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Sample records for multisystem langerhans cell

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

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    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.

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

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    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.

  3. 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.

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

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    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.)

  5. [Langerhans cell histiocytosis in adults].

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    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.

  6. 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

  7. Pulmonary langerhans cell histiocytosis

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    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.

  8. 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.)

  9. 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

  10. 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.

  11. Partial hypopituitarism and Langerhans cell histiocytosis

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    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

  12. 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

  13. 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

  14. 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)

  15. 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.

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

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    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.

  17. 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

  18. A Rare Disease in Adult: Langerhans Cell Histiocytosis

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    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

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

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    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.

  20. 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.)

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

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    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.

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

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    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.

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

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    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.)

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

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    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.

  5. 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

  6. 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.)

  7. Changes of Langerhans cells during skin ageing

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

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    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.

  9. 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...

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

    Directory of Open Access Journals (Sweden)

    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.

  11. 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

  12. 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)

  13. 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)

  14. 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 ...

  15. 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

  16. 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.

  17. 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.)

  18. 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

  19. 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

  20. 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.

  1. 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...

  2. 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.

  3. 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.

  4. 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.

  5. New insights in lymphangioleiomyomatosis and pulmonary Langerhans cell histiocytosis

    Directory of Open Access Journals (Sweden)

    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.

  6. 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.

  7. 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

  8. 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.

  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. 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.

  11. 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.)

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. 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.

  18. 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.

  19. 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

  20. 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.

  1. 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....

  2. 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

  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. 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

    Langerhans cell histiocytosis followed at Hospital das Clínicas, Universidade Federal de Minas Gerais, Brazil, between 1988 and 2004. RESULTS: Age at diagnosis ranged from 2 months to 16 years (median: 2.5 years. Seventeen children were male. The follow-up period varied from 21 days to 16.2 years (median: 3.4 years. The most common clinical manifestations at diagnosis were osteolytic lesions, enlarged lymph nodes and skin lesions. The overall survival rate for the whole group was 86.1% at 16 years (95%CI 66.6-94.6%. Deaths occurred in patients with multisystem disease and organ dysfunction at diagnosis. Those patients who had a "better" response to treatment in the sixth week were likely to have a significantly higher overall survival rate than those who showed disease progression. Overall survival rate was significantly higher for patients with single-system disease. The disease-free survival rate for the whole group was 30.9% at 16 years (95%CI 15.6-47.5%, and was significantly higher for those with single-system disease. Age groups were not associated with different disease-free survival rates. Diabetes insipidus was the most common sequela. No cases of secondary neoplasms were observed. CONCLUSION: The clinical manifestations of Langerhans cell histiocytosis vary widely, with a high relapse rate and low mortality rate.

  5. 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

  6. 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.

  7. 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

  8. Langerhans cell histiocytosis: A case presentation and literature ...

    African Journals Online (AJOL)

    evaluation imaging (skeletal survey, skeletal isotopes and CT ... recent imaging confirmed that he still has .... include small stature, growth hormone deficiency, hypothyroidism, ... lesions or multisystem non-risk organ involvement, even a short.

  9. [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.

  10. 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)

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.)

  14. 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...

  15. 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.)

  16. 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

  17. 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

  18. 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.

  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. 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

  1. 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.

  2. 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

  3. 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.

  4. 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

  5. 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

  6. 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

  7. 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.

  8. 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

  9. 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

  10. 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.)

  11. 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.)

  12. 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

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

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    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.

  14. 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.

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

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    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.

  16. 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

  17. 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.

  18. 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....

  19. 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...

  20. 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

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

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    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.

  2. 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.)

  3. 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.

  4. [Xanthoma disseminatum with asymptomatic multisystem involvement].

    Science.gov (United States)

    Zinoun, M; Hali, F; Marnissi, F; Lazaar, S; Benchikhi, H

    2015-04-01

    Xanthogranulomas belong to non-Langerhans histiocytosis of the second group in the Histiocyte Society classification. They comprise a heterogeneous group of rare entities frequently involving cutaneous tropism. Xanthoma disseminatum belongs to this group of non-Langerhans histiocytosis. We report a case of xanthoma disseminatum (XD) in which localized skin and mucous impairment revealed multisystem involvement. A 28-year-old man presented with a two-year history of progressive yellow-orange and infiltrated xanthomatous papulonodular lesions of the face. Lesions of the oral mucosa and genital region were seen, with no functional repercussions. No ophthalmic or other complications were found. Histopathology showed a dense histiocytic infiltrate within the dermis with Touton giant cells, foamy multinucleated giant cells and inflammatory cells, without necrobiosis. Histiocytes were positive for CD68 but negative for CD1a. Gastric and lung involvement was seen and was confirmed at histology. Bone scintigraphy showed suspicious left ulnar hyperfixation suggesting bone involvement. No monoclonal gammopathy or diabetes insipidus was seen. Our patient was treated with corticosteroids 1mg/kg/day and thalidomide 100 mg/day. The outcome was marked by regression and exfiltration of the cutaneous lesions from the second week of treatment, with subsidence continuing at 3 months. This case involves a very rare form of xanthoma disseminatum. The localized facial skin lesions revealed multifocal non-Langerhans histiocytosis that was in fact asymptomatic. The diagnosis of XD was based on clinical, histological and immunohistochemical criteria. Xanthoma disseminatum is a non-Langerhans histiocytic proliferation first described by Montgomery in 1938. This rare entity is characterized by skin and mucous membrane xanthomatosis in which the facial involvement is common, together with diabetes insipidus and normal lipid metabolism. The prognosis is determined by the presence of mucosal

  5. 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.

  6. [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.

  7. 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)

  8. 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.)

  9. 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

  10. 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.

  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. 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

  13. 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.)

  14. 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.)

  15. 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

  16. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

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

    Science.gov (United States)

    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.

  4. 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.

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

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    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.

  6. 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.

  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. 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

  9. 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.

  10. 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

  11. 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.

  12. 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.)

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

    Science.gov (United States)

    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.

  14. 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

  15. 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

  16. 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

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

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    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.

  18. 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

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

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    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.

  20. Langerhans Cells Histiocytosis: Features of Clinical and Laboratory Manifestations and Course of the Disease

    Directory of Open Access Journals (Sweden)

    O.I. Dorosh

    2014-08-01

    Results of the Study. An analysis of 25 cases of LCH in children was presented. Monosystem LCH most often affects the skeletal system. Multisystem LCH is characterized by diversity of clinical manifestations, more severe course and high risk of death. One third of patients with multisystem LCH are infants. In children with monosystem LCH we observed complete clinical response to first-line therapy. At the same time, complete response to polychemotherapy is observed only in 30 % of children with multisystem LCH. Prognosis of the disease depends on the initial affection of risk organs (bone marrow, liver, lungs, spleen, their dysfunction and the child’s age at the time of diagnosis. Process reactivation in children with multisystem LCH occurs in the first 12 months from the onset of the disease.

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

    Directory of Open Access Journals (Sweden)

    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.

  2. 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.

  3. 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.

  4. 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.

  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. 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

  7. 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

  8. 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.)

  9. 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

  10. 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

  11. 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

  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. 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

  14. 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.

  15. 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.

  16. 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

  17. 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.

  18. 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.

  19. 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...

  20. 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.)

  1. 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.

  2. 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.

  3. [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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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)

  10. 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.

  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. 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)

  13. 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.

  14. 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.

  15. 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.)

  16. 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.)

  17. 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.

  18. 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.

  19. 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)

  20. Significant association of inflammation grade with the number of Langerhans cells in odontogenic keratocysts

    Directory of Open Access Journals (Sweden)

    Chun-Han Chang

    2017-10-01

    Conclusion: A significant association of inflammation grade with the number of LCs in OKCs is found. The paucity of finding LCs in the lining epithelia of OKCs without inflammation indicates 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.

  1. 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)

  2. 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)

  3. 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.

  4. 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.

  5. 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)

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

    Directory of Open Access Journals (Sweden)

    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.

  7. 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.

  8. 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.

  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. 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.

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. Influence of chain length of pyrene fatty acids on their uptake and metabolism by Epstein-Barr-virus-transformed lymphoid cell lines from a patient with multisystemic lipid storage myopathy and from control subjects.

    OpenAIRE

    Radom, J; Salvayre, R; Levade, T; Douste-Blazy, L

    1990-01-01

    The uptake and intracellular metabolism of 4-(1-pyrene)butanoic acid (P4), 10-(1-pyrene)decanoic acid (P10) and 12-(1-pyrene)dodecanoic acid (P12) were investigated in cultured lymphoid cell lines from normal individuals and from a patient with multisystemic lipid storage myopathy (MLSM). The cellular uptake was shown to be dependent on the fatty-acid chain length, but no significant difference in the uptake of pyrene fatty acids was observed between MLSM and control lymphoid cells. After inc...

  16. 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.

  17. 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

  18. 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

  19. Multisystem involvement in neuromyelitis optica

    Directory of Open Access Journals (Sweden)

    Megan M Langille

    2015-01-01

    Full Text Available We describe a case of pediatric neuromyelitis optica (NMO with muscle and lung involvement in addition to central nervous system disease. Our patient initially presented with features of area postrema syndrome, then subsequently with optic neuritis. The patient also had recurrent hyperCKemia that responded to corticosteroids. Finally, axillary and hilar adenopathy with pulmonary consolidation were noted as well and responded to immunomodulation. Our case highlights multisystem involvement in NMO including non-infectious pulmonary findings which have not been described in the pediatric population previously.

  20. Eye features in three Danish patients with multisystemic smooth muscle dysfunction syndrome

    DEFF Research Database (Denmark)

    Moller, Hans Ulrik; Fledelius, Hans C; Milewicz, Dianna M

    2012-01-01

    A de novo mutation of the ACTA2 gene encoding the smooth muscle cell α-actin has been established in patients with multisystemic smooth muscle dysfunction syndrome associated with patent ductus arteriosus and mydriasis present at birth....

  1. 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

  2. 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...

  3. 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

  4. 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.

  5. 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.

  6. Influence of chain length of pyrene fatty acids on their uptake and metabolism by Epstein-Barr-virus-transformed lymphoid cell lines from a patient with multisystemic lipid storage myopathy and from control subjects.

    Science.gov (United States)

    Radom, J; Salvayre, R; Levade, T; Douste-Blazy, L

    1990-01-01

    The uptake and intracellular metabolism of 4-(1-pyrene)butanoic acid (P4), 10-(1-pyrene)decanoic acid (P10) and 12-(1-pyrene)dodecanoic acid (P12) were investigated in cultured lymphoid cell lines from normal individuals and from a patient with multisystemic lipid storage myopathy (MLSM). The cellular uptake was shown to be dependent on the fatty-acid chain length, but no significant difference in the uptake of pyrene fatty acids was observed between MLSM and control lymphoid cells. After incubation for 1 h the distribution of fluorescent fatty acids taken up by the lymphoid cell lines also differed with the chain length, most of the fluorescence being associated with phospholipid and triacylglycerols. In contrast with P10 and P12, P4 was not incorporated into neutral lipids. When the cells were incubated for 24 h with the pyrene fatty acids, the amount of fluorescent lipids synthesized by the cells was proportional to the fatty acid concentration in the culture medium. After a 24 h incubation in the presence of P10 or P12, at any concentration, the fluorescent triacylglycerol content of MLSM cells was 2-5-fold higher than that of control cells. Concentrations of pyrene fatty acids higher than 40 microM seemed to be more toxic for mutant cells than for control cells. This cytotoxicity was dependent on the fluorescent-fatty-acid chain length (P12 greater than P10 greater than P4). Pulse-chase experiments permitted one to demonstrate the defect in the degradation of endogenously biosynthesized triacylglycerols in MLSM cells (residual activity was around 10-25% of controls on the basis of half-lives and initial rates of P10- or P12-labelled-triacylglycerol catabolism); MLSM lymphoid cells exhibited a mild phenotypic expression of the lipid storage (less severe than that observed in fibroblasts). P4 was not utilized in the synthesis of triacylglycerols, and thus did not accumulate in MLSM cells: this suggests that natural short-chain fatty acids might induce a lesser

  7. 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

  8. Combined basal cell carcinoma and Langerhans cell histiocytosis of the scrotum in a patient with occupational exposure to coal tar and dust

    Energy Technology Data Exchange (ETDEWEB)

    Izikson, L.; Vanderpool, J.; Brodsky, G.; Mihm, M.C.; Zembowicz, A. [Harvard University, Boston, MA (US). Massachusetts General Hospital

    2004-09-01

    The patient was a 77-year-old male former smoker, with history of several basal cell carcinomas (BCCs) in sun-protected areas around the waistline, who presented with another small ulceration on the anterior right upper scrotum near the base of the penis. BCC was suspected clinically and the lesion was treated with cryosurgery. The tumor recurred, became raised, and began to bleed. An excisional biopsy was performed. It showed nodular BCC surrounded by a cellular proliferation of round histiocytic cells with convoluted, lobulated and reniform nuclei and abundant cytoplasm . The patient had no history of exposure to ionizing radiation, chemotherapy, immunosuppressive medications, prior lymphoma or other malignancy. However, he spent 4 years on a ship loading coal into the furnace of a steam engine, during which he slept in adjacent quarters that were covered with coal dust. Additionally, he had a several-year history of occupational skin exposure to machine oil, oil refinery waste, sulfur waste, hydraulic fluid, and asbestos. He also reported a history of nude sunbathing. The scrotal lesion was re-excised and the patient remains disease-free more than 1 year after the diagnosis.

  9. NOMID - a neonatal syndrome of multisystem inflammation

    Energy Technology Data Exchange (ETDEWEB)

    Torbiak, R.P.; Cockshott, W.P. (Chedoke-McMaster Hospitals, Hamilton, ON (Canada). Dept. of Radiology); Dent, P.B. (Chedoke-McMaster Hospitals, Hamilton, ON (Canada). Dept. of Pediatrics)

    1989-08-01

    Neonatal onset multisystem inflammatory disease is a rare disorder first described by Lorber in 1973. An additional 29 cases have been recorded. Two patients are described here, one with a 17 year follow-up. The typical features are a rash, fever, adenopathy, hepatosplenomegaly, and a severe, deforming arthropathy predominantly affecting large joints. The most striking feature is the onset in the neonatal period. Other associated features include inflammation, chronic meningitis, anemia, and persistent leukocytosis. Most, if not all, patients develop bizarre epiphyseal radiographic findings that are virtually pathognomonic. This disease is distinct from Still disease. (orig.).

  10. 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.

  11. The international implementation of multisystemic therapy.

    Science.gov (United States)

    Schoenwald, Sonja K; Heiblum, Naamith; Saldana, Lisa; Henggeler, Scott W

    2008-06-01

    The purpose of this article is to consider, through the lenses of theory and research on technology transfer and the adoption and implementation of innovation, the international transport of evidence-based psychosocial treatments for youth, using Multisystemic Therapy (MST) as an example. MST is a well-validated family and community-based approach originally developed in the United States to treat serious juvenile offenders. This article describes challenges to MST transport internationally by virtue of the political, legal, economic, and cultural contexts in different nations. Modifications used to address these challenges and facilitate the international implementation of MST are described and pertain to pre-implementation processes, clinical staff, training materials and procedures, and clinical service delivery.

  12. A K ATP channel-dependent pathway within alpha cells regulates glucagon release from both rodent and human islets of Langerhans.

    Science.gov (United States)

    MacDonald, Patrick E; De Marinis, Yang Zhang; Ramracheya, Reshma; Salehi, Albert; Ma, Xiaosong; Johnson, Paul R V; Cox, Roger; Eliasson, Lena; Rorsman, Patrik

    2007-06-01

    Glucagon, secreted from pancreatic islet alpha cells, stimulates gluconeogenesis and liver glycogen breakdown. The mechanism regulating glucagon release is debated, and variously attributed to neuronal control, paracrine control by neighbouring beta cells, or to an intrinsic glucose sensing by the alpha cells themselves. We examined hormone secretion and Ca(2+) responses of alpha and beta cells within intact rodent and human islets. Glucose-dependent suppression of glucagon release persisted when paracrine GABA or Zn(2+) signalling was blocked, but was reversed by low concentrations (1-20 muM) of the ATP-sensitive K(+) (KATP) channel opener diazoxide, which had no effect on insulin release or beta cell responses. This effect was prevented by the KATP channel blocker tolbutamide (100 muM). Higher diazoxide concentrations (>/=30 muM) decreased glucagon and insulin secretion, and alpha- and beta-cell Ca(2+) responses, in parallel. In the absence of glucose, tolbutamide at low concentrations (10 muM) were inhibitory. In the presence of a maximally inhibitory concentration of tolbutamide (0.5 mM), glucose had no additional suppressive effect. Downstream of the KATP channel, inhibition of voltage-gated Na(+) (TTX) and N-type Ca(2+) channels (omega-conotoxin), but not L-type Ca(2+) channels (nifedipine), prevented glucagon secretion. Both the N-type Ca(2+) channels and alpha-cell exocytosis were inactivated at depolarised membrane potentials. Rodent and human glucagon secretion is regulated by an alpha-cell KATP channel-dependent mechanism. We propose that elevated glucose reduces electrical activity and exocytosis via depolarisation-induced inactivation of ion channels involved in action potential firing and secretion.

  13. A K ATP channel-dependent pathway within alpha cells regulates glucagon release from both rodent and human islets of Langerhans.

    Directory of Open Access Journals (Sweden)

    Patrick E MacDonald

    2007-06-01

    Full Text Available Glucagon, secreted from pancreatic islet alpha cells, stimulates gluconeogenesis and liver glycogen breakdown. The mechanism regulating glucagon release is debated, and variously attributed to neuronal control, paracrine control by neighbouring beta cells, or to an intrinsic glucose sensing by the alpha cells themselves. We examined hormone secretion and Ca(2+ responses of alpha and beta cells within intact rodent and human islets. Glucose-dependent suppression of glucagon release persisted when paracrine GABA or Zn(2+ signalling was blocked, but was reversed by low concentrations (1-20 muM of the ATP-sensitive K(+ (KATP channel opener diazoxide, which had no effect on insulin release or beta cell responses. This effect was prevented by the KATP channel blocker tolbutamide (100 muM. Higher diazoxide concentrations (>/=30 muM decreased glucagon and insulin secretion, and alpha- and beta-cell Ca(2+ responses, in parallel. In the absence of glucose, tolbutamide at low concentrations (10 muM were inhibitory. In the presence of a maximally inhibitory concentration of tolbutamide (0.5 mM, glucose had no additional suppressive effect. Downstream of the KATP channel, inhibition of voltage-gated Na(+ (TTX and N-type Ca(2+ channels (omega-conotoxin, but not L-type Ca(2+ channels (nifedipine, prevented glucagon secretion. Both the N-type Ca(2+ channels and alpha-cell exocytosis were inactivated at depolarised membrane potentials. Rodent and human glucagon secretion is regulated by an alpha-cell KATP channel-dependent mechanism. We propose that elevated glucose reduces electrical activity and exocytosis via depolarisation-induced inactivation of ion channels involved in action potential firing and secretion.

  14. Gliadin Fragments and a Specific Gliadin 33-mer Peptide Close KATP Channels and Induce Insulin Secretion in INS-1E Cells and Rat Islets of Langerhans

    DEFF Research Database (Denmark)

    Dall, Morten; Calloe, Kirstine; Haupt-Jorgensen, Martin

    2013-01-01

    . A similar effect was observed in isolated rat islets (1.6-fold increase). In INS-1E cells, diazoxide reduced the stimulatory effect of gliadin digest. Additionally, gliadin digest was shown to decrease current through KATP-channels. A specific gliadin 33-mer had a similar effect, both on current and insulin...

  15. Enterovirus infection of human islets of Langerhans affects β-cell function resulting in disintegrated islets, decreased glucose stimulated insulin secretion and loss of Golgi structure

    NARCIS (Netherlands)

    Hodik, M; Skog, O; Lukinius, A; Isaza-Correa, J M; Kuipers, Jeroen; Giepmans, B N G; Frisk, G

    AIMS/HYPOTHESIS: In type 1 diabetes (T1D), most insulin-producing β cells are destroyed, but the trigger is unknown. One of the possible triggers is a virus infection and the aim of this study was to test if enterovirus infection affects glucose stimulated insulin secretion and the effect of virus

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

    OpenAIRE

    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...

  17. 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.

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

    Directory of Open Access Journals (Sweden)

    . 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.

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

    Science.gov (United States)

    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.

  20. CubeSat Handling of Multisystem Precision Time Transfer (CHOMPTT)

    Data.gov (United States)

    National Aeronautics and Space Administration — The CubeSat Handling of Multisystem Precision Time Transfer (CHOMPTT) mission is a precision timing satellite equipped with atomic clocks synchronized with a ground...

  1. Histiocitosis de Células de Langerhans

    Directory of Open Access Journals (Sweden)

    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.

  2. General Information about Langerhans Cell Histiocytosis (LCH)

    Science.gov (United States)

    ... speaking. Trouble seeing. Headaches. Changes in behavior or personality. Memory problems. These signs and symptoms may be ... National Institutes of Health FOLLOW US Facebook Twitter Instagram YouTube Google+ LinkedIn GovDelivery RSS CONTACT INFORMATION Contact ...

  3. Pulmonary Langerhans Cell Histiocytosis Case with Diabetes ...

    African Journals Online (AJOL)

    2016-07-12

    Jul 12, 2016 ... thin-walled cystic lesions in different sizes more dominantly in the upper lobes and consolidated areas ... zones inside, which started from the hilar region on ... increase of infiltrations in the control PA radiography. Right lung ...

  4. 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.

  5. 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.

  6. 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.

  7. 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 ...

  8. Amyotrophic Lateral Sclerosis, a Multisystem Pathology: Insights into the Role of TNFα

    Directory of Open Access Journals (Sweden)

    Massimo Tortarolo

    2017-01-01

    Full Text Available Amyotrophic lateral sclerosis (ALS is considered a multifactorial, multisystem disease in which inflammation and the immune system play important roles in development and progression. The pleiotropic cytokine TNFα is one of the major players governing the inflammation in the central nervous system and peripheral districts such as the neuromuscular and immune system. Changes in TNFα levels are reported in blood, cerebrospinal fluid, and nerve tissues of ALS patients and animal models. However, whether they play a detrimental or protective role on the disease progression is still not clear. Our group and others have recently reported opposite involvements of TNFR1 and TNFR2 in motor neuron death. TNFR2 mediates TNFα toxic effects on these neurons presumably through the activation of MAP kinase-related pathways. On the other hand, TNFR2 regulates the function and proliferation of regulatory T cells (Treg whose expression is inversely correlated with the disease progression rate in ALS patients. In addition, TNFα is considered a procachectic factor with a direct catabolic effect on skeletal muscles, causing wasting. We review and discuss the role of TNFα in ALS in the light of its multisystem nature.

  9. Experimental Airborne Transmission of Porcine Postweaning Multisystemic Wasting Syndrome

    DEFF Research Database (Denmark)

    Kristensen, C. S.; Hjulsager, Charlotte Kristiane; Vestergaard, K.

    2013-01-01

    The objective of these studies was to investigate if porcine postweaning multisystemic wasting syndrome (PMWS) could be induced in healthy pigs following contact with air from pigs with clinical signs of PMWS. The pigs were housed in different units. Either 31 (study I) or 25 (study II) pigs with...... typical of PMWS. Sequence analysis revealed that the PCV2 isolate belonged to genotype 2b. In conclusion, the present study showed that PMWS can be induced in pigs from a PMWS-free herd by airborne contact with pigs from a PMWS-affected herd....

  10. 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...

  11. Thyrotoxic and pheochromocytoma multisystem crisis: a case report.

    Science.gov (United States)

    Suzuki, Kodai; Miyake, Takahito; Okada, Hideshi; Yamaji, Fuminori; Kitagawa, Yuichiro; Fukuta, Tetsuya; Yasuda, Ryu; Tanaka, Yoshihito; Okamoto, Haruka; Nachi, Sho; Doi, Tomoaki; Yoshida, Takahiro; Kumada, Keisuke; Yoshida, Shozo; Ushikoshi, Hiroaki; Toyoda, Izumi; Ogura, Shinji

    2017-06-23

    Thyrotoxic crisis and pheochromocytoma multisystem crisis are rare, life-threatening, emergency endocrine diseases with various clinical manifestations. Here we report a case of a patient who simultaneously developed thyrotoxic crisis and pheochromocytoma multisystem crisis and required intensive cardiovascular management. A 60-year-old Asian man experienced nausea and vomiting, and subsequently developed dyspnea and cold sweats while farming. His serum free thyroxine, free triiodothyronine, and thyrotropin receptor antibody levels were elevated at 2.9 ng/dL, 7.2 pg/dL, and 4.7 IU/L, respectively. Serum thyrotropin levels were suppressed at less than 0.01 μIU/mL. Thyroid echography demonstrated no thyroid swelling (23 × 43 mm). A whole body computed tomography was performed for systemic evaluation. This revealed exophthalmos and a mass of size 57 × 64 mm in the anterior pararenal space. Based on these findings, we made an initial diagnosis of thyrotoxic crisis secondary to exacerbation of Grave's hyperthyroidism. Treatment was begun with an iodine agent at a dose of 36 mg/day, thiamazole at a dose of 30 mg/day, and hydrocortisone at a dose of 300 mg daily for 3 consecutive days. To control tachycardia, continuous intravenously administered propranolol and diltiazem infusions were given. At the same time, small doses of doxazosin and carvedilol were used for both alpha and beta adrenergic blockade. On hospital day 5, his blood pressure and serum catecholamine concentrations (adrenalin 42,365 pg/mL, dopamine 6409 pg/mL, noradrenalin 72,212 pg/mL) were still high despite higher beta blocker and calcium channel blocker doses. These findings contributed to the diagnosis of pheochromocytoma multisystem crisis with simultaneous thyrotoxic crisis. We increased the doses of doxazosin and carvedilol, which stabilized his hemodynamic status. On hospital day 16, metaiodobenzylguanidine scintigraphy showed high accumulation in the right adrenal gland tumor

  12. Economic Impact of Multisystemic Therapy for Child Abuse and Neglect.

    Science.gov (United States)

    Dopp, Alex R; Schaeffer, Cindy M; Swenson, Cynthia Cupit; Powell, Jennifer S

    2018-04-04

    This study evaluated the economics of Multisystemic Therapy for Child Abuse and Neglect (MST-CAN) by applying the Washington State Institute for Public Policy (WSIPP) cost-benefit model to data from a randomized effectiveness trial with 86 families (Swenson et al. in JFP 24:497-507, 2010b). The net benefit of MST-CAN, versus enhanced outpatient treatment, was $26,655 per family at 16 months post-baseline. Stated differently, every dollar spent on MST-CAN recovered $3.31 in savings to participants, taxpayers, and society at large. Policymakers and public service agencies should consider these findings when making investments into interventions for high-need families involved with child protective services.

  13. The Resilience of Kepler Multi-systems to Stellar Obliquity

    Science.gov (United States)

    Spalding, Christopher; Marx, Noah W.; Batygin, Konstantin

    2018-04-01

    The Kepler mission and its successor K2 have brought forth a cascade of transiting planets. Many of these planetary systems exhibit multiple transiting members. However, a large fraction possesses only a single transiting planet. This high abundance of singles, dubbed the "Kepler Dichotomy," has been hypothesized to arise from significant mutual inclinations between orbits in multi-planet systems. Alternatively, the single-transiting population truly possesses no other planets in the system, but the true origin of the overabundance of single systems remains unresolved. In this work, we propose that planetary systems typically form with a coplanar, multiple-planetary architecture, but that quadrupolar gravitational perturbations from their rapidly-rotating host star subsequently disrupt this primordial coplanarity. We demonstrate that, given sufficient stellar obliquity, even systems beginning with 2 planetary constituents are susceptible to dynamical instability soon after planet formation, as a result of the stellar quadrupole moment. This mechanism stands as a widespread, yet poorly explored pathway toward planetary system instability. Moreover, by requiring that observed multi-systems remain coplanar on Gyr timescales, we are able to place upper limits on the stellar obliquity in systems such as K2-38 (obliquity < 20 degrees), where other methods of measuring spin-orbit misalignment are not currently available.

  14. A Multi-Systems Life Course Perspective of Economic Abuse

    Directory of Open Access Journals (Sweden)

    Kameri Christy

    2017-09-01

    Full Text Available Intimate partner violence (IPV against women slowly moved out of the private sphere and into the public realm in the United States in the early 1970’s. While progress has been made regarding psychological, physical, and sexual trauma related to IPV, it has been only in the last decade that attention about IPV has included an examination of the impact of economic abuse (EA. This is disturbing given that EA is one of the eight spokes on the Power and Control wheel (PCW and many women state that they are not able to leave or get away from the abusive relationship due to financial reasons. Using a multi-systems life course (MSLC perspective, this paper considers the importance of elevating EA as a form of IPV-related trauma. We examine EA’s differential impact among women, review current practices and policies, and conclude with implications for micro, mezzo, and macro levels of trauma-informed practice with survivors of EA.

  15. Arthropathy of neonatal onset multisystem inflammatory disease (NOMID/CINCA)

    Energy Technology Data Exchange (ETDEWEB)

    Hill, Suvimol C.; Dwyer, Andrew [Warren G. Magnuson Clinical Center, Diagnostic Radiology, National Institutes of Health (NIH), Bethesda, MD (United States); Namde, Madjimbaye; Canna, Scott; Goldbach-Mansky, Raphaela [National Institutes of Health (NIH), National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, MD (United States); Poznanski, Andrew [Northwestern University, Department of Radiology, Medical Imaging, Children' s Memorial Hospital, Chicago, IL (United States)

    2007-02-15

    Neonatal onset multisystem inflammatory disease (NOMID), an autoinflammatory disease, is characterized by fever, chronic urticarial rash, CNS manifestations, and arthropathy. Approximately 50% of patients with NOMID have de novo missense mutations in CIAS1, which is associated with modulation of the IL-1b and apoptotic pathways. Approximately 60% of NOMID patients have prominent arthropathy, most commonly involving the knees, the cause of which remains poorly understood. To more fully describe the findings of NOMID arthropathy on MRI and radiography and to provide a better understanding of the origin of the bony lesions. We imaged 20 patients with NOMID to further investigate NOMID-associated bony lesions. Bony abnormalities were seen in the knees of 11/20 patients. The knee findings included enlarged, deformed femora and patellae in all and tibiae in the majority, without evidence of synovitis. Some patients had other joint involvement. Most had short stature and valgus or varus knee deformities. No association was noted between bony abnormalities and CIAS1 mutations. The abnormalities appeared to be the result of a mass-producing process. The resulting heterogeneously calcified masses appeared to originate in the physis and deformed the adjacent metaphysis and epiphysis. These findings suggest that the arthropathy of NOMID is the result of abnormal endochondral bone growth. Further investigation is needed to determine whether this deformity is triggered by inflammation early in development or by CIAS1 mutations causing abnormal chondrocyte apoptosis. (orig.)

  16. Arthropathy of neonatal onset multisystem inflammatory disease (NOMID/CINCA)

    International Nuclear Information System (INIS)

    Hill, Suvimol C.; Dwyer, Andrew; Namde, Madjimbaye; Canna, Scott; Goldbach-Mansky, Raphaela; Poznanski, Andrew

    2007-01-01

    Neonatal onset multisystem inflammatory disease (NOMID), an autoinflammatory disease, is characterized by fever, chronic urticarial rash, CNS manifestations, and arthropathy. Approximately 50% of patients with NOMID have de novo missense mutations in CIAS1, which is associated with modulation of the IL-1b and apoptotic pathways. Approximately 60% of NOMID patients have prominent arthropathy, most commonly involving the knees, the cause of which remains poorly understood. To more fully describe the findings of NOMID arthropathy on MRI and radiography and to provide a better understanding of the origin of the bony lesions. We imaged 20 patients with NOMID to further investigate NOMID-associated bony lesions. Bony abnormalities were seen in the knees of 11/20 patients. The knee findings included enlarged, deformed femora and patellae in all and tibiae in the majority, without evidence of synovitis. Some patients had other joint involvement. Most had short stature and valgus or varus knee deformities. No association was noted between bony abnormalities and CIAS1 mutations. The abnormalities appeared to be the result of a mass-producing process. The resulting heterogeneously calcified masses appeared to originate in the physis and deformed the adjacent metaphysis and epiphysis. These findings suggest that the arthropathy of NOMID is the result of abnormal endochondral bone growth. Further investigation is needed to determine whether this deformity is triggered by inflammation early in development or by CIAS1 mutations causing abnormal chondrocyte apoptosis. (orig.)

  17. Emergent multisystemic Enterococcus infection threatens endangered Christmas Island reptile populations.

    Directory of Open Access Journals (Sweden)

    Karrie Rose

    Full Text Available Multisystemic infections with a morphologically unusual bacterium were first observed in captive critically endangered Lister's geckos (Lepidodactylus listeri on Christmas Island in October 2014. Since then the infection was identified in another captive critically endangered lizard species, the blue-tailed skink (Cryptoblepharus egeriae and two species of invasive geckos; the four clawed gecko (Gehyra mutilata and Asian house gecko (Hemidactylus frenatus, in a wide geographic range across the east side of the island. The Gram and periodic acid-Schiff positive cocci to diplococci have a propensity to form chains surrounded by a matrix, which ultrastructurally appears to be formed by fibrillar capsular projections. The bacterium was associated with severe and extensive replacement of tissues, but minimal host inflammatory response. Attempts to grow the organism in culture and in embryonated eggs were unsuccessful. Molecular characterisation of the organism placed it as a novel member of the genus Enterococcus. Disease Risk Analyses including this organism should now be factored into conservation management actions and island biosecurity.

  18. [BIPOLAR DISORDER AS A MULTI-SYSTEM ILLNESS].

    Science.gov (United States)

    Fenchel, Daphna; Levkovitz, Yechiel; Kotler, Moshe

    2017-12-01

    Bipolar disorder is a chronic condition, characterized by high distress in patients and high suicide rates (30%). Most patients suffer from medical and other psychiatric comorbidities, which worsen the psychiatric symptoms and decrease the likelihood of remission. More than 70% of bipolar patients have cardio-metabolic symptoms, with higher rates compared to other psychiatric disorders. Cardiovascular disease is the major cause of high mortality rates in these patients, with 1.5-2 fold increased risk of mortality, compared to the general population without psychiatric symptoms. The rates of cardiovascular risk factors and their resulting increased mortality rates are similar to those found in schizophrenia. In addition to cardio-metabolic conditions, 50% of patients with bipolar disorder suffer from other medical symptoms, which are also associated with worse outcomes. Therefore, the current perspective is that bipolar disorder is not only a psychiatric disorder, but rather a multi-system illness, affecting the entire body. The optimal treatment for these patients should include diagnosis, monitoring and treatment of both psychiatric and physical symptoms, which would improve their prognosis.

  19. A young patient with multisystem complications after cytomegalovirus infection

    Directory of Open Access Journals (Sweden)

    Swaroopa Pulivarthi

    2014-01-01

    Full Text Available We are describing a case of an 18-year-old male patient with cytomegalovirus (CMV associated guillain-barre syndrome (GBS who presented with an acute onset of generalized weakness and numbness in the extremities, dysphagia, and facial diplegia, followed by respiratory failure, which led to mechanical ventilation. He had positive immunoglobulin G and immunoglobulin M antibodies against CMV, and CMV polymerase chain reaction was positive with <2000 copies of deoxyribonucleic acid. Human immunodeficiency virus test was negative. He received a course of ganciclovir, intravenous immunoglobulin, and plasmapheresis. After improving from acute episode, patient was transferred to a rehabilitation facility for physical and occupational therapy. At the rehabilitation facility, he exhibited signs of acute abdomen with pain in the left upper quadrant secondary to peritonitis from dislodged gastrostomy tube and underwent exploratory laparotomy. During the hospital course he was found to have splenic infarct and colitis on the computed tomography of abdomen. This case showed an immunocompetent young patient with multisystem complications including guillain-barre syndrome (GBS, splenic infarct, hepatitis, and colitis due to CMV.

  20. Paternal involvement in Multisystemic Therapy: Effects on adolescent outcomes and maternal depression

    NARCIS (Netherlands)

    Gervan, S.; Granic, I.; Solomon, T.; Blokland, K.; Ferguson, B.

    2012-01-01

    The association between paternal involvement in therapy, adolescent outcomes and maternal depression was examined within the context of Multisystemic Therapy (MST), an empirically supported, family- and community-based treatment for antisocial adolescents. Ninety-nine families were recruited from

  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. Topical or oral administration with an extract of Polypodium leucotomos prevents acute sunburn and psoralen-induced phototoxic reactions as well as depletion of Langerhans cells in human skin

    Energy Technology Data Exchange (ETDEWEB)

    Gonzalez, S.; Pathak, M.A.; Fitzpatrick, T.B. [Massachusetts General Hospital, Harvard Medical School, Dept. of Dermatology, Boston, MA (United States); Cuevas, J. [Hospital Universitario de Guadalajara, Dept. of Pathology, Guadalajara (Spain); Villarrubia, V.G. [I.F. Cantabria SA, Medical Dept., Immunology Sect., Madrid (Spain)

    1997-12-31

    Sunburn, immune suppression, photo-aging, and skin cancers result from uncontrolled overexposure of human skin to solar ultraviolet radiation (UVR). Preventive measures, including photo-protection, are helpful and can be achieved by topical sun-screening agents. Polypodium leucotomos (PL) has been used for the treatment of inflammatory diseases and has shown some in vitro and in vivo immunomodulating properties. Its beneficial photo-protective effects in the treatment of vitiligo and its antioxidant properties encouraged us to evaluate in vivo the potentially useful photo-protective property of natural extract of PL after topical application or oral ingestion. Twenty-one healthy volunteers [either untreated or treated with oral psoralens (8-MOP or 5-MOP)] were enrolled in this study and exposed to solar radiation for evaluation of the following clinical parameters: immediate pigment darkening (IPD), minimal erythema dose (MED), minimal melanogenic dose (MMD), and minimal phototoxic dose (MPD) before and after topical or oral administration of PL. Immunohistochemical assessment of CD1a-expressing epidermal cells were also performed. PL was found to be photo-protective after topical application as well as oral administration. PL increased UV dose required for IPD (P<0.01), MED (P<0.001) and MPD (P<0.001). After oral administration of PL, MED increased 2.,8{+-}0.59 times and MPD increased 2.75{+-}0.5 and 6.8{+-}1.3 times depending upon the type of psoralen used. Immunohistochemical study revealed photo-protection of Langherhans cells by oral as well as topical PL. The observed photo-protective activities of oral or topical PL reveal a new avenue in examining the potentially useful field of systemic photo-protection and suggests that PL can be used as adjunct treatment and can make photochemotherapy and phototherapy possibly safe and effective when the control of cutaneous phototoxicity to PUVA or UVB is a limiting factor in such photo-therapies. (au). 50 refs.

  3. An Evaluation of Multisystemic Therapy with Australian Families.

    Science.gov (United States)

    Porter, Mark; Nuntavisit, Leartluk

    2016-12-01

    This study aims to evaluate the effectiveness of the Multisystemic Therapy (MST) intervention for Australian families invloved with the Specialist Child and Adolescent Mental Health Service (CAMHS). This program was implemented within the Western Australian Department of Health in 2005, and has continually operated two small clinical teams within the Perth metropolitan area since then. This intervention was specifically chosen to improve service access, engagement, and intervention with vulnerable families having young persons with a history of significant and enduring behavioural problems. The study reports on data collected from July 2007 to July 2013 which includes baseline, post-treatment, 6-month, and 12-month follow-up. There were 153 MST families participating in the research at all time points (71% male; 11% Australian Aboriginal; average youth age was 13.6 years). Caregivers completed a set of questionnaires including Child Behaviour Checklist, Parenting Styles and Dimensions Questionnaire, and Depression, Anxiety and Stress Scale. One-way repeated measure ANOVA were used to measure changes over time. Significant caregiver-reported improvements in all measures were reported at post-treatment, and most improvements were maintained at the follow-up periods of 6 and 12 months post-intervention. These preliminary outcomes demonstrate that the 4-5 month MST intervention significantly reduces behavioural problems and emotional difficulties in young Australians and these improvements are generally maintained by caregivers over time. Primary caregivers reported improved skills and mental health functioning that were also maintained over the follow-up period. A proposed randomised controlled trial of the program will address potential placebo and selection bias effects.

  4. Topical or oral administration with an extract of Polypodium leucotomos prevents acute sunburn and psoralen-induced phototoxic reactions as well as depletion of Langerhans cells in human skin

    International Nuclear Information System (INIS)

    Gonzalez, S.; Pathak, M.A.; Fitzpatrick, T.B.; Cuevas, J.; Villarrubia, V.G.

    1997-01-01

    Sunburn, immune suppression, photo-aging, and skin cancers result from uncontrolled overexposure of human skin to solar ultraviolet radiation (UVR). Preventive measures, including photo-protection, are helpful and can be achieved by topical sun-screening agents. Polypodium leucotomos (PL) has been used for the treatment of inflammatory diseases and has shown some in vitro and in vivo immunomodulating properties. Its beneficial photo-protective effects in the treatment of vitiligo and its antioxidant properties encouraged us to evaluate in vivo the potentially useful photo-protective property of natural extract of PL after topical application or oral ingestion. Twenty-one healthy volunteers [either untreated or treated with oral psoralens (8-MOP or 5-MOP)] were enrolled in this study and exposed to solar radiation for evaluation of the following clinical parameters: immediate pigment darkening (IPD), minimal erythema dose (MED), minimal melanogenic dose (MMD), and minimal phototoxic dose (MPD) before and after topical or oral administration of PL. Immunohistochemical assessment of CD1a-expressing epidermal cells were also performed. PL was found to be photo-protective after topical application as well as oral administration. PL increased UV dose required for IPD (P<0.01), MED (P<0.001) and MPD (P<0.001). After oral administration of PL, MED increased 2.,8±0.59 times and MPD increased 2.75±0.5 and 6.8±1.3 times depending upon the type of psoralen used. Immunohistochemical study revealed photo-protection of Langherhans cells by oral as well as topical PL. The observed photo-protective activities of oral or topical PL reveal a new avenue in examining the potentially useful field of systemic photo-protection and suggests that PL can be used as adjunct treatment and can make photochemotherapy and phototherapy possibly safe and effective when the control of cutaneous phototoxicity to PUVA or UVB is a limiting factor in such photo-therapies. (au)

  5. 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

  6. 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.

  7. 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

  8. Acute tubulointerstitial nephritis with severe renal impairment associated with multisystem IgG4-related disease

    Directory of Open Access Journals (Sweden)

    Rafael Coimbra Ferreira Beltrame

    Full Text Available Abstract The IgG4-related disease has a wide clinical spectrum where multiple organs can be affected, and the diagnosis depends on typical histopathological findings and an elevated IgG4 expression in plasma cells in the affected tissue. We describe the clinical presentation and evolution of a patient with acute tubulointerstitial nephritis, severe kidney failure and systemic manifestations such as lymphadenomegaly and chronic pancreatitis. The diagnosis was confirmed by the clinical picture and kidney and lymph node histopathology, in which immunohistochemistry of the lymphoid tissue showed policlonality and increased expression of IgG4, with a IgG4/total IgG ratio > 80%. The patient was treated with prednisone at a dose of 60 mg/day, followed by mycophenolate mofetil, and showed clinical and renal function improvement at 6 months of follow-up. The high index of suspicion of IgG4-related disease with multisystem involvement and the early treatment of this condition are essential to improve the prognosis of affected patients.

  9. Percutaneous vertebroplasty in osteoporosis, myeloma and Langerhans' cell histiocytosis.

    LENUS (Irish Health Repository)

    Kevane, B

    2012-01-09

    This review aims to assess the effectiveness of percutaneous vertebroplasty as a treatment for the severe refractory pain associated with vertebral fracture, in a group of patients with fractures secondary to either osteoporotic or neoplastic disease. A retrospective review of 20 patients treated with percutaneous vertebroplasty in Cork University Hospital up until March 2007 was carried out and a questionnaire was prepared and distributed. Prior to vertebroplasty, patients had been symptomatic with severe pain for a mean of 20.9 weeks. Of those thirteen whom replied to a postal questionnaire, 12 (92.3%) reported pain relief and this improvement occurred within 7 days in 9 (81.8%). This was associated with decreased analgesic requirements, as determined on chart review. Prior to the procedure only 5 (38.4%) were independently mobile and this figure rose to 10 (76.9%) afterwards, occurring within one week in the majority. Subjective outcomes were better in the group of patients with neoplasm-induced fractures.

  10. 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.

  11. Mutations in PTRH2 cause novel infantile-onset multisystem disease with intellectual disability, microcephaly, progressive ataxia, and muscle weakness.

    Science.gov (United States)

    Hu, Hao; Matter, Michelle L; Issa-Jahns, Lina; Jijiwa, Mayumi; Kraemer, Nadine; Musante, Luciana; de la Vega, Michelle; Ninnemann, Olaf; Schindler, Detlev; Damatova, Natalia; Eirich, Katharina; Sifringer, Marco; Schrötter, Sandra; Eickholt, Britta J; van den Heuvel, Lambert; Casamina, Chanel; Stoltenburg-Didinger, Gisela; Ropers, Hans-Hilger; Wienker, Thomas F; Hübner, Christoph; Kaindl, Angela M

    2014-12-01

    To identify the cause of a so-far unreported phenotype of infantile-onset multisystem neurologic, endocrine, and pancreatic disease (IMNEPD). We characterized a consanguineous family of Yazidian-Turkish descent with IMNEPD. The two affected children suffer from intellectual disability, postnatal microcephaly, growth retardation, progressive ataxia, distal muscle weakness, peripheral demyelinating sensorimotor neuropathy, sensorineural deafness, exocrine pancreas insufficiency, hypothyroidism, and show signs of liver fibrosis. We performed whole-exome sequencing followed by bioinformatic analysis and Sanger sequencing on affected and unaffected family members. The effect of mutations in the candidate gene was studied in wild-type and mutant mice and in patient and control fibroblasts. In a consanguineous family with two individuals with IMNEPD, we identified a homozygous frameshift mutation in the previously not disease-associated peptidyl-tRNA hydrolase 2 (PTRH2) gene. PTRH2 encodes a primarily mitochondrial protein involved in integrin-mediated cell survival and apoptosis signaling. We show that PTRH2 is highly expressed in the developing brain and is a key determinant in maintaining cell survival during human tissue development. Moreover, we link PTRH2 to the mTOR pathway and thus the control of cell size. The pathology suggested by the human phenotype and neuroimaging studies is supported by analysis of mutant mice and patient fibroblasts. We report a novel disease phenotype, show that the genetic cause is a homozygous mutation in the PTRH2 gene, and demonstrate functional effects in mouse and human tissues. Mutations in PTRH2 should be considered in patients with undiagnosed multisystem neurologic, endocrine, and pancreatic disease.

  12. Mutations in PTRH2 cause novel infantile-onset multisystem disease with intellectual disability, microcephaly, progressive ataxia, and muscle weakness

    Science.gov (United States)

    Hu, Hao; Matter, Michelle L; Issa-Jahns, Lina; Jijiwa, Mayumi; Kraemer, Nadine; Musante, Luciana; de la Vega, Michelle; Ninnemann, Olaf; Schindler, Detlev; Damatova, Natalia; Eirich, Katharina; Sifringer, Marco; Schrötter, Sandra; Eickholt, Britta J; van den Heuvel, Lambert; Casamina, Chanel; Stoltenburg-Didinger, Gisela; Ropers, Hans-Hilger; Wienker, Thomas F; Hübner, Christoph; Kaindl, Angela M

    2014-01-01

    Objective To identify the cause of a so-far unreported phenotype of infantile-onset multisystem neurologic, endocrine, and pancreatic disease (IMNEPD). Methods We characterized a consanguineous family of Yazidian-Turkish descent with IMNEPD. The two affected children suffer from intellectual disability, postnatal microcephaly, growth retardation, progressive ataxia, distal muscle weakness, peripheral demyelinating sensorimotor neuropathy, sensorineural deafness, exocrine pancreas insufficiency, hypothyroidism, and show signs of liver fibrosis. We performed whole-exome sequencing followed by bioinformatic analysis and Sanger sequencing on affected and unaffected family members. The effect of mutations in the candidate gene was studied in wild-type and mutant mice and in patient and control fibroblasts. Results In a consanguineous family with two individuals with IMNEPD, we identified a homozygous frameshift mutation in the previously not disease-associated peptidyl-tRNA hydrolase 2 (PTRH2) gene. PTRH2 encodes a primarily mitochondrial protein involved in integrin-mediated cell survival and apoptosis signaling. We show that PTRH2 is highly expressed in the developing brain and is a key determinant in maintaining cell survival during human tissue development. Moreover, we link PTRH2 to the mTOR pathway and thus the control of cell size. The pathology suggested by the human phenotype and neuroimaging studies is supported by analysis of mutant mice and patient fibroblasts. Interpretation We report a novel disease phenotype, show that the genetic cause is a homozygous mutation in the PTRH2 gene, and demonstrate functional effects in mouse and human tissues. Mutations in PTRH2 should be considered in patients with undiagnosed multisystem neurologic, endocrine, and pancreatic disease. PMID:25574476

  13. 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

  14. 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

  15. 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

  16. 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...

  17. Amyotrophic Lateral Sclerosis, a Multisystem Pathology: Insights into the Role of TNFα

    NARCIS (Netherlands)

    Tortarolo, Massimo; Lo Coco, Daniele; Veglianese, Pietro; Vallarola, Antonio; Giordana, Maria Teresa; Marcon, Gabriella; Beghi, Ettore; Poloni, Marco; Strong, Michael J.; Iyer, Anand M.; Aronica, Eleonora; Bendotti, Caterina

    2017-01-01

    Amyotrophic lateral sclerosis (ALS) is considered a multifactorial, multisystem disease in which inflammation and the immune system play important roles in development and progression. The pleiotropic cytokine TNFα is one of the major players governing the inflammation in the central nervous system

  18. Melding Infant Mental Health and Multisystemic Therapy Approaches to Community-Based Treatment

    Science.gov (United States)

    Willoughby, Jay C.; Carubia, Beau A.; Murgolo, Marisa A.; Carter, Debbie R.; Frankel, Karen A.

    2013-01-01

    A recent partnership between the Irving Harris Program in Child Development and Infant Mental Health and the Community Based Psychiatry Program at University of Colorado Hospital joined two different approaches to child mental health treatment: infant mental health and multisystemic therapy (MST). This article illustrates the compatibility of…

  19. Ethnic Similarity, Therapist Adherence, and Long-Term Multisystemic Therapy Outcomes

    Science.gov (United States)

    Chapman, Jason E.; Schoenwald, Sonja K.

    2011-01-01

    The current study investigated relations among ethnic similarity in caregiver-therapist pairs of youth participating in Multisystemic Therapy, therapist adherence, and youth long-term behavioral and criminal outcomes. Participants were 1,979 youth and families treated by 429 therapists across provider organizations in 45 sites. Relations were…

  20. Multisystemic Therapy for Child Non-Externalizing Psychological and Health Problems: A Preliminary Review

    Science.gov (United States)

    Pane, Heather T.; White, Rachel S.; Nadorff, Michael R.; Grills-Taquechel, Amie; Stanley, Melinda A.

    2013-01-01

    Multisystemic therapy (MST) is effective for decreasing or preventing delinquency and other externalizing behaviors and increasing prosocial or adaptive behaviors. The purpose of this project was to review the literature examining the efficacy of MST for other child psychological and health problems reflecting non-externalizing behaviors,…

  1. We Are, Therefore I Am: A Multisystems Approach with Families in Poverty.

    Science.gov (United States)

    Brown, Shunda L.

    2002-01-01

    Although many individuals living in poverty are referred for family counseling services via schools, court systems, and social service agencies, theories have failed to provide an adequate framework for treatment. This article addresses the common principles of the multisystems approach and feminist family therapies and how they can be applied in…

  2. Paternal Involvement in Multisystemic Therapy: Effects on Adolescent Outcomes and Maternal Depression

    Science.gov (United States)

    Gervan, Shannon; Granic, Isabela; Solomon, Tracy; Blokland, Kirsten; Ferguson, Bruce

    2012-01-01

    The association between paternal involvement in therapy, adolescent outcomes and maternal depression was examined within the context of Multisystemic Therapy (MST), an empirically supported, family- and community-based treatment for antisocial adolescents. Ninety-nine families were recruited from five mental health agencies providing MST. We…

  3. NBAS mutations cause a multisystem disorder involving bone, connective tissue, liver, immune system, and retina

    NARCIS (Netherlands)

    Segarra, Nuria Garcia; Ballhausen, Diana; Crawford, Heather; Perreau, Matthieu; Campos-Xavier, Belinda; van Spaendonck-Zwarts, Karin; Vermeer, Cees; Russo, Michel; Zambelli, Pierre-Yves; Stevenson, Brian; Royer-Bertrand, Beryl; Rivolta, Carlo; Candotti, Fabio; Unger, Sheila; Munier, Francis L.; Superti-Furga, Andrea; Bonafé, Luisa

    2015-01-01

    We report two unrelated patients with a multisystem disease involving liver, eye, immune system, connective tissue, and bone, caused by biallelic mutations in the neuroblastoma amplified sequence (NBAS) gene. Both presented as infants with recurrent episodes triggered by fever with vomiting,

  4. 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.

  5. 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

  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. 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

  8. Can bipolar disorder be viewed as a multi-system inflammatory disease?

    Science.gov (United States)

    Leboyer, Marion; Soreca, Isabella; Scott, Jan; Frye, Mark; Henry, Chantal; Tamouza, Ryad; Kupfer, David J.

    2012-01-01

    Background Patients with bipolar disorder are known to be at high risk of premature death. Comorbid cardio-vascular diseases are a leading cause of excess mortality, well above the risk associated with suicide. In this review, we explore comorbid medical disorders, highlighting evidence that bipolar disorder can be effectively conceptualized as a multi-systemic inflammatory disease. Methods We conducted a systematic PubMed search of all English-language articles recently published with bipolar disorder cross-referenced with the following terms: mortality and morbidity, cardio-vascular, diabetes, obesity, metabolic syndrome, inflammation, auto-antibody, retro-virus, stress, sleep and circadian rhythm. Results Evidence gathered so far suggests that the multi-system involvement is present from the early stages, and therefore requires proactive screening and diagnostic procedures, as well as comprehensive treatment to reduce progression and premature mortality. Exploring the biological pathways that could account for the observed link show that dysregulated inflammatory background could be a common factor underlying cardio-vascular and bipolar disorders. Viewing bipolar disorder as a multi-system disorder should help us to re-conceptualize disorders of the mind as “disorders of the brain and the body”. Limitations The current literature substantially lacks longitudinal and mechanistic studies, as well as comparison studies to explore the magnitude of the medical burden in bipolar disorder compared to major mood disorders as well as psychotic disorders. It is also necessary to look for subgroups of bipolar disorder based on their rates of comorbid disorders. Conclusions Comorbid medical illnesses in bipolar disorder might be viewed not only as the consequence of health behaviors and of psychotropic medications, but rather as an early manifestation of a multi-systemic disorder. Medical monitoring is thus a critical component of case assessment. Exploring common

  9. 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.

  10. A review of "music and movement" therapies for children with autism: embodied interventions for multisystem development.

    Science.gov (United States)

    Srinivasan, Sudha M; Bhat, Anjana N

    2013-01-01

    The rising incidence of Autism Spectrum Disorders (ASDs) has led to a surge in the number of children needing autism interventions. This paper is a call to clinicians to diversify autism interventions and to promote the use of embodied music-based approaches to facilitate multisystem development. Approximately 12% of all autism interventions and 45% of all alternative treatment strategies in schools involve music-based activities. Musical training impacts various forms of development including communication, social-emotional, and motor development in children with ASDs and other developmental disorders as well as typically developing children. In this review, we will highlight the multisystem impairments of ASDs, explain why music and movement therapies are a powerful clinical tool, as well as describe mechanisms and offer evidence in support of music therapies for children with ASDs. We will support our claims by reviewing results from brain imaging studies reporting on music therapy effects in children with autism. We will also discuss the critical elements and the different types of music therapy approaches commonly used in pediatric neurological populations including autism. We provide strong arguments for the use of music and movement interventions as a multisystem treatment tool for children with ASDs. Finally, we also make recommendations for assessment and treatment of children with ASDs, and provide directions for future research.

  11. Acute tubulointerstitial nephritis with severe renal impairment associated with multisystem IgG4-related disease.

    Science.gov (United States)

    Beltrame, Rafael Coimbra Ferreira; Friderichs, Maurício; Fior, Bárbara Rayanne; Schaefer, Pedro Guilherme; Thomé, Gustavo Gomes; Silva, Dirceu Reis da; Barros, Elvino José Guardão; Seligman, Renato; Veronese, Francisco Veríssimo

    2016-01-01

    The IgG4-related disease has a wide clinical spectrum where multiple organs can be affected, and the diagnosis depends on typical histopathological findings and an elevated IgG4 expression in plasma cells in the affected tissue. We describe the clinical presentation and evolution of a patient with acute tubulointerstitial nephritis, severe kidney failure and systemic manifestations such as lymphadenomegaly and chronic pancreatitis. The diagnosis was confirmed by the clinical picture and kidney and lymph node histopathology, in which immunohistochemistry of the lymphoid tissue showed policlonality and increased expression of IgG4, with a IgG4/total IgG ratio > 80%. The patient was treated with prednisone at a dose of 60 mg/day, followed by mycophenolate mofetil, and showed clinical and renal function improvement at 6 months of follow-up. The high index of suspicion of IgG4-related disease with multisystem involvement and the early treatment of this condition are essential to improve the prognosis of affected patients. Resumo A doença relacionada à IgG4 tem um espectro clínico amplo em que múltiplos órgãos podem ser afetados, e o diagnóstico depende de achados histopatológicos típicos e elevada expressão de IgG4 em plasmócitos no tecido afetado. Descrevemos o quadro clínico e a evolução de um paciente com nefrite túbulo-intersticial aguda, insuficiência renal grave e manifestações sistêmicas como linfoadenomegalias e pancreatite crônica. O diagnóstico foi confirmado pelas características clínicas e pela histopatologia renal e de linfonodo, na qual a imunohistoquímica mostrou tecido linfoide com policlonalidade e expressão aumentada de IgG4, com uma relação IgG4/IgG total > 80%. O paciente foi tratado com prednisona na dose de 60 mg/dia, seguido de micofenolato mofetil, e apresentou melhora clínica e da função renal depois de 6 meses de tratamento. O alto índice de suspeição da doença relacionada ao IgG4 com comprometimento multissist

  12. Multisystem Radiologic Manifestations of Erdheim-Chester Disease

    Directory of Open Access Journals (Sweden)

    Umairullah Lodhi

    2016-01-01

    Full Text Available Erdheim-Chester Disease is a rare form of multiorgan non-Langerhans’ cell histiocytosis that affects individuals between the ages of 50 and 70 with an equal distribution among males and females. It is associated with significant morbidity and mortality that is mostly due to infiltration of critical organs. Some of the sites that Erdheim-Chester Disease affects include the skeletal system, central nervous system, cardiovascular system, lungs, kidneys (retroperitoneum, and skin. The most common presenting symptom of Erdheim-Chester Disease is bone pain although a large majority of patients are diagnosed incidentally during a workup for a different disease process. Diagnosing Erdheim-Chester Disease is challenging due its rarity and mimicry to other infiltrative processes. Therefore, a multimodality diagnostic approach is employed with imaging being at the forefront. As of date, a comprehensive radiologic review of the manifestations of Erdheim-Chester Disease has rarely been reported. Here we present radiologic findings of an individual suffering from Erdheim-Chester Disease.

  13. COMPARATIVE ANALYSIS OF CONVERTER STRUCTURES OF THE TRACTION DRIVE PROSPECTIVE MULTI-SYSTEM ELECTRIC LOCOMOTIVES WITH DC TRACTION MOTORS

    Directory of Open Access Journals (Sweden)

    A. M. Muha

    2009-03-01

    Full Text Available In the article the structured schemes of steady-state converter are offered for traction drive of promising multisystem electric locomotives with traction engines of direct current and their comparative analysis is conducted.

  14. 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

  15. Nitrogen and phosphorus in cascade multi-system tropical reservoirs: water and sediment

    Directory of Open Access Journals (Sweden)

    Pompêo Marcelo

    2017-09-01

    Full Text Available The aim of this research was to analyze the horizontal spatial heterogeneity of both water and superficial sediment quality among and within the reservoirs of the Cantareira System (CS, focusing on concentrations of N and P, attributed to the dumping of raw domestic sewage into water bodies, which is the main cause of water pollution in São Paulo State (Brazil. The CS is a multi-system complex composed of five interconnected reservoirs, with water transported by gravity through 48 km of tunnels and channels. From the last reservoir of the CS, with an output of 33 m3 s−1, the water is conducted to a water treatment plant, producing half of the water consumed by 19 million people inhabiting São Paulo city. The upstream reservoirs are more eutrophic than the downstream ones. Data also suggest that the low phytoplankton biomass (ranging from 0.9 to 14.4 μg dm−3 is regulated by the low nutrient availability, mainly of phosphorus (TP ranging from below the detection limit, <9.0 μg dm−3, to 47.3 μg dm−3. For water, the DIN/TP ratios values range from 19 to 380. The upstream reservoirs function as nutrient accumulators and the sediment is the main compartment in which P and N are stored. Although the reservoirs are located in different river basins and are not in sequence along the same river, the results suggest a marked gradient between the reservoirs, with features similar to those of cascade reservoirs. The large volumes flowing through the canals and tunnels could explain the observed pattern. The CS reservoirs can therefore be considered multi-system reservoirs in cascade, constituting a particular case of multi-system reservoirs.

  16. A case of vascular Ehlers-Danlos Syndrome with a cardiomyopathy and multi-system involvement.

    Science.gov (United States)

    Lan, Nick Si Rui; Fietz, Michael; Pachter, Nicholas; Paul, Vincent; Playford, David

    Ehlers-Danlos Syndrome comprises a heterogeneous group of heritable connective tissue disorders resulting from various gene mutations. We present an unusual case of vascular Ehlers-Danlos Syndrome with distinctive physical characteristics and a cardiomyopathy with features suggesting isolated left ventricular non-compaction. The cardiac features represent the first report of a cardiomyopathy associated with a mutation in the COL3A1 gene. This case also illustrates the multi-system nature of Ehlers-Danlos Syndrome and the complexity of managing patients with the vascular subtype. Copyright © 2018 Elsevier Inc. All rights reserved.

  17. Nursing Integration and Innovation Across a Multisystem Enterprise: Priorities for Nurse Leaders.

    Science.gov (United States)

    Pappas, Sharon; McCauley, Linda

    There is no escaping the fact that the ability to skillfully influence change is a requirement for nurse leaders. This need is intensified as the national health care system reforms and as the morphology of health care systems continues to change, especially in academic health care systems. The purpose of this article was 2-fold. The first objective was to relay the experience of the integration of nursing practice, education, and research within an academic health care system. The second was to, through this story of integration, expose the uniqueness and importance of nurse leader roles influencing innovation across a multisystem enterprise to fulfill the organization's mission.

  18. 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

  19. Novel large-range mitochondrial DNA deletions and fatal multisystemic disorder with prominent hepatopathy

    Energy Technology Data Exchange (ETDEWEB)

    Bianchi, Marzia; Rizza, Teresa; Verrigni, Daniela [Unit of Molecular Medicine for Neuromuscular and Neurodegenerative Diseases, ' Bambino Gesu' Children' s Hospital, Rome (Italy); Martinelli, Diego [Division of Metabolism, ' Bambino Gesu' Children' s Hospital, Rome (Italy); Tozzi, Giulia; Torraco, Alessandra; Piemonte, Fiorella [Unit of Molecular Medicine for Neuromuscular and Neurodegenerative Diseases, ' Bambino Gesu' Children' s Hospital, Rome (Italy); Dionisi-Vici, Carlo [Division of Metabolism, ' Bambino Gesu' Children' s Hospital, Rome (Italy); Nobili, Valerio [Gastroenterology and Liver Unit, ' Bambino Gesu' Children' s Hospital, Rome (Italy); Francalanci, Paola; Boldrini, Renata; Callea, Francesco [Dept. Pathology, ' Bambino Gesu' Children' s Hospital, Rome (Italy); Santorelli, Filippo Maria [UOC Neurogenetica e Malattie Neuromuscolari, Fondazione Stella Maris, Pisa (Italy); Bertini, Enrico [Unit of Molecular Medicine for Neuromuscular and Neurodegenerative Diseases, ' Bambino Gesu' Children' s Hospital, Rome (Italy); and others

    2011-11-18

    Highlights: Black-Right-Pointing-Pointer Expanded array of mtDNA deletions. Black-Right-Pointing-Pointer Pearson syndrome with prominent hepatopathy associated with single mtDNA deletions. Black-Right-Pointing-Pointer Detection of deletions in fibroblasts and blood avoids muscle and liver biopsy. Black-Right-Pointing-Pointer Look for mtDNA deletions before to study nuclear genes related to mtDNA depletion. -- Abstract: Hepatic involvement in mitochondrial cytopathies rarely manifests in adulthood, but is a common feature in children. Multiple OXPHOS enzyme defects in children with liver involvement are often associated with dramatically reduced amounts of mtDNA. We investigated two novel large scale deletions in two infants with a multisystem disorder and prominent hepatopathy. Amount of mtDNA deletions and protein content were measured in different post-mortem tissues. The highest levels of deleted mtDNA were in liver, kidney, pancreas of both patients. Moreover, mtDNA deletions were detected in cultured skin fibroblasts in both patients and in blood of one during life. Biochemical analysis showed impairment of mainly complex I enzyme activity. Patients manifesting multisystem disorders in childhood may harbour rare mtDNA deletions in multiple tissues. For these patients, less invasive blood specimens or cultured fibroblasts can be used for molecular diagnosis. Our data further expand the array of deletions in the mitochondrial genomes in association with liver failure. Thus analysis of mtDNA should be considered in the diagnosis of childhood-onset hepatopathies.

  20. Novel large-range mitochondrial DNA deletions and fatal multisystemic disorder with prominent hepatopathy

    International Nuclear Information System (INIS)

    Bianchi, Marzia; Rizza, Teresa; Verrigni, Daniela; Martinelli, Diego; Tozzi, Giulia; Torraco, Alessandra; Piemonte, Fiorella; Dionisi-Vici, Carlo; Nobili, Valerio; Francalanci, Paola; Boldrini, Renata; Callea, Francesco; Santorelli, Filippo Maria; Bertini, Enrico

    2011-01-01

    Highlights: ► Expanded array of mtDNA deletions. ► Pearson syndrome with prominent hepatopathy associated with single mtDNA deletions. ► Detection of deletions in fibroblasts and blood avoids muscle and liver biopsy. ► Look for mtDNA deletions before to study nuclear genes related to mtDNA depletion. -- Abstract: Hepatic involvement in mitochondrial cytopathies rarely manifests in adulthood, but is a common feature in children. Multiple OXPHOS enzyme defects in children with liver involvement are often associated with dramatically reduced amounts of mtDNA. We investigated two novel large scale deletions in two infants with a multisystem disorder and prominent hepatopathy. Amount of mtDNA deletions and protein content were measured in different post-mortem tissues. The highest levels of deleted mtDNA were in liver, kidney, pancreas of both patients. Moreover, mtDNA deletions were detected in cultured skin fibroblasts in both patients and in blood of one during life. Biochemical analysis showed impairment of mainly complex I enzyme activity. Patients manifesting multisystem disorders in childhood may harbour rare mtDNA deletions in multiple tissues. For these patients, less invasive blood specimens or cultured fibroblasts can be used for molecular diagnosis. Our data further expand the array of deletions in the mitochondrial genomes in association with liver failure. Thus analysis of mtDNA should be considered in the diagnosis of childhood-onset hepatopathies.

  1. Plasmodium coatneyi in Rhesus Macaques Replicates the Multisystemic Dysfunction of Severe Malaria in Humans

    Science.gov (United States)

    Cabrera-Mora, Monica; Garcia, AnaPatricia; Orkin, Jack; Strobert, Elizabeth; Barnwell, John W.; Galinski, Mary R.

    2013-01-01

    Severe malaria, a leading cause of mortality among children and nonimmune adults, is a multisystemic disorder characterized by complex clinical syndromes that are mechanistically poorly understood. The interplay of various parasite and host factors is critical in the pathophysiology of severe malaria. However, knowledge regarding the pathophysiological mechanisms and pathways leading to the multisystemic disorders of severe malaria in humans is limited. Here, we systematically investigate infections with Plasmodium coatneyi, a simian malaria parasite that closely mimics the biological characteristics of P. falciparum, and develop baseline data and protocols for studying erythrocyte turnover and severe malaria in greater depth. We show that rhesus macaques (Macaca mulatta) experimentally infected with P. coatneyi develop anemia, coagulopathy, and renal and metabolic dysfunction. The clinical course of acute infections required suppressive antimalaria chemotherapy, fluid support, and whole-blood transfusion, mimicking the standard of care for the management of severe malaria cases in humans. Subsequent infections in the same animals progressed with a mild illness in comparison, suggesting that immunity played a role in reducing the severity of the disease. Our results demonstrate that P. coatneyi infection in rhesus macaques can serve as a highly relevant model to investigate the physiological pathways and molecular mechanisms of malaria pathogenesis in naïve and immune individuals. Together with high-throughput postgenomic technologies, such investigations hold promise for the identification of new clinical interventions and adjunctive therapies. PMID:23509137

  2. A review of music and movement therapies for children with autism: Embodied interventions for multisystem development

    Directory of Open Access Journals (Sweden)

    Anjana Narayan Bhat

    2013-04-01

    Full Text Available The rising incidence of Autism Spectrum Disorders (ASDs has led to a surge in the number of children needing autism interventions. This paper is a call to clinicians to diversify autism interventions and to promote the use of embodied music-based approaches to facilitate multisystem development. Approximately 12% of all autism interventions and 45% of all alternative treatment strategies in schools involve music-based activities. Evidence suggests that musical training significantly impacts various forms of development including communication, social-emotional, motor, and behavioral development, in children with ASDs, typically developing individuals, and children with other neurological disabilities such as dyslexia and intellectual disabilities. In this review, we first highlight mechanisms and evidence for how music and movement interventions can enhance communication, social-emotional, behavioral, and motor skills in individuals with autism. We will support our claims by reviewing results from brain imaging studies in children with autism that provide neuroanatomical evidence for the effects of music therapies in autism. We will also discuss the critical elements and the different types of music therapy approaches commonly used in pediatric neurological populations including autism. We provide strong arguments for the use of music and movement interventions as a multisystem treatment tool for children with ASDs. Finally, we also make recommendations for assessment and treatment of children with ASDs, and provide directions for future research.

  3. Moral Judgment, Sensitivity To Reasons, and the Multi-system View

    Directory of Open Access Journals (Sweden)

    Francesco Orsi

    2012-11-01

    Full Text Available In this paper I attempt a critical examination of the multi-system or dual-process view of moral judgment. This view aims to provide a psychological explanation of moral sensitivity, and in particular an explanation of conflicting moral sensitivities in dilemma cases such as the crying baby scenario. I argue that proponents of the multi-system view owe us a satisfactory account of the mechanisms underlying “consequentialist” responses to such scenarios. For one thing, the “cognitive” processes involved in consequentialist reasoning only seem to play a subserving role with respect to the final judgment (providing non-moral inputs to judgment, or exerting additional strength to override the immediate “deontological” response. In this sense, Greene and colleagues fail to identify a peculiar system of moral judgment specularly opposed to the affective “deontological” one. For another, Greene and colleagues’ work on the emotion-cognition dichotomy and the distinction between alarm-bell and currency emotions, though promising, still falls short of providing an adequate and consistent picture of the psychological mechanisms underlying “cognitive” evaluations and verdicts in dilemma scenarios. It is suggested that alongside further experimental work, proponents of this view should pay more attention to the conceptual underpinnings of their distinctions.

  4. Improvement of Transient Stability in a Hybrid Power Multi-System Using a Designed NIDC (Novel Intelligent Damping Controller

    Directory of Open Access Journals (Sweden)

    Ting-Chia Ou

    2017-04-01

    Full Text Available This paper endeavors to apply a novel intelligent damping controller (NIDC for the static synchronous compensator (STATCOM to reduce the power fluctuations, voltage support and damping in a hybrid power multi-system. In this paper, we discuss the integration of an offshore wind farm (OWF and a seashore wave power farm (SWPF via a high-voltage, alternating current (HVAC electric power transmission line that connects the STATCOM and the 12-bus hybrid power multi-system. The hybrid multi-system consists of a battery energy storage system (BESS and a micro-turbine generation (MTG. The proposed NIDC consists of a designed proportional–integral–derivative (PID linear controller, an adaptive critic network and a proposed functional link-based novel recurrent fuzzy neural network (FLNRFNN. Test results show that the proposed controller can achieve better damping characteristics and effectively stabilize the network under unstable conditions.

  5. Islets of Langerhans in the parakeet, Psittacula krameri.

    Science.gov (United States)

    Gupta, Y K; Kumar, S

    1980-01-01

    The pancreatic gland of Psittacula krameri is divisible into 4 lobes i.e. dorsal, ventral, third and splenic. The endocrine part is composed of alpha 1-, alpha 2- and beta-cells. The islets are of 4 kinds viz., alpha islets (having alpha 1- and alpha 2-cells), beta islets (having beta- and alpha 1-cells), pure beta islets (consisting of beta-cells exclusively) and mixed islets (with beta-, alpha 1- and alpha 2-cells). The distribution of alpha islets is mostly restricted to the splenic and third lobes whereas the beta islets are found in all 4 lobes. Though the alpha islets are only few in the dorsal lobe, their size is best developed in the third and dorsal lobes. Sometimes beta and alpha islets are present in very close proximity but their cells never mingle. An interesting feature was the complete absence of alpha islets from the ventral lobe.A relative abundance of alpha 2- cells in this bird seems to be associated with its comparatively higher blood glucose level and frugivorous habit. Tinctorial reactions suggest that the insulin content of the endocrine pancreas is low. There were no seasonal changes in the islet tissue of P. krameri.

  6. Discerning Primary and Secondary Factors Responsible for Clinical Fatigue in Multisystem Diseases

    Directory of Open Access Journals (Sweden)

    David Maughan

    2014-09-01

    Full Text Available Fatigue is a common symptom of numerous acute and chronic diseases, including myalgic encephalomyelitis/chronic fatigue syndrome, multiple sclerosis, heart failure, cancer, and many others. In these multi-system diseases the physiological determinants of enhanced fatigue encompass a combination of metabolic, neurological, and myofibrillar adaptations. Previous research studies have focused on adaptations specific to skeletal muscle and their role in fatigue. However, most have neglected the contribution of physical inactivity in assessing disease syndromes, which, through deconditioning, likely contributes to symptomatic fatigue. In this commentary, we briefly review disease-related muscle phenotypes in the context of whether they relate to the primary disease or whether they develop secondary to reduced physical activity. Knowledge of the etiology of the skeletal muscle adaptations in these conditions and their contribution to fatigue symptoms is important for understanding the utility of exercise rehabilitation as an intervention to alleviate the physiological precipitants of fatigue.

  7. Phenotype variability of infantile-onset multisystem neurologic, endocrine, and pancreatic disease IMNEPD.

    Science.gov (United States)

    Picker-Minh, Sylvie; Mignot, Cyril; Doummar, Diane; Hashem, Mais; Faqeih, Eissa; Josset, Patrice; Dubern, Béatrice; Alkuraya, Fowzan S; Kraemer, Nadine; Kaindl, Angela M

    2016-04-29

    Infantile-onset multisystem neurologic, endocrine, and pancreatic disease (IMNEPD) has been recently linked to biallelic mutation of the peptidyl-tRNA hydrolase 2 gene PTRH2. Two index patients with IMNEPD in the original report had multiple neurological symptoms such as postnatal microcephaly, intellectual disability, developmental delay, sensorineural deafness, cerebellar atrophy, ataxia, and peripheral neuropathy. In addition, distal muscle weakness and abnormalities of thyroid, pancreas, and liver were found. Here, we report five further IMNEPD patients with a different homozygous PTRH2 mutation, broaden the phenotypic spectrum of the disease and differentiate common symptoms and interindividual variability in IMNEPD associated with a unique mutation. We thereby hope to better define IMNEPD and promote recognition and diagnosis of this novel disease entity.

  8. 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.

  9. Fresh frozen plasma resuscitation attenuates platelet dysfunction compared with normal saline in a large animal model of multisystem trauma

    DEFF Research Database (Denmark)

    Sillesen, Martin; Johansson, Pär I; Rasmussen, Lars S

    2014-01-01

    to multisystem trauma (traumatic brain injury, liver injury, rib fracture, and soft tissue injury) with hemorrhagic shock (40% of estimated blood volume). Animals were left in shock (mean arterial pressure, 30-35 mm Hg) for 2 hours followed by resuscitation with three times shed volume NS (n = 6) or one times...

  10. The lack of cross-national equivalence of a therapist adherence measure (TAM-R) in multisystemic therapy (MST)

    NARCIS (Netherlands)

    Lange, A.M.C.; Scholte, R.H.J.; Geffen, W. van; Timman, R.; Busschbach, J.J.V. van; Rijken, R.E.A. van der

    2016-01-01

    This two-study report investigates the equivalence of the Dutch Therapist Adherence Measure Revised (TAM-R) to the US original. The TAM-R is a questionnaire measuring therapist adherence to the treatment model of Multisystemic Therapy (MST). Monitoring of therapist adherence is essential for

  11. A randomized controlled trial of the effectiveness of multisystemic therapy in the Netherlands: post-treatment changes and moderator effects

    NARCIS (Netherlands)

    Asscher, J.J.; Dekovic, M.; Manders, W.A.; Prins, P.J.M.; van der Laan, P.H.

    2013-01-01

    Objective: In the present randomized controlled trial, the effectiveness of multisystemic therapy (MST) in The Netherlands was examined. Moderator tests were conducted for ethnicity, age and gender. Methods: The sample consisted of N = 256 adolescents, referred because of conduct problems, and

  12. A randomized controlled trial of the effectiveness of multisystemic therapy in the Netherlands: post-treatment changes and moderator effects

    NARCIS (Netherlands)

    Asscher, J.J.; Deković, M.; Manders, W.A.; van der Laan, P.H.; Prins, P.J.M.

    2013-01-01

    Objective: In the present randomized controlled trial, the effectiveness of multisystemic therapy (MST) in The Netherlands was examined. Moderator tests were conducted for ethnicity, age and gender. Methods: The sample consisted of N = 256 adolescents, referred because of conduct problems, and

  13. Childhood abuse, parental warmth, and adult multisystem biological risk in the Coronary Artery Risk Development in Young Adults study.

    Science.gov (United States)

    Carroll, Judith E; Gruenewald, Tara L; Taylor, Shelley E; Janicki-Deverts, Denise; Matthews, Karen A; Seeman, Teresa E

    2013-10-15

    Childhood abuse increases adult risk for morbidity and mortality. Less clear is how this "toxic" stress becomes embedded to influence health decades later, and whether protective factors guard against these effects. Early biological embedding is hypothesized to occur through programming of the neural circuitry that influences physiological response patterns to subsequent stress, causing wear and tear across multiple regulatory systems. To examine this hypothesis, we related reports of childhood abuse to a comprehensive 18-biomarker measure of multisystem risk and also examined whether presence of a loving parental figure buffers against the impact of childhood abuse on adult risk. A total of 756 subjects (45.8% white, 42.7% male) participated in this ancillary substudy of the Coronary Artery Risk Development in Young Adults Study. Childhood stress was determined by using the Risky Families Questionnaire, a well-validated retrospective self-report scale. Linear regression models adjusting for age, sex, race, parental education, and oral contraceptive use found a significant positive relationship between reports of childhood abuse and multisystem health risks [B (SE) = 0.68 (0.16); P childhood was associated with lower multisystem health risks [B (SE) = -0.40 (0.14); P childhood had the highest multisystem risk in adulthood.

  14. 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.

  15. 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.

  16. 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.

  17. 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

  18. Ehlers–Danlos Syndrome—Hypermobility Type: A Much Neglected Multisystemic Disorder

    Directory of Open Access Journals (Sweden)

    Yael Gazit

    2016-10-01

    Full Text Available Ehlers–Danlos syndrome (EDS—hypermobility type (HT is considered to be the most common subtype of EDS and the least severe one; EDS-HT is considered to be identical to the joint hypermobility syndrome and manifests with musculoskeletal complaints, joint instability, and soft tissue overuse injury. Musculoskeletal complaints manifest with joint pain of non-inflammatory origin and/or spinal pain. Joint instability leads to dislocation or subluxation and involves peripheral joints as well as central joints, including the temporomandibular joints, sacroiliac joints, and hip joints. Soft tissue overuse injury may lead to tendonitis and bursitis without joint inflammation in most cases. Ehlers–Danlos syndrome-HT carries a high potential for disability due to recurrent dislocations and subluxations and chronic pain. Throughout the years, extra-articular manifestations have been described, including cardiovascular, autonomic nervous system, gastrointestinal, hematologic, ocular, gynecologic, neurologic, and psychiatric manifestations, emphasizing the multisystemic nature of EDS-HT. Unfortunately, EDS-HT is under-recognized and inadequately managed, leading to neglect of these patients, which may lead to severe disability that almost certainly could have been avoided. In this review article we will describe the known manifestations of the extra-articular systems.

  19. A multisystemic Acanthamoeba infection in a dog in Tenerife, Canary Islands, Spain.

    Science.gov (United States)

    Valladares, María; Reyes-Batlle, María; Mora-Peces, Inmaculada; Martín-Navarro, Carmen M; López-Arencibia, Atteneri; Dorta-Gorrín, Alexis; Comyn-Afonso, Estefanía; Martínez-Carretero, Enrique; Maciver, Sutherland K; Piñero, José E; Valladares, Basilio; Lorenzo-Morales, Jacob

    2014-10-15

    A 22-month-old male Spanish water dog was hospitalized after its physical examination revealed fever and movement difficulty. After 24h, the dog was found to have a high fever (39.5 °C) and was treated empirically with doxycycline/ciprofloxacin. At 48 h, after submission the fever rose to 41 °C and the animal presented with a stiff neck and dehydration. Peripheral blood and cerebrospinal fluid (CSF) were sampled and trophozoites with an Acanthamoeba-like morphology were observed in the CSF. PCR specific for Acanthamoeba, Naegleria fowleri and Balamuthia mandrillaris were performed and the CSF sample found positive for Acanthamoeba. Lungs, kidney, liver and spleen samples were collected post mortem. All collected organ samples were positive for Acanthamoeba by PCR, thus confirming a multisystemic infection. Water samples taken at a suspected site of infection yielded an almost identical PCR fragment to those of the clinical samples, indicating that this was probably where the infection originated. This is the first report of a fatal case of Acanthamoeba disseminated infection in a dog in Spain. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Neuroimaging to Investigate Multisystem Involvement and Provide Biomarkers in Amyotrophic Lateral Sclerosis

    Science.gov (United States)

    Pradat, Pierre-François; El Mendili, Mohamed-Mounir

    2014-01-01

    Neuroimaging allows investigating the extent of neurological systems degeneration in amyotrophic lateral sclerosis (ALS). Advanced MRI methods can detect changes related to the degeneration of upper motor neurons but have also demonstrated the participation of other systems such as the sensory system or basal ganglia, demonstrating in vivo that ALS is a multisystem disorder. Structural and functional imaging also allows studying dysfunction of brain areas associated with cognitive signs. From a biomarker perspective, numerous studies using diffusion tensor imaging showed a decrease of fractional anisotropy in the intracranial portion of the corticospinal tract but its diagnostic value at the individual level remains limited. A multiparametric approach will be required to use MRI in the diagnostic workup of ALS. A promising avenue is the new methodological developments of spinal cord imaging that has the advantage to investigate the two motor system components that are involved in ALS, that is, the lower and upper motor neuron. For all neuroimaging modalities, due to the intrinsic heterogeneity of ALS, larger pooled banks of images with standardized image acquisition and analysis procedures are needed. In this paper, we will review the main findings obtained with MRI, PET, SPECT, and nuclear magnetic resonance spectroscopy in ALS. PMID:24949452

  1. Chanarin-Dorfman Syndrome with Multi-System Involvement in Two Siblings

    Directory of Open Access Journals (Sweden)

    Seçil Arslansoyu Çamlar

    2013-03-01

    Full Text Available Chanarin-Dorfman syndrome (CDS is a very rare autosomal recessive inherited neutral lipid metabolism disorder associated with congenital ichthyosis and multi-system involvement. Observation of lipid vacuoles in neutrophils (Jordan’s anomaly in peripheral blood smears in patients with ichthyosiform erythroderma is diagnostic. Herein we present 2 siblings with CDS that were referred to Dokuz Eylul University School of Medicine Department of Pediatrics due to ichthyosis. They had hepatomegaly, cataract, growth retardation, and sensorineural hearing loss. Some lipid vacuoles in neutrophils were noted in peripheral blood smear evaluation. Genetic analysis showed homozygous N209X mutation in both patients. They were put on a low-fat high-carbohydrate diet supplemented with medium-chain fatty acids. During 6 months of follow-up, no improvement was observed in both patients. In conclusion, although CDS is a rare lipid storage disease, it should always be a consideration in patients with congenital ichthyosis, especially those with extracutaneous symptoms or signs. The diagnosis of CDS is made based on a very simple test-peripheral blood smear.

  2. 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....

  3. 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).

  4. 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.

  5. Multisystem Disease, Including Eosinophilia and Progressive Hyper-Creatine-Kinase-emia over 10 Years, Suggests Mitochondrial Disorder

    Directory of Open Access Journals (Sweden)

    Josef Finsterer

    2017-04-01

    Full Text Available Background: Eosinophilia has not been reported as a manifestation of a mitochondrial disorder (MID. Here, we report a patient with clinical features suggesting a MID and permanent eosinophilia, multisystem disease, and progressive hyper-creatine-kinase (CK-emia for at least 10 years. Materials and Methods: Methods applied included a clinical exam, blood chemical investigations, electrophysiological investigations, imaging, and invasive cardiological investigations. The patient was repeatedly followed up over several years. He required replacement cardiac surgery. Results: In a 57-year-old male, eosinophilia was first detected at the age of 44 years and has remained almost constantly present until today. In addition to eosinophilia, he developed progressive hyper-CK-emia at the age of 47 years. His history was further positive for hepatopathy, hyperlipidemia, hypothyroidism, renal insufficiency, spontaneous Achilles tendon rupture, double vision, exercise intolerance, muscle aching, mild hypoacusis, sensory neuropathy, seizures, and mitral insufficiency/stenosis requiring valve replacement therapy, oral anticoagulation, and pacemaker implantation. Based on the multisystem nature of his abnormalities and permanent hyper-CK-emia, a MID was suspected. Conclusion: Eosinophilia can be associated with a MID with myopathy, possibly as a reaction to myofiber necrosis. If eosinophilia is associated with progressive hyper-CK-emia and multisystem disease, a MID should be suspected.

  6. A review of “music and movement” therapies for children with autism: embodied interventions for multisystem development

    Science.gov (United States)

    Srinivasan, Sudha M.; Bhat, Anjana N.

    2013-01-01

    The rising incidence of Autism Spectrum Disorders (ASDs) has led to a surge in the number of children needing autism interventions. This paper is a call to clinicians to diversify autism interventions and to promote the use of embodied music-based approaches to facilitate multisystem development. Approximately 12% of all autism interventions and 45% of all alternative treatment strategies in schools involve music-based activities. Musical training impacts various forms of development including communication, social-emotional, and motor development in children with ASDs and other developmental disorders as well as typically developing children. In this review, we will highlight the multisystem impairments of ASDs, explain why music and movement therapies are a powerful clinical tool, as well as describe mechanisms and offer evidence in support of music therapies for children with ASDs. We will support our claims by reviewing results from brain imaging studies reporting on music therapy effects in children with autism. We will also discuss the critical elements and the different types of music therapy approaches commonly used in pediatric neurological populations including autism. We provide strong arguments for the use of music and movement interventions as a multisystem treatment tool for children with ASDs. Finally, we also make recommendations for assessment and treatment of children with ASDs, and provide directions for future research. PMID:23576962

  7. A multi-system interface module for automating the patient treatment cycle

    International Nuclear Information System (INIS)

    Fox, Tim; Brooks, Ken; Davis, Larry

    1996-01-01

    using the PC-based Windows NT environment. Results: The developed multi-system interface module accesses and shares data from a commercial CT-simulator, a research-based treatment planning system, and a commercial radiation oncology information system in the departmental wide-area network (WAN). The software tool shares the CT-simulator's anatomical contours, images, and plan information with the treatment planning system which eliminates the need for the oncologist to redraw the tumor volumes or custom blocks. The plan and treatment information is updated in the treatment delivery information system. The system runs on any standard PC platform located on the WAN and supports remote data access over phone lines. The interface module directly improves the efficiency of the department by the reduction of redundant data entry. Conclusion: The introduction of a multi-system interface module for sharing common radiation therapy data has decreased the overall treatment planning times without adding complexity. The use of other emerging standards such as DICOM are also being investigated to provide additional support in the future. The concept of the interface module can be used to connect to any data system that supports open connectivity standards

  8. Multi-System Deconditioning in 3-Day Dry Immersion without Daily Raise

    Directory of Open Access Journals (Sweden)

    Steven De Abreu

    2017-10-01

    Full Text Available Dry immersion (DI is a Russian-developed, ground-based model to study the physiological effects of microgravity. It accurately reproduces environmental conditions of weightlessness, such as enhanced physical inactivity, suppression of hydrostatic pressure and supportlessness. We aimed to study the integrative physiological responses to a 3-day strict DI protocol in 12 healthy men, and to assess the extent of multi-system deconditioning. We recorded general clinical data, biological data and evaluated body fluid changes. Cardiovascular deconditioning was evaluated using orthostatic tolerance tests (Lower Body Negative Pressure + tilt and progressive tilt. Metabolic state was tested with oral glucose tolerance test. Muscular deconditioning was assessed via muscle tone measurement.Results: Orthostatic tolerance time dropped from 27 ± 1 to 9 ± 2 min after DI. Significant impairment in glucose tolerance was observed. Net insulin response increased by 72 ± 23% on the third day of DI compared to baseline. Global leg muscle tone was approximately 10% reduced under immersion. Day-night changes in temperature, heart rate and blood pressure were preserved on the third day of DI. Day-night variations of urinary K+ diminished, beginning at the second day of immersion, while 24-h K+ excretion remained stable throughout. Urinary cortisol and melatonin metabolite increased with DI, although within normal limits. A positive correlation was observed between lumbar pain intensity, estimated on the second day of DI, and mean 24-h urinary cortisol under DI. In conclusion, DI represents an accurate and rapid model of gravitational deconditioning. The extent of glucose tolerance impairment may be linked to constant enhanced muscle inactivity. Muscle tone reduction may reflect the reaction of postural muscles to withdrawal of support. Relatively modest increases in cortisol suggest that DI induces a moderate stress effect. In prospect, this advanced ground

  9. Multisystemic Therapy and Functional Family Therapy Compared on their Effectiveness Using the Propensity Score Method.

    Science.gov (United States)

    Eeren, Hester V; Goossens, Lucas M A; Scholte, Ron H J; Busschbach, Jan J V; van der Rijken, Rachel E A

    2018-01-09

    Multisystemic Therapy (MST) and Functional Family Therapy (FFT) have overlapping target populations and treatment goals. In this study, these interventions were compared on their effectiveness using a quasi-experimental design. Between October, 2009 and June, 2014, outcome data were collected from 697 adolescents (mean age 15.3 (SD 1.48), 61.9% male) assigned to either MST or FFT (422 MST; 275 FFT). Data were gathered during Routine Outcome Monitoring. The primary outcome was externalizing problem behavior (Child Behavior Checklist and Youth Self Report). Secondary outcomes were the proportion of adolescents living at home, engaged in school or work, and who lacked police contact during treatment. Because of the non-random assignment, a propensity score method was used to control for observed pre-treatment differences. Because the risk-need-responsivity (RNR) model guided treatment assignment, effectiveness was also estimated in youth with and without a court order as an indicator of their risk level. Looking at the whole sample, no difference in effect was found with regard to externalizing problems. For adolescents without a court order, effects on externalizing problems were larger after MST. Because many more adolescents with a court order were assigned to MST compared to FFT, the propensity score method could not balance the treatment groups in this subsample. In conclusion, few differences between MST and FFT were found. In line with the RNR model, higher risk adolescents were assigned to the more intensive treatment, namely MST. In the group with lower risk adolescents, this more intensive treatment was more effective in reducing externalizing problems.

  10. 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

  11. Multisystemic Therapy for social, emotional, and behavioral problems in youth aged 10-17.

    Science.gov (United States)

    Littell, J H; Popa, M; Forsythe, B

    2005-07-20

    Multisystemic Therapy (MST) is an intensive, home-based intervention for families of youth with social, emotional, and behavioral problems. Masters-level therapists engage family members in identifying and changing individual, family, and environmental factors thought to contribute to problem behavior. Intervention may include efforts to improve communication, parenting skills, peer relations, school performance, and social networks. Most MST trials were conducted by program developers in the USA; results of one independent trial are available and others are in progress. To provide unbiased estimates of the impacts of MST on restrictive out-of-home living placements, crime and delinquency, and other behavioral and psychosocial outcomes for youth and families. Electronic searches were made of bibliographic databases including the Cochrane Library, C2-SPECTR, PsycINFO, Science Direct and Sociological Abstracts) as well as government and professional websites, from 1985 to January 2003. Reference lists of articles were examined, and experts were contacted. Studies where youth (age 10-17) with social, emotional, and/or behavioral problems were randomised to licensed MST programs or other conditions (usual services or alternative treatments). Two reviewers independently reviewed 266 titles and abstracts; 95 full-text reports were retrieved, and 35 unique studies were identified. Two reviewers independently read all study reports for inclusion. Eight studies were eligible for inclusion. Two reviewers independently assessed study quality and extracted data from these studies.Significant heterogeneity among studies was identified (assessed using Chi-square and I(2)), hence random effects models were used to pool data across studies. Odds ratios were used in analyses of dichotomous outcomes; standardised mean differences were used with continuous outcomes. Adjustments were made for small sample sizes (using Hedges g). Pooled estimates were weighted with inverse variance

  12. 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.

  13. 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.

  14. SAFETY OF MIXED ARTIFICIAL NUTRITION IN PATIENTS WITH SEVERE MULTISYSTEM CRANIOCEREBRAL TRAUM

    Directory of Open Access Journals (Sweden)

    A. P. Shakotko

    2017-01-01

    when mixed artificial nutrition was initiated (on day 3 of artificial nutrition in 11 patients, on day 5 in 3 patients and by day 7 in 6 patients. The introduction of PN “three in one” mixture was accompanied by a slight increase in the concentration of TG 2 hours after the start of the infusion and did not affect the dynamics of pulmonary gas exchange. The introduction of PN was accompanied by the development of hyperglycemia. The increase of glucose in venous blood serum was noted 2 and 12 hours after the onset of PN.CONCLUSION. Mixed artificial nutrition in patients with severe multisystem craniocerebral trauma does not lead to the development of hypertriglyceridemia and violation of pulmonary gas exchange and allows to achieve nutritional therapy goals.

  15. Nicotinic acid-induced flushing is mediated by activation of epidermal langerhans cells

    NARCIS (Netherlands)

    Benyó, Zoltán; Gille, Andreas; Bennett, Clare L.; Clausen, Björn E.; Offermanns, Stefan

    2006-01-01

    The antidyslipidemic drug nicotinic acid (niacin) has been used for decades. One of the major problems of the therapeutical use of nicotinic acid is a strong cutaneous vasodilation called flushing, which develops in almost every patient taking nicotinic acid. Nicotinic acid-induced flushing has been

  16. Herpes Simplex Virus Type 2 Enhances HIV-1 Susceptibility by Affecting Langerhans Cell Function

    NARCIS (Netherlands)

    de Jong, Marein A. W. P.; de Witte, Lot; Taylor, Maureen E.; Geijtenbeek, Teunis B. H.

    2010-01-01

    Genital herpes is the most prevalent viral sexually transmitted infection worldwide and is mainly caused by HSV type 2 (HSV-2). HSV-2 infection enhances HIV-1 susceptibility, even in the absence of clinical symptoms. In this study, we investigated the effect of HSV-2 on HIV-1 transmission by mucosal

  17. The pathogenesis of allergic rhinitis : cellular aspects with special emphasis on Langerhans cells

    NARCIS (Netherlands)

    W.J. Fokkens (Wytske)

    1991-01-01

    textabstractPresent ideas concerning the pathogenesis of allergic rhinitis are largely deduced from systemic investigations and extrapolated from studies in the skin and the lung. Studies on allergic rhinitis generally comprise clinical aspects and/or biochemical, humoral and cellular features of

  18. Experimental reproduction of postweaning multisystemic wasting syndrome (PMWS) in pigs in Sweden and Denmark with a Swedish isolate of porcine circovirus type 2

    DEFF Research Database (Denmark)

    Hasslung, F.; Wallgren, P.; Hansen, Anne-Sofie Ladekjær

    2005-01-01

    An experimental model using 3-day-old snatch-farrowed colostrum-deprived piglets co-infected with porcine circovirus type 2 (PCV2) and porcine parvovirus (PPV) is at present one of the best methods to study factors affecting development of postweaning multisystemic wasting syndrome (PMWS). A Swed......An experimental model using 3-day-old snatch-farrowed colostrum-deprived piglets co-infected with porcine circovirus type 2 (PCV2) and porcine parvovirus (PPV) is at present one of the best methods to study factors affecting development of postweaning multisystemic wasting syndrome (PMWS...

  19. 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.

  20. 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

  1. Desmin common mutation is associated with multi-systemic disease manifestations and depletion of mitochondria and mitochondrial DNA

    Directory of Open Access Journals (Sweden)

    Elizabeth eMcCormick

    2015-06-01

    Full Text Available Desmin (DES is a major muscle scaffolding protein that also functions to anchor mitochondria. Pathogenic DES mutations, however, have not previously been recognized as a cause of multi-systemic mitochondrial disease. Here, we describe a 45-year-old man who presented to The Children’s Hospital of Philadelphia Mitochondrial-Genetics Diagnostic Clinic for evaluation of progressive cardiac, neuromuscular, gastrointestinal, and mood disorders. Muscle biopsy at age 45 was remarkable for cytoplasmic bodies, as well as ragged red fibers and SDH positive/COX negative fibers that were suggestive of a mitochondrial myopathy. Muscle also showed significant reductions in mitochondrial content (16% of control mean for citrate synthase activity and mitochondrial DNA (35% of control mean. His family history was significant for cardiac conduction defects and myopathy in multiple maternal relatives. Multiple single gene and panel-based sequencing studies were unrevealing. Whole exome sequencing identified a known pathogenic p.S13F mutation in DES that had previously been associated with desmin-related myopathy. Desmin-related myopathy is an autosomal dominant disorder characterized by right ventricular hypertrophic cardiomyopathy, myopathy, and arrhythmias. However, neuropathy, gastrointestinal dysfunction, and depletion of both mitochondria and mitochondrial DNA have not previously been widely recognized in this disorder. Recognition that mitochondrial dysfunction occurs in desmin-related myopathy clarifies the basis for the multi-systemic manifestations, as are typical of primary mitochondrial disorders. Understanding the mitochondrial pathophysiology of desmin-related myopathy highlights the possibility of new therapies for the otherwise untreatable and often fatal class of disease. We postulate that drug treatments aimed at improving mitochondrial biogenesis or reducing oxidative stress may be effective therapies to ameliorate the effects of desmin

  2. Dynamics of porcine circovirus type 2 infection and excretion in pigs from postweaning multisystemic wasting syndrome affected farms from Spain and Denmark

    DEFF Research Database (Denmark)

    Grau-Roma, L.; Hjulsager, Charlotte Kristiane; Sibila, M.

    Serological and non-quantitative DNA detection techniques (PCR) have been widely used to monitor porcine circovirus type 2 (PCV2) infection dynamics (1,2). In spite of available epidemiological information, very few data on PCV2 load dynamics of Postweaning multisystemic wasting syndrome (PMWS) a...

  3. Effects of Multisystemic Therapy through Midlife: A 21.9-Year Follow-Up to a Randomized Clinical Trial with Serious and Violent Juvenile Offenders

    Science.gov (United States)

    Sawyer, Aaron M.; Borduin, Charles M.

    2011-01-01

    Objective: Although current evidence suggests that the positive effects of multisystemic therapy (MST) on serious crime reach as far as young adulthood, the longer term impact of MST on criminal and noncriminal outcomes in midlife has not been evaluated. In the present study, the authors examined a broad range of criminal and civil court outcomes…

  4. 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

  5. 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

  6. A multi-system approach assessing the interaction of anticonvulsants with P-gp.

    Directory of Open Access Journals (Sweden)

    David Dickens

    Full Text Available 30% of epilepsy patients receiving antiepileptic drugs (AEDs are not fully controlled by therapy. The drug transporter hypothesis for refractory epilepsy proposes that P-gp is over expressed at the epileptic focus with a role of P-gp in extruding AEDs from the brain. However, there is controversy regarding whether all AEDs are substrates for this transporter. Our aim was to investigate transport of phenytoin, lamotrigine and carbamazepine by using seven in-vitro transport models. Uptake assays in CEM/VBL cell lines, oocytes expressing human P-gp and an immortalised human brain endothelial cell line (hCMEC/D3 were carried out. Concentration equilibrium transport assays were performed in Caco-2, MDCKII ±P-gp and LLC-PK1±P-gp in the absence or presence of tariquidar, an inhibitor of P-gp. Finally, primary porcine brain endothelial cells were used to determine the apparent permeability (Papp of the three AEDs in the absence or presence of P-gp inhibitors. We detected weak transport of phenytoin in two of the transport systems (MDCK and LLC-PK1 cells transfected with human P-gp but not in the remaining five. No P-gp interaction was observed for lamotrigine or carbamazepine in any of the seven validated in-vitro transport models. Neither lamotrigine nor carbamazepine was a substrate for P-gp in any of the model systems tested. Our data suggest that P-gp is unlikely to contribute to the pathogenesis of refractory epilepsy through transport of carbamazepine or lamotrigine.

  7. 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

  8. 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,

  9. Novel nervous and multi-system regenerative therapeutic strategies for diabetes mellitus with mTOR

    Directory of Open Access Journals (Sweden)

    Kenneth Maiese

    2016-01-01

    Full Text Available Throughout the globe, diabetes mellitus (DM is increasing in incidence with limited therapies presently available to prevent or resolve the significant complications of this disorder. DM impacts multiple organs and affects all components of the central and peripheral nervous systems that can range from dementia to diabetic neuropathy. The mechanistic target of rapamycin (mTOR is a promising agent for the development of novel regenerative strategies for the treatment of DM. mTOR and its related signaling pathways impact multiple metabolic parameters that include cellular metabolic homeostasis, insulin resistance, insulin secretion, stem cell proliferation and differentiation, pancreatic β-cell function, and programmed cell death with apoptosis and autophagy. mTOR is central element for the protein complexes mTOR Complex 1 (mTORC1 and mTOR Complex 2 (mTORC2 and is a critical component for a number of signaling pathways that involve phosphoinositide 3-kinase (PI 3-K, protein kinase B (Akt, AMP activated protein kinase (AMPK, silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae (SIRT1, Wnt1 inducible signaling pathway protein 1 (WISP1, and growth factors. As a result, mTOR represents an exciting target to offer new clinical avenues for the treatment of DM and the complications of this disease. Future studies directed to elucidate the delicate balance mTOR holds over cellular metabolism and the impact of its broad signaling pathways should foster the translation of these targets into effective clinical regimens for DM.

  10. PGC-1alpha Deficiency Causes Multi-System Energy Metabolic Derangements: Muscle Dysfunction, Abnormal Weight Control and Hepatic Steatosis

    Directory of Open Access Journals (Sweden)

    Leone Teresa C

    2005-01-01

    Full Text Available The gene encoding the transcriptional coactivator peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha was targeted in mice. PGC-1alpha null (PGC-1alpha-/- mice were viable. However, extensive phenotyping revealed multi-system abnormalities indicative of an abnormal energy metabolic phenotype. The postnatal growth of heart and slow-twitch skeletal muscle, organs with high mitochondrial energy demands, is blunted in PGC-1alpha-/- mice. With age, the PGC-1alpha-/- mice develop abnormally increased body fat, a phenotype that is more severe in females. Mitochondrial number and respiratory capacity is diminished in slow-twitch skeletal muscle of PGC-1alpha-/- mice, leading to reduced muscle performance and exercise capacity. PGC-1alpha-/- mice exhibit a modest diminution in cardiac function related largely to abnormal control of heart rate. The PGC-1alpha-/- mice were unable to maintain core body temperature following exposure to cold, consistent with an altered thermogenic response. Following short-term starvation, PGC-1alpha-/- mice develop hepatic steatosis due to a combination of reduced mitochondrial respiratory capacity and an increased expression of lipogenic genes. Surprisingly, PGC-1alpha-/- mice were less susceptible to diet-induced insulin resistance than wild-type controls. Lastly, vacuolar lesions were detected in the central nervous system of PGC-1alpha-/- mice. These results demonstrate that PGC-1alpha is necessary for appropriate adaptation to the metabolic and physiologic stressors of postnatal life.

  11. PGC-1alpha deficiency causes multi-system energy metabolic derangements: muscle dysfunction, abnormal weight control and hepatic steatosis.

    Directory of Open Access Journals (Sweden)

    Teresa C Leone

    2005-04-01

    Full Text Available The gene encoding the transcriptional coactivator peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha was targeted in mice. PGC-1alpha null (PGC-1alpha(-/- mice were viable. However, extensive phenotyping revealed multi-system abnormalities indicative of an abnormal energy metabolic phenotype. The postnatal growth of heart and slow-twitch skeletal muscle, organs with high mitochondrial energy demands, is blunted in PGC-1alpha(-/- mice. With age, the PGC-1alpha(-/- mice develop abnormally increased body fat, a phenotype that is more severe in females. Mitochondrial number and respiratory capacity is diminished in slow-twitch skeletal muscle of PGC-1alpha(-/- mice, leading to reduced muscle performance and exercise capacity. PGC-1alpha(-/- mice exhibit a modest diminution in cardiac function related largely to abnormal control of heart rate. The PGC-1alpha(-/- mice were unable to maintain core body temperature following exposure to cold, consistent with an altered thermogenic response. Following short-term starvation, PGC-1alpha(-/- mice develop hepatic steatosis due to a combination of reduced mitochondrial respiratory capacity and an increased expression of lipogenic genes. Surprisingly, PGC-1alpha(-/- mice were less susceptible to diet-induced insulin resistance than wild-type controls. Lastly, vacuolar lesions were detected in the central nervous system of PGC-1alpha(-/- mice. These results demonstrate that PGC-1alpha is necessary for appropriate adaptation to the metabolic and physiologic stressors of postnatal life.

  12. 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.

  13. Stem cells in psoriasis.

    Science.gov (United States)

    Hou, Ruixia; Li, Junqin; Niu, Xuping; Liu, Ruifeng; Chang, Wenjuan; Zhao, Xincheng; Wang, Qiang; Li, Xinhua; Yin, Guohua; Zhang, Kaiming

    2017-06-01

    Psoriasis is a complex chronic relapsing inflammatory disease. Although the exact mechanism remains unknown, it is commonly accepted that the development of psoriasis is a result of multi-system interactions among the epidermis, dermis, blood vessels, immune system, neuroendocrine system, metabolic system, and hematopoietic system. Many cell types have been confirmed to participate in the pathogenesis of psoriasis. Here, we review the stem cell abnormalities related to psoriasis that have been investigated recently. Copyright © 2016. Published by Elsevier B.V.

  14. Efficacy of multisystemic therapy in youths aged 10-17 with severe antisocial behaviour and emotional disorders: systematic review.

    Science.gov (United States)

    Tan, Jia Xuan; Fajardo, Maria Lourdes Restrepo

    2017-11-01

    Antisocial behaviour and conduct disorders are the most common behavioural and mental health problems in children and young people globally. An efficacious intervention is needed to manage these antisocial behaviours that have costly consequences. Multisystemic Therapy (MST), an intensive home-based intervention for youths with psychosocial and behavioural problems, is recommended under National Institute for Health and Clinical Excellence guidelines for conduct disorder. However, reviews on the efficacy of MST are mixed. To review randomised controlled trials (RCTs) reporting efficacy of MST among youths presenting with antisocial behaviour and emotional disorder respectively. A systematic map term to subject heading search was conducted in PsycINFO, Embase, and Ovid Medline databases for articles up to November 2015. RCTs comparing MST vs.treatment as usual (TAU) in youths presenting with antisocial behaviour and emotional disorder were included. 12 RCTs ( n  = 1425) reported efficacy of MST vs. TAU in youths presenting with antisocial behaviour and emotional disorder. Clinically significant treatment effects of MST showed a reduction of antisocial behaviour which includes delinquency. MST, vs. psychiatric hospitalisation, was associated with a reduction of suicidal attempts in youths presenting with psychiatric emergencies. 4 studies showed that MST was less costly than TAU in the short term, with further analysis required for long-term cost-effectiveness. MST is an efficacious intervention for severe antisocial behaviours in reduction of delinquency and should be included in clinical practices. MST was shown to have a positive effect on emotional disorder but further research is needed to evaluate the efficacy of MST with emotional disorder. Further analysis is required to assess the services utilized for long-term cost effectiveness.

  15. Descriptive summary of an outbreak of porcine post-weaning multisystemic wasting syndrome (PMWS ) in New Zealand.

    Science.gov (United States)

    Neumann, E J; Dobbinson, S S A; Welch, E B M; Morris, R S

    2007-12-01

    Investigations were conducted to determine the cause of an acute, multi-farm outbreak of porcine respiratory disease that included diarrhoea and subsequent loss of body condition in affected pigs. A definition for post-weaning multisystemic wasting syndrome (PMWS) including both clinical and pathological features, previously developed for the pig industry in New Zealand, was applied to the current outbreak. In addition to self-reporting by owners of affected farms, local veterinarians, disease and epidemiology consultants, and animal health officials from the Ministry of Agriculture and Forestry (MAF) were involved in conducting farm visits and submission of diagnostic specimens. Pathogens known to be endemic in the pig industry in New Zealand as well as likely exotic diseases were excluded as causative agents of the outbreak. Clinical signs including dyspnoea, diarrhoea, and rapid loss of body condition were consistent with the New Zealand case definition for PMWS. Interstitial pneumonia, pulmonary oedema, generalised lymph-node enlargement, and presence of porcine circovirus type 2 (PCV2) inclusion bodies were consistently identified in affected pigs. Classical swine fever virus (CSFv), Porcine reproductive and respiratory syndrome virus (PRRSv), and Influenza virus were ruled out, using molecular and traditional virological techniques. Spread of the disease between farms was hypothesised to be facilitated by locally migrating flocks of black-backed seagulls. The original source of the disease incursion was not identified. Based on the consistent presence of circovirus-associated lesions in lymphoid tissues in combination with generalised enlargement of lymph nodes, histiocytic interstitial pneumonia, clinical wasting, and poor response to antibiotic therapy, a diagnosis of PMWS was made. PMWS should be considered in the differential diagnoses of sudden onset of respiratory dyspnoea, diarrhoea, and rapid loss of body condition in young pigs in New Zealand pig

  16. Panhypopituitarism after multisystem trauma.

    Science.gov (United States)

    Wiechecka, Joanna; Krzewska, Aleksandra; Droń, Izabela; Beń-Skowronek, Iwona

    2013-01-01

    The pituitary gland plays a key role in hormonal regulation in the organism, contributing to maintenance of balance of basic vital functions. To emphasise the need for assessment of pituitary function after head injury, as correct diagnosis and hormone replacement therapy prove to be a life-saving therapy accelerating the recovery process. A healthy, normally developing 9-year-old girl, a child of young and healthy parents, was struck by a falling tree. The results of severe head trauma included adrenal crisis, hypothyroidism, and diabetes insipidus as manifestations of damage to the anterior and posterior pituitary gland. Administration of hormone replacement therapy, i.e. hydrocortisone, L-thyroxine, and desmopressin greatly improved the patient´s condition and facilitated effective rehabilitation. Determination of pituitary hormones in children after severe head injury should be an important part of diagnosis allowing identification of an early stage of acute hypopituitarism and acceleration of recovery through hormone replacement therapy.

  17. Cooling and denudation history of the Tsuruga body of Kojaku granite, southwest Japan, constrained from multi-system thermochronology

    International Nuclear Information System (INIS)

    Sueoka, Shigeru; Shimada, Koji; Ishimaru, Tsuneari; Umeda, Koji; Yasue, Ken-ichi; Niwa, Masakazu; Danhara, Tohru; Iwano, Hideki; Yagi, Koshi

    2016-01-01

    In this study, multi-system thermochronology, i.e., fission-track (FT), K-Ar and U-Pb methods are used to identify the cooling and denudation history of the Tsuruga body of Kojaku granite, southwest Japan. Apatite FT age of 51.8 ± 6.5 Ma, zircon FT age of 70.4 ± 2.0 Ma, biotite K-Ar ages of 66.7–62.0 Ma, and zircon U-Pb age of 68.5 ± 0.7 Ma were obtained for granitic samples, whereas plagioclase K-Ar ages of 19.1–18.8 Ma and whole-rock K-Ar age of 19.0 ± 2.9 Ma were inferred for the basaltic dyke intruding into the granite. The zircon FT lengths are not significantly shorter than their initial lengths, implying rapid cooling at the zircon FT partial annealing zone (PAZ). On the other hand, the apatite FT length distribution shows a typical pattern for granitic pluton without reheating, indicating a slow cooling history at the apatite FT PAZ. Based on the results of these thermochronometric analyses, inverse thermal calculations using the FT data, and simple thermal conduction modeling of the granitic body, the cooling and denudation histories of the Tsuruga body are reconstructed: (1) the Tsuruga body intruded at ca. 68 Ma, late Cretaceous, at a depth of several kilometers, (2) rapidly cooled to below the zircon FT PAZ by heat conduction within a few million years or less, and (3) slowly cooled due to peneplanation during the past 50–60 million years. On the other hand, the whole-rock Rb-Sr age previously reported for the Kojaku body is younger than when the cooling curve of the Tsuruga body obtained by this study intersects with the closure temperature of the whole-rock Rb-Sr system. This may imply a time lag between the formation ages of these bodies, but more thermochronometric studies are required to draw a definitive conclusion. The K-Ar ages of the basaltic dyke are interpreted as its formation age, indicating that dyke intrusion was associated with the Green Tuff movement. (author)

  18. Multisystemic engagement & nephrology based educational intervention: a randomized controlled trial protocol on the kidney team at home-study

    Directory of Open Access Journals (Sweden)

    Ismail Sohal Y

    2012-07-01

    Full Text Available Abstract Background Living donor kidney transplantation (LDKT is the most successful form of renal replacement therapy in terms of wait time and survival rates. However, we observed a significant inequality in the number of LDKT performed between the Dutch and the non-Dutch patients. The objective of this study is to adapt, implement and test an educational home-based intervention to contribute to the reduction of this inequality. Our aim is to establish this through guided communication together with the social network of the patients in an attempt that well-informed decisions regarding renal replacement therapy can be made: Multisystemic Engagement & Nephrology. This manuscript is a detailed description of the Kidney Team At Home-study protocol. Methods and design All patients (>18 yrs that are referred to the pre-transplantation outpatient clinic are eligible to participate in the study. Patients will be randomly assigned to either an experimental or a control group. The control group will continue to receive standard care. The experimental group will receive standard care plus a home-based educational intervention. The intervention consists of two sessions at the patient’s home, an initial session with the patient and a second session for which individuals from their social network are invited to take part. Based on the literature and behavioural change theories we hypothesize that reducing hurdles in knowledge, risk perception, subjective norm, self-efficacy, and communication contribute to well-informed decision making and reducing inequality in accessing LDKT programs. A change in these factors is consequently our primary outcome-measure. Based on power calculations, we aim to include 160 patients over a period of two years. Discussion If we are able to show that this home-based group educational intervention contributes to 1 achieving well-informed decision regarding treatment and 2 reducing the inequality in LDKT, the quality of life

  19. 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

  20. Reproduction of post-weaning multi-systemic wasting syndrome in an animal disease model as a tool for vaccine testing under controlled conditions.

    Science.gov (United States)

    McKillen, John; McNair, Irene; Lagan, Paula; McKay, Karen; McClintock, Julie; Casement, Veronica; Charreyre, Catherine; Allan, Gordon

    2016-04-01

    Snatch farrowed, colostrum deprived piglets were inoculated with different combinations of porcine circovirus 2, porcine parvovirus and Erysipelothrix rhusiopathiae candidate vaccines. 10 piglets were mock-vaccinated. Following virus challenge with a combined porcine circovirus 2/porcine parvovirus inoculum, all animals were monitored and samples taken for serology, immunohistochemistry and qPCR. At 24 dpc all non-vaccinated animals remaining were exhibiting signs of post-weaning multi-systemic wasting syndrome which was confirmed by laboratory analysis. Details of the study, analysis of samples and performance of the candidate vaccines are described. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. A Polytropic Caprine Arthritis Encephalitis Virus Promoter Isolated from Multiple Tissues from a Sheep with Multisystemic Lentivirus-Associated Inflammatory Disease

    Directory of Open Access Journals (Sweden)

    Brian Murphy

    2013-08-01

    Full Text Available Caprine arthritis encephalitis virus (CAEV is a lentivirus that infects both goats and sheep and is closely related to maedi-visna virus that infects sheep; collectively, these viruses are known as small ruminant lentiviruses (SRLV. Infection of goats and sheep with SRLV typically results in discrete inflammatory diseases which include arthritis, mastitis, pneumonia or encephalomyelitis. SRLV-infected animals concurrently demonstrating lentivirus-associated lesions in tissues of lung, mammary gland, joint synovium and the central nervous system are either very rare or have not been reported. Here we describe a novel CAEV promoter isolated from a sheep with multisystemic lentivirus-associated inflammatory disease including interstitial pneumonia, mastitis, polyarthritis and leukomyelitis. A single, novel SRLV promoter was cloned and sequenced from five different anatomical locations (brain stem, spinal cord, lung, mammary gland and carpal joint synovium, all of which demonstrated lesions characteristic of lentivirus associated inflammation. This SRLV promoter isolate was found to be closely related to CAEV promoters isolated from goats in northern California and other parts of the world. The promoter was denoted CAEV-ovine-MS (multisystemic disease; the stability of the transcription factor binding sites within the U3 promoter sequence are discussed.

  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. [Juvenile xanthogranuloma: 3 cases report and literature review].

    Science.gov (United States)

    Liu, Zi-qin; Liu, Rong; Shi, Xiao-dong; Li, Jing-xian; Zou, Ji-zhen

    2011-09-01

    To report the clinical characteristics and treatment of 3 patients with juvenile xanthogranuloma (JXG). A retrospective review of the medical records of 3 patients with JXG. JXG was characterized by solitary or multiple yellowish cutaneous nodules, or eye involvement . It could also affect pituitary. JXG was easily misdiagnosed as Langerhans cell histiocytosis (LCH). Treatment for JXG was surgical excision of a solitary skin lesion and some cases might be, spontaneous regression. In cases with multisystem involvement, chemotherapy regimens used to treat LCH may be effective. JXG is one of the more common non-Langerhans histiocytic proliferations and is frequently seen in infants and children. LCH-like chemotherapy is effective for patients with symptomatic multisystem JXG.

  4. Effect Of Aqueous And Hydroalcoholic Extract Of Beberis Vulgaris On Insulin Secretion From Islets Of Langerhans Isolated From Male Mice

    Directory of Open Access Journals (Sweden)

    A Ahangarpour

    2012-10-01

    Full Text Available Background & Aim: considering the use of Beberis vulgaris in traditional medicine as a blood sugar depressant, in this study, the effect of Beberis vulgaris extracts were investigated on the level of insulin secretion from islets isolated of langerhans in male mice. Methods: This experimental study was carried out on 90 adult male mice, NMARI strains weighing 20-25 g. Pancreatic islets from normal mice were isolated by collagenase digestion method. Then the aqueous and hydro-alcoholic extract of Beberis vulgaris at 0.05, 0.1, and 1 mg/ml concentrations and glyburide at 1 and 10 μM concentrations were applied on islets isolated in three different concentration of glucose solution (2.8, 5.6 and 16.7 mM. Insulin secretion from hand-picked islets were evaluated in the static incubation system. The level of Insulin secretion was measured by the ELISA insulin kit. Data were analyzed with variance analysis. Results: Insulin secretion was significantly increased at 16.7 mM glucose concentration in comparison with 2.8 and 5.6 mM glucose concentration (p<0.05. Incubation of pancreatic islets isolated at 2.8 and 5.6 mM glucose concentration and low concentrations of extract (0.05 and 0.1mg/ml significantly increased the insulin secretion (p<0.05. Glyburide at 10 μM concentration was more effective than aqueous and hydro alcoholic extract of Beberis vulgaris at 16.7 mM glucose. Conclusion: The present study supported the anti-diabetic effect of Beberis vulgaris extracts in vitro with low glucose concentration and it suggests that one of the anti diabetic mechanisms of this plant is via pancreatic islets.

  5. Cytokines cause functional and structural damage to isolated islets of Langerhans

    DEFF Research Database (Denmark)

    Mandrup-Poulsen, T; Bendtzen, K; Bendixen, G

    1985-01-01

    Cytokines are soluble, antigen non-specific, non-immunoglobulin mediators produced and secreted by blood mononuclear cells interacting in the cellular immune-response. To test the possibility that cytokines participate in the autoimmune destruction of the pancreatic beta-cells leading to insulin-......-release, and contents of insulin and glucagon in islets incubated with cytokine-rich supernatants were markedly reduced. This impairment of islet function was due to a cytotoxic effect of cytokine-rich supernatants as judged by disintegration of normal light-microscopic morphology....

  6. Effects of low or high doses of short wavelength ultraviolet light (UVB) on Langerhans cells and skin allograft survival

    International Nuclear Information System (INIS)

    Odling, K.A.; Halliday, G.M.; Muller, H.K.

    1987-01-01

    Donor C57BL mouse shaved dorsal trunk or tail skin was exposed to high (200 mJ/cm 2 ) or low (40 mJ/cm 2 ) doses of short wavelength ultraviolet light (UVB) before grafting on to the thorax of BALB/c mouse recipients of the same sex. Skin grafted 1-14 days following a single high dose of UVB irradiation was ultrastructurally depleted of LC and survived significantly longer than unirradiated skin before being rejected. After a 21-day interval between exposure and grafting when LC were again present in the epidermis there was no significant difference between treated and control graft survival. Exposure to low dose UVB irradiation only significantly increased graft survival for skin transplanted 1-3 days after irradiation; skin grafted 4 days following irradiation survived for a similar period to unirradiated control skin grafts. Electronmicroscopy showed that the low UVB dose did not deplete LC from the epidermis. We conclude that after low dose UVB treatment the class II MHC antigens on the LC Plasma membrane were lost temporarily, thus prolonging graft survival, but when the plasma membrane antigens were re-expressed graft survival returned to normal. In contrast, high-dose UVB irradiation prolonged graft survival by depleting LC from the epidermis, with graft survival only returning to control values as LC repopulated the epidermis

  7. A case of congenital Langerhans cell histiocytosis with skin and thymic lesions: Exploring the prognostic value of thymus involvement

    Directory of Open Access Journals (Sweden)

    M.M. Escudero-Góngora

    2016-10-01

    Full Text Available Thymus evaluation is not included in the guidelines of the Histiocyte Society, so its prevalence, management and prognosis are not well established. We present a newborn with self-healing cutaneous LCH and thymic involvement that was evaluated with a thoracic ultrasound. With the current evidence we are unable to predict the prognosis of the thymus association in neonatal LCH. We suggest that performing thymic ultrasound study, which is a non-invasive technique, would allow us to know the incidence of thymic involvement and its role on prognosis.

  8. Fatal Attraction: Interactions between antigen-presenting cells and islets of Langerhans in the pathogenesis of autoimmune diabetes

    NARCIS (Netherlands)

    J.G.M. Rosmalen (Judith)

    2000-01-01

    textabstractThe onset of diabetes mellitus is characterized by various symptoms, all the result of a disturbed glucose metabolism. The main symptoms are thirst and an excessive production of urine. The disturbed glucose metabolism underlying these symptoms is due to an absolute deficiency of insulin

  9. hnRNPA2B1 and hnRNPA1 mutations are rare in patients with "multisystem proteinopathy" and frontotemporal lobar degeneration phenotypes.

    Science.gov (United States)

    Le Ber, Isabelle; Van Bortel, Inge; Nicolas, Gael; Bouya-Ahmed, Kawtar; Camuzat, Agnès; Wallon, David; De Septenville, Anne; Latouche, Morwena; Lattante, Serena; Kabashi, Edor; Jornea, Ludmila; Hannequin, Didier; Brice, Alexis

    2014-04-01

    hnRNPA2B1 and hnRNPA1 mutations have been recently identified by exome sequencing in three families presenting with multisystem proteinopathy (MSP), a rare complex phenotype associating frontotemporal lobar degeneration (FTLD), Paget disease of bone (PDB), inclusion body myopathy (IBM), and amyotrophic lateral sclerosis (ALS). No study has evaluated the exact frequency of these genes in cohorts of MSP or FTD patients so far. We sequenced both genes in 17 patients with MSP phenotypes, and in 60 patients with FTLD and FTLD-ALS to test whether mutations could be implicated in the pathogenesis of these disorders. No disease-causing mutation was identified. We conclude that hnRNPA2B1 and hnRNPA1 mutations are rare in MSP and FTLD spectrum of diseases, although further investigations in larger populations are needed. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Infection, excretion and seroconversion dynamics of porcine circovirus type 2 (PCV2) in pigs from post-weaning multisystemic wasting syndrome (PMWS) affected farms in Spain and Denmark

    DEFF Research Database (Denmark)

    Grau-Roma, L.; Hjulsager, Charlotte Kristiane; Sibila, M.

    2009-01-01

    Longitudinal case-control studies were performed in post-weaning multisystemic wasting syndrome (PMWS) affected farms from Denmark and Spain using similar designs. Fourteen independent batches of 100-154 pigs per batch were monitored from birth to PMWS outbreak occurrence. Pigs displaying PMWS......-like signs and matched healthy cohorts were euthanized during the clinical outbreak. PMWS was diagnosed according to internationally accepted criteria and pigs were classified as: (i) PMWS cases, (ii) wasted non-PMWS cases and (iii) healthy pigs. Porcine circovirus type 2 (PCV2) quantitative PCR (q...... prevalence and/or viral load than healthy pigs in all collected samples at necropsy (p sampling prior to PMWS outbreak (p

  11. Spatial and temporal patterns of pig herds diagnosed with Postweaning Multisystemic Wasting Syndrome (PMWS) during the first two years of its occurrence in Denmark

    DEFF Research Database (Denmark)

    Vigre, Håkan; Bækbo, P.; Jorsal, Sven Erik Lind

    2005-01-01

    two years after the first herd was diagnosed, and we tested for spatial and spatio-temporal clustering using scan statistics. The study population consisted of pig herds that during the study period (October 2001 - September 2003) performed diagnostic submissions to the two major veterinary diagnostic......The clinical syndrome Postweaning Multisystemic Wasting Syndrome (PMWS) in pigs has emerged globally during the last decade. In October 2001, the first pig herd diagnosed with PMWS was reported in Denmark, and since then the number of herds diagnosed with PMWS has increased markedly. The etiology...... laboratories in Denmark (6724 herds). Of these, 277 herds were diagnosed with PMWS. Two statistically significant spatial clusters of herds diagnosed with PMWS were identified. These clusters included 11% and 8% of the study herds, respectively. Within these two clusters the relative risk for a herd...

  12. Pig major acute-phase protein and haptoglobin serum concentrations correlate with PCV2 viremia and the clinical course of postweaning multisystemic wasting syndrome

    DEFF Research Database (Denmark)

    Grau-Roma, Llorenc; Heegaard, Peter M. H.; Hjulsager, Charlotte Kristiane

    2009-01-01

    -PMWS affected pigs. In addition, evidence of infection with other pathogens and its relation with variations in APP's concentrations was also assessed. Fourteen independent batches of 100 to 154 pigs were monitored from birth to PMWS outbreak occurrence in 11 PMWS affected farms. Pigs displaying PMWS-like signs......The aim of the present longitudinal study was to assess the evolution of two acute phase proteins (APPs), pig-major acute phase protein (pig-MAP) and haptoglobin (HPT), in serum from pigs that developed postweaning multisystemic wasting syndrome (PMWS) in comparison to healthy and wasted non...... and age-matched healthy controls were euthanized during the clinical outbreak. PMWS was diagnosed according to internationally accepted creteria and pigs were classified as: i)PMWS cases, ii) wasted non-PMWS cases and iii) healthy pigs. At the moment of PMWS occurrence, pig-MAP and HPT concentration...

  13. Rapamycin and chloroquine: the in vitro and in vivo effects of autophagy-modifying drugs show promising results in valosin containing protein multisystem proteinopathy.

    Directory of Open Access Journals (Sweden)

    Angèle Nalbandian

    Full Text Available Mutations in the valosin containing protein (VCP gene cause hereditary Inclusion body myopathy (hIBM associated with Paget disease of bone (PDB, frontotemporal dementia (FTD, more recently termed multisystem proteinopathy (MSP. Affected individuals exhibit scapular winging and die from progressive muscle weakness, and cardiac and respiratory failure, typically in their 40s to 50s. Histologically, patients show the presence of rimmed vacuoles and TAR DNA-binding protein 43 (TDP-43-positive large ubiquitinated inclusion bodies in the muscles. We have generated a VCPR155H/+ mouse model which recapitulates the disease phenotype and impaired autophagy typically observed in patients with VCP disease. Autophagy-modifying agents, such as rapamycin and chloroquine, at pharmacological doses have previously shown to alter the autophagic flux. Herein, we report results of administration of rapamycin, a specific inhibitor of the mechanistic target of rapamycin (mTOR signaling pathway, and chloroquine, a lysosomal inhibitor which reverses autophagy by accumulating in lysosomes, responsible for blocking autophagy in 20-month old VCPR155H/+ mice. Rapamycin-treated mice demonstrated significant improvement in muscle performance, quadriceps histological analysis, and rescue of ubiquitin, and TDP-43 pathology and defective autophagy as indicated by decreased protein expression levels of LC3-I/II, p62/SQSTM1, optineurin and inhibiting the mTORC1 substrates. Conversely, chloroquine-treated VCPR155H/+ mice revealed progressive muscle weakness, cytoplasmic accumulation of TDP-43, ubiquitin-positive inclusion bodies and increased LC3-I/II, p62/SQSTM1, and optineurin expression levels. Our in vitro patient myoblasts studies treated with rapamycin demonstrated an overall improvement in the autophagy markers. Targeting the mTOR pathway ameliorates an increasing list of disorders, and these findings suggest that VCP disease and related neurodegenerative multisystem

  14. 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...

  15. Improved survival of macroencapsulated islets of Langerhans by preimplantation of the immunoisolating device: a morphometric study.

    Science.gov (United States)

    Rafael, E; Wu, G S; Hultenby, K; Tibell, A; Wernerson, A

    2003-01-01

    Encapsulation of cells in a semipermeable membrane may in the future provide an opportunity to treat a variety of endocrine and neurological disorders, without the need for lifelong immunosuppression. The physiological conditions in the device are crucial factors for graft survival. Previously, we have shown that the exchange across the immunoisolating membrane and the microcirculation around the TheraCyte device increase around 3 months after implantation. The aim of this study was to determine whether preimplantation of the TheraCyte device would improve the survival of a later transplanted islet graft. A TheraCyte device was implanted SC on one side of the back of a nondiabetic SD rat. After 3 months, 1500 islets isolated from SD rats were transplanted via the device port. At the same time, another device, loaded with the same number of islets, was implanted on the other side of the back. Both devices were explanted 2 weeks after islet transplantation (i.e., 3.5 months and 0.5 month after device implantation, respectively). Six pairs of devices were evaluated by morphometery. The volume densities of viable islets were 0.22 +/- 0.04 in the preimplanted device vs. 0.06 +/- 0.03 in the nonpreimplanted one (p TheraCyte device seems to improve the survival of an encapsulated islet graft and reduce fibroblast outgrowth in the device.

  16. 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

  17. 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.

  18. 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

  19. Minireview: Clinical severity in sickle cell disease: the challenges of definition and prognostication.

    Science.gov (United States)

    Quinn, Charles T

    2016-04-01

    Sickle cell disease (SCD) is a monogenic, yet highly phenotypically variable disease with multisystem pathology. This manuscript provides an overview of many of the known determinants, modifiers, and correlates of disease severity in SCD. Despite this wealth of data, modeling the variable and multisystem pathology of SCD continues to be difficult. The current status of prediction of specific adverse outcomes and global disease severity in SCD is also reviewed, highlighting recent successes and ongoing challenges. © 2016 by the Society for Experimental Biology and Medicine.

  20. 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.

  1. Refining the multisystem view of the stress response: coordination among cortisol, alpha-amylase, and subjective stress in response to relationship conflict.

    Science.gov (United States)

    Laurent, Heidemarie K; Powers, Sally I; Granger, Douglas A

    2013-07-02

    This study investigated associations among young adults' hypothalamic-pituitary-adrenal axis activity, autonomic nervous system activity, and subjective stress in response to interpersonal conflict to better characterize coordination across stress systems. Seven saliva samples were collected from 199 young adult opposite-sex couples before, during, and after they discussed an unresolved relationship conflict. Samples were later assayed for cortisol and alpha-amylase (sAA). Couples rated anticipatory stress prior to the conflict and perceived stress immediately following the task. Growth curve modeling was used to examine two possible levels of within-person coordination across physiological systems: alignment between cortisol and sAA responses throughout the sampling period ("matched phase coordination"), and association between overall levels of cortisol and sAA in response to conflict ("average level coordination"). Whereas both partners showed the former type of coordination, only women showed the latter type. Positive anticipation of the stressor predicted stronger cortisol-sAA matched phase coordination for women. Pre-task ratings related to women's sAA, and post-task ratings related to both partners' cortisol responses. Implications for a multisystem interpretation of normal and pathological responses to daily stress are discussed. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. Refining the multisystem view of the stress response: Coordination among cortisol, alpha-amylase, and subjective stress in response to relationship conflict

    Science.gov (United States)

    Powers, Sally I.; Granger, Douglas A.

    2013-01-01

    This study investigated associations among young adults' hypothalamic-pituitary-adrenal axis activity, autonomic nervous system activity, and subjective stress in response to interpersonal conflict to better characterize coordination across stress systems. Seven saliva samples were collected from 199 young adult opposite-sex couples before, during, and after they discussed an unresolved relationship conflict. Samples were later assayed for cortisol and alpha-amylase (sAA). Couples rated anticipatory stress prior to the conflict and perceived stress immediately following the task. Growth curve modeling was used to examine two possible levels of within-person coordination across physiological systems: alignment between cortisol and sAA responses throughout the sampling period (“matched phase coordination”), and association between overall levels of cortisol and sAA in response to conflict (“average level coordination”). Whereas both partners showed the former type of coordination, only women showed the latter type. Positive anticipation of the stressor predicted stronger cortisol-sAA matched phase coordination for women. Pre-task ratings related to women's sAA, and post-task ratings related to both partners' cortisol responses. Implications for a multisystem interpretation of normal and pathological responses to daily stress are discussed. PMID:23684904

  3. 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....

  4. IgG4-Related Sclerosing Disease, an Emerging Entity: A Review of a Multi-System Disease

    Science.gov (United States)

    Divatia, Mukul; Kim, Sun A

    2012-01-01

    Immunoglobulin G4-related systemic disease (IgG4-RSD) is a recently defined emerging entity characterized by a diffuse or mass forming inflammatory reaction rich in IgG4-positive plasma cells associated with fibrosclerosis and obliterative phlebitis. IgG4-RSD usually affects middle aged and elderly patients, with a male predominance. It is associated with an elevated serum titer of IgG4, which acts as a marker for this recently characterized entity. The prototype is IgG4-related sclerosing pancreatitis or autoimmune pancreatitis (AIP). Other common sites of involvement are the hepatobiliary tract, salivary gland, orbit, and lymph node, however practically any organ can be involved, including upper aerodigestive tract, lung, aorta, mediastinum, retroperitoneum, soft tissue, skin, central nervous system, breast, kidney, and prostate. Fever or constitutional symptoms usually do not comprise part of the clinical picture. Laboratory findings detected include raised serum globulin, IgG and IgG4. An association with autoantibody detection (such as antinuclear antibodies and rheumatoid factor) is seen in some cases. Steroid therapy comprises the mainstay of treatment. Disease progression with involvement of multiple organ-sites may be encountered in a subset of cases and may follow a relapsing-remitting course. The principal histopathologic findings in several extranodal sites include lymphoplasmacytic infiltration, lymphoid follicle formation, sclerosis and obliterative phlebitis, along with atrophy and destruction of tissues. Immunohistochemical staining shows increased IgG4+ cells in the involved tissues (>50 per high-power field, with IgG4/IgG ratio >40%). IgG4-RSD may potentially be rarely associated with the development of lymphoma and carcinoma. However, the nature and pathogenesis of IgG4-RSD are yet to be fully elucidated and provide immense scope for further studies. PMID:22187229

  5. 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.

  6. A 3.7 Mb Deletion Encompassing ZEB2 Causes a Novel Polled and Multisystemic Syndrome in the Progeny of a Somatic Mosaic Bull

    Science.gov (United States)

    Capitan, Aurélien; Allais-Bonnet, Aurélie; Pinton, Alain; Marquant-Le Guienne, Brigitte; Le Bourhis, Daniel; Grohs, Cécile; Bouet, Stéphan; Clément, Laëtitia; Salas-Cortes, Laura; Venot, Eric; Chaffaux, Stéphane; Weiss, Bernard; Delpeuch, Arnaud; Noé, Guy; Rossignol, Marie-Noëlle; Barbey, Sarah; Dozias, Dominique; Cobo, Emilie; Barasc, Harmonie; Auguste, Aurélie; Pannetier, Maëlle; Deloche, Marie-Christine; Lhuilier, Emeline; Bouchez, Olivier; Esquerré, Diane; Salin, Gérald; Klopp, Christophe; Donnadieu, Cécile; Chantry-Darmon, Céline; Hayes, Hélène; Gallard, Yves; Ponsart, Claire; Boichard, Didier; Pailhoux, Eric

    2012-01-01

    Polled and Multisystemic Syndrome (PMS) is a novel developmental disorder occurring in the progeny of a single bull. Its clinical spectrum includes polledness (complete agenesis of horns), facial dysmorphism, growth delay, chronic diarrhea, premature ovarian failure, and variable neurological and cardiac anomalies. PMS is also characterized by a deviation of the sex-ratio, suggesting male lethality during pregnancy. Using Mendelian error mapping and whole-genome sequencing, we identified a 3.7 Mb deletion on the paternal bovine chromosome 2 encompassing ARHGAP15, GTDC1 and ZEB2 genes. We then produced control and affected 90-day old fetuses to characterize this syndrome by histological and expression analyses. Compared to wild type individuals, affected animals showed a decreased expression of the three deleted genes. Based on a comparison with human Mowat-Wilson syndrome, we suggest that deletion of ZEB2, is responsible for most of the effects of the mutation. Finally sperm-FISH, embryo genotyping and analysis of reproduction records confirmed somatic mosaicism in the founder bull and male-specific lethality during the first third of gestation. In conclusion, we identified a novel locus involved in bovid horn ontogenesis and suggest that epithelial-to-mesenchymal transition plays a critical role in horn bud differentiation. We also provide new insights into the pathogenicity of ZEB2 loss of heterozygosity in bovine and humans and describe the first case of male-specific lethality associated with an autosomal locus in a non-murine mammalian species. This result sets PMS as a unique model to study sex-specific gene expression/regulation. PMID:23152852

  7. Intestinal lesions in pigs affected with postweaning multisystemic wasting syndrome Lesões entéricas em suínos afetados por síndrome multissistêmica do definhamento dos suínos

    Directory of Open Access Journals (Sweden)

    Priscila Zlotowski

    2008-06-01

    Full Text Available Samples of mesenteric lymph nodes and intestines from 79 unthrifty 3- to 5-month-old postweaning pigs, confirmed as naturally affected with postweaning multisystemic wasting syndrome (PMWS, were studied. Pigs originated from 12 farms in southern Brazil and were selected on the basis of clinical signs and/or gross lesions suggestive of enteric disorder. Lymphohistiocytic infiltrates of varying intensity were associated with anti-porcine circovirus type 2 (anti-PCV2 immunostaining (IS in samples of intestines and mesenteric lymph nodes from all pigs. Although most findings were similar to those described in PCV2-associated enteritis, anti-PCV2 IS in association with depletion of the goblet cell mucin stores (24 pigs, diffuse ileal villous atrophy and fusion (18 pigs, and dilatation of the lymphatic vessels (11 pigs combined or not with lymphangitis were also observed. PCV2 antigen was immunohistochemically demonstrated in the cytoplasm and nuclei from intralesional epithelial cells, histiocytes, and endothelial-like cells in intestinal tissues. Together these findings imply an association with PCV2. The presence of co-infections by Lawsonia intracellularis, Brachyspira spp., Mycobacterium spp., Salmonella spp., rotavirus, parvovirus, coronavirus and enteric calicivirus with PCV2 in the intestinal lesions was investigated.Amostras de linfonodos mesentéricos e intestinos de 79 leitões desmamados refugos, entre 3 e 5 meses de idade e confirmados como naturalmente afetados pela síndrome multissistêmica do definhamento foram estudadas. Os suínos eram oriundos de 12 criações no sul do país e foram selecionados em função dos sinais clínicos e/ou lesões macroscópicas sugestivos de doença entérica. Infiltrados linfoistiocíticos de intensidades variáveis foram associados com marcação positiva anti-circovirus suíno tipo 2 (anti-PCV2 em amostras de intestinos e linfonodos mesentéricos de todos os 79 animais. Embora a maioria dos achados

  8. Mobile Multi-System Overview

    Science.gov (United States)

    Witoff, Robert J.; Doody, David F.

    2012-01-01

    At the time of this reporting, there are 2,589 rich mobile devices used at JPL, including 1,550 iPhones and 968 Blackberrys. Considering a total JPL population of 5,961 employees, mobile applications have a total addressable market of 43 percent of the employees at JPL, and that number is rising. While it was found that no existing desktop tools can realistically be replaced by a mobile application, there is certainly a need to improve access to these desktop tools. When an alarm occurs and an engineer is away from his desk, a convenient means of accessing relevant data can save an engineer a great deal of time and improve his job efficiency. To identify which data is relevant, an engineer benefits from a succinct overview of the data housed in 13+ tools. This need can be well met by a single, rich, mobile application that provides access to desired data across tools in the ops infrastructure.

  9. A case of multisystem endometriosis.

    Science.gov (United States)

    Athwal, Pardeep; Patel, Krishna; Hassani, Cameron; Bahadori, Shapour; Nardi, Peter

    2013-10-01

    Catamenial pneumothorax is a rare complication secondary to pleural endometriosis. We present a case of a 37-year-old-female with a history of recurrent pneumothoraces with an associated temporal relationship to the onset of her menses. In addition to her recurrent pneumothoraces, on further evaluation, she was found to have multiple nodular masses within the omentum. A thoracoscopic biopsy was subsequently performed, which showed endometrial implants within the pleural space and within the omental cavity. The radiological features and pathogenesis of this rare disease are reviewed and discussed with reference to relevant literature.

  10. The role of C-type lectin receptors in human skin immunity: immunological interactions between dendritic cells, Langerhans cells and keratinocytes

    NARCIS (Netherlands)

    van den Berg, L.M.

    2013-01-01

    Langerhanscellen kunnen actief contact met elkaar maken in de huid waardoor ze informatie over binnendringende ziekteverwekkers uitwisselen. Dit leidt tot een efficiënte afweerreactie. Linda van den Berg geeft hier een beschrijving van. Daarnaast ontdekte ze dat een koolhydraat afkomstig van een

  11. Intradermally administered TLR4 agonist GLA-SE enhances the capacity of human skin DCs to activate T cells and promotes emigration of Langerhans cells

    NARCIS (Netherlands)

    Schneider, Laura P.; Schoonderwoerd, Antoinet J.; Moutaftsi, Magdalini; Howard, Randall F.; Reed, Steven G.; de Jong, Esther C.; Teunissen, Marcel B. M.

    2012-01-01

    The natural TLR4 agonist lipopolysaccharide (LPS) has notable adjuvant activity. However, it is not useful as a vaccine adjuvant due to its toxicity. Glucopyranosyl lipid A (GLA) is a synthetic derivative of the lipid A tail of LPS with limited cytotoxicity, but strong potential to induce immune

  12. Erdheim-Chester disease: a comprehensive review.

    Science.gov (United States)

    Abdelfattah, Ahmed Maher; Arnaout, Karim; Tabbara, Imad A

    2014-07-01

    Erdheim-Chester disease is a rare form of non-Langerhans' cell histiocytosis characterized by multi-system infiltration by xanthogranulomas composed of foamy histiocytes surrounded by fibrosis. Approximately 400 cases have been reported in the literature, and the recent increase in the number of cases is likely due to the increased awareness of its associated morbidity and mortality. The etiology of this disease remains unknown, the clinical course is variable and treatment is still not well-established. The objective of this review is to describe the pathogenesis, clinical manifestations, and diagnosis of this rare disorder, and to review its prognosis and treatment. Erdheim-Chester disease (ECD) is a rare form of non-Langerhans' cell histiocytosis. It was first described in 1930. Approximately 400 cases have been reported in the literature. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  13. Análise quantitativa das células de Langerhans em mucosa bucal de pacientes submetidos ao transplante de medula óssea alogênico com doença enxerto contra hospedeiro crônica

    OpenAIRE

    Érika Sinara Lenharo Orti-Raduan

    2007-01-01

    A doença enxerto contra hospedeiro é uma complicação comum nos pacientes submetidos ao transplante de medula óssea alogênico. Com o objetivo de contribuir para o esclarecimento da participação das células de Langerhans na doença enxerto contra hospedeiro crônica (GVHDc) quando de sua ocorrência na mucosa bucal, foram analisados 40 pacientes oncohematológicos e hematológicos submetidos ao transplante de medula óssea alogênico no Hospital Amaral Carvalho, Jaú - SP. Cortes microscópicos de 3µm d...

  14. 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

  15. Cost of post-weaning multi-systemic wasting syndrome and porcine circovirus type-2 subclinical infection in England - an economic disease model.

    Science.gov (United States)

    Alarcon, Pablo; Rushton, Jonathan; Wieland, Barbara

    2013-06-01

    Post-weaning multi-systemic wasting syndrome (PMWS) is a multi-factorial disease with major economic implications for the pig industry worldwide. The present study aimed to assess the economic impact of PMWS and porcine circovirus type 2 (PCV2) subclinical infections (PCV2SI) for farrow-to-finish farms and to estimate the resulting cost to the English pig industry. A disease model was built to simulate the varying proportions of pigs in a batch that get infected with PCV2 and develop either PMWS, subclinical disease (reduce growth without evident clinical signs) or remain healthy (normal growth and no clinical signs), depending on the farm level PMWS severity. This PMWS severity measure accounted for the level of post-weaning mortality, PMWS morbidity and proportion of PCV2 infected pigs observed on farms. The model generated six outcomes: infected pigs with PMWS that die (PMWS-D); infected pigs with PMWS that recover (PMWS-R); subclinical pigs that die (Sub-D); subclinical pigs that reach slaughter age (Sub-S); healthy pigs sold (H-S); and pigs, infected or non-infected by PCV2, that die due to non-PCV2 related causes (nonPCV2-D). Enterprise and partial budget analyses were used to assess the deficit/profits and the extra costs/extra benefits of a change in disease status, respectively. Results from the economic analysis at pig level were combined with the disease model's estimates of the proportion of different pigs produced at different severity scores to assess the cost of PMWS and subclinical disease at farm level, and these were then extrapolated to estimate costs at national level. The net profit for a H-S pig was £19.2. The mean loss for a PMWS-D pig was £84.1 (90% CI: 79.6-89.1), £24.5 (90% CI: 15.1-35.4) for a PMWS-R pig, £82.3 (90% CI: 78.1-87.5) for a Sub-D pig, and £8.1 (90% CI: 2.18-15.1) for a Sub-S pig. At farm level, the greatest proportion of negative economic impact was attributed to PCV2 subclinical pigs. The economic impact for the English

  16. 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.

  17. 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

  18. Uptake of the glycosphingolipid sulfatide in the gastrointestinal tract and pancreas in vivo and in isolated islets of Langerhans

    Directory of Open Access Journals (Sweden)

    Fredman Pam

    2006-10-01

    Full Text Available Abstract Background The glycosphingolipid sulfatide has previously been found in several mammalian tissues, but information on the uptake of exogenously administered sulfatide in different organs in vivo is limited. In pancreatic beta cells, sulfatide has been shown to be involved in insulin processing and secretion in vitro. In this study, we examined the uptake of exogenously administered sulfatide and its distribution to the pancreatic beta cells. This might encourage future studies of the function(s of sulfatide in beta cell physiology in vivo. Radioactive sulfatide was given orally to mice whereafter the uptake of sulfatide in the gastrointestinal tract and subsequent delivery to the pancreas was examined. Sulfatide uptake in pancreas was also studied in vivo by i.p. administration of radioactive sulfatide in mice, and in vitro in isolated rat islets. Isolated tissue/islets were analysed by scintillation counting, autoradiography and thin-layer chromatography-ELISA. Results Sulfatide was taken up in the gastrointestinal tract for degradation or further transport to other organs. A selective uptake of short chain and/or hydroxylated sulfatide fatty acid isoforms was observed in the small intestine. Exogenously administered sulfatide was found in pancreas after i.p, but not after oral administration. The in vitro studies in isolated rat islets support that sulfatide, independently of its fatty acid length, is endocytosed and metabolised by pancreatic islets. Conclusion Our study supports a selective uptake and/or preservation of sulfatide in the gastrointestinal tract after oral administration and with emphasises on pancreatic sulfatide uptake, i.p. administration results in sulfatide at relevant location.

  19. 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.

  20. Histiocitosis de células de Langerhans. Serie de casos en población pediátrica. INOR 1980 – 2008

    Directory of Open Access Journals (Sweden)

    Yandry Medina González

    2015-11-01

    Full Text Available Se realizó un estudio descriptivo, retrospectivo, de los pacientes inscritos en el Instituto Nacional de Oncología (INOR, con edad igual o menor a 15 años y diagnóstico de Histiocitosis de células de Langerhans, en el período 1980-2008; con una muestra de 32 pacientes e identificándose las características clínicas, histopatológicas; del tratamiento y la supervivencia. Los datos se obtuvieron de las historias clínicas, fueron consultados los archivos de anatomía patológica y las bases de datos correspondientes. Se confeccionó un modelo para la recolección de los datos primarios. Se empleó para el análisis: distribución de frecuencias, Chi-cuadrado, Kaplan-Meier y test de Log-Rank. Los resultados se presentaron de forma resumida en tablas y gráficos. Predominó el grupo etáreo de menores o igual a 2 años (40,6%, los sujetos blancos (78,1%, el sexo masculino con el 65,6%, con una relación hombre/mujer de 1,9:1. Prevaleció el dolor óseo localizado (84,4%, la afectación ósea (90,6% y la enfermedad localizada (84,4%. Predominó el estrato de diagnóstico presuntivo (65,6%. El tratamiento más utilizado fue la quimioterapia, como modalidad única y combinada; el protocolo más empleado fue el de quimioterapia oral secuencial. En la evaluación de la respuesta predominó la categoría de mejoría (75%. Se obtuvieron valores de supervivencia global a los 10 años de 86,9%. En el análisis de supervivencia se observó asociación estadísticamente significativa con respecto a la edad, clasificación de la enfermedad según extensión y respuesta al tratamiento. Constituye la mayor serie de casos de la enfermedad publicada en nuestro país hasta la fecha.

  1. A Unique Cause of Intestinal and Splenic Infarction in a Sickle Cell Trait Patient

    OpenAIRE

    Asfaw, Sofya H.; Falk, Gavin A.; Morris-Stiff, Gareth; Tuthill, Ralph J.; Moorman, Matthew L.; Samotowka, Michael A.

    2013-01-01

    Sickle-cell trait is a common genetic abnormality in the African American population. A sickle-cell crisis in a patient with sickle-cell trait is uncommon at best. Abdominal painful crises are typical of patients with sickle cell anemia. The treatment for an abdominal painful crisis is usually medical and rarely surgical. We present the case of a cocaine-induced sickle-cell crisis in a sickle-cell trait patient that resulted in splenic, intestinal, and cerebral infarctions and multisystem org...

  2. 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

  3. 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

    DEFF Research Database (Denmark)

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

    2015-01-01

    BACKGROUND: 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 re...

  4. Comparative potency of different UV sources in reducing the density and antigen-presenting capacity of Langerhans cells in C3H mice

    NARCIS (Netherlands)

    Pierik, F.H.

    1994-01-01

    Although broadband UV.B irradiation has been shown to induce selective immunosuppression in a variety of experimental systems, the wavelength dependence of the immunornodulation and the initial events in the skin remain unclear. In the present study three UV lamps werc used at suberythermal doses on

  5. A lack of Birbeck granules in Langerhans cells is associated with a naturally occurring point mutation in the human Langerin gene.

    Science.gov (United States)

    Verdijk, Pauline; Dijkman, Remco; Plasmeijer, Elsemieke I; Mulder, Aat A; Zoutman, Willem H; Mieke Mommaas, A; Tensen, Cornelis P

    2005-04-01

    A heterozygous mutation in the Langerin gene corresponding to position 837 in the Langerin mRNA was identified in a person deficient in Birbeck granules (BG). This mutation results in an amino acid replacement of tryptophan by arginine at position 264 in the carbohydrate recognition domain of the Langerine protein. Expression of mutated Langerin in human fibroblasts induces tubular-like structures that are negative for BG-specific antibodies and do not resemble the characteristic structural features of BG.

  6. 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.

  7. Current Standards of Care and Long Term Outcomes for Thalassemia and Sickle Cell Disease.

    Science.gov (United States)

    Chonat, Satheesh; Quinn, Charles T

    2017-01-01

    Thalassemia and sickle cell disease (SCD) are disorders of hemoglobin that affect millions of people worldwide. The carrier states for these diseases arose as common, balanced polymorphisms during human history because they afforded protection against severe forms of malaria. These complex, multisystem diseases are reviewed here with a focus on current standards of clinical management and recent research findings. The importance of a comprehensive, multidisciplinary and lifelong system of care is also emphasized.

  8. 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...

  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. Lyme carditis mimicking giant cell arteritis

    Directory of Open Access Journals (Sweden)

    Krati Chauhan

    2015-10-01

    Full Text Available Presenting an interesting case of a patient who complained of myalgias, fatigue, headache, jaw claudication and scalp tenderness. Patient’s physical examination was unremarkable. Laboratory findings showed elevated erythrocyte sedimentation rate and C-reactive protein, bilateral temporal artery biopsy results were negative and first degree atrioventricular block was seen on electrocardiogram. Serology for Borrelia burgdorferi was positive; patient was diagnosed with Lyme carditis and treated with doxycycline. Lyme is a tick-borne, multi-system disease and occasionally its presentation may mimic giant cell arteritis. On follow-up there was complete resolution of symptoms and electrocardiogram findings.

  11. 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.

  12. 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

  13. 18F-FDG PET/CT for Monitoring Response of Merkel Cell Carcinoma to the Novel Programmed Cell Death Ligand 1 Inhibitor Avelumab.

    Science.gov (United States)

    Eshghi, Naghmehossadat; Lundeen, Tamara F; MacKinnon, Lea; Avery, Ryan; Kuo, Phillip H

    2018-05-01

    An 85-year-old man with stage IIIA Merkel cell carcinoma of the left arm was initially treated with local excision and axillary node dissection followed by radiation therapy. Eight months after surgery, whole-body FDG PET/CT demonstrated intensely hypermetabolic hepatic metastases and abdominal lymphadenopathy. Given his age and comorbidities, he was considered a poor candidate for chemotherapy, and therefore the novel programmed cell death ligand 1 inhibitor avelumab was initiated. FDG PET/CT after 4 cycles showed complete resolution of hepatic and nodal metastases. Whole-body FDG PET/CT can be used for monitoring response of multisystem metastases from Merkel cell carcinoma to active immunotherapy.

  14. Characterization of inflammatory cell infiltration in feline allergic skin disease.

    Science.gov (United States)

    Taglinger, K; Day, M J; Foster, A P

    2007-11-01

    Sixteen cats with allergic dermatitis and six control cats with no skin disease were examined. Lymphoid and histiocytic cells in skin sections were examined immunohistochemically and mast cells were identified by toluidine blue staining. The 16 allergic cats showed one or more of several features (alopecia, eosinophilic plaques or granulomas, papulocrusting lesions), and histopathological findings were diverse. In control cats there were no cells that expressed IgM or MAC387, a few that were immunolabelled for IgG, IgA or CD3, and moderate numbers of mast cells. In allergic cats, positively labelled inflammatory cells were generally more numerous in lesional than in non-lesional skin sections, and were particularly associated with the superficial dermis and perifollicular areas. There were low numbers of plasma cells expressing cytoplasmic immunoglobulin; moderate numbers of MHC II-, MAC387- and CD3-positive cells; and moderate to numerous mast cells. MHC class II expression was associated with inflammatory cells morphologically consistent with dermal dendritic cells and macrophages, and epidermal Langerhans cells. Dendritic cells expressing MHC class II were usually associated with an infiltrate of CD3 lymphocytes, suggesting that these cells participate in maintenance of the local immune response by presenting antigen to T lymphocytes. These findings confirm that feline allergic skin disease is characterized by infiltration of activated antigen-presenting cells and T lymphocytes in addition to increased numbers of dermal mast cells. This pattern mimics the dermal inflammation that occurs in the chronic phase of both canine and human atopic dermatitis.

  15. 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.

  16. Immunoregulation of NKT Cells in Systemic Lupus Erythematosus.

    Science.gov (United States)

    Chen, Junwei; Wu, Meng; Wang, Jing; Li, Xiaofeng

    2015-01-01

    Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with different variety of clinical manifestations. Natural killer T (NKT) cells are innate lymphocytes that play a regulatory role during broad range of immune responses. A number of studies demonstrated that the quantity and quality of invariant NKT (iNKT) cells showed marked defects in SLE patients in comparison to healthy controls. This finding suggests that iNKT cells may play a regulatory role in the occurrence and development of this disease. In this review, we mainly summarized the most recent findings about the behavior of NKT cells in SLE patients and mouse models, as well as how NKT cells affect the proportion of T helper cells and the production of autoreactive antibodies in the progress of SLE. This will help people better understand the role of NKT cells in the development of SLE and improve the therapy strategy.

  17. B cell depletion reduces T cell activation in pancreatic islets in a murine autoimmune diabetes model.

    Science.gov (United States)

    Da Rosa, Larissa C; Boldison, Joanne; De Leenheer, Evy; Davies, Joanne; Wen, Li; Wong, F Susan

    2018-06-01

    Type 1 diabetes is a T cell-mediated autoimmune disease characterised by the destruction of beta cells in the islets of Langerhans, resulting in deficient insulin production. B cell depletion therapy has proved successful in preventing diabetes and restoring euglycaemia in animal models of diabetes, as well as in preserving beta cell function in clinical trials in the short term. We aimed to report a full characterisation of B cell kinetics post B cell depletion, with a focus on pancreatic islets. Transgenic NOD mice with a human CD20 transgene expressed on B cells were injected with an anti-CD20 depleting antibody. B cells were analysed using multivariable flow cytometry. There was a 10 week delay in the onset of diabetes when comparing control and experimental groups, although the final difference in the diabetes incidence, following prolonged observation, was not statistically significant (p = 0.07). The co-stimulatory molecules CD80 and CD86 were reduced on stimulation of B cells during B cell depletion and repopulation. IL-10-producing regulatory B cells were not induced in repopulated B cells in the periphery, post anti-CD20 depletion. However, the early depletion of B cells had a marked effect on T cells in the local islet infiltrate. We demonstrated a lack of T cell activation, specifically with reduced CD44 expression and effector function, including IFN-γ production from both CD4 + and CD8 + T cells. These CD8 + T cells remained altered in the pancreatic islets long after B cell depletion and repopulation. Our findings suggest that B cell depletion can have an impact on T cell regulation, inducing a durable effect that is present long after repopulation. We suggest that this local effect of reducing autoimmune T cell activity contributes to delay in the onset of autoimmune diabetes.

  18. 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.

  19. 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

  20. 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...

  1. 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.

  2. 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...

  3. Prevalence of the Novel Torque Teno Sus Virus Species k2b from Pigs in the United States and Lack of Association with Post-Weaning Multisystemic Wasting Syndrome or Mulberry Heart Disease.

    Science.gov (United States)

    Rogers, A J; Huang, Y-W; Heffron, C L; Opriessnig, T; Patterson, A R; Meng, X-J

    2017-12-01

    The family Anelloviridae includes a number of viruses infecting humans (Torque teno viruses, TTV) and other animals including swine (Torque teno sus viruses, TTSuV). Two genetically distinct TTSuV species have been identified from swine thus far (TTSuV1 and TTSuVk2), although their definitive association with disease remains debatable. In 2012, a novel TTSuV species was identified from commercial swine serum and classified in the genus Kappatorquevirus as TTSuVk2b. The other Kappatorquevirus species, TTSuVk2a, has been associated with post-weaning multisystemic wasting syndrome (PMWS) when coinfected with porcine circovirus type 2 (PCV2). Therefore, in this study, we initially amplified a portion of TTSuVk2b ORF1 and, subsequently, assessed the molecular prevalence of the virus in pigs in the United States. A total of 127 serum and 115 tissue samples were obtained from pigs with PMWS or mulberry heart disease (MHD) in six states and tested by PCR for the presence of TTSuVk2b DNA. Approximately 27.6% of the serum and 21.7% of tissue samples tested positive for TTSuVk2b DNA, and the positive products were confirmed by sequencing. However, we did not detect a correlation between TTSuVk2b infection and PMWS or MHD. The near full-length genomic sequence of US TTSuVk2b was determined, and sequence analysis revealed that the US TTSuVk2b isolates were 95% identical to the TTSuVk2b isolate from Spain, with most of the variations clustering in ORF1. We conclude that the novel TTSuVk2b species is present in pigs in the United States and its potential association with a disease warrants further investigation. © 2016 Blackwell Verlag GmbH.

  4. 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...

  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. 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.

  8. 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 ...

  9. MANAGEMENT OF SICKLE CELL DISEASE

    Directory of Open Access Journals (Sweden)

    Rajesh

    2016-02-01

    Full Text Available Sickle cell disease (SCD is a genetically transmitted multisystem disease1 which includes a group of disorders that differs in severity sign and symptoms, The disease is not uniformly seen everywhere but it has some topographical distribution. In India, it is frequently seen in Central India, in and around the vicinity of Chhattisgarh in some religions in caste like kurmis, satnami, mahar, other backward caste and some tribes, it has great pathological significance considering the high morbidity and mortality resulting from the disease process. We have studied the cases of SCD from 2001 to 2015 series of such patients, since there is no cure of this disease, in regards to prevention of this genetic autosomal recessive disorder by marriage counseling, the incidence can be significantly reduced by avoiding consanguineous marriages in the susceptible community.

  10. Protein-Mediated Interactions of Pancreatic Islet Cells

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    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.

  11. 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.

  12. 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.

  13. Acute Ischemia Induced by High-Density Culture Increases Cytokine Expression and Diminishes the Function and Viability of Highly Purified Human Islets of Langerhans.

    Science.gov (United States)

    Smith, Kate E; Kelly, Amy C; Min, Catherine G; Weber, Craig S; McCarthy, Fiona M; Steyn, Leah V; Badarinarayana, Vasudeo; Stanton, J Brett; Kitzmann, Jennifer P; Strop, Peter; Gruessner, Angelika C; Lynch, Ronald M; Limesand, Sean W; Papas, Klearchos K

    2017-11-01

    Encapsulation devices have the potential to enable cell-based insulin replacement therapies (such as human islet or stem cell-derived β cell transplantation) without immunosuppression. However, reasonably sized encapsulation devices promote ischemia due to high β cell densities creating prohibitively large diffusional distances for nutrients. It is hypothesized that even acute ischemic exposure will compromise the therapeutic potential of cell-based insulin replacement. In this study, the acute effects of high-density ischemia were investigated in human islets to develop a detailed profile of early ischemia induced changes and targets for intervention. Human islets were exposed in a pairwise model simulating high-density encapsulation to normoxic or ischemic culture for 12 hours, after which viability and function were measured. RNA sequencing was conducted to assess transcriptome-wide changes in gene expression. Islet viability after acute ischemic exposure was reduced compared to normoxic culture conditions (P < 0.01). Insulin secretion was also diminished, with ischemic β cells losing their insulin secretory response to stimulatory glucose levels (P < 0.01). RNA sequencing revealed 657 differentially expressed genes following ischemia, with many that are associated with increased inflammatory and hypoxia-response signaling and decreased nutrient transport and metabolism. In order for cell-based insulin replacement to be applied as a treatment for type 1 diabetes, oxygen and nutrient delivery to β cells will need to be maintained. We demonstrate that even brief ischemic exposure such as would be experienced in encapsulation devices damages islet viability and β cell function and leads to increased inflammatory signaling.

  14. Nonalcoholic fatty liver disease - A multisystem disease?

    Science.gov (United States)

    Mikolasevic, Ivana; Milic, Sandra; Turk Wensveen, Tamara; Grgic, Ivana; Jakopcic, Ivan; Stimac, Davor; Wensveen, Felix; Orlic, Lidija

    2016-01-01

    Non-alcoholic fatty liver disease (NAFLD) is one of the most common comorbidities associated with overweight and metabolic syndrome (MetS). Importantly, NAFLD is one of its most dangerous complications because it can lead to severe liver pathologies, including fibrosis, cirrhosis and hepatic cellular carcinoma. Given the increasing worldwide prevalence of obesity, NAFLD has become the most common cause of chronic liver disease and therefore is a major global health problem. Currently, NAFLD is predominantly regarded as a hepatic manifestation of MetS. However, accumulating evidence indicates that the effects of NAFLD extend beyond the liver and are negatively associated with a range of chronic diseases, most notably cardiovascular disease (CVD), diabetes mellitus type 2 (T2DM) and chronic kidney disease (CKD). It is becoming increasingly clear that these diseases are the result of the same underlying pathophysiological processes associated with MetS, such as insulin resistance, chronic systemic inflammation and dyslipidemia. As a result, they have been shown to be independent reciprocal risk factors. In addition, recent data have shown that NAFLD actively contributes to aggravation of the pathophysiology of CVD, T2DM, and CKD, as well as several other pathologies. Thus, NAFLD is a direct cause of many chronic diseases associated with MetS, and better detection and treatment of fatty liver disease is therefore urgently needed. As non-invasive screening methods for liver disease become increasingly available, detection and treatment of NAFLD in patients with MetS should therefore be considered by both (sub-) specialists and primary care physicians. PMID:27920470

  15. 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)

  16. 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

  17. Evaluation of RT-PCR and immunohistochemistry as tools for detection of enterovirus in the human pancreas and islets of Langerhans.

    Science.gov (United States)

    Skog, Oskar; Ingvast, Sofie; Korsgren, Olle

    2014-10-01

    Enteroviruses have been implicated in the etiology of type 1 diabetes, supported by immunoreactivity of enteroviral protein in islets, but presence of enteroviral genome has rarely been reported. Failure to detect enterovirus with RT-PCR has been attributed to the possible presence of PCR inhibitors and that only few cells are infected. The aim of this study was to evaluate strategies for detection of enterovirus in human islets. A scenario was modeled with defined infected islets among a large number of uninfected pancreatic cells and the sensitivity of immunohistochemistry and PCR for detection of enterovirus was evaluated. Enterovirus was detected with PCR when only one single human islet, infected in vitro with a low dose of virus, was mixed with an uninfected pancreatic biopsy. Enterovirus could not be detected by immunohistochemistry under the same conditions, demonstrating the superior sensitivity of PCR also in pancreatic tissue with only a small fraction of infected cells. In addition, we demonstrate that pancreatic cell culture supernatant does not cause degradation of enterovirus at 37°C, indicating that under normal culture conditions released virus is readily detectable. Utilizing PCR, the pancreases of two organ donors that died at onset of type 1 diabetes were found negative for enterovirus genome despite islet cells being positive using immunohistochemistry. These data suggest that PCR should be the preferred screening method for enterovirus in the pancreas and suggest cautious interpretation of immunostaining for enterovirus that cannot be confirmed with PCR. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. 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

  19. 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

  20. 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.

  1. Chronic inflammation triggered by the NLRP3 inflammasome in myeloid cells promotes growth plate dysplasia by mesenchymal cells.

    Science.gov (United States)

    Wang, Chun; Xu, Can-Xin; Alippe, Yael; Qu, Chao; Xiao, Jianqiu; Schipani, Ernestina; Civitelli, Roberto; Abu-Amer, Yousef; Mbalaviele, Gabriel

    2017-07-07

    Skeletal complications are common features of neonatal-onset multisystem inflammatory disease (NOMID), a disorder caused by NLRP3-activating mutations. NOMID mice in which NLRP3 is activated globally exhibit several characteristics of the human disease, including systemic inflammation and cartilage dysplasia, but the mechanisms of skeletal manifestations remain unknown. In this study, we find that activation of NLRP3 in myeloid cells, but not mesenchymal cells triggers chronic inflammation, which ultimately, causes growth plate and epiphyseal dysplasia in mice. These responses are IL-1 signaling-dependent, but independent of PARP1, which also functions downstream of NLRP3 and regulates skeletal homeostasis. Mechanistically, inflammation causes severe anemia and hypoxia in the bone environment, yet down-regulates the HIF-1α pathway in chondrocytes, thereby promoting the demise of these cells. Thus, activation of NLRP3 in hematopoietic cells initiates IL-1β-driven paracrine cascades, which promote abnormal growth plate development in NOMID mice.

  2. A unique cause of intestinal and splenic infarction in a sickle cell trait patient.

    Science.gov (United States)

    Asfaw, Sofya H; Falk, Gavin A; Morris-Stiff, Gareth; Tuthill, Ralph J; Moorman, Matthew L; Samotowka, Michael A

    2013-01-01

    Sickle-cell trait is a common genetic abnormality in the African American population. A sickle-cell crisis in a patient with sickle-cell trait is uncommon at best. Abdominal painful crises are typical of patients with sickle cell anemia. The treatment for an abdominal painful crisis is usually medical and rarely surgical. We present the case of a cocaine-induced sickle-cell crisis in a sickle-cell trait patient that resulted in splenic, intestinal, and cerebral infarctions and multisystem organ failure necessitating a splenectomy, subtotal colectomy, and small bowel resection. This case highlights the diagnostic dilemma that abdominal pain can present in the sickle-cell population and illustrates the importance of recognizing the potential for traditionally medically managed illnesses to become surgical emergencies.

  3. A Unique Cause of Intestinal and Splenic Infarction in a Sickle Cell Trait Patient

    Directory of Open Access Journals (Sweden)

    Sofya H. Asfaw

    2013-01-01

    Full Text Available Sickle-cell trait is a common genetic abnormality in the African American population. A sickle-cell crisis in a patient with sickle-cell trait is uncommon at best. Abdominal painful crises are typical of patients with sickle cell anemia. The treatment for an abdominal painful crisis is usually medical and rarely surgical. We present the case of a cocaine-induced sickle-cell crisis in a sickle-cell trait patient that resulted in splenic, intestinal, and cerebral infarctions and multisystem organ failure necessitating a splenectomy, subtotal colectomy, and small bowel resection. This case highlights the diagnostic dilemma that abdominal pain can present in the sickle-cell population and illustrates the importance of recognizing the potential for traditionally medically managed illnesses to become surgical emergencies.

  4. Skewed Helper T-Cell Responses to IL-12 Family Cytokines Produced by Antigen-Presenting Cells and the Genetic Background in Behcet’s Disease

    Directory of Open Access Journals (Sweden)

    Jun Shimizu

    2013-01-01

    Full Text Available Behcet’s disease (BD is a multisystemic inflammatory disease and is characterized by recurrent attacks on eyes, brain, skin, and gut. There is evidence that skewed T-cell responses contributed to its pathophysiology in patients with BD. Recently, we found that Th17 cells, a new helper T (Th cell subset, were increased in patients with BD, and both Th type 1 (Th1 and Th17 cell differentiation signaling pathways were overactivated. Several researches revealed that genetic polymorphisms in Th1/Th17 cell differentiation signaling pathways were associated with the onset of BD. Here, we summarize current findings on the Th cell subsets, their contribution to the pathogenesis of BD and the genetic backgrounds, especially in view of IL-12 family cytokine production and pattern recognition receptors of macrophages/monocytes.

  5. Advances in generation of functional β-cells from induced pluripotent stem cells as a cure for diabetes mellitus.

    Science.gov (United States)

    Kalra, Kunal; Chandrabose, Srijaya Thekkeparambil; Ramasamy, Thamil Selvee; Kasim, Noor Hayaty Binti Abu

    2018-06-04

    Diabetes mellitus is one of the leading cause for death worldwide. Loss and functional failure of pancreatic β-cells, the parenchyma cells in the islets of Langerhans onsets and progresses diabetes mellitus. The increasing incidence of this metabolic disorder necessitates efficient strategies to produce functional β-cells for treating diabetes mellitus. Human induced pluripotent stem cells (hiPSC), holds potential for treating diabetes owning to their self-renewal capacity and ability to differentiate into β-cells. iPSC technology also provides unlimited starting material to generate differentiated cells for regenerative applications. Progress has also been made in establishing in-vitro culture protocols to yield definitive endoderm, pancreatic endoderm progenitor cells and β-cells via different reprogramming strategies and growth factor supplementation. However, these generated β-cells are still immature, lack functional characteristics and exhibit lower capability in reversing the diseases conditions. Current methods employed to generate mature and functional β-cells include; use of small and large molecules to enhance the reprogramming and differentiation efficiency, 3D culture systems to improve the functional properties and heterogeneity of differentiated cells. This review details recent advancements in the generation of mature β-cells by reprogramming stem cells into iPSCs that is further programmed to β-cells. It also provides deeper insight of current reprogramming protocols and their efficacy, focusing on the underlying mechanism of chemical based approach to generate iPSCs. Furthermore, we have highlighted the recent differentiation strategies both in-vitro and in-vivo to date and the future prospects in generation of mature β-cells. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  6. 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

  7. Nevoid basal cell carcinoma syndrome (Gorlin-Goltz syndrome

    Directory of Open Access Journals (Sweden)

    N K Kiran

    2012-01-01

    Full Text Available The Gorlin-Goltz syndrome, also known as nevoid basal cell carcinoma syndrome (NBCCS, is an infrequent multisystemic disease inherited in a dominant autosomal way, which shows a high level of penetrance and variable expressiveness. It is characterized by odontogenic keratocysts in the jaw, multiple basal cell nevi carcinomas and skeletal abnormalities. This syndrome may be diagnosed early by a dentist by routine radiographic exams in the first decade of life, since the odontogenic keratocysts are usually one of the first manifestations of the syndrome. This case report presents a patient diagnosed as NBCCS by clinical, radiographic and histological findings in a 13-year-old boy. This paper highlights the importance of early diagnosis of NBCCS which can help in preventive multidisciplinary approach to provide a better prognosis for the patient.

  8. Nevoid basal cell carcinoma syndrome (Gorlin-Goltz syndrome).

    Science.gov (United States)

    Kiran, N K; Tilak Raj, T N; Mukunda, K S; Rajashekar Reddy, V

    2012-10-01

    The Gorlin-Goltz syndrome, also known as nevoid basal cell carcinoma syndrome (NBCCS), is an infrequent multisystemic disease inherited in a dominant autosomal way, which shows a high level of penetrance and variable expressiveness. It is characterized by odontogenic keratocysts in the jaw, multiple basal cell nevi carcinomas and skeletal abnormalities. This syndrome may be diagnosed early by a dentist by routine radiographic exams in the first decade of life, since the odontogenic keratocysts are usually one of the first manifestations of the syndrome. This case report presents a patient diagnosed as NBCCS by clinical, radiographic and histological findings in a 13-year-old boy. This paper highlights the importance of early diagnosis of NBCCS which can help in preventive multidisciplinary approach to provide a better prognosis for the patient.

  9. 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.

  10. Identification of 5-hydroxytryptamine-producing cells by detection of fluorescence in paraffin-embedded tissue sections

    Directory of Open Access Journals (Sweden)

    Y. Kaneko

    2016-09-01

    Full Text Available 5-Hydroxytryptamine (5-HT produced by enterochromaffin (EC cells is an important enteric mucosal signaling ligand and has been implicated in several gastrointestinal diseases, including inflammatory bowel disease and functional disorders such as irritable bowel syndrome. The present study reports a new, simple and rapid visualization method of 5-HT-producing EC cells utilizing detection of autofluorescence in paraffin-embedded tissue sections after formalin fixation. In human samples, there was a high incidence of autofluorescence+ cells in the 5-HT+ cells in the pyloric, small intestinal and colonic glands, while co-localization was lacking between autofluorescence+ and gastrin+ cells in the pyloric and small intestinal glands. Autofluorescence+ EC cells were detected in the colon of mice and rats. Autofluorescence+ cells were also observed in 5-HT+ β cells in the pancreatic islets of Langerhans in pregnant mice, while non-pregnant mouse pancreatic islet cells showed no 5-HT immunoreactivity or autofluorescence. These results suggest that autofluorescence+ cells are identical to 5-HT+ cells, and the source of autofluorescence may be 5-HT itself or molecules related to its synthesis or degradation. This autofluorescence signal detection method may be applicable for monitoring of inflammatory status of inflammatory bowel diseases in both the experimental and clinical settings.

  11. 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.

  12. Generation of glucose-responsive functional islets with a three-dimensional structure from mouse fetal pancreatic cells and iPS cells in vitro.

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    Hiroki Saito

    Full Text Available Islets of Langerhans are a pancreatic endocrine compartment consisting of insulin-producing β cells together with several other hormone-producing cells. While some insulin-producing cells or immature pancreatic cells have been generated in vitro from ES and iPS cells, islets with proper functions and a three-dimensional (3D structure have never been successfully produced. To test whether islets can be formed in vitro, we first examined the potential of mouse fetal pancreatic cells. We found that E16.5 pancreatic cells, just before forming islets, were able to develop cell aggregates consisting of β cells surrounded by glucagon-producing α cells, a structure similar to murine adult islets. Moreover, the transplantation of these cells improved blood glucose levels in hyperglycemic mice. These results indicate that functional islets are formed in vitro from fetal pancreatic cells at a specific developmental stage. By adopting these culture conditions to the differentiation of mouse iPS cells, we developed a two-step system to generate islets, i.e. immature pancreatic cells were first produced from iPS cells, and then transferred to culture conditions that allowed the formation of islets from fetal pancreatic cells. The islets exhibited distinct 3D structural features similar to adult pancreatic islets and secreted insulin in response to glucose concentrations. Transplantation of the islets improved blood glucose levels in hyperglycemic mice. In conclusion, the two-step culture system allows the generation of functional islets with a 3D structure from iPS cells.

  13. Modulation of Female Genital Tract-Derived Dendritic Cell Migration and Activation in Response to Inflammatory Cytokines and Toll-Like Receptor Agonists.

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    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.

  14. Modulation of Female Genital Tract-Derived Dendritic Cell Migration and Activation in Response to Inflammatory Cytokines and Toll-Like Receptor Agonists.

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    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.

  15. 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.

  16. Protective immunity to UV radiation-induced skin tumours induced by skin grafts and epidermal cells

    International Nuclear Information System (INIS)

    Ronald Sluyter; Kylie S Yuen; Gary M Halliday

    2001-01-01

    There is little evidence that cutaneous dendritic cells (DC), including epidermal Langerhans cells (LC), can induce immunity to UV radiation (UVR)-induced skin tumours. Here, it is shown that cells within skin can induce protective antitumour immunity against a UVR-induced fibrosarcoma. Transplantation of the skin overlying subcutaneous tumours onto naive recipients could induce protective antitumour immunity, probably because the grafting stimulated the tumour Ag-loaded DC to migrate to local lymph nodes. This suggests that cutaneous APC can present tumour Ag to induce protective antitumour immunity. Previously, it has been shown that immunization of mice with MHC class II+ epidermal cells (EC) pulsed with tumour extracts could induce delayed-type hypersensitivity against tumour cells. Here, this same immunization protocol could induce protective immunity against a minimum tumorigenic dose of UVR-induced fibrosarcoma cells, but not higher doses. Epidermal cells obtained from semiallogeneic donors and pulsed with tumour extract could also induce protective immunity. However, presentation of BSA Ag from the culture medium was found to contribute to this result using semiallogeneic EC. The results suggest that LC overlying skin tumours may be able to induce protective immunity to UVR-induced tumours if stimulated to migrate from the skin. Copyright (2001) Australasian Society of Immunology Inc

  17. Oral dendritic cells mediate antigen-specific tolerance by stimulating TH1 and regulatory CD4+ T cells.

    Science.gov (United States)

    Mascarell, Laurent; Lombardi, Vincent; Louise, Anne; Saint-Lu, Nathalie; Chabre, Henri; Moussu, Hélène; Betbeder, Didier; Balazuc, Anne-Marie; Van Overtvelt, Laurence; Moingeon, Philippe

    2008-09-01

    A detailed characterization of oral antigen-presenting cells is critical to improve second-generation sublingual allergy vaccines. To characterize oral dendritic cells (DCs) within lingual and buccal tissues from BALB/c mice with respect to their surface phenotype, distribution, and capacity to polarize CD4(+) T-cell responses. In situ analysis of oral DCs was performed by immunohistology. Purified DCs were tested in vitro for their capacity to capture, process, and present the ovalbumin antigen to naive CD4(+) T cells. In vivo priming of ovalbumin-specific T cells adoptively transferred to BALB/c mice was analyzed by cytofluorometry in cervical lymph nodes after sublingual administration of mucoadhesive ovalbumin. Three subsets of oral DCs with a distinct tissue distribution were identified: (1) a minor subset of CD207(+) Langerhans cells located in the mucosa itself, (2) a major subpopulation of CD11b(+)CD11c(-) and CD11b(+)CD11c(+) myeloid DCs at the mucosal/submucosal interface, and (3) B220(+)120G8(+) plasmacytoid DCs found in submucosal tissues. Purified myeloid and plasmacytoid oral DCs capture and process the antigen efficiently and are programmed to elicit IFN-gamma and/or IL-10 production together with a suppressive function in naive CD4(+) T cells. Targeting the ovalbumin antigen to oral DCs in vivo by using mucoadhesive particles establishes tolerance in the absence of cell depletion through the stimulation of IFN-gamma and IL-10-producing CD4(+) regulatory T cells in cervical lymph nodes. The oral immune system is composed of various subsets of tolerogenic DCs organized in a compartmentalized manner and programmed to induce T(H)1/regulatory T-cell responses.

  18. The cytokine-dependent MUTZ-3 cell line as an in vitro model for the screening of contact sensitizers

    International Nuclear Information System (INIS)

    Azam, Philippe; Peiffer, Jean-Luc; Chamousset, Delphine; Tissier, Marie-Helene; Bonnet, Pierre-Antoine; Vian, Laurence; Fabre, Isabelle; Ourlin, Jean-Claude

    2006-01-01

    Langerhans cells (LC) are key mediators of contact allergenicity in the skin. However, no in vitro methods exist which are based on the activation process of LC to predict the sensitization potential of chemicals. In this study, we have evaluated the performances of MUTZ-3, a cytokine-dependent human monocytic cell line, in its response to sensitizers. First, we compared undifferentiated MUTZ-3 cells with several standard human cells such as THP-1, KG-1, HL-60, K-562, and U-937 in their response to the strong sensitizer DNCB and the irritant SDS by monitoring the expression levels of HLA-DR, CD54, and CD86 by flow cytometry. Only MUTZ-3 and THP-1 cells show a strong and specific response to sensitizer, while other cell lines showed very variable responses. Then, we tested MUTZ-3 cells against a wider panel of sensitizers and irritants on a broader spectrum of cell surface markers (HLA-DR, CD40, CD54, CD80, CD86, B7-H1, B7-H2, B7-DC). Of these markers, CD86 proved to be the most reliable since it detected all sensitizers, including benzocaine, a classical false negative in local lymph node assay (LLNA) but not irritants. We confirmed the MUTZ-3 response to DNCB by real-time PCR analysis. Taken together, our data suggest that undifferentiated MUTZ-3 cells may represent a valuable in vitro model for the screening of potential sensitizers

  19. Transplanted Human Umbilical Cord Mesenchymal Stem Cells Facilitate Lesion Repair in B6.Fas Mice

    Directory of Open Access Journals (Sweden)

    Guang-ping Ruan

    2014-01-01

    Full Text Available Background. Systemic lupus erythematosus (SLE is a multisystem disease that is characterized by the appearance of serum autoantibodies. No effective treatment for SLE currently exists. Methods. We used human umbilical cord mesenchymal stem cell (H-UC-MSC transplantation to treat B6.Fas mice. Results. After four rounds of cell transplantation, we observed a statistically significant decrease in the levels of mouse anti-nuclear, anti-histone, and anti-double-stranded DNA antibodies in transplanted mice compared with controls. The percentage of CD4+CD25+Foxp3+ T cells in mouse peripheral blood significantly increased after H-UC-MSC transplantation. Conclusions. The results showed that H-UC-MSCs could repair lesions in B6.Fas mice such that all of the relevant disease indicators in B6.Fas mice were restored to the levels observed in normal C57BL/6 mice.

  20. IgG4-related tubulointerstitial nephritis with plasma cell-rich renal arteritis.

    Science.gov (United States)

    Sharma, Shree G; Vlase, Horia L; D'Agati, Vivette D

    2013-04-01

    Immunoglobulin G4 (IgG4)-related tubulointerstitial nephritis is a newly recognized clinicopathologic entity that may occur as an isolated renal lesion or as part of a multisystem disorder. It is characterized by plasma cell-rich interstitial nephritis with abundant IgG4-positive plasma cells and IgG-dominant tubulointerstitial immune deposits. We report the first case of IgG4-related tubulointerstitial nephritis with multifocal plasma cell-rich renal arteritis presenting as acute kidney injury in a 72-year-old man. Seven weeks of prednisone therapy led to nearly complete recovery of kidney function. This case enlarges the morphologic spectrum of this disorder and emphasizes the need to distinguish it from other causes of renal vasculitis. Copyright © 2013 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  1. Multilayer network representation of membrane potential and cytosolic calcium concentration dynamics in beta cells

    International Nuclear Information System (INIS)

    Gosak, Marko; Dolenšek, Jurij; Markovič, Rene; Slak Rupnik, Marjan; Marhl, Marko; Stožer, Andraž

    2015-01-01

    Highlights: • Physiological processes within and among pancreatic beta cells are very complex. • We analyze the simultaneous recordings of membrane potential and calcium dynamics. • We represent the interaction patterns among beta cells as a multilayer network. • The nature of the intracellular dynamics is found to rely on the network structure. - Abstract: Modern theory of networks has been recognized as a very successful methodological concept for the description and analysis of complex systems. However, some complex systems are more complex than others. For instance, several real-life systems are constituted by interdependent subsystems and their elements are subjected to different types of interactions that can also change with time. Recently, the multilayer network formalism has been proposed as a general theoretical framework for the description and analysis of such multi-dimensional complex systems and is acquiring more and more prominence in terms of a new research direction. In the present study, we use this methodology for the description of functional connectivity patterns and signal propagation between pancreatic beta cells in an islet of Langerhans at the levels of membrane potential (MP) and cytosolic calcium concentration ([Ca"2"+]_c) dynamics to study the extent of overlap in the two networks and to clarify whether time lags between the two signals in individual cells are in any way dependent on the role these cells play in the functional networks. The two corresponding network layers are constructed on the basis of signal directions and pairwise correlations, whereas the interlayer connections represent the time lag between both measured signals. Our results confirm our previous finding that both MP and [Ca"2"+]_c change spread across an islet in the form of a depolarization and a [Ca"2"+]_c wave, respectively. Both types of waves follow nearly the same path and the networks in both layers have a similar but not entirely the same structure

  2. 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.

  3. Chemistry and biology of reactive species with special reference to the antioxidative defence status in pancreatic β-cells.

    Science.gov (United States)

    Lenzen, Sigurd

    2017-08-01

    Diabetes mellitus is a serious metabolic disease. Dysfunction and subsequent loss of the β-cells in the islets of Langerhans through apoptosis ultimately cause a life-threatening insulin deficiency. The underlying reason for the particular vulnerability of the β-cells is an extraordinary sensitivity to the toxicity of reactive oxygen and nitrogen species (ROS and RNS) due to its low antioxidative defense status. This review considers the different aspects of the chemistry and biology of the biologically most important reactive species and their chemico-biological interactions in the β-cell toxicity of proinflammatory cytokines in type 1 diabetes and of lipotoxicity in type 2 diabetes development. The weak antioxidative defense equipment in the different subcellular organelles makes the β-cells particularly vulnerable and prone to mitochondrial, peroxisomal and ER stress. Looking upon the enzyme deficiencies which are responsible for the low antioxidative defense status of the pancreatic β-cells it is the lack of enzymatic capacity for H 2 O 2 inactivation at all major subcellular sites. Diabetes is the most prevalent metabolic disorder with a steadily increasing incidence of both type 1 and type 2 diabetes worldwide. The weak protection of the pancreatic β-cells against oxidative stress is a major reason for their particular vulnerability. Thus, careful protection of the β-cells is required for prevention of the disease. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Endothelial cell study in a case of Werner′s syndrome undergoing phacoemulsification and Yettrium-Aluminum-Garnet laser capsulotomy

    Directory of Open Access Journals (Sweden)

    Vasudha Kemmanu

    2012-01-01

    Full Text Available Werner′s syndrome (WS is a rare autosomal recessive disorder with multisystem manifestations of premature aging from the second decade of life. Cataract is one of the features of WS. Cataract surgery is complicated with postoperative wound dehiscence and bullous keratopathy when the surgery is done by intracapsular or conventional extracapsular method. We report the short-term result of phacoemulsification and Neodymimum Yettrium-Aluminum-Garnet laser (Nd YAG capsulotomy in a case of WS with bilateral cataracts. Postoperatively and post capsulotomy, there was no change in the endothelial cell morphology. There was an 8.6% decrease in endothelial cell count at the end of 15 months postoperatively and 11 months post YAG capsulotomy. This decrease is within the acceptable range of cell loss after phacoemulsification and YAG capsulotomy. To the best of our knowledge, this is the first reported case of YAG laser capsulotomy in WS.

  5. From Lysosomal Storage Diseases to NKT Cell Activation and Back

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    Cátia S. Pereira

    2017-02-01

    Full Text Available Lysosomal storage diseases (LSDs are inherited metabolic disorders characterized by the accumulation of different types of substrates in the lysosome. With a multisystemic involvement, LSDs often present a very broad clinical spectrum. In many LSDs, alterations of the immune system were described. Special emphasis was given to Natural Killer T (NKT cells, a population of lipid-specific T cells that is activated by lipid antigens bound to CD1d (cluster of differentiation 1 d molecules at the surface of antigen-presenting cells. These cells have important functions in cancer, infection, and autoimmunity and were altered in a variety of LSDs’ mouse models. In some cases, the observed decrease was attributed to defects in either lipid antigen availability, trafficking, processing, or loading in CD1d. Here, we review the current knowledge about NKT cells in the context of LSDs, including the alterations detected, the proposed mechanisms to explain these defects, and the relevance of these findings for disease pathology. Furthermore, the effect of enzyme replacement therapy on NKT cells is also discussed.

  6. 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.

  7. Skin allografts in lethally irradiated animals repopulated with syngeneic hemopoietic cells

    International Nuclear Information System (INIS)

    Schwadron, R.B.

    1983-01-01

    Total body irradiation and repopulation with syngeneic hemopoietic cells can be used to induce tolerance to major histocompatibility complex (MHC) mismatched heart and kidney grafts in rats and mice. However, this protocol does not work for MHC mismatched skin grafts in rats or mice. Furthermore, LEW rats that accept WF cardiac allografts after irradiation and repopulation reject subsequent WF skin grafts. Treatment of skin allograft donors with methotrexate prior to grafting onto irradiated and reconstituted mice resulted in doubling of the mean survival time. Analysis of which antigens provoked skin graft rejection by irradiation and reconstituted animals revealed the importance of I region antigens. Cardiac allograft acceptance by irradiated and reconstituted animals is mediated by suppressor cells found in the spleen. Adoptively tolerant LEW rats accepted WF skin grafts in 50% of grafted animals. Analysis of this phenomenon revealed that the adoptive transfer procedure itself was important in achieving skin allograft acceptance by these animals. In general, it seems that the lack of ability of irradiated and reconstituted animals to accept fully MHC disparate skin grafts results from the inability of these animals to suppress lymph node effector cells against I region antigen seen on highly immunogenic allogeneic Langerhans cells in the skin

  8. Synergistic effects of dendritic cell targeting and laser-microporation on enhancing epicutaneous skin vaccination efficacy.

    Science.gov (United States)

    Machado, Yoan; Duinkerken, Sanne; Hoepflinger, Veronika; Mayr, Melissa; Korotchenko, Evgeniia; Kurtaj, Almedina; Pablos, Isabel; Steiner, Markus; Stoecklinger, Angelika; Lübbers, Joyce; Schmid, Maximillian; Ritter, Uwe; Scheiblhofer, Sandra; Ablinger, Michael; Wally, Verena; Hochmann, Sarah; Raninger, Anna M; Strunk, Dirk; van Kooyk, Yvette; Thalhamer, Josef; Weiss, Richard

    2017-11-28

    Due to its unique immunological properties, the skin is an attractive target tissue for allergen-specific immunotherapy. In our current work, we combined a dendritic cell targeting approach with epicutaneous immunization using an ablative fractional laser to generate defined micropores in the upper layers of the skin. By coupling the major birch pollen allergen Bet v 1 to mannan from S. cerevisiae via mild periodate oxidation we generated hypoallergenic Bet-mannan neoglycoconjugates, which efficiently targeted CD14 + dendritic cells and Langerhans cells in human skin explants. Mannan conjugation resulted in sustained release from the skin and retention in secondary lymphoid organs, whereas unconjugated antigen showed fast renal clearance. In a mouse model, Bet-mannan neoglycoconjugates applied via laser-microporated skin synergistically elicited potent humoral and cellular immune responses, superior to intradermal injection. The induced antibody responses displayed IgE-blocking capacity, highlighting the therapeutic potential of the approach. Moreover, application via micropores, but not by intradermal injection, resulted in a mixed TH1/TH17-biased immune response. Our data clearly show that applying mannan-neoglycoconjugates to an organ rich in dendritic cells using laser-microporation is superior to intradermal injection. Due to their low IgE binding capacity and biodegradability, mannan neoglycoconjugates therefore represent an attractive formulation for allergen-specific epicutaneous immunotherapy. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Visualizing pancreatic {beta}-cell mass with [{sup 11}C]DTBZ

    Energy Technology Data Exchange (ETDEWEB)

    Simpson, Norman Ray [Department of Radiology, Columbia University Medical School, New York, NY 10032 (United States); Souza, Fabiola [Department of Surgery, Columbia University Medical School, New York, NY 10032 (United States); Witkowski, Piotr [Department of Medicine, Columbia University Medical School, New York, NY 10032 (United States); Maffei, Antonella [Institute of Genetics and Biophysics ' Adriano Buzzati-Traverso' , CNR, Naples 80131 (Italy); Raffo, Anthony [Department of Surgery, Columbia University Medical School, New York, NY 10032 (United States); Herron, Alan [Center for Comparative Medicine and The Department of Pathology, Baylor College of Medicine, Houston, TX 77030 (United States); Kilbourn, Michael [Department of Radiology, University of Michigan, Ann Arbor, MI 48109-0638 (United States); Jurewicz, Agata [Department of Radiology, Columbia University Medical School, New York, NY 10032 (United States); Herold, Kevan [Department of Surgery, Columbia University Medical School, New York, NY 10032 (United States); Liu, Eric [Diabetes Branch, NIDDK, National Institutes of Health, Bethesda, MD 20854 (United States); Hardy, Mark Adam [Department of Medicine, Columbia University Medical School, New York, NY 10032 (United States); Van Heertum, Ronald [Department of Radiology, Columbia University Medical School, New York, NY 10032 (United States); Harris, Paul Emerson [Department of Surgery, Columbia University Medical School, New York, NY 10032 (United States)]. E-mail: peh1@columbia.edu

    2006-10-15

    {beta}-Cell mass (BCM) influences the total amount of insulin secreted, varies by individual and by the degree of insulin resistance, and is affected by physiologic and pathologic conditions. The islets of Langerhans, however, appear to have a reserve capacity of insulin secretion and, overall, assessments of insulin and blood glucose levels remain poor measures of BCM, {beta}-cell function and progression of diabetes. Thus, novel noninvasive determinations of BCM are needed to provide a quantitative endpoint for novel therapies of diabetes, islet regeneration and transplantation. Built on previous gene expression studies, we tested the hypothesis that the targeting of vesicular monoamine transporter 2 (VMAT2), which is expressed by {beta} cells, with [{sup 11}C]dihydrotetrabenazine ([{sup 11}C]DTBZ), a radioligand specific for VMAT2, and the use of positron emission tomography (PET) can provide a measure of BCM. In this report, we demonstrate decreased radioligand uptake within the pancreas of Lewis rats with streptozotocin-induced diabetes relative to their euglycemic historical controls. These studies suggest that quantitation of VMAT2 expression in {beta} cells with the use of [{sup 11}C]DTBZ and PET represents a method for noninvasive longitudinal estimates of changes in BCM that may be useful in the study and treatment of diabetes.

  10. Visualizing pancreatic β-cell mass with [11C]DTBZ

    International Nuclear Information System (INIS)

    Simpson, Norman Ray; Souza, Fabiola; Witkowski, Piotr; Maffei, Antonella; Raffo, Anthony; Herron, Alan; Kilbourn, Michael; Jurewicz, Agata; Herold, Kevan; Liu, Eric; Hardy, Mark Adam; Van Heertum, Ronald; Harris, Paul Emerson

    2006-01-01

    β-Cell mass (BCM) influences the total amount of insulin secreted, varies by individual and by the degree of insulin resistance, and is affected by physiologic and pathologic conditions. The islets of Langerhans, however, appear to have a reserve capacity of insulin secretion and, overall, assessments of insulin and blood glucose levels remain poor measures of BCM, β-cell function and progression of diabetes. Thus, novel noninvasive determinations of BCM are needed to provide a quantitative endpoint for novel therapies of diabetes, islet regeneration and transplantation. Built on previous gene expression studies, we tested the hypothesis that the targeting of vesicular monoamine transporter 2 (VMAT2), which is expressed by β cells, with [ 11 C]dihydrotetrabenazine ([ 11 C]DTBZ), a radioligand specific for VMAT2, and the use of positron emission tomography (PET) can provide a measure of BCM. In this report, we demonstrate decreased radioligand uptake within the pancreas of Lewis rats with streptozotocin-induced diabetes relative to their euglycemic historical controls. These studies suggest that quantitation of VMAT2 expression in β cells with the use of [ 11 C]DTBZ and PET represents a method for noninvasive longitudinal estimates of changes in BCM that may be useful in the study and treatment of diabetes

  11. E2-2 Dependent Plasmacytoid Dendritic Cells Control Autoimmune Diabetes.

    Directory of Open Access Journals (Sweden)

    Lisbeth Hansen

    Full Text Available Autoimmune diabetes is a consequence of immune-cell infiltration and destruction of pancreatic β-cells in the islets of Langerhans. We analyzed the cellular composition of the insulitic lesions in the autoimmune-prone non-obese diabetic (NOD mouse and observed a peak in recruitment of plasmacytoid dendritic cells (pDCs to NOD islets around 8-9 weeks of age. This peak coincides with increased spontaneous expression of type-1-IFN response genes and CpG1585 induced production of IFN-α from NOD islets. The transcription factor E2-2 is specifically required for the maturation of pDCs, and we show that knocking out E2-2 conditionally in CD11c+ cells leads to a reduced recruitment of pDCs to pancreatic islets and reduced CpG1585 induced production of IFN-α during insulitis. As a consequence, insulitis has a less aggressive expression profile of the Th1 cytokine IFN-γ and a markedly reduced diabetes incidence. Collectively, these observations demonstrate a disease-promoting role of E2-2 dependent pDCs in the pancreas during autoimmune diabetes in the NOD mouse.

  12. [Skin cell response after jellyfish sting].

    Science.gov (United States)

    Adamicová, Katarína; Výbohová, Desanka; Fetisovová, Želmíra; Nováková, Elena; Mellová, Yvetta

    2016-01-01

    Jellyfish burning is not commonly part of the professional finding in the central Europe health care laboratory. Holiday seaside tourism includes different and unusual presentations of diseases for our worklplaces. Sea water-sports and leisure is commonly connected with jellyfish burning and changes in the skin, that are not precisely described. Authors focused their research on detection of morphological and quantitative changes of some inflammatory cells in the skin biopsy of a 59-years-old woman ten days after a jellyfish stinging. Because of a comparison of findings the biopsy was performed in the skin with lesional and nonlesional skin. Both excisions of the skin were tested by imunohistochemical methods to detect CD68, CD163, CD30, CD4, CD3, CD8, CD20 a CD1a, to detect histiocytes, as well as several clones of lymphocytes and Langerhans cells (antigen presenting cells of skin), CD 117, toluidin blue and chloracetase esterase to detect mastocytes and neutrophils. Material was tested by immunofluorescent methods to detect IgA, IgM, IgG, C3, C4, albumin and fibrinogen. Representative view-fields were documented by microscope photocamera Leica DFC 420 C. Registered photos from both samples of the skin were processed by morphometrical analysis by the Vision Assistant software. A student t-test was used for statistical analysis of reached results. Mean values of individual found cells in the sample with lesion and without lesion were as follows: CD117 -2.64/0.37, CD68-6.86/1.63, CD163-3.13/2.23, CD30-1.36/0.02, CD4-3.51/0.32, CD8-8.22/0.50, CD3-10.69/0.66, CD20-0.56/0.66, CD1a-7.97/0.47 respectively. Generally mild elevation of eosinofils in lesional skin was detected. Increased values of tested cells seen in excision from lesional skin when compared with nonlesional ones were statistically significant in eight case at the level p = 0.033 to 0.001. A not statistically significant difference was found only in the group of CD163+ histiocytes. Authors detected numbers

  13. Changes in corneal epithelial layer inflammatory cells in aqueous tear-deficient dry eye.

    Science.gov (United States)

    Lin, Hui; Li, Wei; Dong, Nuo; Chen, Wensheng; Liu, Jing; Chen, Lelei; Yuan, Hongxia; Geng, Zhixin; Liu, Zuguo

    2010-01-01

    To investigate the morphology, distribution, and density of inflammatory cells in the corneal epithelium of aqueous tear-deficient dry eye. Thirty-two patients with non-Sjögren's syndrome (NSS) dry eye, 14 patients with Sjögren's syndrome (SS) dry eye, and 33 healthy volunteers were studied. In vivo laser scanning confocal microscopy was used to investigate both Langerhans cell (LCs) and leukocyte distribution and density in the peripheral and central corneal epithelium. LC morphology was also evaluated. Multifactor regression analysis assessed whether there is a correlation between clinical manifestations and inflammatory cell densities. LCs were present in both central (34.9 +/- 5.7 cells/mm(2)) and peripheral (90.7 +/- 8.2 cells/mm(2)) parts of the normal corneal epithelium. Moreover, LC density increased dramatically in the central corneal epithelium in patients with NSS (89.8 +/- 10.8 cells/mm(2)) and SS (127.9 +/- 23.7 cells/mm(2)). The ratio of LCs with obvious processes was much higher in patients with dry eye than in healthy volunteers. LC density also increased in peripheral corneal epithelium in patients with SS, but not in those with NSS. Leukocyte density in normal corneal epithelium was very low, whereas it increased in the central corneal epithelium (4.6 +/- 1.0 cells/mm(2)) in NSS and in both central (49.0 +/- 12.9 cells/mm(2)) and peripheral (84.2 +/- 36.8 cells/mm(2)) corneal epithelium in SS. Densities of LCs and leukocytes showed significant correlation with the severity found in clinical evaluation. The LC and leukocyte changes in the corneal epithelium suggest their involvement in aqueous tear-deficient dry eye pathophysiology. In vivo dynamic assessment of central corneal inflammatory cell density may serve as an indicator of dry eye severity and provide new insight for dry eye treatment.

  14. Synthetic antimicrobial and LPS-neutralising peptides suppress inflammatory and immune responses in skin cells and promote keratinocyte migration.

    Science.gov (United States)

    Pfalzgraff, Anja; Heinbockel, Lena; Su, Qi; Gutsmann, Thomas; Brandenburg, Klaus; Weindl, Günther

    2016-08-11

    The stagnation in the development of new antibiotics and the concomitant high increase of resistant bacteria emphasize the urgent need for new therapeutic options. Antimicrobial peptides are promising agents for the treatment of bacterial infections and recent studies indicate that Pep19-2.5, a synthetic anti-lipopolysaccharide (LPS) peptide (SALP), efficiently neutralises pathogenicity factors of Gram-negative (LPS) and Gram-positive (lipoprotein/-peptide, LP) bacteria and protects against sepsis. Here, we investigated the potential of Pep19-2.5 and the structurally related compound Pep19-4LF for their therapeutic application in bacterial skin infections. SALPs inhibited LP-induced phosphorylation of NF-κB p65 and p38 MAPK and reduced cytokine release and gene expression in primary human keratinocytes and dermal fibroblasts. In LPS-stimulated human monocyte-derived dendritic cells and Langerhans-like cells, the peptides blocked IL-6 secretion, downregulated expression of maturation markers and inhibited dendritic cell migration. Both SALPs showed a low cytotoxicity in all investigated cell types. Furthermore, SALPs markedly promoted cell migration via EGFR transactivation and ERK1/2 phosphorylation and accelerated artificial wound closure in keratinocytes. Peptide-induced keratinocyte migration was mediated by purinergic receptors and metalloproteases. In contrast, SALPs did not affect proliferation of keratinocytes. Conclusively, our data suggest a novel therapeutic target for the treatment of patients with acute and chronic skin infections.

  15. Detección de Mycoplasma suis en casos clínicos de síndrome del desmedro multisistémico posdestete en porcinos Detection of Mycoplasma suis in clinical cases with postweaning multisystemic wasting syndrome in swine

    Directory of Open Access Journals (Sweden)

    N. B. Pereyra

    2006-09-01

    Full Text Available Mycoplasma suis es un parásito obligado de los eritrocitos del cerdo. Produce anemia aguda o crónica y afecta a distintas categorías de animales. El síndrome del desmedro multisistémico posdestete (PMWS se considera causado por el circovirus porcino tipo 2 (PCV-2, aunque muchos aspectos de la patogenia del síndrome permanecen sin aclarar. Se manifiesta a través de retraso del crecimiento, anemia e ictericia en cerdos de 5 a 12 semanas de edad, en los que se produce una inmunosupresión que deriva en coinfecciones bacterianas. Se estudiaron tres granjas porcinas con sintomatología asociada a la presencia de estos dos agentes etiológicos. Se observaron formas compatibles con M. suis en extendidos de sangre y en lesiones histopatológicas indicativas de PMWS, en cortes de tejidos. Esta es la primera comunicación acerca de la asociación clínica entre las dos entidades mencionadas.Mycoplasma suis is a swine erythrocyte obligatory parasite. Its presence may result in chronic or acute anaemia in different pig categories. It is considered that the postweaning multisystemic wasting syndrome (PMWS is caused by porcine circovirus type 2, but some aspects of the pathogenesis remain unknown. PMWS signs are impaired weight gain, anaemia and jaundice in 5 to 12 week-old pigs that suffer from immunosuppression and bacterial co-infections. The pigs with signs of these diseases on three porcine farms were studied. Compatible M. suis forms in blood smears and typical PMWS lesions in tissue cuts were seen. This is the first communication of the clinical association between these two entities.

  16. 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.

  17. Characterization of dendritic cells subpopulations in skin and afferent lymph in the swine model.

    Directory of Open Access Journals (Sweden)

    Florian Marquet

    Full Text Available Transcutaneous delivery of vaccines to specific skin dendritic cells (DC subsets is foreseen as a promising strategy to induce strong and specific types of immune responses such as tolerance, cytotoxicity or humoral immunity. Because of striking histological similarities between human and pig skin, pig is recognized as the most suitable model to study the cutaneous delivery of medicine. Therefore improving the knowledge on swine skin DC subsets would be highly valuable to the skin vaccine field. In this study, we showed that pig skin DC comprise the classical epidermal langerhans cells (LC and dermal DC (DDC that could be divided in 3 subsets according to their phenotypes: (1 the CD163(neg/CD172a(neg, (2 the CD163(highCD172a(pos and (3 the CD163(lowCD172a(pos DDC. These subtypes have the capacity to migrate from skin to lymph node since we detected them in pseudo-afferent lymph. Extensive phenotyping with a set of markers suggested that the CD163(high DDC resemble the antibody response-inducing human skin DC/macrophages whereas the CD163(negCD172(low DDC share properties with the CD8(+ T cell response-inducing murine skin CD103(pos DC. This work, by showing similarities between human, mouse and swine skin DC, establishes pig as a model of choice for the development of transcutaneous immunisation strategies targeting DC.

  18. Effects of a new bifunctional psoralen, 4,4',5'-trimethylazapsoralen and ultraviolet-A radiation on murine dendritic epidermal cells.

    Science.gov (United States)

    Aubin, F; Alcalay, J; Dall'Acqua, F; Kripke, M L

    1990-06-01

    Although some psoralens are therapeutically active in the treatment of cutaneous hyperproliferative diseases when combined with UVA (320-400 nm) radiation, the toxic effects of these compounds have led physicians to seek new photochemotherapeutic agents. One such agent is 4,4',5'-trimethylazapsoralen (TMAP), a new bifunctional psoralen compound. We investigated the effects of repetitive treatments with TMAP plus UVA radiation on the number of dendritic immune cells in murine epidermis and on the induction of phototoxicity. Mice treated 3 times per week for 4 weeks with 129 microgram TMAP plus 10 kJ/m2 UVA radiation exhibited no gross or microscopic evidence of phototoxicity. During this treatment, the numbers of ATPase+, Ia+, and Thy-l+ dendritic epidermal cells were greatly reduced, and by the end of the treatment period, few dendritic immune cells could be detected. We conclude that morphological alterations of cutaneous immune cells can occur in the absence of overt phototoxicity, and that TMAP plus low-dose UVA radiation decreases the numbers of detectable Langerhans cells and Thy-1+ cells in murine skin.

  19. Chronic myelomonocytic leukemia masquerading as cutaneous indeterminate dendritic cell tumor: Expanding the spectrum of skin lesions in chronic myelomonocytic leukemia.

    Science.gov (United States)

    Loghavi, Sanam; Curry, Jonathan L; Garcia-Manero, Guillermo; Patel, Keyur P; Xu, Jie; Khoury, Joseph D; Torres-Cabala, Carlos A; Nagarajan, Priyadharsini; Aung, Phyu P; Gibson, Bernard R; Goodwin, Brandon P; Kelly, Brent C; Korivi, Brinda R; Medeiros, L Jeffrey; Prieto, Victor G; Kantarjian, Hagop M; Bueso-Ramos, Carlos E; Tetzlaff, Michael T

    2017-12-01

    Chronic myelomonocytic leukemia (CMML) is a hematopoietic stem cell neoplasm exhibiting both myelodysplastic and myeloproliferative features. Cutaneous involvement by CMML is critical to recognize as it typically is a harbinger of disease progression and an increased incidence of transformation to acute myeloid leukemia. Cutaneous lesions of CMML exhibit heterogeneous histopathologic features that can be challenging to recognize as CMML. We describe a 67-year-old man with a 3-year history of CMML who had been managed on single-agent azacitidine with stable disease before developing splenomegaly and acute onset skin lesions. Examination of these skin lesions revealed a dense infiltrate of histiocytic cells morphologically resembling Langerhans type cells (lacking frank histopathologic atypia), and with the immunophenotype of an indeterminate cell histiocytosis (S100+ CD1a+ and langerin-). Given the history of CMML, next-generation sequencing studies were performed on the skin biopsy. These revealed a KRAS (p.G12R) mutation identical to that seen in the CMML 3 years prior, establishing a clonal relationship between the 2 processes. This case expands the spectrum for and underscores the protean nature of cutaneous involvement by CMML and underscores the importance of heightened vigilance when evaluating skin lesions of CMML patients. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Lack of retinoic acid leads to increased langerin-expressing dendritic cells in gut-associated lymphoid tissues.

    Science.gov (United States)

    Chang, Sun-Young; Cha, Hye-Ran; Chang, Jae-Hoon; Ko, Hyun-Jeong; Yang, Hyungjun; Malissen, Bernard; Iwata, Makoto; Kweon, Mi-Na

    2010-04-01

    Retinoic acid (RA) is a crucial factor for maintaining homeostasis in the gut, including lymphocyte homing, immunoglobulin (Ig) A production, and T regulatory cells (Treg) and T helper cell 17 (T(H)17) generation. Until now, most attention has focused on the function of dendritic cells (DCs) to initiate adaptive immunity including T and B lymphocytes through RA. To investigate the effects of RA on DCs of gut-associated lymphoid tissue (GALT), we analyzed the phenotype and function of DC subsets from GALT of vitamin A-deficient (VAD) mice. VAD mice were prepared by feeding them a VAD diet over 12 weeks from gestational days 10-14. Here, we report that tremendous increase of langerin(+) DCs occurred in the mesenteric lymph nodes (MLNs) and gut lamina propria of VAD mice dependent on CCR7 signaling. Langerin(+) DCs have phenotypes more similar to those of bone marrow-derived dermal langerin(+) DCs than epidermal Langerhans cells. Moreover, RA receptor antagonists enhance the differentiation of langerin(+) DCs from mouse and human precursors of bone marrow and peripheral blood. Langerin(+) DCs were highly differentiated but less inflammatory than langerin(-) DCs of MLNs of VAD mice. Moreover, tolerance to orally delivered antigen was completely abrogated by depletion of langerin(+) DCs in the VAD mice. These results suggest that generation of langerin(+) DCs in the GALT is tightly regulated by RA and that the microenvironment of tissues determines the phenotype of DCs. 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.

  1. UV-induced transcription from the human immunodeficiency virus type 1 (HIV-1) long terminal repeat and UV-induced secretion of an extracellular factor that induces HIV-1 transcription in nonirradiated cells

    International Nuclear Information System (INIS)

    Stein, B.; Kraemer, M.R.; Rahmsdorf, H.J.; Ponta, H.; Herrlich, P.

    1989-01-01

    UV irradiation, but not visible sunlight, induces the transcription of human immunodeficiency virus type 1 (HIV-1). Chimeric constructs carrying all or parts of the HIV-1 long terminal repeat linked to an indicator gene were transfected into HeLa cells or murine and human T-cell lines, and their response to irradiation was tested. The cis-acting element conferring UV responsiveness is identical to the sequence binding transcription factor NF kappa B. UV irradiation enhances NF kappa B binding activity as assayed by gel retardation experiments. Interestingly, the requirement for UV irradiation can be replaced by cocultivation of transfected cells with UV-irradiated nontransfected (HIV-1-negative) cells. A UV-induced extracellular protein factor is detected in the culture medium conditioned by UV-treated cells. The factor is produced upon UV irradiation by several murine and human cell lines, including HeLa, Molt-4, and Jurkat, and acts on several cells. These data suggest that the UV response of keratinocytes in human skin can be magnified and spread to deeper layers that are more shielded, including the Langerhans cells, and that this indirect UV response may contribute to the activation of HIV-1 in humans

  2. Current advanced therapy cell-based medicinal products for type-1-diabetes treatment.

    Science.gov (United States)

    Cañibano-Hernández, Alberto; Del Burgo, Laura Sáenz; Espona-Noguera, Albert; Ciriza, Jesús; Pedraz, Jose Luis

    2018-03-27

    In the XXI century diabetes mellitus has become one of the main threats to human health with higher incidence in regions such as Europe and North America. Type 1 diabetes mellitus (T1DM) occurs as a consequence of the immune-mediated destruction of insulin producing β-cells located in the endocrine part of the pancreas, the islets of Langerhans. The administration of exogenous insulin through daily injections is the most prominent treatment for T1DM but its administration is frequently associated to failure in glucose metabolism control, finally leading to hyperglycemia episodes. Other approaches have been developed in the past decades, such as whole pancreas and islet allotransplantation, but they are restricted to patients who exhibit frequent episodes of hypoglycemia or renal failure because the lack of donors and islet survival. Moreover, patients transplanted with either whole pancreas or islets require of immune suppression to avoid the rejection of the transplant. Currently, advanced therapy medicinal products (ATMP), such as implantable devices, have been developed in order to reduce immune rejection response while increasing cell survival. To overcome these issues, ATMPs must promote vascularization, guaranteeing the nutritional contribution, while providing O 2 until vasculature can surround the device. Moreover, it should help in the immune-protection to avoid acute and chronic rejection. The transplanted cells or islets should be embedded within biomaterials with tunable properties like injectability, stiffness and porosity mimicking natural ECM structural characteristics. And finally, an infinitive cell source that solves the donor scarcity should be found such as insulin producing cells derived from mesenchymal stem cells (MSCs), embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). Several companies have registered their ATMPs and future studies envision new prototypes. In this review, we will discuss the mechanisms and etiology of

  3. Abnormalities in iNKT cells are associated with impaired ability of monocytes to produce IL-10 and suppress T-cell proliferation in sarcoidosis.

    Science.gov (United States)

    Crawshaw, Anjali; Kendrick, Yvonne R; McMichael, Andrew J; Ho, Ling-Pei

    2014-07-01

    Sarcoidosis is a multisystem granulomatous disorder characterized by marked T-cell expansion of T helper 1 (Th1) cells. The cause of T-cell overactivity is unknown. We hypothesized that interleukin-10 (IL-10) production by a yet undefined cell type might be defective, resulting in loss of regulation of T-cell activity. Focusing on IL-10-producing monocytes, we first showed that monocytes isolated from the peripheral blood of corticosteroid-naïve sarcoidosis patients (n = 51) produced less IL-10 compared to controls, and were less able to suppress T-cell proliferation. In addition, monocytic IL-10 production correlated negatively with disease activity score. As invariant natural killer T (iNKT) cells are known to both interact with monocytes and be reduced in sarcoidosis patients, we then asked whether iNKT-specific defects might be responsible for this reduced IL-10 production. We found that greater numbers of circulating iNKT cells was associated with higher IL-10 production. Moreover, iNKT cells enhanced monocytic IL-10 production in vitro. Defective IL-10 production and T-cell suppression by sarcoidosis monocytes could be restored following their coculture with iNKT cells, in a CD1d- and cell contact-dependent process. We suggest that reduced iNKT-cell numbers in sarcoidosis may lead to impaired monocytic IL-10 production and unchecked T-cell expansion in sarcoidosis. These findings provide fresh insight into the mechanism of sarcoidosis disease, and interaction between iNKT cells and monocytes. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Genetics Home Reference: neonatal onset multisystem inflammatory disease

    Science.gov (United States)

    ... Nowak M, Mallah M, Chae JJ, Watford WT, Hofmann SR, Stein L, Russo R, Goldsmith D, Dent ... Review. Citation on PubMed Dollfus H, Häfner R, Hofmann HM, Russo RA, Denda L, Gonzales LD, DeCunto ...

  5. Modifiers and mechanisms of multi-system polyglutamine ...

    Indian Academy of Sciences (India)

    case of polyQ repeat disorders such as HD (reviewed in Lutz. 2007). The different .... saccades, h ypertrophic cardiomyopath y, diabetes mellitus. Campuzano et al . (1996), ...... serine–threonine kinase Akt which phosphorylates mutant huntingtin at ...... systematic analysis of human disease-associated gene sequences.

  6. Alcoholism: A Multi-Systemic Cellular Insult to Organs

    Directory of Open Access Journals (Sweden)

    Ucee Dguzeh

    2018-05-01

    Full Text Available Alcohol abuse can affect more than the heart and the liver. Many observers often do not appreciate the complex and differing aspects of alcohol’s effects in pathophysiologies that have been reported in multiple organs. Chronic alcohol abuse is known to be associated with pathophysiological changes that often result in life-threatening clinical outcomes, e.g., breast and colon cancer, pancreatic disease, cirrhosis of the liver, diabetes, osteoporosis, arthritis, kidney disease, immune system dysfunction, hypertension, coronary artery disease, cardiomyopathy, and can be as far-reaching as to cause central nervous system disorders. In this review article, we will discuss the various organs impacted by alcohol abuse. The lack of clear guidelines on the amount and frequency of alcohol intake, complicated by personal demographics, make extrapolations to real-life practices at best difficult for public health policy-makers.

  7. Multisystemic Organ Involvement by an Inflammatory Pseudotumor: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Woo Jeong; Kwon, Hee Jin; Cho, Jin Han; Oh, Jong Yeong; Nam, Kyung Jin; Ha, Dong Ho [Dept. of Radiology, Dong A University College of Medicine, Pusan (Korea, Republic of)

    2011-07-15

    Inflammatory pseudotumors are benign soft tissue tumors that in rare cases can also manifest in multiple organs. We report here on the radiologic findings of a case of inflammatory pseudotomor mimicking malignant lymphoma involving the liver, pancreas, common bile duct, kidney, renal pelvis and lymph nodes of the abdomen and mediastinum, as well as the bronchus in an adult.

  8. Treatment of Conduct Disorder with a Multisystemic and Multimodal Approach

    Science.gov (United States)

    Ubinger, Nicole

    2006-01-01

    Conduct disorder is a childhood disorder that is often resistant to treatment. Current treatment methods often focus on separate interventions for each environment that the child or adolescent is exhibiting antisocial behavior. Additionally the focus is on the behavior of the child and often does not focus on the family unit or the biology behind…

  9. Multisystem involvement of alveolar echinococcosis in a child.

    Science.gov (United States)

    Kantarci, Mecit; Bayraktutan, Ummugulsum; Pirimoglu, Berhan; Ogul, Hayri; Oral, Akgun; Eren, Suat; Gundogdu, Betul

    2014-11-13

    Alveolar echinococcosis (AE) is a chronic progressive infestation inducing a slowly progressing, life-threatening tumor-like growth in the liver. It may spread to other organs by regional extension or hematogenous or lymphatic metastasis. Herein, we report a fifteen-year-old patient diagnosed with AE of the liver and simultaneous lung and brain metastasis with a literature review.

  10. Design of a multisystem remote maintenance control room

    International Nuclear Information System (INIS)

    Draper, J.V.; Handel, S.J.; Kring, C.T.; Kawatsuma, S.

    1988-01-01

    The Remote Systems Development Section of the Consolidated Fuel Reprocessing Program at the Oak Ridge National Laboratory (ORNL) and Japan's Power Reactor and Nuclear Fuel Development Corporation (PNC) recently collaborated in the development of a control room concept for remote operations. This report describes design methods and the resulting control room concept. The design project included five stages. The first was compilation of a complete function list; functions are tasks performed by operators in the control room while operating equipment located in the remote area. The second step was organization of the function list into ''function groups;'' function groups are sets of functions that operate one piece of equipment. The third stage was determination of crew size and requirements for supervision. The fourth stage was development of conceptual designs of displays and controls. The fifth stage was development of plans for placement of crew stations within the control room. 5 figs., 1 tab

  11. Discovery of molecular pathways mediating 1,25-dihydroxyvitamin D3 protection against cytokine-induced inflammation and damage of human and male mouse islets of Langerhans

    DEFF Research Database (Denmark)

    Wolden-Kirk, Heidi; Rondas, D; Bugliani, M

    2014-01-01

    Protection against insulitis and diabetes by active vitamin D, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), in nonobese diabetic mice has until now mainly been attributed to its immunomodulatory effects, but also protective effects of this hormone on inflammation-induced β-cell death have been reporte...

  12. A unique dermal dendritic cell subset that skews the immune response toward Th2.

    Directory of Open Access Journals (Sweden)

    Ryuichi Murakami

    Full Text Available Dendritic cell (DC subsets in the skin and draining lymph nodes (LNs are likely to elicit distinct immune response types. In skin and skin-draining LNs, a dermal DC subset expressing macrophage galactose-type C-type lectin 2 (MGL2/CD301b was found distinct from migratory Langerhans cells (LCs or CD103(+ dermal DCs (dDCs. Lower expression levels of Th1-promoting and/or cross-presentation-related molecules were suggested by the transcriptome analysis and verified by the quantitative real-time PCR analysis in MGL2(+ dDCs than in CD103(+ dDCs. Transfer of MGL2(+ dDCs but not CD103(+ dDCs from FITC-sensitized mice induced a Th2-type immune response in vivo in a model of contact hypersensitivity. Targeting MGL2(+ dDCs with a rat monoclonal antibody against MGL2 efficiently induced a humoral immune response with Th2-type properties, as determined by the antibody subclass. We propose that the properties of MGL2(+ dDCs, are complementary to those of CD103(+ dDCs and skew the immune response toward a Th2-type response.

  13. Langerin+ dermal dendritic cells are critical for CD8+ T cell activation and IgH γ-1 class switching in response to gene gun vaccines.

    Science.gov (United States)

    Stoecklinger, Angelika; Eticha, Tekalign D; Mesdaghi, Mehrnaz; Kissenpfennig, Adrien; Malissen, Bernard; Thalhamer, Josef; Hammerl, Peter

    2011-02-01

    The C-type lectin langerin/CD207 was originally discovered as a specific marker for epidermal Langerhans cells (LC). Recently, additional and distinct subsets of langerin(+) dendritic cells (DC) have been identified in lymph nodes and peripheral tissues of mice. Although the role of LC for immune activation or modulation is now being discussed controversially, other langerin(+) DC appear crucial for protective immunity in a growing set of infection and vaccination models. In knock-in mice that express the human diphtheria toxin receptor under control of the langerin promoter, injection of diphtheria toxin ablates LC for several weeks whereas other langerin(+) DC subsets are replenished within just a few days. Thus, by careful timing of diphtheria toxin injections selective states of deficiency in either LC only or all langerin(+) cells can be established. Taking advantage of this system, we found that, unlike selective LC deficiency, ablation of all langerin(+) DC abrogated the activation of IFN-γ-producing and cytolytic CD8(+) T cells after gene gun vaccination. Moreover, we identified migratory langerin(+) dermal DC as the subset that directly activated CD8(+) T cells in lymph nodes. Langerin(+) DC were also critical for IgG1 but not IgG2a Ab induction, suggesting differential polarization of CD4(+) T helper cells by langerin(+) or langerin-negative DC, respectively. In contrast, protein vaccines administered with various adjuvants induced IgG1 independently of langerin(+) DC. Taken together, these findings reflect a highly specialized division of labor between different DC subsets both with respect to Ag encounter as well as downstream processes of immune activation.

  14. Epithelium Expressing the E7 Oncoprotein of HPV16 Attracts Immune-Modulatory Dendritic Cells to the Skin and Suppresses Their Antigen-Processing Capacity.

    Directory of Open Access Journals (Sweden)

    Janin Chandra

    Full Text Available Antigen presenting cells (APCs in skin can promote either antigen-specific effector functions or antigen tolerance, and thus determine clearance or persistence of cutaneous viral infections. Human papillomavirus (HPV infections can persist in squamous epithelium in immunocompetent individuals, and some persisting HPV infections, particularly with HPV16, promote malignant epithelial transformation. Here, we investigate whether local expression of the HPV16 protein most associated with malignant transformation, HPV16-E7, affects the phenotype and function of APC subsets in the skin. We demonstrate an expanded population of Langerhans cells in HPV16-E7 transgenic skin with distinct cell surface markers which express immune-modulatory enzymes and cytokines not expressed by cells from non transgenic skin. Furthermore, HPV16-E7 transgene expression in keratinocytes attracts new APC subsets to the epidermis. In vivo migration and transport of antigen to the draining lymph node by these APCs is markedly enhanced in HPV16-E7 expressing skin, whereas antigen-processing, as measured by proteolytic cleavage of DQ-OVA and activation of T cells in vivo by APCs, is significantly impaired. These data suggest that local expression of HPV16-E7 in keratinocytes can contribute to persisting infection with this oncogenic virus, by altering the phenotype and function of local APCs.

  15. Preventive effect of Dioscorea japonica on squamous cell carcinoma of mouse skin involving down-regulation of prostaglandin E2 synthetic pathway.

    Science.gov (United States)

    Tsukayama, Izumi; Toda, Keisuke; Takeda, Yasunori; Mega, Takuto; Tanaka, Mitsuki; Kawakami, Yuki; Takahashi, Yoshitaka; Kimoto, Masumi; Yamamoto, Kei; Miki, Yoshimi; Murakami, Makoto; Suzuki-Yamamoto, Toshiko

    2018-03-01

    Hyperproduced prostaglandin E 2 by cyclooxygenase-2 and microsomal prostaglandin E synthase-1 evokes several pathophysiological responses such as inflammation and carcinogenesis. Our recent study demonstrated that Dioscorea japonica extract suppressed the expression of cyclooxygenase-2 and microsomal prostaglandin E synthase-1 and induced apoptosis in lung carcinoma A549 cells. In the present study, we investigated the effects of Dioscorea japonica on squamous cell carcinoma of mouse skin. Dioscorea japonica feeding and Dioscorea japonica extract topical application suppressed the expression of cyclooxygenase-2, microsomal prostaglandin E synthase-1, interleukin-1β and interleukin-6 and inhibited tumor formation, hyperplasia and inflammatory cell infiltration. Immunohistochemical analyses showed the immunoreactivities of cyclooxygenase-2 and microsomal prostaglandin E synthase-1 in tumor keratinocytes and stronger immunoreactivities of cyclooxygenase-2 and hematopoietic prostaglandin D synthase in epidermal dendritic cells (Langerhans cells). Treatment with Dioscorea japonica decreased the immunoreactivity of cyclooxygenase-2 and microsomal prostaglandin E synthase-1. These results indicate that Dioscorea japonica may have inhibitory effects on inflammation and carcinogenesis via suppression of the prostaglandin E 2 synthetic pathway.

  16. In vivo and in vitro evaluation of the effects of Urtica dioica and swimming activity on diabetic factors and pancreatic beta cells.

    Science.gov (United States)

    Ranjbari, Abbas; Azarbayjani, Mohammad Ali; Yusof, Ashril; Halim Mokhtar, Abdul; Akbarzadeh, Samad; Ibrahim, Mohamed Yousif; Tarverdizadeh, Bahman; Farzadinia, Parviz; Hajiaghaee, Reza; Dehghan, Firouzeh

    2016-03-15

    Urtica dioica (UD) has been identified as a traditional herbal medicine. This study aimed to investigate the effect of UD extract and swimming activity on diabetic parameters through in vivo and in vitro experiments. Adult WKY male rats were randomly distributed in nine groups: intact control, diabetic control, diabetic + 625 mg/kg, 1.25 g/kg UD, diabetic + 100 mg/kg Metformin, diabetic + swimming, diabetic + swimming 625 mg/kg, 1.25 g/kg UD, and diabetic +100 mg/kg Metformin + swimming. The hearts of the animals were punctured, and blood samples were collected for biochemical analysis. The entire pancreas was exposed for histologic examination. The effect of UD on insulin secretion by RIN-5F cells in 6.25 or 12.5 mM glucose dose was examined. Glucose uptake by cultured L6 myotubes was determined. The serum glucose concentration decreased, the insulin resistance and insulin sensitivity significantly increased in treated groups. These changes were more pronounced in the group that received UD extract and swimming training. Regeneration and less beta cell damage of Langerhans islets were observed in the treated groups. UD treatment increased insulin secretion in the RIN-5F cells and glucose uptake in the L6 myotubes cells. Swimming exercises accompanied by consuming UD aqueous extracts effectively improved diabetic parameters, repaired pancreatic tissues in streptozotocin-induced diabetics in vivo, and increased glucose uptake or insulin in UD-treated cells in vitro.

  17. Targeting BCL2 Family in Human Myeloid Dendritic Cells: A Challenge to Cure Diseases with Chronic Inflammations Associated with Bone Loss

    Directory of Open Access Journals (Sweden)

    Selma Olsson Åkefeldt

    2013-01-01

    Full Text Available Rheumatoid arthritis (RA and Langerhans cell histiocytosis (LCH are common and rare diseases, respectively. They associate myeloid cell recruitment and survival in inflammatory conditions with tissue destruction and bone resorption. Manipulating dendritic cell (DC, and, especially, regulating their half-life and fusion, is a challenge. Indeed, these myeloid cells display pathogenic roles in both diseases and may be an important source of precursors for differentiation of osteoclasts, the bone-resorbing multinucleated giant cells. We have recently documented that the proinflammatory cytokine IL-17A regulates long-term survival of DC by inducing BCL2A1 expression, in addition to the constitutive MCL1 expression. We summarize bibliography of the BCL2 family members and their therapeutic targeting, with a special emphasis on MCL1 and BCL2A1, discussing their potential impact on RA and LCH. Our recent knowledge in the survival pathway, which is activated to perform DC fusion in the presence of IL-17A, suggests that targeting MCL1 and BCL2A1 in infiltrating DC may affect the clinical outcomes in RA and LCH. The development of new therapies, interfering with MCL1 and BCL2A1 expression, to target long-term surviving inflammatory DC should be translated into preclinical studies with the aim to increase the well-being of patients with RA and LCH.

  18. MGL2 Dermal dendritic cells are sufficient to initiate contact hypersensitivity in vivo.

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    Yosuke Kumamoto

    Full Text Available Dendritic cells (DCs are the most potent antigen-presenting cells in the mammalian immune system. In the skin, epidermal Langerhans cells (LCs and dermal dendritic cells (DDCs survey for invasive pathogens and present antigens to T cells after migration to the cutaneous lymph nodes (LNs. So far, functional and phenotypic differences between these two DC subsets remain unclear due to lack of markers to identify DDCs.In the present report, we demonstrated that macrophage galactose-type C-type lectin (MGL 2 was exclusively expressed in the DDC subset in the skin-to-LN immune system. In the skin, MGL2 was expressed on the majority (about 88% of MHCII(+CD11c(+ cells in the dermis. In the cutaneous LN, MGL2 expression was restricted to B220(-CD8alpha(loCD11b(+CD11c(+MHCII(hi tissue-derived DC. MGL2(+DDC migrated from the dermis into the draining LNs within 24 h after skin sensitization with FITC. Distinct from LCs, MGL2(+DDCs localized near the high endothelial venules in the outer T cell cortex. In FITC-induced contact hypersensitivity (CHS, adoptive transfer of FITC(+MGL2(+DDCs, but not FITC(+MGL2(-DCs into naive mice resulted in the induction of FITC-specific ear swelling, indicating that DDCs played a key role in initiation of immune responses in the skin.These results demonstrated the availability of MGL2 as a novel marker for DDCs and suggested the contribution of MGL2(+ DDCs for initiating CHS.

  19. Transcriptional dysregulation in NIPBL and cohesin mutant human cells.

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    Jinglan Liu

    2009-05-01

    Full Text Available Cohesin regulates sister chromatid cohesion during the mitotic cell cycle with Nipped-B-Like (NIPBL facilitating its loading and unloading. In addition to this canonical role, cohesin has also been demonstrated to play a critical role in regulation of gene expression in nondividing cells. Heterozygous mutations in the cohesin regulator NIPBL or cohesin structural components SMC1A and SMC3 result in the multisystem developmental disorder Cornelia de Lange Syndrome (CdLS. Genome-wide assessment of transcription in 16 mutant cell lines from severely affected CdLS probands has identified a unique profile of dysregulated gene expression that was validated in an additional 101 samples and correlates with phenotypic severity. This profile could serve as a diagnostic and classification tool. Cohesin binding analysis demonstrates a preference for intergenic regions suggesting a cis-regulatory function mimicking that of a boundary/insulator interacting protein. However, the binding sites are enriched within the promoter regions of the dysregulated genes and are significantly decreased in CdLS proband, indicating an alternative role of cohesin as a transcription factor.

  20. A rare case of sarcoid-like reaction of lymph nodes associated with squamous cell carcinoma of alveolar mucosa

    Directory of Open Access Journals (Sweden)

    Nag Shweta

    2009-01-01

    Full Text Available Non-necrotizing granulomas are occasionally seen in patients with certain malignant disorders and are termed as "sarcoid-like reaction," which have many similarities with sarcoidosis. Sarcoidosis is a multisystem granulomatous disease of unknown etiology characterized by organ involvement and interference of organ function by granuloma or fibrosis. Sarcoidosis is occasionally found in a variety of malignant diseases with an overall incidence of 4.4% in carcinoma patients. We present here a rare case of moderately differentiated squamous cell carcinoma of alveolar mucosa with regard to mandible associated with sarcoid-like reaction of cervical lymph nodes in a female patient in the absence of clinical evidence of systemic sarcoidosis. The relevant literature including pathogenesis is also discussed.

  1. 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

  2. Recent Insights in Islet Amyloid Polypeptide-Induced Membrane Disruption and Its Role in β-Cell Death in Type 2 Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Lucie Khemtémourian

    2008-01-01

    Full Text Available The presence of fibrillar protein deposits (amyloid of human islet amyloid polypeptide (hIAPP in the pancreatic islets of Langerhans is thought to be related to death of the insulin-producing islet β-cells in type 2 diabetes mellitus (DM2. The mechanism of hIAPP-induced β-cell death is not understood. However, there is growing evidence that hIAPP-induced disruption of β-cell membranes is the cause of hIAPP cytotoxicity. Amyloid cytotoxicity by membrane damage has not only been suggested for hIAPP, but also for peptides and proteins related to other misfolding diseases, like Alzheimer’s disease, Parkinson’s disease, and prion diseases. Here we review the interaction of hIAPP with membranes, and discuss recent progress in the field, with a focus on hIAPP structure and on the proposed mechanisms of hIAPP-induced membrane damage in relation to β-cell death in DM2.

  3. The relationship between CD86/CD54 expression and THP-1 cell viability in an in vitro skin sensitization test--human cell line activation test (h-CLAT).

    Science.gov (United States)

    Sakaguchi, Hitoshi; Ashikaga, Takao; Miyazawa, Masaaki; Kosaka, Nanae; Ito, Yuichi; Yoneyama, Katsurako; Sono, Sakiko; Itagaki, Hiroshi; Toyoda, Hidekazu; Suzuki, Hiroyuki

    2009-04-01

    Recent regulations for cosmetics in Europe prohibit animal testing for evaluating the sensitization potential of chemicals to improve animal welfare. Yet, there is not an acceptable Organization for Economic Co-operation and Development non-animal skin sensitization test method. Several in vitro skin sensitization methods that focus on the activation of Langerhans cells, including human cell lines, are being evaluated as possible alternatives. In our previous study, we optimized our human cell line activation test (h-CLAT) using THP-1 cells (monocytic leukemia cell line) and conducted an inter-laboratory study. We found that measuring CD86/CD54 expression may be useful for predicting skin sensitization. The aim of this study was to confirm the relationship between CD86/CD54 expression and THP-1 cell viability in the h-CLAT. In this study, 21 allergens (e.g., dinitrochlorobenzene, p-phenylenediamine, Ni) and 8 non-allergens (e.g., SLS, lactic acid) were evaluated. For each chemical, more than 10 concentrations that gave a predicted cell viability range of 20-95% were used. The data showed that expression patterns of CD86/CD54 differed depending on chemical. For most allergens, cytotoxicity (65-90% cell viability) was needed for enhancement of CD86/CD54 expression. The criteria of "CD86 > or = 150 or CD54 > or = 200" resulted in an accuracy of 93%, which confirms appropriate cut-off criteria for h-CLAT. Furthermore, a good correlation was observed between EC3 of local lymph node assay and EC150(CD86) or EC200(CD54) of h-CLAT (12 or 16 chemicals, respectively), which would provide a useful estimate of allergic potency. These findings suggest that h-CLAT would be a good robust in vitro skin sensitization test.

  4. Generation of insulin-producing cells from rat mesenchymal stem cells using an aminopyrrole derivative XW4.4.

    Science.gov (United States)

    Ouyang, Jingfeng; Huang, Wei; Yu, Wanwan; Xiong, Wei; Mula, Ramanjaneya V R; Zou, Hongbin; Yu, Yongping

    2014-02-05

    Type 1 diabetes mellitus (T1DM), a multisystem disease with both biochemical and anatomical/structural consequences, is a major health concern worldwide. Pancreatic islet transplantation provides a promising treatment for T1DM. However, the limited availability of islet tissue or new sources of insulin producing cells (IPCs) that are responsive to glucose hinder this promising approach. Though slow, the development of pancreatic beta-cell lines from rodent or human origin has been steadily progressing. Bone marrow-derived mesenchymal stem cells (MSCs) are multipotent, culture-expanded, non-hematopoietic cells that are currently being investigated as a novel cellular therapy. The in vitro differentiation potential of IPCs has raised hopes for a treatment of clinical diseases associated with autoimmunity. We screened for small molecules that induce pancreatic differentiation of IPCs. There are some compounds which showed positive effects on the DTZ staining. The aminopyrrole derivative compound XW4.4 which shows the best activity among them was found to induce pancreatic differentiation of rat MSCs (rMSCs). The in vitro studies indicated that treatment of rMSCs with compound XW4.4 resulted in differentiated cells with characteristics of IPCs including islet-like clusters, spherical, grape-like morphology, insulin secretion, positive for dithizone, glucose stimulation and expression of pancreatic endocrine cell marker genes. The data has also suggested that hepatocyte nuclear factor 3β (HNF 3β) may be involved in pancreatic differentiation of rMSCs when treated with XW4.4. Results indicate that XW4.4 induced rMSCs support the efforts to derive functional IPCs and serve as a means to alleviate limitations surrounding islet cell transplantation in the treatment of T1DM. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  5. Inhibition of the Inflammasome NLRP3 by Arglabin Attenuates Inflammation, Protects Pancreatic β-Cells from Apoptosis, and Prevents Type 2 Diabetes Mellitus Development in ApoE2Ki Mice on a Chronic High-Fat Diet.

    Science.gov (United States)

    Abderrazak, Amna; El Hadri, Khadija; Bosc, Elodie; Blondeau, Bertrand; Slimane, Mohamed-Naceur; Büchele, Berthold; Simmet, Thomas; Couchie, Dominique; Rouis, Mustapha

    2016-06-01

    Intraperitoneal injection of arglabin (2.5 ng/g of body weight, twice daily, 13 weeks) into female human apolipoprotein E2 gene knock-in (ApoE2Ki) mice fed a high-fat Western-type diet (HFD) reduced plasma levels of glucose and insulin by ∼20.0% ± 3.5% and by 50.0% ± 2.0%, respectively, in comparison with vehicle-treated mice. Immunohistochemical analysis revealed the absence of active caspase-3 in islet sections from ApoE2Ki mice fed a HFD and treated with arglabin. In addition, arglabin reduced interleukin-1β (IL-1β) production in a concentration-dependent manner in Langerhans islets isolated from ApoE2Ki mice treated with lipopolysaccharide (LPS) and with cholesterol crystals. This inhibitory effect is specific for the inflammasome NOD-like receptor family, pyrin domain-containing 3 (NLRP3) because IL-1β production was abolished in Langerhans islets isolated from Nlrp3(-/-) mice. In the insulin-secreting INS-1 cells, arglabin inhibited, in a concentration-dependent manner, the maturation of pro-IL-1β into biologically active IL-1β probably through the inhibition of the maturation of procaspase-1 into active capsase-1. Moreover, arglabin reduced the susceptibility of INS-1 cells to apoptosis by increasing Bcl-2 levels. Similarly, autophagy activation by rapamycin decreased apoptosis susceptibility while autophagy inhibition by 3-methyladenin treatment promoted apoptosis. Arglabin further increased the expression of the autophagic markers Bcl2-interacting protein (Beclin-1) and microtubule-associated protein 1 light chain 3 II (LC3-II) in a concentration-dependent manner. Thus, arglabin reduces NLRP3-dependent inflammation as well as apoptosis in pancreatic β-cells in vivo and in the INS-1 cell line in vitro, whereas it increases autophagy in cultured INS-1 cells, indicating survival-promoting properties of the compound in these cells. Hence, arglabin may represent a new promising compound to treat inflammation and type 2 diabetes mellitus development

  6. RelB+ Steady-State Migratory Dendritic Cells Control the Peripheral Pool of the Natural Foxp3+ Regulatory T Cells

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    Anja Döhler

    2017-06-01

    Full Text Available Thymus-derived natural Foxp3+ CD4+ regulatory T cells (nTregs play a key role in maintaining immune tolerance and preventing autoimmune disease. Several studies indicate that dendritic cells (DCs are critically involved in the maintenance and proliferation of nTregs. However, the mechanisms how DCs manage to keep the peripheral pool at constant levels remain poorly understood. Here, we describe that the NF-κB/Rel family transcription factor RelB controls the frequencies of steady-state migratory DCs (ssmDCs in peripheral lymph nodes and their numbers control peripheral nTreg homeostasis. DC-specific RelB depletion was investigated in CD11c-Cre × RelBfl/fl mice (RelBDCko, which showed normal frequencies of resident DCs in lymph nodes and spleen while the subsets of CD103− Langerin− dermal DCs (dDCs and Langerhans cells but not CD103+ Langerin+ dDC of the ssmDCs in skin-draining lymph nodes were increased. Enhanced frequencies and proliferation rates were also observed for nTregs and a small population of CD4+ CD44high CD25low memory-like T cells (Tml. Interestingly, only the Tml but not DCs showed an increase in IL-2-producing capacity in lymph nodes of RelBDCko mice. Blocking of IL-2 in vivo reduced the frequency of nTregs but increased the Tml frequencies, followed by a recovery of nTregs. Taken together, by employing RelBDCko mice with increased frequencies of ssmDCs our data indicate a critical role for specific ssmDC subsets for the peripheral nTreg and IL-2+ Tml frequencies during homeostasis.

  7. Metaherpetic corneal disease in a dog associated with partial limbal stem cell deficiency and neurotrophic keratitis.

    Science.gov (United States)

    Ledbetter, Eric C; Marfurt, Carl F; Dubielzig, Richard R

    2013-07-01

    To describe clinical, in vivo confocal microscopic, histopathologic, and immunohistochemical features of a dog with metaherpetic corneal disease that developed subsequent to a protracted episode of canine herpesvirus-1 (CHV-1) dendritic ulcerative keratitis. A 7-year-old, spayed-female, Miniature Schnauzer was treated for bilateral CHV-1 dendritic ulcerative keratitis. Following resolution of ulcerative keratitis, sectoral peripheral superficial corneal gray opacification, vascularization, and pigmentation slowly migrated centripetally to the axial cornea of both eyes. Corneal sensitivity measured with a Cochet-Bonnet esthesiometer was dramatically and persistently reduced. In vivo corneal confocal microscopic examination revealed regions of epithelium with a conjunctival phenotype. In these areas, the surface epithelium was thin, disorganized, and composed of hyper-reflective epithelial cells. Goblet cells and Langerhans cells were frequent, and the subbasal nerve plexus was completely absent or markedly diminished. Histopathologic abnormalities in the globes were restricted to the superficial cornea and included sectoral corneal conjunctivalization, increased anterior stromal spindle cells, and vascularization. Immunohistochemical evaluation of the corneas with anti-neurotublin antibody demonstrated attenuation of the epithelial and subbasal nerve plexuses with marked stromal hyperinnervation and increased numbers of morphologically abnormal neurites. Similar to herpes simplex virus keratitis in humans, CHV-1 ulcerative keratitis may be associated with the development of chronic degenerative corneal disease in dogs. In the described dog, this chronic corneal disease included progressive corneal opacification because of partial limbal stem cell deficiency and neurotrophic keratitis. Long-term monitoring of dogs following resolution of active CHV-1 keratitis may be indicated, particularly when ulcerations persist for an extended period. © 2012 American College of

  8. Highly efficient gene delivery by mRNA electroporation in human hematopoietic cells: superiority to lipofection and passive pulsing of mRNA and to electroporation of plasmid cDNA for tumor antigen loading of dendritic cells.

    Science.gov (United States)

    Van Tendeloo, V F; Ponsaerts, P; Lardon, F; Nijs, G; Lenjou, M; Van Broeckhoven, C; Van Bockstaele, D R; Berneman, Z N

    2001-07-01

    Designing effective strategies to load human dendritic cells (DCs) with tumor antigens is a challenging approach for DC-based tumor vaccines. Here, a cytoplasmic expression system based on mRNA electroporation to efficiently introduce tumor antigens into DCs is described. Preliminary experiments in K562 cells using an enhanced green fluorescent protein (EGFP) reporter gene revealed that mRNA electroporation as compared with plasmid DNA electroporation showed a markedly improved transfection efficiency (89% versus 40% EGFP(+) cells, respectively) and induced a strikingly lower cell toxicity (15% death rate with mRNA versus 51% with plasmid DNA). Next, mRNA electroporation was applied for nonviral transfection of different types of human DCs, including monocyte-derived DCs (Mo-DCs), CD34(+) progenitor-derived DCs (34-DCs) and Langerhans cells (34-LCs). High-level transgene expression by mRNA electroporation was obtained in more than 50% of all DC types. mRNA-electroporated DCs retained their phenotype and maturational potential. Importantly, DCs electroporated with mRNA-encoding Melan-A strongly activated a Melan-A-specific cytotoxic T lymphocyte (CTL) clone in an HLA-restricted manner and were superior to mRNA-lipofected or -pulsed DCs. Optimal stimulation of the CTL occurred when Mo-DCs underwent maturation following mRNA transfection. Strikingly, a nonspecific stimulation of CTL was observed when DCs were transfected with plasmid DNA. The data clearly demonstrate that Mo-DCs electroporated with mRNA efficiently present functional antigenic peptides to cytotoxic T cells. Therefore, electroporation of mRNA-encoding tumor antigens is a powerful technique to charge human dendritic cells with tumor antigens and could serve applications in future DC-based tumor vaccines.

  9. Ubiquitin fold modifier 1 (UFM1 and its target UFBP1 protect pancreatic beta cells from ER stress-induced apoptosis.

    Directory of Open Access Journals (Sweden)

    Katleen Lemaire

    Full Text Available UFM1 is a member of the ubiquitin like protein family. While the enzymatic cascade of UFM1 conjugation has been elucidated in recent years, the biological function remains largely unknown. In this report we demonstrate that the recently identified C20orf116, which we name UFM1-binding protein 1 containing a PCI domain (UFBP1, and CDK5RAP3 interact with UFM1. Components of the UFM1 conjugation pathway (UFM1, UFBP1, UFL1 and CDK5RAP3 are highly expressed in pancreatic islets of Langerhans and some other secretory tissues. Co-localization of UFM1 with UFBP1 in the endoplasmic reticulum (ER depends on UFBP1. We demonstrate that ER stress, which is common in secretory cells, induces expression of Ufm1, Ufbp1 and Ufl1 in the beta-cell line INS-1E. siRNA-mediated Ufm1 or Ufbp1 knockdown enhances apoptosis upon ER stress. Silencing the E3 enzyme UFL1, results in similar outcomes, suggesting that UFM1-UFBP1 conjugation is required to prevent ER stress-induced apoptosis. Together, our data suggest that UFM1-UFBP1 participate in preventing ER stress-induced apoptosis in protein secretory cells.

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

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    Elena Arellano-Orden

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

  11. 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 ...

  12. Lysosomal cross-correction by hematopoietic stem cell-derived macrophages via tunneling nanotubes

    Science.gov (United States)

    Naphade, Swati; Sharma, Jay; Chevronnay, Héloïse P. Gaide; Shook, Michael A.; Yeagy, Brian A.; Rocca, Celine J.; Ur, Sarah N.; Lau, Athena J.; Courtoy, Pierre J.; Cherqui, Stephanie

    2014-01-01

    Despite controversies on the potential of hematopoietic stem cells (HSCs) to promote tissue repair, we previously showed that HSC transplantation could correct cystinosis, a multi-systemic lysosomal storage disease, caused by a defective lysosomal membrane cystine transporter, cystinosin (CTNS). Addressing the cellular mechanisms, we here report vesicular cross-correction after HSC differentiation into macrophages. Upon co-culture with cystinotic fibroblasts, macrophages produced tunneling nanotubes (TNTs) allowing transfer of cystinosin-bearing lysosomes into Ctns-deficient cells, which exploited the same route to retrogradely transfer cystine-loaded lysosomes to macrophages, providing a bidirectional correction mechanism. TNT formation was enhanced by contact with diseased cells. In vivo, HSCs grafted to cystinotic kidneys also generated nanotubular extensions resembling invadopodia that crossed the dense basement membranes and delivered cystinosin into diseased proximal tubular cells. This is the first report of correction of a genetic lysosomal defect by bidirectional vesicular exchange via TNTs and suggests broader potential for HSC transplantation for other disorders due to defective vesicular proteins. PMID:25186209

  13. B cell subsets and dysfunction of regulatory B cells in IgG4-related diseases and primary Sjögren’s syndrome: the similarities and differences

    Science.gov (United States)

    2014-01-01

    Introduction IgG4-related disease (IgG4-RD) is a multisystem-involved autoimmune disease. Abnormally activated and differentiated B cells may play important roles. Regulatory B cells (Breg) are newly defined B cell subgroups with immunosuppressive functions. In this study, we investigated the differences of B cell subsets, the expressions of co-stimulatory molecules on B cells, and the function of Breg cells in patients with IgG4-RD, primary Sjögren’s syndrome (pSS) as well as in healthy controls (HC). Methods Newly diagnosed IgG4-RD patients (n = 48) were enrolled, 38 untreated pSS patients and 30 healthy volunteers were recruited as disease and healthy controls. To analyze B cell subsets and B cell activity, PBMCs were surface stained and detected by flow cytometry. The function of Breg cells was tested by coculturing isolated CD19 + CD24hiCD38hi Breg cells with purified CD4 + CD25- T cells. Serum cytokines were measured by ELISA and cytometric bead array. Relationship between clinical data and laboratory findings were analyzed as well. Results Compared with pSS patients and HC, IgG4-RD patients had a lower frequency of peripheral Breg cells. Interestingly, CD19 + CD24-CD38hi B cell subsets were significantly higher in peripheral B cells from IgG4-RD patients than in pSS patients and HC, which correlated with serum IgG4 levels. The expression of BAFF-R and CD40 on B cells was significantly lower in IgG4-RD patients compared with those in pSS patients and HC. Unlike HC, Breg cells from pSS patients lacked suppressive functions. Conclusions B cells in patients with IgG4-RD and pSS display a variety of abnormalities, including disturbed B cell subpopulations, abnormal expression of key signaling molecules, co-stimulatory molecules, and inflammatory cytokines. In addition, a significantly increased B cell subset, CD19 + CD24-CD38hi B cells, may play an important role in the pathogenesis of IgG4-RD. PMID:24887143

  14. THP-1 monocytes but not macrophages as a potential alternative for CD34+ dendritic cells to identify chemical skin sensitizers

    International Nuclear Information System (INIS)

    Lambrechts, Nathalie; Verstraelen, Sandra; Lodewyckx, Hanne; Felicio, Ana; Hooyberghs, Jef; Witters, Hilda; Tendeloo, Viggo van; Cauwenberge, Paul van; Nelissen, Inge; Heuvel, Rosette van den; Schoeters, Greet

    2009-01-01

    Early detection of the sensitizing potential of chemicals is an emerging issue for chemical, pharmaceutical and cosmetic industries. In our institute, an in vitro classification model for prediction of chemical-induced skin sensitization based on gene expression signatures in human CD34 + progenitor-derived dendritic cells (DC) has been developed. This primary cell model is able to closely mimic the induction phase of sensitization by Langerhans cells in the skin, but it has drawbacks, such as the availability of cord blood. The aim of this study was to investigate whether human in vitro cultured THP-1 monocytes or macrophages display a similar expression profile for 13 predictive gene markers previously identified in DC and whether they also possess a discriminating capacity towards skin sensitizers and non-sensitizers based on these marker genes. To this end, the cell models were exposed to 5 skin sensitizers (ammonium hexachloroplatinate IV, 1-chloro-2,4-dinitrobenzene, eugenol, para-phenylenediamine, and tetramethylthiuram disulfide) and 5 non-sensitizers (L-glutamic acid, methyl salicylate, sodium dodecyl sulfate, tributyltin chloride, and zinc sulfate) for 6, 10, and 24 h, and mRNA expression of the 13 genes was analyzed using real-time RT-PCR. The transcriptional response of 7 out of 13 genes in THP-1 monocytes was significantly correlated with DC, whereas only 2 out of 13 genes in THP-1 macrophages. After a cross-validation of a discriminant analysis of the gene expression profiles in the THP-1 monocytes, this cell model demonstrated to also have a capacity to distinguish skin sensitizers from non-sensitizers. However, the DC model was superior to the monocyte model for discrimination of (non-)sensitizing chemicals.

  15. Can p63 serve as a biomarker for giant cell tumor of bone? A Moroccan experience

    Directory of Open Access Journals (Sweden)

    Hammas Nawal

    2012-09-01

    Full Text Available Abstract Background Multinucleated giant cell-containing tumors and pseudotumors of bone represent a heterogeneous group of benign and malignant lesions. Differential diagnosis can be challenging, particularly in instances of limited sampling. The purpose of this study was to evaluate the contribution of the P63 in the positive and differential diagnosis of giant cell tumor of bone. Methods This study includes 48 giant cell-containing tumors and pseudotumors of bone. P63 expression was evaluated by immunohistochemistry. Data analysis was performed using Epi-info software and SPSS software package (version 17. Results Immunohistochemical analysis showed a P63 nuclear expression in all giant cell tumors of bone, in 50% of osteoid osteomas, 40% of aneurysmal bone cysts, 37.5% of osteoblastomas, 33.3% of chondromyxoide fibromas, 25% of non ossifiant fibromas and 8.3% of osteosarcomas. Only one case of chondroblastoma was included in this series and expressed p63. No P63 immunoreactivity was detected in any of the cases of central giant cell granulomas or langerhans cells histiocytosis. The sensitivity and negative predictive value (NPV of P63 immunohistochemistry for the diagnosis of giant cell tumor of bone were 100%. The specificity and positive predictive value (PPV were 74.42% and 59.26% respectively. Conclusions This study found not only that GCTOB expresses the P63 but it also shows that this protein may serve as a biomarker for the differential diagnosis between two morphologically similar lesions particularly in instances of limited sampling. Indeed, P63 expression seems to differentiate between giant cell tumor of bone and central giant cell granuloma since the latter does not express P63. Other benign and malignant giant cell-containing lesions express P63, decreasing its specificity as a diagnostic marker, but a strong staining was seen, except a case of chondroblastoma, only in giant cell tumor of bone. Clinical and radiological

  16. Stem Cells

    Science.gov (United States)

    Stem cells are cells with the potential to develop into many different types of cells in the body. ... the body. There are two main types of stem cells: embryonic stem cells and adult stem cells. Stem ...

  17. Evaluation of the skin sensitization potential of chemicals using expression of co-stimulatory molecules, CD54 and CD86, on the naive THP-1 cell line.

    Science.gov (United States)

    Yoshida, Y; Sakaguchi, H; Ito, Y; Okuda, M; Suzuki, H

    2003-04-01

    It has been known that dendritic cells (DCs) including Langerhans cells (LCs) play a critical role in the skin sensitization process. Many attempts have been made to develop in vitro sensitization tests that employ DCs derived from peripheral blood mononuclear cells (PBMC-DC) or CD34+ hematopoietic progenitor cells (CD34+ HPC) purified from cord blood or bone marrow. However, the use of the DCs in in vitro methods has been difficult due to the nature of these cells such as low levels in the source and/or donor-to-donor variability. In our studies, we employed the human monocytic leukemia cell line, THP-1, in order to avoid some of these difficulties. At the start, we examined whether treatment of the cells with various cytokines could produce DCs from THP-1. Treatment of THP-1 cells with cytokines such as GM-CSF, IL-4, TNF-alpha, and/or PMA did induce some phenotypic changes in THP-1 cells that were characteristic of DCs. Subsequently, responses to a known sensitizer, dinitrochlorobenzene (DNCB), and a non-sensitizer, dimethyl sulfoxide (DMSO) or sodium lauryl sulfate (SLS), on the expression of co-stimulatory molecules, CD54 and CD86, were examined between the naive cells and the cytokine-treated cells. Interestingly, the naive THP-1 cells responded only to DNCB and the response to the sensitizer was more distinct than cytokine-treated THP-1 cells. Similar phenomena were also observed in the human myeloid leukemia cell line, KG-1. Furthermore, with treatment of DNCB, naive THP-1 cells showed augmented expression of HLA, CD80 and secretion of IL-1 beta. The response of THP-1 cells to a sensitizer was similar to that of LCs/DCs. Upon demonstrating the differentiation of monocyte cells in our system, we then evaluated a series of chemicals, including known sensitizers and non-sensitizers, for their potential to augment CD54 and CD86 expression on naive THP-1 cells. Indeed, known sensitizers such as PPD and 2-MBT significantly augmented CD54 and CD86 expression in a

  18. Keratinocyte-Derived Chemokines Orchestrate T-Cell Positioning in the Epidermis during Vitiligo and May Serve as Biomarkers of Disease.

    Science.gov (United States)

    Richmond, Jillian M; Bangari, Dinesh S; Essien, Kingsley I; Currimbhoy, Sharif D; Groom, Joanna R; Pandya, Amit G; Youd, Michele E; Luster, Andrew D; Harris, John E

    2017-02-01

    Vitiligo is an autoimmune disease of the skin that results in the destruction of melanocytes and the clinical appearance of white spots. Disease pathogenesis depends on IFN-γ and IFN-γ-induced chemokines to promote T-cell recruitment to the epidermis where melanocytes reside. The skin is a complex organ, with a variety of resident cell types. We sought to better define the microenvironment and distinct cellular contributions during autoimmunity in vitiligo, and we found that the epidermis is a chemokine-high niche in both a mouse model and human vitiligo. Analysis of chemokine expression in mouse skin showed that CXCL9 and CXCL10 expression strongly correlate with disease activity, whereas CXCL10 alone correlates with severity, supporting them as potential biomarkers for following disease progression. Further studies in both our mouse model and human patients showed that keratinocytes were the major chemokine producers throughout the course of disease, and functional studies using a conditional signal transducer and activator of transcription (STAT)-1 knockout mouse showed that IFN-γ signaling in keratinocytes was critical for disease progression and proper autoreactive T-cell homing to the epidermis. In contrast, epidermal immune cell populations including endogenous T cells, Langerhans cells, and γδ T cells were not required. These results have important clinical implications, because topical therapies that target IFN-γ signaling in keratinocytes could be safe and effective new treatments, and skin expression of these chemokines could be used to monitor disease activity and treatment responses. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  19. Proangiogenic hematopoietic cells of monocytic origin: roles in vascular regeneration and pathogenic processes of systemic sclerosis.

    Science.gov (United States)

    Yamaguchi, Yukie; Kuwana, Masataka

    2013-02-01

    New blood vessel formation is critical, not only for organ development and tissue regeneration, but also for various pathologic processes, such as tumor development and vasculopathy. The maintenance of the postnatal vascular system requires constant remodeling, which occurs through angiogenesis, vasculogenesis, and arteriogenesis. Vasculogenesis is mediated by the de novo differentiation of mature endothelial cells from endothelial progenitor cells (EPCs). Early studies provided evidence that bone marrow-derived CD14⁺ monocytes can serve as a subset of EPCs because of their expression of endothelial markers and ability to promote neovascularization in vitro and in vivo. However, the current consensus is that monocytic cells do not give rise to endothelial cells in vivo, but function as support cells, by promoting vascular formation and repair through their immediate recruitment to the site of vascular injury, secretion of proangiogenic factors, and differentiation into mural cells. These monocytes that function in a supporting role in vascular repair are now termed monocytic pro-angiogenic hematopoietic cells (PHCs). Systemic sclerosis (SSc) is a multisystem connective tissue disease characterized by excessive fibrosis and microvasculopathy, along with poor vascular formation and repair. We recently showed that in patients with SSc, circulating monocytic PHCs increase dramatically and have enhanced angiogenic potency. These effects may be induced in response to defective vascular repair machinery. Since CD14⁺ monocytes can also differentiate into fibroblast-like cells that produce extracellular matrix proteins, here we propose a new hypothesis that aberrant monocytic PHCs, once mobilized into circulation, may also contribute to the fibrotic process of SSc.

  20. Las histiocitosis Histiocytosis

    Directory of Open Access Journals (Sweden)

    Eva Svarch

    2001-12-01

    Full Text Available El término histiocitosis identifica un grupo de alteraciones que tienen en común la proliferación de células dendríticas (CD y los macrófagos, y se diagnostican más frecuentemente en niños. Dentro de las relacionadas con las CD las fundamentales son las histiocitosis a células de Langerhans (HCL. Las HCL tienen un comportamiento clínico muy variable, que puede ir desde una lesión que involucra un solo sitio o sistema hasta una enfermedad multisistémica. El tratamiento depende de la extensión del proceso. Una lesión única tiende a desaparecer espontáneamente. También la biopsia diagnóstica con o sin inyección de un esteroide puede iniciar la curación. Los pacientes con enfermedad multisistémica pueden beneficiarse con el tratamiento esteroideo y citostático o inclusive con el trasplante de células progenitoras hematopoyéticas. La histiocitosis sinusal con linfoadenopatías masivas o enfermedad de Rosai Dorfman se debe a la proliferación de los macrófagos, es de naturaleza benigna y usualmente autolimitada. Afecta sobre todo a niños y adultos jóvenes. La linfohistiocitosis hemofagocítica también se produce por la proliferación de los macrófagos y es una enfermedad rara con una alta mortalidad. Puede ser familiar (autosómica recesiva o secundaria a infecciones virales. Esta última forma se presenta más frecuentemente en el lactante pequeño. En la actualidad, sobre todo en la variedad familiar, el trasplante alogénico de células progenitoras hematopoyéticas puede ser la única medida curativaThe term histiocytosis identifies a group of disorders that have in common the proliferation of dentritic cells (DC and macrophages and is frequently diagnosed in children. Among the fundamental variants of histiocytosis related with DC, we find Langerhans cell histiocytosis (LCH. Langerhans cell histiocytosis has very variable clinical behavior that ranges from a lesion involving only one site or system to a multisystem