile hepatocellular carcinoma cells preferentially secret sugar metabolism regulatory proteins via exosomes.

    Science.gov (United States)

    Zhang, Jing; Lu, Shaohua; Zhou, Ye; Meng, Kun; Chen, Zhipeng; Cui, Yizhi; Shi, Yunfeng; Wang, Tong; He, Qing-Yu

    2017-07-01

    Exosomes are deliverers of critically functional proteins, capable of transforming target cells in numerous cancers, including hepatocellular carcinoma (HCC). We hypothesize that the motility of HCC cells can be featured by comparative proteome of exosomes. Hence, we performed the super-SILAC-based MS analysis on the exosomes secreted by three human HCC cell lines, including the non-motile Hep3B cell, and the motile 97H and LM3 cells. More than 1400 exosomal proteins were confidently quantified in each MS analysis with highly biological reproducibility. We justified that 469 and 443 exosomal proteins represented differentially expressed proteins (DEPs) in the 97H/Hep3B and LM3/Hep3B comparisons, respectively. These DEPs focused on sugar metabolism-centric canonical pathways per ingenuity pathway analysis, which was consistent with the gene ontology analysis on biological process enrichment. These pathways included glycolysis I, gluconeogenesis I and pentose phosphate pathways; and the DEPs enriched in these pathways could form a tightly connected network. By analyzing the relative abundance of proteins and translating mRNAs, we found significantly positive correlation between exosomes and cells. The involved exosomal proteins were again focusing on sugar metabolism. In conclusion, motile HCC cells tend to preferentially export more sugar metabolism-associated proteins via exosomes that differentiate them from non-motile HCC cells. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Regulation of allergic airway inflammation by adoptive transfer of CD4+ T cells preferentially producing IL-10.

    Science.gov (United States)

    Matsuda, Masaya; Doi, Kana; Tsutsumi, Tatsuya; Fujii, Shinya; Kishima, Maki; Nishimura, Kazuma; Kuroda, Ikue; Tanahashi, Yu; Yuasa, Rino; Kinjo, Toshihiko; Kuramoto, Nobuyuki; Mizutani, Nobuaki; Nabe, Takeshi

    2017-10-05

    Anti-inflammatory pharmacotherapy for asthma has mainly depended on the inhalation of glucocorticoids, which non-specifically suppress immune responses. If the anti-inflammatory cytokine interleukin (IL)-10 can be induced by a specific antigen, asthmatic airway inflammation could be suppressed when individuals are exposed to the antigen. The purpose of this study was to develop cellular immunotherapeutics for atopic diseases using IL-10-producing CD4 + T cells. Spleen cells isolated from ovalbumin (OVA)-sensitized mice were cultured with the antigen, OVA and growth factors, IL-21, IL-27 and TGF-β for 7 days. After the 7-day culture, the CD4 + T cells were purified using a murine CD4 magnetic beads system. When the induced CD4 + T cells were stimulated by OVA in the presence of antigen-presenting cells, IL-10 was preferentially produced in vitro. When CD4 + T cells were adoptively transferred to OVA-sensitized mice followed by intratracheal OVA challenges, IL-10 was preferentially produced in the serum and bronchoalveolar lavage fluid in vivo. IL-10 production coincided with the inhibition of eosinophilic airway inflammation and epithelial mucus plugging. Most of the IL-10-producing CD4 + T cells were negative for Foxp3 and GATA-3, transcription factors of naturally occurring regulatory T cells and Th2 cells, respectively, but double positive for LAG-3 and CD49b, surface markers of inducible regulatory T cells, Tr1 cells. Collectively, most of the induced IL-10-producing CD4 + T cells could be Tr1 cells, which respond to the antigen to produce IL-10, and effectively suppressed allergic airway inflammation. The induced Tr1 cells may be useful for antigen-specific cellular immunotherapy for atopic diseases. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Improving the use of donor organs in pancreas and islet of Langerhans transplantation

    NARCIS (Netherlands)

    Hilling, Denise Eline

    2012-01-01

    Pancreas transplantation and islet of Langerhans transplantation are potential solutions to treat patients with type 1 diabetes. However, pancreas grafts are scarce and there is a shortage of donor pancreata relative to the number of patients needing a transplant. The aim of this thesis was to

  9. Reversal of Human Papillomavirus-Specific T Cell Immune Suppression through TLR Agonist Treatment of Langerhans Cells Exposed to Human Papillomavirus Type 161

    Science.gov (United States)

    Fahey, Laura M.; Raff, Adam B.; Da Silva, Diane M.; Kast, W. Martin

    2009-01-01

    Human papillomavirus (HPV) type 16 infects the epithelial layer of cervical mucosa and is causally associated with the generation of cervical cancer. Langerhans cells (LC) are the resident antigen-presenting cells at the site of infection and therefore are responsible for initiating an immune response against HPV16. On the contrary, LC exposed to HPV16 do not induce a specific T cell immune response, which leads to the immune evasion of HPV16. Demonstrating that Toll-like receptor 7 (TLR7) and TLR8 are expressed on human LC, we hypothesized that imidazoquinolines would activate LC exposed to HPV16, leading to the induction of an HPV16-specific cell-mediated immune response. Surprisingly both phenotypic and functional hallmarks of activation are not observed when LC are exposed to HPV16 virus-like particles (VLP) and treated with imiquimod (TLR7 agonist). However, we found that LC are activated by 3M-002 (TLR8 agonist) and resiquimod (TLR8/7 agonist). LC exposed to HPV16 VLP and subsequently treated with 3M-002 or resiquimod highly up-regulate surface activation markers, secrete pro-inflammatory cytokines and chemokines, induce CCL21-directed migration, and initiate an HPV16-specific CD8+ T cell response. These data strongly indicate that 3M-002 and resiquimod are promising therapeutics for treatment of HPV-infections and HPV-induced cervical lesions. This is an author-produced version of a manuscript accepted for publication in The Journal of Immunology (The JI). The American Association of Immunologists, Inc. (AAI), publisher of The JI, holds the copyright to this manuscript. This version of the manuscript has not yet been copyedited or subjected to editorial proofreading by The JI; hence, it may differ from the final version published in The JI (online and in print). AAI (The JI) is not liable for errors or omissions in this author-produced version of the manuscript or in any version derived from it by the U.S. National Institutes of Health or any other third

  10. Type II and III Taste Bud Cells Preferentially Expressed Kainate Glutamate Receptors in Rats.

    Science.gov (United States)

    Lee, Sang-Bok; Lee, Cil-Han; Kim, Se-Nyun; Chung, Ki-Myung; Cho, Young-Kyung; Kim, Kyung-Nyun

    2009-12-01

    Glutamate-induced cobalt uptake reveals that non-NMDA glutamate receptors (GluRs) are present in rat taste bud cells. Previous studies involving glutamate induced cobalt staining suggest this uptake mainly occurs via kainate type GluRs. It is not known which of the 4 types of taste bud cells express subunits of kainate GluR. Circumvallate and foliate papillae of Sprague-Dawley rats (45~60 days old) were used to search for the mRNAs of subunits of non-NMDA GluRs using RT-PCR with specific primers for GluR1-7, KA1 and KA2. We also performed RT-PCR for GluR5, KA1, PLCbeta2, and NCAM/SNAP 25 in isolated single cells from taste buds. Taste epithelium, including circumvallate or foliate papilla, express mRNAs of GluR5 and KA1. However, non-taste tongue epithelium expresses no subunits of non-NMDA GluRs. Isolated single cell RT-PCR reveals that the mRNAs of GluR5 and KA1 are preferentially expressed in Type II and Type III cells over Type I cells.

  11. Langerhans cell histiocytosis of the urinary bladder in a patient with bladder cancer previously treated with intravesical Bacillus Calmette-Guérin therapy.

    Science.gov (United States)

    Numakura, Satoe; Morikawa, Teppei; Ushiku, Tetsuo; Toyoshima, Toyoaki; Fukayama, Masashi

    2014-02-01

    We report an extremely rare case of Langerhans cell histiocytosis (LCH) of the urinary bladder. A 68-year-old man presented with gross hematuria. Cystoscopy showed multiple papillary tumors in the urinary bladder, and transurethral resection was performed. Pathological diagnosis was high-grade papillary urothelial carcinoma with lamina propria invasion. The patient received six treatments with intravesical Bacillus Calmette-Guérin (BCG) therapy. Seven months after surgery, follow-up cystoscopy showed three elevated lesions in the urinary bladder, two of which were identified histologically as recurrent urothelial carcinoma. Microscopic examination of the lesion at the anterior wall revealed diffuse infiltration of medium to large histiocytoid cells in the lamina propria, many of which had distorted nuclei and nuclear grooves. Dense eosinophilic infiltration was also observed. Immunohistochemically, the histiocytoid cells were diffusely positive for S-100 and CD1a, but negative for cytokeratin AE1/AE3 and melanosome-associated antigen recognized by HMB-45. Based on the histological and immunohistochemical features, we diagnosed the lesion as LCH of the urinary bladder. There was no evidence of recurrence of either bladder cancer or LCH after an 18-month follow-up. To avoid misdiagnosis, urologists and pathologists should be aware that LCH may develop in the urinary bladder after intravesical BCG therapy for bladder cancer. Copyright © 2013 Elsevier GmbH. All rights reserved.

  12. Xanthophylls are preferentially taken up compared with beta-carotene by retinal cells via a SRBI-dependent mechanism.

    Science.gov (United States)

    During, Alexandrine; Doraiswamy, Sundari; Harrison, Earl H

    2008-08-01

    The purpose of this study was to investigate the mechanisms by which carotenoids [xanthophylls vs. beta-carotene(beta-C)] are taken up by retinal pigment epithelial (RPE) cells. The human RPE cell line, ARPE-19, was used. When ARPE-19 cells were fully differentiated (7-9 weeks), the xanthophylls lutein (LUT) and zeaxanthin (ZEA) were taken up by cells to an extent 2-fold higher than beta-C (P xanthophylls versus the carotene by a process that appears to be entirely SR-BI-dependent for ZEA and partly so for beta-C. This mechanism may explain, in part, the preferential accumulation of xanthophylls in the macula of the retina.

  13. Follicles in gut-associated lymphoid tissues create preferential survival niches for follicular Th cells escaping Thy-1-specific depletion in mice.

    Science.gov (United States)

    Mihalj, Martina; Kellermayer, Zoltán; Balogh, Peter

    2013-07-01

    Although a substantial number of T cells may escape depletion following in vivo mAb treatment in patients undergoing immunosuppression, their specific tissue location and phenotypic characteristics in different peripheral lymphoid tissues have not been analyzed in detail. Here we investigated the survival of CD4(+) T cells immediately following anti-Thy-1 mAb treatment in mice. We found a preferential survival of CD4(+) T cells expressing Thy-1 antigen in the Peyer's patches (PP) and also in mesenteric lymph nodes (MLN), where the relative majority of the surviving CD4(+) T cells displayed CD44(high)/CD62L(-) phenotype corresponding to effector memory T-cell features. These CD4(+) T cells also expressed CXCR5 and PD-1 (programmed cell death-1) markers characteristic for follicular Th cells (TFH). We also demonstrate that the immediate survival of these cells does not involve proliferation and is independent of IL-7. Induction of germinal center formation in spleen enhanced while the dissolution of follicular architecture by lymphotoxin-β receptor antagonist treatment slightly reduced TFH survival. Our results thus raise the possibility that the follicles within PP and MLN may create natural support niches for the preferential survival of TFH cells of the memory phenotype, thus allowing their escape during T-cell depletion.

  14. CD34+ (Non-Malignant) Stem Cell Selection for Patients Receiving Allogeneic Stem Cell Transplantation

    Science.gov (United States)

    2017-07-13

    Bone Marrow Failure Syndrome; Severe Aplastic Anemia; Severe Congenital Neutropenia; Amegakaryocytic Thrombocytopenia; Diamond-Blackfan Anemia; Schwachman Diamond Syndrome; Primary Immunodeficiency Syndromes; Acquired Immunodeficiency Syndromes; Histiocytic Syndrome; Familial Hemophagocytic Lymphocytosis; Lymphohistiocytosis; Macrophage Activation Syndrome; Langerhans Cell Histiocytosis (LCH); Hemoglobinopathies; Sickle Cell Disease; Sickle Cell-beta-thalassemia

  15. Arctigenin preferentially induces tumor cell death under glucose deprivation by inhibiting cellular energy metabolism.

    Science.gov (United States)

    Gu, Yuan; Qi, Chunting; Sun, Xiaoxiao; Ma, Xiuquan; Zhang, Haohao; Hu, Lihong; Yuan, Junying; Yu, Qiang

    2012-08-15

    Selectively eradicating cancer cells with minimum adverse effects on normal cells is a major challenge in the development of anticancer therapy. We hypothesize that nutrient-limiting conditions frequently encountered by cancer cells in poorly vascularized solid tumors might provide an opportunity for developing selective therapy. In this study, we investigated the function and molecular mechanisms of a natural compound, arctigenin, in regulating tumor cell growth. We demonstrated that arctigenin selectively promoted glucose-starved A549 tumor cells to undergo necrosis by inhibiting mitochondrial respiration. In doing so, arctigenin elevated cellular level of reactive oxygen species (ROS) and blocked cellular energy metabolism in the glucose-starved tumor cells. We also demonstrated that cellular ROS generation was caused by intracellular ATP depletion and played an essential role in the arctigenin-induced tumor cell death under the glucose-limiting condition. Furthermore, we combined arctigenin with the glucose analogue 2-deoxyglucose (2DG) and examined their effects on tumor cell growth. Interestingly, this combination displayed preferential cell-death inducing activity against tumor cells compared to normal cells. Hence, we propose that the combination of arctigenin and 2DG may represent a promising new cancer therapy with minimal normal tissue toxicity. Crown Copyright © 2012. Published by Elsevier Inc. All rights reserved.

  16. Clinical features and treatment outcomes of Langerhans cell histiocytosis: a nationwide survey from Korea histiocytosis working party.

    Science.gov (United States)

    Kim, Bo Eun; Koh, Kyung-Nam; Suh, Jin Kyung; Im, Ho Joon; Song, Joon Sup; Lee, Ji Won; Kang, Hyoung Jin; Park, Kyung Duck; Shin, Hee Young; Choi, Hyoung Soo; Lee, Soo Hyun; Yoo, Keon Hee; Sung, Ki Woong; Koo, Hong Hoe; Jung, Hye Lim; Chung, Nak-Gyun; Cho, Bin; Kim, Hack Ki; Lyu, Chuhl Joo; Baek, Hee Jo; Kook, Hoon; Park, Jun Eun; Park, Hyeon Jin; Park, Byung-Kiu; Yoo, Eun Sun; Ryu, Kyung Ha; Lee, Kun Soo; Kim, Heung Sik; Lee, Jae Min; Park, Eun Sil; Yoon, Hoi Soo; Lee, Kwang Chul; Lee, Mee Jeong; Lim, Young Tak; Kim, Hwang Min; Park, Sang Kyu; Park, Jeong-A; Kim, Soon Ki; Park, Meerim; Lim, Yeon-Jung; Lee, Young Ho; Seo, Jong Jin

    2014-03-01

    A nationwide survey was conducted to clarify the clinical features and outcomes of Korean children with Langerhans cell histiocytosis (LCH). Korea Histiocytosis Working Party analyzed the data of 603 patients who were diagnosed with LCH between 1986 and 2010 from 28 institutions in Korea. Median age at diagnosis was 65 months (range, 0 to 276 mo). Bone was the most frequently affected organ (79.6%) followed by skin (19.2%). Initially, 419 patients (69.5%) had single-system involvement (SS), 85 (14.1%) with multisystem (MS) disease without risk organ involvement (MS-RO), and 99 (16.4%) multisystem disease with risk organ involvement (MS-RO). The 5-year overall survival (OS) rates in the SS, MS-RO, and MS-RO groups were 99.8%, 98.4%, and 77.0%, respectively (P<0.001), and the 5-year reactivation rates were 17.9%, 33.5%, and 34.3%, respectively (P<0.001). The OS rate was lower in patients with RO involvement (P=0.025) and lack of response to initial treatment (P=0.001). MS involvement (P=0.036) was an independent risk factor for reactivation. Permanent consequences were documented in 99 patients (16.4%). Reactivation of disease, MS involvement, and age at diagnosis ≤ 2 years were associated with higher incidence of permanent consequences. This study emphasized that further efforts are required to improve survival of MS-RO patients and reduce reactivation in younger patients with MS involvement.

  17. Label-Free Detection of Insulin and Glucagon within Human Islets of Langerhans Using Raman Spectroscopy

    NARCIS (Netherlands)

    Hilderink, J.; Otto, Cornelis; Slump, Cornelis H.; Lenferink, Aufrid T.M.; Engelse, M.A.; van Blitterswijk, Clemens; de Koning, E.J.P.; Karperien, Hermanus Bernardus Johannes; van Apeldoorn, Aart A.

    2013-01-01

    Intrahepatic transplantation of donor islets of Langerhans is a promising therapy for patients with type 1 diabetes. It is of critical importance to accurately monitor islet quality before transplantation, which is currently done by standard histological methods that are performed off-line and

  18. Pulmonary Langerhans cell histiocytosis with cervical lymph node involvement, and coexistence with pulmonary tuberculosis and right pneumothorax: a case report and review of literature.

    Science.gov (United States)

    Gao, Limin; Li, Huifang; Li, Gandi; Liu, Weiping; Li, Jinnan; Zhang, Wenyan

    2015-01-01

    We report an uncommon 22-year-old male Pulmonary Langerhans Cell Histiocytosis (PLCH) case which co-existed with pulmonary tuberculosis (TB). Unlike the common PLCH cases, this PLCH case has cervical lymph node involvement and right pneumothorax. The diagnosis was established by the imaging of lung and the biopsies of the lung and left neck lymph node. Imaging of the chest showed characteristic small nodules and thin-walled cysts and right pneumothorax. The LCH cells in the lung and left neck lymph node were characterized by large convoluted nuclei with cerebriform indentations of the nuclear envelope and longitudinal grooves. The nuclei contained small eosinophilic nucleoli and moderate amount cytoplasm. Immunohistochemically, the histiocytoid cells were positive for Langerin, CD1a and S-100. Acid-fast bacilli were found in sputum and lung biopsy tissue. To the best of our knowledge, this is the first case of PLCH with cervical lymph node involvement, and coexisted with pulmonary tuberculosis, right pneumothorax. A contribution of this case and review three of the five cases of PLCH with extrapulmonary involvement to lymph nodes resolved spontaneously after smoking cessation constitute a novel addition that it is inappropriate to regard pulmonary/nodal LCH as multi-organ or disseminated disease, and the treatment methods are the same whether the PLCH patient with lymph node involvement or not.

  19. Effect of Nitric Oxide Synthesis Blockade on the Morphology of Langerhans Islets in August and Wistar Rats with Acute Alloxan Diabetes.

    Science.gov (United States)

    Smirnova, E A; Michunskaya, A B; Terekhina, O L; Kobozeva, L P; Kruglov, S V; Belkina, L M; Pozdnyakov, O M

    2015-06-01

    Alloxan diabetes was modeled in August rats with high activity of the NO system and in Wistar rats, and the effects of NO system blockade (by a course treatment with L-NNA) on Langerhans islet β cells were studied in 15 days. The toxic effects of diabetes on the rat β cells and islets were similar: the content of active β cells in the islets decreased to 15-20%, the number of islets to 24-29% of control. A course of L-NNA reduced the β cell and islet death, in August cells greater than in Wistar: the number of islets in August rats was restored to 81%, in Wistar rats to 60% of initial level; the activity of β cells remained at the control level in the former and 2-fold lower than in the control in the latter. It seems that a less pronounced protective effect of L-NNA in Wistar rats was explained by excessive reduction of NO level essential for β cell regeneration.

  20. Preferential retrotransposition in aging yeast mother cells is correlated with increased genome instability.

    Science.gov (United States)

    Patterson, Melissa N; Scannapieco, Alison E; Au, Pak Ho; Dorsey, Savanna; Royer, Catherine A; Maxwell, Patrick H

    2015-10-01

    Retrotransposon expression or mobility is increased with age in multiple species and could promote genome instability or altered gene expression during aging. However, it is unclear whether activation of retrotransposons during aging is an indirect result of global changes in chromatin and gene regulation or a result of retrotransposon-specific mechanisms. Retromobility of a marked chromosomal Ty1 retrotransposon in Saccharomyces cerevisiae was elevated in mother cells relative to their daughter cells, as determined by magnetic cell sorting of mothers and daughters. Retromobility frequencies in aging mother cells were significantly higher than those predicted by cell age and the rate of mobility in young populations, beginning when mother cells were only several generations old. New Ty1 insertions in aging mothers were more strongly correlated with gross chromosome rearrangements than in young cells and were more often at non-preferred target sites. Mother cells were more likely to have high concentrations and bright foci of Ty1 Gag-GFP than their daughter cells. Levels of extrachromosomal Ty1 cDNA were also significantly higher in aged mother cell populations than their daughter cell populations. These observations are consistent with a retrotransposon-specific mechanism that causes retrotransposition to occur preferentially in yeast mother cells as they begin to age, as opposed to activation by phenotypic changes associated with very old age. These findings will likely be relevant for understanding retrotransposons and aging in many organisms, based on similarities in regulation and consequences of retrotransposition in diverse species. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Human Langerhans cells use an IL-15R-α/IL-15/pSTAT5-dependent mechanism to break T-cell tolerance against the self-differentiation tumor antigen WT1.

    Science.gov (United States)

    Romano, Emanuela; Cotari, Jesse W; Barreira da Silva, Rosa; Betts, Brian C; Chung, David J; Avogadri, Francesca; Fink, Mitsu J; St Angelo, Erin T; Mehrara, Babak; Heller, Glenn; Münz, Christian; Altan-Bonnet, Gregoire; Young, James W

    2012-05-31

    Human CD34(+) progenitor-derived Langerhans-type dendritic cells (LCs) are more potent stimulators of T-cell immunity against tumor and viral antigens in vitro than are monocyte-derived DCs (moDCs). The exact mechanisms have remained elusive until now, however. LCs synthesize the highest amounts of IL-15R-α mRNA and protein, which binds IL-15 for presentation to responder lymphocytes, thereby signaling the phosphorylation of signal transducer and activator of transcription 5 (pSTAT5). LCs electroporated with Wilms tumor 1 (WT1) mRNA achieve sufficiently sustained presentation of antigenic peptides, which together with IL-15R-α/IL-15, break tolerance against WT1 by stimulating robust autologous, WT1-specific cytolytic T-lymphocytes (CTLs). These CTLs develop from healthy persons after only 7 days' stimulation without exogenous cytokines and lyse MHC-restricted tumor targets, which include primary WT1(+) leukemic blasts. In contrast, moDCs require exogenous rhuIL-15 to phosphorylate STAT5 and attain stimulatory capacity comparable to LCs. LCs therefore provide a more potent costimulatory cytokine milieu for T-cell activation than do moDCs, thus accounting for their superior stimulation of MHC-restricted Ag-specific CTLs without need for exogenous cytokines. These data support the use of mRNA-electroporated LCs, or moDCs supplemented with exogenous rhuIL-15, as vaccines for cancer immunotherapy to break tolerance against self-differentiation antigens shared by tumors.

  2. Histiocitosis de células de Langerhans, granuloma eosinofílico de hueso temporal en adolescente. Caso clínico

    Directory of Open Access Journals (Sweden)

    Rosa Isabel Milanés Pérez

    2013-01-01

    Full Text Available El granuloma eosinofílico es la forma localizada de la histiocitosis de células de Langerhans. Es una rara enfermedad que puede simular un proceso infeccioso del oído medio y áreas vecinas, especialmente en la población pediátrica. Se presenta caso clínico de una adolescente con enfermedad de histiocitosis de Langerhans monofocal en hueso temporal. Su diagnóstico presentó dificultades inherentes a su presentación clínica y a los estudios anatomopatológicos. La respuesta al tratamiento con radioterapia a dosis bajas fue satisfactoria.

  3. Distribuição anatômica da árvore ductal pancreática do cão: implicações para o isolamento das ilhotas de Langerhans Anatomical distribution of pancraatic ductal tree and its implications for isolating Langerhans islets

    Directory of Open Access Journals (Sweden)

    Jaques Waisberg

    1999-09-01

    Full Text Available O conhecimento da anatomia normal da árvore ductal pancreática no cão e de sua variações reveste-se de importância para a execução dos protocolos de preparação e isolamento das ilhotas de Langerhans. A proposta deste estudo é demonstrar a configuração anatômica da dutal pancreática com especial atenção para as implicações sobre as técnicas de preparação do tecido pancreático para o transplante de ilhotas de Langerhans no cão. Os autores realizaram a dissecção do duto pancreático principal (Santorini e a cateterização dos seus ramos ascendente e descendente. Em seguida procederam à pancreatectomia total sem duodenectomia. Através destes cateteres, infundiu-se solução de acetona no interior dos ductos e solução de tinta nanquim de cor azul no ramo ascendente e de cor vermelha no ramo descendente. Posteriormente, os autores dissecaram a árvore ductal pancreática com pinças delicadas e digitoclasia. Através desta técnica, os autores verificaram a distensão universal do parênquima pancreático devido ao envolvimento de toda a glândula pelos ramos tributários do ducto pancreático principal. O ramos descendente distendeu exclusivamente a região do processo uncinado, ao passo que o ramo ascendente distendeu exclusivamente as regiões do corpo e cauda do pâncreas canino. Esta constatação enfatiza a utilização destas vias para a infusão das soluções apropriadas nos procedimentos de isolamento das ilhotas de Langerhans no modelo canino.The knowledge of normal pancreatic ductal tree anatomy in dogs is important for the preparation and isolation of islets of Langerhans. The aim of this study is to demonstrate the anatomical configuration of the pancreatic ductal tree, especially concerning its implications in the preparation of pancreatic tissue for Langerhans islets transplantation techniques. The main pancreatic duct ( Santorini was dissected, and the upper and the lower branches were catheterized

  4. Cellular location of rat muscle ferritins and their preferential loss during cell isolation.

    Science.gov (United States)

    Linder, M C; Roboz, M; McKown, M J; Pardridge, W M; Zak, R

    1984-04-10

    Heart and other muscles of the rat contain two forms of ferritin separable in polyacrylamide gel electrophoresis. The cellular location of the fast- and slow-migrating ferritins was investigated using primary cultures of hindlimb skeletal muscle, and isolated myocardial cell populations. Muscle and non-muscle cells were isolated in good yield from hearts of adult rats pretreated with large doses of iron to increase their ferritin content. In virtually all cases, the isolated muscle cells contained traces only of the fast-migrating species and the non-muscle cells contained small amounts of the slow-migrating ferritin. During cell isolation, 90-100% of both ferritins was lost and could be recovered in the perfusates and solutions employed, while one third of the total tissue protein, and a larger percentage of creatine phosphokinase, was recovered in the isolated cells. Primary cultures of thigh muscle from adult rats which had differentiated into multi-nucleated myotubes, were incubated for 1-3 days with chelated iron. These cells contained substantial amounts of the electrophoretically fast migrating ferritin, with its characteristic larger Stokes' radius (determined by quantitative polyacrylamide gel electrophoresis). None of the slow-migrating ferritin species was detected, although hindlimb muscle from iron-treated rats contained both forms. It is concluded that the fast-migrating ferritin of muscle, which is much larger and more asymmetric than other ferritins, is confined to the muscle cell population, while the other form is predominantly or exclusively in the non-muscle cells. Both ferritins are lost preferentially over other proteins during procedures which injure muscle tissue.

  5. Xanthophylls are preferentially taken up compared with β-carotene by retinal cells via a SRBI-dependent mechanism*1

    Science.gov (United States)

    During, Alexandrine; Doraiswamy, Sundari; Harrison, Earl H.

    2008-01-01

    The purpose of this study was to investigate the mechanisms by which carotenoids [xanthophylls vs. β-carotene(β-C)] are taken up by retinal pigment epithelial (RPE) cells. The human RPE cell line, ARPE-19, was used. When ARPE-19 cells were fully differentiated (7–9 weeks), the xanthophylls lutein (LUT) and zeaxanthin (ZEA) were taken up by cells to an extent 2-fold higher than β-C (P xanthophylls versus the carotene by a process that appears to be entirely SR-BI-dependent for ZEA and partly so for β-C. This mechanism may explain, in part, the preferential accumulation of xanthophylls in the macula of the retina. PMID:18424859

  6. Homogenization of heterogeneously coupled bistable ODE's - applied to excitation waves in pancreatic islets of Langerhans

    DEFF Research Database (Denmark)

    Pedersen, Morten Gram

    2004-01-01

    We consider a lattice of coupled identical differential equations. The coupling is between nearest neighbors and of resistance type, but the strength of coupling varies from site to site. Such a lattice can, for example, model an islet of Langerhans, where the sites in the lattice model individua...

  7. Transcriptome-wide identification of preferentially expressed genes in the hypothalamus and pituitary gland

    Directory of Open Access Journals (Sweden)

    Jonny eSt-Amand

    2012-01-01

    Full Text Available To identify preferentially expressed genes in the central endocrine organs of the hypothalamus and pituitary gland, we generated transcriptome-wide mRNA profiles of the mouse hypothalamus, pituitary gland and parietal cortex using serial analysis of gene expression (SAGE. Total counts of SAGE tags for the hypothalamus, pituitary gland and parietal cortex were 165824, 126688 and 161045 tags, respectively. This represented 59244, 45151 and 55131 distinct tags, respectively. Comparison of these mRNA profiles revealed that 22 mRNA species, including three potential novel transcripts, were preferentially expressed in the hypothalamus. In addition to well-known hypothalamic transcripts, such as hypocretin, several genes involved in hormone function, intracellular transduction, metabolism, protein transport, steroidogenesis, extracellular matrix and brain disease were identified as preferentially expressed hypothalamic transcripts. In the pituitary gland, 106 mRNA species, including 60 potential novel transcripts, were preferentially expressed. In addition to well-known pituitary genes, such as growth hormone and thyroid stimulating hormone beta, a number of genes classified to function in transport, amino acid metabolism, intracellular transduction, cell adhesion, disulfide bond formation, stress response, transcription, protein synthesis and turnover, cell differentiation, the cell cycle and in the cytoskeleton and extracellular matrix were also preferentially expressed. In conclusion, the current study identified not only well-known hypothalamic and pituitary transcripts but also a number of new candidates likely to be involved in endocrine homeostatic systems regulated by the hypothalamus and pituitary gland.

  8. Transcriptome-wide identification of preferentially expressed genes in the hypothalamus and pituitary gland.

    Science.gov (United States)

    St-Amand, Jonny; Yoshioka, Mayumi; Tanaka, Keitaro; Nishida, Yuichiro

    2011-01-01

    To identify preferentially expressed genes in the central endocrine organs of the hypothalamus and pituitary gland, we generated transcriptome-wide mRNA profiles of the hypothalamus, pituitary gland, and parietal cortex in male mice (12-15 weeks old) using serial analysis of gene expression (SAGE). Total counts of SAGE tags for the hypothalamus, pituitary gland, and parietal cortex were 165824, 126688, and 161045 tags, respectively. This represented 59244, 45151, and 55131 distinct tags, respectively. Comparison of these mRNA profiles revealed that 22 mRNA species, including three potential novel transcripts, were preferentially expressed in the hypothalamus. In addition to well-known hypothalamic transcripts, such as hypocretin, several genes involved in hormone function, intracellular transduction, metabolism, protein transport, steroidogenesis, extracellular matrix, and brain disease were identified as preferentially expressed hypothalamic transcripts. In the pituitary gland, 106 mRNA species, including 60 potential novel transcripts, were preferentially expressed. In addition to well-known pituitary genes, such as growth hormone and thyroid stimulating hormone beta, a number of genes classified to function in transport, amino acid metabolism, intracellular transduction, cell adhesion, disulfide bond formation, stress response, transcription, protein synthesis, and turnover, cell differentiation, the cell cycle, and in the cytoskeleton and extracellular matrix were also preferentially expressed. In conclusion, the current study identified not only well-known hypothalamic and pituitary transcripts but also a number of new candidates likely to be involved in endocrine homeostatic systems regulated by the hypothalamus and pituitary gland.

  9. Dynamic visualization of dendritic cell-antigen interactions in the skin following transcutaneous immunization.

    Directory of Open Access Journals (Sweden)

    Teerawan Rattanapak

    Full Text Available Delivery of vaccines into the skin provides many advantages over traditional parenteral vaccination and is a promising approach due to the abundance of antigen presenting cells (APC residing in the skin including Langerhans cells (LC and dermal dendritic cells (DDC. However, the main obstacle for transcutaneous immunization (TCI is the effective delivery of the vaccine through the stratum corneum (SC barrier to the APC in the deeper skin layers. This study therefore utilized microneedles (MN and a lipid-based colloidal delivery system (cubosomes as a synergistic approach for the delivery of vaccines to APC in the skin. The process of vaccine uptake and recruitment by specific types of skin APC was investigated in real-time over 4 hours in B6.Cg-Tg (Itgax-EYFP 1 Mnz/J mice by two-photon microscopy. Incorporation of the vaccine into a particulate delivery system and the use of MN preferentially increased vaccine antigen uptake by a highly motile subpopulation of skin APC known as CD207⁺ DC. No uptake of antigen or any response to immunisation by LC could be detected.

  10. Empty conformers of HLA-B preferentially bind CD8 and regulate CD8+ T cell function.

    Science.gov (United States)

    Geng, Jie; Altman, John D; Krishnakumar, Sujatha; Raghavan, Malini

    2018-05-09

    When complexed with antigenic peptides, human leukocyte antigen (HLA) class I (HLA-I) molecules initiate CD8 + T cell responses via interaction with the T cell receptor (TCR) and co-receptor CD8. Peptides are generally critical for the stable cell surface expression of HLA-I molecules. However, for HLA-I alleles such as HLA-B*35:01, peptide-deficient (empty) heterodimers are thermostable and detectable on the cell surface. Additionally, peptide-deficient HLA-B*35:01 tetramers preferentially bind CD8 and to a majority of blood-derived CD8 + T cells via a CD8-dependent binding mode. Further functional studies reveal that peptide-deficient conformers of HLA-B*35:01 do not directly activate CD8 + T cells, but accumulate at the immunological synapse in antigen-induced responses, and enhance cognate peptide-induced cell adhesion and CD8 + T cell activation. Together, these findings indicate that HLA-I peptide occupancy influences CD8 binding affinity, and reveal a new set of regulators of CD8 + T cell activation, mediated by the binding of empty HLA-I to CD8. © 2018, Geng et al.

  11. Lower levels of interleukin-1β gene expression are associated with impaired Langerhans' cell migration in aged human skin.

    Science.gov (United States)

    Pilkington, Suzanne M; Ogden, Stephanie; Eaton, Laura H; Dearman, Rebecca J; Kimber, Ian; Griffiths, Christopher E M

    2018-01-01

    Langerhans' cells (LC) play pivotal roles in skin immune responses, linking innate and adaptive immunity. In aged skin there are fewer LC and migration is impaired compared with young skin. These changes may contribute to declining skin immunity in the elderly, including increased skin infections and skin cancer. Interleukin-1β (IL-1β) and tumour necrosis factor-α (TNF-α) are mandatory signals for LC migration and previous studies suggest that IL-1β signalling may be dysregulated in aged skin. Therefore, we sought to explore the mechanisms underlying these phenomena. In skin biopsies of photoprotected young ( 70 years) human skin ex vivo, we assessed the impact of trauma, and mandatory LC mobilizing signals on LC migration and gene expression. Biopsy-related trauma induced LC migration from young epidermis, whereas in aged skin, migration was greatly reduced. Interleukin-1β treatment restored LC migration in aged epidermis whereas TNF-α was without effect. In uncultured, aged skin IL-1β gene expression was lower compared with young skin; following culture, IL-1βmRNA remained lower in aged skin under control and TNF-α conditions but was elevated after culture with IL-1β. Interleukin-1 receptor type 2 (IL1R2) gene expression was significantly increased in aged, but not young skin, after cytokine treatment. Keratinocyte-derived factors secreted from young and aged primary cells did not restore or inhibit LC migration from aged and young epidermis, respectively. These data suggest that in aged skin, IL-1β signalling is diminished due to altered expression of IL1B and decoy receptor gene IL1R2. © 2017 The Authors. Immunology Published by John Wiley & Sons Ltd., Immunology.

  12. MRI and clinical features of Langerhans cell histiocytosis (LCH) in the pelvis and extremities: can LCH really look like anything?

    International Nuclear Information System (INIS)

    Samet, Jonathan; Weinstein, Joanna; Fayad, Laura M.

    2016-01-01

    To assess clinical and MRI features of Langerhans cell histiocytosis in the pelvis and extremities. The MRI and clinical features of 21 pathologically proven cases of LCH involving the pelvis and extremities were studied. Multiple characteristics of the lesions were evaluated (location, size, T1/ T2/post-contrast features, perilesional bone and soft tissue signal, endosteal scalloping, periosteal reaction, soft tissue mass, pathologic fracture). Pre-biopsy radiologic diagnoses were collected from the original clinical reports. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), temperature, and white blood cell count (WBC) were collected at the time of diagnosis when available. The locations of the LCH lesions included five humerus, four femur, five ilium, one tibia, one clavicle, and three scapula. Lesional size ranged from 1.8 to 7.1 cm, with a mean of 3.6 cm. All lesions demonstrated perilesional bone marrow edema, periosteal reaction, endosteal scalloping, and post-contrast enhancement. An associated soft tissue mass was present in 15/21 (71.4 %). Clinically, the WBC, ESR, and CRP were elevated in 2/14 (14 %), 8/12 (67 %), and 4/10 (40 %) of cases, respectively. Fever was documented in 1/15 (7 %) patients and pain was reported in 15/15 (100 %). The clinical and radiologic features of LCH in the pelvis and extremities overlap with infection and malignancy, but LCH must be considered in the differential diagnosis, as it routinely presents with aggressive MRI features, including endosteal scalloping, periosteal reaction, perilesional edema, and a soft tissue mass. Furthermore, an unknown skeletal lesion at presentation without aggressive MRI features is unlikely to represent LCH. (orig.)

  13. MRI and clinical features of Langerhans cell histiocytosis (LCH) in the pelvis and extremities: can LCH really look like anything?

    Energy Technology Data Exchange (ETDEWEB)

    Samet, Jonathan [Northwestern University Feinberg School of Medicine, Department of Medical Imaging, Ann and Robert H. Lurie Children' s Hospital of Chicago, Chicago, IL (United States); Weinstein, Joanna [Northwestern University Feinberg School of Medicine, Departments of Pediatrics, Division of Hematology/Oncology/Stem Cell Transplant, Ann and Robert H. Lurie Children' s Hospital of Chicago, Chicago, IL (United States); Fayad, Laura M. [The Johns Hopkins University School of Medicine, The Russell H. Morgan Department of Radiology and Radiological Science, Baltimore, MD (United States)

    2016-05-15

    To assess clinical and MRI features of Langerhans cell histiocytosis in the pelvis and extremities. The MRI and clinical features of 21 pathologically proven cases of LCH involving the pelvis and extremities were studied. Multiple characteristics of the lesions were evaluated (location, size, T1/ T2/post-contrast features, perilesional bone and soft tissue signal, endosteal scalloping, periosteal reaction, soft tissue mass, pathologic fracture). Pre-biopsy radiologic diagnoses were collected from the original clinical reports. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), temperature, and white blood cell count (WBC) were collected at the time of diagnosis when available. The locations of the LCH lesions included five humerus, four femur, five ilium, one tibia, one clavicle, and three scapula. Lesional size ranged from 1.8 to 7.1 cm, with a mean of 3.6 cm. All lesions demonstrated perilesional bone marrow edema, periosteal reaction, endosteal scalloping, and post-contrast enhancement. An associated soft tissue mass was present in 15/21 (71.4 %). Clinically, the WBC, ESR, and CRP were elevated in 2/14 (14 %), 8/12 (67 %), and 4/10 (40 %) of cases, respectively. Fever was documented in 1/15 (7 %) patients and pain was reported in 15/15 (100 %). The clinical and radiologic features of LCH in the pelvis and extremities overlap with infection and malignancy, but LCH must be considered in the differential diagnosis, as it routinely presents with aggressive MRI features, including endosteal scalloping, periosteal reaction, perilesional edema, and a soft tissue mass. Furthermore, an unknown skeletal lesion at presentation without aggressive MRI features is unlikely to represent LCH. (orig.)

  14. Inhibition of Langerhans cell maturation by human papillomavirus type 16: a novel role for the annexin A2 heterotetramer in immune suppression.

    Science.gov (United States)

    Woodham, Andrew W; Raff, Adam B; Raff, Laura M; Da Silva, Diane M; Yan, Lisa; Skeate, Joseph G; Wong, Michael K; Lin, Yvonne G; Kast, W Martin

    2014-05-15

    High-risk human papillomaviruses (HPVs) are sexually transmitted viruses causally associated with several cancers. During its natural life cycle, HPV16, the most common high-risk genotype, infects the epithelial basal cells in a process facilitated through a recently identified receptor, the annexin A2 heterotetramer (A2t). During infection, HPV16 also interacts with Langerhans cells (LC), the APC of the epithelium, inducing immune suppression, which is mediated by the HPV16 L2 minor capsid protein. Despite the importance of these virus-immune cell interactions, the specific mechanisms of HPV16 entry into LC and HPV16-induced immune suppression remain undefined. An N-terminal peptide of HPV16 L2 (aa 108-126) has been shown to specifically interact with A2t. In this study, we show that incubation of human LC with this peptide blocks binding of HPV16. Inhibiting this interaction with an A2t ligand or by small interfering RNA downregulation of A2t significantly decreases HPV16 internalization into LC in an L2-dependent manner. A2t is associated with suppression of LC maturation as demonstrated through attenuated secretion of Th1-associated cytokines and decreased surface expression of MHC class II on LC exposed to A2t. Conversely, small molecule inhibition of A2t prevents HPV16-induced suppression of LC immune function as indicated by significantly increased secretion of inflammatory cytokines and surface expression of CD86 in HPV16 treated LC pre-exposed to A2t inhibitors. These results demonstrate that HPV16 suppresses LC maturation through an interaction with A2t, revealing a novel role for this protein.

  15. Microfluidic perfusion system for automated delivery of temporal gradients to islets of Langerhans.

    Science.gov (United States)

    Zhang, Xinyu; Roper, Michael G

    2009-02-01

    A microfluidic perfusion system was developed for automated delivery of stimulant waveforms to cells within the device. The 3-layer glass/polymer device contained two pneumatic pumps, a 12 cm mixing channel, and a 0.2 microL cell chamber. By altering the flow rate ratio of the pumps, a series of output concentrations could be produced while a constant 1.43 +/- 0.07 microL/min flow rate was maintained. The output concentrations could be changed in time producing step gradients and other waveforms, such as sine and triangle waves, at different amplitudes and frequencies. Waveforms were analyzed by comparing the amplitude of output waveforms to the amplitude of theoretical waveforms. Below a frequency of 0.0098 Hz, the output waveforms had less than 20% difference than input waveforms. To reduce backflow of solutions into the pumps, the operational sequence of the valving program was modified, as well as differential etching of the valve seat depths. These modifications reduced backflow to the point that it was not detected. Gradients in glucose levels were applied in this work to stimulate single islets of Langerhans. Glucose gradients between 3 and 20 mM brought clear and intense oscillations of intracellular [Ca(2+)] indicating the system will be useful in future studies of cellular physiology.

  16. Constitutive nitric oxide synthase (cNOS activity in Langerhans islets from streptozotocin diabetic rats

    Directory of Open Access Journals (Sweden)

    Fonovich de Schroeder T.M.

    1998-01-01

    Full Text Available Nitric oxide synthase activity was measured in Langerhans islets isolated from control and streptozotocin diabetic rats. The activity of the enzyme was linear up to 150 µg of protein from control rats and was optimal at 0.1 µM calcium, when it was measured after 45 min of incubation at 37oC in the presence of 200 µM arginine. Specific activity of the enzyme was 25 x 10-4 nmol [3H]citrulline 45 min-1 mg protein-1. Streptozotocin diabetic rats exhibited less enzyme activity both in total pancreas homogenate and in isolated Langerhans islets when compared to control animals. Nitric oxide synthase activity measured in control and diabetic rats 15 days after the last streptozotocin injection in the second group of animals corresponded only to a constitutive enzyme since it was not inhibited by aminoguanidine in any of the mentioned groups. Hyperglycemia in diabetic rats may be the consequence of impaired insulin release caused at least in part by reduced positive modulation mediated by constitutive nitric oxide synthase activity, which was dramatically reduced in islets severely damaged after streptozotocin treatment.

  17. Glucose-stimulated calcium dynamics in islets of Langerhans in acute mouse pancreas tissue slices.

    Directory of Open Access Journals (Sweden)

    Andraž Stožer

    Full Text Available In endocrine cells within islets of Langerhans calcium ions couple cell stimulation to hormone secretion. Since the advent of modern fluorimetry, numerous in vitro studies employing primarily isolated mouse islets have investigated the effects of various secretagogues on cytoplasmic calcium, predominantly in insulin-secreting beta cells. Due to technical limitations, insights of these studies are inherently limited to a rather small subpopulation of outermost cells. The results also seem to depend on various factors, like culture conditions and duration, and are not always easily reconcilable with findings in vivo. The main controversies regard the types of calcium oscillations, presence of calcium waves, and the level of synchronized activity. Here, we set out to combine the in situ acute mouse pancreas tissue slice preparation with noninvasive fluorescent calcium labeling and subsequent confocal laser scanning microscopy to shed new light on the existing controversies utilizing an innovative approach enabling the characterization of responses in many cells from all layers of islets. Our experiments reproducibly showed stable fast calcium oscillations on a sustained plateau rather than slow oscillations as the predominant type of response in acute tissue slices, and that calcium waves are the mechanistic substrate for synchronization of oscillations. We also found indirect evidence that even a large amplitude calcium signal was not sufficient and that metabolic activation was necessary to ensure cell synchronization upon stimulation with glucose. Our novel method helped resolve existing controversies and showed the potential to help answer important physiological questions, making it one of the methods of choice for the foreseeable future.

  18. Acrolein preferentially damages nucleolus eliciting ribosomal stress and apoptosis in human cancer cells.

    Science.gov (United States)

    Wang, Hsiang-Tsui; Chen, Tzu-Ying; Weng, Ching-Wen; Yang, Chun-Hsiang; Tang, Moon-Shong

    2016-12-06

    Acrolein (Acr) is a potent cytotoxic and DNA damaging agent which is ubiquitous in the environment and abundant in tobacco smoke. Acr is also an active cytotoxic metabolite of the anti-cancer drugs cyclophosphamide and ifosfamide. The mechanisms via which Acr exerts its anti-cancer activity and cytotoxicity are not clear. In this study, we found that Acr induces cytotoxicity and cell death in human cancer cells with different activities of p53. Acr preferentially binds nucleolar ribosomal DNA (rDNA) to form Acr-deoxyguanosine adducts, and induces oxidative damage to both rDNA and ribosomal RNA (rRNA). Acr triggers ribosomal stress responses, inhibits rRNA synthesis, reduces RNA polymerase I binding to the promoter of rRNA gene, disrupts nucleolar integrity, and impairs ribosome biogenesis and polysome formation. Acr causes an increase in MDM2 levels and phosphorylation of MDM2 in A549 and HeLa cells which are p53 active and p53 inactive, respectively. It enhances the binding of ribosomal protein RPL11 to MDM2 and reduces the binding of p53 and E2F-1 to MDM2 resulting in stabilization/activation of p53 in A549 cells and degradation of E2F-1 in A549 and HeLa cells. We propose that Acr induces ribosomal stress which leads to activation of MDM2 and RPL11-MDM2 binding, consequently, activates p53 and enhances E2F-1 degradation, and that taken together these two processes induce apoptosis and cell death.

  19. La célula de langerhans.

    Directory of Open Access Journals (Sweden)

    Ladys Sarmiento

    2002-12-01

    Full Text Available La célula de Langerhans es una presentadora de antígenos profesional que juega un papel clave en el inicio y en la regulación de la respuesta inmune. Se localiza en la epidermis y en otros epitelios estratificados desde donde emigra a los órganos linfoides secundarios para presentar a los linfocitos T aquellos antígenos que penetran por la piel e iniciar la respuesta inmune específica. Presentamos una serie de imágenes de microscopía de luz y electrónica de estas células tal y como se encuentran en la epidermis y su morfología después de emigrar al medio de cultivo. Se reseñan algunos factores que inducen su migración, así como los usos terapéuticos potenciales como moduladoras de la respuesta inmune, ya sea para generarla, como en el caso del tratamiento del melanoma; aumentarla, en infecciones causadas por microorganismos intracelulares, o evitarla para el tratamiento de alergias.

  20. Telomerase and Tel1p Preferentially Associate with Short Telomeres in S. cerevisiae

    Science.gov (United States)

    Sabourin, Michelle; Tuzon, Creighton T.; Zakian, Virginia A.

    2009-01-01

    SUMMARY In diverse organisms, telomerase preferentially elongates short telomeres. We generated a single short telomere in otherwise wild-type (WT) S. cerevisiae cells. The binding of the positive regulators Ku and Cdc13p was similar at short and WT-length telomeres. The negative regulators Rif1p and Rif2p were present at the short telomere, although Rif2p levels were reduced. Two telomerase holoenzyme components, Est1p and Est2p, were preferentially enriched at short telomeres in late S/G2 phase, the time of telomerase action. Tel1p, the yeast ATM-like checkpoint kinase, was highly enriched at short telomeres from early S through G2 phase and even into the next cell cycle. Nonetheless, induction of a single short telomere did not elicit a cell-cycle arrest. Tel1p binding was dependent on Xrs2p and required for preferential binding of telomerase to short telomeres. These data suggest that Tel1p targets telomerase to the DNA ends most in need of extension. PMID:17656141

  1. The Antidiabetic Activity of Curry Leaves “Murraya Koenigii” on the Glucose Levels, Kidneys, and Islets of Langerhans of Rats with Streptozotocin Induced Diabetes

    Directory of Open Access Journals (Sweden)

    Imad M Al-Ani

    2017-08-01

    Full Text Available Background: The aims of this study were to explore the antihyperglycemic effect of curry leaves, Murraya koenigii "MK" aqueous extract, and to examine its possible protective effects on the islets of Langerhans and kidneys of streptozotocin (STZ diabetic rats. Methods: Thirty healthy adult male Sprague Dawley rats were randomized into five groups (n=6; normal control, normal treated with "MK" control, diabetic control (non-treated with "MK", diabetic treated with 200 mg/kg MK aqueous leaf extract and diabetic treated with 400 mg/kg MK aqueous leaf extract. Blood glucose levels and body weight were monitored gravimetrically. The animals were sacrificed on the 30th day; the kidney and pancreatic tissues were processed for histological studies. Results: The diabetic group showed considerable loss of body weight and increase in blood glucose levels and degeneration of the glomeruli and renal convoluted tubules and atrophied islets with disintegration of β-cells. Treatment of diabetic rats with MK extract showed significant (p < 0.001 improvement in blood glucose levels and body weight gain. The MK extract also caused an improvement in tissue injury induced by STZ injection in the kidney and islets of Langerhans. Conclusions: These findings highlighted the beneficial effects of MK aqueous extract against cellular oxidative damage in STZ-induced diabetic rats.

  2. Preferential antitumor effect of the Src inhibitor dasatinib associated with a decreased proportion of aldehyde dehydrogenase 1-positive cells in breast cancer cells of the basal B subtype

    Directory of Open Access Journals (Sweden)

    Watanabe Mika

    2010-10-01

    Full Text Available Abstract Background Recent studies have suggested that the Src inhibitor dasatinib preferentially inhibits the growth of breast cancer cells of the basal-like subtype. To clarify this finding and further investigate combined antitumor effects of dasatinib with cytotoxic agents, a panel of breast cancer cell lines of various subtypes was treated with dasatinib and/or chemotherapeutic agents. Methods Seven human breast cancer cell lines were treated with dasatinib and/or seven chemotherapeutic agents. Effects of the treatments on c-Src activation, cell growth, cell cycle, apoptosis and the proportion of aldehyde dehydrogenase (ALDH 1-positive cells were examined. Results The 50%-growth inhibitory concentrations (IC50s of dasatinib were much lower in two basal B cell lines than those in the other cell lines. The IC50s of chemotherapeutic agents were not substantially different among the cell lines. Dasatinib enhanced antitumor activity of etoposide in the basal B cell lines. Dasatinib induced a G1-S blockade with a slight apoptosis, and a combined treatment of dasatinib with etoposide also induced a G1-S blockade in the basal B cell lines. Dasatinib decreased the expression levels of phosphorylated Src in all cell lines. Interestingly, dasatinib significantly decreased the proportion of ALDH1-positive cells in the basal B cell lines but not in the other cell lines. Conclusions The present study indicates that dasatinib preferentially inhibits the growth of breast cancer cells of the basal B subtype associated with a significant loss of putative cancer stem cell population. A combined use of dasatinib with etoposide additively inhibits their growth. Further studies targeting breast cancers of the basal B subtype using dasatinib with cytotoxic agents are warranted.

  3. Inhibition of Langerhans cell maturation by human papillomavirus type 16: a novel role for the annexin A2 heterotetramer in immune suppression1

    Science.gov (United States)

    Woodham, Andrew W.; Raff, Adam B.; Raff, Laura M.; Da Silva, Diane M.; Yan, Lisa; Skeate, Joseph G.; Wong, Michael K.; Lin, Yvonne G.; Kast, W. Martin

    2014-01-01

    High-risk human papillomaviruses (HPV) are sexually transmitted viruses causally associated with several cancers. During its natural life cycle, HPV16, the most common high-risk genotype, infects the epithelial basal cellsin a process facilitated through a recently identified receptor, the annexin A2 heterotetramer (A2t). During infection, HPV16 also interacts with Langerhans cells (LC), the antigen presenting cells of the epithelium, inducing immune suppression, which is mediated by the HPV16 L2 minor capsid protein. Despite the importance of these virus-immune cell interactions, the specific mechanisms of HPV16 entry into LC and HPV16-induced immune suppression remain undefined. An N-terminal peptide of HPV16 L2 (aa 108-126) has been shown to specifically interact with A2t. Here, we show that incubation of human LC with this peptide blocks binding of HPV16. Inhibiting this interaction with an A2t ligand or by siRNA downregulation of A2t, significantly decreases HPV16 internalization into LC in an L2-dependent manner. A2t is associated with suppression of LC maturation as demonstrated through attenuated secretion of Th1-associated cytokines and decreased surface expression of MHC II on LC exposed to A2t. Conversely, small molecule inhibition of A2t prevents HPV16-induced suppression of LC immune function as indicated by significantly increased secretion of inflammatory cytokines and surface expression of CD86 in HPV16 treated LC pre-exposed to A2t inhibitors. These results demonstrate that HPV16 suppresses LC maturation through an interaction with A2t, revealing a novel role for this protein. PMID:24719459

  4. Preferential localization of Lactococcus lactis cells entrapped in a caseinate/alginate phase separated system.

    Science.gov (United States)

    Léonard, Lucie; Gharsallaoui, Adem; Ouaali, Fahima; Degraeve, Pascal; Waché, Yves; Saurel, Rémi; Oulahal, Nadia

    2013-09-01

    This study aimed to entrap bioprotective lactic acid bacteria in a sodium caseinate/sodium alginate aqueous two-phase system. Phase diagram at pH=7 showed that sodium alginate and sodium caseinate were not miscible when their concentrations exceeded 1% (w/w) and 6% (w/w), respectively. The stability of the caseinate/alginate two-phase system was also checked at pH values of 6.0 and 5.5. Lactococcus lactis subsp. lactis LAB3 cells were added in a 4% (w/w) caseinate/1.5% (w/w) alginate two-phase system at pH=7. Fluorescence microscopy allowed to observe that the caseinate-rich phase formed droplets dispersed in a continuous alginate-rich phase. The distribution of bacteria in such a system was observed by epifluorescence microscopy: Lc. lactis LAB3 cells stained with Live/Dead(®) Baclight kit™ were located exclusively in the protein phase. Since zeta-potential measurements indicated that alginate, caseinate and bacterial cells all had an overall negative charge at pH 7, the preferential adhesion of LAB cells was assumed to be driven by hydrophobic effect or by depletion phenomena in such biopolymeric systems. Moreover, LAB cells viability was significantly higher in the ternary mixture obtained in the presence of both caseinate and alginate than in single alginate solution. Caseinate/alginate phase separated systems appeared thus well suited for Lc. lactis LAB3 cells entrapment. Copyright © 2013 Elsevier B.V. All rights reserved.

  5. Transplante isogênico de ilhotas de Langerhans no fígado de ratos: metodologia para separação e purificação das ilhotas de Langerhans Isogenic islet transplantation on the rat liver: Method for isolation and purification of the rat islets

    Directory of Open Access Journals (Sweden)

    Eleazar CHAIB

    2000-01-01

    Full Text Available A maior indicação do transplante de pâncreas ou de ilhotas de Langerhans é o diabetes mellitus do tipo I. O processo deve suprir as necessidades de insulina mantendo os níveis glicêmicos dentro da normalidade. Estudou-se o transplante isogênico de ilhotas de Langerhans no fígado de ratos WAG-RT1u. Com o método de separação e purificação das ilhotas de Langerhans obteve-se 2.834 ± 551,64 ilhotas com pureza de 83 ± 2,45%. O transplante de 2.834 ± 551,64 ilhotas de Langerhans no fígado destes animais, normalizou a glicemia que chegou a 35 mmol/L após indução do diabetes pela estreptozotocina, ficando em 9,62 ± 2,65 mmol/L nos primeiros 10 dias após o enxerto e 7,43 ± 0,27 mmol/L nos dias subseqüentes (P The major indication for pancreas or islet transplantation is diabetes mellitus type I. This process has to supply the insulin necessity keeping glucose under control. We have studied isogenic islet transplantation on the rat (WAG-RT1u liver. The method of isolation and purification of the islets obtained 2.834 ± 551,64 islets with purity of 83 ± 2,45%. Diabetes was induced by streptozotocin and seric glucose prior transplantation was 35 mmol/L. The islet transplantation of 2.834 ± 551,64 islets in the rat liver has normalized glucose test from 9,62 ± 2,65 mmol/L 10 days after transplantation to 7,43 ± 0,27 mmol/L later in the follow-up (P <0,05. The median survival time of the islets was 73 days. In conclusion both the method of isolation and purification of the islets and islet transplantation was effective in the control of the diabetes induced by streptozotocin with median survival time of both islet and rat more than 73 days when rats were sacrificied.

  6. Differential Recruitment of Dendritic Cells Subsets to Lymph Nodes Correlates with a Protective or Permissive T-Cell Response during Leishmania (Viannia) Braziliensis or Leishmania (Leishmania) Amazonensis Infection.

    Science.gov (United States)

    Carvalho, A K; Carvalho, K; Passero, L F D; Sousa, M G T; da Matta, V L R; Gomes, C M C; Corbett, C E P; Kallas, G E; Silveira, F T; Laurenti, M D

    2016-01-01

    Leishmania (L.) amazonensis (La) and L. (V.) braziliensis (Lb) are responsible for a large clinical and immunopathological spectrum in human disease; while La may be responsible for anergic disease, Lb infection leads to cellular hypersensitivity. To better understand the dichotomy in the immune response caused by these Leishmania species, we evaluated subsets of dendritic cells (DCs) and T lymphocyte in draining lymph nodes during the course of La and Lb infection in BALB/c mice. Our results demonstrated a high involvement of DCs in La infection, which was characterized by the greater accumulation of Langerhans cells (LCs); conversely, Lb infection led to an increase in dermal DCs (dDCs) throughout the infection. Considering the T lymphocyte response, an increase of effector, activated, and memory CD4(+) T-cells was observed in Lb infection. Interleukin- (IL-) 4- and IL-10-producing CD4(+)and CD8(+) T-cells were present in both La and Lb infection; however, interferon- (IFN-) γ-producing CD4(+)and CD8(+) T-cells were detected only in Lb infection. The results suggest that during Lb infection, the dDCs were the predominant subset of DCs that in turn was associated with the development of Th1 immune response; in contrast La infection was associated with a preferential accumulation of LCs and total blockage of the development of Th1 immune response.

  7. Preliminary study on the evaluation of Langerhans cell histiocytosis using F-18-fluoro-deoxy-glucose PET/CT

    Institute of Scientific and Technical Information of China (English)

    Zhou Wenlan; Wu Hubing; Han Yanjiang; Wang Shaobo; Dong Ye; Wang Quanshi

    2014-01-01

    Background Limited number of studies have been reported regarding the utilization of F-18-fluoro-deoxy-glucose (F-18-FDG) positron emission tomography/computed tomography (F-18-FDG PET/CT) in Langerhans cell histiocytosis (LCH).The aim of this study was to assess the role of F-18-FDG PET/CT in the diagnosis and treatment of LCH.Methods Eight newly diagnosed and seven recurrent patients with LCH received F-18-FDG PET/CT scans.The diagnosis of LCH was established by pathology,multi-modality imaging,and clinical follow-up.Results F-18-FDG PET/CT was positive in 14 patients with 13 true positives and one false positive.All 45 LCH lesions were F-18-FDG avid including six small bone lesions <1.0 cm in diameter.The mean maximal standardized uptake value (SUVmax) was 7.13±4.91.F-18-FDG uptake showed no significant difference between newly diagnosed lesions vs recurrent lesions (SUVmax:6.50±2.97 vs.7.93±6.60,t=-0.901,P=0.376).Among 45 LCH lesions,68.9% (31/45) were found in bones and 31.1% (14/45) in soft tissue.The most commonly involved bones were the pelvis and vertebrae.There was no significant difference in F-18-FDG uptake between bone lesions vs.non-bone lesions (SUVmax:6.30±2.87 vs.8.97±7.58,t=1.277,P=0.221).In two patients,changes in F-18-FDG uptake on serial PET/CT scans reflected response of lesions to treatment.Conclusions The present study suggests that F-18-FDG PET/CT may be useful for diagnosis and assessing the treatment response of LCH.Because of the small sample size,further research is warranted to confirm our findings.

  8. Ultraviolet A irradiation of the eye activates a nitric oxide-dependent hypothalamo-pituitary pro-opiomelanocortin pathway and modulates the functions of Langerhans cells.

    Science.gov (United States)

    Hiramoto, Keiichi

    2009-06-01

    Ultraviolet A (UV-A) radiation decreases Langerhans cells (LC) in the skin specifically at the site of exposure. Unexpectedly, UV-A irradiation of the eye has been found systemically downregulating epidermal LC in mice. Male C57BL/6j mice and an inducible type of nitric oxide synthase knockout mice (iNOS(-/-)) were used in this study. The eye or ear was locally exposed to UV-A after covering the remaining body surface with aluminum foil at a dose of 110 kJ/m(2) using a sunlamp. Localized UV-A irradiation of the eye downregulated epidermal LC. The hypophysectomy strongly inhibited the UV-A-induced downregulation of LC. To elucidate the pathway by UV-A irradiation of the eye, the effect of a bilateral ciliary ganglionectomy and denervation of the optic nerves was examined. Optic nerve denervation strongly inhibited LC downregulation in response to localized irradiation of the eye. Furthermore, no LC downregulation in response to localized UV-A irradiation of the eye was observed in iNOS(-/-) mice. These results clearly indicate that a signal evoked by UV-A irradiation of the eye is transmitted in a nitric oxide-dependent manner through the optic nerves to the hypothalamo-pituitary pro-opiomelanocortin system.

  9. 111In-Octreotide and 99mTc-MDP scintigraphy in the detection of bone lesions in Langerhans cell histiocytosis

    International Nuclear Information System (INIS)

    Hervas, I.; Bello, P.; Gonzalez-Cabezas, P.; Flores, D.; Perez-Velasco, R.; Torres, I.; Castel, V.; Mateo, A.; Canete, A.

    2002-01-01

    Aim: Langerhans cell histiocytosis (LCH) is a granulomatous disease which can involve multiples sites of the body. Diagnostic imaging is of utmost importance in the management of these patients. Since now radiographic skeletal survey and bone scintigraphy (BS) have been used to assess bone involvement (both with low specificity). Magnetic resonance and CT have been used to assess visceral involvement but with the limitation that can not give information about the functional status. Recently two groups of investigators (Lastoria et al. and Calming et al.) have proposed somatostatin receptor scintigraphy (SSRS) to detect active lesions and for monitoring the response to treatment, due to the somatostatin analogue octreotide binds to the cell membrane of activated lymphocytes expressing somatostatine receptors. The aim of this study is to assess bone and somatostatine receptor scintigraphy in the detection of bone involvement in LCH in children. Visceral involvement has not been assessed due to none of the patients presented it at the moment of the SRS. Methods: 17 scintigraphies (11 SSRS and 6 BS) were performed in seven patients (3 girls and 4 boys) aged at diagnosis: 18 month- 12 years (mean age 6,2 years). The findings obtained in the scintigraphies were compared with clinical evolution and other imaging techniques. Results: All the BS detected the diagnosed lesions, that decreased the uptake after the treatment. In three cases BS detected one unknown bone lesion. Two SSRS could not detect a lesion on right rib in two patients, both at the moment of diagnosis. SSRS was true negative in one patient (clinical and other imaging remission) and true positive in the other four cases. SSRS detected three new unknown bone lesions. SRSS showed decreased uptake after treatment and increased uptake in the relapses. Conclusions: Somatostatin receptor and Bone scintigraphy can be used to detect active LCH bone lesions in children and can help in monitoring the response to

  10. Targeted detection of in vivo endogenous DNA base damage reveals preferential base excision repair in the transcribed strand.

    Science.gov (United States)

    Reis, António M C; Mills, Wilbur K; Ramachandran, Ilangovan; Friedberg, Errol C; Thompson, David; Queimado, Lurdes

    2012-01-01

    Endogenous DNA damage is removed mainly via base excision repair (BER), however, whether there is preferential strand repair of endogenous DNA damage is still under intense debate. We developed a highly sensitive primer-anchored DNA damage detection assay (PADDA) to map and quantify in vivo endogenous DNA damage. Using PADDA, we documented significantly higher levels of endogenous damage in Saccharomyces cerevisiae cells in stationary phase than in exponential phase. We also documented that yeast BER-defective cells have significantly higher levels of endogenous DNA damage than isogenic wild-type cells at any phase of growth. PADDA provided detailed fingerprint analysis at the single-nucleotide level, documenting for the first time that persistent endogenous nucleotide damage in CAN1 co-localizes with previously reported spontaneous CAN1 mutations. To quickly and reliably quantify endogenous strand-specific DNA damage in the constitutively expressed CAN1 gene, we used PADDA on a real-time PCR setting. We demonstrate that wild-type cells repair endogenous damage preferentially on the CAN1 transcribed strand. In contrast, yeast BER-defective cells accumulate endogenous damage preferentially on the CAN1 transcribed strand. These data provide the first direct evidence for preferential strand repair of endogenous DNA damage and documents the major role of BER in this process.

  11. Cytotoxic T cells are preferentially activated in the duodenal epithelium from patients with florid coeliac disease.

    Science.gov (United States)

    Buri, Caroline; Burri, Philipp; Bähler, Peter; Straumann, Alex; Müller-Schenker, Beatrice; Birrer, Stefan; Mueller, Christoph

    2005-06-01

    Villous atrophy and increased numbers of intraepithelial T cells in duodenal biopsies represent a hallmark of coeliac disease. In the present study, an attempt has been made to define whether cytotoxic cell subsets are activated in situ in the affected mucosa of susceptible individuals early after ingestion of a gluten-containing diet. Duodenal biopsies from 11 patients with coeliac disease who repeatedly underwent endoscopic biopsy after ingestion of individually dosed amounts of gluten were used for immunohistochemistry and in situ hybridization. To identify the cell subsets expressing perforin mRNA and protein, in situ hybridization and FACS analyses were performed on cells isolated from fresh biopsies. Compared with normal mucosa, the number of intraepithelial lymphocytes containing perforin mRNA and protein increased significantly in tissue samples showing moderate or florid coeliac disease and closely paralleled the severity of morphological alteration, whereas the frequency of perforin-expressing lamina propria lymphocytes increased only moderately. Cells isolated from florid biopsies that expressed perforin mRNA and protein were preferentially T-cell receptor (TCR) alphabeta T cells. The increase in both the absolute number and the percentage of lymphocytes expressing perforin mRNA indicates in situ activation of lymphocytes within the epithelial compartment in florid coeliac disease upon ingestion of a gluten-containing diet in patients predisposed to coeliac disease. Copyright 2005 Pathological Society of Great Britain and Ireland

  12. Transcriptional regulation of pancreas development and β-cell function [Review].

    Science.gov (United States)

    Fujitani, Yoshio

    2017-05-30

    A small number of cells in the adult pancreas are endocrine cells. They are arranged in clusters called islets of Langerhans. The islets make insulin, glucagon, and other endocrine hormones, and release them into the blood circulation. These hormones help control the level of blood glucose. Therefore, a dysfunction of endocrine cells in the pancreas results in impaired glucose homeostasis, or diabetes mellitus. The pancreas is an organ that originates from the evaginations of pancreatic progenitor cells in the epithelium of the foregut endoderm. Pancreas organogenesis and maturation of the islets of Langerhans occurs via a coordinated and complex interplay of transcriptional networks and signaling molecules, which guide a stepwise and repetitive process of the propagation of progenitor cells and their maturation, eventually resulting in a fully functional organ. Increasing our understanding of the extrinsic, as well as intrinsic mechanisms that control these processes should facilitate the efforts to generate surrogate β cells from ES or iPS cells, or to reactivate the function of important cell types within pancreatic islets that are lost in diabetes.

  13. Comparação das contagens das células de Langerhans de tecidos contendo carcinoma anal em doentes com e sem infecção pelo HIV Comparison of Langerhans cells counts from tissues containing anal carcinoma of patients with and without HIV infection

    Directory of Open Access Journals (Sweden)

    Sidney Roberto Nadal

    2006-09-01

    Full Text Available INTRODUÇÃO: As células de Langerhans (LC são derivadas da medula óssea e constituem-se nas principais apresentadoras de antígeno da pele.conferindo desta forma, a resposta imune cutânea. Seu número está reduzido nos imunodeprimidos, incluindo na infecção pelo HIV, e a presença do tumor inibe sua migração, impedindo que os linfócitos T promovam regressão das células neoplásicas. OBJETIVO: Conhecer as diferenças entre as contagens de LC no tecido tumoral de doentes de carcinomas anais com e sem AIDS. MÉTODO: Avaliamos 24 doentes, sendo 14 com HIV e 10 outros sem HIV . O tratamento para o carcinoma foi semelhante nos dois grupos. Cortes retirados de blocos parafinados submetidos ao teste imunoistoquímico com anticorpo anti-CD68. Contamos as LC com método da histometria e os comparamos aos números obtidos com amostras previamente conhecidas de doentes sem doença infecciosa anorretal ou infecção pelo HIV. Revisamos também a evolução e as contagens séricas de linfócitos T CD4+ de doentes HIV-positivos. RESULTADOS: Observamos que o carcinoma anal foi mais freqüente em mulheres HIV-negativas e em homens HIV-positivos e que esses ultimos eram mais jovens. As LC foram menos numerosas nos doentes HIV-positivos e as maiores contagens estavam associadas com pior evolução. Os doentes HIV-positivos com os níveis mais baixos de linfócitos T CD4+ também tiveram as piores evoluções. CONCLUSÃO: Concluímos que as LC estavam diminuídas nos doentes HIV-positivos, portadores de carcinoma anal, quando comparados aos soronegativos.Langerhans cells (LC are bone marrow derived dendritic cells that represent the major antigen-presenting cells (APC in the skin, thus representing an integral part of the cutaneous immune response. Immunossupression decreases their number, including HIV infection, and skin tumors products are sufficient to immobilize LC within the tumor, preventing their migration to lymph nodes. This reduces the

  14. The pituitary gland in patients with Langerhans cell histiocytosis: a clinical and radiological evaluation.

    Science.gov (United States)

    Kurtulmus, Neslihan; Mert, Meral; Tanakol, Refik; Yarman, Sema

    2015-04-01

    Langerhans cell histiocytosis (LCH) is a rare disease in which the most common endocrine manifestation is diabetes insipidus (DI). Data on anterior pituitary function in patients with LCH are limited. Thus, the present study investigated anterior pituitary function in LCH patients with DI via the evaluation of clinical and radiological findings at disease onset and during follow-up. The present study retrospectively evaluated nine patients with LCH (five males and four females). All diagnoses of LCH were made following histological and/or immunophenotypic analyses of tissue biopsies, bronchoalveolar lavage, or cerebrospinal fluid (CSF). Basal and, if necessary, dynamic pituitary function tests were used to assess anterior pituitary function, and magnetic resonance imaging (MRI) scans were used to image the pituitary. The LCH treatment modality was based on organ involvement. The mean age at onset of DI was 27.6 years (range 15-60 years). One patient (11%) exhibited single organ involvement, while eight patients (89%) displayed multisystem organ involvement. On admittance, one patient had hypogonadotropic hypogonadism, one patient exhibited panhypopituitarism [hypogonadotropic hypogonadism, central hypothyroidism, hypocortisolism, and growth hormone (GH) deficiency], and four patients (44%) displayed hyperprolactinemia. The MRI data revealed infundibular enlargement in seven patients (78%), a thalamic mass in one patient (11%), and the absence of the bright spot in all patients. A single patient (11%) showed a mass in the pons that had a partially empty sella. The patients were treated with radiation therapy (RT), chemotherapy (CT), or a combination of both (RT+CT) and were followed up for a median of 91.8 months (range 2-318 months). Seven patients were assessed during the follow-up period, of whom four patients (57.1%) developed anterior pituitary hormone deficiency, three (43%) were diagnosed with GH deficiency, and one (14%) exhibited gonadotropin deficiency

  15. {sup 18}F-fluorodeoxyglucose positron emission tomography-computed tomography in the management of adult multisystem Langerhans cell histiocytosis

    Energy Technology Data Exchange (ETDEWEB)

    Obert, Julie [Universite Paris Diderot, Paris (France); Assistance Publique-Hopitaux de Paris, Centre National de Reference de l' Histiocytose Langerhansienne, Service de Pneumologie, Hopital Saint-Louis, Paris (France); Vercellino, Laetitia [Assistance Publique-Hopitaux de Paris, Service de Medecine Nucleaire, Hopital Saint-Louis, Paris (France); Van der Gucht, Axel [Universite Paris Diderot, Paris (France); Assistance Publique-Hopitaux de Paris, Service de Medecine Nucleaire, Hopital Saint-Louis, Paris (France); De Margerie-Mellon, Constance [Universite Paris Diderot, Paris (France); Assistance Publique-Hopitaux de Paris, Service de Radiologie, Hopital Saint-Louis, Paris (France); Bugnet, Emmanuelle; Lorillon, Gwenael [Assistance Publique-Hopitaux de Paris, Centre National de Reference de l' Histiocytose Langerhansienne, Service de Pneumologie, Hopital Saint-Louis, Paris (France); Chevret, Sylvie [Universite Paris Diderot, Paris (France); Assistance Publique-Hopitaux de Paris, Service de Biostatistique et Information Medicale, Hopital Saint-Louis, Paris (France); Biostatistics and Clinical Epidemiology Research Team, U1153 CRESS, Paris (France); Tazi, Abdellatif [Universite Paris Diderot, Paris (France); Assistance Publique-Hopitaux de Paris, Centre National de Reference de l' Histiocytose Langerhansienne, Service de Pneumologie, Hopital Saint-Louis, Paris (France); Biostatistics and Clinical Epidemiology Research Team, U1153 CRESS, Paris (France)

    2017-04-15

    The standard evaluation of multisystem Langerhans cell histiocytosis (LCH) includes a clinical evaluation, laboratory tests and a skeleton/skull X-ray survey, with chest high-resolution computed tomography (HRCT) in the case of pulmonary involvement. Preliminary reports suggest that {sup 18}F-fluorodeoxyglucose positron emission tomography-computed tomography ({sup 18}F-FDG PET-CT) may be useful for evaluating patients with LCH. Fourteen consecutive adult patients with multisystem LCH were included in this retrospective study, and were evaluated using standard procedures and {sup 18}F-FDG PET-CT. The two sets of findings were compared both at baseline and during follow-up. Serial HRCT and pulmonary function tests were used to evaluate outcome in patients with lung involvement. At the baseline evaluation, PET-CT identified every LCH localization found with the standard evaluation (except a mild cecum infiltration). PET-CT showed additional lesions in seven patients, mostly involving bones, and differentiated inactive from active lesions. Thyroid {sup 18}F-FDG uptake was identified in three cases. No pituitary stalk {sup 18}F-FDG uptake was observed in patients with pituitary LCH. Only 3/12 (25 %) patients with pulmonary LCH displayed moderate pulmonary {sup 18}F-FDG uptake. During follow-up, variations (≥50 % of maximum standardized uptake) in bone {sup 18}F-FDG uptake intensity were correlated with disease state and response to treatment. The absence of lung {sup 18}F-FDG uptake did not preclude lung function improvement after treatment. Except for cases with pulmonary and pituitary involvement, {sup 18}F-FDG PET-CT could replace the standard evaluation for staging of adult patients with multisystem LCH. Serial PET-CT scans are useful for evaluating treatment responses, particularly in cases with bone LCH involvement. (orig.)

  16. Preferential lentiviral targeting of astrocytes in the central nervous system.

    Directory of Open Access Journals (Sweden)

    Michael Fassler

    Full Text Available The ability to visualize and genetically manipulate specific cell populations of the central nervous system (CNS is fundamental to a better understanding of brain functions at the cellular and molecular levels. Tools to selectively target cells of the CNS include molecular genetics, imaging, and use of transgenic animals. However, these approaches are technically challenging, time consuming, and difficult to control. Viral-mediated targeting of cells in the CNS can be highly beneficial for studying and treating neurodegenerative diseases. Yet, despite specific marking of numerous cell types in the CNS, in vivo selective targeting of astrocytes has not been optimized. In this study, preferential targeting of astrocytes in the CNS was demonstrated using engineered lentiviruses that were pseudotyped with a modified Sindbis envelope and displayed anti-GLAST IgG on their surfaces as an attachment moiety. Viral tropism for astrocytes was initially verified in vitro in primary mixed glia cultures. When injected into the brains of mice, lentiviruses that displayed GLAST IgG on their surface, exhibited preferential astrocyte targeting, compared to pseudotyped lentiviruses that did not incorporate any IgG or that expressed a control isotype IgG. Overall, this approach is highly flexible and can be exploited to selectively target astrocytes or other cell types of the CNS. As such, it can open a window to visualize and genetically manipulate astrocytes or other cells of the CNS as means of research and treatment.

  17. Effects of Energy Dissipation Rate on Islets of Langerhans: Implications for Isolation and Transplantation

    Science.gov (United States)

    Shenkman, Rustin M.; Godoy-Silva, Ruben; Papas, Klearchos K.; Chalmers, Jeffrey J.

    2010-01-01

    Acute physical stresses can occur in the procurement and isolation process and potentially can contribute to islet death or malfunction upon transplantation. A contractional flow device, previously used to subject suspended cells to well-defined hydrodynamic forces, has been modified and used to assess the vulnerability of porcine islets of Langerhans to hydrodynamic forces. The flow profiles and velocity gradients in this modified device were modeled using commercial CFD software and characterized, as in previous studies, with the scalar parameter, energy dissipation rate (EDR). Porcine islets were stressed in a single pass at various stress levels (i.e., values of EDR). Membrane integrity, oxygen uptake rate, caspase 3/7 activity, and insulin release were not affected by the levels of fluid stress tested up to an EDR of 2 × 103 W/m3. Visual observation of the stressed islets suggested that cells at the islet exterior were peeled away at EDR greater than 10,000 W/m3, however, this observation could not be confirmed using image analysis software, which determined the ratio of surface perimeter to total area. The result of this study suggests an upper limit in fluid stress to which islets can be subjected. Such upper limits assist in the design and operation of future islet processing equipment and processes. PMID:19191351

  18. Preferential repair of nuclear matrix associated DNA in xeroderma pigmentosum complementation group C

    International Nuclear Information System (INIS)

    Mullenders, L.H.F.; Kesteren, A.C. van; Bussmann, C.J.M.; Zeeland, A.A. van; Natarajan, A.T.

    1984-01-01

    The distribution of ultraviolet-induced DNA repair patches in the genome of xeroderma pigmentosum cells of complementation group C was investigated by determining the molecular weight distribution of repair labeled DNA and prelabeled DNA in alkaline sucrose gradients after treatment with the dimer-specific endonuclease V of bacteriophage T 4 . The results suggest that DNA-repair synthesis in xeroderma pigmentosum cells of complementation group C occurs in localized regions of the genome. Analysis of the spatial distribution of ultraviolet-induced repair patches in DNA loops attached to the nuclear matrix revealed that in xeroderma pigmentosum cells of complementation group C repair patches are preferentially situated near the attachment sites of DNA loops at the nuclear matrix. In normal human fibroblasts the authors observed no enrichment of repair-labeled DNA at the nuclear matrix and repair patches appeared to be distributed randomly along the DNA loops. The enrichment of repair-labeled DNA at the nuclear matrix in xeroderma pigmentosum cells of complementation group C may indicate that the residual DNA-repair synthesis in these cells occurs preferentially in regions of the genome. (Auth.)

  19. Farnesyltransferase inhibitor tipifarnib (R115777) preferentially inhibits in vitro autonomous erythropoiesis of polycythemia vera patient cells.

    Science.gov (United States)

    Larghero, Jérôme; Gervais, Nathalie; Cassinat, Bruno; Rain, Jean-Didier; Schlageter, Marie-Hélène; Padua, Rose Ann; Chomienne, Christine; Rousselot, Philippe

    2005-05-01

    Polycythemia vera (PV) is an acquired myeloproliferative disorder with primary expansion of the red cell mass leading to an increased risk of thrombosis and less frequently to myelofibrosis and secondary acute leukemia. Standard therapies include cytoreduction with either phlebotomy or chemotherapeutic agents and antithrombotic drugs. Because long-term exposure to cytotoxic chemotherapy may increase the risk of acute transformation, new therapeutic options are needed. Tipifarnib is a nonpeptidomimetic inhibitor of farnesyl transferase that was developed as a potential inhibitor of RAS signaling. In the present study we report that tipifarnib used at pharmacologically achievable concentrations strongly inhibits the erythroid burst-forming unit (BFU-E) autonomous growth that characterizes patients with PV. Moreover, at low tipifarnib concentrations (0.15 muM), the inhibitory effect was preferentially observed in PV BFU-E progenitors and not in normal BFU-E progenitors and was not rescued by erythropoietin (EPO). Thus tipifarnib may specifically target PV stem cells and may be of clinical interest in the treatment of patients with PV.

  20. 18F-fluorodeoxyglucose positron emission tomography/computed tomography for primary thyroid langerhans histiocytosis: A case report and literature review

    International Nuclear Information System (INIS)

    Long, Qi; Shaoyan, Wang; Hui, Wang

    2015-01-01

    Langerhans cell histiocytosis (LCH) is a rare clonal proliferative disease, with an incidence rate of 4.0–5.4/1 million individuals. LCH encompasses a spectrum of disorders with diverse clinical presentations ranging from a single organ to multiple organ involvement. LCH rarely involves the thyroid gland. We presented a case with LCH of thyroid gland. The patient had painless progressive neck enlargement and then diabetes insipidus. Ultrasonic scan and magnetic resonance imaging scan revealed nodular goiter and pituitary stalk enlargement, respectively. Histopathological analysis revealed features of histiocytoid cells. 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) was performed in order to rule out the presence of whole body infiltration. 18F-FDG PET/CT also demonstrated increased uptake in the thickening pituitary stalk and maxillofacial skin lesion, in addition to the bilateral thyroid nodules, CT showed the left lung nodule and the skull destruction without 18F-FDG uptake. This report emphasizes the role of 18F-FDG PET/CT in multiple organs involvement of patients with LCH

  1. Langerhans cells in 60 odontogenic keratocysts

    Directory of Open Access Journals (Sweden)

    Chun-Han Chang

    2017-09-01

    Conclusion: There is a significant association of inflammation grade with the number of LCs in OKCs. The scarce LCs in the lining epithelia of OKCs without inflammation suggests the loss of immunosurveillance ability against the OKC lining epithelial cells; this can explain why OKCs have aggressive clinical behavior, a great growth potential, and a high recurrence rate.

  2. An Aqueous Extract of Marine Microalgae Exhibits Antimetastatic Activity through Preferential Killing of Suspended Cancer Cells and Anticolony Forming Activity

    Science.gov (United States)

    Somasekharan, Syam Prakash; El-Naggar, Amal; Sorensen, Poul H.

    2016-01-01

    Research on marine natural products as potential anticancer agents is still limited. In the present study, an aqueous extract of a Canadian marine microalgal preparation was assessed for anticancer activities using various assays and cell lines of human cancers, including lung, prostate, stomach, breast, and pancreatic cancers, as well as an osteosarcoma. In vitro, the microalgal extract exhibited marked anticolony forming activity. In addition, it was more toxic, as indicated by increased apoptosis, to nonadherent cells (grown in suspension) than to adherent cells. In vivo, an antimetastatic effect of the extract was observed in NOD-SCID mice carrying subrenal capsule xenografts of PC3 prostate cancer cells. The results of the present study suggest that the antimetastatic effect of the aqueous microalgal extract is based on inhibition of colony forming ability of cancer cells and the preferential killing of suspended cancer cells. Further research aimed at identification of the molecular basis of the anticancer activities of the microalgal extract appears to be warranted. PMID:27656243

  3. An Aqueous Extract of Marine Microalgae Exhibits Antimetastatic Activity through Preferential Killing of Suspended Cancer Cells and Anticolony Forming Activity

    Directory of Open Access Journals (Sweden)

    Syam Prakash Somasekharan

    2016-01-01

    Full Text Available Research on marine natural products as potential anticancer agents is still limited. In the present study, an aqueous extract of a Canadian marine microalgal preparation was assessed for anticancer activities using various assays and cell lines of human cancers, including lung, prostate, stomach, breast, and pancreatic cancers, as well as an osteosarcoma. In vitro, the microalgal extract exhibited marked anticolony forming activity. In addition, it was more toxic, as indicated by increased apoptosis, to nonadherent cells (grown in suspension than to adherent cells. In vivo, an antimetastatic effect of the extract was observed in NOD-SCID mice carrying subrenal capsule xenografts of PC3 prostate cancer cells. The results of the present study suggest that the antimetastatic effect of the aqueous microalgal extract is based on inhibition of colony forming ability of cancer cells and the preferential killing of suspended cancer cells. Further research aimed at identification of the molecular basis of the anticancer activities of the microalgal extract appears to be warranted.

  4. Non-preferential Trading Clubs

    DEFF Research Database (Denmark)

    Raimondos-Møller, Pascalis; Woodland, Alan D.

    2006-01-01

    This paper examines the welfare implications of non-discriminatory tariff reforms by a subset of countries, which we term a non-preferential trading club. We show that there exist coordinated tariff reforms, accompanied by appropriate income transfers between the member countries, that unambiguou......This paper examines the welfare implications of non-discriminatory tariff reforms by a subset of countries, which we term a non-preferential trading club. We show that there exist coordinated tariff reforms, accompanied by appropriate income transfers between the member countries...

  5. Palbociclib in Treating Patients With Relapsed or Refractory Rb Positive Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Activating Alterations in Cell Cycle Genes (A Pediatric MATCH Treatment Trial)

    Science.gov (United States)

    2018-05-15

    Advanced Malignant Solid Neoplasm; RB1 Positive; Recurrent Childhood Ependymoma; Recurrent Ewing Sarcoma; Recurrent Glioma; Recurrent Hepatoblastoma; Recurrent Kidney Wilms Tumor; Recurrent Langerhans Cell Histiocytosis; Recurrent Malignant Germ Cell Tumor; Recurrent Malignant Glioma; Recurrent Medulloblastoma; Recurrent Neuroblastoma; Recurrent Non-Hodgkin Lymphoma; Recurrent Osteosarcoma; Recurrent Peripheral Primitive Neuroectodermal Tumor; Recurrent Rhabdoid Tumor; Recurrent Rhabdomyosarcoma; Recurrent Soft Tissue Sarcoma; Refractory Ependymoma; Refractory Ewing Sarcoma; Refractory Glioma; Refractory Hepatoblastoma; Refractory Langerhans Cell Histiocytosis; Refractory Malignant Germ Cell Tumor; Refractory Malignant Glioma; Refractory Medulloblastoma; Refractory Neuroblastoma; Refractory Non-Hodgkin Lymphoma; Refractory Osteosarcoma; Refractory Peripheral Primitive Neuroectodermal Tumor; Refractory Rhabdoid Tumor; Refractory Rhabdomyosarcoma; Refractory Soft Tissue Sarcoma

  6. Preferential sampling in veterinary parasitological surveillance

    Directory of Open Access Journals (Sweden)

    Lorenzo Cecconi

    2016-04-01

    Full Text Available In parasitological surveillance of livestock, prevalence surveys are conducted on a sample of farms using several sampling designs. For example, opportunistic surveys or informative sampling designs are very common. Preferential sampling refers to any situation in which the spatial process and the sampling locations are not independent. Most examples of preferential sampling in the spatial statistics literature are in environmental statistics with focus on pollutant monitors, and it has been shown that, if preferential sampling is present and is not accounted for in the statistical modelling and data analysis, statistical inference can be misleading. In this paper, working in the context of veterinary parasitology, we propose and use geostatistical models to predict the continuous and spatially-varying risk of a parasite infection. Specifically, breaking with the common practice in veterinary parasitological surveillance to ignore preferential sampling even though informative or opportunistic samples are very common, we specify a two-stage hierarchical Bayesian model that adjusts for preferential sampling and we apply it to data on Fasciola hepatica infection in sheep farms in Campania region (Southern Italy in the years 2013-2014.

  7. A generalized theory of preferential linking

    Science.gov (United States)

    Hu, Haibo; Guo, Jinli; Liu, Xuan; Wang, Xiaofan

    2014-12-01

    There are diverse mechanisms driving the evolution of social networks. A key open question dealing with understanding their evolution is: How do various preferential linking mechanisms produce networks with different features? In this paper we first empirically study preferential linking phenomena in an evolving online social network, find and validate the linear preference. We propose an analyzable model which captures the real growth process of the network and reveals the underlying mechanism dominating its evolution. Furthermore based on preferential linking we propose a generalized model reproducing the evolution of online social networks, and present unified analytical results describing network characteristics for 27 preference scenarios. We study the mathematical structure of degree distributions and find that within the framework of preferential linking analytical degree distributions can only be the combinations of finite kinds of functions which are related to rational, logarithmic and inverse tangent functions, and extremely complex network structure will emerge even for very simple sublinear preferential linking. This work not only provides a verifiable origin for the emergence of various network characteristics in social networks, but bridges the micro individuals' behaviors and the global organization of social networks.

  8. Comparing perceptual and preferential decision making.

    Science.gov (United States)

    Dutilh, Gilles; Rieskamp, Jörg

    2016-06-01

    Perceptual and preferential decision making have been studied largely in isolation. Perceptual decisions are considered to be at a non-deliberative cognitive level and have an outside criterion that defines the quality of decisions. Preferential decisions are considered to be at a higher cognitive level and the quality of decisions depend on the decision maker's subjective goals. Besides these crucial differences, both types of decisions also have in common that uncertain information about the choice situation has to be processed before a decision can be made. The present work aims to acknowledge the commonalities of both types of decision making to lay bare the crucial differences. For this aim we examine perceptual and preferential decisions with a novel choice paradigm that uses the identical stimulus material for both types of decisions. This paradigm allows us to model the decisions and response times of both types of decisions with the same sequential sampling model, the drift diffusion model. The results illustrate that the different incentive structure in both types of tasks changes people's behavior so that they process information more efficiently and respond more cautiously in the perceptual as compared to the preferential task. These findings set out a perspective for further integration of perceptual and preferential decision making in a single ramework.

  9. Preferential Attachment in Online Networks: Measurement and Explanations

    NARCIS (Netherlands)

    Kunegis, J; Blattner, M; Moser, C.

    2013-01-01

    We perform an empirical study of the preferential attachment phenomenon in temporal networks and show that on the Web, networks follow a nonlinear preferential attachment model in which the exponent depends on the type of network considered. The classical preferential attachment model for networks

  10. Systematic screening of imaging biomarkers for the Islets of Langerhans, among clinically available positron emission tomography tracers

    International Nuclear Information System (INIS)

    Karlsson, Filip; Antonodimitrakis, Pantelis Clewemar; Eriksson, Olof

    2015-01-01

    Introduction: Functional imaging could be utilized for visualizing pancreatic islets of Langerhans. Therefore, we present a stepwise algorithm for screening of clinically available positron emission tomography (PET) tracers for their use in imaging of the neuroendocrine pancreas in the context of diabetes. Methods: A stepwise procedure was developed for screening potential islet imaging agents. Suitable PET-tracer candidates were identified by their molecular mechanism of targeting. Clinical abdominal examinations were retrospectively analyzed for pancreatic uptake and retention. The target protein localization in the pancreas was assessed in silico by –omics approaches and the in vitro by binding assays to human pancreatic tissue. Results: Six putative candidates were identified and screened by using the stepwise procedure. Among the tested PET tracers, only [ 11 C]5-Hydroxy-tryptophan passed all steps. The remaining identified candidates were falsified as candidates and discarded following in silico and in vitro screening. Conclusions: Of the six clinically available PET tracers identified, [ 11 C]5-HTP was found to be a promising candidate for beta cell imaging, based on intensity of in vivo pancreatic uptake in humans, and islet specificity as assessed on human pancreatic cell preparations. The flow scheme described herein constitutes a methodology for evaluating putative islet imaging biomarkers among clinically available PET tracers

  11. Carbohydrate-dependent binding of langerin to SodC, a cell wall glycoprotein of Mycobacterium leprae.

    Science.gov (United States)

    Kim, Hee Jin; Brennan, Patrick J; Heaslip, Darragh; Udey, Mark C; Modlin, Robert L; Belisle, John T

    2015-02-01

    Langerhans cells participate in the immune response in leprosy by their ability to activate T cells that recognize the pathogen, Mycobacterium leprae, in a langerin-dependent manner. We hypothesized that langerin, the distinguishing C-type lectin of Langerhans cells, would recognize the highly mannosylated structures in pathogenic Mycobacterium spp. The coding region for the extracellular and neck domain of human langerin was cloned and expressed to produce a recombinant active trimeric form of human langerin (r-langerin). Binding assays performed in microtiter plates, by two-dimensional (2D) Western blotting, and by surface plasmon resonance demonstrated that r-langerin possessed carbohydrate-dependent affinity to glycoproteins in the cell wall of M. leprae. This lectin, however, yielded less binding to mannose-capped lipoarabinomannan (ManLAM) and even lower levels of binding to phosphatidylinositol mannosides. However, the superoxide dismutase C (SodC) protein of the M. leprae cell wall was identified as a langerin-reactive ligand. Tandem mass spectrometry verified the glycosylation of a recombinant form of M. leprae SodC (rSodC) produced in Mycobacterium smegmatis. Analysis of r-langerin affinity by surface plasmon resonance revealed a carbohydrate-dependent affinity of rSodC (equilibrium dissociation constant [KD] = 0.862 μM) that was 20-fold greater than for M. leprae ManLAM (KD = 18.69 μM). These data strongly suggest that a subset of the presumptively mannosylated M. leprae glycoproteins act as ligands for langerin and may facilitate the interaction of M. leprae with Langerhans cells. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  12. Hypoxia preferentially destroys GABAergic neurons in developing rat neocortex explants in culture

    NARCIS (Netherlands)

    Romijn, H. J.; Ruijter, J. M.; Wolters, P. S.

    1988-01-01

    The hypothesis that hypoxic ischemia before or during the human birth process preferentially destroys GABAergic nerve cells, particularly in the neocortex, was tested in a tissue culture model system. To that end, rat neocortex explants dissected from 6-day-old rat pups and cultured to a

  13. Defects in Antigen-Presenting Cells in the BB-DP Rat Model of Diabetes

    NARCIS (Netherlands)

    V. Sommandas (Vinod)

    2008-01-01

    textabstractType-1 diabetes is the result of a T cell mediated immune response against the insulin-producing β cells in the islet of Langerhans. In humans, until now, the disease is only clearly detectable at the onset of the disease. Therefore studies to identify initial factors involved in

  14. MAPK13 is preferentially expressed in gynecological cancer stem cells and has a role in the tumor-initiation

    Energy Technology Data Exchange (ETDEWEB)

    Yasuda, Kazuyo [Department of Pathology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-Ku, Sapporo, 060-8556 (Japan); Hirohashi, Yoshihiko, E-mail: hirohash@sapmed.ac.jp [Department of Pathology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-Ku, Sapporo, 060-8556 (Japan); Kuroda, Takafumi [Department of Obstetrics and Gynecology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-Ku, Sapporo, 060-8556 (Japan); Takaya, Akari; Kubo, Terufumi; Kanaseki, Takayuki; Tsukahara, Tomohide [Department of Pathology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-Ku, Sapporo, 060-8556 (Japan); Hasegawa, Tadashi [Department of Surgical Pathology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-Ku, Sapporo, 060-8556 (Japan); Saito, Tsuyoshi [Department of Obstetrics and Gynecology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-Ku, Sapporo, 060-8556 (Japan); Sato, Noriyuki [Department of Pathology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-Ku, Sapporo, 060-8556 (Japan); Torigoe, Toshihiko, E-mail: torigoe@sapmed.ac.jp [Department of Pathology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-Ku, Sapporo, 060-8556 (Japan)

    2016-04-15

    Cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) are defined as small subpopulation of cancer cells that are endowed with higher tumor-initiating ability. CSCs/CICs are resistant to standard cancer therapies including chemotherapy and radiotherapy, and they are thus thought to be responsible for cancer recurrence and metastasis. Therefore, elucidation of molecular mechanisms of CSCs/CICs is essential to cure cancer. In this study, we analyzed the gene expression profiles of gynecological CSCs/CICs isolated as aldehyde dehydrogenase high (ALDH{sup high}) cells, and found that MAPK13, PTTG1IP, CAPN1 and UBQLN2 were preferentially expressed in CSCs/CICs. MAPK13 is expressed in uterine, ovary, stomach, colon, liver and kidney cancer tissues at higher levels compared with adjacent normal tissues. MAPK13 gene knockdown using siRNA reduced the ALDH{sup high} population and abrogated the tumor-initiating ability. These results indicate that MAPK13 is expressed in gynecological CSCs/CICs and has roles in the maintenance of CSCs/CICs and tumor-initiating ability, and MAPK13 might be a novel molecular target for treatment-resistant CSCs/CICs.

  15. Immunomodulation and safety of topical calcineurin inhibitors for the treatment of atopic dermatitis.

    Science.gov (United States)

    Hultsch, Thomas; Kapp, Alexander; Spergel, Jonathan

    2005-01-01

    Atopic dermatitis (AD) is a chronic or chronically relapsing inflammatory skin condition that primarily affects children. Topical corticosteroids have been the mainstay of treatment since the late 1950s. While providing excellent short-term efficacy, topical corticosteroid usage is limited by potential adverse effects, including impairment of the function and viability of Langerhans cells/dendritic cells. The recently introduced topical calcineurin inhibitors pimecrolimus cream 1% (Elidel) and tacrolimus ointment 0.03 and 0.1% (Protopic) exhibit a more selective mechanism of action and do not affect Langerhans cells/dendritic cells. For the immune system of young children 'learning' to mount a balanced Th1/Th2 response, this selective effect has particular benefits. In clinical experience, topical calcineurin inhibitors have been shown to be a safe and effective alternative to topical corticosteroids in almost 7 million patients (>5 million on pimecrolimus; >1.7 million on tacrolimus). Topical pimecrolimus is primarily used in children with mild and moderate AD, whereas tacrolimus is used preferentially in more severe cases. None of the topical calcineurin inhibitors have been associated with systemic immunosuppression-related malignancies known to occur following long-term sustained systemic immunosuppression with oral immunosuppressants (e.g., tacrolimus, cyclosporine A, and corticosteroids) in transplant patients. Preclinical and clinical data suggest a greater skin selectivity and larger safety margin for topical pimecrolimus. (c) 2005 S. Karger AG, Basel

  16. Preferential flow occurs in unsaturated conditions

    Science.gov (United States)

    Nimmo, John R.

    2012-01-01

    Because it commonly generates high-speed, high-volume flow with minimal exposure to solid earth materials, preferential flow in the unsaturated zone is a dominant influence in many problems of infiltration, recharge, contaminant transport, and ecohydrology. By definition, preferential flow occurs in a portion of a medium – that is, a preferred part, whether a pathway, pore, or macroscopic subvolume. There are many possible classification schemes, but usual consideration of preferential flow includes macropore or fracture flow, funneled flow determined by macroscale heterogeneities, and fingered flow determined by hydraulic instability rather than intrinsic heterogeneity. That preferential flow is spatially concentrated associates it with other characteristics that are typical, although not defining: it tends to be unusually fast, to transport high fluxes, and to occur with hydraulic disequilibrium within the medium. It also has a tendency to occur in association with large conduits and high water content, although these are less universal than is commonly assumed. Predictive unsaturated-zone flow models in common use employ several different criteria for when and where preferential flow occurs, almost always requiring a nearly saturated medium. A threshold to be exceeded may be specified in terms of the following (i) water content; (ii) matric potential, typically a value high enough to cause capillary filling in a macropore of minimum size; (iii) infiltration capacity or other indication of incipient surface ponding; or (iv) other conditions related to total filling of certain pores. Yet preferential flow does occur without meeting these criteria. My purpose in this commentary is to point out important exceptions and implications of ignoring them. Some of these pertain mainly to macropore flow, others to fingered or funneled flow, and others to combined or undifferentiated flow modes.

  17. Dendritic cell migration assay: a potential prediction model for identification of contact allergens.

    Science.gov (United States)

    Gibbs, Susan; Spiekstra, Sander; Corsini, Emanuela; McLeod, Julie; Reinders, Judith

    2013-04-01

    This manuscript describes methodology and a prediction model for the MUTZ-LC migration assay. The assay represents the physiological change in Langerhans cell (LC) behavior after exposure to a sensitizing chemical, resulting in LC migration from the epidermis to the dermis. MUTZ-LC are derived from the commercially available MUTZ-3 cell line. Upon exposure to a sensitizer MUTZ-LC migrate preferentially towards CXCL12 whereas upon exposure to a non-sensitizer MUTZ-LC migrate towards CCL5. A CXCL12/CCL5 ratio >1.10 in 2/3 independent experiments is indicative of a sensitizer, whereas a CXCL12/CCL5 ratio ≤1.10 is indicative of a non-sensitizer. At non cytotoxic chemical concentrations 9 sensitizers (2,4-dinitrochlorobenzene, paraphenylendiamine, cinnamaldehyde, isoeugenol, nickel-sulfate, tetramethylthiuram disulfide, eugenol, cinnamic-alcohol, ammonium-hexachloroplatinate) were distinguished from 4 non sensitizers (sodium lauryl sulfate, salicylic acid, phenol, octanoic acid). Critical points in assay performance are (i) MUTZ-3 passage number after thawing (p6-p40); (ii) cell viability (>80%); (iii) standard curve to optimize correlation of fluorescence with cell number; and (iv) optimization of the concentration of rhCXCL12 and rhCCL5 in transwell. The protocol has been tested in three European laboratories and results suggest that it may provide working conditions for performing the DC migration assay which is aimed at distinguishing sensitizers from non sensitizers. Copyright © 2012 Elsevier Ltd. All rights reserved.

  18. Preferential role restrictions

    CSIR Research Space (South Africa)

    Britz, K

    2013-07-01

    Full Text Available ., Pozzato, G.: ALC+T : a preferential exten- sion of description logics. Fundamenta Informaticae 96(3), 341–372 (2009) 15. Giordano, L., Olivetti, N., Gliozzi, V., Pozzato, G.: A minimal model semantics for nonmonotonic reasoning. In: Proc. JELIA. pp. 228...

  19. Preferential Generation of 15-HETE-PE Induced by IL-13 Regulates Goblet Cell Differentiation in Human Airway Epithelial Cells.

    Science.gov (United States)

    Zhao, Jinming; Minami, Yoshinori; Etling, Emily; Coleman, John M; Lauder, Sarah N; Tyrrell, Victoria; Aldrovandi, Maceler; O'Donnell, Valerie; Claesson, Hans-Erik; Kagan, Valerian; Wenzel, Sally

    2017-12-01

    Type 2-associated goblet cell hyperplasia and mucus hypersecretion are well known features of asthma. 15-Lipoxygenase-1 (15LO1) is induced by the type 2 cytokine IL-13 in human airway epithelial cells (HAECs) in vitro and is increased in fresh asthmatic HAECs ex vivo. 15LO1 generates a variety of products, including 15-hydroxyeicosatetraenoic acid (15-HETE), 15-HETE-phosphatidylethanolamine (15-HETE-PE), and 13-hydroxyoctadecadienoic acid (13-HODE). In this study, we investigated the 15LO1 metabolite profile at baseline and after IL-13 treatment, as well as its influence on goblet cell differentiation in HAECs. Primary HAECs obtained from bronchial brushings of asthmatic and healthy subjects were cultured under air-liquid interface culture supplemented with arachidonic acid and linoleic acid (10 μM each) and exposed to IL-13 for 7 days. Short interfering RNA transfection and 15LO1 inhibition were applied to suppress 15LO1 expression and activity. IL-13 stimulation induced expression of 15LO1 and preferentially generated 15-HETE-PE in vitro, both of which persisted after removal of IL-13. 15LO1 inhibition (by short interfering RNA and chemical inhibitor) decreased IL-13-induced forkhead box protein A3 (FOXA3) expression and enhanced FOXA2 expression. These changes were associated with reductions in both mucin 5AC and periostin. Exogenous 15-HETE-PE stimulation (alone) recapitulated IL-13-induced FOXA3, mucin 5AC, and periostin expression. The results of this study confirm the central importance of 15LO1 and its primary product, 15-HETE-PE, for epithelial cell remodeling in HAECs.

  20. Phosphatidylcholine biosynthesis and insulin release in rat islets of Langerhans

    International Nuclear Information System (INIS)

    Hoffman, J.M.

    1988-01-01

    Turnover of phosphatidylcholine (PC) has been demonstrated to play a role in glucose stimulation of insulin release by pancreatic islets of Langerhans. The activity of the islet CDP-choline pathway of PC synthesis was determined by measuring the incorporation of radiolabeled choline or 32 PO 4 into PC, phosphorylcholine and CDP-choline. Concurrently, insulin release was measured by radioimmunoassay to correlate insulin release and PC synthesis. Glucose concentrations greater than 8.5 mM stimulated CDP-choline pathway activity. However, measurement of PC lipid phosphorus tended to decrease, suggesting that stimulation of the CDP-choline pathway was a means of replenishing PC pools diminished by hydrolysis of PC. Inhibition of glucose oxidation by mannoheptulose or incubations under hypoxic conditions prevented stimulation of the CDP-choline pathway, while inhibition of phospholipase A 2 (PLA 2 ) and secretion by the removal of extracellular Ca 2+ potentiated the stimulation seen with glucose

  1. Acute aerobic exercise induces a preferential mobilisation of plasmacytoid dendritic cells into the peripheral blood in man.

    Science.gov (United States)

    Brown, Frankie F; Campbell, John P; Wadley, Alex J; Fisher, James P; Aldred, Sarah; Turner, James E

    2018-05-31

    30 min of exercise cessation. These results show that there is a preferential mobilisation of plasmacytoid DCs during exercise. Given the functional repertoire of plasmacytoid DCs, which includes the production of interferons against viral and bacterial pathogens, these findings indicate that exercise may augment immune-surveillance by preferentially mobilising effector cells; these findings have general implications for the promotion of exercise for health, and specifically for the optimisation of DC harvest for cancer immunotherapy. Copyright © 2018 Elsevier Inc. All rights reserved.

  2. Modeling online social networks based on preferential linking

    International Nuclear Information System (INIS)

    Hu Hai-Bo; Chen Jun; Guo Jin-Li

    2012-01-01

    We study the phenomena of preferential linking in a large-scale evolving online social network and find that the linear preference holds for preferential creation, preferential acceptance, and preferential attachment. Based on the linear preference, we propose an analyzable model, which illustrates the mechanism of network growth and reproduces the process of network evolution. Our simulations demonstrate that the degree distribution of the network produced by the model is in good agreement with that of the real network. This work provides a possible bridge between the micro-mechanisms of network growth and the macrostructures of online social networks

  3. Preferential Affirmative Action.

    Science.gov (United States)

    Bell, Derrick A., Jr.

    1982-01-01

    Discusses the philosophical rationale for preferential affirmative action presented by Daniel C. Maguire in "A New American Justice." Maintains that self-interest bars present society's acceptance of Maguire's theories of justice, as demonstrated in negative reactions to the Harvard Law Review's affirmative action plan. (MJL)

  4. Preferential cytotoxicity of bortezomib toward highly malignant human liposarcoma cells via suppression of MDR1 expression and function

    International Nuclear Information System (INIS)

    Hu, Yamei; Wang, Lingxian; Wang, Lu; Wu, Xuefeng; Wu, Xudong; Gu, Yanhong; Shu, Yongqian; Sun, Yang; Shen, Yan; Xu, Qiang

    2015-01-01

    Liposarcoma is the most common soft tissue sarcoma with a high risk of relapse. Few therapeutic options are available for the aggressive local or metastatic disease. Here, we report that the clinically used proteasome inhibitor bortezomib exhibits significantly stronger cytotoxicity toward highly malignant human liposarcoma SW872-S cells compared with its parental SW872 cells, which is accompanied by enhanced activation of apoptotic signaling both in vitro and in vivo. Treatment of cells with Jun-N-terminal kinase (JNK) inhibitor SP60015 or the translation inhibitor cycloheximide ameliorated this enhanced apoptosis. Bortezomib inhibited MDR1 expression and function more effectively in SW872-S cells than in SW872 cells, indicating that the increased cytotoxicity relies on the degree of proteasome inhibition. Furthermore, the pharmacological or genetic inhibition of sarco/endoplasmic reticulum calcium-ATPase (SERCA) 2, which is highly expressed in SW872-S cells, resulted in partial reversal of cell growth inhibition and increase of MDR1 expression in bortezomib-treated SW872-S cells. These results show that bortezomib exhibits preferential cytotoxicity toward SW872-S cells possibly via highly expressed SERCA2-associated MDR1 suppression and suggest that bortezomib may serve as a potent agent for treating advanced liposarcoma. - Highlights: • We compare the cytotoxicity of different drugs between SW872-S and SW872 cells. • Highly malignant liposarcoma cells SW872-S show hypersensitivity to bortezomib. • Apoptotic signaling is robustly enhanced in bortezomib-treated SW872-S cells. • Bortezomib has strong suppression on MDR1 expression and function in SW872-S cells. • Inhibition of SERCA2 protects SW872-S cells from bortezomib

  5. Preferential cytotoxicity of bortezomib toward highly malignant human liposarcoma cells via suppression of MDR1 expression and function

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Yamei; Wang, Lingxian; Wang, Lu; Wu, Xuefeng; Wu, Xudong [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093 (China); Gu, Yanhong; Shu, Yongqian [Department of Clinical Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029 (China); Sun, Yang [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093 (China); Shen, Yan, E-mail: shenyan@nju.edu.cn [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093 (China); Xu, Qiang, E-mail: molpharm@163.com [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093 (China)

    2015-02-15

    Liposarcoma is the most common soft tissue sarcoma with a high risk of relapse. Few therapeutic options are available for the aggressive local or metastatic disease. Here, we report that the clinically used proteasome inhibitor bortezomib exhibits significantly stronger cytotoxicity toward highly malignant human liposarcoma SW872-S cells compared with its parental SW872 cells, which is accompanied by enhanced activation of apoptotic signaling both in vitro and in vivo. Treatment of cells with Jun-N-terminal kinase (JNK) inhibitor SP60015 or the translation inhibitor cycloheximide ameliorated this enhanced apoptosis. Bortezomib inhibited MDR1 expression and function more effectively in SW872-S cells than in SW872 cells, indicating that the increased cytotoxicity relies on the degree of proteasome inhibition. Furthermore, the pharmacological or genetic inhibition of sarco/endoplasmic reticulum calcium-ATPase (SERCA) 2, which is highly expressed in SW872-S cells, resulted in partial reversal of cell growth inhibition and increase of MDR1 expression in bortezomib-treated SW872-S cells. These results show that bortezomib exhibits preferential cytotoxicity toward SW872-S cells possibly via highly expressed SERCA2-associated MDR1 suppression and suggest that bortezomib may serve as a potent agent for treating advanced liposarcoma. - Highlights: • We compare the cytotoxicity of different drugs between SW872-S and SW872 cells. • Highly malignant liposarcoma cells SW872-S show hypersensitivity to bortezomib. • Apoptotic signaling is robustly enhanced in bortezomib-treated SW872-S cells. • Bortezomib has strong suppression on MDR1 expression and function in SW872-S cells. • Inhibition of SERCA2 protects SW872-S cells from bortezomib.

  6. Comparative analysis of B7-1 and B7-2 expression in Langerhans cells: differential regulation by T helper type 1 and T helper type 2 cytokines.

    Science.gov (United States)

    Kawamura, T; Furue, M

    1995-07-01

    Epidermal Langerhans cells (LC) are Ia-bearing potent antigen-presenting cells (APC) of dendritic cell lineage that play a crucial role in primary and secondary T cell-dependent immune responses. LC express several costimulatory molecules such as B7, which has been implicated as one of the important determinants of professional APC. Recently, B7 antigens have been shown to include three distinct molecules termed B7-1, B7-2, and B7-3, and the expression of B7-1 and B7-2 in LC has been already confirmed. However, little is known of the regulation of B7-1 and B7-2 expression in LC. We demonstrated that LC do not express B7-1 and B7-2 in situ; however, the expression of both molecules is rapidly induced during the first 3 days of culture, and high levels of expression are maintained at least until day 6. We show that the expression of B7-2 in LC is much higher than that of B7-1 in each experiment, and that B7-1 and B7-2 expression is reproducibly augmented by interleukin (IL)-4 in a dose-dependent manner; however, IL-2 affected expression very little. Finally, B7-1 expression is significantly and dose-dependently down-regulated by interferon (IFN)-gamma or IL-10, and B7-2 expression is consistently inhibited by IL-10, but not by IFN-gamma. The effects of these cytokines are active only in the induction phase (during first 3 days of culture) of B7 expression: the modulatory effects of cytokines are hardly detected in the plateau phase (days 4 to 6 of culture) of B7 expression in LC. These findings suggest that B7-1 and B7-2 expression are indeed selectively and differentially regulated by these T cell-derived cytokines, and that the cytokines may modulate the synthesis of B7 molecules rather than the degradation of already-expressed B7 molecules.

  7. Concept model semantics for DL preferential reasoning

    CSIR Research Space (South Africa)

    Britz, K

    2011-07-01

    Full Text Available ., Olivetti, N., Gliozzi, V., Pozzato, G.: ALC +T : a preferential exten- sion of description logics. Fund. Informatica 96(3), 341{372 (2009) 7. Kraus, S., Lehmann, D., Magidor, M.: Nonmonotonic reasoning, preferential mod- els and cumulative logics. Arti...

  8. Solitary Langerhans cell histiocytosis of the occipital condyle: a case report and review of the literature.

    Science.gov (United States)

    Teranishi, Yu; Shin, Masahiro; Yoshino, Masanori; Saito, Nobuhito

    2016-02-01

    Despite the recent advent of various radiographic imaging techniques, it is still very difficult to correctly distinguish a pediatric osteolytic lesion in the occipital condyle, which makes it further complicated to decide on the necessity of and the adequate timing for radical resection and craniocervical fusions. To establish a legitimate therapeutic strategy for this deep-seated lesion, surgical biopsy is a reasonable choice for first-line intervention. The choice of surgical approach becomes very important because a sufficient amount of histological specimen must be obtained to confirm the diagnosis but, ideally, the residual bony structures and the muscular structures should be preserved so as not to increase craniocervical instability. In this report, we present our experience with a case of solitary Langerhans cell histiocytosis (LCH) involving the occipital condyle that was successfully treated with minimally invasive surgical biopsy with a far lateral condylar approach supported by preoperative 3D computer graphic simulation. An 8-year-old girl presented with neck pain. Magnetic resonance imaging and computed tomography (CT) revealed an osteolytic lesion of the left occipital condyle. At surgery, the patient was placed in the prone position. A 3-cm skin incision was made in the posterior auricular region, and the sternocleidomastoid and splenius capitis muscles were dissected in the middle of the muscle bundle along the direction of the muscle fiber. Under a navigation system, we approached the occipital condyle through the space between the longissimus capitis muscle and the posterior belly of the digastric muscle and lateral to the superior oblique muscle, verifying each muscle at each depth of the surgical field and, finally, obtained sufficient surgical specimen. After the biopsy, her craniocervical instability had not worsened, and chemotherapy was performed. Twelve weeks after chemotherapy, her neck pain had gradually disappeared along with her

  9. Human Induced Pluripotent Stem Cell-Derived Macrophages Share Ontogeny with MYB-Independent Tissue-Resident Macrophages

    Directory of Open Access Journals (Sweden)

    Julian Buchrieser

    2017-02-01

    Full Text Available Tissue-resident macrophages, such as microglia, Kupffer cells, and Langerhans cells, derive from Myb-independent yolk sac (YS progenitors generated before the emergence of hematopoietic stem cells (HSCs. Myb-independent YS-derived resident macrophages self-renew locally, independently of circulating monocytes and HSCs. In contrast, adult blood monocytes, as well as infiltrating, gut, and dermal macrophages, derive from Myb-dependent HSCs. These findings are derived from the mouse, using gene knockouts and lineage tracing, but their applicability to human development has not been formally demonstrated. Here, we use human induced pluripotent stem cells (iPSCs as a tool to model human hematopoietic development. By using a CRISPR-Cas9 knockout strategy, we show that human iPSC-derived monocytes/macrophages develop in an MYB-independent, RUNX1-, and SPI1 (PU.1-dependent fashion. This result makes human iPSC-derived macrophages developmentally related to and a good model for MYB-independent tissue-resident macrophages, such as alveolar and kidney macrophages, microglia, Kupffer cells, and Langerhans cells.

  10. Isolation, transplantation, and functional studies of adult porcine islets of Langerhans

    DEFF Research Database (Denmark)

    Nielsen, Thomas Buschmann; Yderstræde, Knud Bonnet; Beck-Nielsen, Henning

    2002-01-01

    that was only partially increased by additional challenge with arginine. More than 50% of DNA and 90% of the insulin content was lost during a one-week culture period. With some batch-to-batch variation, in 15 of 25 cases, 4,000 to 7,000 porcine islets cured streptozotocin diabetic nude mice within three weeks......Transplantation of islets of Langerhans is a possible treatment for type-I diabetes mellitus. However, there is a shortage of donors for such transplantations and the pig may be an alternative source of donor organs. The aims of the study reported here were to establish a method for adult porcine...... following transplantation. In conclusion, it is possible to isolate viable islets from adult pigs, using a semiautomatic set-up. With batch-to-batch variation, the islets are able to revert diabetes mellitus when transplanted to diabetic nude mice....

  11. Preferential attachment in evolutionary earthquake networks

    Science.gov (United States)

    Rezaei, Soghra; Moghaddasi, Hanieh; Darooneh, Amir Hossein

    2018-04-01

    Earthquakes as spatio-temporal complex systems have been recently studied using complex network theory. Seismic networks are dynamical networks due to addition of new seismic events over time leading to establishing new nodes and links to the network. Here we have constructed Iran and Italy seismic networks based on Hybrid Model and testified the preferential attachment hypothesis for the connection of new nodes which states that it is more probable for newly added nodes to join the highly connected nodes comparing to the less connected ones. We showed that the preferential attachment is present in the case of earthquakes network and the attachment rate has a linear relationship with node degree. We have also found the seismic passive points, the most probable points to be influenced by other seismic places, using their preferential attachment values.

  12. Experimental evidence for the origin of ductal-type adenocarcinoma from the islets of Langerhans.

    Science.gov (United States)

    Pour, P. M.; Weide, L.; Liu, G.; Kazakoff, K.; Scheetz, M.; Toshkov, I.; Ikematsu, Y.; Fienhold, M. A.; Sanger, W.

    1997-01-01

    To investigate the role of the islets of Langerhans in pancreatic carcinogenesis, freshly isolated islets from male Syrian hamsters were transplanted into the right submandibular glands of 50 female hamsters that were or were not pre-treated with streptozotocin. Thyroid gland fragments, cellulose powder, and immortal hamster pancreatic ductal cells were injected into the left submandibular gland of the same hamsters. All recipient hamsters were then treated with the potent pancreatic carcinogen N-nitrosobis(2-oxopropyl)amine weekly at a dose of 40 mg/kg of body weight for 3 weeks. Between 3 and 8 weeks later, 18 of 75 (24%) hamsters developed large ductal-type adenocarcinomas in the submandibular gland region, where islets were transplanted, but none developed tumors in the left submandibular gland. In 9 of 18 hamsters, tumors were multiple so that a total of 31 cancers were found. Eleven of these carcinomas were in the vicinity of transplanted islets, eight of which showed intra-insular ductular or cyst formation as seen in the pancreas of hamsters during pancreatic carcinogenesis. The formation of ductular structures within islets was also demonstrated in vitro. Some tumor cells in the vicinity of these islets were reactive with anti-insulin. Y chromosome message was found by polymerase chain reaction analysis in one of the three tumors examined. Also, like the induced pancreatic tumors, all three submandibular gland tumors that were examined had the mutation of the c-Ki-ras oncogene at codon 12 and all tumors expressed blood group A antigen. These and other findings strongly suggest that some components of islets, most probably stem cells, are the origin of ductal-type adenocarcinomas in this model. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 PMID:9176407

  13. Calcipotriol inhibits the proliferation of hyperproliferative CD29 positive keratinocytes in psoriatic epidermis in the absence of an effect on the function and number of antigen-presenting cells

    DEFF Research Database (Denmark)

    Jensen, A.M.; Llado, Minna Fyhn Lykke; Skov, L.

    1998-01-01

    The aim of this study was to elucidate some of the possible mechanisms of action of the vitamin D analogue calcipotriol in vivo. Calcipotriol is finding increasing use in the treatment of psoriasis, but the primary target cell in vivo has not yet been identified. We treated psoriatic patients...... psoriatic and normal skin, calcipotriol treatment did not alter the capacity of epidermal antigen-presenting cells to stimulate the proliferation of autologous T cells, either in the absence or in the presence of exogenous antigen. Epidermal cell suspensions were analysed further by staining...... for infiltrating leucocytes (CD45+) and Langerhans cells (CD1a+). Flow cytometric analysis showed that calcipotriol did not alter the number of CD45+ cells or Langerhans cells in psoriatic skin. These results indicate that calcipotriol does not alter either the number of the function of epidermal antigen...

  14. Label-free detection of insulin and glucagon within human islets of Langerhans using Raman spectroscopy.

    Directory of Open Access Journals (Sweden)

    Janneke Hilderink

    Full Text Available Intrahepatic transplantation of donor islets of Langerhans is a promising therapy for patients with type 1 diabetes. It is of critical importance to accurately monitor islet quality before transplantation, which is currently done by standard histological methods that are performed off-line and require extensive sample preparation. As an alternative, we propose Raman spectroscopy which is a non-destructive and label-free technique that allows continuous real-time monitoring of the tissue to study biological changes as they occur. By performing Raman spectroscopic measurements on purified insulin and glucagon, we showed that the 520 cm(-1 band assigned to disulfide bridges in insulin, and the 1552 cm(-1 band assigned to tryptophan in glucagon are mutually exclusive and could therefore be used as indirect markers for the label-free distinction between both hormones. High-resolution hyperspectral Raman imaging for these bands showed the distribution of disulfide bridges and tryptophan at sub-micrometer scale, which correlated with the location of insulin and glucagon as revealed by conventional immunohistochemistry. As a measure for this correlation, quantitative analysis was performed comparing the Raman images with the fluorescence images, resulting in Dice coefficients (ranging between 0 and 1 of 0.36 for insulin and 0.19 for glucagon. Although the use of separate microscope systems with different spatial resolution and the use of indirect Raman markers cause some image mismatch, our findings indicate that Raman bands for disulfide bridges and tryptophan can be used as distinctive markers for the label-free detection of insulin and glucagon in human islets of Langerhans.

  15. Preferential attachment in the evolution of metabolic networks

    Directory of Open Access Journals (Sweden)

    Elofsson Arne

    2005-11-01

    Full Text Available Abstract Background Many biological networks show some characteristics of scale-free networks. Scale-free networks can evolve through preferential attachment where new nodes are preferentially attached to well connected nodes. In networks which have evolved through preferential attachment older nodes should have a higher average connectivity than younger nodes. Here we have investigated preferential attachment in the context of metabolic networks. Results The connectivities of the enzymes in the metabolic network of Escherichia coli were determined and representatives for these enzymes were located in 11 eukaryotes, 17 archaea and 46 bacteria. E. coli enzymes which have representatives in eukaryotes have a higher average connectivity while enzymes which are represented only in the prokaryotes, and especially the enzymes only present in βγ-proteobacteria, have lower connectivities than expected by chance. Interestingly, the enzymes which have been proposed as candidates for horizontal gene transfer have a higher average connectivity than the other enzymes. Furthermore, It was found that new edges are added to the highly connected enzymes at a faster rate than to enzymes with low connectivities which is consistent with preferential attachment. Conclusion Here, we have found indications of preferential attachment in the metabolic network of E. coli. A possible biological explanation for preferential attachment growth of metabolic networks is that novel enzymes created through gene duplication maintain some of the compounds involved in the original reaction, throughout its future evolution. In addition, we found that enzymes which are candidates for horizontal gene transfer have a higher average connectivity than other enzymes. This indicates that while new enzymes are attached preferentially to highly connected enzymes, these highly connected enzymes have sometimes been introduced into the E. coli genome by horizontal gene transfer. We speculate

  16. Conceptualization of preferential flow for hillslope stability assessment

    Science.gov (United States)

    Kukemilks, Karlis; Wagner, Jean-Frank; Saks, Tomas; Brunner, Philip

    2018-03-01

    This study uses two approaches to conceptualize preferential flow with the goal to investigate their influence on hillslope stability. Synthetic three-dimensional hydrogeological models using dual-permeability and discrete-fracture conceptualization were subsequently integrated into slope stability simulations. The slope stability simulations reveal significant differences in slope stability depending on the preferential flow conceptualization applied, despite similar small-scale hydrogeological responses of the system. This can be explained by a local-scale increase of pore-water pressures observed in the scenario with discrete fractures. The study illustrates the critical importance of correctly conceptualizing preferential flow for slope stability simulations. It further demonstrates that the combination of the latest generation of physically based hydrogeological models with slope stability simulations allows for improvement to current modeling approaches through more complex consideration of preferential flow paths.

  17. Langerhans′ cell histiocytosis involving posterior elements of the dorsal spine: An unusual cause of extradural spinal mass in an adult

    Directory of Open Access Journals (Sweden)

    Devendra K Tyagi

    2011-01-01

    Full Text Available Langerhans cell histiocytosis (LCH is a clonal proliferation of Langerhans cells occurring as an isolated lesion or as part of a systemic proliferation. It is commoner in children younger than 10 years of age with sparing of the posterior elements in more than 95% of cases. We describe a case of LCH in an adult female presenting with paraplegia. MRI revealed a well-defined extradural contrast enhancing mass at D2-D4 vertebral level involving the posterior elements of spine. D2-5 laminectomy with excision of lesion was performed which lead to marked improvement of patients neurological status. Histopathology was suggestive of eosinophilic granuloma. We describe the case, discuss its uniqueness and review the literature on this rare tumor presentation.

  18. Normal modal preferential consequence

    CSIR Research Space (South Africa)

    Britz, K

    2012-12-01

    Full Text Available beyond the basic (propositional) KLM postulates, thereby making use of the additional expressivity provided by modal logic. In particular, we show that the additional constraints we impose on the preferential semantics ensure that the rule...

  19. Phosphatidylcholine (PC) biosynthesis in pancreatic islets of Langerhans

    International Nuclear Information System (INIS)

    Hoffman, J.M.; Laychock, S.G.

    1986-01-01

    Islets of Langerhans isolated from rat pancreata were incubated with [ 14 C]choline to determine the biosynthesis of PC by the CDP choline to determine the biosynthesis of PC by the CDPcholine pathway. Recovery of [ 14 C]PC in islet membranes was time-related, and stimulated by glucose (17mM) during 60 min. The rate of PC synthesis was constant during 60 min with glucose stimulation. In contrast, the sulfonylurea tolbutamide (2 mM) reduced the recovery of [ 14 C]choline in PC, and 8-bromo-cyclic AMP (5 mM) did not significantly affect [ 14 C]PC recovery. Incubation of islets in Ca 2+ -free medium enhanced glucose-stimulated recovery of [ 14 C]choline-labeled PC due to the inhibition of phospholipase and phospholipid hydrolysis. Inhibition of CTP:phosphocholine cytidylyltransferase with 5-deoxy-5'-isobutylthioadenosine (SIBA) reduced [ 14 C]PC levels and insulin release in a concentration dependent manner. Treatment with SIBA also reduced Mg 2+ -dependent Ca 2+ -ATPase activity in islet microsomes. Quantitation of membrane PC showed that glucose stimulation did not alter islet P levels. Thus, islet PC biosynthesis is linked to glucose stimulation and contributes to the maintenance of PC levels in membranes undergoing exocytosis and phospholipid hydrolysis. Adequate PC levels support Ca 2+ pump activity and secretory mechanisms

  20. A Decrease in the Density of HLA-DR-Positive Cells Occurs Faster in Corneas Stored in Organ Culture than under Hypothermic Conditions

    Czech Academy of Sciences Publication Activity Database

    Al-Fakih, A.; Faltus, Václav; Jirsová, K.

    2012-01-01

    Roč. 47, č. 1 (2012), s. 39-46 ISSN 0030-3747 Institutional research plan: CEZ:AV0Z10300504 Keywords : antigen-presenting cells * langerhans cells * dendritic cells * allograft survival * transplantation * sensitization * rejection * storage * atpase * HLA-DR positivity * Organ culture * Hypothermic storage * Immunohistochemistry Impact factor: 1.562, year: 2012

  1. Preferential Market Access, Foreign Aid and Economic Development

    DEFF Research Database (Denmark)

    Afesorgbor, Sylvanus Kwaku; Abreha, Kaleb Girma

    contributed to the economic development of the beneficiary countries. Focusing on the ACP countries over the period 1970-2009, we show that only the EU preferential scheme is effective in promoting exports and that market access plays a significant and economically large role in the development of beneficiary......Several studies highlight that exporters in developing countries face substantial trade costs. To reduce these costs, a few developed countries mainly Canada, the EU, Japan and the USA granted preferential market access to these exporters. We assess whether these preferential accesses have...

  2. Early detection of preferential channeling in reverse electrodialysis

    NARCIS (Netherlands)

    Vermaas, David; Saakes, Michel; Nijmeijer, Dorothea C.

    2014-01-01

    Membrane applications often experience fouling, which prevent uniform flow distribution through the feed water compartments, i.e. preferential channeling may occur. This research shows the effect of preferential channeling on energy generation from mixing salt water and fresh water using reverse

  3. Preferential flow from pore to landscape scales

    Science.gov (United States)

    Koestel, J. K.; Jarvis, N.; Larsbo, M.

    2017-12-01

    In this presentation, we give a brief personal overview of some recent progress in quantifying preferential flow in the vadose zone, based on our own work and those of other researchers. One key challenge is to bridge the gap between the scales at which preferential flow occurs (i.e. pore to Darcy scales) and the scales of interest for management (i.e. fields, catchments, regions). We present results of recent studies that exemplify the potential of 3-D non-invasive imaging techniques to visualize and quantify flow processes at the pore scale. These studies should lead to a better understanding of how the topology of macropore networks control key state variables like matric potential and thus the strength of preferential flow under variable initial and boundary conditions. Extrapolation of this process knowledge to larger scales will remain difficult, since measurement technologies to quantify macropore networks at these larger scales are lacking. Recent work suggests that the application of key concepts from percolation theory could be useful in this context. Investigation of the larger Darcy-scale heterogeneities that generate preferential flow patterns at the soil profile, hillslope and field scales has been facilitated by hydro-geophysical measurement techniques that produce highly spatially and temporally resolved data. At larger regional and global scales, improved methods of data-mining and analyses of large datasets (machine learning) may help to parameterize models as well as lead to new insights into the relationships between soil susceptibility to preferential flow and site attributes (climate, land uses, soil types).

  4. Discovering Preferential Patterns in Sectoral Trade Networks.

    Science.gov (United States)

    Cingolani, Isabella; Piccardi, Carlo; Tajoli, Lucia

    2015-01-01

    We analyze the patterns of import/export bilateral relations, with the aim of assessing the relevance and shape of "preferentiality" in countries' trade decisions. Preferentiality here is defined as the tendency to concentrate trade on one or few partners. With this purpose, we adopt a systemic approach through the use of the tools of complex network analysis. In particular, we apply a pattern detection approach based on community and pseudocommunity analysis, in order to highlight the groups of countries within which most of members' trade occur. The method is applied to two intra-industry trade networks consisting of 221 countries, relative to the low-tech "Textiles and Textile Articles" and the high-tech "Electronics" sectors for the year 2006, to look at the structure of world trade before the start of the international financial crisis. It turns out that the two networks display some similarities and some differences in preferential trade patterns: they both include few significant communities that define narrow sets of countries trading with each other as preferential destinations markets or supply sources, and they are characterized by the presence of similar hierarchical structures, led by the largest economies. But there are also distinctive features due to the characteristics of the industries examined, in which the organization of production and the destination markets are different. Overall, the extent of preferentiality and partner selection at the sector level confirm the relevance of international trade costs still today, inducing countries to seek the highest efficiency in their trade patterns.

  5. A Review on Preferential Oxidation of Carbon Monoxide in Hydrogen Rich Gases

    Directory of Open Access Journals (Sweden)

    A. Mishra

    2011-05-01

    Full Text Available In this review, recent works on the preferential oxidation of carbon monoxide in hydrogen rich gases for fuel cell applications are summarized. H2 is used as a fuel for polymer-electrolyte membrane fuel cell (PEMFC. It is produced by reforming of natural gas or liquid fuels followed by water gas shift reaction. The produced gas consists of H2, CO, and CO2. In which CO content is around 1%, which is highly poisonous for the Pt anode of the PEMFC so that further removal of CO is needed. Catalytic preferential oxidation of CO (CO-PROX is one of the most suitable methods of purification of H2 because of high CO conversion rate at low temperature range, which is preferable for PEMFC operating conditions. Catalysts used for COPROX are mainly noble metal based; gold based and base metal oxide catalysts among them Copper-Ceria based catalysts are the most appropriate due to its low cost, easy availability and result obtained by these catalysts are comparable with the conventional noble metal catalysts. Copyright © 2011 BCREC UNDIP. All rights reserved(Received: 22nd October 2010, Revised: 12nd January 2011, Accepted: 19th January 2011[How to Cite: A. Mishra, R. Prasad. (2011. A Review on Preferential Oxidation of Carbon Monoxide in Hydrogen Rich Gases. Bulletin of Chemical Reaction Engineering & Catalysis, 6 (1: 1-14. doi:10.9767/bcrec.6.1.191.1-14][How to Link / DOI: http://dx.doi.org/10.9767/bcrec.6.1.191.1-14 || or local:  http://ejournal.undip.ac.id/index.php/bcrec/article/view/191] | View in 

  6. Despite the presence of UVB-induced DNA damage, HLA-DR+ cells from ex vivo UVB-exposed human skin are able to migrate and show no impaired allostimulatory capacity

    NARCIS (Netherlands)

    Kremer, I. B.; Sylva-Steenland, R. M.; Bos, J. D.; Teunissen, M. B.

    1997-01-01

    In this study, we investigated the effect of ultraviolet B radiation on human Langerhans cell function. Normal human skin was irradiated ex vivo with single doses of ultraviolet B. For assessment of T-cell stimulatory function, cells that spontaneously migrated from epidermal sheets were used,

  7. Emergence of global preferential attachment from local interaction

    International Nuclear Information System (INIS)

    Li Menghui; Fan Ying; Wu Jinshan; Di Zengru; Gao Liang

    2010-01-01

    Global degree/strength-based preferential attachment is widely used as an evolution mechanism of networks. But it is hard to believe that any individual can get global information and shape the network architecture based on it. In this paper, it is found that the global preferential attachment emerges from the local interaction models, including the distance-dependent preferential attachment (DDPA) evolving model of weighted networks (Li et al 2006 New J. Phys. 8 72), the acquaintance network model (Davidsen et al 2002 Phys. Rev. Lett. 88 128701) and the connecting nearest-neighbor (CNN) model (Vazquez 2003 Phys. Rev. E 67 056104). For the DDPA model and the CNN model, the attachment rate depends linearly on the degree or vertex strength, whereas for the acquaintance network model, the dependence follows a sublinear power law. It implies that for the evolution of social networks, local contact could be more fundamental than the presumed global preferential attachment.

  8. Profile of blood glucose and ultrastucture of beta cells pancreatic islet in alloxan compound induced rats

    Directory of Open Access Journals (Sweden)

    I Nyoman Suarsana

    2010-06-01

    Full Text Available Diabetes is marked by elevated levels of blood glucose, and progressive changes of the structure of pancreatic islet histopathology. The objective of this research was to analyse the glucose level and histophatological feature in pancreatic islet in alloxan compound induced rats. A total of ten male Spraque Dawley rats of 2 months old were used in this study. The rats were divided into two groups: (1 negative control group (K-, and (2 positif induced alloxan group (diabetic group =DM. The rats were induced by a single dose intraperitonial injection of alloxan compound 120 mg/kg of body weight. The treatment was conducted for 28 days. Blood glucose levels of rats were analysed at 0, 4, 7, 14, 21, and 28 days following treatment. At the end of the experiment, rats were sacrificed by cervical dislocation. Pancreas was collected for analysis of histopathological study by Immunohistochemical technique, and ultrastructural study using transmission electron microscope (TEM. The result showed that Langerhans islet of diabetic rat (rat of DM group showed a marked reduction of size, number of Langerhans islet of diabetic rat decrease, and characterized by hyperglycemic condition. By using TEM, beta cells of DM group showed the rupture of mitochondrial membrane, the lost of cisternal structure of inner membrane of mitocondria, reduction of insulin secretory granules, linkage between cells acinar with free Langerhans islet, and the caryopicnotic of nucleus.

  9. Functional and histological findings of the islets of Langerhans in mice after fractioned telecobalt irradiations with tumor doses

    International Nuclear Information System (INIS)

    Konermann, G.; Petersen, K.G.; Slanina, J.; Blachnitzky, E.O.; Kraft, C.; Freiburg Univ.

    1979-01-01

    After a local radiation exposure of the pancreas of mice to a total dose of 5000 rd ( 60 Co gamma radiation over five weeks with 5 x 200 rd per week), there is no demonstrable alteration, even at long term, of the glucose tolerance and the insulin secretion of isolated islets of Langerhans in vitro and of the density of a histochemically prepared islet secretion. However, the proinsuline synthesis under glucose loading is reduced by about 40%. A radiogenic reduction of the total insulin content in the islet tissue of 27,6% is accompanied by a diminution of the body weight of 10% and a reduction of the organ weight of pancreas, liver and spleen of 20%, 13% and 47%. In view of these findings and taking into account a cellular death rate in the islet tissue of 21% immediately after the radiotherapy and of 5,8% eight weeks post irradiationem, the authors suppose a compensating secretion by the remaining islet cells which is sufficient under normal conditions. Signs of a tissue degeneration near the vessels are clearer in the exocrine pancreas than in the islet tissue. (orig.) 891 MG/orig. 892 RKD [de

  10. Cigarette smoke promotes dendritic cell accumulation in COPD; a Lung Tissue Research Consortium study

    Directory of Open Access Journals (Sweden)

    Yi Eunhee S

    2010-04-01

    Full Text Available Abstract Background Abnormal immune responses are believed to be highly relevant in the pathogenesis of chronic obstructive pulmonary disease (COPD. Dendritic cells provide a critical checkpoint for immunity by their capacity to both induce and suppress immunity. Although evident that cigarette smoke, the primary cause of COPD, significantly influences dendritic cell functions, little is known about the roles of dendritic cells in the pathogenesis of COPD. Methods The extent of dendritic cell infiltration in COPD tissue specimens was determined using immunohistochemical localization of CD83+ cells (marker of matured myeloid dendritic cells, and CD1a+ cells (Langerhans cells. The extent of tissue infiltration with Langerhans cells was also determined by the relative expression of the CD207 gene in COPD versus control tissues. To determine mechanisms by which dendritic cells accumulate in COPD, complimentary studies were conducted using monocyte-derived human dendritic cells exposed to cigarette smoke extract (CSE, and dendritic cells extracted from mice chronically exposed to cigarette smoke. Results In human COPD lung tissue, we detected a significant increase in the total number of CD83+ cells, and significantly higher amounts of CD207 mRNA when compared with control tissue. Human monocyte-derived dendritic cells exposed to CSE (0.1-2% exhibited enhanced survival in vitro when compared with control dendritic cells. Murine dendritic cells extracted from mice exposed to cigarette smoke for 4 weeks, also demonstrated enhanced survival compared to dendritic cells extracted from control mice. Acute exposure of human dendritic cells to CSE induced the cellular pro-survival proteins heme-oxygenase-1 (HO-1, and B cell lymphoma leukemia-x(L (Bcl-xL, predominantly through oxidative stress. Although activated human dendritic cells conditioned with CSE expressed diminished migratory CCR7 expression, their migration towards the CCR7 ligand CCL21 was not

  11. Reverse preferential spread in complex networks

    Science.gov (United States)

    Toyoizumi, Hiroshi; Tani, Seiichi; Miyoshi, Naoto; Okamoto, Yoshio

    2012-08-01

    Large-degree nodes may have a larger influence on the network, but they can be bottlenecks for spreading information since spreading attempts tend to concentrate on these nodes and become redundant. We discuss that the reverse preferential spread (distributing information inversely proportional to the degree of the receiving node) has an advantage over other spread mechanisms. In large uncorrelated networks, we show that the mean number of nodes that receive information under the reverse preferential spread is an upper bound among any other weight-based spread mechanisms, and this upper bound is indeed a logistic growth independent of the degree distribution.

  12. Preferential repair of ionizing radiation-induced damage in the transcribed strand of an active human gene is defective in Cockayne syndrome

    International Nuclear Information System (INIS)

    Leadon, S.A.; Copper, P.K.

    1993-01-01

    Cells from patients with Cockayne syndrome (CS), which are sensitive to killing by UV although overall damage removal appears normal, are specifically defective in repair of UV damage in actively transcribe genes. Because several CS strains display cross-sensitivity to killing by ionizing radiation, the authors examined whether ionizing radiation-induced damage in active genes is preferentially repaired by normal cells and whether the radiosensitivity of CS cells can be explained by a defect in this process. They found that ionizing radiation-induced damage was repaired more rapidly in the transcriptionally active metallothionein IIA (MTIIA) gene than in the inactive MTIIB gene or in the genome overall in normal cells as a result of faster repair on the transcribed strand of MTIIA. Cells of the radiosensitive CS strain CS1AN are completely defective in this strand-selective repair of ionizing radiation-induced damage, although their overall repair rate appears normal. CS3BE cells, which are intermediate in radiosensitivity, do exhibit more rapid repair of the transcribed strand but at a reduced rate compared to normal cells. Xeroderma pigmentosum complementation group A cells, which are hypersensitive to UV light because of a defect in the nucleotide excision repair pathway but do not show increased sensitivity to ionizing radiation, preferentially repair ionizing radiation-induced damage on the transcribed strand of MTIIA. Thus, the ability to rapidly repair ionizing radiation-induced damage in actively transcribing genes correlates with cell survival. The results extend the generality of preferential repair in active genes to include damage other than bulky lesions

  13. [Role of Langerhans cells in the physiopathology of atopic dermatitis].

    Science.gov (United States)

    Bieber, T

    1995-12-01

    The demonstration of IgE receptors on the surface of epidermal dendritic cells and on other antigen presenting cells is a crucial element in the understanding of the pathophysiological role of these cells in the genesis of atopic disease, and especially the atopic dermatitis (AD). The sensibilisation phase to an aeroallergen at the level of nasal or bronchial mucosa and even at the skin may be mediated by dendritic cells expressing Fc epsilon RI. Distinct forms of AD may then represent the equivalent of the ellicitation phase of the classical allergic contact dermatitis. Fc epsilon RI would lead, via specific IgE, to an efficient antigen capture, to the activation of the dendritic cells and finally to an antigen presentation. Thus, AD may represent the paradigma of an IgE-mediated type IV reaction.

  14. Effects of fluid dynamic stress on fracturing of cell-aggregated tissue during purification for islets of Langerhans transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Shintaku, H; Kawano, S [Department of Mechanical Science and Bioengineering, Graduate School of Engineering Science, Osaka University, Machikaneyama-cho, Toyonaka, Osaka 560-8531 (Japan); Okitsu, T [Transplantation Unit, Kyoto University Hospital, Kawara-cho Shogoin, Sakyo-ku, Kyoto 606-8507 (Japan); Matsumoto, S [Baylor Research Institute Islet Cell Laboratory, 1400 Eight Avenue, Fort Worth, TX 76104 (United States); Suzuki, T; Kanno, I; Kotera, H [Department of Microengineering, Kyoto University, Yoshida-Honmachi, Sakyo-ku, Kyoto 606-8501 (Japan)], E-mail: shintaku@me.es.osaka-u.ac.jp

    2008-06-07

    Among clinical treatments for type 1 diabetes mellitus, the transplantation of islets of Langerhans to the portal vein of the hepar is a commonly used treatment for glucose homeostasis. Islet purification using the density gradient of a solution in a centrifuge separator is required for safety and efficiency. In the purification, the number of tissues to be transplanted is reduced by removing the acinar tissue and gathering the islet from the digest of pancreas. However, the mechanical effects on the fracture of islets in the centrifuge due to fluid dynamic stress are a serious problem in the purification process. In this study, a preliminary experiment using a cylindrical rotating viscometer with a simple geometry is conducted in order to systematically clarify the effect of fluid dynamic stress on the fracture of islets. The effects of fluid dynamic stress on the islet configuration is quantitatively measured for various flow conditions, and a predictive fracture model is developed based on the experimental results. Furthermore, in the practical purification process in the COBE (Gambro BCT), which is widely used in clinical applications, we perform a numerical analysis of the fluid dynamic stress based on Navier-Stokes equations to estimate the stress conditions for islets. Using the fracture model and numerical analysis, the islet fracture characteristics using the COBE are successfully investigated. The results obtained in this study provide crucial information for the purification of islets by centrifuge in practical and clinical applications.

  15. Effects of fluid dynamic stress on fracturing of cell-aggregated tissue during purification for islets of Langerhans transplantation

    International Nuclear Information System (INIS)

    Shintaku, H; Kawano, S; Okitsu, T; Matsumoto, S; Suzuki, T; Kanno, I; Kotera, H

    2008-01-01

    Among clinical treatments for type 1 diabetes mellitus, the transplantation of islets of Langerhans to the portal vein of the hepar is a commonly used treatment for glucose homeostasis. Islet purification using the density gradient of a solution in a centrifuge separator is required for safety and efficiency. In the purification, the number of tissues to be transplanted is reduced by removing the acinar tissue and gathering the islet from the digest of pancreas. However, the mechanical effects on the fracture of islets in the centrifuge due to fluid dynamic stress are a serious problem in the purification process. In this study, a preliminary experiment using a cylindrical rotating viscometer with a simple geometry is conducted in order to systematically clarify the effect of fluid dynamic stress on the fracture of islets. The effects of fluid dynamic stress on the islet configuration is quantitatively measured for various flow conditions, and a predictive fracture model is developed based on the experimental results. Furthermore, in the practical purification process in the COBE (Gambro BCT), which is widely used in clinical applications, we perform a numerical analysis of the fluid dynamic stress based on Navier-Stokes equations to estimate the stress conditions for islets. Using the fracture model and numerical analysis, the islet fracture characteristics using the COBE are successfully investigated. The results obtained in this study provide crucial information for the purification of islets by centrifuge in practical and clinical applications

  16. Increased Arginine and Ornithine Flux in Islets of Langerhans Cultured in a Microgravity Model System

    Science.gov (United States)

    Tobin, B. W.; Sams, C. F.; Smith, S. M.

    2000-01-01

    Microgravity is associated with alterations in protein metabolism of both muscle and bone. That pancreas-derived insulin is essential to the normal maintenance of body protein balance is well known. The importance of altered endocrine pancreas function in microgravity is not yet established. We proposed to examine the influence of a microgravity model system, the High Aspect Ratio Vessel (HARV) upon islets of Langerhans from Wistar Furth rats. Islets were cultured in the HARV for 48 hr in Medium-199 and contrasted to static control islets (PLATE). Nitrogenous compounds elaborated into the media (micromoles/ml) were analyzed at 0 and 48 hr of culture and compared to PLATE with a 2-way ANOVA (HARV vs Hour).

  17. Histiocytosis X | Mohammed | Annals of African Medicine

    African Journals Online (AJOL)

    Histiocytosis X (Langerhan's cell granulomatosis) is a disease of unknown aetiology, but viral origin has been implicated.1 It is a clinicopathologic entity characterized by proliferation of Langerhan's cell (which are not primarily phagocytic) in an appropriate milieu.2 ...

  18. MicroRNA genes preferentially expressed in dendritic cells contain sites for conserved transcription factor binding motifs in their promoters

    Directory of Open Access Journals (Sweden)

    Huynen Martijn A

    2011-06-01

    Full Text Available Abstract Background MicroRNAs (miRNAs play a fundamental role in the regulation of gene expression by translational repression or target mRNA degradation. Regulatory elements in miRNA promoters are less well studied, but may reveal a link between their expression and a specific cell type. Results To explore this link in myeloid cells, miRNA expression profiles were generated from monocytes and dendritic cells (DCs. Differences in miRNA expression among monocytes, DCs and their stimulated progeny were observed. Furthermore, putative promoter regions of miRNAs that are significantly up-regulated in DCs were screened for Transcription Factor Binding Sites (TFBSs based on TFBS motif matching score, the degree to which those TFBSs are over-represented in the promoters of the up-regulated miRNAs, and the extent of conservation of the TFBSs in mammals. Conclusions Analysis of evolutionarily conserved TFBSs in DC promoters revealed preferential clustering of sites within 500 bp upstream of the precursor miRNAs and that many mRNAs of cognate TFs of the conserved TFBSs were indeed expressed in the DCs. Taken together, our data provide evidence that selected miRNAs expressed in DCs have evolutionarily conserved TFBSs relevant to DC biology in their promoters.

  19. Preferential reasoning for modal logics

    CSIR Research Space (South Africa)

    Britz, K

    2011-11-01

    Full Text Available Modal logic is the foundation for a versatile and well-established class of knowledge representation formalisms in artificial intelligence. Enriching modal logics with non-monotonic reasoning capabilities such as preferential reasoning as developed...

  20. ATP-ase positive cells in human oral mucosa transplanted to nude mice

    DEFF Research Database (Denmark)

    Dabelsteen, E; Kirkeby, S

    1981-01-01

    A model to study the differentiation of human oral epithelium in vivo utilizing transplantation of human tissue to nude mice has been described. Previous studies have described the epithelial cells in this model. In this study we demonstrate that 8 d after transplantation, Langerhans cells, ident......, identified as ATP-ase positive dendritic cells, have almost disappeared from the transplanted epithelium whereas at day 21 after transplantation such cells were abundant. It is suggested that the ATP-ase positive cells which reappear in the transplanted epithelium are of mouse origin....

  1. Surface-Selective Preferential Production of Reactive Oxygen Species on Piezoelectric Ceramics for Bacterial Killing.

    Science.gov (United States)

    Tan, Guoxin; Wang, Shuangying; Zhu, Ye; Zhou, Lei; Yu, Peng; Wang, Xiaolan; He, Tianrui; Chen, Junqi; Mao, Chuanbin; Ning, Chengyun

    2016-09-21

    Reactive oxygen species (ROS) can be used to kill bacterial cells, and thus the selective generation of ROS from material surfaces is an emerging direction in antibacterial material discovery. We found the polarization of piezoelectric ceramic causes the two sides of the disk to become positively and negatively charged, which translate into cathode and anode surfaces in an aqueous solution. Because of the microelectrolysis of water, ROS are preferentially formed on the cathode surface. Consequently, the bacteria are selectively killed on the cathode surface. However, the cell experiment suggested that the level of ROS is safe for normal mammalian cells.

  2. Distributed network generation based on preferential attachment in ABS

    NARCIS (Netherlands)

    K. Azadbakht (Keyvan); N. Bezirgiannis (Nikolaos); F.S. de Boer (Frank)

    2017-01-01

    textabstractGeneration of social networks using Preferential Attachment (PA) mechanism is proposed in the Barabasi-Albert model. In this mechanism, new nodes are introduced to the network sequentially and they attach to the existing nodes preferentially where the preference can be based on the

  3. Preferential flow through intact soil cores: Effects of matrix head

    Energy Technology Data Exchange (ETDEWEB)

    Langner, H.W.; Gaber, H.M.; Wraith, J.M.; Huwe, B.; Inskeep, W.P.

    1999-12-01

    Continuous soil pores may act as pathways for preferential flow depending on their size and water status (filled or drained), the latter being largely controlled by the soil matrix head (h). The literature contains a wide range of proposed minimal pore sizes that may contribute to preferential flow. The objective of this study was to examine the relationship between h (and corresponding pore sizes) and preferential solute transport in a naturally structured soil. Tracer ({sup 3}H{sub 2}O and pentafluorobenzoic acid, [PFBA]) miscible displacement experiments were performed at several h values in intact soil cores (15-cm diameter, 30-cm length) using an apparatus especially suited to maintain constant h while collecting large effluent volumes. To test for the occurrence of preferential flow, observed breakthrough curves (BTCs) were evaluated for physical nonequilibrium (PNE) using a comparison between fitted local equilibrium (PNE) and PNE models. Fitting results of the observed BTCs indicated absence of PNE in all solute transport experiments at h {le} {minus}10 cm. Experiments at h {ge} {minus}5 cm consistently exhibited PNE conditions, indicating the presence of preferential flow. These results suggest that soil pores with effective radii of 150 {micro}m and smaller (water-filled at h = {minus}10 cm) do not contribute to preferential flow. Observed pore water velocities were not indicative of the presence or absence of preferential flow conditions. Continuous measurements of soil water content ({theta}) using time domain reflectometry (TDR) revealed that at h = {minus}10 cm, <2% of the soil volume had drained.

  4. 15 CFR 700.14 - Preferential scheduling.

    Science.gov (United States)

    2010-01-01

    ...) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE NATIONAL SECURITY INDUSTRIAL BASE REGULATIONS DEFENSE PRIORITIES AND ALLOCATIONS SYSTEM Industrial Priorities § 700.14 Preferential scheduling. (a) A...

  5. Oral tolerance is determined at the level of draining lymph nodes

    NARCIS (Netherlands)

    Wilsem, van E.G.; BrevÃ, J.; Savelkoul, H.; Claessen, A.; Scheper, R.J.; Kraal, G.

    1995-01-01

    In the skin and in the epithelium of the oral mucosa a comparable network of Langerhans cells can be found. Antigen application on either epithelium leads to rapid emigration of Langerhans cells to the draining lymph nodes. Application on the oral mucosa leads to tolerance induction while

  6. The hypothalamic satiety peptide CART is expressed in anorectic and non-anorectic pancreatic islet tumors and in the normal islet of Langerhans.

    Science.gov (United States)

    Jensen, P B; Kristensen, P; Clausen, J T; Judge, M E; Hastrup, S; Thim, L; Wulff, B S; Foged, C; Jensen, J; Holst, J J; Madsen, O D

    1999-03-26

    The hypothalamic satiety peptide CART (cocaine and amphetamine regulated transcript) is expressed at high levels in anorectic rat glucagonomas but not in hypoglycemic insulinomas. However, a non-anorectic metastasis derived from the glucagonoma retained high CART expression levels and produced circulating CART levels comparable to that of the anorectic tumors. Moreover, distinct glucagonoma lines derived by stable HES-1 transfection of the insulinoma caused severe anorexia but retained low circulating levels of CART comparable to that of insulinoma bearing or control rats. Islet tumor associated anorexia and circulating CART levels are thus not correlated, and in line with this peripheral administration of CART (5-50 mg/kg) produced no effect on feeding behavior. In the rat two alternatively spliced forms of CART mRNA exist and quantitative PCR revealed expression of both forms in the hypothalamus, in the different islet tumors, and in the islets of Langerhans. Immunocytochemistry as well as in situ hybridization localized CART expression to the somatostatin producing islet D cell. A potential endocrine/paracrine role of islet CART remains to be clarified.

  7. Semantic foundation for preferential description logics

    CSIR Research Space (South Africa)

    Britz, K

    2011-12-01

    Full Text Available Description logics are a well-established family of knowledge representation formalisms in Artificial Intelligence. Enriching description logics with non-monotonic reasoning capabilities, especially preferential reasoning as developed by Lehmann...

  8. Soil properties and preferential solute transport at the field scale

    DEFF Research Database (Denmark)

    Koestel, J K; Minh, Luong Nhat; Nørgaard, Trine

    An important fraction of water flow and solute transport through soil takes place through preferential flow paths. Although this had been already observed in the nineteenth century, it had been forgotten by the scientific community until it was rediscovered during the 1970s. The awareness...... of the relevance of preferential flow was broadly re-established in the community by the early 1990s. However, since then, the notion remains widespread among soil scientists that the occurrence and strength of preferential flow cannot be predicted from measurable proxy variables such as soil properties or land...

  9. Defeasible modes of inference: A preferential perspective

    CSIR Research Space (South Africa)

    Britz, K

    2012-06-01

    Full Text Available . Hence UM = f(Mi; wj) j i 2 f1; 2g; j 2 f1; 2; 3; 4gg. We construct a preferential model (Definition 4) in which to check the satisfiability and truth of a few sentences. The purpose is to illustrate the semantics of our notion of defea- sibility... exceptional situations would the pile be on while the cooler is off, e.g. during a serious malfunction (states s7 and s8). In the preferential model P depicted above, one can check that s6 2 Jh^ p p f:hK: at s6 we have a hazardous situ- ation...

  10. Integration of HIV in the Human Genome: Which Sites Are Preferential? A Genetic and Statistical Assessment

    Science.gov (United States)

    Gonçalves, Juliana; Moreira, Elsa; Sequeira, Inês J.; Rodrigues, António S.; Rueff, José; Brás, Aldina

    2016-01-01

    Chromosomal fragile sites (FSs) are loci where gaps and breaks may occur and are preferential integration targets for some viruses, for example, Hepatitis B, Epstein-Barr virus, HPV16, HPV18, and MLV vectors. However, the integration of the human immunodeficiency virus (HIV) in Giemsa bands and in FSs is not yet completely clear. This study aimed to assess the integration preferences of HIV in FSs and in Giemsa bands using an in silico study. HIV integration positions from Jurkat cells were used and two nonparametric tests were applied to compare HIV integration in dark versus light bands and in FS versus non-FS (NFSs). The results show that light bands are preferential targets for integration of HIV-1 in Jurkat cells and also that it integrates with equal intensity in FSs and in NFSs. The data indicates that HIV displays different preferences for FSs compared to other viruses. The aim was to develop and apply an approach to predict the conditions and constraints of HIV insertion in the human genome which seems to adequately complement empirical data. PMID:27294106

  11. Preferential elevation of Prx I and Trx expression in lung cancer cells following hypoxia and in human lung cancer tissues.

    Science.gov (United States)

    Kim, H J; Chae, H Z; Kim, Y J; Kim, Y H; Hwangs, T S; Park, E M; Park, Y M

    2003-10-01

    Transient/chronic microenvironmental hypoxia that exists within a majority of solid tumors has been suggested to have a profound influence on tumor growth and therapeutic outcome. Since the functions of novel antioxidant proteins, peroxiredoxin I (Prx I) and II, have been implicated in regulating cell proliferation, differentiation, and apoptosis, it was of our special interest to probe a possible role of Prx I and II in the context of hypoxic tumor microenvironment. Since both Prx I and II use thioredoxin (Trx) as an electron donor and Trx is a substrate for thioredoxin reductase (TrxR), we investigated the regulation of Trx and TrxR as well as Prx expression following hypoxia. Here we show a dynamic change of glutathione homeostasis in lung cancer A549 cells and an up-regulation of Prx I and Trx following hypoxia. Western blot analysis of 10 human lung cancer and paired normal lung tissues also revealed an elevated expression of Prx I and Trx proteins in lung cancer tissues. Immunohistochemical analysis of the lung cancer tissues confirmed an augmented Prx I and Trx expression in cancer cells with respect to the parenchymal cells in adjacent normal lung tissue. Based on these results, we suggest that the redox changes in lung tumor microenvironment could have acted as a trigger for the up-regulation of Prx I and Trx in lung cancer cells. Although the clinical significance of our finding awaits more rigorous future study, preferential augmentation of the Prx I and Trx in lung cancer cells may well represent an attempt of cancer cells to manipulate a dynamic redox change in tumor microenvironment in a manner that is beneficial for their proliferation and malignant progression.

  12. Intravenous delivery of HIV-based lentiviral vectors preferentially transduces F4/80+ and Ly-6C+ cells in spleen, important target cells in autoimmune arthritis.

    Directory of Open Access Journals (Sweden)

    Ben T van den Brand

    Full Text Available Antigen presenting cells (APCs play an important role in arthritis and APC specific gene therapeutic targeting will enable intracellular modulation of cell activity. Viral mediated overexpression is a potent approach to achieve adequate transgene expression levels and lentivirus (LV is useful for sustained expression in target cells. Therefore, we studied the feasibility of lentiviral mediated targeting of APCs in experimental arthritis. Third generation VSV-G pseudotyped self-inactivating (SIN-LV were injected intravenously and spleen cells were analyzed with flow cytometry for green fluorescent protein (GFP transgene expression and cell surface markers. Collagen-induced arthritis (CIA was induced by immunization with bovine collagen type II in complete Freund's adjuvant. Effect on inflammation was monitored macroscopically and T-cell subsets in spleen were analyzed by flow cytometry. Synovium from arthritic knee joints were analyzed for proinflammatory cytokine expression. Lentiviruses injected via the tail vein preferentially infected the spleen and transduction peaks at day 10. A dose escalating study showed that 8% of all spleen cells were targeted and further analysis showed that predominantly Ly6C+ and F4/80+ cells in spleen were targeted by the LV. To study the feasibility of blocking TAK1-dependent pathways by this approach, a catalytically inactive mutant of TAK1 (TAK1-K63W was overexpressed during CIA. LV-TAK1-K63W significantly reduced incidence and arthritis severity macroscopically. Further histological analysis showed a significant decrease in bone erosion in LV-TAK1-K63W treated animals. Moreover, systemic Th17 levels were decreased by LV-TAK1-K63W treatment in addition to diminished IL-6 and KC production in inflamed synovium. In conclusion, systemically delivered LV efficiently targets monocytes and macrophages in spleen that are involved in autoimmune arthritis. Moreover, this study confirms efficacy of TAK1 targeting in

  13. Activated Allogeneic NK Cells Preferentially Kill Poor Prognosis B-Cell Chronic Lymphocytic Leukemia Cells.

    Science.gov (United States)

    Sánchez-Martínez, Diego; Lanuza, Pilar M; Gómez, Natalia; Muntasell, Aura; Cisneros, Elisa; Moraru, Manuela; Azaceta, Gemma; Anel, Alberto; Martínez-Lostao, Luis; Villalba, Martin; Palomera, Luis; Vilches, Carlos; García Marco, José A; Pardo, Julián

    2016-01-01

    Mutational status of TP53 together with expression of wild-type (wt) IGHV represents the most widely accepted biomarkers, establishing a very poor prognosis in B-cell chronic lymphocytic leukemia (B-CLL) patients. Adoptive cell therapy using allogeneic HLA-mismatched Natural killer (NK) cells has emerged as an effective and safe alternative in the treatment of acute myeloid and lymphoid leukemias that do not respond to traditional therapies. We have described that allogeneic activated NK cells eliminate hematological cancer cell lines with multidrug resistance acquired by mutations in the apoptotic machinery. This effect depends on the activation protocol, being B-lymphoblastoid cell lines (LCLs) the most effective stimulus to activate NK cells. Here, we have further analyzed the molecular determinants involved in allogeneic NK cell recognition and elimination of B-CLL cells, including the expression of ligands of the main NK cell-activating receptors (NKG2D and NCRs) and HLA mismatch. We present preliminary data suggesting that B-CLL susceptibility significantly correlates with HLA mismatch between NK cell donor and B-CLL patient. Moreover, we show that the sensitivity of B-CLL cells to NK cells depends on the prognosis based on TP53 and IGHV mutational status. Cells from patients with worse prognosis (mutated TP53 and wt IGHV ) are the most susceptible to activated NK cells. Hence, B-CLL prognosis may predict the efficacy of allogenic activated NK cells, and, thus, NK cell transfer represents a good alternative to treat poor prognosis B-CLL patients who present a very short life expectancy due to lack of effective treatments.

  14. Anther-preferential expressing gene PMR is essential for the mitosis of pollen development in rice.

    Science.gov (United States)

    Liu, Yaqin; Xu, Ya; Ling, Sheng; Liu, Shasha; Yao, Jialing

    2017-06-01

    Phenotype identification, expression examination, and function prediction declared that the anther-preferential expressing gene PMR may participate in regulation of male gametophyte development in rice. Male germline development in flowering plants produces the pair of sperm cells for double fertilization and the pollen mitosis is a key process of it. Although the structural features of male gametophyte have been defined, the molecular mechanisms regulating the mitotic cell cycle are not well elucidated in rice. Here, we reported an anther-preferential expressing gene in rice, PMR (Pollen Mitosis Relative), playing an essential role in male gametogenesis. When PMR gene was suppressed via RNAi, the mitosis of microspore was severely damaged, and the plants formed unmatured pollens containing only one or two nucleuses at the anthesis, ultimately leading to serious reduction of pollen fertility and seed-setting. The CRISPR mutants, pmr-1 and pmr-2, both showed the similar defects as the PMR-RNAi lines. Further analysis revealed that PMR together with its co-expressing genes were liable to participate in the regulation of DNA metabolism in the nucleus, and affected the activities of some enzymes related to the cell cycle. We finally discussed that unknown protein PMR contained the PHD, SWIB and Plus-3 domains and they might have coordinating functions in regulation pathway of the pollen mitosis in rice.

  15. Current challenges in quantifying preferential flow through the vadose zone

    Science.gov (United States)

    Koestel, John; Larsbo, Mats; Jarvis, Nick

    2017-04-01

    In this presentation, we give an overview of current challenges in quantifying preferential flow through the vadose zone. A review of the literature suggests that current generation models do not fully reflect the present state of process understanding and empirical knowledge of preferential flow. We believe that the development of improved models will be stimulated by the increasingly widespread application of novel imaging technologies as well as future advances in computational power and numerical techniques. One of the main challenges in this respect is to bridge the large gap between the scales at which preferential flow occurs (pore to Darcy scales) and the scale of interest for management (fields, catchments, regions). Studies at the pore scale are being supported by the development of 3-D non-invasive imaging and numerical simulation techniques. These studies are leading to a better understanding of how macropore network topology and initial/boundary conditions control key state variables like matric potential and thus the strength of preferential flow. Extrapolation of this knowledge to larger scales would require support from theoretical frameworks such as key concepts from percolation and network theory, since we lack measurement technologies to quantify macropore networks at these large scales. Linked hydro-geophysical measurement techniques that produce highly spatially and temporally resolved data enable investigation of the larger-scale heterogeneities that can generate preferential flow patterns at pedon, hillslope and field scales. At larger regional and global scales, improved methods of data-mining and analyses of large datasets (machine learning) may help in parameterizing models as well as lead to new insights into the relationships between soil susceptibility to preferential flow and site attributes (climate, land uses, soil types).

  16. Preferential effects of leptin on CD4 T cells in central and peripheral immune system are critically linked to the expression of leptin receptor

    Energy Technology Data Exchange (ETDEWEB)

    Kim, So Yong; Lim, Ju Hyun [Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746 (Korea, Republic of); Choi, Sung Won [Department of Molecular Biology, School of Arts and Sciences (S.W.C), Cornell University, Ithaca, NY 18450 (United States); Kim, Miyoung; Kim, Seong-Tae [Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746 (Korea, Republic of); Kim, Min-Seon; Cho, You Sook [Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul 138-600 (Korea, Republic of); Chun, Eunyoung, E-mail: chun.eunyoung@gmail.com [Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746 (Korea, Republic of); Lee, Ki-Young, E-mail: thylee@med.skku.ac.kr [Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746 (Korea, Republic of)

    2010-04-09

    Leptin can enhance thymopoiesis and modulate the T-cell immune response. However, it remains controversial whether these effects correlate with the expression of leptin receptor, ObR. We herein addressed this issue by using in vivo animal models and in vitro culture systems. Leptin treatment in both ob/ob mice and normal young mice induced increases of CD4 SP thymocytes in thymus and CD4 T cells in the periphery. Interestingly, expression of the long form ObR was significantly restricted to DN, DP and CD4 SP, but not CD8 SP thymocytes. Moreover, in the reaggregated DP thymocyte cultures with leptin plus TSCs, leptin profoundly induced differentiation of CD4 SP but not CD8 SP thymocytes, suggesting that the effects of leptin on thymocyte differentiation might be closely related to the expression of leptin receptor in developing thymocytes. Surprisingly, ObR expression was markedly higher in peripheral CD4 T cells than that in CD8 T cells. Furthermore, leptin treatment with or without IL-2 and PHA had preferential effects on cell proliferation of CD4 T cells compared to that of CD8 T cells. Collectively, these data provide evidence that the effects of leptin on differentiation and proliferation of CD4 T cells might be closely related to the expression of leptin receptor.

  17. Preferential effects of leptin on CD4 T cells in central and peripheral immune system are critically linked to the expression of leptin receptor

    International Nuclear Information System (INIS)

    Kim, So Yong; Lim, Ju Hyun; Choi, Sung Won; Kim, Miyoung; Kim, Seong-Tae; Kim, Min-Seon; Cho, You Sook; Chun, Eunyoung; Lee, Ki-Young

    2010-01-01

    Leptin can enhance thymopoiesis and modulate the T-cell immune response. However, it remains controversial whether these effects correlate with the expression of leptin receptor, ObR. We herein addressed this issue by using in vivo animal models and in vitro culture systems. Leptin treatment in both ob/ob mice and normal young mice induced increases of CD4 SP thymocytes in thymus and CD4 T cells in the periphery. Interestingly, expression of the long form ObR was significantly restricted to DN, DP and CD4 SP, but not CD8 SP thymocytes. Moreover, in the reaggregated DP thymocyte cultures with leptin plus TSCs, leptin profoundly induced differentiation of CD4 SP but not CD8 SP thymocytes, suggesting that the effects of leptin on thymocyte differentiation might be closely related to the expression of leptin receptor in developing thymocytes. Surprisingly, ObR expression was markedly higher in peripheral CD4 T cells than that in CD8 T cells. Furthermore, leptin treatment with or without IL-2 and PHA had preferential effects on cell proliferation of CD4 T cells compared to that of CD8 T cells. Collectively, these data provide evidence that the effects of leptin on differentiation and proliferation of CD4 T cells might be closely related to the expression of leptin receptor.

  18. Activated allogeneic NK cells preferentially kill poor prognosis B-cell chronic lymphocytic leukemia cells

    Directory of Open Access Journals (Sweden)

    Diego Sanchez-Martinez

    2016-10-01

    Full Text Available Mutational status of TP53 together with expression of wild type (wt IGHV represents the most widely accepted biomarkers, establishing a very poor prognosis in B-cell chronic lymphocytic leukemia (B-CLL patients. Adoptive cell therapy using allogeneic HLA mismatched Natural Killer (NK cells has emerged as an effective and safe alternative in the treatment of acute myeloid and lymphoid leukemias that do not respond to traditional therapies. We have described that allogeneic activated NK cells eliminate hematological cancer cell lines with multidrug resistance acquired by mutations in the apoptotic machinery. This effect depends on the activation protocol, being B-lymphoblastoid cell lines (LCLs the most effective stimulus to activate NK cells. Here we have further analyzed the molecular determinants involved in allogeneic NK cell recognition and elimination of B-CLL cells, including the expression of ligands of the main NK cell activating receptors (NKG2D and NCRs and HLA mismatch. We present preliminary data suggesting that B-CLL susceptibility significantly correlates with HLA mismatch between NK cell donor and B-CLL patient. Moreover, we show that the sensitivity of B-CLL cells to NK cells depends on the prognosis based on TP53 and IGHV mutational status. Cells from patients with worse prognosis (mutated TP53 and wt IGHV are the most susceptible to activated NK cells. Hence, B-CLL prognosis may predict the efficacy of allogenic activated NK cells and, thus, NK cell transfer represents a good alternative to treat poor prognosis B-CLL patients who present a very short life expectancy due to lack of effective treatments.□

  19. Efficient Differentiation of Mouse Embryonic Stem Cells into Insulin-Producing Cells

    Directory of Open Access Journals (Sweden)

    Szu-Hsiu Liu

    2012-01-01

    Full Text Available Embryonic stem (ES cells are a potential source of a variety of differentiated cells for cell therapy, drug discovery, and toxicology screening. Here, we present an efficacy strategy for the differentiation of mouse ES cells into insulin-producing cells (IPCs by a two-step differentiation protocol comprising of (i the formation of definitive endoderm in monolayer culture by activin A, and (ii this monolayer endoderm being induced to differentiate into IPCs by nicotinamide, insulin, and laminin. Differentiated cells can be obtained within approximately 7 days. The differentiation IPCs combined application of RT-PCR, ELISA, and immunofluorescence to characterize phenotypic and functional properties. In our study, we demonstrated that IPCs produced pancreatic transcription factors, endocrine progenitor marker, definitive endoderm, pancreatic β-cell markers, and Langerhans α and δ cells. The IPCs released insulin in a manner that was dose dependent upon the amount of glucose added. These techniques may be able to be applied to human ES cells, which would have very important ramifications for treating human disease.

  20. 18F-FDG PET/CT in follow-up evaluation in pediatric patients with Langerhans histiocytosis.

    Science.gov (United States)

    Garcia, J R; Riera, E; Bassa, P; Mourelo, S; Soler, M

    We evaluated the impact of 18 F-FDG PET/CT in identifying sites of active disease and to assess therapeutic follow up in a group of pediatric patients with Langerhans cell histiocytosis (LCH). During 2007-2013, 13 18 F-FDG PET/CT studies were performed for follow-up in 7 patients with a diagnosis of LCH (4 female, 3 male; 1-12 years-old). PET findings were analyzed and correlated with the CT and MRI. Findings were also follow-up by these techniques. PET was negative in 4 patients (all diagnosed with bone lesions and one with pituitary involvement also). CT findings showed residual morphological bone lesions in all patients, and hypophysis MRI study showed no abnormal signal. PET remained negative at 10, 14, 25 and 28 months, and no new lesions on CT and MRI were detected. PET was positive in 3 patients (one with cervical lymphadenopathy and 2 with bone lesions, one also with pituitary involvement not identified by PET). CT findings showed pathological cervical lymphadenopathy (n=1), bone lesions (n=2) and also a pituitary MRI lesion (n=1). In a patient with cervical lymphadenopathy histology demonstrated LCH involvement. In the other 2 patients, PET remained positive with an increase of 18 F-FDG bone uptake at 17 and 19 months. In our preliminar study, 18 F-FDG PET is a useful imaging procedure, along with other diagnostic tools, for identification of active lesions. Copyright © 2017 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

  1. Surface-Selective Preferential Production of Reactive Oxygen Species on Piezoelectric Ceramics for Bacterial Killing

    OpenAIRE

    Tan, Guoxin; Wang, Shuangying; Zhu, Ye; Zhou, Lei; Yu, Peng; Wang, Xiaolan; He, Tianrui; Chen, Junqi; Mao, Chuanbin; Ning, Chengyun

    2016-01-01

    Reactive oxygen species (ROS) can be used to kill bacterial cells, and thus the selective generation of ROS from material surfaces is an emerging direction in antibacterial material discovery. We found the polarization of piezoelectric ceramic causes the two sides of the disk to become positively and negatively charged, which translate into cathode and anode surfaces in an aqueous solution. Because of the microelectrolysis of water, ROS are preferentially formed on the cathode surface. Conseq...

  2. Cerebellar leukoencephalopathy: most likely histiocytosis-related

    NARCIS (Netherlands)

    van der Knaap, M.S.; Arts, W.F.M.; Garbern, J.Y.; Hedlund, G.; Winkler, F.; Barbosa, C.; King, M.D.; Bjornstad, A.; Hussain, N.; Beyer, M.K.; Gomez, C.; Patterson, M.C.; Grattan-Smith, P.; Timmons, M.; van der Valk, P.

    2008-01-01

    Background: Histiocytosis, both Langerhans and non-Langerhans cell type, can be associated with cerebellar white matter abnormalities, thought to be paraneoplastic. The associated clinical picture consists of ataxia, spasticity, and cognitive decline. Hormonal dysfunction is frequent. MRI shows

  3. Affecting factors of preferential flow in the forest of the Three Gorges area, Yangtze River

    Institute of Scientific and Technical Information of China (English)

    CHENG Jinhua; ZHANG Hongjiang; HE Fan; QI Shenglin; SUN Yanhong; ZHANG Youyan; SHI Yuhu

    2007-01-01

    In order to study the factors affecting preferential flow,a 2.9 m-long,2.6 m-deep soil profile was dug in the Quxi watershed,Yangtze River.To analyze the influence of rainfall on preferential flow,the preferential flow process was observed when the rainfalls were recorded.Soil physical and infiltration characteristics were also measured to study their effect on preferential flow.The results showed that the rainfall amount that could cause preferential flow was over 26 mm.There are four types of rainfall in the Three Gorges area,namely gradually dropping rain,even rain,sudden rain and peak rain.Preferential flow process was found to be relevant to the rainfall process.It was determined that with different rainfall types,preferential flow appeared at different times,occurring first in peak rain,followed by sudden rain,gradually dropping rain,and then even rain.Preferential flow would appear when the rainfall intensity was over 0.075 mm/min.In the studied area,the coarse soil particles increased with the soil depth,and for the deeper soil layer,the coarse particles promote the formation of preferential flow.Preferential flow accelerates the steady infiltration rate in the 83-110 cm soil horizon,and the quickly moving water in this horizon also enhanced the further formation and development of preferential flow.

  4. Spreading dynamics of an e-commerce preferential information model on scale-free networks

    Science.gov (United States)

    Wan, Chen; Li, Tao; Guan, Zhi-Hong; Wang, Yuanmei; Liu, Xiongding

    2017-02-01

    In order to study the influence of the preferential degree and the heterogeneity of underlying networks on the spread of preferential e-commerce information, we propose a novel susceptible-infected-beneficial model based on scale-free networks. The spreading dynamics of the preferential information are analyzed in detail using the mean-field theory. We determine the basic reproductive number and equilibria. The theoretical analysis indicates that the basic reproductive number depends mainly on the preferential degree and the topology of the underlying networks. We prove the global stability of the information-elimination equilibrium. The permanence of preferential information and the global attractivity of the information-prevailing equilibrium are also studied in detail. Some numerical simulations are presented to verify the theoretical results.

  5. LGR5 and Nanog identify stem cell signature of pancreas beta cells which initiate pancreatic cancer.

    Science.gov (United States)

    Amsterdam, Abraham; Raanan, Calanit; Schreiber, Letizia; Polin, Nava; Givol, David

    2013-04-05

    Pancreas cancer, is the fourth leading cause of cancer death but its cell of origin is controversial. We compared the localization of stem cells in normal and cancerous pancreas using antibodies to the stem cell markers Nanog and LGR5. Here we show, for the first time, that LGR5 is expressed in normal pancreas, exclusively in the islets of Langerhans and it is co-localized, surprisingly, with Nanog and insulin in clusters of beta cells. In cancerous pancreas Nanog and LGR5 are expressed in the remaining islets and in all ductal cancer cells. We observed insulin staining among the ductal cancer cells, but not in metastases. This indicates that the islet's beta cells, expressing LGR5 and Nanog markers are the initiating cells of pancreas cancer, which migrated from the islets to form the ductal cancerous tissue, probably after mutation and de-differentiation. This discovery may facilitate treatment of this devastating cancer. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. The chemokines CCL11, CCL20, CCL21, and CCL24 are preferentially expressed in polarized human secondary lymphoid follicles.

    Science.gov (United States)

    Buri, Caroline; Gutersohn, Andreas; Hauser, Chantal; Kappeler, Andreas; Mueller, Christoph

    2004-10-01

    Chemokines regulate cellular trafficking to and from lymphoid follicles. Here, the distribution pattern of four CCL chemokines is defined by in situ hybridization in human lymphoid follicles from tonsils and lymph nodes (LNs) of newborns and adults. Cells expressing CCL11 (eotaxin) and CCL20 (Exodus) were preferentially located within follicles, while cells expressing CCL21 (secondary lymphoid-tissue chemokine) and CCL24 (eotaxin-2) mRNA were almost exclusively found in the perifollicular areas. Hence, the two CCR3-binding chemokines, CCL11 and CCL24, showed a mutually exclusive expression pattern in the intra- and extra-follicular areas, respectively. Chemokine gene expression paralleled follicular maturation: in tonsils, where approximately 80% of follicles are polarized, CCL11 and CCL20 mRNA-positive cells were detected more frequently than in lymph nodes from adults, where about half of follicles are non-polarized. No intrafollicular chemokine expression was detectable in the primary follicles from newborns. Extrafollicular cells expressing CCL21 and CCL24 were again more frequent in tonsils than in LNs from adults. The observed preferential presence of cells expressing CC chemokines in polarized human lymphoid follicles indicates that chemokines are not only instrumental in the induction of follicle formation, but may also be involved in their further differentiation.

  7. Preferential ascus discharge during cross maturation in Sordaria brevicollis.

    Science.gov (United States)

    MacDonald, D J; Bond, D J

    1974-02-01

    Crosses involving spore color mutants of Sordaria brevicollis all showed a decline in the frequency of second division asymmetric asci (2:2:2:2's) as the cross matured. This decline was due to the preferential maturation and/or discharge of these asci. The proportion of spindle overlap and recombinational asci within the group did not change as shown by ascus dissection. The preferential discharge was also found to occur in two-point crosses where the asci did not contain wild-type spores.

  8. Preferential uptake of ribose by primitive cells might explain why RNA was favored over its analogs

    Science.gov (United States)

    Pohorille, Andrew; Wei, Chenyu

    Permeation of molecules through membranes is a fundamental process in biological systems, which not only involves mass and signal transfers between the interior of a contemporary cell and its environment, but was also of crucial importance in the origin of life. In the absence of complex protein transporters, nutrients and building blocks of biopolymers must have been able to permeate membranes at sufficient rates to support primordial metabolism and cel-lular reproduction. From this perspective one class of solutes that is of special interest are monosaccharides, which serve not only as nutritional molecules but also as building blocks for information molecules. In particular, ribose is a part of the RNA backbone, but RNA analogs containing a number of other sugars have also been shown to form stable duplexes. Why, among these possibilities, ribose (and, subsequently, deoxyribose) was selected for the backbone of information polymers is still poorly understood. It was recently found that ribose permeates membranes an order of magnitude faster than its diastereomers, arabinose and xylose [1]. On this basis it was hypothesized that differences in membrane permeability to aldopentoses provide a mechanism for preferential delivery of ribose to primitive cells for subsequent, selective incorporation into nucleotides and their polymers. However, the origins of these unusually large differences had not been well understood. We addressed this issue in molecular dynamics simulations combined with free energy calculations. It was found that the free energy barrier for transferring ribose from water to the bilayer is lower by 1.5-2 kcal/mol than the barrier for transferring the other two aldopentoses. The calculated [2] and measured [1] permeability coefficients are in an excellent agreement. The sugar structures that permeate the membrane are -pyranoses, with a possible contribution of the -anomer for arabinose. The furanoid form of ribose is not substantially involved in

  9. A young man with multiple pulmonary cysts | Ibrahim | Libyan ...

    African Journals Online (AJOL)

    Several diseases cause cystic or cyst-like parenchymal lung abnormalities including adult pulmonary Langerhan\\'s cell histiocytosis (PLCH), lymphangioleiomyomatosis (LAM), emphysema, end-stage interstitial lung disease, and cystic bronchiectasis. Many of these diseases can now be diagnosed with high accuracy by ...

  10. Numerical modeling of the effect of preferential flow on hillslope hydrology and slope stability

    NARCIS (Netherlands)

    Shao, W.

    2017-01-01

    The topic of this thesis is the quantification of the influence of preferential flow on landslide-triggering in potentially unstable slopes. Preferential flow paths (e.g., cracks, macropores, fissures, pipes, etc.) commonly exists in slopes. Flow velocities in preferential flow paths can be

  11. A Weighted Evolving Network with Community Size Preferential Attachment

    International Nuclear Information System (INIS)

    Zhuo Zhiwei; Shan Erfang

    2010-01-01

    Community structure is an important characteristic in real complex network. It is a network consists of groups of nodes within which links are dense but among which links are sparse. In this paper, the evolving network include node, link and community growth and we apply the community size preferential attachment and strength preferential attachment to a growing weighted network model and utilize weight assigning mechanism from BBV model. The resulting network reflects the intrinsic community structure with generalized power-law distributions of nodes' degrees and strengths.

  12. Protein-solvent preferential interactions, protein hydration, and the modulation of biochemical reactions by solvent components.

    Science.gov (United States)

    Timasheff, Serge N

    2002-07-23

    Solvent additives (cosolvents, osmolytes) modulate biochemical reactions if, during the course of the reaction, there is a change in preferential interactions of solvent components with the reacting system. Preferential interactions can be expressed in terms of preferential binding of the cosolvent or its preferential exclusion (preferential hydration). The driving force is the perturbation by the protein of the chemical potential of the cosolvent. It is shown that the measured change of the amount of water in contact with protein during the course of the reaction modulated by an osmolyte is a change in preferential hydration that is strictly a measure of the cosolvent chemical potential perturbation by the protein in the ternary water-protein-cosolvent system. It is not equal to the change in water of hydration, because water of hydration is a reflection strictly of protein-water forces in a binary system. There is no direct relation between water of preferential hydration and water of hydration.

  13. The Probabilistic Nature of Preferential Choice

    Science.gov (United States)

    Rieskamp, Jorg

    2008-01-01

    Previous research has developed a variety of theories explaining when and why people's decisions under risk deviate from the standard economic view of expected utility maximization. These theories are limited in their predictive accuracy in that they do not explain the probabilistic nature of preferential choice, that is, why an individual makes…

  14. Controlled surface chemistry of diamond/β-SiC composite films for preferential protein adsorption.

    Science.gov (United States)

    Wang, Tao; Handschuh-Wang, Stephan; Yang, Yang; Zhuang, Hao; Schlemper, Christoph; Wesner, Daniel; Schönherr, Holger; Zhang, Wenjun; Jiang, Xin

    2014-02-04

    Diamond and SiC both process extraordinary biocompatible, electronic, and chemical properties. A combination of diamond and SiC may lead to highly stable materials, e.g., for implants or biosensors with excellent sensing properties. Here we report on the controllable surface chemistry of diamond/β-SiC composite films and its effect on protein adsorption. For systematic and high-throughput investigations, novel diamond/β-SiC composite films with gradient composition have been synthesized using the hot filament chemical vapor deposition (HFCVD) technique. As revealed by scanning electron microscopy (SEM), the diamond/β-SiC ratio of the composite films shows a continuous change from pure diamond to β-SiC over a length of ∼ 10 mm on the surface. X-ray photoelectron spectroscopy (XPS) and time-of-flight secondary ion mass spectrometry (ToF-SIMS) was employed to unveil the surface termination of chemically oxidized and hydrogen treated surfaces. The surface chemistry of the composite films was found to depend on diamond/β-SiC ratio and the surface treatment. As observed by confocal fluorescence microscopy, albumin and fibrinogen were preferentially adsorbed from buffer: after surface oxidation, the proteins preferred to adsorb on diamond rather than on β-SiC, resulting in an increasing amount of proteins adsorbed to the gradient surfaces with increasing diamond/β-SiC ratio. By contrast, for hydrogen-treated surfaces, the proteins preferentially adsorbed on β-SiC, leading to a decreasing amount of albumin adsorbed on the gradient surfaces with increasing diamond/β-SiC ratio. The mechanism of preferential protein adsorption is discussed by considering the hydrogen bonding of the water self-association network to OH-terminated surfaces and the change of the polar surface energy component, which was determined according to the van Oss method. These results suggest that the diamond/β-SiC gradient film can be a promising material for biomedical applications which

  15. Preferential aerosolization of bacteria in bioaerosols generated in vitro.

    Science.gov (United States)

    Perrott, P; Turgeon, N; Gauthier-Levesque, L; Duchaine, C

    2017-09-01

    Little is known about how bacteria are aerosolized in terms of whether some bacteria will be found in the air more readily than others that are present in the source. This report describes in vitro experiments to compare aerosolization rates (also known as preferential aerosolization) of Gram-positive and Gram-negative bacteria as well as rod- and coccus-shaped bacteria, using two nebulization conditions. A consortium of five bacterial species was aerosolized in a homemade chamber. Aerosols generated with a commercial nebulizer and a homemade bubble-burst aerosol generator were compared. Data suggest that Pseudomonas aeruginosa was preferentially aerosolized in comparison to Moraxella catarrhalis, Lactobacillus paracasei, Staphylococcus aureus and Streptococcus suis, independently of the method of aerosolization. Bacterial integrity of Strep. suis was more preserved compared to other bacteria studied as revealed with PMA-qPCR. We reported the design of an aerosol chamber and bubble-burst generator for the in vitro study of preferential aerosolization. In our setting, preferential aerosolization was influenced by bacterial properties instead of aerosolization mechanism. These findings could have important implications for predicting the composition of bioaerosols in various locations such as wastewater treatment plants, agricultural settings and health care settings. © 2017 The Society for Applied Microbiology.

  16. Microwell Scaffolds for the Extrahepatic Transplantation of Islets of Langerhans

    Science.gov (United States)

    Buitinga, Mijke; Truckenmüller, Roman; Engelse, Marten A.; Moroni, Lorenzo; Ten Hoopen, Hetty W. M.; van Blitterswijk, Clemens A.; de Koning, Eelco JP.; van Apeldoorn, Aart A.; Karperien, Marcel

    2013-01-01

    Allogeneic islet transplantation into the liver has the potential to restore normoglycemia in patients with type 1 diabetes. However, the suboptimal microenvironment for islets in the liver is likely to be involved in the progressive islet dysfunction that is often observed post-transplantation. This study validates a novel microwell scaffold platform to be used for the extrahepatic transplantation of islet of Langerhans. Scaffolds were fabricated from either a thin polymer film or an electrospun mesh of poly(ethylene oxide terephthalate)-poly(butylene terephthalate) (PEOT/PBT) block copolymer (composition: 4000PEOT30PBT70) and were imprinted with microwells, ∼400 µm in diameter and ∼350 µm in depth. The water contact angle and water uptake were 39±2° and 52.1±4.0 wt%, respectively. The glucose flux through electrospun scaffolds was three times higher than for thin film scaffolds, indicating enhanced nutrient diffusion. Human islets cultured in microwell scaffolds for seven days showed insulin release and insulin content comparable to those of free-floating control islets. Islet morphology and insulin and glucagon expression were maintained during culture in the microwell scaffolds. Our results indicate that the microwell scaffold platform prevents islet aggregation by confinement of individual islets in separate microwells, preserves the islet’s native rounded morphology, and provides a protective environment without impairing islet functionality, making it a promising platform for use in extrahepatic islet transplantation. PMID:23737999

  17. Dependence of crystallite formation and preferential backbone orientations on the side chain pattern in PBDTTPD polymers

    KAUST Repository

    El Labban, Abdulrahman

    2014-11-26

    (Figure Presented) Alkyl substituents appended to the π-conjugated main chain account for the solution-processability and film-forming properties of most π-conjugated polymers for organic electronic device applications, including field-effect transistors (FETs) and bulk-heterojunction (BHJ) solar cells. Beyond film-forming properties, recent work has emphasized the determining role that side-chain substituents play on polymer self-assembly and thin-film nanostructural order, and, in turn, on device performance. However, the factors that determine polymer crystallite orientation in thin-films, implying preferential backbone orientation relative to the device substrate, are a matter of some debate, and these structural changes remain difficult to anticipate. In this report, we show how systematic changes in the side-chain pattern of poly(benzo[1,2-b:4,5-b′]dithiophene-alt-thieno[3,4-c]pyrrole-4,6-dione) (PBDTTPD) polymers can (i) influence the propensity of the polymer to order in the π-stacking direction, and (ii) direct the preferential orientation of the polymer crystallites in thin films (e.g., "face-on" vs "edge-on"). Oriented crystallites, specifically crystallites that are well-ordered in the π-stacking direction, are believed to be a key contributor to improved thin-film device performance in both FETs and BHJ solar cells.

  18. Hand-Schüller-Christian disease

    Directory of Open Access Journals (Sweden)

    Deepak Bhargava

    2012-01-01

    Full Text Available Langerhan cell histiocytosis, formerly known as histiocytosis X, traditionally denotes a group of diseases that stem from proliferative reticuloendothelial disturbances.The etiology and pathogenesis of the disease remain debatable. In this paper we report a case of Langerhan cell histiocytosis in a 3 1 / 2 -year-old child who reported to the department of oral pathology with gingival enlargements. The radiological features and histopathological features are also discussed.

  19. Preferential flow in water-repellent sandy soils : model development and lysimeter experiments

    NARCIS (Netherlands)

    Rooij, de G.H.

    1996-01-01


    When water enters a water-repellent topsoil, preferential flow paths develop and the flow bypasses a large part of the unsaturated zone. Therefore, preferential flow caused by water- repellency is expected to accelerate solute leaching to the groundwater. In soils with water-repellent

  20. The anti-tumor drug bleomycin preferentially cleaves at the transcription start sites of actively transcribed genes in human cells.

    Science.gov (United States)

    Murray, Vincent; Chen, Jon K; Galea, Anne M

    2014-04-01

    The genome-wide pattern of DNA cleavage at transcription start sites (TSSs) for the anti-tumor drug bleomycin was examined in human HeLa cells using next-generation DNA sequencing. It was found that actively transcribed genes were preferentially cleaved compared with non-transcribed genes. The 143,600 identified human TSSs were split into non-transcribed genes (82,596) and transcribed genes (61,004) for HeLa cells. These transcribed genes were further split into quintiles of 12,201 genes comprising the top 20, 20-40, 40-60, 60-80, and 80-100 % of expressed genes. The bleomycin cleavage pattern at highly transcribed gene TSSs was greatly enhanced compared with purified DNA and non-transcribed gene TSSs. The top 20 and 20-40 % quintiles had a very similar enhanced cleavage pattern, the 40-60 % quintile was intermediate, while the 60-80 and 80-100 % quintiles were close to the non-transcribed and purified DNA profiles. The pattern of bleomycin enhanced cleavage had peaks that were approximately 200 bp apart, and this indicated that bleomycin was identifying the presence of phased nucleosomes at TSSs. Hence bleomycin can be utilized to detect chromatin structures that are present at actively transcribed genes. In this study, for the first time, the pattern of DNA damage by a clinically utilized cancer chemotherapeutic agent was performed on a human genome-wide scale at the nucleotide level.

  1. Stratification of TAD boundaries reveals preferential insulation of super-enhancers by strong boundaries.

    Science.gov (United States)

    Gong, Yixiao; Lazaris, Charalampos; Sakellaropoulos, Theodore; Lozano, Aurelie; Kambadur, Prabhanjan; Ntziachristos, Panagiotis; Aifantis, Iannis; Tsirigos, Aristotelis

    2018-02-07

    The metazoan genome is compartmentalized in areas of highly interacting chromatin known as topologically associating domains (TADs). TADs are demarcated by boundaries mostly conserved across cell types and even across species. However, a genome-wide characterization of TAD boundary strength in mammals is still lacking. In this study, we first use fused two-dimensional lasso as a machine learning method to improve Hi-C contact matrix reproducibility, and, subsequently, we categorize TAD boundaries based on their insulation score. We demonstrate that higher TAD boundary insulation scores are associated with elevated CTCF levels and that they may differ across cell types. Intriguingly, we observe that super-enhancers are preferentially insulated by strong boundaries. Furthermore, we demonstrate that strong TAD boundaries and super-enhancer elements are frequently co-duplicated in cancer patients. Taken together, our findings suggest that super-enhancers insulated by strong TAD boundaries may be exploited, as a functional unit, by cancer cells to promote oncogenesis.

  2. Preferential radiosensitization of human prostatic carcinoma cells by mild hyperthermia

    International Nuclear Information System (INIS)

    Ryu, Samuel; Brown, Stephen L.; Kim, Sang-Hie; Khil, Mark S.; Kim, Jae Ho

    1996-01-01

    Purpose: Recent cell culture studies by us and others suggest that some human carcinoma cells are more sensitive to heat than are rodent cells following mild hyperthermia. In studying the cellular mechanism of enhanced thermosensitivity of human tumor cells to hyperthermia, prostatic carcinoma cells of human origin were found to be more sensitive to mild hyperthermia than other human cancer cells. The present study was designed to determine the magnitude of radiosensitization of human prostatic carcinoma cells by mild hyperthermia and to examine whether the thermal radiosensitization is related to the intrinsic thermosensitivity of cancer cells. Methods and Materials: Two human prostatic carcinoma cell lines (DU-145 and PC-3) and other carcinoma cells of human origin, in particular, colon (HT-29), breast (MCF-7), lung (A-549), and brain (U-251) were exposed to temperatures of 40-41 deg. C. Single acute dose rate radiation and fractionated radiation were combined with mild hyperthermia to determine thermal radiosensitization. The end point of the study was the colony-forming ability of single-plated cells. Results: DU-145 and PC-3 cells were found to be exceedingly thermosensitive to 41 deg. C for 24 h, relative to other cancer cell lines. Ninety percent of the prostatic cancer cells were killed by a 24 h heat exposure. Prostatic carcinoma cells exposed to a short duration of heating at 41 deg. C for 2 h resulted in a substantial enhancement of radiation-induced cytotoxicity. The thermal enhancement ratios (TERs) of single acute dose radiation following heat treatment 41 deg. C for 2 h were 2.0 in DU-145 cells and 1.4 in PC-3 cells. The TERs of fractionated irradiation combined with continuous heating at 40 deg. C were similarly in the range of 2.1 to 1.4 in prostate carcinoma cells. No significant radiosensitization was observed in MCF-7 and HT-29 cells under the same conditions. Conclusion: The present data suggest that a significant radiosensitization of

  3. Preferential Allele Expression Analysis Identifies Shared Germline and Somatic Driver Genes in Advanced Ovarian Cancer

    Science.gov (United States)

    Halabi, Najeeb M.; Martinez, Alejandra; Al-Farsi, Halema; Mery, Eliane; Puydenus, Laurence; Pujol, Pascal; Khalak, Hanif G.; McLurcan, Cameron; Ferron, Gwenael; Querleu, Denis; Al-Azwani, Iman; Al-Dous, Eman; Mohamoud, Yasmin A.; Malek, Joel A.; Rafii, Arash

    2016-01-01

    Identifying genes where a variant allele is preferentially expressed in tumors could lead to a better understanding of cancer biology and optimization of targeted therapy. However, tumor sample heterogeneity complicates standard approaches for detecting preferential allele expression. We therefore developed a novel approach combining genome and transcriptome sequencing data from the same sample that corrects for sample heterogeneity and identifies significant preferentially expressed alleles. We applied this analysis to epithelial ovarian cancer samples consisting of matched primary ovary and peritoneum and lymph node metastasis. We find that preferentially expressed variant alleles include germline and somatic variants, are shared at a relatively high frequency between patients, and are in gene networks known to be involved in cancer processes. Analysis at a patient level identifies patient-specific preferentially expressed alleles in genes that are targets for known drugs. Analysis at a site level identifies patterns of site specific preferential allele expression with similar pathways being impacted in the primary and metastasis sites. We conclude that genes with preferentially expressed variant alleles can act as cancer drivers and that targeting those genes could lead to new therapeutic strategies. PMID:26735499

  4. Effects of the beta-carbolines, harmane and pinoline, on insulin secretion from isolated human islets of Langerhans.

    Science.gov (United States)

    Cooper, E Jane; Hudson, Alan L; Parker, Christine A; Morgan, Noel G

    2003-12-15

    It is well known that certain imidazoline compounds can stimulate insulin secretion and this has been attributed to the activation of imidazoline I(3) binding sites in the pancreatic beta-cell. Recently, it has been proposed that beta-carbolines may be endogenous ligands having activity at imidazoline sites and we have, therefore, studied the effects of beta-carbolines on insulin secretion. The beta-carbolines harmane, norharmane and pinoline increased insulin secretion two- to threefold from isolated human islets of Langerhans. The effects of harmane and pinoline were dose-dependent (EC(50): 5 and 25 microM, respectively) and these agents also blocked the inhibitory effects of the potassium channel agonist, diazoxide, on glucose-induced insulin release. Stimulation of insulin secretion by harmane was glucose-dependent but, unlike the imidazoline I(3) receptor agonist efaroxan, it increased the rate of insulin release beyond that elicited by 20 mM glucose (20 mM glucose alone: 253+/-34% vs. basal; 20 mM glucose plus 100 microM harmane: 327+/-15%; P<0.01). Stimulation of insulin secretion by harmane was attenuated by the imidazoline I(3) receptor antagonist KU14R (2 (2-ethyl 2,3-dihydro-2-benzofuranyl)-2-imidazole) and was reduced when islets were treated with efaroxan for 18 h, prior to the addition of harmane. The results reveal that beta-carbolines can potentiate the rate of insulin secretion from human islets and suggest that these agents may be useful prototypes for the development of novel insulin secretagogues.

  5. Using DC electrical resistivity tomography to quantify preferential flow in fractured rock environments

    CSIR Research Space (South Africa)

    May, F

    2011-09-01

    Full Text Available . This investigation aims to identify preferential flow paths in fractured rock environments. Time-lapse Electrical Resistivity Tomography (TLERT, Lund Imaging System), is regarded as a suitable method for identifying preferential water flow....

  6. Spatial connectivity in a highly heterogeneous aquifer: From cores to preferential flow paths

    Science.gov (United States)

    Bianchi, M.; Zheng, C.; Wilson, C.; Tick, G.R.; Liu, Gaisheng; Gorelick, S.M.

    2011-01-01

    This study investigates connectivity in a small portion of the extremely heterogeneous aquifer at the Macrodispersion Experiment (MADE) site in Columbus, Mississippi. A total of 19 fully penetrating soil cores were collected from a rectangular grid of 4 m by 4 m. Detailed grain size analysis was performed on 5 cm segments of each core, yielding 1740 hydraulic conductivity (K) estimates. Three different geostatistical simulation methods were used to generate 3-D conditional realizations of the K field for the sampled block. Particle tracking calculations showed that the fastest particles, as represented by the first 5% to arrive, converge along preferential flow paths and exit the model domain within preferred areas. These 5% fastest flow paths accounted for about 40% of the flow. The distribution of preferential flow paths and particle exit locations is clearly influenced by the occurrence of clusters formed by interconnected cells with K equal to or greater than the 0.9 decile of the data distribution (10% of the volume). The fraction of particle paths within the high-K clusters ranges from 43% to 69%. In variogram-based K fields, some of the fastest paths are through media with lower K values, suggesting that transport connectivity may not require fully connected zones of relatively homogenous K. The high degree of flow and transport connectivity was confirmed by the values of two groups of connectivity indicators. In particular, the ratio between effective and geometric mean K (on average, about 2) and the ratio between the average arrival time and the arrival time of the fastest particles (on average, about 9) are consistent with flow and advective transport behavior characterized by channeling along preferential flow paths. ?? 2011 by the American Geophysical Union.

  7. Identification of Homophily and Preferential Recruitment in Respondent-Driven Sampling.

    Science.gov (United States)

    Crawford, Forrest W; Aronow, Peter M; Zeng, Li; Li, Jianghong

    2018-01-01

    Respondent-driven sampling (RDS) is a link-tracing procedure used in epidemiologic research on hidden or hard-to-reach populations in which subjects recruit others via their social networks. Estimates from RDS studies may have poor statistical properties due to statistical dependence in sampled subjects' traits. Two distinct mechanisms account for dependence in an RDS study: homophily, the tendency for individuals to share social ties with others exhibiting similar characteristics, and preferential recruitment, in which recruiters do not recruit uniformly at random from their network alters. The different effects of network homophily and preferential recruitment in RDS studies have been a source of confusion and controversy in methodological and empirical research in epidemiology. In this work, we gave formal definitions of homophily and preferential recruitment and showed that neither is identified in typical RDS studies. We derived nonparametric identification regions for homophily and preferential recruitment and showed that these parameters were not identified unless the network took a degenerate form. The results indicated that claims of homophily or recruitment bias measured from empirical RDS studies may not be credible. We applied our identification results to a study involving both a network census and RDS on a population of injection drug users in Hartford, Connecticut (2012-2013). © The Author(s) 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  8. Fitness networks for real world systems via modified preferential attachment

    Science.gov (United States)

    Shang, Ke-ke; Small, Michael; Yan, Wei-sheng

    2017-05-01

    Complex networks are virtually ubiquitous, and the Barabási and Albert model (BA model) has became an acknowledged standard for the modelling of these systems. The so-called BA model is a kind of preferential attachment growth model based on the intuitive premise that popularity is attractive. However, preferential attachment alone is insufficient to describe the diversity of complex networks observed in the real world. In this paper we first use the accuracy of a link prediction method, as a metric for network fitness. The link prediction method predicts the occurrence of links consistent with preferential attachment, the performance of this link prediction scheme is then a natural measure of the ;preferential-attachment-likeness; of a given network. We then propose several modification methods and modified BA models to construct networks which more accurately describe the fitness properties of real networks. We find that all features assortativity, degree distribution and rich-club formation can play significant roles for the network construction and eventual structure. Moreover, link sparsity and the size of a network are key factors for network reconstruction. In addition, we find that the structure of the network which is limited by geographic location (nodes are embedded in a Euclidean space and connectivity is correlated with distances) differs from other typical networks. In social networks, we observe that the high school contact network has similar structure as the friends network and so we speculate that the contact behaviours can reflect real friendships.

  9. Nanofibrillar scaffolds induce preferential activation of Rho GTPases in cerebral cortical astrocytes

    Science.gov (United States)

    Tiryaki, Volkan Mujdat; Ayres, Virginia M; Khan, Adeel A; Ahmed, Ijaz; Shreiber, David I; Meiners, Sally

    2012-01-01

    Cerebral cortical astrocyte responses to polyamide nanofibrillar scaffolds versus poly-L-lysine (PLL)-functionalized planar glass, unfunctionalized planar Aclar coverslips, and PLL-functionalized planar Aclar surfaces were investigated by atomic force microscopy and immunocytochemistry. The physical properties of the cell culture environments were evaluated using contact angle and surface roughness measurements and compared. Astrocyte morphological responses, including filopodia, lamellipodia, and stress fiber formation, and stellation were imaged using atomic force microscopy and phalloidin staining for F-actin. Activation of the corresponding Rho GTPase regulators was investigated using immunolabeling with Cdc42, Rac1, and RhoA. Astrocytes cultured on the nanofibrillar scaffolds showed a unique response that included stellation, cell–cell interactions by stellate processes, and evidence of depression of RhoA. The results support the hypothesis that the extracellular environment can trigger preferential activation of members of the Rho GTPase family, with demonstrable morphological consequences for cerebral cortical astrocytes. PMID:22915841

  10. Heterogeneous Ribosomes Preferentially Translate Distinct Subpools of mRNAs Genome-wide.

    Science.gov (United States)

    Shi, Zhen; Fujii, Kotaro; Kovary, Kyle M; Genuth, Naomi R; Röst, Hannes L; Teruel, Mary N; Barna, Maria

    2017-07-06

    Emerging studies have linked the ribosome to more selective control of gene regulation. However, an outstanding question is whether ribosome heterogeneity at the level of core ribosomal proteins (RPs) exists and enables ribosomes to preferentially translate specific mRNAs genome-wide. Here, we measured the absolute abundance of RPs in translating ribosomes and profiled transcripts that are enriched or depleted from select subsets of ribosomes within embryonic stem cells. We find that heterogeneity in RP composition endows ribosomes with differential selectivity for translating subpools of transcripts, including those controlling metabolism, cell cycle, and development. As an example, mRNAs enriched in binding to RPL10A/uL1-containing ribosomes are shown to require RPL10A/uL1 for their efficient translation. Within several of these transcripts, this level of regulation is mediated, at least in part, by internal ribosome entry sites. Together, these results reveal a critical functional link between ribosome heterogeneity and the post-transcriptional circuitry of gene expression. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. PREFERENTIAL SECRETION OF INDUCIBLE HSP70 BY VITILIGO MELANOCYTES UNDER STRESS

    Science.gov (United States)

    Mosenson, Jeffrey A.; Flood, Kelsey; Klarquist, Jared; Eby, Jonathan M.; Koshoffer, Amy; Boissy, Raymond E.; Overbeck, Andreas; C.Tung, Rebecca; Poole, I. Caroline Le

    2014-01-01

    SUMMARY Inducible HSP70 (HSP70i) chaperones peptides from stressed cells, protecting them from apoptosis. Upon extracellular release, HSP70i serves an adjuvant function, enhancing immune responses to bound peptides. We questioned whether HSP70i differentially protects control and vitiligo melanocytes from stress and subsequent immune responses. We compared expression of HSP70i in skin samples, evaluated the viability of primary vitiligo and control melanocytes exposed to bleaching phenols, and measured secreted HSP70i. We determined whether HSP70i traffics to melanosomes to contact immunogenic proteins by cell fractionation, western blotting, electron microscopy and confocal microscopy. Viability of vitiligo and control melanocytes was equally affected under stress. However, vitiligo melanocytes secreted increased amounts of HSP70i in response to MBEH, corroborating with aberrant HSP70i expression in patient skin. Intracellular HSP70i colocalized with melanosomes, and more so in response to MBEH in vitiligo melanocytes. Thus whereas either agent is cytotoxic to melanocytes, MBEH preferentially induces immune responses to melanocytes. PMID:24354861

  12. Dendritic cells and skin sensitization: Biological roles and uses in hazard identification

    International Nuclear Information System (INIS)

    Ryan, Cindy A.; Kimber, Ian; Basketter, David A.; Pallardy, Marc; Gildea, Lucy A.; Gerberick, G. Frank

    2007-01-01

    Recent advances have been made in our understanding of the roles played by cutaneous dendritic cells (DCs) in the induction of contact allergy. A number of associated changes in epidermal Langerhans cell phenotype and function required for effective skin sensitization are providing the foundations for the development of cellular assays (using DC and DC-like cells) for skin sensitization hazard identification. These alternative approaches to the identification and characterization of skin sensitizing chemicals were the focus of a Workshop entitled 'Dendritic Cells and Skin Sensitization: Biological Roles and Uses in Hazard Identification' that was given at the annual Society of Toxicology meeting held March 6-9, 2006 in San Diego, California. This paper reports information that was presented during the Workshop

  13. Preferential adsorption of uranium ions in aqueous solutions by polymers

    International Nuclear Information System (INIS)

    Sakuragi, Masako; Ichimura, Kunihiro; Fujishige, Shoei; Kato, Masao

    1981-01-01

    Amidoxime fiber and triazine fiber were prepared by chemical modification of commercially available polyacrylonitril fiber. It was found that the Amidoxime fiber is efficient to adsorb uranium ions in the artificial sea water. The efficiency of the preferential adsorption decreases by treatment the material with an acid-or an alkaline-solution. The triazine fiber adsorbs uranium ions only in aqueous solutions of such uranyl acetate, in the absence of other ions. In the artificial sea water, it adsorbs other ions instead of uranium. The preferential adsorption of uranium ions was further investigated with a series of polystyrenesulfonamides. Among the polystyrene derivatives, those having carboxyl groups, derived from imino diacetic acid (PSt-Imi), β-alanine (PSt-Ala), glycine (PSt-Gly), and sarcosine (PSt-Sar) were qualified for further discussion. However, it was found that the amount of adsorption of uranium ions by PSt-Imi decreases with increasing the volume of the artificial sea water and/or the duration of the treatment. Taking into account the facts, the preferential adsorption of uranium ions by PSt-Imi in aqueous solution was discussed in detail. (author)

  14. Stem cells and the pancreas: from discovery to clinical approach

    Directory of Open Access Journals (Sweden)

    Angelica Dessì

    2016-02-01

    Full Text Available The existence of stem cells within the adult pancreas is supported by the ability of this organ to regenerate its endocrine component in various conditions such as pregnancy and following partial pancreatectomy. Several studies have shown that progenitor or adult stem cells may reside within the pancreas and particularly in the pancreatic ducts, including acinar cells and islets of Langerhans. The discovery of human pluripotent stem cells in the pancreas, and the possibility of development of strategies for generating these, represented a turning point for the therapeutic interventions of type 1 diabetes.Proceedings of the 2nd International Course on Perinatal Pathology (part of the 11th International Workshop on Neonatology · October 26th-31st, 2015 · Cagliari (Italy · October 31st, 2015 · Stem cells: present and future Guest Editors: Gavino Faa, Vassilios Fanos, Antonio Giordano

  15. TWO MEASURES OF THE DEPENDENCE OF PREFERENTIAL RANKINGS ON CATEGORICAL VARIABLES

    Directory of Open Access Journals (Sweden)

    Lissowski Grzegorz

    2017-06-01

    Full Text Available The aim of this paper is to apply a general methodology for constructing statistical methods, which is based on decision theory, to give a statistical description of preferential rankings, with a focus on the rankings’ dependence on categorical variables. In the paper, I use functions of description errors that are based on the Kemeny and Hamming distances between preferential orderings, but the proposed methodology can also be applied to other methods of estimating description errors.

  16. Growth of preferential attachment random graphs via continuous ...

    Indian Academy of Sciences (India)

    Preferential attachment processes have a long history dating back at least to Yule ... We remark that some connections to branching and continuous-time Markov ..... convenience, we provide a short proof of Lemma 2.1 in the general form in ...

  17. Estimating preferential flow in karstic aquifers using statistical mixed models.

    Science.gov (United States)

    Anaya, Angel A; Padilla, Ingrid; Macchiavelli, Raul; Vesper, Dorothy J; Meeker, John D; Alshawabkeh, Akram N

    2014-01-01

    Karst aquifers are highly productive groundwater systems often associated with conduit flow. These systems can be highly vulnerable to contamination, resulting in a high potential for contaminant exposure to humans and ecosystems. This work develops statistical models to spatially characterize flow and transport patterns in karstified limestone and determines the effect of aquifer flow rates on these patterns. A laboratory-scale Geo-HydroBed model is used to simulate flow and transport processes in a karstic limestone unit. The model consists of stainless steel tanks containing a karstified limestone block collected from a karst aquifer formation in northern Puerto Rico. Experimental work involves making a series of flow and tracer injections, while monitoring hydraulic and tracer response spatially and temporally. Statistical mixed models (SMMs) are applied to hydraulic data to determine likely pathways of preferential flow in the limestone units. The models indicate a highly heterogeneous system with dominant, flow-dependent preferential flow regions. Results indicate that regions of preferential flow tend to expand at higher groundwater flow rates, suggesting a greater volume of the system being flushed by flowing water at higher rates. Spatial and temporal distribution of tracer concentrations indicates the presence of conduit-like and diffuse flow transport in the system, supporting the notion of both combined transport mechanisms in the limestone unit. The temporal response of tracer concentrations at different locations in the model coincide with, and confirms the preferential flow distribution generated with the SMMs used in the study. © 2013, National Ground Water Association.

  18. Global investigation of interleukin-1β signaling in primary β-cells using quantitative phosphoproteomics

    DEFF Research Database (Denmark)

    Engholm-Keller, Kasper; Størling, Joachim; Pociot, Flemming

    in β-cells by which this cytokine can modulate cell-matrix interactions during inflammation, a regulation shown in other cell types. Further data analysis is currently ongoing, and the collective results of the experiments will hopefully facilitate additional insights into the effect of IL-1β......Novel Aspect: Global phosphoproteomic analysis of cytokine signaling in primary β-cells Introduction The insulin-producing β-cells of the pancreatic islets of Langerhans are targeted by aberrant immune system responses in diabetes mellitus involving cytokines, especially interleukin-1β (IL-1 β......), which initiate apoptosis of the β-cells. As only limited amounts of primary β-cells can be isolated from model organisms like mouse and rat, global phosphoproteomic analysis of these signaling events by mass spectrometry has generally been unfeasible. We have therefore developed a strategy...

  19. Preferential acceleration in collisionless supernova shocks

    International Nuclear Information System (INIS)

    Hainebach, K.; Eichler, D.; Schramm, D.

    1979-01-01

    The preferential acceleration and resulting cosmic ray abundance enhancements of heavy elements (relative to protons) are calculated in the collisionless supernova shock acceleration model described by Eichler in earlier work. Rapidly increasing enhancements up to several tens times solar ratios are obtained as a function of atomic weight over charge at the time of acceleration. For material typical of hot phase interstellar medium, good agreement is obtained with the observed abundance enhancements

  20. Epidermal Langerhans' cell induction of immunity against an ultraviolet-induced skin tumour

    International Nuclear Information System (INIS)

    Cavanagh, L.L.; Sluyter, R.; Henderson, K.G.; Barnetson, R.St.C.; Halliday, G.M.

    1996-01-01

    Lanerghans' cells (LC) have been shown experimentally to induce immune response against many antigens; however, their role in the initiation of anti-tumour immunity has received little attention. This study examined the ability of murine epidermal LC to induce immunity to an ultraviolet radiation (UV)-induced skin tumour. Freshly prepared epidermal cells (EC) were cultured for 2 or 20 hr with granulocyte-macrophage colony-stimulating factor (GM-CSF), pulsed with an extract of the UV-13-1 tumour, then used to immunize naive syngeneic mice. Delayed type hypersensitivity (DTH) was elicited 10 days after immunization by injection of UV-13-1 tumour cells into the ear pinna, and measured 24 hr later. EC cultured with GM-CSF for 2 hr induced anti-tumour DTH, as did EC cultured for 20 hr without GM-CSF. Conversely, EC cultured for 2 hr without GM-CSF, or EC cultured for 20 hr with GM-CSF were unable to induce a DTH. Induction of immunity required active presentation of tumour antigens by Ia + EC and was tumour specific. Thus Ia + epidermal cells are capable of inducing anti-tumour immunity to UV-induced skin tumours, but only when they contact antigen in particular states of maturation. (author)

  1. On the coherent behavior of pancreatic beta cell clusters

    Energy Technology Data Exchange (ETDEWEB)

    Loppini, Alessandro, E-mail: a.loppini@unicampus.it [Nonlinear Physics and Mathematical Modeling Lab, University Campus Bio-Medico, Via A. del Portillo 21, I-00128 Rome (Italy); Capolupo, Antonio, E-mail: capolupo@sa.infn.it [Physics Department, University of Salerno, Fisciano, 84084 (Italy); Cherubini, Christian, E-mail: c.cherubini@unicampus.it [Nonlinear Physics and Mathematical Modeling Lab, University Campus Bio-Medico, Via A. del Portillo 21, I-00128 Rome (Italy); International Center for Relativistic Astrophysics, University Campus Bio-Medico, Via A. del Portillo 21, I-00128, Rome (Italy); Gizzi, Alessio, E-mail: a.gizzi@unicampus.it [Nonlinear Physics and Mathematical Modeling Lab, University Campus Bio-Medico, Via A. del Portillo 21, I-00128 Rome (Italy); Bertolaso, Marta, E-mail: m.bertolaso@unicampus.it [Faculty of Engineering and Institute of Philosophy of Scientific and Technological Practice, University Campus Bio-Medico, Via A. del Portillo 21, I-00128 Rome (Italy); Filippi, Simonetta, E-mail: s.filippi@unicampus.it [Nonlinear Physics and Mathematical Modeling Lab, University Campus Bio-Medico, Via A. del Portillo 21, I-00128 Rome (Italy); International Center for Relativistic Astrophysics, University Campus Bio-Medico, Via A. del Portillo 21, I-00128, Rome (Italy); Vitiello, Giuseppe, E-mail: vitiello@sa.infn.it [Physics Department, University of Salerno, Fisciano, 84084 (Italy)

    2014-09-12

    Beta cells in pancreas represent an example of coupled biological oscillators which via communication pathways, are able to synchronize their electrical activity, giving rise to pulsatile insulin release. In this work we numerically analyze scale free self-similarity features of membrane voltage signal power density spectrum, through a stochastic dynamical model for beta cells in the islets of Langerhans fine tuned on mouse experimental data. Adopting the algebraic approach of coherent state formalism, we show how coherent molecular domains can arise from proper functional conditions leading to a parallelism with “phase transition” phenomena of field theory. - Highlights: • Beta cells in pancreas are coupled oscillators able to synchronize their activity. • We analyze scale free self-similarity features for beta cells. • We adopt the algebraic approach of coherent state formalism. • We show that coherent molecular domains arise from functional conditions.

  2. Preferential selection based on degree difference in the spatial prisoner's dilemma games

    Science.gov (United States)

    Huang, Changwei; Dai, Qionglin; Cheng, Hongyan; Li, Haihong

    2017-10-01

    Strategy evolution in spatial evolutionary games is generally implemented through imitation processes between individuals. In most previous studies, it is assumed that individuals pick up one of their neighbors randomly to learn from. However, by considering the heterogeneity of individuals' influence in the real society, preferential selection is more realistic. Here, we introduce a preferential selection mechanism based on degree difference into spatial prisoner's dilemma games on Erdös-Rényi networks and Barabási-Albert scale-free networks and investigate the effects of the preferential selection on cooperation. The results show that, when the individuals prefer to choose the neighbors who have small degree difference with themselves to imitate, cooperation is hurt by the preferential selection. In contrast, when the individuals prefer to choose those large degree difference neighbors to learn from, there exists optimal preference strength resulting in the maximal cooperation level no matter what the network structure is. In addition, we investigate the robustness of the results against variations of the noise, the average degree and the size of network in the model, and find that the qualitative features of the results are unchanged.

  3. Preferential interactions and the effect of protein PEGylation

    DEFF Research Database (Denmark)

    Holm, Louise Stenstrup; Thulstrup, Peter Waaben; Kasimova, Marina Robertovna

    2015-01-01

    enthalpy was decreased to half the value for PEGylated lysozyme. The ratio between calorimetric and van't Hoff enthalpy suggests that our PEGylated lysozyme is a dimer. CONCLUSION/SIGNIFICANCE: The PEGylated model protein displayed similar stability responses to the addition of preferentially active...

  4. Performance evaluation and comparison of fuel processors integrated with PEM fuel cell based on steam or autothermal reforming and on CO preferential oxidation or selective methanation

    International Nuclear Information System (INIS)

    Ercolino, Giuliana; Ashraf, Muhammad A.; Specchia, Vito; Specchia, Stefania

    2015-01-01

    Highlights: • Modeling of different fuel processors integrated with PEM fuel cell stack. • Steam or autothermal reforming + CO selective methanation or preferential oxidation. • Reforming of different hydrocarbons: gasoline, light diesel oil, natural gas. • 5 kW e net systems comparison via energy efficiency and primary fuel rate consumed. • Highest net efficiency: steam reformer + CO selective methanation based system. - Abstract: The performances of four different auxiliary power unit (APU) schemes, based on a 5 kW e net proton exchange membrane fuel cell (PEM-FC) stack, are evaluated and compared. The fuel processor section of each APU is characterized by a reformer (autothermal ATR or steam SR), a non-isothermal water gas shift (NI-WGS) reactor and a final syngas catalytic clean-up step: the CO preferential oxidation (PROX) reactor or the CO selective methanation (SMET) one. Furthermore, three hydrocarbon fuels, the most commonly found in service stations (gasoline, light diesel oil and natural gas) are considered as primary fuels. The comparison is carried out examining the results obtained by a series of steady-state system simulations in Aspen Plus® of the four different APU schemes by varying the fed fuel. From the calculated data, the performance of CO-PROX is not very different compared to that of the CO-SMET, but the performance of the SR based APUs is higher than the scheme of the ATR based APUs. The most promising APU scheme with respect to an overall performance target is the scheme fed with natural gas and characterized by a fuel processor chain consisting of SR, NI-WGS and CO-SMET reactors. This processing reactors scheme together with the fuel cell section, notwithstanding having practically the same energy efficiency of the scheme with SR, NI-WGS and CO-PROX reactors, ensures a less complex scheme, higher hydrogen concentration in the syngas, lower air mass rate consumption, the absence of nitrogen in the syngas and higher potential

  5. Transplantation of co-aggregates of Sertoli cells and islet cells into liver without immunosuppression.

    Science.gov (United States)

    Takemoto, Naohiro; Liu, Xibao; Takii, Kento; Teramura, Yuji; Iwata, Hiroo

    2014-02-15

    Transplantation of islets of Langerhans (islets) was used to treat insulin-dependent diabetes mellitus. However, islet grafts must be maintained by administration of immunosuppressive drugs, which can lead to complications in the long term. An approach that avoids immunosuppressive drug use is desirable. Co-aggregates of Sertoli cells and islet cells from BALB/c mice that were prepared by the hanging drop method were transplanted into C57BL/6 mouse liver through the portal vein as in human clinical islet transplantation. The core part of the aggregates contained mainly Sertoli cells, and these cells were surrounded by islet cells. The co-aggregates retained the functions of both Sertoli and islet cells. When 800 co-aggregates were transplanted into seven C57BL/6 mice via the portal vein, six of seven recipient mice demonstrated quasi-normoglycemia for more than 100 days. The hanging drop method is suitable for preparing aggregates of Sertoli and islet cells for transplantation. Notably, transplantation of these allogeneic co-aggregates into mice with chemically induced diabetes via the portal vein resulted in long-term graft survival without systemic immunosuppression.

  6. Post-learning hippocampal dynamics promote preferential retention of rewarding events

    Science.gov (United States)

    Gruber, Matthias J.; Ritchey, Maureen; Wang, Shao-Fang; Doss, Manoj K.; Ranganath, Charan

    2016-01-01

    Reward motivation is known to modulate memory encoding, and this effect depends on interactions between the substantia nigra/ ventral tegmental area complex (SN/VTA) and the hippocampus. It is unknown, however, whether these interactions influence offline neural activity in the human brain that is thought to promote memory consolidation. Here, we used functional magnetic resonance imaging (fMRI) to test the effect of reward motivation on post-learning neural dynamics and subsequent memory for objects that were learned in high- or low-reward motivation contexts. We found that post-learning increases in resting-state functional connectivity between the SN/VTA and hippocampus predicted preferential retention of objects that were learned in high-reward contexts. In addition, multivariate pattern classification revealed that hippocampal representations of high-reward contexts were preferentially reactivated during post-learning rest, and the number of hippocampal reactivations was predictive of preferential retention of items learned in high-reward contexts. These findings indicate that reward motivation alters offline post-learning dynamics between the SN/VTA and hippocampus, providing novel evidence for a potential mechanism by which reward could influence memory consolidation. PMID:26875624

  7. Preferential Solvation of Silver (I) Bromate in Methanol-Dimethylsulfoxide Mixtures

    Science.gov (United States)

    Janardhanan, S.; Kalidas, C.

    1984-06-01

    The solubiltiy of silver bromate, the Gibbs transfer energy of Ag+ and BrO3- and the solvent transport number in methanol-dimethyl sulfoxide mixtures are reported. The solubility of silver bromate increases with addition of DMSO. The Gibbs energy of transfer of the silver ion (based on the ferrocene reference method) decreases, while that of the bromate ion becomes slightly negative with the addition of DMSO. The solvent transport number A passes through a maximum (⊿ = 1.0 at XDMSO = 0.65. From these results, it is concluded that the silver ion is preferentially solvated by DMSO whereas the bromate ion shows no preferential solvation.

  8. Imaging dynamics of CD11c+ cells and Foxp3+ cells in progressive autoimmune insulitis in the NOD mouse model of type 1 diabetes

    DEFF Research Database (Denmark)

    Schmidt-Christensen, Anja; Hansen, Lisbeth; Ilegems, Erwin

    2013-01-01

    the endocrine pancreas during initiation and progression of insulitis in the NOD mouse. Individual, ACE-transplanted islets of Langerhans were longitudinally and repetitively imaged by stereomicroscopy and two-photon microscopy to follow fluorescently labelled leucocyte subsets. Results We demonstrate that......, in spite of the immune privileged status of the eye, the ACE-transplanted islets develop infiltration and beta cell destruction, recapitulating the autoimmune insulitis of the pancreas, and exemplify this by analysing reporter cell populations expressing green fluorescent protein under the Cd11c or Foxp3......Aims/hypothesis The aim of this study was to visualise the dynamics and interactions of the cells involved in autoimmune-driven inflammation in type 1 diabetes. Methods We adopted the anterior chamber of the eye (ACE) transplantation model to perform non-invasive imaging of leucocytes infiltrating...

  9. CSF-1 Receptor Signaling in Myeloid Cells

    Science.gov (United States)

    Stanley, E. Richard; Chitu, Violeta

    2014-01-01

    The CSF-1 receptor (CSF-1R) is activated by the homodimeric growth factors colony-stimulating factor-1 (CSF-1) and interleukin-34 (IL-34). It plays important roles in development and in innate immunity by regulating the development of most tissue macrophages and osteoclasts, of Langerhans cells of the skin, of Paneth cells of the small intestine, and of brain microglia. It also regulates the differentiation of neural progenitor cells and controls functions of oocytes and trophoblastic cells in the female reproductive tract. Owing to this broad tissue expression pattern, it plays a central role in neoplastic, inflammatory, and neurological diseases. In this review we summarize the evolution, structure, and regulation of expression of the CSF-1R gene. We review, the structures of CSF-1, IL-34, and the CSF-1R and the mechanism of ligand binding to and activation of the receptor. We further describe the pathways regulating macrophage survival, proliferation, differentiation, and chemotaxis downstream from the CSF-1R. PMID:24890514

  10. Preferential induction of the AhR gene battery in HepaRG cells after a single or repeated exposure to heterocyclic aromatic amines

    International Nuclear Information System (INIS)

    Dumont, Julie; Josse, Rozenn; Lambert, Carine; Antherieu, Sebastien; Laurent, Veronique; Loyer, Pascal; Robin, Marie-Anne; Guillouzo, Andre

    2010-01-01

    2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) are two of the most common heterocyclic aromatic amines (HAA) produced during cooking of meat, fish and poultry. Both HAA produce different tumor profiles in rodents and are suspected to be carcinogenic in humans. In order to better understand the molecular basis of HAA toxicity, we have analyzed gene expression profiles in the metabolically competent human HepaRG cells using pangenomic oligonucleotide microarrays, after either a single (24-h) or a repeated (28-day) exposure to 10 μM PhIP or MeIQx. The most responsive genes to both HAA were downstream targets of the arylhydrocarbon receptor (AhR): CYP1A1 and CYP1A2 after both time points and CYP1B1 and ALDH3A1 after 28 days. Accordingly, CYP1A1/1A2 induction in HAA-treated HepaRG cells was prevented by chemical inhibition or small interference RNA-mediated down-regulation of the AhR. Consistently, HAA induced activity of the CYP1A1 promoter, which contains a consensus AhR-related xenobiotic-responsive element (XRE). In addition, several other genes exhibited both time-dependent and compound-specific expression changes with, however, a smaller magnitude than previously reported for the prototypical AhR target genes. These changes concerned genes mainly related to cell growth and proliferation, apoptosis, and cancer. In conclusion, these results identify the AhR gene battery as the preferential target of PhIP and MeIQx in HepaRG cells and further support the hypothesis that intake of HAA in diet might increase human cancer risk.

  11. α-chymotrypsin in water-acetone and water-dimethyl sulfoxide mixtures: Effect of preferential solvation and hydration.

    Science.gov (United States)

    Sirotkin, Vladimir A; Kuchierskaya, Alexandra A

    2017-10-01

    We investigated water/organic solvent sorption and residual enzyme activity to simultaneously monitor preferential solvation/hydration of protein macromolecules in the entire range of water content at 25°C. We applied this approach to estimate protein destabilization/stabilization due to the preferential interactions of bovine pancreatic α-chymotrypsin with water-acetone (moderate-strength H-bond acceptor) and water-DMSO (strong H-bond acceptor) mixtures. There are three concentration regimes for the dried α-chymotrypsin. α-Chymotrypsin is preferentially hydrated at high water content. The residual enzyme activity values are close to 100%. At intermediate water content, the dehydrated α-chymotrypsin has a higher affinity for acetone/DMSO than for water. Residual enzyme activity is minimal in this concentration range. The acetone/DMSO molecules are preferentially excluded from the protein surface at the lowest water content, resulting in preferential hydration. The residual catalytic activity in the water-poor acetone is ∼80%, compared with that observed after incubation in pure water. This effect is very small for the water-poor DMSO. Two different schemes are operative for the hydrated enzyme. At high and intermediate water content, α-chymotrypsin exhibits preferential hydration. However, at intermediate water content, in contrast to the dried enzyme, the initially hydrated α-chymotrypsin possesses increased preferential hydration parameters. At low water content, no residual enzyme activity was observed. Preferential binding of DMSO/acetone to α-chymotrypsin was detected. Our data clearly demonstrate that the hydrogen bond accepting ability of organic solvents and the protein hydration level constitute key factors in determining the stability of protein-water-organic solvent systems. © 2017 Wiley Periodicals, Inc.

  12. When and where does preferential flow matter - from observation to large scale modelling

    Science.gov (United States)

    Weiler, Markus; Leistert, Hannes; Steinbrich, Andreas

    2017-04-01

    Preferential flow can be of relevance in a wide range of soils and the interaction of different processes and factors are still difficult to assess. As most studies (including our own studies) focusing on the effect of preferential flow are based on relatively high precipitation rates, there is always the question how relevant preferential flow is under natural conditions, considering the site specific precipitation characteristics, the effect of the drying and wetting cycle on the initial soil water condition and shrinkage cracks, the site specific soil properties, soil structure and rock fragments, and the effect of plant roots and soil fauna (e.g. earthworm channels). In order to assess this question, we developed the distributed, process-based model RoGeR (Runoff Generation Research) to include a large number relevant features and processes of preferential flow in soils. The model was developed from a large number of process based research and experiments and includes preferential flow in roots, earthworm channels, along rock fragments and shrinkage cracks. We parameterized the uncalibrated model at a high spatial resolution of 5x5m for the whole state of Baden-Württemberg in Germany using LiDAR data, degree of sealing, landuse, soil properties and geology. As the model is an event based model, we derived typical event based precipitation characteristics based on rainfall duration, mean intensity and amount. Using the site-specific variability of initial soil moisture derived from a water balance model based on the same dataset, we simulated the infiltration and recharge amounts of all event classes derived from the event precipitation characteristics and initial soil moisture conditions. The analysis of the simulation results allowed us to extracts the relevance of preferential flow for infiltration and recharge considering all factors above. We could clearly see a strong effect of the soil properties and land-use, but also, particular for clay rich soils a

  13. Specific insulin binding in bovine chromaffin cells; demonstration of preferential binding to adrenalin-storing cells

    International Nuclear Information System (INIS)

    Serck-Hanssen, G.; Soevik, O.

    1987-01-01

    Insulin binding was studied in subpopulations of bovine chromaffin cells enriched in adrenalin-producing cells (A-cells) or noradrenalin-producing cells (NA-cells). Binding of 125 I-insulin was carried out at 15 0 C for 3 hrs in the absence or presence of excess unlabeled hormone. Four fractions of cells were obtained by centrifugation on a stepwise bovine serum albumin gradient. The four fractions were all shown to bind insulin in a specific manner and the highest binding was measured in the cell layers of higher densities, containing mainly A-cells. The difference in binding of insulin to the four subpopulations of chromaffin cells seemed to be related to differences in numbers of receptors as opposed to receptor affinities. The authors conclude that bovine chromaffin cells possess high affinity binding sites for insulin and that these binding sites are mainly confined to A-cells. 24 references, 2 figures, 1 table

  14. Which key properties controls the preferential transport in the vadose zone under transient hydrological conditions

    Science.gov (United States)

    Groh, J.; Vanderborght, J.; Puetz, T.; Gerke, H. H.; Rupp, H.; Wollschlaeger, U.; Stumpp, C.; Priesack, E.; Vereecken, H.

    2015-12-01

    Understanding water flow and solute transport in the unsaturated zone is of great importance for an appropriate land use management strategy. The quantification and prediction of water and solute fluxes through the vadose zone can help to improve management practices in order to limit potential risk on our fresh water resources. Water related solute transport and residence time is strongly affected by preferential flow paths in the soil. Water flow in soils depends on soil properties and site factors (climate or experiment conditions, land use) and are therefore important factors to understand preferential solute transport in the unsaturated zone. However our understanding and knowledge of which on-site properties or conditions define and enhance preferential flow and transport is still poor and mostly limited onto laboratory experimental conditions (small column length and steady state boundary conditions). Within the TERENO SOILCan lysimeter network, which was designed to study the effects of climate change on soil functions, a bromide tracer was applied on 62 lysimeter at eight different test sites between Dec. 2013 and Jan. 2014. The TERENO SOILCan infrastructure offers the unique possibility to study the occurrence of preferential flow and transport of various soil types under different natural transient hydrological conditions and land use (crop, bare and grassland) at eight TERENO SOILCan observatories. Working with lysimeter replicates at each observatory allows defining the spatial variability of preferential transport and flow. Additionally lysimeters in the network were transferred within and between observatories in order to subject them to different rainfall and temperature regimes and enable us to relate the soil type susceptibility of preferential flow and transport not only to site specific physical and land use properties, but also to different transient boundary conditions. Comparison and statistical analysis between preferential flow indicators 5

  15. Hematopoietic cell phosphatase is recruited to CD22 following B cell antigen receptor ligation

    NARCIS (Netherlands)

    Lankester, A. C.; van Schijndel, G. M.; van Lier, R. A.

    1995-01-01

    Hematopoietic cell phosphatase is a nonreceptor protein tyrosine phosphatase that is preferentially expressed in hematopoietic cell lineages. Motheaten mice, which are devoid of (functional) hematopoietic cell phosphatase, have severe disturbances in the regulation of B cell activation and

  16. Basal cell carcinoma preferentially arises from stem cells within hair follicle and mechanosensory niches.

    Science.gov (United States)

    Peterson, Shelby C; Eberl, Markus; Vagnozzi, Alicia N; Belkadi, Abdelmadjid; Veniaminova, Natalia A; Verhaegen, Monique E; Bichakjian, Christopher K; Ward, Nicole L; Dlugosz, Andrzej A; Wong, Sunny Y

    2015-04-02

    Basal cell carcinoma (BCC) is characterized by frequent loss of PTCH1, leading to constitutive activation of the Hedgehog pathway. Although the requirement for Hedgehog in BCC is well established, the identity of disease-initiating cells and the compartments in which they reside remain controversial. By using several inducible Cre drivers to delete Ptch1 in different cell compartments in mice, we show here that multiple hair follicle stem cell populations readily develop BCC-like tumors. In contrast, stem cells within the interfollicular epidermis do not efficiently form tumors. Notably, we observed that innervated Gli1-expressing progenitors within mechanosensory touch dome epithelia are highly tumorigenic. Sensory nerves activate Hedgehog signaling in normal touch domes, while denervation attenuates touch dome-derived tumors. Together, our studies identify varying tumor susceptibilities among different stem cell populations in the skin, highlight touch dome epithelia as "hot spots" for tumor formation, and implicate cutaneous nerves as mediators of tumorigenesis. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. THE DISTRIBUTION OF PREFERENTIAL PATHS AND ITS RELATION TO THE SOIL CHARACTERISTICS IN THE THREE GORGES AREA, CHINA

    Institute of Scientific and Technical Information of China (English)

    Hongjiang ZHANG; Jinhua CHENG; Yuhu SHI; Yun CHENG

    2007-01-01

    To study the characteristics of the distribution of the preferential paths and the affecting factors in the Three Gorges area, four soil profiles were dug to observe the distribution of preferential paths in the Quxi watershed in the Yangtze River basin. The Morisita exponential test method was used to examine the distribution type of preferential paths. The physical properties and infiltration characteristics of the soil were also measured to evaluate their relationship to preferential paths. The results showed that in this area, preferential paths clustered and mainly distributed in the 80-100 cm soil layer, and along the interface between the weathered layer and semi-weathered layer. There were more non-capillary pores in the 83-110 cm layer than in the other layers. It can be derived that most non-capillary pores in this layer were preferential paths caused by geological processes and rotten plant roots. The percentage of coarse soil particles increased with the depth of the soil layer. In the deeper soil layer, the coarse soil particles helped the formation of preferential paths. The fastest steady infiltration rate was observed in the of 83-110cm layer, which is inferred to be due to the greater number of preferential paths.

  18. 9-β-arabinofuranosyladenine preferentially sensitizes radioresistant squamous cell carcinoma cell lines to x-rays

    International Nuclear Information System (INIS)

    Heaton, D.

    1992-06-01

    The effect of 9-β-arabinofuranosyladenine (ara-A) on sensitivity to the deleterious effects of x-rays was studied in six squamous cell carcinoma cell lines. Three lines were relatively radioresistant, having D 0 values of 2.31 to 2.89 Gy, and the other three lines were relatively radiosensitive, having D 0 values of between 1.07 and 1.45 Gy. Ara-A (50 or 500 μM) was added to cultures 30 min prior to irradiation and removed 30 min after irradiation, and sensitivity was measured in terms of cell survival. The radiosensitizing effect of ara-A was very dependent on the inherent radiosensitivity of the tumor cell line. Fifty micromolar concentrations of ara-A sensitized only the two most radioresistant lines, SCC-12B.2 and JSQ-3. Five hundred micromolar concentrations of ara-A sensitized the more sensitive cell lines, SQ-20B and SQ-9G, but failed to have any effect on the radiation response of the two most sensitive cell lines, SQ-38 and SCC-61. Concentrations of ara-A as low as 10 μM were equally efficient in inhibiting DNA synthesis in all six cell lines. These results suggest that the target for the radiosensitizing effect of ara-A is probably related to the factor controlling the inherent radiosensitivity of human tumor cells. Therefore, ara-A might be useful in overcoming radiation resistance in vivo

  19. 9-{beta}-arabinofuranosyladenine preferentially sensitizes radioresistant squamous cell carcinoma cell lines to x-rays

    Energy Technology Data Exchange (ETDEWEB)

    Heaton, D. [Rush Univ. Medical Center, Chicago, IL (United States). Therapeutic Radiology; Mustafi, R. [Chicago Univ., IL (United States). Dept. of Radiation and Cellular Oncology; Schwartz, J.L. [Chicago Univ., IL (United States). Dept. of Radiation and Cellular Oncology]|[Argonne National Lab., IL (United States)

    1992-06-01

    The effect of 9-{beta}-arabinofuranosyladenine (ara-A) on sensitivity to the deleterious effects of x-rays was studied in six squamous cell carcinoma cell lines. Three lines were relatively radioresistant, having D{sub 0} values of 2.31 to 2.89 Gy, and the other three lines were relatively radiosensitive, having D{sub 0} values of between 1.07 and 1.45 Gy. Ara-A (50 or 500 {mu}M) was added to cultures 30 min prior to irradiation and removed 30 min after irradiation, and sensitivity was measured in terms of cell survival. The radiosensitizing effect of ara-A was very dependent on the inherent radiosensitivity of the tumor cell line. Fifty micromolar concentrations of ara-A sensitized only the two most radioresistant lines, SCC-12B.2 and JSQ-3. Five hundred micromolar concentrations of ara-A sensitized the more sensitive cell lines, SQ-20B and SQ-9G, but failed to have any effect on the radiation response of the two most sensitive cell lines, SQ-38 and SCC-61. Concentrations of ara-A as low as 10 {mu}M were equally efficient in inhibiting DNA synthesis in all six cell lines. These results suggest that the target for the radiosensitizing effect of ara-A is probably related to the factor controlling the inherent radiosensitivity of human tumor cells. Therefore, ara-A might be useful in overcoming radiation resistance in vivo.

  20. Continuous flow electrophoretic separation of proteins and cells from mammalian tissues

    Science.gov (United States)

    Hymer, W. C.; Barlow, Grant H.; Blaisdell, Steven J.; Cleveland, Carolyn; Farrington, Mary Ann; Feldmeier, Mary; Hatfield, J. Michael; Lanham, J. Wayne; Grindeland, Richard; Snyder, Robert S.

    1987-01-01

    This paper describes an apparatus for continuous flow electrophoresis (CFE), designed to separate macromolecules and cells at conditions of microgravity. In this CFE, buffer flows upward in a 120-cm long flow chamber, which is 16-cm wide x 3.0-mm thick in the microgravity version (and 6-cm wide x 1.5-mm thick in the unit-gravity laboratory version). Ovalbumin and rat serum albumin were separated in space (flight STS-4) with the same resolution of the two proteins achieved at 25 percent total w/v concentration that was obtained in the laboratory at 0.2 percent w/v concentration. Rat anterior pituitary cells, cultured human embryonic kidney cells, and canine Langerhans cells were separated into subpopulations (flight STS-8) more effectively than in unit gravity, with comparable resolution having been achieved at 100 times the concentration possible on earth.

  1. Field investigation of preferential fissure flow paths with hydrochemical analysis of small-scale sprinkling experiments

    NARCIS (Netherlands)

    Krzeminska, D.M.; Bogaard, T.A.; Debieche, T.H.; Cervi, F.; Marc, V.; Malet, J.P.

    2014-01-01

    The unsaturated zone largely controls groundwater recharge by buffering precipitation while at the same time providing preferential flow paths for infiltration. The importance of preferential flow on landslide hydrology is recognised in the literature; however, its monitoring and quantification

  2. The L-alpha-amino acid receptor GPRC6A is expressed in the islets of Langerhans but is not involved in L-arginine-induced insulin release

    DEFF Research Database (Denmark)

    Smajilovic, Sanela; Clemmensen, Christoffer; Johansen, Lars Dan

    2013-01-01

    insulin secretion; therefore, the receptor has been hypothesized to have a role in regulating glucose metabolism. In this study, we demonstrate that GPRC6A is expressed in islets of Langerhans, but activation of the receptor by L-arginine did not stimulate insulin secretion. We also investigated central...... metabolic parameters in GPRC6A knockout mice compared with wildtype littermates and found no difference in glucose metabolism or body fat percentage when mice were administered a standard chow diet. In conclusion, our data do not support a role for GPRC6A in L-arginine-induced insulin release and glucose...

  3. Can resting B cells present antigen to T cells

    International Nuclear Information System (INIS)

    Ashwell, J.D.; DeFranco, A.L.; Paul, W.E.; Schwartz, R.H.

    1985-01-01

    Antigen stimulation of T lymphocytes can occur only in the presence of an antigen-presenting cell (APC). An ever-increasing number of cell types have been found to act as APCs; these include macrophages, splenic and lymph node dendritic cells, and Langerhans cells of the skin. Although activated B lymphocytes and B cell lymphomas are known to serve as APCs, it has been generally believed that resting B cells cannot perform this function. However, in recent studies the authors have found that resting B cells can indeed present soluble antigen to T cell clones as well as to antigen-primed T cells. The previous difficulty in demonstrating this activity can be explained by the finding that, in contrast to macrophages and dendritic cells, the antigen-presenting ability of resting B cells is very radiosensitive. Macrophages are usually irradiated with 2000-3300 rads to prevent them from incorporating [ 3 H]thymidine in the T cell proliferation assay. Resting B cells, however, begin to lose presenting function at 1500 rads and have completely lost this activity at 3300 rads. It was also possible to distinguish two distinct T cell clonal phenotypes when resting B cells were used as APCs on the basis of two different assays (T cell proliferation, and B cell proliferation resulting from T cell activation). The majority of T cell clones tested were capable of both proliferating themselves and inducing the proliferation of B cells. Some T cells clones, however, could not proliferate in the presence of antigen and B cell APCs, although they were very good at inducing the proliferation of B cells

  4. Regulatory T Cells in Skin Facilitate Epithelial Stem Cell Differentiation.

    Science.gov (United States)

    Ali, Niwa; Zirak, Bahar; Rodriguez, Robert Sanchez; Pauli, Mariela L; Truong, Hong-An; Lai, Kevin; Ahn, Richard; Corbin, Kaitlin; Lowe, Margaret M; Scharschmidt, Tiffany C; Taravati, Keyon; Tan, Madeleine R; Ricardo-Gonzalez, Roberto R; Nosbaum, Audrey; Bertolini, Marta; Liao, Wilson; Nestle, Frank O; Paus, Ralf; Cotsarelis, George; Abbas, Abul K; Rosenblum, Michael D

    2017-06-01

    The maintenance of tissue homeostasis is critically dependent on the function of tissue-resident immune cells and the differentiation capacity of tissue-resident stem cells (SCs). How immune cells influence the function of SCs is largely unknown. Regulatory T cells (Tregs) in skin preferentially localize to hair follicles (HFs), which house a major subset of skin SCs (HFSCs). Here, we mechanistically dissect the role of Tregs in HF and HFSC biology. Lineage-specific cell depletion revealed that Tregs promote HF regeneration by augmenting HFSC proliferation and differentiation. Transcriptional and phenotypic profiling of T regs and HFSCs revealed that skin-resident Tregs preferentially express high levels of the Notch ligand family member, Jagged 1 (Jag1). Expression of Jag1 on Tregs facilitated HFSC function and efficient HF regeneration. Taken together, our work demonstrates that Tregs in skin play a major role in HF biology by promoting the function of HFSCs. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Aminopropyltransferases involved in polyamine biosynthesis localize preferentially in the nucleus of plant cells.

    Directory of Open Access Journals (Sweden)

    Borja Belda-Palazón

    Full Text Available Plant aminopropyltransferases consist of a group of enzymes that transfer aminopropyl groups derived from decarboxylated S-adenosyl-methionine (dcAdoMet or dcSAM to propylamine acceptors to produce polyamines, ubiquitous metabolites with positive charge at physiological pH. Spermidine synthase (SPDS uses putrescine as amino acceptor to form spermidine, whereas spermine synthase (SPMS and thermospermine synthase (TSPMS use spermidine as acceptor to synthesize the isomers spermine and thermospermine respectively. In previous work it was shown that both SPDS1 and SPDS2 can physically interact with SPMS although no data concerning the subcellular localization was reported. Here we study the subcellular localization of these enzymes and their protein dimer complexes with gateway-based Bimolecular Fluorescence Complementation (BiFC binary vectors. In addition, we have characterized the molecular weight of the enzyme complexes by gel filtration chromatography with in vitro assembled recombinant enzymes and with endogenous plant protein extracts. Our data suggest that aminopropyltransferases display a dual subcellular localization both in the cytosol and nuclear enriched fractions, and they assemble preferably as dimers. The BiFC transient expression data suggest that aminopropyltransferase heterodimer complexes take place preferentially inside the nucleus.

  6. The impact of preferential procurement in South African construction ...

    African Journals Online (AJOL)

    The impact of preferential procurement in South African construction industry. ... The outcome of this study shows that there are problems in the implementation of PPPFA during tendering and procurement processes and procedures for achieving success in government projects. Key words: HDIs, PPPFA, Policies, ...

  7. Formal requirements for exclusion of the preferential right to shares

    Directory of Open Access Journals (Sweden)

    Marjanski Vladimir

    2014-01-01

    Full Text Available A preferential subscription right to shares is a subjective property right of a shareholder based on which he or she has a preferential right of subscription to shares from a new issue in proportion to the number of fully paid-in shares of that class he or she holds on the date of adoption of the decision on issuing of shares compared with the total number of shares of that class. However, this right of a shareholder can be completely or partially excluded, if formal and substantial requirements for such exclusion are met. This paper focuses primarily on analysis of formal requirements for exclusion envisaged by the Serbian Law on Companies with a brief review of EU law and comparative law. According to the Serbian Law on Companies, there are three formal requirements for exclusion of a preferential subscription right: 1. shares are issued through the offer for which there is no obligation to publish a prospectus; 2. there is a written proposal for exclusion from the Board of Directors, or of the Supervisory Board if a company has a two-tier management system; 3. the exclusion is based on a decision of the General Meeting of the Joint-stock company. With regards formal requirements, the paper concentrates on several weaknesses of the Serbian Law on Companies which considerably undermine the position of the so-called small shareholders.

  8. Preferential control of basal dendritic protrusions by EphB2.

    Directory of Open Access Journals (Sweden)

    Matthew S Kayser

    2011-02-01

    Full Text Available The flow of information between neurons in many neural circuits is controlled by a highly specialized site of cell-cell contact known as a synapse. A number of molecules have been identified that are involved in central nervous system synapse development, but knowledge is limited regarding whether these cues direct organization of specific synapse types or on particular regions of individual neurons. Glutamate is the primary excitatory neurotransmitter in the brain, and the majority of glutamatergic synapses occur on mushroom-shaped protrusions called dendritic spines. Changes in the morphology of these structures are associated with long-lasting modulation of synaptic strength thought to underlie learning and memory, and can be abnormal in neuropsychiatric disease. Here, we use rat cortical slice cultures to examine how a previously-described synaptogenic molecule, the EphB2 receptor tyrosine kinase, regulates dendritic protrusion morphology in specific regions of the dendritic arbor in cortical pyramidal neurons. We find that alterations in EphB2 signaling can bidirectionally control protrusion length, and knockdown of EphB2 expression levels reduces the number of dendritic spines and filopodia. Expression of wild-type or dominant negative EphB2 reveals that EphB2 preferentially regulates dendritic protrusion structure in basal dendrites. Our findings suggest that EphB2 may act to specify synapse formation in a particular subcellular region of cortical pyramidal neurons.

  9. Preferential and Non-Preferential Approaches to Trade Liberalization in East Asia: What Differences Do Utilization Rates and Reciprocity Make?

    OpenAIRE

    Menon, Jayant

    2013-01-01

    Previous studies on the impacts of free trade agreements (FTAs) in East Asia have assumed full utilization of preferences. The evidence suggests that this assumption is seriously in error, with the estimated uptake particularly low in East Asia. In this paper, we assume a more realistic utilization rate in estimating impacts. We find that actual utilization rates significantly diminish the benefits from preferential liberalization, but in a non-linear way. Reciprocity is an important motivati...

  10. Bioclogging in Porous Media: Preferential Flow Paths and Anomalous Transport

    Science.gov (United States)

    Holzner, M.; Carrel, M.; Morales, V.; Derlon, N.; Beltran, M. A.; Morgenroth, E.; Kaufmann, R.

    2016-12-01

    Biofilms are sessile communities of microorganisms held together by an extracellular polymeric substance that enables surface colonization. In porous media (e.g. soils, trickling filters etc.) biofilm growth has been shown to affect the hydrodynamics in a complex fashion at the pore-scale by clogging individual pores and enhancing preferential flow pathways and anomalous transport. These phenomena are a direct consequence of microbial growth and metabolism, mass transfer processes and complex flow velocity fields possibly exhibiting pronounced three-dimensional features. Despite considerable past work, however, it is not fully understood how bioclogging interacts with flow and mass transport processes in porous media. In this work we use imaging techniques to determine the flow velocities and the distribution of biofilm in a porous medium. Three-dimensional millimodels are packed with a transparent porous medium and a glucose solution to match the optical refractive index. The models are inoculated with planktonic wildtype bacteria and biofilm cultivated for 60 h under a constant flow and nutrient conditions. The pore flow velocities in the increasingly bioclogged medium are measured using 3D particle tracking velocimetry (3D-PTV). The three-dimensional spatial distribution of the biofilm within the pore space is assessed by imaging the model with X-Ray microtomography. We find that biofilm growth increases the complexity of the pore space, leading to the formation of preferential flow pathways and "dead" pore zones. The probability of persistent high and low velocity regions (within preferential paths resp. stagnant flow regions) thus increases upon biofilm growth, leading to an enhancement of anomalous transport. The structural data seems to indicate that the largest pores are not getting clogged and carry the preferential flow, whereas intricated structures develop in the smallest pores, where the flow becomes almost stagnant. These findings may be relevant for

  11. Innovation and nested preferential growth in chess playing behavior

    Science.gov (United States)

    Perotti, J. I.; Jo, H.-H.; Schaigorodsky, A. L.; Billoni, O. V.

    2013-11-01

    Complexity develops via the incorporation of innovative properties. Chess is one of the most complex strategy games, where expert contenders exercise decision making by imitating old games or introducing innovations. In this work, we study innovation in chess by analyzing how different move sequences are played at the population level. It is found that the probability of exploring a new or innovative move decreases as a power law with the frequency of the preceding move sequence. Chess players also exploit already known move sequences according to their frequencies, following a preferential growth mechanism. Furthermore, innovation in chess exhibits Heaps' law suggesting similarities with the process of vocabulary growth. We propose a robust generative mechanism based on nested Yule-Simon preferential growth processes that reproduces the empirical observations. These results, supporting the self-similar nature of innovations in chess are important in the context of decision making in a competitive scenario, and extend the scope of relevant findings recently discovered regarding the emergence of Zipf's law in chess.

  12. UVA-induced immune suppression in human skin: protective effect of vitamin E in human epidermal cells in vitro

    International Nuclear Information System (INIS)

    Clement-Lacroix, P.; Michel, L.; Moysan, A.; Morliere, P.; Dubertret, L.

    1996-01-01

    UVA (320-400 nm) radiation damage to membranes, proteins, DNA and other cellular targets is predominantly related to oxidative processes. In the present study, we demonstrated that cutaneous UVA-induced immunosuppression can be related, at least in part, to the appearance of these oxidative processes. The UVA-induced oxidative processes in freshly isolated epidermal cells were monitored by measuring the thiobarbituric acid reactive substances (TBARS) as an index of peroxidation. The in vitro immunosuppressive effects of UVA were demonstrated by measuring the allogenic lymphocyte proliferation induced by epidermal cells or purified Langerhans cells in the mixed epidermal cell-lymphocyte reaction (MECLR). In addition, the effects of a potent antioxidant (vitamin E) on these two UVA-induced processes were analysed. (author)

  13. Preferential flow in the vadose zone and interface dynamics: Impact of microbial exudates

    Science.gov (United States)

    Li, Biting; Pales, Ashley R.; Clifford, Heather M.; Kupis, Shyla; Hennessy, Sarah; Liang, Wei-Zhen; Moysey, Stephen; Powell, Brian; Finneran, Kevin T.; Darnault, Christophe J. G.

    2018-03-01

    In the hydrological cycle, the infiltration process is a critical component in the distribution of water into the soil and in the groundwater system. The nonlinear dynamics of the soil infiltration process yield preferential flow which affects the water distribution in soil. Preferential flow is influenced by the interactions between water, soil, plants, and microorganisms. Although the relationship among the plant roots, their rhizodeposits and water transport in soil has been the subject of extensive study, the effect of microbial exudates has been studied in only a few cases. Here the authors investigated the influence of two artificial microbial exudates-catechol and riboflavin-on the infiltration process, particularly unstable fingered flow, one form of preferential flow. Flow experiments investigating the effects of types and concentrations of microbial exudates on unstable fingered flow were conducted in a two-dimensional tank that was filled with ASTM

  14. Solution thermodynamics and preferential solvation of sulfamethazine in (methanol + water) mixtures

    International Nuclear Information System (INIS)

    Delgado, Daniel R.; Almanza, Ovidio A.; Martínez, Fleming; Peña, María A.; Jouyban, Abolghasem; Acree, William E.

    2016-01-01

    Highlights: • Solubility of sulfamethazine (SMT) was measured in (methanol + water) mixtures. • SMT solubility was correlated with Jouyban–Acree model. • Gibbs energy, enthalpy, and entropy of dissolution of SMT were calculated. • Non-linear enthalpy–entropy relationship was observed for SMT. • Preferential solvation of SMT by methanol was analyzed by using the IKBI method. - Abstract: The solubility of sulfamethazine (SMT) in {methanol (1) + water (2)} co-solvent mixtures was determined at five different temperatures from (293.15 to 313.15) K. The sulfonamide exhibited its highest mole fraction solubility in pure methanol (δ 1 = 29.6 MPa 1/2 ) and its lowest mole fraction solubility in water (δ 2 = 47.8 MPa 1/2 ) at each of the five temperatures studied. The Jouyban–Acree model was used to correlate/predict the solubility values. The respective apparent thermodynamic functions Gibbs energy, enthalpy, and entropy of solution were obtained from the solubility data through the van’t Hoff and Gibbs equations. Apparent thermodynamic quantities of mixing were also calculated for this drug using values of the ideal solubility reported in the literature. A non-linear enthalpy–entropy relationship was noted for SMT in plots of both the enthalpy vs. Gibbs energy of mixing and the enthalpy vs. entropy of mixing. These plots suggest two different trends according to the slopes obtained when the composition of the mixtures changes. Accordingly, the mechanism for SMT transfer processes in water-rich mixtures from water to the mixture with 0.70 in mass fraction of methanol is entropy driven. Conversely, the mechanism is enthalpy driven in mixtures whenever the methanol composition exceeds 0.70 mol fraction. An inverse Kirkwood–Buff integral analysis of the preferential solvation of SMT indicated that the drug is preferentially solvated by water in water-rich mixtures but is preferentially solvated by methanol in methanol-rich mixtures.

  15. The fictional transition of the preferential orientation of yttria-stabilized zirconia thin films

    International Nuclear Information System (INIS)

    Lamas, J.S.; Leroy, W.P.; Depla, D.

    2012-01-01

    The fundamental study of the microstructural and textural evolution of yttria-stabilized zirconia (YSZ) thin films is of great importance given that the crystallographic properties are intimately related to their extrinsic or functional properties. In order to study these properties, YSZ thin films were obtained using dual magnetron sputtering. The results of a polar plot graph, based on X-ray diffraction (XRD) data, seem to indicate a transition from [200] out-of-plane preferential orientation to [111], indicating a dependence on composition and yttrium target–substrate (Y T–S) distance at low pressure. However, no transition is identified at high pressure, showing only [111] out-of-plane orientation, independent of composition and Y T–S distance. Scanning electron microscopy (SEM) indicates a tilt in the columnar structure of the film but no other microstructural change is in evidence, possibly related to the growth transition from [200] to [111]. Pole figures were used to clarify the texture transition in the YSZ thin films. These results indicate that there is indeed no transition in the preferential orientation of the films from [200] to [111] but a tilt of the [200] orientation towards the zirconium source. Detailed study using pole figures and SEM, clearly indicated that no growth zone transition was present and the effect is caused by geometrical configuration, contradicting expectations from standard θ/2θ XRD measurements. - Highlights: ► Study of the preferential orientation of Yttria-stabilized zirconia thin films ► Comparison of the preferential orientation at two different chamber pressures ► Correlation with the energy per adparticle and the extended structure zone model ► Use of pole figures analyses to clarify the change in the preferential orientation

  16. The fictional transition of the preferential orientation of yttria-stabilized zirconia thin films

    Energy Technology Data Exchange (ETDEWEB)

    Lamas, J.S., E-mail: Jerika.Lamas@UGent.be; Leroy, W.P.; Depla, D.

    2012-12-15

    The fundamental study of the microstructural and textural evolution of yttria-stabilized zirconia (YSZ) thin films is of great importance given that the crystallographic properties are intimately related to their extrinsic or functional properties. In order to study these properties, YSZ thin films were obtained using dual magnetron sputtering. The results of a polar plot graph, based on X-ray diffraction (XRD) data, seem to indicate a transition from [200] out-of-plane preferential orientation to [111], indicating a dependence on composition and yttrium target-substrate (Y T-S) distance at low pressure. However, no transition is identified at high pressure, showing only [111] out-of-plane orientation, independent of composition and Y T-S distance. Scanning electron microscopy (SEM) indicates a tilt in the columnar structure of the film but no other microstructural change is in evidence, possibly related to the growth transition from [200] to [111]. Pole figures were used to clarify the texture transition in the YSZ thin films. These results indicate that there is indeed no transition in the preferential orientation of the films from [200] to [111] but a tilt of the [200] orientation towards the zirconium source. Detailed study using pole figures and SEM, clearly indicated that no growth zone transition was present and the effect is caused by geometrical configuration, contradicting expectations from standard {theta}/2{theta} XRD measurements. - Highlights: Black-Right-Pointing-Pointer Study of the preferential orientation of Yttria-stabilized zirconia thin films Black-Right-Pointing-Pointer Comparison of the preferential orientation at two different chamber pressures Black-Right-Pointing-Pointer Correlation with the energy per adparticle and the extended structure zone model Black-Right-Pointing-Pointer Use of pole figures analyses to clarify the change in the preferential orientation.

  17. Preferential Iron Trafficking Characterizes Glioblastoma Stem-like Cells

    DEFF Research Database (Denmark)

    Schonberg, David L; Miller, Tyler E; Wu, Qiulian

    2015-01-01

    Glioblastomas display hierarchies with self-renewing cancer stem-like cells (CSCs). RNA sequencing and enhancer mapping revealed regulatory programs unique to CSCs causing upregulation of the iron transporter transferrin, the top differentially expressed gene compared with tissue......, to propagate and form tumors in vivo. Depleting ferritin disrupted CSC mitotic progression, through the STAT3-FoxM1 regulatory axis, revealing an iron-regulated CSC pathway. Iron is a unique, primordial metal fundamental for earliest life forms, on which CSCs have an epigenetically programmed, targetable...

  18. Protein-Mediated Interactions of Pancreatic Islet Cells

    Directory of Open Access Journals (Sweden)

    Paolo Meda

    2013-01-01

    Full Text Available The islets of Langerhans collectively form the endocrine pancreas, the organ that is soley responsible for insulin secretion in mammals, and which plays a prominent role in the control of circulating glucose and metabolism. Normal function of these islets implies the coordination of different types of endocrine cells, noticeably of the beta cells which produce insulin. Given that an appropriate secretion of this hormone is vital to the organism, a number of mechanisms have been selected during evolution, which now converge to coordinate beta cell functions. Among these, several mechanisms depend on different families of integral membrane proteins, which ensure direct (cadherins, N-CAM, occludin, and claudins and paracrine communications (pannexins between beta cells, and between these cells and the other islet cell types. Also, other proteins (integrins provide communication of the different islet cell types with the materials that form the islet basal laminae and extracellular matrix. Here, we review what is known about these proteins and their signaling in pancreatic β-cells, with particular emphasis on the signaling provided by Cx36, given that this is the integral membrane protein involved in cell-to-cell communication, which has so far been mostly investigated for effects on beta cell functions.

  19. Heterogeneity of limbal basal epithelial progenitor cells.

    Science.gov (United States)

    Hayashida, Yasutaka; Li, Wei; Chen, Ying-Ting; He, Hua; Chen, Szu-yu; Kheirkah, Ahmad; Zhu, Ying-Tien; Matsumoto, Yukihiro; Tseng, Scheffer C G

    2010-11-01

    Although corneal epithelial stem cells (SCs) are located at the limbus between the cornea and the conjunctiva, not all limbal basal epithelial cells are SCs. Using 2 dispase digestions to remove different amounts of limbal basal epithelial cells for cross-sections, flat mounts, and cytospin preparations, double immunostaining to pancytokeratins (PCK) and vimentin (Vim) identified 3 p63+ epithelial progenitors such as PCK-/Vim+, PCK/Vim, and PCK-/Vim+ and 1 p63+ mesenchymal cell, PCK-/Vim+. PCK-/Vim- progenitors had the smallest cell size were 10-20 times more enriched on collagen I-coated dishes in the 5-minute rapid adherent fraction that contained the highest percentage of p63+ cells but the lowest percentage of cytokeratin12+ cells, and gave rise to high Ki67 labeling and vivid clonal growth. In contrast, PCK+/Vim+ and PCK+/Vim- progenitors were found more in the slow-adherent fraction and yielded poor clonal growth. PCK/Vim progenitors and clusters of PCK-/Vim+ mesenchymal cells, which were neither melanocytes nor Langerhans cells, were located in the limbal basal region. Therefore, differential expression of PCK and Vim helps identify small PCK-/Vim- cells as the most likely candidate for SCs among a hierarchy of heterogeneous limbal basal progenitors, and their close association with PCK-/Vim+ presumed "niche" cells.

  20. How Medical Tourism Enables Preferential Access to Care: Four Patterns from the Canadian Context.

    Science.gov (United States)

    Snyder, Jeremy; Johnston, Rory; Crooks, Valorie A; Morgan, Jeff; Adams, Krystyna

    2017-06-01

    Medical tourism is the practice of traveling across international borders with the intention of accessing medical care, paid for out-of-pocket. This practice has implications for preferential access to medical care for Canadians both through inbound and outbound medical tourism. In this paper, we identify four patterns of medical tourism with implications for preferential access to care by Canadians: (1) Inbound medical tourism to Canada's public hospitals; (2) Inbound medical tourism to a First Nations reserve; (3) Canadian patients opting to go abroad for medical tourism; and (4) Canadian patients traveling abroad with a Canadian surgeon. These patterns of medical tourism affect preferential access to health care by Canadians by circumventing domestic regulation of care, creating jurisdictional tensions over the provision of health care, and undermining solidarity with the Canadian health system.

  1. Kinds and meaning of preferential credits for development of agriculture and rural areas

    Directory of Open Access Journals (Sweden)

    Antoni Mickiewicz

    2013-06-01

    Full Text Available The theme of the paper was of preferential credits granted in two periods, that means after Poland’s accession to the European Union (2004-2006 and in the period after introduction of new legal regulations (2007-2010. The institution responsible for realisation of preferential credits was Agency of Restructuring and Modernisation of Agriculture which delegated its rights to banks. The credit policy in first period of our functioning in the European Union relied on gradual ending old legal regulations, not compliant with EU standards and undertaking activities in adaptation of Polish agriculture to standards obeyed in EU-15 Member States. Directions of preferential credits granting were changed in 2007. There were introduced 7 credit lines which aim was improvement of production efficiency, better use of production base in agricultural farms and acceleration of agrarian changes. The biggest beneficiaries of structural pensions were young farmers and farmers who wanted to increase the size of their farms.

  2. Dipeptidyl peptidase IV is sorted to the secretory granules in pancreatic islet A-cells

    DEFF Research Database (Denmark)

    Poulsen, Mona Dam; Hansen, Gert Helge; Dabelsteen, Erik

    1993-01-01

    Dipeptidyl peptidase IV (DP IV:EC 3.4.14.5) was localized in endocrine cells of pig pancreas by immunohistochemical and enzyme histochemical methods. Immunolight microscopy with both monoclonal and polyclonal antibodies demonstrated DP IV immunoreactivity in cells located in the peripheral part...... of the islets of Langerhans. The antigen is enzymatically active, as shown by enzyme histochemical analysis with a synthetic DP IV substrate. By immunoelectron microscopy (immunogold labeling), the labeling of DP IV in the islets was associated with the secretory granules of the A-cells, as identified by double...... labeling using a monoclonal glucagon antibody as the second primary antibody. These results show that DP IV is sorted to secretory granules in the pig pancreatic islet A-cells. Furthermore, this secretory granule enzyme, as opposed to intestinal brush border DP IV, is suggested to be a soluble protein...

  3. Inflammation increases cells expressing ZSCAN4 and progenitor cell markers in the adult pancreas

    Science.gov (United States)

    Azuma, Sakiko; Yokoyama, Yukihiro; Yamamoto, Akiko; Kyokane, Kazuhiro; Niida, Shumpei; Ishiguro, Hiroshi; Ko, Minoru S. H.

    2013-01-01

    We have recently identified the zinc finger and SCAN domain containing 4 (Zscan4), which is transiently expressed and regulates telomere elongation and genome stability in mouse embryonic stem (ES) cells. The aim of this study was to examine the expression of ZSCAN4 in the adult pancreas and elucidate the role of ZSCAN4 in tissue inflammation and subsequent regeneration. The expression of ZSCAN4 and other progenitor or differentiated cell markers in the human pancreas was immunohistochemically examined. Pancreas sections of alcoholic or autoimmune pancreatitis patients before and under maintenance corticosteroid treatment were used in this study. In the adult human pancreas a small number of ZSCAN4-positive (ZSCAN4+) cells are present among cells located in the islets of Langerhans, acini, ducts, and oval-shaped cells. These cells not only express differentiated cell markers for each compartment of the pancreas but also express other tissue stem/progenitor cell markers. Furthermore, the number of ZSCAN4+ cells dramatically increased in patients with chronic pancreatitis, especially in the pancreatic tissues of autoimmune pancreatitis actively regenerating under corticosteroid treatment. Interestingly, a number of ZSCAN4+ cells in the pancreas of autoimmune pancreatitis returned to the basal level after 1 yr of maintenance corticosteroid treatment. In conclusion, coexpression of progenitor cell markers and differentiated cell markers with ZSCAN4 in each compartment of the pancreas may indicate the presence of facultative progenitors for both exocrine and endocrine cells in the adult pancreas. PMID:23599043

  4. The gsdf gene locus harbors evolutionary conserved and clustered genes preferentially expressed in fish previtellogenic oocytes.

    Science.gov (United States)

    Gautier, Aude; Le Gac, Florence; Lareyre, Jean-Jacques

    2011-02-01

    The gonadal soma-derived factor (GSDF) belongs to the transforming growth factor-β superfamily and is conserved in teleostean fish species. Gsdf is specifically expressed in the gonads, and gene expression is restricted to the granulosa and Sertoli cells in trout and medaka. The gsdf gene expression is correlated to early testis differentiation in medaka and was shown to stimulate primordial germ cell and spermatogonia proliferation in trout. In the present study, we show that the gsdf gene localizes to a syntenic chromosomal fragment conserved among vertebrates although no gsdf-related gene is detected on the corresponding genomic region in tetrapods. We demonstrate using quantitative RT-PCR that most of the genes localized in the synteny are specifically expressed in medaka gonads. Gsdf is the only gene of the synteny with a much higher expression in the testis compared to the ovary. In contrast, gene expression pattern analysis of the gsdf surrounding genes (nup54, aff1, klhl8, sdad1, and ptpn13) indicates that these genes are preferentially expressed in the female gonads. The tissue distribution of these genes is highly similar in medaka and zebrafish, two teleostean species that have diverged more than 110 million years ago. The cellular localization of these genes was determined in medaka gonads using the whole-mount in situ hybridization technique. We confirm that gsdf gene expression is restricted to Sertoli and granulosa cells in contact with the premeiotic and meiotic cells. The nup54 gene is expressed in spermatocytes and previtellogenic oocytes. Transcripts corresponding to the ovary-specific genes (aff1, klhl8, and sdad1) are detected only in previtellogenic oocytes. No expression was detected in the gonocytes in 10 dpf embryos. In conclusion, we show that the gsdf gene localizes to a syntenic chromosomal fragment harboring evolutionary conserved genes in vertebrates. These genes are preferentially expressed in previtelloogenic oocytes, and thus, they

  5. Maternal Rat Diabetes Mellitus Deleteriously Affects Insulin Sensitivity and Beta-Cell Function in the Offspring

    Directory of Open Access Journals (Sweden)

    Abdel-Baset M. Aref

    2013-01-01

    Full Text Available This study was designed to assess the effect of maternal diabetes in rats on serum glucose and insulin concentrations, insulin resistance, histological architecture of pancreas and glycogen content in liver of offspring. The pregnant rat females were allocated into two main groups: normal control group and streptozotocin-induced diabetic group. After birth, the surviving offspring were subjected to biochemical and histological examination immediately after delivery and at the end of the 1st and 2nd postnatal weeks. In comparison with the offspring of normal control dams, the fasting serum glucose level of offspring of diabetic mothers was significantly increased at the end of the 1st and 2nd postnatal weeks. Serum insulin level of offspring of diabetic dams was significantly higher at birth and decreased significantly during the following 2 postnatal weeks, while in normal rat offspring, it was significantly increased with progress of time. HOMA Insulin Resistance (HOMA-IR was significantly increased in the offspring of diabetic dams at birth and after 1 week than in normal rat offspring, while HOMA insulin sensitivity (HOMA-IS was significantly decreased. HOMA beta-cell function was significantly decreased at all-time intervals in offspring of diabetic dams. At birth, islets of Langerhans as well as beta cells in offspring of diabetic dams were hypertrophied. The cells constituting islets seemed to have a high division rate. However, beta-cells were degenerated during the following 2 post-natal weeks and smaller insulin secreting cells predominated. Vacuolation and necrosis of the islets of Langerhans were also observed throughout the experimental period. The carbohydrate content in liver of offspring of diabetic dams was at all-time intervals lower than that in control. The granule distribution was more random. Overall, the preexisting maternal diabetes leads to glucose intolerance, insulin resistance, and impaired insulin sensitivity and β-cell

  6. Characterization of Putative cis-Regulatory Elements in Genes Preferentially Expressed in Arabidopsis Male Meiocytes

    Directory of Open Access Journals (Sweden)

    Junhua Li

    2014-01-01

    Full Text Available Meiosis is essential for plant reproduction because it is the process during which homologous chromosome pairing, synapsis, and meiotic recombination occur. The meiotic transcriptome is difficult to investigate because of the size of meiocytes and the confines of anther lobes. The recent development of isolation techniques has enabled the characterization of transcriptional profiles in male meiocytes of Arabidopsis. Gene expression in male meiocytes shows unique features. The direct interaction of transcription factors (TFs with DNA regulatory sequences forms the basis for the specificity of transcriptional regulation. Here, we identified putative cis-regulatory elements (CREs associated with male meiocyte-expressed genes using in silico tools. The upstream regions (1 kb of the top 50 genes preferentially expressed in Arabidopsis meiocytes possessed conserved motifs. These motifs are putative binding sites of TFs, some of which share common functions, such as roles in cell division. In combination with cell-type-specific analysis, our findings could be a substantial aid for the identification and experimental verification of the protein-DNA interactions for the specific TFs that drive gene expression in meiocytes.

  7. Assessing preferential flow by simultaneously injecting nanoparticle and chemical tracers

    KAUST Repository

    Subramanian, S. K.; Li, Yan; Cathles, L. M.

    2013-01-01

    The exact manner in which preferential (e.g., much faster than average) flow occurs in the subsurface through small fractures or permeable connected pathways of other kinds is important to many processes but is difficult to determine, because most chemical tracers diffuse quickly enough from small flow channels that they appear to move more uniformly through the rock than they actually do. We show how preferential flow can be assessed by injecting 2 to 5 nm carbon particles (C-Dots) and an inert KBr chemical tracer at different flow rates into a permeable core channel that is surrounded by a less permeable matrix in laboratory apparatus of three different designs. When the KBr tracer has a long enough transit through the system to diffuse into the matrix, but the C-Dot tracer does not, the C-Dot tracer arrives first and the KBr tracer later, and the separation measures the degree of preferential flow. Tracer sequestration in the matrix can be estimated with a Peclet number, and this is useful for experiment design. A model is used to determine the best fitting core and matrix dispersion parameters and refine estimates of the core and matrix porosities. Almost the same parameter values explain all experiments. The methods demonstrated in the laboratory can be applied to field tests. If nanoparticles can be designed that do not stick while flowing through the subsurface, the methods presented here could be used to determine the degree of fracture control in natural environments, and this capability would have very wide ranging value and applicability.

  8. Linking soil moisture balance and source-responsive models to estimate diffuse and preferential components of groundwater recharge

    Directory of Open Access Journals (Sweden)

    M. O. Cuthbert

    2013-03-01

    Full Text Available Results are presented of a detailed study into the vadose zone and shallow water table hydrodynamics of a field site in Shropshire, UK. A conceptual model is presented and tested using a range of numerical models, including a modified soil moisture balance model (SMBM for estimating groundwater recharge in the presence of both diffuse and preferential flow components. Tensiometry reveals that the loamy sand topsoil wets up via preferential flow and subsequent redistribution of moisture into the soil matrix. Recharge does not occur until near-positive pressures are achieved at the top of the sandy glaciofluvial outwash material that underlies the topsoil, about 1 m above the water table. Once this occurs, very rapid water table rises follow. This threshold behaviour is attributed to the vertical discontinuity in preferential flow pathways due to seasonal ploughing of the topsoil and to a lower permeability plough/iron pan restricting matrix flow between the topsoil and the lower outwash deposits. Although the wetting process in the topsoil is complex, a SMBM is shown to be effective in predicting the initiation of preferential flow from the base of the topsoil into the lower outwash horizon. The rapidity of the response at the water table and a water table rise during the summer period while flow gradients in the unsaturated profile were upward suggest that preferential flow is also occurring within the outwash deposits below the topsoil. A variation of the source-responsive model proposed by Nimmo (2010 is shown to reproduce the observed water table dynamics well in the lower outwash horizon when linked to a SMBM that quantifies the potential recharge from the topsoil. The results reveal new insights into preferential flow processes in cultivated soils and provide a useful and practical approach to accounting for preferential flow in studies of groundwater recharge estimation.

  9. Predicting Alcohol, Cigarette, and Marijuana Use from Preferential Music Consumption

    Science.gov (United States)

    Oberle, Crystal D.; Garcia, Javier A.

    2015-01-01

    This study investigated whether use of alcohol, cigarettes, and marijuana may be predicted from preferential consumption of particular music genres. Undergraduates (257 women and 78 men) completed a questionnaire assessing these variables. Partial correlation analyses, controlling for sensation-seeking tendencies and behaviors, revealed that…

  10. Information filtering via preferential diffusion

    Science.gov (United States)

    Lü, Linyuan; Liu, Weiping

    2011-06-01

    Recommender systems have shown great potential in addressing the information overload problem, namely helping users in finding interesting and relevant objects within a huge information space. Some physical dynamics, including the heat conduction process and mass or energy diffusion on networks, have recently found applications in personalized recommendation. Most of the previous studies focus overwhelmingly on recommendation accuracy as the only important factor, while overlooking the significance of diversity and novelty that indeed provide the vitality of the system. In this paper, we propose a recommendation algorithm based on the preferential diffusion process on a user-object bipartite network. Numerical analyses on two benchmark data sets, MovieLens and Netflix, indicate that our method outperforms the state-of-the-art methods. Specifically, it can not only provide more accurate recommendations, but also generate more diverse and novel recommendations by accurately recommending unpopular objects.

  11. Interaction between host T cells and Reed-Sternberg cells in Hodgkin lymphomas

    NARCIS (Netherlands)

    Poppema, S; van den Berg, Anke

    2000-01-01

    Recent studies provide evidence that Reed-Sternberg (R-S) cells produce factors that may explain the characteristic inflammatory infiltrate in the affected tissues of Hodgkin lymphoma. The various chemokines and cytokines that are produced lead to a preferential influx of Th2-type T cells and

  12. Preferential transport of isoproturon at a plot scale and a field scale tile-drained site

    Science.gov (United States)

    Zehe, Erwin; Flühler, Hannes

    2001-06-01

    Irrigation experiments using the tracers Brilliant Blue (BB) and Bromide (Br) were conducted on three plots of 1.4×1.4 m 2 (plot scale) and a field scale subsurface drained test site (900 m 2) to clarify mechanisms causing rapid transport of surface applied Isoproturon (IPU) during preferential flow events. One of the small plots (site 10) and the field scale test site are located on the same field. One day after irrigation of the plot scale sites the Br and IPU concentration in two vertical soil profiles as well as the macroporousity on separate profiles and hydraulic properties of single macropores were determined. During irrigation of the field scale test site discharge, soil moisture as well as the concentration of IPU and Br in the drainage outlet were measured. Preferential flow in deep penetrating earthworm burrows caused a fast breakthrough of IPU and Br into the tile drain (1.2 m depth) at the field scale site as well as leaching of IPU into the subsoil (>0.8 m) at site 10. The results suggest a hierarchy of preconditions for the occurrence of preferential flow events of which a sufficient number of deep penetrating macropores interconnected to the soil surface seems to be the most important one. Moreover there is evidence that facilitated transport of IPU attached to mobile soil particles occurred during the preferential flow events at the field scale site and site 10. The susceptibility for preferential flow as well as the susceptibility for facilitated transport appear to be intrinsic properties of the investigated soil.

  13. Evidence for preferential flux flow at the grain boundaries of superconducting RF-quality niobium

    Science.gov (United States)

    Sung, Z.-H.; Lee, P. J.; Gurevich, A.; Larbalestier, D. C.

    2018-04-01

    The question of whether grain boundaries (GBs) in niobium can be responsible for lowered operating field (B RF) or quality factor (Q 0) in superconducting radio frequency (SRF) cavities is still controversial. Here, we show by direct DC transport across planar GBs isolated from a slice of very large-grain SRF-quality Nb that vortices can preferentially flow along the grain boundary when the external magnetic field lies in the GB plane. However, increasing the misalignment between the GB plane and the external magnetic field vector markedly reduces preferential flux flow along the GB. Importantly, we find that preferential GB flux flow is more prominent for a buffered chemical polished than for an electropolished bi-crystal. The voltage-current characteristics of GBs are similar to those seen in low angle grain boundaries of high temperature superconductors where there is clear evidence of suppression of the superconducting order parameter at the GB. While local weakening of superconductivity at GBs in cuprates and pnictides is intrinsic, deterioration of current transparency of GBs in Nb appears to be extrinsic, since the polishing method clearly affect the local GB degradation. The dependence of preferential GB flux flow on important cavity preparation and experimental variables, particularly the final chemical treatment and the angle between the magnetic field and the GB plane, suggests two more reasons why real cavity performance can be so variable.

  14. Common mycorrhizal networks amplify competition by preferential mineral nutrient allocation to large host plants.

    Science.gov (United States)

    Weremijewicz, Joanna; Sternberg, Leonel da Silveira Lobo O'Reilly; Janos, David P

    2016-10-01

    Arbuscular mycorrhizal (AM) fungi interconnect plants in common mycorrhizal networks (CMNs) which can amplify competition among neighbors. Amplified competition might result from the fungi supplying mineral nutrients preferentially to hosts that abundantly provide fixed carbon, as suggested by research with organ-cultured roots. We examined whether CMNs supplied (15) N preferentially to large, nonshaded, whole plants. We conducted an intraspecific target-neighbor pot experiment with Andropogon gerardii and several AM fungi in intact, severed or prevented CMNs. Neighbors were supplied (15) N, and half of the target plants were shaded. Intact CMNs increased target dry weight (DW), intensified competition and increased size inequality. Shading decreased target weight, but shaded plants in intact CMNs had mycorrhizal colonization similar to that of sunlit plants. AM fungi in intact CMNs acquired (15) N from the substrate of neighbors and preferentially allocated it to sunlit, large, target plants. Sunlit, intact CMN, target plants acquired as much as 27% of their nitrogen from the vicinity of their neighbors, but shaded targets did not. These results suggest that AM fungi in CMNs preferentially provide mineral nutrients to those conspecific host individuals best able to provide them with fixed carbon or representing the strongest sinks, thereby potentially amplifying asymmetric competition below ground. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

  15. Development of Functional Microfold (M Cells from Intestinal Stem Cells in Primary Human Enteroids.

    Directory of Open Access Journals (Sweden)

    Joshua D Rouch

    Full Text Available Intestinal microfold (M cells are specialized epithelial cells that act as gatekeepers of luminal antigens in the intestinal tract. They play a critical role in the intestinal mucosal immune response through transport of viruses, bacteria and other particles and antigens across the epithelium to immune cells within Peyer's patch regions and other mucosal sites. Recent studies in mice have demonstrated that M cells are generated from Lgr5+ intestinal stem cells (ISCs, and that infection with Salmonella enterica serovar Typhimurium increases M cell formation. However, it is not known whether and how these findings apply to primary human small intestinal epithelium propagated in an in vitro setting.Human intestinal crypts were grown as monolayers with growth factors and treated with recombinant RANKL, and assessed for mRNA transcripts, immunofluorescence and uptake of microparticles and S. Typhimurium.Functional M cells were generated by short-term culture of freshly isolated human intestinal crypts in a dose- and time-dependent fashion. RANKL stimulation of the monolayer cultures caused dramatic induction of the M cell-specific markers, SPIB, and Glycoprotein-2 (GP2 in a process primed by canonical WNT signaling. Confocal microscopy demonstrated a pseudopod phenotype of GP2-positive M cells that preferentially take up microparticles. Furthermore, infection of the M cell-enriched cultures with the M cell-tropic enteric pathogen, S. Typhimurium, led to preferential association of the bacteria with M cells, particularly at lower inoculum sizes. Larger inocula caused rapid induction of M cells.Human intestinal crypts containing ISCs can be cultured and differentiate into an epithelial layer with functional M cells with characteristic morphological and functional properties. This study is the first to demonstrate that M cells can be induced to form from primary human intestinal epithelium, and that S. Typhimurium preferentially infect these cells in an

  16. Statistical properties and attack tolerance of growing networks with algebraic preferential attachment

    International Nuclear Information System (INIS)

    Liu Zonghua; Lai Yingcheng; Ye Nong

    2002-01-01

    We consider growing networks with algebraic preferential attachment and address two questions: (1) what is the effect of temporal fluctuations in the number of new links acquired by the network? and (2) what is the network tolerance against random failures and intentional attacks? We find that the fluctuations generally have little effect on the network properties, although they lead to a plateau behavior for small degrees in the connectivity distribution. Formulas are derived for the evolution and distribution of the network connectivity, which are tested by numerical simulations. Numerical study of the effect of failures and attacks suggests that networks constructed under algebraic preferential attachment are more robust than scale-free networks

  17. Preferential Alignment of Hydroxyapatite Crystallites in Nanocomposites with Chemically Disintegrated Silk Fibroin

    International Nuclear Information System (INIS)

    Nemoto, Rei; Wang Li; Ikoma, Toshiyuki; Tanaka, Junzo; Senna, Mamoru

    2004-01-01

    Hydroxyapatite (HAp) nanocrystals were prepared at room temperature by a coprecipitation method from Ca(OH) 2 and H 3 PO 4 , in the presence of chemically disintegrated silk fibroin (SF). Adsorbed amounts of cations on SF and crystallinity of HAp in the composite were increased by the chemical disintegration of SF higher order structure. Preferential alignment of c-axis of HAp crystallites along the longitudinal direction of ca. 150nm SF fibril was observed. These changes due to disintegration of SF were discussed in terms of the chemical interaction between HAp and SF. The resulted composite with preferential alignment of HAp nanocrystals is a good candidate as a starting material for bone substitutes

  18. Opiate-prostaglandin interactions in the regulation of insulin secretion from rat islets of Langerhans in vitro

    International Nuclear Information System (INIS)

    Green, I.C.; Tadayyon, M.

    1988-01-01

    The inadequate insulin secretory response to glucose stimulation in non-insulin dependent diabetes has been attributed to many factors including high PGE 2 levels blunting the secretory response, and to the existence of inhibitory opiate activity in vivo. The purpose of the present work was to see if there was a connection between these two independent theories. Radioimmunoassayable PGE 2 in islets of Langerhans was found to be proportional to islet number and protein content and was typically 4 to 5pg/μg islet protein. Indomethacin sodium salicylate and chlorpropamide all lowered islet PGE 2 levels and stimulated insulin release in vitro. Dynorphin stimulated insulin release at a concentration of 6 x 10 -9 M, while lowering islet PGE 2 . Conversely, at a higher concentration, dynorphin had no stimulatory effect on insulin secretion and did not lower PGE 2 levels in islets or in the incubation media. The stimulatory effects of dynorphin and sodium salicylate on insulin secretion were blocked by exogenous PGE 2 . PGE 2 at a lower concentration did not exert any inhibitory effect on dynorphin- or sodium salicylate-induced insulin release. This concentration of exogenous PGE 2 stimulated insulin release in the presence of 6mM glucose

  19. The effect of trees on preferential flow and soil infiltrability in an agroforestry parkland in semiarid Burkina Faso.

    Science.gov (United States)

    Bargués Tobella, A; Reese, H; Almaw, A; Bayala, J; Malmer, A; Laudon, H; Ilstedt, U

    2014-04-01

    Water scarcity constrains the livelihoods of millions of people in tropical drylands. Tree planting in these environments is generally discouraged due to the large water consumption by trees, but this view may neglect their potential positive impacts on water availability. The effect of trees on soil hydraulic properties linked to groundwater recharge is poorly understood. In this study, we performed 18 rainfall simulations and tracer experiments in an agroforestry parkland in Burkina Faso to investigate the effect of trees and associated termite mounds on soil infiltrability and preferential flow. The sampling points were distributed in transects each consisting of three positions: (i) under a single tree, (ii) in the middle of an open area, and (iii) under a tree associated with a termite mound. The degree of preferential flow was quantified through parameters based on the dye infiltration patterns, which were analyzed using image analysis of photographs. Our results show that the degree of preferential flow was highest under trees associated with termite mounds, intermediate under single trees, and minimal in the open areas. Tree density also had an influence on the degree of preferential flow, with small open areas having more preferential flow than large ones. Soil infiltrability was higher under single trees than in the open areas or under trees associated with a termite mound. The findings from this study demonstrate that trees have a positive impact on soil hydraulic properties influencing groundwater recharge, and thus such effects must be considered when evaluating the impact of trees on water resources in drylands. Trees in dryland landscapes increase soil infiltrability and preferential flow Termite mounds in association with trees further enhance preferential flow.

  20. Modulation of Female Genital Tract-Derived Dendritic Cell Migration and Activation in Response to Inflammatory Cytokines and Toll-Like Receptor Agonists.

    Science.gov (United States)

    Shey, Muki S; Maharaj, Niren; Archary, Derseree; Ngcapu, Sinaye; Garrett, Nigel; Abdool Karim, Salim; Passmore, Jo-Ann S

    2016-01-01

    HIV transmission across the genital mucosa is a major mode of new HIV infections in women. The probability of infection may be influenced by several factors including recruitment and activation of HIV target cells, such as dendritic cells (DCs) and cytokine production, associated with genital inflammation. We evaluated the role of inflammatory cytokines and TLR signaling in migration and activation of genital tract DCs in the human cervical explant model. Hysterectomy tissues from 10 HIV-negative and 7 HIV-positive donor women were separated into ecto- and endocervical explants, and incubated with inflammatory cytokines (TNF-α, IL-1β, IL-8, MIP-1β) or agonists for TLR4 (LPS), TLR2/1 (PAM3) and TLR7/8 (R848). Migration (frequency) and activation (HLA-DR expression) of myeloid and plasmacytoid DCs and Langerhans cells were measured by flow cytometry. We observed that cytokines, LPS and PAM3 induced activation of migrating myeloid and plasmacytoid DCs. LPS induced a 3.6 fold lower levels of migration of plasmacytoid DCs from HIV-infected women compared with HIV-uninfected women (median activation indices of 2.932 vs 0.833). There was however a 4.5 fold increase in migration of Langerhans cells in HIV-infected compared with HIV-uninfected women in response to cytokines (median activation indices of 3.539 vs 0.77). Only TLR agonists induced migration and activation of DCs from endocervical explants. Hormonal contraception use was associated with an increase in activation of DC subsets in the endo and ectocervical explants. We conclude that inflammatory signals in the female genital tract induced DC migration and activation, with possible important implications for HIV susceptibility of cervical tissues.

  1. Inhibition of ammonia poisoning by addition of platinum to Ru/α-Al2 O3 for preferential CO oxidation in fuel cells.

    Science.gov (United States)

    Sato, Katsutoshi; Yagi, Sho; Zaitsu, Shuhei; Kitayama, Godai; Kayada, Yuto; Teramura, Kentaro; Takita, Yusaku; Nagaoka, Katsutoshi

    2014-12-01

    In polymer electrolyte fuel cell (PEFC) systems, small amounts of ammonia (NH3 ) present in the reformate gas deactivate the supported ruthenium catalysts used for preferential oxidation (PROX) of carbon monoxide (CO). In this study, we investigated how the addition of a small amount of platinum to a Ru/α-Al2 O3 catalyst (Pt/Ru=1:9 w/w) affected the catalyst's PROX activity in both the absence and the presence of NH3 (130 ppm) under conditions mimicking the reformate conditions during steam reforming of natural gas. The activity of undoped Ru/α-Al2 O3 decreased sharply upon addition of NH3 , whereas Pt/Ru/α-Al2 O3 exhibited excellent PROX activity even in the presence of NH3 . Ruthenium K-edge X-ray absorption near-edge structure (XANES) spectra indicated that in the presence of NH3 , some of the ruthenium in the undoped catalyst was oxidized in the presence of NH3 , whereas ruthenium oxidation was not observed with Pt/Ru/α-Al2 O3 . These results suggest that ruthenium oxidation is retarded by the platinum, so that the catalyst shows high activity even in the presence of NH3 . © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Refinement by Rietveld method of a rolled sheet Al-Mg-Si 6063 alloy with preferential orientation

    International Nuclear Information System (INIS)

    Carrio, J.A.G.; Hattori, C.S.; Miranda, L.F.; Domingues Junior, N.I.; Lima, N.B.; Couto, A.A.; Aguiar, A.A.

    2010-01-01

    The Rietveld refinement of a sample with preferential orientation was accomplished using data of X ray diffraction of a rolled 6063 aluminum alloy. The refinement of the preferential orientation by spherical harmonic was accomplished using a symmetry of sample mmm (rolling) until the order of 8 and was compared with experimental pole figures. The four pole figures presented indicate a sharp texture of the planes (111), (200), (220) and (311). The calculated pole figures obtained from the refinement of the X ray diffraction spectrum can incur in mistakes of preferential orientation. This happens because the measure is restricted to the planes parallel to the surface without inference to the symmetry of the sample. (author)

  3. A summary of the theory of the preferential sputtering of alloys

    International Nuclear Information System (INIS)

    Kelly, R.; Harrison, D.E.

    1985-01-01

    Preferential sputtering of alloys arises from mass differences, chemical binding differences and bombardment-induced gibbsian segregation. The relations underlying the mass effect, the chemical binding effect and bombardment-induced gibbsian segregation in binary alloys are given. (Auth.)

  4. An Apparent Deficiency of Lymphatic Capillaries in the Islets of Langerhans in the Human Pancreas.

    Science.gov (United States)

    Korsgren, Erik; Korsgren, Olle

    2016-04-01

    The lymphatic system is crucial for efficient immune surveillance and for the maintenance of a physiological pressure in the interstitial space. Even so, almost no information is available concerning the lymph drainage of the islets of Langerhans in the human pancreas. Immunohistochemical staining allowed us to distinguish lymphatic capillaries from blood capillaries. Almost no lymphatic capillaries were found within the islets in pancreatic biopsy specimens from subjects without diabetes or from subjects with type 1 or type 2 diabetes. Lymphatic capillaries were, however, found at the islet-exocrine interface, frequently located along blood capillaries and other fibrotic structures within or close to the islet capsule. Lymphatic capillaries were regularly found in the exocrine pancreas, with small lymphatic vessels located close to and around acini. Larger collecting lymphatic vessels were located in fibrotic septa between the exocrine lobules and adjacent to the ductal system of the pancreas. In summary, we report a pronounced deficiency of lymphatic capillaries in human islets, a finding with implications for immune surveillance and the regulation of interstitial fluid transport in the endocrine pancreas as well as for the pathophysiology of both type 1 and type 2 diabetes. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  5. Ultraviolet B irradiation of skin induces mast cell degranulation and release of tumour necrosis factor-α

    International Nuclear Information System (INIS)

    Walsh, L.J.

    1995-01-01

    In the 'sunburn' response in skin, dermal blood vessels are activated and traffic of dendritic Langerhans' cells altered. While these changes have been attributed to the cytokine TNF-α, the source of this acutely released TNF has not been identified. This report demonstrates that the 'sunburn' response, both in vivo and in vitro, is accompanied by rapid degranulation of cutaneous mast cells, with consequential release of intracellular stores of TNF. Epidermal keratinocytes were only minor contributors to local TNF production. Expression of the TNF-inducible CD62E (E-selectin/ELAM-1) and CD54 adhesion molecules on cutaneous endothelium occurred 2 hours following mast cell degranulation, and this event was sensitive to blockade of mast cells with disodium cromoglycate. These results indicate that TNF release in skin in the acute sunburn response can largely be attributed to mast cells. 47 refs., 5 tabs., 2 figs

  6. Ultraviolet B irradiation of skin induces mast cell degranulation and release of tumour necrosis factor-{alpha}

    Energy Technology Data Exchange (ETDEWEB)

    Walsh, L.J. [University of Queensland, Brisbane, QLD (Australia). Dept. of Dentistry, Immunopathology Unit

    1995-06-01

    In the `sunburn` response in skin, dermal blood vessels are activated and traffic of dendritic Langerhans` cells altered. While these changes have been attributed to the cytokine TNF-{alpha}, the source of this acutely released TNF has not been identified. This report demonstrates that the `sunburn` response, both in vivo and in vitro, is accompanied by rapid degranulation of cutaneous mast cells, with consequential release of intracellular stores of TNF. Epidermal keratinocytes were only minor contributors to local TNF production. Expression of the TNF-inducible CD62E (E-selectin/ELAM-1) and CD54 adhesion molecules on cutaneous endothelium occurred 2 hours following mast cell degranulation, and this event was sensitive to blockade of mast cells with disodium cromoglycate. These results indicate that TNF release in skin in the acute sunburn response can largely be attributed to mast cells. 47 refs., 5 tabs., 2 figs.

  7. Preferential Price and Trade Tied Aid in Fiji: Implications on Price ...

    African Journals Online (AJOL)

    Pacific island countries (PICs) have been receiving the highest percapita aid .... dimension of the preferential price by examining the role of forecast price as an ..... Abbot, D and S. Pollard (2004) Hardship and Poverty in the Pacific, Asian.

  8. Role for early-differentiated natural killer cells in infectious mononucleosis.

    Science.gov (United States)

    Azzi, Tarik; Lünemann, Anna; Murer, Anita; Ueda, Seigo; Béziat, Vivien; Malmberg, Karl-Johan; Staubli, Georg; Gysin, Claudine; Berger, Christoph; Münz, Christian; Chijioke, Obinna; Nadal, David

    2014-10-16

    A growing body of evidence suggests that the human natural killer (NK)-cell compartment is phenotypically and functionally heterogeneous and is composed of several differentiation stages. Moreover, NK-cell subsets have been shown to exhibit adaptive immune features during herpes virus infection in experimental mice and to expand preferentially during viral infections in humans. However, both phenotype and role of NK cells during acute symptomatic Epstein-Barr virus (EBV) infection, termed infectious mononucleosis (IM), remain unclear. Here, we longitudinally assessed the kinetics, the differentiation, and the proliferation of subsets of NK cells in pediatric IM patients. Our results indicate that acute IM is characterized by the preferential proliferation of early-differentiated CD56(dim) NKG2A(+) immunoglobulin-like receptor(-) NK cells. Moreover, this NK-cell subset exhibits features of terminal differentiation and persists at higher frequency during at least the first 6 months after acute IM. Finally, we demonstrate that this NK-cell subset preferentially degranulates and proliferates on exposure to EBV-infected B cells expressing lytic antigens. Thus, early-differentiated NK cells might play a key role in the immune control of primary infection with this persistent tumor-associated virus. © 2014 by The American Society of Hematology.

  9. Origin of preferential flow and its controlling factors on emission potential using numerical simulations and lab experiments

    NARCIS (Netherlands)

    Baviskar, S.M.; Heimovaara, T.J.

    2015-01-01

    We believe the unsaturated and heterogeneous nature of landfills leads to the emergence of preferential pathways of water and dissolved compounds through the waste body. In this research we explore the origin of preferential flow in a porous media with a deterministic numerical model. In this model

  10. 19 CFR 10.233 - Articles eligible for preferential tariff treatment.

    Science.gov (United States)

    2010-04-01

    ... control of the customs authority of the intermediate country; (ii) Did not enter into the commerce of the... 19 Customs Duties 1 2010-04-01 2010-04-01 false Articles eligible for preferential tariff treatment. 10.233 Section 10.233 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND...

  11. Antigen-Specific Th17 Cells Are Primed by Distinct and Complementary Dendritic Cell Subsets in Oropharyngeal Candidiasis.

    Directory of Open Access Journals (Sweden)

    Kerstin Trautwein-Weidner

    2015-10-01

    Full Text Available Candida spp. can cause severe and chronic mucocutaneous and systemic infections in immunocompromised individuals. Protection from mucocutaneous candidiasis depends on T helper cells, in particular those secreting IL-17. The events regulating T cell activation and differentiation toward effector fates in response to fungal invasion in different tissues are poorly understood. Here we generated a Candida-specific TCR transgenic mouse reactive to a novel endogenous antigen that is conserved in multiple distant species of Candida, including the clinically highly relevant C. albicans and C. glabrata. Using TCR transgenic T cells in combination with an experimental model of oropharyngeal candidiasis (OPC we investigated antigen presentation and Th17 priming by different subsets of dendritic cells (DCs present in the infected oral mucosa. Candida-derived endogenous antigen accesses the draining lymph nodes and is directly presented by migratory DCs. Tissue-resident Flt3L-dependent DCs and CCR2-dependent monocyte-derived DCs collaborate in antigen presentation and T cell priming during OPC. In contrast, Langerhans cells, which are also present in the oral mucosa and have been shown to prime Th17 cells in the skin, are not required for induction of the Candida-specific T cell response upon oral challenge. This highlights the functional compartmentalization of specific DC subsets in different tissues. These data provide important new insights to our understanding of tissue-specific antifungal immunity.

  12. Inert Carbon Nanoparticles for the Assessment of Preferential Flow in Saturated Dual-Permeability Porous Media

    KAUST Repository

    Yao, Chuanjin

    2017-06-07

    Knowledge of preferential flow in heterogeneous environments is essential for enhanced hydrocarbon recovery, geothermal energy extraction, and successful sequestration of chemical waste and carbon dioxide. Dual tracer tests using nanoparticles with a chemical tracer could indicate the preferential flow. A dual-permeability model with a high permeable core channel surrounded by a low permeable annulus was constructed and used to determine the viability of an inert carbon nanoparticle tracer for this application. A series of column experiments were conducted to demonstrate how this nanoparticle tracer can be used to implement the dual tracer tests in heterogeneous environments. The results indicate that, with the injection rate selected and controlled appropriately, nanoparticles together with a chemical tracer can assess the preferential flow in heterogeneous environments. The results also implement the dual tracer tests in heterogeneous environments by simultaneously injecting chemical and nanoparticle tracers.

  13. Preferential Phosphorylation on Old Histones during Early Mitosis in Human Cells.

    Science.gov (United States)

    Lin, Shu; Yuan, Zuo-Fei; Han, Yumiao; Marchione, Dylan M; Garcia, Benjamin A

    2016-07-15

    How histone post-translational modifications (PTMs) are inherited through the cell cycle remains poorly understood. Canonical histones are made in the S phase of the cell cycle. Combining mass spectrometry-based technologies and stable isotope labeling by amino acids in cell culture, we question the distribution of multiple histone PTMs on old versus new histones in synchronized human cells. We show that histone PTMs can be grouped into three categories according to their distributions. Most lysine mono-methylation and acetylation PTMs are either symmetrically distributed on old and new histones or are enriched on new histones. In contrast, most di- and tri-methylation PTMs are enriched on old histones, suggesting that the inheritance of different PTMs is regulated distinctly. Intriguingly, old and new histones are distinct in their phosphorylation status during early mitosis in the following three human cell types: HeLa, 293T, and human foreskin fibroblast cells. The mitotic hallmark H3S10ph is predominantly associated with old H3 at early mitosis and becomes symmetric with the progression of mitosis. This same distribution was observed with other mitotic phosphorylation marks, including H3T3/T6ph, H3.1/2S28ph, and H1.4S26ph but not S28/S31ph on the H3 variant H3.3. Although H3S10ph often associates with the neighboring Lys-9 di- or tri-methylations, they are not required for the asymmetric distribution of Ser-10 phosphorylation on the same H3 tail. Inhibition of the kinase Aurora B does not change the distribution despite significant reduction of H3S10ph levels. However, K9me2 abundance on the new H3 is significantly reduced after Aurora B inhibition, suggesting a cross-talk between H3S10ph and H3K9me2. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  14. Preferential Phosphorylation on Old Histones during Early Mitosis in Human Cells*

    Science.gov (United States)

    Lin, Shu; Yuan, Zuo-Fei; Han, Yumiao; Marchione, Dylan M.; Garcia, Benjamin A.

    2016-01-01

    How histone post-translational modifications (PTMs) are inherited through the cell cycle remains poorly understood. Canonical histones are made in the S phase of the cell cycle. Combining mass spectrometry-based technologies and stable isotope labeling by amino acids in cell culture, we question the distribution of multiple histone PTMs on old versus new histones in synchronized human cells. We show that histone PTMs can be grouped into three categories according to their distributions. Most lysine mono-methylation and acetylation PTMs are either symmetrically distributed on old and new histones or are enriched on new histones. In contrast, most di- and tri-methylation PTMs are enriched on old histones, suggesting that the inheritance of different PTMs is regulated distinctly. Intriguingly, old and new histones are distinct in their phosphorylation status during early mitosis in the following three human cell types: HeLa, 293T, and human foreskin fibroblast cells. The mitotic hallmark H3S10ph is predominantly associated with old H3 at early mitosis and becomes symmetric with the progression of mitosis. This same distribution was observed with other mitotic phosphorylation marks, including H3T3/T6ph, H3.1/2S28ph, and H1.4S26ph but not S28/S31ph on the H3 variant H3.3. Although H3S10ph often associates with the neighboring Lys-9 di- or tri-methylations, they are not required for the asymmetric distribution of Ser-10 phosphorylation on the same H3 tail. Inhibition of the kinase Aurora B does not change the distribution despite significant reduction of H3S10ph levels. However, K9me2 abundance on the new H3 is significantly reduced after Aurora B inhibition, suggesting a cross-talk between H3S10ph and H3K9me2. PMID:27226594

  15. Colonic stem cell data are consistent with the immortal model of stem cell division under non-random strand segregation.

    Science.gov (United States)

    Walters, K

    2009-06-01

    Colonic stem cells are thought to reside towards the base of crypts of the colon, but their numbers and proliferation mechanisms are not well characterized. A defining property of stem cells is that they are able to divide asymmetrically, but it is not known whether they always divide asymmetrically (immortal model) or whether there are occasional symmetrical divisions (stochastic model). By measuring diversity of methylation patterns in colon crypt samples, a recent study found evidence in favour of the stochastic model, assuming random segregation of stem cell DNA strands during cell division. Here, the effect of preferential segregation of the template strand is considered to be consistent with the 'immortal strand hypothesis', and explore the effect on conclusions of previously published results. For a sample of crypts, it is shown how, under the immortal model, to calculate mean and variance of the number of unique methylation patterns allowing for non-random strand segregation and compare them with those observed. The calculated mean and variance are consistent with an immortal model that incorporates non-random strand segregation for a range of stem cell numbers and levels of preferential strand segregation. Allowing for preferential strand segregation considerably alters previously published conclusions relating to stem cell numbers and turnover mechanisms. Evidence in favour of the stochastic model may not be as strong as previously thought.

  16. Effects of preferential concentration on direct radiation transmission in a turbulent duct flow

    Science.gov (United States)

    Villafane, Laura; Banko, Andrew; Kim, Ji Hoon; Elkins, Chris; Eaton, John

    2017-11-01

    Inertial particles in turbulent flows preferentially concentrate, giving rise to spatial and temporal fluctuations of particle number density that affect radiation transmission through the medium. Positive particle correlations enhance direct transmission when compared to the exponential attenuation predicted by the Beer's Law for randomly distributed particles. In the context of a particle based solar receiver, this work studies the effects of preferential concentration and optical depth on direct transmission through a particle laden turbulent duct flow. Time resolved measurements of transmission through the mixture were performed for various particle loadings and Reynolds numbers, thus varying particle correlation lengths, optical depth and concentration fluctuations. These measurements were made using a photodiode to record the transmission of a collimated laser beam along the wall bisector of the duct. A synchronized high-speed camera provided particle positions along most of the beam path. Average and fluctuating radiation transmission results are compared to predictions derived from the imaged number density fields and to simplified analytical models. Simplified models are able to capture the correct trends with varying loading and preferential concentration. This work is funded by the Department of Energy's National Nuclear Security Administration, Grant #DE-NA0002373-1.

  17. Ultrastructural findings in Hashimoto's thyroiditis and focal lymphocytic thyroiditis with reference to giant cell formation.

    Science.gov (United States)

    Knecht, H; Hedinger, C E

    1982-09-01

    Ultrastructural findings in two cases of Hashimoto's disease and two cases of focal lymphocytic thyroiditis are reported. Stimulated thyrocytes, oncocytes and degenerating thyrocytes were observed in all cases. Multinucleated thyrocytes and epithelial pseudogiant cells were identified in Hashimoto's disease only. Infiltrating lymphocytes, plasma cells, monocytes and macrophages were present in all cases. The ultrastructure of germinal centres was similar to that seen in lymphatic organs. Giant cells of both intra- and extrafollicular localization were seen in Hashimoto's disease. Most of the giant cells were macrophage-derived. Two different ways of giant cell formation were identified: besides the familiar dissolution of plasma membranes of adjacent macrophages, another mechanism of fusion was observed. At sites of contact, peculiar membrane structures were developed and disintegration of plasma membranes occurred in parts adjacent to these structures. These are not identical to desmosomes and are different from Langerhans' granules. They probably represent special organelles for the initiation of cellular fusion.

  18. Motility and chemotaxis mediate the preferential colonization of gastric injury sites by Helicobacter pylori.

    Directory of Open Access Journals (Sweden)

    Eitaro Aihara

    2014-07-01

    Full Text Available Helicobacter pylori (H. pylori is a pathogen contributing to peptic inflammation, ulceration, and cancer. A crucial step in the pathogenic sequence is when the bacterium first interacts with gastric tissue, an event that is poorly understood in vivo. We have shown that the luminal space adjacent to gastric epithelial damage is a microenvironment, and we hypothesized that this microenvironment might enhance H. pylori colonization. Inoculation with 106 H. pylori (wild-type Sydney Strain 1, SS1 significantly delayed healing of acetic-acid induced ulcers at Day 1, 7 and 30 post-inoculation, and wild-type SS1 preferentially colonized the ulcerated area compared to uninjured gastric tissue in the same animal at all time points. Gastric resident Lactobacillus spp. did not preferentially colonize ulcerated tissue. To determine whether bacterial motility and chemotaxis are important to ulcer healing and colonization, we analyzed isogenic H. pylori mutants defective in motility (ΔmotB or chemotaxis (ΔcheY. ΔmotB (10(6 failed to colonize ulcerated or healthy stomach tissue. ΔcheY (10(6 colonized both tissues, but without preferential colonization of ulcerated tissue. However, ΔcheY did modestly delay ulcer healing, suggesting that chemotaxis is not required for this process. We used two-photon microscopy to induce microscopic epithelial lesions in vivo, and evaluated accumulation of fluorescently labeled H. pylori at gastric damage sites in the time frame of minutes instead of days. By 5 min after inducing damage, H. pylori SS1 preferentially accumulated at the site of damage and inhibited gastric epithelial restitution. H. pylori ΔcheY modestly accumulated at the gastric surface and inhibited restitution, but did not preferentially accumulate at the injury site. H. pylori ΔmotB neither accumulated at the surface nor inhibited restitution. We conclude that bacterial chemosensing and motility rapidly promote H. pylori colonization of injury sites

  19. Motility and Chemotaxis Mediate the Preferential Colonization of Gastric Injury Sites by Helicobacter pylori

    Science.gov (United States)

    Aihara, Eitaro; Closson, Chet; Matthis, Andrea L.; Schumacher, Michael A.; Engevik, Amy C.; Zavros, Yana; Ottemann, Karen M.; Montrose, Marshall H.

    2014-01-01

    Helicobacter pylori (H. pylori) is a pathogen contributing to peptic inflammation, ulceration, and cancer. A crucial step in the pathogenic sequence is when the bacterium first interacts with gastric tissue, an event that is poorly understood in vivo. We have shown that the luminal space adjacent to gastric epithelial damage is a microenvironment, and we hypothesized that this microenvironment might enhance H. pylori colonization. Inoculation with 106 H. pylori (wild-type Sydney Strain 1, SS1) significantly delayed healing of acetic-acid induced ulcers at Day 1, 7 and 30 post-inoculation, and wild-type SS1 preferentially colonized the ulcerated area compared to uninjured gastric tissue in the same animal at all time points. Gastric resident Lactobacillus spp. did not preferentially colonize ulcerated tissue. To determine whether bacterial motility and chemotaxis are important to ulcer healing and colonization, we analyzed isogenic H. pylori mutants defective in motility (ΔmotB) or chemotaxis (ΔcheY). ΔmotB (106) failed to colonize ulcerated or healthy stomach tissue. ΔcheY (106) colonized both tissues, but without preferential colonization of ulcerated tissue. However, ΔcheY did modestly delay ulcer healing, suggesting that chemotaxis is not required for this process. We used two-photon microscopy to induce microscopic epithelial lesions in vivo, and evaluated accumulation of fluorescently labeled H. pylori at gastric damage sites in the time frame of minutes instead of days. By 5 min after inducing damage, H. pylori SS1 preferentially accumulated at the site of damage and inhibited gastric epithelial restitution. H. pylori ΔcheY modestly accumulated at the gastric surface and inhibited restitution, but did not preferentially accumulate at the injury site. H. pylori ΔmotB neither accumulated at the surface nor inhibited restitution. We conclude that bacterial chemosensing and motility rapidly promote H. pylori colonization of injury sites, and thereby biases

  20. The spermatogonial stem cell niche

    NARCIS (Netherlands)

    de Rooij, Dirk G.

    2009-01-01

    Spermatogonial stem cells (SSCs; A(s) spermatogonia) and their direct descendants (A(pr) and A(al) spermatogonia) are preferentially located in those areas of the seminiferous tubules that border on the interstitial tissue. Fewer of these cells are present in tubule areas directly bordering on

  1. Intradermal delivery of Shigella IpaB and IpaD type III secretion proteins: kinetics of cell recruitment and antigen uptake, mucosal and systemic immunity, and protection across serotypes.

    Science.gov (United States)

    Heine, Shannon J; Diaz-McNair, Jovita; Andar, Abhay U; Drachenberg, Cinthia B; van de Verg, Lillian; Walker, Richard; Picking, Wendy L; Pasetti, Marcela F

    2014-02-15

    Shigella is one of the leading pathogens contributing to the vast pediatric diarrheal disease burden in low-income countries. No licensed vaccine is available, and the existing candidates are only partially effective and serotype specific. Shigella type III secretion system proteins IpaB and IpaD, which are conserved across Shigella spp., are candidates for a broadly protective, subunit-based vaccine. In this study, we investigated the immunogenicity and protective efficacy of IpaB and IpaD administered intradermally (i.d.) with a double-mutant of the Escherichia coli heat-labile enterotoxin (dmLT) adjuvant using microneedles. Different dosage levels of IpaB and IpaD, with or without dmLT, were tested in mice. Vaccine delivery into the dermis, recruitment of neutrophils, macrophages, dendritic cells, and Langerhans cells, and colocalization of vaccine Ag within skin-activated APC were demonstrated through histology and immunofluorescence microscopy. Ag-loaded neutrophils, macrophages, dendritic cells, and Langerhans cells remained in the tissue at least 1 wk. IpaB, IpaD, and dmLT-specific serum IgG- and IgG-secreting cells were produced following i.d. immunization. The protective efficacy was 70% against Shigella flexneri and 50% against Shigella sonnei. Similar results were obtained when the vaccine was administered intranasally, with the i.d. route requiring 25-40 times lower doses. Distinctively, IgG was detected in mucosal secretions; secretory IgA, as well as mucosal and systemic IgA Ab-secreting cells, were seemingly absent. Vaccine-induced T cells produced IFN-γ, IL-2, TNF-α, IL-17, IL-4, IL-5, and IL-10. These results demonstrate the potential of i.d. vaccination with IpaB and IpaD to prevent Shigella infection and support further studies in humans.

  2. PAFit: A Statistical Method for Measuring Preferential Attachment in Temporal Complex Networks.

    Directory of Open Access Journals (Sweden)

    Thong Pham

    Full Text Available Preferential attachment is a stochastic process that has been proposed to explain certain topological features characteristic of complex networks from diverse domains. The systematic investigation of preferential attachment is an important area of research in network science, not only for the theoretical matter of verifying whether this hypothesized process is operative in real-world networks, but also for the practical insights that follow from knowledge of its functional form. Here we describe a maximum likelihood based estimation method for the measurement of preferential attachment in temporal complex networks. We call the method PAFit, and implement it in an R package of the same name. PAFit constitutes an advance over previous methods primarily because we based it on a nonparametric statistical framework that enables attachment kernel estimation free of any assumptions about its functional form. We show this results in PAFit outperforming the popular methods of Jeong and Newman in Monte Carlo simulations. What is more, we found that the application of PAFit to a publically available Flickr social network dataset yielded clear evidence for a deviation of the attachment kernel from the popularly assumed log-linear form. Independent of our main work, we provide a correction to a consequential error in Newman's original method which had evidently gone unnoticed since its publication over a decade ago.

  3. Preferential treatment and exemption policy impacts energy

    International Nuclear Information System (INIS)

    Doelle, R.R.

    1991-01-01

    This paper reports on the preferential treatment and exemption policy of the Federal Energy Regulatory Commission (FERC) for State and State Agencies which creates an anticompetitive and restraint of trade attitude in California against the development of alternative energy resources by the private sector when such development competes directly with state owned power generation under the State Water and Central Valley Water Projects, particularly in the area of water and power supply. The existing state water policy fails to address the effects of global warming and the adverse potential of the greenhouse effect in California, i.e. rising tides can seriously impact sea water intrusion problems of the San Francisco Bay-Delta Area by not only flooding agricultural lands in the Delta and Central Valley, but impacting the supply of water to large population areas in Southern and Northern California, especially when coupled with drought conditions. The California investigative research results herein reported demonstrates the fallacy of a preferential treatment and exemption policy in a free market economy, especially when such policy creates the potential for excessive state budget burdens upon the public in the face of questionable subsidies to special interest, i.e., allowing the resulting windfall profits to be passed onto major utilities and commingled at the expense of public interest so as to undermine the financial means for development of alternative energy resources. The cited Congressional and State Legislative Laws which provide the ways and means to resolve any energy or water resource problems are only as good as the enforcement and the commitment by the executive branch of government and the lawmakers to up-hold existing laws

  4. Geostatistical integration and uncertainty in pollutant concentration surface under preferential sampling

    Directory of Open Access Journals (Sweden)

    Laura Grisotto

    2016-04-01

    Full Text Available In this paper the focus is on environmental statistics, with the aim of estimating the concentration surface and related uncertainty of an air pollutant. We used air quality data recorded by a network of monitoring stations within a Bayesian framework to overcome difficulties in accounting for prediction uncertainty and to integrate information provided by deterministic models based on emissions meteorology and chemico-physical characteristics of the atmosphere. Several authors have proposed such integration, but all the proposed approaches rely on representativeness and completeness of existing air pollution monitoring networks. We considered the situation in which the spatial process of interest and the sampling locations are not independent. This is known in the literature as the preferential sampling problem, which if ignored in the analysis, can bias geostatistical inferences. We developed a Bayesian geostatistical model to account for preferential sampling with the main interest in statistical integration and uncertainty. We used PM10 data arising from the air quality network of the Environmental Protection Agency of Lombardy Region (Italy and numerical outputs from the deterministic model. We specified an inhomogeneous Poisson process for the sampling locations intensities and a shared spatial random component model for the dependence between the spatial location of monitors and the pollution surface. We found greater predicted standard deviation differences in areas not properly covered by the air quality network. In conclusion, in this context inferences on prediction uncertainty may be misleading when geostatistical modelling does not take into account preferential sampling.

  5. Huntingtin-interacting protein 14 is a type 1 diabetes candidate protein regulating insulin secretion and β-cell apoptosis

    DEFF Research Database (Denmark)

    Berchtold, Lukas Adrian; Størling, Zenia Marian; Ortis, Fernanda

    2011-01-01

    Type 1 diabetes (T1D) is a complex disease characterized by the loss of insulin-secreting β-cells. Although the disease has a strong genetic component, and several loci are known to increase T1D susceptibility risk, only few causal genes have currently been identified. To identify disease...... genes in T1D, including the INS gene. An unexpected top-scoring candidate gene was huntingtin-interacting protein (HIP)-14/ZDHHC17. Immunohistochemical analysis of pancreatic sections demonstrated that HIP14 is almost exclusively expressed in insulin-positive cells in islets of Langerhans. RNAi...... knockdown experiments established that HIP14 is an antiapoptotic protein required for β-cell survival and glucose-stimulated insulin secretion. Proinflammatory cytokines (IL-1β and IFN-γ) that mediate β-cell dysfunction in T1D down-regulated HIP14 expression in insulin-secreting INS-1 cells and in isolated...

  6. Surface morphology and preferential orientation growth of TaC crystals formed by chemical vapor deposition

    Energy Technology Data Exchange (ETDEWEB)

    Xiong Xiang, E-mail: Xiong228@sina.co [State Key Lab for Powder Metallurgy, Central South University, Changsha 410083 (China); Chen Zhaoke; Huang Baiyun; Li Guodong [State Key Lab for Powder Metallurgy, Central South University, Changsha 410083 (China); Zheng Feng [School of Material Science and Engineering, Central South University, Changsha 410083 (China); Xiao Peng; Zhang Hongbo [State Key Lab for Powder Metallurgy, Central South University, Changsha 410083 (China)

    2009-04-02

    TaC film was deposited on (002) graphite sheet by isothermal chemical vapor deposition using TaCl{sub 5}-Ar-C{sub 3}H{sub 6} mixtures, with deposition temperature 1200 {sup o}C and pressure about 200 Pa. The influence of deposition position (or deposition rate) on preferential orientation and surface morphology of TaC crystals were investigated by X-ray diffraction and scanning electron microscopy methods. The deposits are TaC plus trace of C. The crystals are large individual columns with pyramidal-shape at deposition rate of 32.4-37.3 {mu}m/h, complex columnar at 37.3-45.6 {mu}m/h, lenticular-like at 45.6-54.6 {mu}m/h and cauliflower-like at 54.6-77.3 {mu}m/h, with <001>, near <001>, <110> and no clear preferential orientation, respectively. These results agree in part with the preditions of the Pangarov's model of the relationship between deposition rate and preferential growth orientation. The growth mechanism of TaC crystals in <001>, near <001>, <111> and no clear preferential orientation can be fairly explained by the growth parameter {alpha} with Van der Drift's model, deterioration model and Meakin model. Furthermore, a nucleation and coalescence model is also proposed to explain the formation mechanism of <110> lenticular-like crystals.

  7. Preferential semantics for action specification in first-order modal action logic

    NARCIS (Netherlands)

    Broersen, Jan; Wieringa, Roelf J.

    In this paper we investigate preferential semantics for declarative specifications in a First Order Modal Action Logic. We address some well known problems: the frame problem, the qualification problem and the ramification problem. We incorporate the assumptions that are inherent to both the frame

  8. Langerin negative dendritic cells promote potent CD8+ T-cell priming by skin delivery of live adenovirus vaccine microneedle arrays.

    Science.gov (United States)

    Bachy, Veronique; Hervouet, Catherine; Becker, Pablo D; Chorro, Laurent; Carlin, Leo M; Herath, Shanthi; Papagatsias, Timos; Barbaroux, Jean-Baptiste; Oh, Sea-Jin; Benlahrech, Adel; Athanasopoulos, Takis; Dickson, George; Patterson, Steven; Kwon, Sung-Yun; Geissmann, Frederic; Klavinskis, Linda S

    2013-02-19

    Stabilization of virus protein structure and nucleic acid integrity is challenging yet essential to preserve the transcriptional competence of live recombinant viral vaccine vectors in the absence of a cold chain. When coupled with needle-free skin delivery, such a platform would address an unmet need in global vaccine coverage against HIV and other global pathogens. Herein, we show that a simple dissolvable microneedle array (MA) delivery system preserves the immunogenicity of vaccines encoded by live recombinant human adenovirus type 5 (rAdHu5). Specifically, dried rAdHu5 MA immunization induced CD8(+) T-cell expansion and multifunctional cytokine responses equipotent with conventional injectable routes of immunization. Intravital imaging demonstrated MA cargo distributed both in the epidermis and dermis, with acquisition by CD11c(+) dendritic cells (DCs) in the dermis. The MA immunizing properties were attributable to CD11c(+) MHCII(hi) CD8α(neg) epithelial cell adhesion molecule (EpCAM(neg)) CD11b(+) langerin (Lang; CD207)(neg) DCs, but neither Langerhans cells nor Lang(+) DCs were required for CD8(+) T-cell priming. This study demonstrates an important technical advance for viral vaccine vectors progressing to the clinic and provides insights into the mechanism of CD8(+) T-cell priming by live rAdHu5 MAs.

  9. Preferential processing of self-relevant stimuli occurs mainly at the perceptual and conscious stages of information processing.

    Science.gov (United States)

    Tacikowski, P; Ehrsson, H H

    2016-04-01

    Self-related stimuli, such as one's own name or face, are processed faster and more accurately than other types of stimuli. However, what remains unknown is at which stage of the information processing hierarchy this preferential processing occurs. Our first aim was to determine whether preferential self-processing involves mainly perceptual stages or also post-perceptual stages. We found that self-related priming was stronger than other-related priming only because of perceptual prime-target congruency. Our second aim was to dissociate the role of conscious and unconscious factors in preferential self-processing. To this end, we compared the "self" and "other" conditions in trials where primes were masked or unmasked. In two separate experiments, we found that self-related priming was stronger than other-related priming but only in the unmasked trials. Together, our results suggest that preferential access to the self-concept occurs mainly at the perceptual and conscious stages of the stimulus processing hierarchy. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  10. Unified Model for Generation Complex Networks with Utility Preferential Attachment

    International Nuclear Information System (INIS)

    Wu Jianjun; Gao Ziyou; Sun Huijun

    2006-01-01

    In this paper, based on the utility preferential attachment, we propose a new unified model to generate different network topologies such as scale-free, small-world and random networks. Moreover, a new network structure named super scale network is found, which has monopoly characteristic in our simulation experiments. Finally, the characteristics of this new network are given.

  11. Quantifying Preferential Flow and Seasonal Storage in an Unsaturated Fracture-Facial Domain

    Science.gov (United States)

    Nimmo, J. R.; Malek-Mohammadi, S.

    2012-12-01

    Preferential flow through deep unsaturated zones of fractured rock is hydrologically important to a variety of contaminant transport and water-resource issues. The unsaturated zone of the English Chalk Aquifer provides an important opportunity for a case study of unsaturated preferential flow in isolation from other flow modes. The chalk matrix has low hydraulic conductivity and stays saturated, owing to its fine uniform pores and the wet climate of the region. Therefore the substantial fluxes observed in the unsaturated chalk must be within fractures and interact minimally with matrix material. Price et al. [2000] showed that irregularities on fracture surfaces provide a significant storage capacity in the chalk unsaturated zone, likely accounting for volumes of water required to explain unexpected dry-season water-table stability during substantial continuing streamflow observed by Lewis et al. [1993] In this presentation we discuss and quantify the dynamics of replenishment and drainage of this unsaturated zone fracture-face storage domain using a modification of the source-responsive model of Nimmo [2010]. This model explains the processes in terms of two interacting flow regimes: a film or rivulet preferential flow regime on rough fracture faces, active on an individual-storm timescale, and a regime of adsorptive and surface-tension influences, resembling traditional diffuse formulations of unsaturated flow, effective mainly on a seasonal timescale. The modified model identifies hydraulic parameters for an unsaturated fracture-facial domain lining the fractures. Besides helping to quantify the unsaturated zone storage described by Price et al., these results highlight the importance of research on the topic of unsaturated-flow relations within a near-fracture-surface domain. This model can also facilitate understanding of mechanisms for reinitiation of preferential flow after temporary cessation, which is important in multi-year preferential flow through deep

  12. Introduction to the Special Issue: Precarious Solidarity-Preferential Access in Canadian Health Care.

    Science.gov (United States)

    Reid, Lynette

    2017-06-01

    Systems of universal health coverage may aspire to provide care based on need and not ability to pay; the complexities of this aspiration (conceptual, practical, and ethical) call for normative analysis. This special issue arises in the wake of a judicial inquiry into preferential access in the Canadian province of Alberta, the Vertes Commission. I describe this inquiry and set out a taxonomy of forms of differential and preferential access. Papers in this special issue focus on the conceptual specification of health system boundaries (the concept of medical need) and on the normative questions raised by complex models of funding and delivery of care, where patients, providers, and services cross system boundaries.

  13. Preferential growth in FeCoV/Ti:N multilayers

    Energy Technology Data Exchange (ETDEWEB)

    Clemens, D.; Senthil Kumar, M.; Boeni, P.; Horisberger, M. [Paul Scherrer Inst. (PSI), Villigen (Switzerland)

    1997-09-01

    The preferential growth in Fe{sub 0.50}Co{sub 0.48}V{sub 0.02}/Ti:N multilayers was studied by X-ray diffraction. X-ray specular reflectometry and subsequent simulation of the spectra was used to extract information about the thickness and interface roughness of individual layers. The investigation gives structural information about the material combination and its potential for the use of neutron polarizers. (author) 2 figs., 1 tab., 2 refs.

  14. Preferential solvation of fluorenone and 4-hydroxyfluorenone in binary solvent mixtures

    International Nuclear Information System (INIS)

    Jozefowicz, Marek; Heldt, Janina R.

    2003-01-01

    Preferential solvation of fluorenone and 4-hydroxyfluorenone in binary solvent mixtures has been studied using steady-state spectroscopic measurements. This study concerns the solvent-induced shift of the absorption and fluorescence spectra of both molecules in two solvent mixtures, i.e., cyclohexane-tetrahydrofuran and cyclohexane-ethanol. The first system contains polar solute molecules, fluorenone and 4-hydroxyfluorenone, in a mixture of polar aprotic (tetrahydrofuran) and non-polar (cyclohexane) solvents. In the second solvents mixture, hydrogen bonding with solute molecules (ethanol) may occur. The results of spectroscopic measurements are analysed using theoretical models of Bakshiev, Mazurenko and Suppan which describe preferential solvation phenomena. In the case of cyclohexane-tetrahydrofuran mixtures, the deviation from linearity in the absorption and fluorescence solvatochromic shifts vs. the solution polarity is due to non-specific dipolar solvent-solute interactions. For cyclohexane-ethanol binary mixtures, both non-specific and specific (hydrogen bond and proton-relay tautomerization) interactions contribute to the observed solvatochromism

  15. Tunable photovoltaic performance of preferentially oriented rutile TiO2 nanorod photoanodes based dye sensitized solar cells with quasi-state electrolyte.

    Science.gov (United States)

    T C, Sabari Girisun; C, Jeganathan; N, Pavithra; Anandan, Sambandam

    2017-12-20

    Photoanodes made of highly oriented TiO2 nanorod arrays with different aspect ratios were synthesized via one-step hydrothermal technique. Preferentially oriented single crystalline rutile TiO2 was confirmed by the single peak in XRD pattern (2θ=63o, (0 0 2)). FESEM image evidence the growth of an array of nanorods having different geometry with respect to reaction time and solution refreshment rate. The length, diameter and aspect ratio of the nanorods increased with reaction time as 4 hours (1.98 μm, 121 nm, 15.32), 8 hours (4 μm, 185 nm, 22.70), 12 hours (5.6 μm, 242 nm, 27.24) and 16 hours (8 μm, 254 nm, 38.02) respectively. Unlike conventional Dye-Sensitized Solar Cell (DSSC) with a liquid electrolyte, DSSC were fabricated here using 1D rutile TiO2 nanorods based photoanodes, N719 dye and quasi-state electrolyte. The charge transport properties were investigated from current-voltage curves and fitted using one-diode model. Interestingly photovoltaic performance of DSSCs increased exponentially with the length of the nanorod and is attributed to the higher surface to volume ratio, more dye anchoring, and channelized electron transport. Higher photovoltaic performance (Jsc=5.99 mA/cm2, Voc=750 mV, η=3.08%) was observed with photoanodes (16 hours) made of densely packed longest TiO2 nanorods (8 µm, 254 nm). © 2017 IOP Publishing Ltd.

  16. The influence of preferential flow on pressure propagation and landslide triggering of the Rocca Pitigliana landslide

    Science.gov (United States)

    Shao, Wei; Bogaard, Thom; Bakker, Mark; Berti, Matteo

    2016-12-01

    The fast pore water pressure response to rain events is an important triggering factor for slope instability. The fast pressure response may be caused by preferential flow that bypasses the soil matrix. Currently, most of the hydro-mechanical models simulate pore water pressure using a single-permeability model, which cannot quantify the effects of preferential flow on pressure propagation and landslide triggering. Previous studies showed that a model based on the linear-diffusion equation can simulate the fast pressure propagation in near-saturated landslides such as the Rocca Pitigliana landslide. In such a model, the diffusion coefficient depends on the degree of saturation, which makes it difficult to use the model for predictions. In this study, the influence of preferential flow on pressure propagation and slope stability is investigated with a 1D dual-permeability model coupled with an infinite-slope stability approach. The dual-permeability model uses two modified Darcy-Richards equations to simultaneously simulate the matrix flow and preferential flow in hillslopes. The simulated pressure head is used in an infinite-slope stability analysis to identify the influence of preferential flow on the fast pressure response and landslide triggering. The dual-permeability model simulates the height and arrival of the pressure peak reasonably well. Performance of the dual-permeability model is as good as or better than the linear-diffusion model even though the dual-permeability model is calibrated for two single pulse rain events only, while the linear-diffusion model is calibrated for each rain event separately. In conclusion, the 1D dual-permeability model is a promising tool for landslides under similar conditions.

  17. Modulation of Female Genital Tract-Derived Dendritic Cell Migration and Activation in Response to Inflammatory Cytokines and Toll-Like Receptor Agonists.

    Directory of Open Access Journals (Sweden)

    Muki S Shey

    Full Text Available HIV transmission across the genital mucosa is a major mode of new HIV infections in women. The probability of infection may be influenced by several factors including recruitment and activation of HIV target cells, such as dendritic cells (DCs and cytokine production, associated with genital inflammation. We evaluated the role of inflammatory cytokines and TLR signaling in migration and activation of genital tract DCs in the human cervical explant model. Hysterectomy tissues from 10 HIV-negative and 7 HIV-positive donor women were separated into ecto- and endocervical explants, and incubated with inflammatory cytokines (TNF-α, IL-1β, IL-8, MIP-1β or agonists for TLR4 (LPS, TLR2/1 (PAM3 and TLR7/8 (R848. Migration (frequency and activation (HLA-DR expression of myeloid and plasmacytoid DCs and Langerhans cells were measured by flow cytometry. We observed that cytokines, LPS and PAM3 induced activation of migrating myeloid and plasmacytoid DCs. LPS induced a 3.6 fold lower levels of migration of plasmacytoid DCs from HIV-infected women compared with HIV-uninfected women (median activation indices of 2.932 vs 0.833. There was however a 4.5 fold increase in migration of Langerhans cells in HIV-infected compared with HIV-uninfected women in response to cytokines (median activation indices of 3.539 vs 0.77. Only TLR agonists induced migration and activation of DCs from endocervical explants. Hormonal contraception use was associated with an increase in activation of DC subsets in the endo and ectocervical explants. We conclude that inflammatory signals in the female genital tract induced DC migration and activation, with possible important implications for HIV susceptibility of cervical tissues.

  18. Preferential binding of yeast Rad4-Rad23 complex to damaged DNA

    International Nuclear Information System (INIS)

    Jansen, L.E.T.; Verhage, R.A.; Brouwer, J.

    1998-01-01

    The yeast Rad4 and Rad23 proteins form a complex that is involved in nucleotide excision repair (NER). Their function in this process is not known yet, but genetic data suggest that they act in an early step in NER. We have purified an epitope-tagged Rad4.Rad23 (tRad4. Rad23) complex from yeast cells, using a clone overproducing Rad4 with a hemagglutinin-tag at its C terminus. tRad4.Rad23 complex purified by both conventional and immuno-affinity chromatography complements the in vitro repair defect of rad4 and rad23 mutant extracts, demonstrating that these proteins are functional in NER. Using electrophoretic mobility shift assays, we show preferential binding of the tRad4.Rad23 complex to damaged DNA in vitro. UV-irradiated, as well as N-acetoxy-2-(acetylamino)fluorene-treated DNA, is efficiently bound by the protein complex. These data suggest that Rad4.Rad23 interacts with DNA damage during NER and may play a role in recognition of the damage

  19. Organelle-specific injury to melanin-containing cells in human skin by pulsed laser irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Murphy, G.F.; Shepard, R.S.; Paul, B.S.; Menkes, A.; Anderson, R.R.; Parrish, J.A.

    1983-12-01

    Physical models predict that ultraviolet laser radiation of appropriately brief pulses can selectively alter melanin-containing cellular targets in human skin. Skin of normal human volunteers was exposed to brief (20 nanosecond) 351-nm wave length pulses from a XeF excimer laser, predicting that those cells containing the greatest quantities of melanized melanosomes (lower half of the epidermis) would be selectively damaged. Transmission electron microscopy revealed the earliest cellular alteration to be immediate disruption of melanosomes, both within melanocytes and basal keratinocytes. This disruption was dose dependent and culminated in striking degenerative changes in these cells. Superficial keratinocytes and Langerhans cells were not affected. It was concluded that the XeF excimer laser is capable of organelle-specific injury to melanosomes. These findings may have important clinical implications in the treatment of both benign and malignant pigmented lesions by laser radiations of defined wave lengths and pulse durations.

  20. Bone marrow cells other than stem cells seed the bone marrow after rescue transfusion of fatally irradiated mice

    International Nuclear Information System (INIS)

    Cronkite, E.P.; Inoue, T.; Bullis, J.E.

    1987-01-01

    In a previous publication, iodinated deoxyuridine ( 125 IUdR) incorporation data were interpreted as indicating that spleen colony-forming units (CFU-S) in DNA synthesis preferentially seeded bone marrow. In the present studies, the CFU-S content of marrow from irradiated, bone-marrow transfused mice was directly determined. Pretreatment of the transfused cells with cytocidal tritiated thymidine resulted in an insignificant diminution in CFU-S content when compared with nontritiated thymidine pretreatment, implying that there is no preferential seeding. The 125 IUdR incorporation data have been reinterpreted as being a result of the proliferation of other progenitor cells present that have seeded the bone marrow

  1. Influence of extra-cellular and intra-cellular acting thiol oxidants on the 45calcium uptake by the islets of Langerhans of the rat

    International Nuclear Information System (INIS)

    Haegele, R.G.

    1981-01-01

    The glucose-stimulated calcium uptake by the islets of Langerhans is dependent on the intra-cellular GSH/GSSG ratios. The inhibition of calcium uptake is not the consequence of a direct oxidation of membrane-fixed thiol groups. In contrast, direct oxidation of extra cellular thiols leads to an increase in calcium uptake when intra-cellular oxidation is simultaneously prevented. Since this effect only occurs at high intra-cellular GSH/GSSG ratios it can be assumed that the redox state of extra-cellular thiols is dependent on the redox state of the intra-cellular GSH/GSSG ratios. These findings support the theory that the oxidation of extra-cellular thiols by thiol oxidants leads to an increase in calcium uptake and that the extent of uptake is higher, the more the redox state of the extra-cellular thiols tends towards the reduced state prior to oxidation. (orig./MG) [de

  2. Study of a diffusion flamelet model, with preferential diffusion effects included

    NARCIS (Netherlands)

    Delhaye, S.; Somers, L.M.T.; Bongers, H.; Oijen, van J.A.; Goey, de L.P.H.; Dias, V.

    2005-01-01

    The non-premixed flamelet model of Peters [1] (model1), which does not include preferential diffusion effects is investigated. Two similar models are presented, but without the assumption of unity Lewis numbers. One of these models was derived by Peters & Pitsch [2] (model2), while the other one was

  3. Depth resolution and preferential sputtering in depth profiling of sharp interfaces

    International Nuclear Information System (INIS)

    Hofmann, S.; Han, Y.S.; Wang, J.Y.

    2017-01-01

    Highlights: • Interfacial depth resolution from MRI model depends on sputtering rate differences. • Depth resolution critically depends on the dominance of roughness or atomic mixing. • True (depth scale) and apparent (time scale) depth resolutions are different. • Average sputtering rate approximately yields true from apparent depth resolution. • Profiles by SIMS and XPS are different but similar to surface concentrations. - Abstract: The influence of preferential sputtering on depth resolution of sputter depth profiles is studied for different sputtering rates of the two components at an A/B interface. Surface concentration and intensity depth profiles on both the sputtering time scale (as measured) and the depth scale are obtained by calculations with an extended Mixing-Roughness-Information depth (MRI)-model. The results show a clear difference for the two extreme cases (a) preponderant roughness and (b) preponderant atomic mixing. In case (a), the interface width on the time scale (Δt(16–84%)) increases with preferential sputtering if the faster sputtering component is on top of the slower sputtering component, but the true resolution on the depth scale (Δz(16–84%)) stays constant. In case (b), the interface width on the time scale stays constant but the true resolution on the depth scale varies with preferential sputtering. For similar order of magnitude of the atomic mixing and the roughness parameters, a transition state between the two extremes is obtained. While the normalized intensity profile of SIMS represents that of the surface concentration, an additional broadening effect is encountered in XPS or AES by the influence of the mean electron escape depth which may even cause an additional matrix effect at the interface.

  4. Depth resolution and preferential sputtering in depth profiling of sharp interfaces

    Energy Technology Data Exchange (ETDEWEB)

    Hofmann, S. [Max Planck Institute for Intelligent Systems (formerly MPI for Metals Research), Heisenbergstrasse 3, D-70569 Stuttgart (Germany); Han, Y.S. [Department of Physics, Shantou University, 243 Daxue Road, Shantou, 515063 Guangdong (China); Wang, J.Y., E-mail: wangjy@stu.edu.cn [Department of Physics, Shantou University, 243 Daxue Road, Shantou, 515063 Guangdong (China)

    2017-07-15

    Highlights: • Interfacial depth resolution from MRI model depends on sputtering rate differences. • Depth resolution critically depends on the dominance of roughness or atomic mixing. • True (depth scale) and apparent (time scale) depth resolutions are different. • Average sputtering rate approximately yields true from apparent depth resolution. • Profiles by SIMS and XPS are different but similar to surface concentrations. - Abstract: The influence of preferential sputtering on depth resolution of sputter depth profiles is studied for different sputtering rates of the two components at an A/B interface. Surface concentration and intensity depth profiles on both the sputtering time scale (as measured) and the depth scale are obtained by calculations with an extended Mixing-Roughness-Information depth (MRI)-model. The results show a clear difference for the two extreme cases (a) preponderant roughness and (b) preponderant atomic mixing. In case (a), the interface width on the time scale (Δt(16–84%)) increases with preferential sputtering if the faster sputtering component is on top of the slower sputtering component, but the true resolution on the depth scale (Δz(16–84%)) stays constant. In case (b), the interface width on the time scale stays constant but the true resolution on the depth scale varies with preferential sputtering. For similar order of magnitude of the atomic mixing and the roughness parameters, a transition state between the two extremes is obtained. While the normalized intensity profile of SIMS represents that of the surface concentration, an additional broadening effect is encountered in XPS or AES by the influence of the mean electron escape depth which may even cause an additional matrix effect at the interface.

  5. DC-STAMP, a novel multimembrane-spanning molecule preferentially expressed by dendritic cells.

    NARCIS (Netherlands)

    Hartgers, F.C.; Vissers, J.L.M.; Looman, M.W.G.; Zoelen, C. van; Huffine, C.; Figdor, C.G.; Adema, G.J.

    2000-01-01

    Dendritic cells (DC) are unique in their ability to present antigen to naive T cells, and therefore play a central role in the initiation of immune responses. Characterization of DC-specific genes may help to unravel the mechanism underlying their potent antigen presenting capacity. Here we describe

  6. Balancing practicality and hydrologic realism: a parsimonious approach for simulating rapid groundwater recharge via unsaturated-zone preferential flow

    Science.gov (United States)

    Mirus, Benjamin B.; Nimmo, J.R.

    2013-01-01

    The impact of preferential flow on recharge and contaminant transport poses a considerable challenge to water-resources management. Typical hydrologic models require extensive site characterization, but can underestimate fluxes when preferential flow is significant. A recently developed source-responsive model incorporates film-flow theory with conservation of mass to estimate unsaturated-zone preferential fluxes with readily available data. The term source-responsive describes the sensitivity of preferential flow in response to water availability at the source of input. We present the first rigorous tests of a parsimonious formulation for simulating water table fluctuations using two case studies, both in arid regions with thick unsaturated zones of fractured volcanic rock. Diffuse flow theory cannot adequately capture the observed water table responses at both sites; the source-responsive model is a viable alternative. We treat the active area fraction of preferential flow paths as a scaled function of water inputs at the land surface then calibrate the macropore density to fit observed water table rises. Unlike previous applications, we allow the characteristic film-flow velocity to vary, reflecting the lag time between source and deep water table responses. Analysis of model performance and parameter sensitivity for the two case studies underscores the importance of identifying thresholds for initiation of film flow in unsaturated rocks, and suggests that this parsimonious approach is potentially of great practical value.

  7. The application of in situ analytical transmission electron microscopy to the study of preferential intergranular oxidation in Alloy 600

    Energy Technology Data Exchange (ETDEWEB)

    Burke, M.G., E-mail: m.g.burke@manchester.ac.uk; Bertali, G.; Prestat, E.; Scenini, F.; Haigh, S.J.

    2017-05-15

    In situ analytical transmission electron microscopy (TEM) can provide a unique perspective on dynamic reactions in a variety of environments, including liquids and gases. In this study, in situ analytical TEM techniques have been applied to examine the localised oxidation reactions that occur in a Ni-Cr-Fe alloy, Alloy 600, using a gas environmental cell at elevated temperatures. The initial stages of preferential intergranular oxidation, shown to be an important precursor phenomenon for intergranular stress corrosion cracking in pressurized water reactors (PWRs), have been successfully identified using the in situ approach. Furthermore, the detailed observations correspond to the ex situ results obtained from bulk specimens tested in hydrogenated steam and in high temperature PWR primary water. The excellent agreement between the in situ and ex situ oxidation studies demonstrates that this approach can be used to investigate the initial stages of preferential intergranular oxidation relevant to nuclear power systems. - Highlights: • In situ analytical TEM has been performed in 1 bar H{sub 2}-H{sub 2}O vapor at 360–480 °C. • Nanoscale GB migration and solute partitioning correlate with ex situ data for Alloy 600 in H{sub 2}-steam. • This technique can provide new insights into localised reactions associated with localised oxidation.

  8. Is there reciprocity in preferential trade agreements on services?

    OpenAIRE

    Marchetti, Juan; Roy, Martin; Zoratto, Laura

    2012-01-01

    Are market access commitments on services in Preferential Trade Agreements (PTAs) reciprocal or simply unilateral? If reciprocal, do concessions granted in services depend on concessions received from the trading partner in other services or in non-services areas as well? In this paper we investigate the presence of reciprocity in bilateral services agreements, by sub-sector, mode of supply and type of agreement (North-North, South-North, South-South). To do so, we use a database of concessio...

  9. Stationary and nonstationary properties of evolving networks with preferential linkage

    International Nuclear Information System (INIS)

    Jezewski, W.

    2002-01-01

    Networks evolving by preferential attachment of both external and internal links are investigated. The rate of adding an external link is assumed to depend linearly on the degree of a preexisting node to which a new node is connected. The process of creating an internal link, between a pair of existing vertices, is assumed to be controlled entirely by the vertex that has more links than the other vertex in the pair, and the rate of creation of such a link is assumed to be, in general, nonlinear in the degree of the more strongly connected vertex. It is shown that degree distributions of networks evolving only by creating internal links display for large degrees a nonstationary power-law decay with a time-dependent scaling exponent. Nonstationary power-law behaviors are numerically shown to persist even when the number of nodes is not fixed and both external and internal connections are introduced, provided that the rate of preferential attachment of internal connections is nonlinear. It is argued that nonstationary effects are not unlikely in real networks, although these effects may not be apparent, especially in networks with a slowly varying mean degree

  10. Estimation of Airline Benefits from Avionics Upgrade under Preferential Merge Re-sequence Scheduling

    Science.gov (United States)

    Kotegawa, Tatsuya; Cayabyab, Charlene Anne; Almog, Noam

    2013-01-01

    Modernization of the airline fleet avionics is essential to fully enable future technologies and procedures for increasing national airspace system capacity. However in the current national airspace system, system-wide benefits gained by avionics upgrade are not fully directed to aircraft/airlines that upgrade, resulting in slow fleet modernization rate. Preferential merge re-sequence scheduling is a best-equipped-best-served concept designed to incentivize avionics upgrade among airlines by allowing aircraft with new avionics (high-equipped) to be re-sequenced ahead of aircraft without the upgrades (low-equipped) at enroute merge waypoints. The goal of this study is to investigate the potential benefits gained or lost by airlines under a high or low-equipped fleet scenario if preferential merge resequence scheduling is implemented.

  11. ATP-ase activity in the human oral mucous membrane, the guinea pig and the rabbit epidermis. A light- and electronmicroscopical investigation

    DEFF Research Database (Denmark)

    Zelander, T; Kirkeby, S

    1984-01-01

    The activity for ATP-ase was investigated in cells of rabbit and guinea pig epidermis and human oral mucosa. Observations both in the light- and electron microscope indicate that the ATP-ase positive cells of guinea pig and human epithelia are Langerhans cells while in the rabbit epidermis...

  12. Progression of nephropathy after islet of langerhans transplantation in alloxan-induced diabetic rats

    Directory of Open Access Journals (Sweden)

    César Tadeu Spadella

    1997-03-01

    Full Text Available We studied the effects of islet of Langerhans transplantation (IT on the kidney lesions of rats with alloxan-induced diabetes. Forty-five inbred male Lewis rats were randomly assigned to 3 experimental groups: group Gl included 15 non-diabetic control rats (NC, group GIT included 15 alloxan-induced diabetic rats (DC, and group III included 15 alloxan-induced diabetic rats that received pancreatic islet transplantation prepared by nonenzymatic method from normal donor Lewis rats and injected into the portal vein (IT. Each group was further divided into 3 subgroups of 5 rats which were sacrificed at 1, 3, and 6 months of follow-up, respectively. Clinical and laboratorial parameters were recorded in the mentioned periods in the 3 experimental groups. For histology, the kidneys of all rats of each subgroup were studied and 50 glomeruli and 50 tubules of each kidney were analyzed using light microscopy by two different investigators in a double blind study. The results showed progressive glomerular basement membrane thickening (GBMT, mesangial enlargement (ME, and Bowman's capsule thickening (BCT in the 3 experimental groups throughout the follow-up. These alterations were significantly more severe in DC rats at 6 months when compared to NC rats (p < 0.01. However, the degree of GBMT, ME, and BCT observed in DC rats was not statistically different from IT rats at 1, 3, and 6 months. In addition, Armanni-Ebstein lesions of the tubules (AE and tubular lumen protein (PRO observed in DC rats were also observed in IT rats all over the study. These lesions were never present in NC rats. We conclude that IT did not prevent progression of kidney lesions in alloxan-induced diabetic rats within 6 months after transplantation.

  13. Modelling the Preferential Solvation of Ferulic Acid in {2-Propanol (1 + Water (2} Mixtures at 298.15 K

    Directory of Open Access Journals (Sweden)

    Abolghasem Jouyban 1,2, Fleming Martínez 3 *

    2017-12-01

    Full Text Available Background: Recently Haq et al. reported the equilibrium solubility in {2-propanol (1 + water (2} mixtures at several temperatures with some numerical correlation analysis. Nevertheless, no attempt was made to evaluate the preferential solvation of this compound by the solvents. Methods: Preferential solvation of ferulic acid in the saturated mixtures at 298.15 K was analyzed based on the inverse Kirkwood-Buff integrals as described in the literature. Results: Ferulic acid is preferentially solvated by water in water-rich mixtures (0.00 < x1 < 0.19 but preferentially solvated by 2-propanol in mixtures with composition 0.19 < x1 < 1.00. Conclusion: These results could be interpreted as a consequence of hydrophobic hydration around the non-polar groups of the solute in the former case (0.00 < x1 < 0.19. Moreover, in the last case (0.19 < x1 < 1.00, the observed trend could be a consequence of the acid behavior of ferulic acid in front to 2-propanol molecules because this cosolvent is more basic than water as described by the respective solvatochromic parameters.

  14. Gene transfer preferentially selects MHC class I positive tumour cells and enhances tumour immunogenicity.

    Science.gov (United States)

    Hacker, Ulrich T; Schildhauer, Ines; Barroso, Margarita Céspedes; Kofler, David M; Gerner, Franz M; Mysliwietz, Josef; Buening, Hildegard; Hallek, Michael; King, Susan B S

    2006-05-01

    The modulated expression of MHC class I on tumour tissue is well documented. Although the effect of MHC class I expression on the tumorigenicity and immunogenicity of MHC class I negative tumour cell lines has been rigorously studied, less is known about the validity of gene transfer and selection in cell lines with a mixed MHC class I phenotype. To address this issue we identified a C26 cell subline that consists of distinct populations of MHC class I (H-2D/K) positive and negative cells. Transient transfection experiments using liposome-based transfer showed a lower transgene expression in MHC class I negative cells. In addition, MHC class I negative cells were more sensitive to antibiotic selection. This led to the generation of fully MHC class I positive cell lines. In contrast to C26 cells, all transfectants were rejected in vivo and induced protection against the parental tumour cells in rechallenge experiments. Tumour cell specificity of the immune response was demonstrated in in vitro cytokine secretion and cytotoxicity assays. Transfectants expressing CD40 ligand and hygromycin phosphotransferase were not more immunogenic than cells expressing hygromycin resistance alone. We suggest that the MHC class I positive phenotype of the C26 transfectants had a bearing on their immunogenicity, because selected MHC class I positive cells were more immunogenic than parental C26 cells and could induce specific anti-tumour immune responses. These data demonstrate that the generation of tumour cell transfectants can lead to the selection of subpopulations that show an altered phenotype compared to the parental cell line and display altered immunogenicity independent of selection marker genes or other immune modulatory genes. Our results show the importance of monitoring gene transfer in the whole tumour cell population, especially for the evaluation of in vivo therapies targeted to heterogeneous tumour cell populations.

  15. Wave-Block Due to a Threshold Gradient Underlies Limited Coordination in Pancreatic Islets

    DEFF Research Database (Denmark)

    Pedersen, Morten Gram; Sørensen, Mads Peter

    2008-01-01

    Two models for coupled pancreatic β cells are used to investigate excited wave propagation in spatially inhomogeneous islets of Langerhans. The application concerns spatial variation of glucose concentration across the islet. A comprehensive model of coupled cells shows that wave blocking occurs ...

  16. Beneficial Effect of Preferential Music on Exercise Induced Changes in Heart Rate Variability.

    Science.gov (United States)

    Archana, R; Mukilan, R

    2016-05-01

    Music is known to reduce pain, anxiety and fear in several stressful conditions in both males and females. Further, listening to preferred music enhances the endurance during running performance of women rather than listening to non-preferred music. In recent years Heart Rate Variability (HRV) has been used as an indicator of autonomic nervous activity. This study was aimed to assess the effectiveness of preferential music on HRV after moderate exercise. This was an experimental study done in 30 healthy students aged between 20-25 years, of either sex. HRV was measured at rest, 15 minutes of exercise only and 15 minutes of exercise with listening preferential music in same participants. Data was analysed by One-Way ANOVA and Tukey HSD Post-hoc Test. Statistical significance was taken to be a p-value of less than 0.05. Low frequency and high frequency component was significantly increased followed by only exercise. Music minimized increase in both high and low frequency component followed by exercise. However, only high frequency change was statistically significant. LF/HF ratio was significantly increased followed by only exercise. Music significantly minimized increase in LF/HF ratio. This study provides the preliminary evidence that listening to preferential music could be an effective method of relaxation, as indicated by a shift of the autonomic balance towards the parasympathetic activity among medical students.

  17. Diagnosis of Oral Lesions associated with HIV/AIDS | Hamza ...

    African Journals Online (AJOL)

    HIV has a lipid envelope that has specific glycoproteins that attach to CD4 protein on cell surface. Cells which express CD4 protein are at risk of infection with HIV including CD4 lymphocytes, monocytes, macrophages, microglial cells, and langerhan's cells in skin. Disturbances in number and function of CD4 cells lead to ...

  18. A Novel Preferential Diffusion Recommendation Algorithm Based on User’s Nearest Neighbors

    Directory of Open Access Journals (Sweden)

    Fuguo Zhang

    2017-01-01

    Full Text Available Recommender system is a very efficient way to deal with the problem of information overload for online users. In recent years, network based recommendation algorithms have demonstrated much better performance than the standard collaborative filtering methods. However, most of network based algorithms do not give a high enough weight to the influence of the target user’s nearest neighbors in the resource diffusion process, while a user or an object with high degree will obtain larger influence in the standard mass diffusion algorithm. In this paper, we propose a novel preferential diffusion recommendation algorithm considering the significance of the target user’s nearest neighbors and evaluate it in the three real-world data sets: MovieLens 100k, MovieLens 1M, and Epinions. Experiments results demonstrate that the novel preferential diffusion recommendation algorithm based on user’s nearest neighbors can significantly improve the recommendation accuracy and diversity.

  19. Self-potential monitoring of a thermal pulse advecting through a preferential flow path

    Science.gov (United States)

    Ikard, S. J.; Revil, A.

    2014-11-01

    There is a need to develop new non-intrusive geophysical methods to detect preferential flow paths in heterogeneous porous media. A laboratory experiment is performed to non-invasively localize a preferential flow pathway in a sandbox using a heat pulse monitored by time-lapse self-potential measurements. Our goal is to investigate the amplitude of the intrinsic thermoelectric self-potential anomalies and the ability of this method to track preferential flow paths. A negative self-potential anomaly (-10 to -15 mV with respect to the background signals) is observed at the surface of the tank after hot water is injected in the upstream reservoir during steady state flow between the upstream and downstream reservoirs of the sandbox. Repeating the same experiment with the same volume of water injected upstream, but at the same temperature as the background pore water, produces a negligible self-potential anomaly. The negative self-potential anomaly is possibly associated with an intrinsic thermoelectric effect, with the temperature dependence of the streaming potential coupling coefficient, or with an apparent thermoelectric effect associated with the temperature dependence of the electrodes themselves. We model the experiment in 3D using a finite element code. Our results show that time-lapse self-potential signals can be used to track the position of traveling heat flow pulses in saturated porous materials, and therefore to find preferential flow pathways, especially in a very permeable environment and in real time. The numerical model and the data allows quantifying the intrinsic thermoelectric coupling coefficient, which is on the order of -0.3 to -1.8 mV per degree Celsius. The temperature dependence of the streaming potential during the experiment is negligible with respect to the intrinsic thermoelectric coupling. However, the temperature dependence of the potential of the electrodes needs to be accounted for and is far from being negligible if the electrodes

  20. Preferential adsorption of polycarboxylate superplasticizers on cement and silica fume in ultra-high performance concrete (UHPC)

    International Nuclear Information System (INIS)

    Schröfl, Ch.; Gruber, M.; Plank, J.

    2012-01-01

    UHPC is fluidized particularly well when a blend of MPEG- and APEG-type PCEs is applied. Here, the mechanism for this behavior was investigated. Testing individual cement and micro silica pastes revealed that the MPEG-PCE disperses cement better than silica whereas the APEG-PCE fluidizes silica particularly well. This behavior is explained by preferential adsorption of APEG-PCE on silica while MPEG-PCEs exhibit a more balanced affinity to both cement and silica. Adsorption data obtained from individual cement and micro silica pastes were compared with those found for the fully formulated UHPC containing a cement/silica blend. In the UHPC formulation, both PCEs still exhibit preferential and selective adsorption similar as was observed for individual cement and silica pastes. Preferential adsorption of PCEs is explained by their different stereochemistry whereby the carboxylate groups have to match with the steric position of calcium ions/atoms situated at the surfaces of cement hydrates or silica.