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Sample records for giant cell lesion

  1. Insight into the pathogenesis and nature of Central giant cell lesions of the jaws

    PubMed Central

    2015-01-01

    Central giant cell lesions of the jaws are not uncommon. While the majority of these represent single, sporadic lesions, histologically identical lesions are seen in association with a number of other bone lesions, as well as in certain syndromes. This manuscript offers a brief update on recent developments in this area that provide new insight into the pathogenesis and nature of Central Giant Cell Lesions of the Jaws. Key words:Central giant cell lesion, RASopathy PMID:25681371

  2. Multiple giant cell lesions in a patient with Noonan syndrome with multiple lentigines.

    PubMed

    van den Berg, Henk; Schreuder, Willem Hans; Jongmans, Marjolijn; van Bommel-Slee, Danielle; Witsenburg, Bart; de Lange, Jan

    2016-08-01

    A patient with Noonan syndrome with multiple lentigines (NSML) and multiple giant cell lesions (MGCL) in mandibles and maxillae is described. A mutation p.Thr468Met in the PTPN11-gene was found. This is the second reported NSML patient with MGCL. Our case adds to the assumption that, despite a different molecular pathogenesis and effect on the RAS/MEK pathway, NSML shares the development of MGCL, with other RASopathies. PMID:27238887

  3. Tenosynovial giant cell tumor presenting as a parotid gland mass: Expanding the differential diagnosis of giant cell-rich lesions in salivary glands.

    PubMed

    Guo, Ling; Qasem, Shadi; Bergman, Simon; Salih, Ziyan T

    2014-01-01

    Tenosynovial giant cell tumors (TGCT) are rare benign soft tissue tumors affecting mostly young adults. The most common affected sites include the knee, ankle, elbow, shoulder, and fingers. The temporomandibular joint is occasionally affected. Herein, we report a case of a 31-year-old Caucasian male who presented clinically with a parotid gland mass. The initial clinical and radiological work-up failed to reveal any involvement of the adjacent temporomandibular joint. Fine-needle aspiration revealed a cellular tumor composed of mononuclear and multinucleated giant cells with fibrosis and hemosiderin deposition. This was subsequently found to be a TGCT arising from the temporomandibular joint. Giant cell-rich lesions are uncommon in salivary glands. Herein, we describe the cytomorphology and clinico-radiographic features of this tumor with emphasis on the differential diagnosis of giant cell-rich lesions presenting in salivary glands. Despite its rare occurrence, this entity should be considered when giant cells are prominent in specimens acquired from this location.

  4. Giant Cell Lesions of Lungs: A Histopathological and Morphometric Study of Seven Autopsy Cases

    PubMed Central

    Natarajan, M.; Biligi, Dayananda S; Raghupathi, A.R

    2015-01-01

    Introduction Macrophages undergo fusion to form multinucleated giant cells (MGC) in several pathologic conditions. The exact mechanism of their generation is still unclear. MGC are a common feature of granulomas that develop during various inflammatory reactions. Aim To study the histopathological features of giant cell lesions in lungs and correlate the characteristics of giant cells with other histopathological findings. Also, to determine the utility of morphometry to differentiate foreign body and Langhans MGC. Materials and Methods Seven cases were analysed. Specimen of lungs was grossed, sectioned and processed. Routinely, tissue sections were stained by Haematoxylin and Eosin (H&E) stain. Polarizing microscopy and special stains were employed in selected cases. Granulomas and MGC were counted and measured. Several other parameters like location, distribution, type and number of MGC, associated predominant inflammatory component and nature of granulomas were analysed. Results Five patterns of lesions were observed in seven cases. Aspiration pneumonia was seen in three cases (42.85%) and constituted the most common pattern. However, aspiration pneumonia as the only cause of MGC was seen in only one case (14.28%). Pulmonary tuberculosis and asteroid bodies constituted two cases (28.57%) each. Cryptococcal pneumonia and cholesterol clefts constituted one case (14.28%) each. Crypococci were demonstrated to be positively birefringent by polarized microscopy on Ziehl-Neelsen stained sections. Based on statistical analysis of morphometric data, a new index (NP index) was proposed to statistically categorize MGC into foreign body type and Langhans type. NP index value of ≤0.016 was found to be statistically significant (p<0.005) in foreign body MGC. It had high sensitivity and efficacy. Conclusion MGC may not be always associated with granulomas. The mechanisms that lead to the occurrence of MGC, independent of granuloma needs to be elucidated. Morphometry may

  5. SOS1 and PTPN11 mutations in five cases of Noonan syndrome with multiple giant cell lesions

    PubMed Central

    Beneteau, Claire; Cavé, Hélène; Moncla, Anne; Dorison, Nathalie; Munnich, Arnold; Verloes, Alain; Leheup, Bruno

    2009-01-01

    We report five cases of multiple giant cell lesions in patients with typical Noonan syndrome. Such association has frequently been referred to as Noonan-like/multiple giant cell (NL/MGCL) syndrome before the molecular definition of Noonan syndrome. Two patients show mutations in PTPN11 (p.Tyr62Asp and p.Asn308Asp) and three in SOS1 (p.Arg552Ser and p.Arg552Thr). The latter are the first SOS1 mutations reported outside PTPN11 in NL/MGCL syndrome. MGCL lesions were observed in jaws (‘cherubism') and joints (‘pigmented villonodular synovitis'). We show through those patients that both types of MGCL are not PTPN11-specific, but rather represent a low penetrant (or perhaps overlooked) complication of the dysregulated RAS/MAPK signaling pathway. We recommend discarding NL/MGCL syndrome from the nosology, as this presentation is neither gene-nor allele-specific of Noonan syndrome; these patients should be described as Noonan syndrome with MGCL (of the mandible, the long bone…). The term cherubism should be used only when multiple giant cell lesions occur without any other clinical and molecular evidence of Noonan syndrome, with or without mutations of the SH3BP2 gene. PMID:19352411

  6. Sensitivity of the Giant LOop Binary LEsion (GLOBLE) cell survival model on parameters characterising dose rate effects.

    PubMed

    Herr, L; Friedrich, T; Durante, M; Scholz, M

    2015-09-01

    The sensitivity of the Giant LOop Binary LEsion model for cell survival probabilities after arbitrary photon irradiation schedules on its parameters is presented. Since these parameters are closely linked to observable features of cell repair, the modelled influence of the parameters on cell survival gives indications about the relation between cell line-specific repair characteristics and the radiation response. To visualise the general findings about the impact of parameter changes on cell survival probabilities, survival curves for an exemplary cell line are shown. Furthermore, the relative change in the effect of radiation after a change in parameter values is investigated over the range of doses and dose rates usually applied in cell survival experiments.

  7. [A model of using magnetic resonance imaging in osteoarticular tumor lesion in case of giant cell tumors].

    PubMed

    Sherman, L A

    2004-01-01

    Fifty-eight patients with giant cell tumors (GCT) underwent a comprehensive radiation diagnosis involving X-ray study and magnetic resonance imaging (MRI). The obtained MR images indicated the high efficiency of this combination of radiation diagnostic techniques in solving the problems in the visualization of osteoarticular tumor lesions. GCT is characterized by well-known primary X-ray semiotics; MR images are also rather pathognomonic of these tumors and they illustrate the process of morphogenesis of these masses. MRI made it possible to solve the specific problems facing a physician (a radiation diagnostician), to determine the site, shape, sizes, volume, and local extent of a tumor, which permitted the planning of surgical treatment policy; to assess its results, to reveal possible inflammatory complications; and to visualize a local recurrence and on-going growth of a tumor, including the signs of GCT malignancy.

  8. Subependymal giant cell astrocytoma: a lesion with activated mTOR pathway and constant expression of glutamine synthetase.

    PubMed

    Buccoliero, Anna Maria; Caporalini, Chiara; Giordano, Flavio; Mussa, Federico; Scagnet, Mirko; Moscardi, Selene; Baroni, Gianna; Genitori, Lorenzo; Taddei, Gian Luigi

    2016-01-01

    Subependymal giant-cell astrocytoma (SEGA) is a rare tumor associated with tuberous sclerosis complex (TSC). TSC mainly involves the central nervous system (CNS) where SEGA, subependymal nodules, and cortical tubers may be present. First studies suggested the astrocytic nature of SEGA while successive studies demonstrated the mixed glio-neuronal nature. There are similarities between TSC-associated CNS lesions and type IIb focal cortical dysplasia (FCD). In all these pathologies, mammalian target of rapamycin (mTOR) pathway activation has been demonstrated. Recent data evidenced that balloon cells in FCD IIb express glutamine synthetase (GS). GS is involved in the clearance of glutamate. Cells expressing GS might exert an antiepileptic role. We evaluated by immunohistochemistry the glial fibrillary acidic protein (GFAP), neurofilaments (NF), and GS expression and the mTOR status (mTOR and phosphorylated ribosomal protein S6) in 16 SEGAs and 2 cortical tubers. Our purpose was to emphasize the mixed nature of SEGA and to further investigate the similarities between TSC-related CNS lesions (in particular SEGA) and FCD IIb. We confirm the glio-neuronal nature and the common activation of the mTOR pathway in SEGAs. In addition, we report for the first time that these tumors, analogously to FCD IIb, commonly express GS. Notably, the expression of mTOR, phosphorylated ribosomal protein S6, and GS was restricted to gemistocytic-like GFAP-negative cells. GS expression and mTOR pathway activation were also documented in cortical tubers. Further studies are necessary to understand the significance of GS expression in SEGAs as well as in cortical tubers. PMID:27390104

  9. Subependymal giant cell astrocytoma: a lesion with activated mTOR pathway and constant expression of glutamine synthetase.

    PubMed

    Buccoliero, Anna Maria; Caporalini, Chiara; Giordano, Flavio; Mussa, Federico; Scagnet, Mirko; Moscardi, Selene; Baroni, Gianna; Genitori, Lorenzo; Taddei, Gian Luigi

    2016-01-01

    Subependymal giant-cell astrocytoma (SEGA) is a rare tumor associated with tuberous sclerosis complex (TSC). TSC mainly involves the central nervous system (CNS) where SEGA, subependymal nodules, and cortical tubers may be present. First studies suggested the astrocytic nature of SEGA while successive studies demonstrated the mixed glio-neuronal nature. There are similarities between TSC-associated CNS lesions and type IIb focal cortical dysplasia (FCD). In all these pathologies, mammalian target of rapamycin (mTOR) pathway activation has been demonstrated. Recent data evidenced that balloon cells in FCD IIb express glutamine synthetase (GS). GS is involved in the clearance of glutamate. Cells expressing GS might exert an antiepileptic role. We evaluated by immunohistochemistry the glial fibrillary acidic protein (GFAP), neurofilaments (NF), and GS expression and the mTOR status (mTOR and phosphorylated ribosomal protein S6) in 16 SEGAs and 2 cortical tubers. Our purpose was to emphasize the mixed nature of SEGA and to further investigate the similarities between TSC-related CNS lesions (in particular SEGA) and FCD IIb. We confirm the glio-neuronal nature and the common activation of the mTOR pathway in SEGAs. In addition, we report for the first time that these tumors, analogously to FCD IIb, commonly express GS. Notably, the expression of mTOR, phosphorylated ribosomal protein S6, and GS was restricted to gemistocytic-like GFAP-negative cells. GS expression and mTOR pathway activation were also documented in cortical tubers. Further studies are necessary to understand the significance of GS expression in SEGAs as well as in cortical tubers.

  10. Giant Cell Arteritis

    MedlinePlus

    Giant cell arteritis is a disorder that causes inflammation of your arteries, usually in the scalp, neck, and arms. ... arteries, which keeps blood from flowing well. Giant cell arteritis often occurs with another disorder called polymyalgia ...

  11. The Giant Cell.

    ERIC Educational Resources Information Center

    Stockdale, Dennis

    1998-01-01

    Provides directions for the construction of giant plastic cells, including details for building and installing the organelles. Also contains instructions for preparing the ribosomes, nucleolus, nucleus, and mitochondria. (DDR)

  12. Ghost cell lesions

    PubMed Central

    Rajesh, E.; Jimson, Sudha; Masthan, K. M. K.; Balachander, N.

    2015-01-01

    Ghost cells have been a controversy for a long time. Ghost cell is a swollen/enlarged epithelial cell with eosnophilic cytoplasm, but without a nucleus. In routine H and E staining these cells give a shadowy appearance. Hence these cells are also called as shadow cells or translucent cells. The appearance of these cells varies from lesion to lesion involving odontogenic and nonodontogenic lesions. This article review about the origin, nature and significance of ghost cells in different neoplasms. PMID:26015694

  13. Giant cell rich osteosarcoma of the mandible with abundant spindle cells and osteoclast-like giant cells mimicking malignancy in giant cell tumor

    PubMed Central

    Sun, Li-Mei; Zhang, Qing-Fu; Tang, Na; Mi, Xiao-Yi; Qiu, Xue-Shan

    2015-01-01

    Giant cell rich osteosarcoma is a relatively unusual histological form of osteosarcoma, common lesion usually presenting in the long bones of the appendicular skeleton. The occurrence in the mandible is exceptional rare. Histologically, this tumor tends to be a highly anaplastic, pleomorphic tumor in which the tumor cells may be: plasmacytoid, fusiform, ovoid, small round cells, clear cells, mono-or multinucleated giant cells, or, spindle cells. Herein, we present a case with the sternum and first thoracic vertebra metastasis from primary giant cell rich osteosarcoma of the mandible in a 28 year-old Chinese female. The tumor was predominantly composed of abundant spindle cells with marked atypia and numerous osteoclast-like giant cells reminiscent of malignancy in giant cell tumor. The unusual histological appearance can pose a great diagnostic challenge. It may be easily misdiagnosed, especially if the specimen is limited or from fine-needle aspiration. PMID:26464744

  14. Peripheral giant cell granuloma: This enormity is a rarity

    PubMed Central

    Rodrigues, Silvia Victor; Mitra, Dipika Kalyan; Pawar, Sudarshana Devendrasing; Vijayakar, Harshad Narayan

    2015-01-01

    Peripheral giant cell granuloma (PGCG) is an infrequent exophytic lesion of the oral cavity, also known as giant cell epulis, osteoclastoma, giant cell reparative granuloma, or giant cell hyperplasia. Lesions vary in appearance from smooth, regularly outlined masses to irregularly shaped, multilobulated protuberances with surface indentations. Ulcerations of the margin are occasionally seen. The lesions are painless, vary in size, and may cover several teeth. It normally presents as a purplish-red nodule consisting of multinucleated giant cells in the background of mononuclear stromal cells and extravasated red blood cells. This case report describes the unusual appearance of a PGCG extending from left maxillary interdental gingiva to palatal area in 32-year-old female patient. PMID:26392701

  15. Giant cell arteritis

    PubMed Central

    Calvo-Romero, J

    2003-01-01

    Giant cell arteritis (GCA), temporal arteritis or Horton's arteritis, is a systemic vasculitis which involves large and medium sized vessels, especially the extracranial branches of the carotid arteries, in persons usually older than 50 years. Permanent visual loss, ischaemic strokes, and thoracic and abdominal aortic aneurysms are feared complications of GCA. The treatment consists of high dose steroids. Mortality, with a correct treatment, in patients with GCA seems to be similar that of controls. PMID:13679546

  16. Giant cell tumor of the spine.

    PubMed

    Ozaki, Toshifumi; Liljenqvist, Ulf; Halm, Henry; Hillmann, Axel; Gosheger, Georg; Winkelmann, Winfried

    2002-08-01

    Six patients with giant cell tumor of the spine had surgery between 1981 and 1995. Three lesions were located in the scrum, two lesions were in the thoracic spine, and one lesion was in the lumbar spine. Preoperatively, all patients had local pain and neurologic symptoms. Two patients had cement implanted after curettage or intralesional excision of the sacral tumor; one patient had a local relapse. After the second curettage and cement implantation, the tumor was controlled. One patient with a sacral lesion had marginal excision and spondylodesis; no relapse developed. Two patients with thoracic lesions had planned marginal excision and spondylodesis; the margins finally became intralesional, but no relapse developed. One patient with a lumbar lesion had incomplete removal of the tumor and received postoperative irradiation. At the final followup (median, 69 months), five of six patients were disease-free and one patient died of disease progression. Two of the five surviving patients had pain after standing or neurologic problems. Although some contamination occurred, planning a marginal excision of the lesion seems beneficial for vertebral lesions above the sacrum. Total sacrectomy of a sacral lesion seems to be too invasive when cement implantation can control the lesion. PMID:12151896

  17. Giant Cell Tumor of Bone - An Overview

    PubMed Central

    Sobti, Anshul; Agrawal, Pranshu; Agarwala, Sanjay; Agarwal, Manish

    2016-01-01

    Giant Cell tumors (GCT) are benign tumors with potential for aggressive behavior and capacity to metastasize. Although rarely lethal, benign bone tumors may be associated with a substantial disturbance of the local bony architecture that can be particularly troublesome in peri-articular locations. Its histogenesis remains unclear. It is characterized by a proliferation of mononuclear stromal cells and the presence of many multi- nucleated giant cells with homogenous distribution. There is no widely held consensus regarding the ideal treatment method selection. There are advocates of varying surgical techniques ranging from intra-lesional curettage to wide resection. As most giant cell tumors are benign and are located near a joint in young adults, several authors favor an intralesional approach that preserves anatomy of bone in lieu of resection. Although GCT is classified as a benign lesion, few patients develop progressive lung metastases with poor outcomes. Treatment is mainly surgical. Options of chemotherapy and radiotherapy are reserved for selected cases. Recent advances in the understanding of pathogenesis are essential to develop new treatments for this locally destructive primary bone tumor. PMID:26894211

  18. Giant Cornu Cutaneum Superimposed on Basal Cell Carcinoma.

    PubMed

    Agirgol, S; Mansur, A T; Bozkurt, K; Azakli, H N; Babacan, A; Dikmen, A

    2015-09-01

    Cornu cutaneum (CC) is a clinical term that describes the horn-like keratotic lesions extending vertically from the skin. Benign, premalignant or malignant lesions may be present at the base of CC. Seborrhoeic keratosis and squamous cell carcinoma (SCC) are the most commonly reported benign and malignant forms, respectively. Basal cell carcinoma (BCC) at the base is rare. Here, we report on an 85-year old female patient having multiple CC lesions, one being giant on her face and two of the lesions diagnosed with BCC at the base. This case is of significance due to the presence of giant and multiple CC and detection of BCC at the base of more than one lesion. This present case indicates the need for the treatment of possible malignant lesions underlying CC in the elderly by total surgical excision.

  19. Giant Cornu Cutaneum Superimposed on Basal Cell Carcinoma

    PubMed Central

    Agirgol, S; Mansur, AT; Bozkurt, K; Azakli, HN; Babacan, A; Dikmen, A

    2015-01-01

    ABSTRACT Cornu cutaneum (CC) is a clinical term that describes the horn-like keratotic lesions extending vertically from the skin. Benign, premalignant or malignant lesions may be present at the base of CC. Seborrhoeic keratosis and squamous cell carcinoma (SCC) are the most commonly reported benign and malignant forms, respectively. Basal cell carcinoma (BCC) at the base is rare. Here, we report on an 85-year old female patient having multiple CC lesions, one being giant on her face and two of the lesions diagnosed with BCC at the base. This case is of significance due to the presence of giant and multiple CC and detection of BCC at the base of more than one lesion. This present case indicates the need for the treatment of possible malignant lesions underlying CC in the elderly by total surgical excision. PMID:26624603

  20. Review of Giant cell arteritis

    PubMed Central

    Chacko, Joseph G.; Chacko, J. Anthony; Salter, Michael W.

    2014-01-01

    Giant-cell arteritis (GCA) is a systemic autoimmune disease affecting primarily the elderly. Giant cell arteritis can cause sudden and potentially bilateral sequential vision loss in the elderly. Therefore, it is considered a medical emergency in ophthalmology and a significant cause of morbidity in an increasingly aging population. Ophthalmologists need to be able to recognize the classic symptoms and signs of this disease, and then be able to work-up and treat these patients in an efficient manner. An in-depth review of GCA from the literature as well as personal clinical experience follows. PMID:25859139

  1. Central giant cell granuloma of the mandible. A case report.

    PubMed

    Granite, E L; Aronoff, A K; Gold, L

    1982-03-01

    Although a benign lesion, the central giant cell granuloma can be locally aggressive and quite destructive. The case reported here involved a giant cell lesion occurring in the mandibular symphysis of an 11-year-old girl. The treatment required four hospital admissions over a period of 4 years. The surgical intervention was complicated by a localized infection requiring closed reduction and bone grafting. The patient was followed over a period of 8 years, during which there was no recurrence of tumor or infection subsequent to the last surgical procedure.

  2. Giant Cell Tumor within the Proximal Tibia after ACL Reconstruction.

    PubMed

    Takahashi, Takashi; MacCormick, Lauren; Ellermann, Jutta; Clohisy, Denis; Marette, Shelly

    2016-01-01

    26-year-old female with prior anterior cruciate ligament reconstruction developed an enlarging lytic bone lesion around the tibial screw with sequential imaging over the course of one year demonstrating progression of this finding, which was confirmed histologically to be a giant cell tumor of bone. The lesion originated around the postoperative bed, making the diagnosis challenging during the early course of the presentation. The case demonstrates giant cell tumor which originated in the metaphysis and subsequently grew to involve the epiphysis; therefore, early course of the disease not involving the epiphysis should not exclude this diagnosis. PMID:26981302

  3. Giant Cell Tumor within the Proximal Tibia after ACL Reconstruction

    PubMed Central

    Takahashi, Takashi; MacCormick, Lauren; Ellermann, Jutta; Clohisy, Denis; Marette, Shelly

    2016-01-01

    26-year-old female with prior anterior cruciate ligament reconstruction developed an enlarging lytic bone lesion around the tibial screw with sequential imaging over the course of one year demonstrating progression of this finding, which was confirmed histologically to be a giant cell tumor of bone. The lesion originated around the postoperative bed, making the diagnosis challenging during the early course of the presentation. The case demonstrates giant cell tumor which originated in the metaphysis and subsequently grew to involve the epiphysis; therefore, early course of the disease not involving the epiphysis should not exclude this diagnosis. PMID:26981302

  4. Reparative giant cell granuloma in a pediatric patient.

    PubMed

    Duarte Ruiz, Blanca; Riba García, Francisco de Asís; Navarro Cuéllar, Carlos; Bucci, Tommaso; Cuesta Gil, Matías; Navarro Vila, Carlos

    2007-08-01

    Reparative giant cell granulomas are benign, infrequent tumors, of non-odontogenic origin, that develop at central or peripheral level. Peripherally located lesions are frequently denominated "giant cell epulis", and never correspond to true neoplasia, but rather to inflammatory reactions secondary to another lesion (hemorrhage, etc.). It should be taken into account, that in general, head and neck tumors of infancy usually demonstrate an atypical biological behaviour. Furthermore, the anatomicopathologic diagnosis is often compromised in this type of lesion. We present the case of a 6-year-old boy, who, three weeks after suffering a slight facial trauma, developed a painless, exophytic swelling of approximately 4 cm, with bleeding on palpation, in the ipsilateral hemimaxilla. The lesion demonstrated rapid, progressive and continuous growth. The facial CT and incisional biopsy confirmed the suspected diagnosis of reparative giant cell granuloma. The patient was surgically treated, carrying out a left marginal maxillectomy associated with the extirpation of the soft-tissue lesion. The resultant defect was reconstructed with a Bichat fat-pad providing the patient with optimal esthetic and functional results. The definitive anatomicopathologic report of the surgical piece is compatible with reparative giant cell granuloma.

  5. Pediatric giant cell fibroma: an unusual case report.

    PubMed

    Uloopi, K S; Vinay, Chandrappa; Deepika, Alluru; Sekhar, Rayala Chandra; Raghu, Dhanapal; Ramesh, Tatapudi

    2012-01-01

    Giant cell fibroma (GCF) is a lesion of oral mucosa which is commonly found on gingiva. The prevalence of GCF is high in Caucasians in the first three decades. It represents 2% to 5% of all fibrous lesions. This report describes a case of GCF on the tongue in a 12 year old Dravidian child. The cause of the lesion could not be determined. Excisional biopsy was performed to establish definitive diagnosis. Microscopically, numerous stellate shaped multi-nucleated giant cells and dense bundles of collagen fibres with a whorled pattern were observed. These collagen fibres were positive for Massons trichrome stain. Immunohistochemical analysis showed stellate cells positive for vimentin and negative for alpha smooth muscle actin suggesting fibroblast phenotype. No recurrence was observed. Pediatric dentists must have a thorough knowledge of this uncommon lesion which can be diagnosed only based on histopathological features.

  6. Observed Properties of Giant Cells

    NASA Technical Reports Server (NTRS)

    Hathaway, David H.; Upton, Lisa; Colegrove, Owen

    2014-01-01

    The existence of Giant Cells has been suggested by both theory and observation for over 45 years. We have tracked the motions of supergranules in SDO/HMI Doppler velocity data and find larger (Giant Cell) flows that persist for months. The flows in these cells are clockwise around centers of divergence in the north and counter-clockwise in the south. Equatorward flows are correlated with prograde flows - giving the transport of angular momentum toward the equator that is needed to maintain the Sun's rapid equatorial rotation. The cells are most pronounced at mid- and high-latitudes where they exhibit the rotation rates representative of those latitudes. These are clearly large, long-lived, cellular features, with the dynamical characteristics expected from the effects of the Sun's rotation, but the shapes of the cells are not well represented in numerical models. While the Giant Cell flow velocities are small (<10 m/s), their long lifetimes should nonetheless substantially impact the transport of magnetic flux in the Sun's near surface layers.

  7. Pediatric aggressive giant cell granuloma of nasal cavity

    PubMed Central

    Seo, Sung Tae; Kwon, Ki Ryun; Rha, Ki-Sang; Kim, Seon-Hwan; Kim, Yong Min

    2015-01-01

    Introduction Giant cell granuloma (GCG) is a non-neoplastic osseous proliferative lesion of unknown etiology. Although a benign disease process, GCG can be locally destructive. It is extremely rare to have a pediatric case of GCG occurring in the nasal cavity with intracranial invasion. Presentation of case We report a case of an aggressive and recurrent giant cell granuloma with intracranial invasion in a 10 years old female patient which was completely excised with endoscopic craniofacial resection. Discussion A literature review on pathogenesis, diagnosis and management is also performed. Conclusion The most common treatment for giant cell granuloma is surgery, ranging from simple curettage to resection. However, it must be completely excised in cases of aggressive and extensive lesion because of the high recurrence rate after incomplete removal. PMID:26433924

  8. Giant gingival pseudoepitheliomatous hyperplasia in lung squamous cell carcinoma.

    PubMed

    Xiang, Guolin; Long, Xing; Han, Qianchao; Tian, Lihua

    2012-07-01

    We here describe a case of giant primary gingival pseudoepitheliomatous hyperplasia in a 53-year-old Chinese male patient with lung squamous cell carcinoma (SCC). The pathogenesis of the lesion and the deferential diagnosis from invasive SCC are also discussed. To our knowledge, such a hugeous primary pseudoepitheliomatous hyperplasia of the gingiva accompanied with lung SCC is unusual.

  9. Case report 207: Giant cell reparative granuloma of left femur arising in polyostatic fibrous dysplasia

    SciTech Connect

    De Smet, A.A.; Travers, H.; Neff, J.R.

    1982-08-01

    Diagnosis and differential diagnosis of lytic lesions in the femur are discussed. Roentgenograms, a tomogram and pathological studies of a giant cell reparative granuloma of left femur arising in polyostotic fibrous dysplasia are presented.

  10. A Comparative Study of Cathepsin D Expression in Peripheral and Central Giant Cell Granuloma of the Jaws by Immunohistochemistry Technique

    PubMed Central

    Zargaran, Massoumeh; Moghimbeigi, Abbas; Afsharmoghadam, Noushin; Nasr Isfahani, Mohsen; Hashemi, Atefeh

    2016-01-01

    Statement of the Problem Peripheral and central giant cell granuloma are two common benign lesions of the oral cavity. In spite of histopathological similarities, they have different clinical behaviors. Cathepsin D is a lysosomal enzyme which has different functions on the basis of protein and applied peptide cleavage. Purpose This research aimed to evaluate and compare the expression level of Cathepsin D in these two lesions to find the reasons for the differences in clinical and biologic characteristics. Materials and Method The expression of Cathepsin D was investigated by using the immunohistochemistry method in 20 samples of peripheral giant cell granuloma and 20 samples of central giant cell granuloma. The percentage of stained giant cells (labeling index), the intensity of staining of giant cells, and staining-intensity-distribution in both groups were calculated and compared. Results The labeling indices of Cathepsin D in peripheral giant cell granuloma and central giant cell granuloma were 95.9±4.03 and 95.6±2.34, respectively. There was no significant difference in the percentages of stained giant cells between the two groups (p= 0.586). The intensity of staining of giant cells in central giant cell granuloma was stronger than that of peripheral giant cell granuloma (p> 0.001). Staining- intensity- distribution of giant cells in central giant cell granuloma was significantly greater than that of the peripheral type of lesion (p= 0.001). Conclusion The higher expression level of Cathepsin D in central giant cell granuloma compared to peripheral type of lesion can explain more aggressive behavior of central giant cell granuloma. PMID:27284554

  11. Histoid leprosy with giant lesions of fingers and toes.

    PubMed

    Rodriguez, Gerzaín; Henríquez, Rafael; Gallo, Shirley; Panqueva, César

    2015-01-01

    This work was conducted at the Facultad de Medicina, Universidad de La Sabana, and at the Facultad de Medicina, Universidad Surcolombiana. Histoid leprosy, a clinical and histological variant of multibacillary leprosy, may offer a challenging diagnosis even for experts. An 83-year-old woman presented with papular, nodular and tumor-like lesions of 3 years of evolution, affecting fingers, toes, hands, thighs and knees, and wide superficial ulcers in her lower calves. Cutaneous lymphoma was suspected. A biopsy of a nodule of the knee showed a diffuse dermal infiltrate with microvacuolated histiocytes, moderate numbers of lymphocytes and plasma cells. Cutaneous lymphoma was suggested. Immunohistochemistry (IHC) showed prominent CD68-positive macrophages, as well as CD3, CD8 and CD20 positive cells. Additional sections suggested cutaneous leishmaniasis. New biopsies were sent with the clinical diagnoses of cutaneous lymphoma, Kaposi´s sarcoma or lepromatous leprosy, as the patient had madarosis. These biopsies showed atrophic epidermis, a thin Grenz zone and diffuse inflammation with fusiform cells and pale vacuolated macrophages. ZiehlNeelsen stain showed abundant solid phagocytized bacilli with no globii formation. Abundant bacilli were demonstrated in the first biopsy. Histoid leprosy was diagnosed. The patient received the WHO multidrug therapy with excellent results. We concluded that Ziehl Neelsen staining should be used in the presence of a diffuse dermal infiltrate with fusiform and vacuolated histiocytes, which suggests a tumor, and an IHC particularly rich in CD68-positive macrophages; this will reveal abundant bacilli if the lesion is leprosy. A good clinical pathological correlation is essential to establish a proper diagnosis and management of the patient.

  12. Multifocal Central Giant Cell Granuloma - A Case Report

    PubMed Central

    Sandhya, Tamgadge; Avinash, Tamgadge; Snehal, Dhauskar; Neha, Tiwari; Uma, Mudaliar

    2016-01-01

    Central giant cell granuloma is a benign, aggressive neoplasm composed of multinucleated giant cells that almost exclusively occurs in the jaws though extra- gnathic incidence is rare. Multifocal CGCGs of the jaws are very rare and suggestive of systemic diseases such as hyperparathyroidism, an inherited syndrome such as Noonan- like multiple giant cell lesion syndrome or other disorders.Very few cases of multifocal CGCGs in the jaws without any concomitant systemic disease have been reported. This paper describes an unusual case reported to the Oral Surgery Department of Dr. D.Y.Patil Dental College & Hospital, Nerul, Navi-Mumbai in 2014 in a 45-year-old male with multifocal central giant cell granuloma involving maxilla and mandible. The serum alkaline phosphatase, calcium and phosphorus levels were within the normal limits. After complete clinical examination hyperparathyroidism and clinical characteristic of any syndromes such as Noonan-like syndrome and neurofibromatosis were ruled out. Thus this paper reports a non-syndromic multifocal central giant cell granuloma. PMID:27799978

  13. Giant cell reparative granuloma of the hallux following enchondroma

    PubMed Central

    Kamoun, Khaled; Sellami, Tarak; Jlailia, Zied; Abid, Layla; Jenzri, Mourad; Bouaziz, Mouna; Zouar, Omar

    2015-01-01

    Giant cell reparative granuloma (GCRG) is a rare, benign intra osseous lytic lesion occurring especially in gnathis bone but also seen in feet and hands. It has similar clinical and radiological presentations than giant cell tumor, chondroblastoma, aneurysmal bone cyst, and hyperparathyroidism brown tumors but with specific histological findings We report a case of a GCRG of hallux phalanx in 18 years old patient appearing many years after enchondroma curettage and grafting. Radiographs showed a multiloculated osteolytic lesions involving whole phalanx with cortical thinning and without fluid-fluid levels in CT view. Expected to be an enchondroma recurrence, second biopsy confirmed diagnosis of GCRG with specific histological findings. Although if aetiopathogeny remains unknown, GCRG is reported to be a local non neoplasic reaction to an intraosseous hemorrhage. Our exceptional case claims that this tumor can appear in reaction to cellular disturbance primary or secondary. PMID:26985281

  14. Giant cell reparative granuloma of the hallux following enchondroma.

    PubMed

    Kamoun, Khaled; Sellami, Tarak; Jlailia, Zied; Abid, Layla; Jenzri, Mourad; Bouaziz, Mouna; Zouar, Omar

    2015-01-01

    Giant cell reparative granuloma (GCRG) is a rare, benign intra osseous lytic lesion occurring especially in gnathis bone but also seen in feet and hands. It has similar clinical and radiological presentations than giant cell tumor, chondroblastoma, aneurysmal bone cyst, and hyperparathyroidism brown tumors but with specific histological findings We report a case of a GCRG of hallux phalanx in 18 years old patient appearing many years after enchondroma curettage and grafting. Radiographs showed a multiloculated osteolytic lesions involving whole phalanx with cortical thinning and without fluid-fluid levels in CT view. Expected to be an enchondroma recurrence, second biopsy confirmed diagnosis of GCRG with specific histological findings. Although if aetiopathogeny remains unknown, GCRG is reported to be a local non neoplasic reaction to an intraosseous hemorrhage. Our exceptional case claims that this tumor can appear in reaction to cellular disturbance primary or secondary. PMID:26985281

  15. Giant intraosseous cyst-like lesions in rheumatoid arthritis report of a case.

    PubMed

    Lohse, Anne; Carbillet, Jean-Pierre; Onimus, Michel; Stevenel, Françoise; Toussirot, Eric; Wendling, Daniel

    2003-02-01

    The term "intraosseous synovial cyst" is used to designate both the epiphyseal cyst-like lesions seen in patients with rheumatoid arthritis (RA) and mucoid cysts, which occur in a different setting. We report the case of a patient in whom a 4-cm cyst-like lesion developed in the left tibia 18 years after onset of RA and 6 years after osmic acid synovectomy of the left knee. Positive contrast arthrography and magnetic resonance imaging visualized a communication between the lesion and the joint space. Preexisting bone and joint lesions and increased intraarticular pressure play a major role in the genesis of cyst-like lesions in RA. In our patient, the osmic acid synovectomy may have contributed to the development of the lesion. "Synovial cyst" is a misnomer for these giant lesions, which are geodes rather than cysts. Despite their low incidence, these lesions deserve attention because they raise diagnostic and therapeutic problems.

  16. Virus-associated papillomatous skin lesions in a giant guitarfish Rhynchobatus djiddensis: a case report.

    PubMed

    Camus, Alvin; Dill, Jennifer; McDermott, Alexa; Camus, Melinda; Fan Ng, Terry Fei

    2016-01-13

    Although elasmobranch species are increasingly displayed in public aquaria, knowledge of disease in wild and captive elasmobranchs, as well as the agents involved, remains limited, and descriptions are often incomplete. This report describes papillomatous skin lesions in a juvenile giant guitarfish Rhynchobatus djiddensis associated with intranuclear viral particles. Skin biopsies were collected from multiple, friable, raised, villonodular skin lesions affecting pigmented and non-pigmented skin of the caudal fin and ventrum, respectively. Microscopic examination revealed papillary proliferation of the epidermis, with widespread marked karyomegaly of squamous epithelial cells. In approximately 75% of nuclei, chromatin was marginated by one to multiple, large, amphophilic inclusions. Large numbers of unencapsulated, 75 nm, icosahedral viral particles were observed to form large arrays in affected nuclei using transmission electron microscopy. Based on intranuclear location, particle size and morphology, a consensus nested-PCR for adenovirus polymerase was attempted. However, no adenoviral gene sequence was amplified. The nature of the involved virus remains unknown and an ongoing area of investigation. Lesions regressed completely over a 6 mo period, during which time the animal showed no signs of systemic illness, and there has been no recrudescence for 6 mo following resolution. Two cohorts of similar age and in close contact with the case animal were unaffected. PMID:26758659

  17. Virus-associated papillomatous skin lesions in a giant guitarfish Rhynchobatus djiddensis: a case report.

    PubMed

    Camus, Alvin; Dill, Jennifer; McDermott, Alexa; Camus, Melinda; Fan Ng, Terry Fei

    2016-01-13

    Although elasmobranch species are increasingly displayed in public aquaria, knowledge of disease in wild and captive elasmobranchs, as well as the agents involved, remains limited, and descriptions are often incomplete. This report describes papillomatous skin lesions in a juvenile giant guitarfish Rhynchobatus djiddensis associated with intranuclear viral particles. Skin biopsies were collected from multiple, friable, raised, villonodular skin lesions affecting pigmented and non-pigmented skin of the caudal fin and ventrum, respectively. Microscopic examination revealed papillary proliferation of the epidermis, with widespread marked karyomegaly of squamous epithelial cells. In approximately 75% of nuclei, chromatin was marginated by one to multiple, large, amphophilic inclusions. Large numbers of unencapsulated, 75 nm, icosahedral viral particles were observed to form large arrays in affected nuclei using transmission electron microscopy. Based on intranuclear location, particle size and morphology, a consensus nested-PCR for adenovirus polymerase was attempted. However, no adenoviral gene sequence was amplified. The nature of the involved virus remains unknown and an ongoing area of investigation. Lesions regressed completely over a 6 mo period, during which time the animal showed no signs of systemic illness, and there has been no recrudescence for 6 mo following resolution. Two cohorts of similar age and in close contact with the case animal were unaffected.

  18. Anaplastic giant cell thyroid carcinoma.

    PubMed

    Wallin, G; Lundell, G; Tennvall, J

    2004-01-01

    Anaplastic (giant cell) thyroid carcinoma (ATC), is one of the most aggressive malignancies in humans with a median survival time after diagnosis of 3-6 months. Death from ATC was earlier seen because of local growth and suffocation. ATC is uncommon, accounting for less than 5 % of all thyroid carcinomas. The diagnosis can be established by means of multiple fine needle aspiration biopsies, which are neither harmful nor troublesome for the patient. The cytological diagnosis of this high-grade malignant tumour is usually not difficult for a well trained cytologist. The intention to treat patients with ATC is cure, although only few of them survive. The majority of the patients are older than 60 years and treatment must be influenced by their high age. We have by using a combined modality regimen succeeded in achieving local control in most patients. Every effort should be made to control the primary tumour and thereby improve the quality of remaining life and it is important for patients, relatives and the personnel to know that cure is not impossible. Different treatment combinations have been used since 30 years including radiotherapy, cytostatic drugs and surgery, when feasible. In our latest combined regimen, 22 patients were treated with hyper fractionated radiotherapy 1.6Gy x 2 to a total target dose of 46 Gy given preoperatively, 20 mg doxorubicin was administered intravenously once weekly and surgery was carried out 2-3 weeks after the radiotherapy. 17 of these 22 patients were operated upon and none of these 17 patients got a local recurrence. In the future we are awaiting the development of new therapeutic approaches to this aggressive type of carcinoma. Inhibitors of angiogenesis might be useful. Combretastatin has displayed cytotoxicity against ATC cell lines and has had a positive effect on ATC in a patient. Sodium iodide symporter (NIS) genetherapy is also being currently considered for dedifferentiated thyroid carcinomas with the ultimate aim of

  19. Giant Cell Arteritis and Mortality

    PubMed Central

    Crow, R. Wade; Warner, Judith E. A.; Alder, Stephen C.; Zhang, Kang; Schulman, Susan; Digre, Kathleen B.

    2009-01-01

    Background Giant cell arteritis (GCA) is a systemic vasculitis of elderly individuals associated with significant morbidity, including blindness, stroke, and myocardial infarction. Previous studies have investigated whether GCA is associated with increased mortality, with conflicting results. The objective of this study is to determine whether GCA, is associated with increased mortality. Methods Forty-four cases with GCA were identified from the University of Utah Health Sciences Center, the major tertiary care center for the Intermountain West. The Utah Population Database, a unique biomedical information resource, selected cases and age- and gender-matched controls. Cases were defined as patients with a temporal artery biopsy-proven diagnosis of GCA (international classification of diseases [ICD]-9 code 446.5) between 1991 and 2005. Exclusion criteria included a negative biopsy, alternative diagnoses, or insufficient clinical data. For each of the 44 cases, 100 controls were identified; thus, 4,400 controls were included in the data analysis. Median survival time and 5-year cumulative survival were measured for cases and controls. Results The median survival time for the 44 GCA cases was 1,357 days (3.71 years) after diagnosis compared with 3,044 days (8.34 years) for the 4,400 controls (p = 0.04). Five-year cumulative survival was 67% for the control group versus 35% for the cases (p < .001). Survival rates for cases and controls converged at approximately 11.12 years. Conclusions Patients with GCA were more likely than age- and gender-matched controls to die within the first 5 years following diagnosis. PMID:19196636

  20. Histological and clinical characteristics of malignant giant cell tumor of bone.

    PubMed

    Gong, Lihua; Liu, Weifeng; Sun, Xiaoqi; Sajdik, Constantin; Tian, Xinxia; Niu, Xiaohui; Huang, Xiaoyuan

    2012-03-01

    Malignant giant cell tumors of bone (MGCTB) are rare, and the diagnosis can be difficult due to the occurrence of a variety of malignant tumors containing giant cells. To better understand its clinicopathological features, we have reviewed our experience with 17 cases of MGCTB. Five cases were primary malignant giant cell tumor of bone (PMGCTB), and 12 cases were giant cell tumors of bone initially diagnosed as benign but malignant in a recurrent lesion (secondary MGCTB, SMGCTB). The patients included six women and 11 men (age ranged from 17 to 52 years; mean, 30.5 years). The tumor arose in the femur (six cases), the tibia (seven cases), the humerus (three cases), and the fibula (one case). Microscopically, PMGCTB showed both conventional giant cell tumor and malignant sarcoma features. SMGCTB were initially diagnosed as conventional giant cell tumor of bone, the recurrent lesion showing malignant features. Histologically, the malignant components included osteosarcoma (11 cases), undifferentiated high-grade pleomorphic sarcoma (two cases), and fibrosarcoma (four cases). SMGCTB cases showed strong expression of p53. Follow-up information revealed that four patients died of lung metastasis, two patients are alive with lung metastases, and 11 patients are alive without tumor. MGCTB should be considered as a high-grade sarcoma. It must be distinguished from GCTB and other malignant tumors containing giant cells. p53 might play a role in the malignant transformation of GCTB. PMID:22350004

  1. What Are Polymyalgia Rheumatica and Giant Cell Arteritis?

    MedlinePlus

    ... Cell Arteritis Find a Clinical Trial Journal Articles What Are Polymyalgia Rheumatica and Giant Cell Arteritis? PDF Version Size: 58 KB November 2014 What Are Polymyalgia Rheumatica and Giant Cell Arteritis? Fast ...

  2. Sunspots and Giant-Cell Convection

    NASA Technical Reports Server (NTRS)

    Moore, Ron L.; Hathaway, David H.; Reichmann, Ed J.

    2000-01-01

    From analysis of Doppler velocity images from SOHO/MDI, Hathaway et al (2000, Solar Phys., in press) have found clear evidence for giant convection cells that fill the solar surface, have diameters 3 - 10 times that typical of supergranules, and have lifetimes approx. greater than 10 days. Analogous to the superposition of the granular convection on the supergranular convection, the approx. 30,000 km diameter supergranules are superposed on these still larger giant cells. Because the giant cells make up the large-scale end of a continuous power spectrum that peaks at the size scale of supergranules, it appears that the giant cells are made by the same mode of convection as the supergranules. This suggests that the giant cells are similar to supergranules, just longer-lived, larger in diameter, and deeper. Here we point out that the range of lengths of large bipolar sunspot groups is similar to the size range of giant cells. This, along with the long lives (weeks) of large sunspots, suggests that large sunspots sit in long-lived, deep downflows at the corners of giant cells, and that the distance from leader to follower sunspots in large bipolar groups is the distance from one giant-cell corner to the next. By this line of reasoning, an unusually large and strong downdraft might pull in both legs of a rising spot-group magnetic flux loop, resulting in the formation of a delta sunspot. This leads us to suggest that a large, strong giant-cell corner downdraft should be present at the birthplaces of large delta sunspots for some time (days to weeks) before the birth. Thus, early detection of such downdrafts by local helioscismology might provide an early warning for the formation of those active regions (large delta sunspot groups) that produce the Sun's most violent flares and coronal mass ejections. This work is supported by NASA's Office of Space Science through the Solar Physics Branch of its Sun-Earth Connection Program.

  3. Correlation of Histopathologic Features with Demographic, Gross and Radiographic Findings in Giant Cell Granulomas of the Jaws

    PubMed Central

    Aghbali, Amirala; Sina, Mahmood; Vahid Pakdel, Seyyed Mahdi; Emamverdizadeh, Parya; Kouhsoltani, Maryam; Mahmoudi, Seyyed Mostafa; Janani, Maryam

    2013-01-01

    Background and aims. The correlation between morphology of giant cells in peripheral granulomas of the jaws and the aggressive behavior of the lesion is unknown. This study investigated the correlation between the histopathologic features with demographic, gross and radiographic findings in giant cell granulomas. Materials and methods. In this analytical study, data from 23 cases of central giant cell granuloma (CGCG) and 42 cases of peripheral giant cell granuloma (PGCG) were analyzed, focusing on age, gender, location, and gross and radiographic features. For each patient, microscopic slides were assessed in terms of histologic features of giant cells and stroma. Results. No significant differences were found in the mean number of nuclei or the size of nuclei and giant cell distribution patterns between the jaws and genders in both lesions (P >0.05). Correlation between the mean number of nuclei and age was positively significant and correlation between the size of nuclei and age was negatively significant (P < 0.05). In addition, correlation between the mean number and size of nuclei and the size of the lesion was significant (P < 0.05). Correlation between stroma and aggressiveness of CGCGs was not statistically significant. Correlation between histopathologic features and radiographic findings was not statistically significant (P > 0.05). Conclusion. There were correlations between the mean number of nuclei per giant cell and the size of the lesion and age, and between the size of nuclei and size of the lesion. No relation was observed between histopathologic and radiographic features. PMID:24578821

  4. Primary osteoclast-like giant cell tumor of parotid gland: A rare extraskeletal presentation with diagnostic challenges

    PubMed Central

    Singh, Ritika; Zaheer, Sufian; Mandal, Ashish K

    2016-01-01

    Primary osteoclast-like giant cell tumor (OC-GCT) has been rarely described in extraskeletal sites. The diagnosis primarily hinges on the detection of giant cells. However, these giant cells are also seen in many giant cell lesions, thus creating diagnostic confusion and dilemma. Here, we describe a rare case of a 24-year-old male with primary extraskeletal, OC-GCT presenting as a swelling in the right parotid region and highlight its cytological, histological and immunohistochemical characteristics with diagnostic challenges. PMID:27601838

  5. Primary osteoclast-like giant cell tumor of parotid gland: A rare extraskeletal presentation with diagnostic challenges.

    PubMed

    Singh, Ritika; Zaheer, Sufian; Mandal, Ashish K

    2016-01-01

    Primary osteoclast-like giant cell tumor (OC-GCT) has been rarely described in extraskeletal sites. The diagnosis primarily hinges on the detection of giant cells. However, these giant cells are also seen in many giant cell lesions, thus creating diagnostic confusion and dilemma. Here, we describe a rare case of a 24-year-old male with primary extraskeletal, OC-GCT presenting as a swelling in the right parotid region and highlight its cytological, histological and immunohistochemical characteristics with diagnostic challenges. PMID:27601838

  6. Floret-like multinucleated giant cells in neurofibroma

    PubMed Central

    Shaktawat, Sameer Singh; Golka, Dariusz

    2007-01-01

    This short report discusses a case of neurofibroma containing floret-like multinucleated giant cells. This being the second such case in the literature. Floret-like multinucleated giant cells have been reported in gynaecomastia and neurofibroma in neurofibromatosis type 1. These cells have been reported in uncommon soft tissue tumours including pleomorphic lipoma, giant cell collagenoma, giant cell fibroblastoma and giant cell angiofibroma. We recommend these cells to be interpreted carefully keeping in mind the rare malignant change in neurofibromas. Immunohistochemistry would help in defining the nature of such cells. PMID:18067673

  7. Floret-like multinucleated giant cells in neurofibroma.

    PubMed

    Shaktawat, Sameer Singh; Golka, Dariusz

    2007-12-08

    This short report discusses a case of neurofibroma containing floret-like multinucleated giant cells. This being the second such case in the literature. Floret-like multinucleated giant cells have been reported in gynaecomastia and neurofibroma in neurofibromatosis type 1. These cells have been reported in uncommon soft tissue tumours including pleomorphic lipoma, giant cell collagenoma, giant cell fibroblastoma and giant cell angiofibroma. We recommend these cells to be interpreted carefully keeping in mind the rare malignant change in neurofibromas. Immunohistochemistry would help in defining the nature of such cells.

  8. Giant cell tumor of lower end of tibia.

    PubMed

    Bami, Monish; Nayak, Ashok R; Kulkarni, Shreepad; Kulkarni, Avinash; Gupta, Rupali

    2013-01-01

    Introduction. Giant cell tumor of bones is an unusual neoplasm that accounts for 4% of all primary tumors of bone, and it represents about 10% of malignant primary bone tumors with its different grades from borderline to high grade malignancy. Case Report. A 35-year-old patient presented with complains of pain and swelling in left ankle since 1 year following a twisting injury to his left ankle. On examination, swelling was present over the distal and anterior part of leg and movements of ankle joint were normal. All routine blood investigations were normal. X-ray and CT ankle showed morphology of subarticular well-defined expansile lytic lesion in lower end of left tibia suggestive of giant cell tumor. Histopathology of the tissue shows multinucleated giant cells with uniform vesicular nucleus and mononuclear cells which are spindle shaped with uniform vesicular nucleus suggestive of GCT. The patient was treated by excision, curettage, and bone cement to fill the defect. Conclusion. The patient at 12-month followup is doing well and walking without any pain comfortably and with full range of motion at ankle joint with articular congruity maintained and no signs of recurrences. PMID:23844298

  9. Giant Cell Reparative Granuloma of the Petrous Temporal Bone

    PubMed Central

    Williams, Joy C.; Thorell, William E.; Treves, John S.; Fidler, Mary E.; Moore, Gary F.; Leibrock, Lyal G.

    2000-01-01

    Giant cell reparative granuloma (GCRG) is an unusual, benign bone lesion that most commonly affects the maxilla and mandible; skull involvement is rare. The etiology is uncertain but may be related to trauma. GCRG is difficult to distinguish from giant cell tumor of the bone and has a lower recurrence rate. Thirteen reports of temporal bone GCRG in 11 patients have been reported. One report of a petrous GCRG in a 3-year-old girl has been identified. A 38-year-old male presented with a 2-year history of fullness in his left ear, ipsilateral hearing loss, and intermittent cacosmia. Computed tomography and magnetic resonance imaging revealed a large left-sided anterior temporal extradural mass. The patient underwent a left frontotemporal craniotomy and resection of a left temporal fossa tumor that involved the petrous and squamous parts of the temporal bone. The patient's post-operative course was uneventful, except for increased hearing loss secondary to opening of the epitympanum. Follow-up at one month revealed no other problems. Histopathology of the specimen was consistent with a giant cell reparative granuloma. ImagesFigure 1Figure 2p91-aFigure 3 PMID:17171108

  10. Giant Cell Tumor of Tendon Sheath in the Knee

    PubMed Central

    Ghnaimat, Malek; Alodat, Mohannad; Aljazazi, Mohammad; Al-Zaben, Raad; Alshwabkah, Jamal

    2016-01-01

    The giant cell tumor of the tendon sheath (GCTTS) is a benign lesion which arises from the synovium of a joint, bursa or tendon sheath, with 85% of the tumors occurring in the fingers and 12% of the tumors located in large joints such as the knee and ankle. The GCTTS is usually monoarticular, slowly proliferative and rarely locally aggressive. This paper reports three cases of this rare lesion in the knee. Patients presented with painful swelling in the anterior knee, MRI showed localized soft tissue masses which were able to be excised. A follow up of the cases showed no recurrences. This case report emphasizes the importance of considering GCTTS in the differential diagnosis of soft tissue swelling and pain in large joints.

  11. Central giant cell reparative granuloma of the ethmoids with bilateral proptosis and intracranial extension.

    PubMed

    Gupta, Subhash C; Jain, Sachin; Mehrotra, Ravi; Singh, Himanshu P

    2013-02-01

    Central giant cell reparative granuloma is an infrequent, benign, proliferating lesion affecting the maxilla, mandible and, rarely, cranial bones. A 16-year-old girl presented with a 6-month history of recurrent nasal bleeding, a mass in the nose, difficulty in nasal breathing, a change in voice, and bilateral proptosis. Radiologically, an extensive ethmoidal mass was seen. Histologic examination revealed a central giant cell reparative granuloma. After endoscopic removal, the patient was symptom-free at the 12-month follow-up. The clinical picture of central giant cell reparative granuloma of the ethmoids is discussed, along with the differential diagnosis, histologic evaluation, appearance on computed tomography, and endoscopic management of this lesion. PMID:23460226

  12. Temporal bone central giant-cell granuloma presenting as a serous otitis media.

    PubMed

    Rudic, Milan; Grayeli, Alexis Bozorg; Cazals-Hatem, Dominique; Cyna-Gorse, Françoise; Bouccara, Didier; Sterkers, Olivier

    2008-05-01

    Central giant cell granuloma is a benign intraosseous lesion that most commonly occurs in the facial bones. Its location in the temporal bone is extremely rare and only 20 cases have been reported in the literature. We report a case of an adult female patient presenting with a right serous otitis media and mastoiditis associated with a mixed hearing loss during 6 months. CT-scan and MRI revealed a temporal bone tumor involving the mastoid, and surrounding the right temporo-mandibular joint. Tumor was totally removed after a canal-wall-down mastoidectomy and middle ear exclusion. Pathology revealed a central giant cell granuloma. Seven months following the surgery there was no evidence of recurrence. Central giant cell granuloma is a rare temporal bone lesion, with non specific clinical and imaging signs but characteristic pathological features. Today, a total surgical removal and regular MRI follow-up is the best management option.

  13. [Giant cell tumours in a pyramidal bone: a clinical case and a review of the literature].

    PubMed

    Gutiérrez-Santiago, M M; González-Arteaga, J; Hidalgo-Ovejero, A M

    2012-01-01

    Giant cell tumours (GCT) of the bone are benign, but locally invasive tumours. We present a new case of carpus GCT, involving the triquetrum. The diagnosis required a prior biopsy before doing the block resection. This treatment is the best option to avoid recurrences. We review the literature on this particular lesion in the carpus bone.

  14. Multiple Giant Cell Tumors of Tendon Sheath Found within a Single Digit of a 9-Year-Old

    PubMed Central

    Fitzhugh, Valerie A.; Gibson, Peter D.; Didesch, Jacob; Ahmed, Irfan

    2016-01-01

    Giant cell tumor of tendon sheath is one of the most common soft tissue tumors of the hand. These tumors typically occur in the third or fourth decade of life and present as solitary nodules on a single digit. Currently, the greatest reported number of lesions found within a single digit is five. Although uncommon, giant cell tumor of tendon sheath does occur in the pediatric population. Herein we present a report of a rare case of GCTTS in a child in which seven lesions were identified within a single digit—the greatest number of lesions within a single digit reported to date. PMID:27595029

  15. Locally administered zoledronic Acid therapy for giant cell tumor of bone.

    PubMed

    Nishisho, Toshihiko; Hanaoka, Naoyoshi; Endo, Kenji; Takahashi, Mitsuhiko; Yasui, Natsuo

    2011-07-07

    Giant cell tumor of bone is locally aggressive and occurs in the meta-epiphyseal region of long bones. Because of its high recurrence rate, local adjuvant therapies such as phenol or liquid nitrogen have been recommended. In the present study, zoledronic acid, a nitrogen-containing bisphosphonate, was administered locally as an adjuvant during a biopsy. An otherwise healthy 43-year-old man presented with pain and swelling in the right knee. Plain radiographs showed an osteolytic lesion of the right proximal tibia. An open biopsy was performed and the intraoperative pathologic diagnosis was giant cell tumor of bone. Following biopsy, the defect was filled with betatricalcium phosphate, and 4 mg of zoledronic acid was locally administered into the tumor lesion. Two months after the biopsy, curettage and bone grafting were performed. Sections were obtained during the curettage for histology to evaluate the response to bisphosphonate treatment. Histologic examination revealed massive tumor cell death in the lesion in which both stromal cells and osteoclast-like giant cells were necrotic. Curettage was performed and the defect was filled with a commercial preshaped hydroxyapatitetricalcium phosphate bone substitute. Eighteen months after curettage, the patient had regained full range of motion and good function of the knee, and radiographs at 18 months after curettage revealed no recurrence of giant cell tumor of bone.

  16. The Clinical Approach Toward Giant Cell Tumor of Bone

    PubMed Central

    van der Heijden, Lizz; Dijkstra, P.D. Sander; van de Sande, Michiel A.J.; Kroep, Judith R.; Nout, Remi A.; van Rijswijk, Carla S.P.; Bovée, Judith V.M.G.; Hogendoorn, Pancras C.W.

    2014-01-01

    We provide an overview of imaging, histopathology, genetics, and multidisciplinary treatment of giant cell tumor of bone (GCTB), an intermediate, locally aggressive but rarely metastasizing tumor. Overexpression of receptor activator of nuclear factor κB ligand (RANKL) by mononuclear neoplastic stromal cells promotes recruitment of numerous reactive multinucleated giant cells. Conventional radiographs show a typical eccentric lytic lesion, mostly located in the meta-epiphyseal area of long bones. GCTB may also arise in the axial skeleton and very occasionally in the small bones of hands and feet. Magnetic resonance imaging is necessary to evaluate the extent of GCTB within bone and surrounding soft tissues to plan a surgical approach. Curettage with local adjuvants is the preferred treatment. Recurrence rates after curettage with phenol and polymethylmethacrylate (PMMA; 8%–27%) or cryosurgery and PMMA (0%–20%) are comparable. Resection is indicated when joint salvage is not feasible (e.g., intra-articular fracture with soft tissue component). Denosumab (RANKL inhibitor) blocks and bisphosphonates inhibit GCTB-derived osteoclast resorption. With bisphosphonates, stabilization of local and metastatic disease has been reported, although level of evidence was low. Denosumab has been studied to a larger extent and seems to be effective in facilitating intralesional surgery after therapy. Denosumab was recently registered for unresectable disease. Moderate-dose radiotherapy (40–55 Gy) is restricted to rare cases in which surgery would lead to unacceptable morbidity and RANKL inhibitors are contraindicated or unavailable. PMID:24718514

  17. Sodium efflux from perfused giant algal cells.

    PubMed

    Clint, G M; Macrobbie, E A

    1987-06-01

    Internodal cells of the giant alga Chara corallina were perfused internally to replace the native cytoplasm, tonoplast and vacuole with artificial cytoplasm. Sodium efflux from perfused cells, measured by including (22)Na in the perfusion media, was increased by increasing the internal sodium concentration and by decreasing the external pH, and was inhibited by external application of the renal diuretic amiloride. The sodium efflux was markedly ATP-dependent, with a 50-fold decrease in efflux observed after perfusion with media lacking ATP. Efflux in the presence of ATP was reduced by 33% by inclusion of 10 μM N,N'-dicyclohexylcarbodiimide in the perfusion medium. The membrane potential of the perfused cells approximated that of intact cells from the same culture. It is suggested that sodium efflux in perfused Chara cells proceeds via a secondary antiporter with protons, regulated by ATP in a catalytic role and with the proton motive force acting as the energy source.

  18. Giant cell granuloma of the temporal bone in a mixed martial arts fighter.

    PubMed

    Maerki, Jennifer; Riddle, Nicole D; Newman, Jason; Husson, Michael A; Lee, John Y K

    2012-10-01

    Background and Importance Giant cell granuloma (GCG) is a rare, benign, non-neoplastic lesion of the head and neck. More common in the jaw bones, there have been few reports of the lesion arising in the temporal bone. Initially referred to as a "giant cell reparative granuloma," due to the previously accepted notion of its nature in attempting to repair areas of injury, the term "giant cell granuloma" is now more frequently used as this lesion has been found in patients without a history of trauma. In addition, several cases with a destructive nature, in contrast to a reparative one, have been observed. Clinical Presentation We report a case of GCG presenting as a head and neck tumor with dural attachments and extension into the middle cranial fossa in a mixed martial arts fighter. Conclusion Giant cell granulomas are typically treated surgically and have a good prognosis; however, care must be taken when they present in unusual locations. This case supports the theory of trauma and inflammation as risk factors for GCG. PMID:23946929

  19. Synchronous Multicentric Giant Cell Tumour of Distal Radius and Sacrum with Pulmonary Metastases

    PubMed Central

    Tandra, Varun Sharma; Kotha, Krishna Mohan Reddy; Satyanarayana, Moorthy Gadisetti Venkata; Vadlamani, Kali Varaprasad; Yerravalli, Vyjayanthi

    2015-01-01

    Giant cell tumour (GCT) is an uncommon primary bone tumour, and its multicentric presentation is exceedingly rare. We report a case of a 45-year-old female who presented to us with GCT of left distal radius. On the skeletal survey, osteolytic lesion was noted in her right sacral ala. Biopsy confirmed both lesions as GCT. Pulmonary metastasis was also present. Resection-reconstruction arthroplasty for distal radius and thorough curettage and bone grafting of the sacral lesion were done. Multicentric GCT involving distal radius and sacrum with primary sacral involvement is not reported so far to our knowledge. PMID:26106496

  20. Synchronous Multicentric Giant Cell Tumour of Distal Radius and Sacrum with Pulmonary Metastases.

    PubMed

    Tandra, Varun Sharma; Kotha, Krishna Mohan Reddy; Satyanarayana, Moorthy Gadisetti Venkata; Vadlamani, Kali Varaprasad; Yerravalli, Vyjayanthi

    2015-01-01

    Giant cell tumour (GCT) is an uncommon primary bone tumour, and its multicentric presentation is exceedingly rare. We report a case of a 45-year-old female who presented to us with GCT of left distal radius. On the skeletal survey, osteolytic lesion was noted in her right sacral ala. Biopsy confirmed both lesions as GCT. Pulmonary metastasis was also present. Resection-reconstruction arthroplasty for distal radius and thorough curettage and bone grafting of the sacral lesion were done. Multicentric GCT involving distal radius and sacrum with primary sacral involvement is not reported so far to our knowledge. PMID:26106496

  1. [Aortitis in giant cell arteritis and its complications].

    PubMed

    Espitia, O; Agard, C

    2013-07-01

    Aortitis is a serious complication of giant cell arteritis (GCA), because of the risk of aortic aneurism, rupture, or dissection. Aortitis is present either at presentation or, more frequently, occurs as a delayed complication, typically as an aortic aneurism of the ascending part of the aorta. An aortic aneurism may occur in up to 10% of patients. Aortitis is sometimes associated to arteritis of the supra-aortic vessels. Risk factors for aortitis remain unknown. Recent clinical studies indicate that prevalence of aortitis was initially under-estimated. Imaging studies show signs of infra-clinical aortitis in 20 to 65% of cases at diagnosis. Using ultrasonography, thickening of the vascular wall with an hypoechoic halo around the abdominal aorta is suggestive of abdominal aortitis. Positron emission tomography shows a metabolic hypersignal of the aorta in about 50% of patients with giant cell arteritis. Aortic computed tomographic (CT) scan visualizes aneurysmal dilatations, ectasia or focal or concentric parietal thickenings. When present at the time of diagnosis of GCA, these findings seem to be associated with frequent relapses and perhaps with a higher long-term vascular mortality rate. Therefore, we recommend the screening of aortitis lesions at GCA diagnosis by an aortic CT-scan and follow-up. Therapeutic trials should be conducted to try to improve the treatment of aortitis in GCA. PMID:23523343

  2. Pulmonary metastasis of giant cell tumor of bones.

    PubMed

    Muheremu, Aikeremujiang; Niu, Xiaohui

    2014-08-20

    Giant cell tumor of bone (GCTB) accounts for 5% of primary skeletal tumors. Although it is considered to be a benign lesion, there are still incidences of pulmonary metastasis. Pulmonary metastasis of GCTB may be affected by tumor grading and localization as well as the age, gender and overall health status of the patient. Patients with local recurrence are more likely to develop pulmonary metastasis of GCTB. High expression of some genes, cytokines and chemokines may also be closely related to the metastatic potential and prognosis of GCTB. The treatment of the primary GCTB is key to the final outcome of the disease, as intralesional curettage has a significantly higher local recurrence and pulmonary metastasis rate than wide resection. However, even patients with pulmonary metastasis seem to have a good prognosis after timely and appropriate surgical resection. It is hoped that with the development of novel surgical methods and drugs, pulmonary metastasis of GCTB can be prevented and treated more effectively.

  3. [Ocular complications of giant cell arteritis].

    PubMed

    Liozon, E; Ly, K-H; Robert, P-Y

    2013-07-01

    Permanent visual loss (PVL) is the most dreaded complication of giant cell arteritis (GCA). It results from anterior ischemic optic neuropathy or, less commonly, retinal artery occlusion. This complication still occurs in 14 to 20% of patients and is typically devastating and permanent, although it is highly preventable by an early diagnosis of giant cell arteritis and appropriate glucocorticoid treatment. Transient ischemic symptoms such as amaurosis fugax, episodes of blurred vision or diplopia may occur, either heralding visual loss or remaining isolated. In studies, the main predictors of PVL are jaw claudication, amaurosis fugax, lack of systemic "B" symptoms, a modestly increased ESR and a higher haemoglobin level. The evaluation of a GCA patient with PVL includes emergency fundoscopy completed by fluorescein angiography, immediate erythrocyte sedimentation rate, C-reactive protein, and complete blood count. Treatment is extremely urgent mainly because, if left untreated, GCA is associated with visual loss in the fellow eye within days in up to 50% of individuals. Treatment may begin with high-dose intravenous methylprednisolone, followed by oral prednisone administered at 1 mg/kg per day. Daily adjunctive aspirin orally may be added since it has been shown, in retrospective studies, to protect against stroke and visual loss. Although treatment duration of complicated GCA is not codified, an initial PVL deserves close monitoring of patient's systemic symptoms, ESR and CRP to avoid relapses due to a significant risk of late recurrence of visual loss during steroid tapering. PMID:23523078

  4. Molecular genetic analysis of giant cell glioblastomas.

    PubMed Central

    Meyer-Puttlitz, B.; Hayashi, Y.; Waha, A.; Rollbrocker, B.; Boström, J.; Wiestler, O. D.; Louis, D. N.; Reifenberger, G.; von Deimling, A.

    1997-01-01

    Glioblastomas (GBMs) are a heterogeneous group of tumors. Recently, distinct molecular genetic alterations have been linked to subgroups of patients with GBM. Giant cell (gc)GBMs are a rare variant of GBM characterized by a marked preponderance of multinucleated giant cells. Several reports have associated this entity with a more favorable prognosis than the majority of GBMs. To evaluate whether gcGBM may also represent a genetically defined subgroup of GBM, we analyzed a series of 19 gcGBMs for mutations in the TP53 gene for amplification of the EGFR and CDK4 genes and for homozygous deletions in the CDKN2A (p16/MTS1) gene. Seventeen of nineteen gcGBMs carried TP53 mutations whereas EGFR and CDK4 gene amplification was seen in only one tumor each and homozygous deletion of CDKN2A was not observed at all. The strikingly high incidence of TP53 mutations and the relative absence of other genetic alterations groups gcGBM together with a previously recognized molecular genetic variant of GBM (type 1 GBM). It is tempting to speculate that the better prognosis of gcGBM patients may result from the low incidence of EGFR amplification and CDKN2A deletion, changes known for their growth-promoting potential. Images Figure 1 PMID:9284834

  5. [Prevalence and clinicopathological characteristics of giant cell tumors].

    PubMed

    Estrada-Villaseñor, E G; Linares-González, L M; Delgado-Cedillo, E A; González-Guzmán, R; Rico-Martínez, G

    2015-01-01

    The frequency of giant cell tumors reported in the literature is very variable. Considering that our population has its own features, which distinguish it from the Anglo-Saxon and Asian populations, we think that both the frequency and the clinical characteristics of giant cell tumors in our population are different. The major aim of this paper was to determine the frequency and clinicopathological characteristics of giant cell tumors of the bone. A cross-sectional descriptive study was conducted of the cases diagnosed at our service as giant cell tumors of the bone from January to December 2013. The electronic clinical records, radiologic records and histologic slides from each case were reviewed. Giant cell tumors represented 17% of total bone tumors and 28% of benign tumors. Patients included 13 females and 18 males. The most frequent locations of giant cell tumors were: the proximal tibia, 9 cases (29%), and the distal femur, 6 cases (19%). Forty-five percent of giant cell tumors were associated with aneurysmal bone cyst (ABC) (14 cases) and one case (3%) was malignant. The frequency of giant cell tumors in this case series was intermediate, that is, higher than the one reported in Anglo-Saxon countries (usually low), but without reaching the frequency rates reported in Asian countries (high).

  6. [Prevalence and clinicopathological characteristics of giant cell tumors].

    PubMed

    Estrada-Villaseñor, E G; Linares-González, L M; Delgado-Cedillo, E A; González-Guzmán, R; Rico-Martínez, G

    2015-01-01

    The frequency of giant cell tumors reported in the literature is very variable. Considering that our population has its own features, which distinguish it from the Anglo-Saxon and Asian populations, we think that both the frequency and the clinical characteristics of giant cell tumors in our population are different. The major aim of this paper was to determine the frequency and clinicopathological characteristics of giant cell tumors of the bone. A cross-sectional descriptive study was conducted of the cases diagnosed at our service as giant cell tumors of the bone from January to December 2013. The electronic clinical records, radiologic records and histologic slides from each case were reviewed. Giant cell tumors represented 17% of total bone tumors and 28% of benign tumors. Patients included 13 females and 18 males. The most frequent locations of giant cell tumors were: the proximal tibia, 9 cases (29%), and the distal femur, 6 cases (19%). Forty-five percent of giant cell tumors were associated with aneurysmal bone cyst (ABC) (14 cases) and one case (3%) was malignant. The frequency of giant cell tumors in this case series was intermediate, that is, higher than the one reported in Anglo-Saxon countries (usually low), but without reaching the frequency rates reported in Asian countries (high). PMID:27403516

  7. Interleukin-1 blockade in refractory giant cell arteritis.

    PubMed

    Ly, Kim-Heang; Stirnemann, Jérôme; Liozon, Eric; Michel, Marc; Fain, Olivier; Fauchais, Anne-Laure

    2014-01-01

    Giant cell arteritis is a primary large-vessel vasculitis characterized by an arterial wall inflammation associated with intimal hyperplasia leading to arterial occlusion. Glucocorticoids remain the mainstay of giant cell arteritis treatment. However, relapses and glucocorticoid-related complications are frequent and therapeutic options for refractory giant cell arteritis are quite limited. Like tumor necrosis factor-α and interleukin-6, interleukin-1β is also highly expressed in inflamed arterial walls of patients with giant cell arteritis and may contribute in the pathogenesis of this disease. We report treatment of three cases of refractory giant cell arteritis successfully treated with anakinra, an interleukin-1 blockade therapy. Anakinra was effective for all patients, yielding improvement in their inflammation biomarkers and/or in their symptoms, as well as a disappearance of arterial inflammation in PET/CT for two of them.

  8. Radionuclide bone scanning in giant cell tumor

    SciTech Connect

    Van Nostrand, D.; Madewell, J.E.; McNiesh, L.M.; Kyle, R.W.; Sweet, D.

    1986-03-01

    Radionuclide bone scan findings are described and correlated with pathology in 23 patients with giant cell tumor (GCT) of the bone. The degree of radionuclide activity was markedly increased in 20 (87%), minimally increased in three (13%), and decreased in none of the patients. Of the 23 patients with increased radioactivity, the pattern was diffuse in 11 (48%) and doughnut in 12 (52%). Extended patterns of radioactivity were present in 19 of 22 patients; however, none were associated with true tumor extension. Bone scanning did not aid in the detection of GCT, was nonspecific, and did not differentiate benign from malignant GCT. Although radioactivity extended beyond the radiographic abnormality in the majority of patients, this was most likely secondary to other bony abnormalities or local and/or regional hyperemia, and caution should be taken in ascribing this extension to either tumor or metastasis.

  9. [Neurological manifestations of giant cell arteritis].

    PubMed

    Grachev, Yu V

    2016-01-01

    The article describes clinical, including neurological manifestations, of giant cell arteritis (GCA) - granulomatous vasculitis of large and medium-sized vessels, predominantly craniofacial, including precerebral and cerebral, arteries. Histopathological features of GCA are illustrated by the schemes of panarteritis and «postarteritis» (proliferative and fibrotic changes in the intima, underlying the development of cerebrovascular disorders). The main clinical manifestations of GCA are described as 3 groups of symptoms: general constitutional symptoms; manifestations of vasculitis of craniofacial, precerebral and cerebral arteries; polymyalgia rheumaticа. The authors present their own version of the taxonomy of visual disturbances in patients with GCA. Diagnostic steps in patients with suggestive signs of GCA are described. Therapeutic regimens of use of glucocorticoids for suggestion/diagnosis of GCA are presented.

  10. [Diffuse tenosenovial giant cell tumor of the wrist revealed by carpal tunnel syndrome: report of a case].

    PubMed

    Ait Essi, F; Younsi, A; Abkari, I; Benhima, M A; Najeb, Y; Latifi, M; Fakhri, A; Belaabidia, B

    2012-10-01

    Giant cell tumour of tendon sheath is a benign proliferative lesion of synovial origin that may affect the joints, bursae and tendon sheaths. It is the second most common soft tissue tumor of the hand after ganglion cyst. The localised (nodular) form is the most common. However, the less-common diffuse-type giant cell tumour is usually located in the peri-articular soft tissue. The authors report the case of a giant cell tumor of the tendon sheath arising from the carpal tunnel of the wrist in a 42-year-old woman. The patient presented a mild carpal tunnel syndrome and a mid-palmar swelling. We present an unusual localization of giant cell tumor of the tendon sheath, causing carpal tunnel syndrome.

  11. Orthopedic and orthodontic treatment in central giant cell granuloma treated with calcitonin.

    PubMed

    Romero, Martín; Romance, Ana; Garcia-Recuero, José Ismael; Fernández, Álvaro

    2011-09-01

    Central giant cell granuloma of the jaw is a benign lesion of unknown etiology that occurs with very low frequency. It mainly occurs in children and young adults and is more common in the mandible. The most common treatment is surgical removal; however, alternative therapies (intralesional injections of corticosteroids, interferon alpha, and calcitonin) have been used in order to avoid undesirable damage to the jaws and teeth. The lesion may cause root resorption, tooth germ displacement, and other dental problems, as well as malocclusion that must be treated orthodontically. The orthodontic, orthopedic, and calcitonin-based treatments of one of these cases is presented.

  12. Orthopedic and orthodontic treatment in central giant cell granuloma treated with calcitonin.

    PubMed

    Romero, Martín; Romance, Ana; Garcia-Recuero, José Ismael; Fernández, Álvaro

    2011-09-01

    Central giant cell granuloma of the jaw is a benign lesion of unknown etiology that occurs with very low frequency. It mainly occurs in children and young adults and is more common in the mandible. The most common treatment is surgical removal; however, alternative therapies (intralesional injections of corticosteroids, interferon alpha, and calcitonin) have been used in order to avoid undesirable damage to the jaws and teeth. The lesion may cause root resorption, tooth germ displacement, and other dental problems, as well as malocclusion that must be treated orthodontically. The orthodontic, orthopedic, and calcitonin-based treatments of one of these cases is presented. PMID:20815718

  13. Paroxysmal hemicrania as the clinical presentation of giant cell arteritis

    PubMed Central

    Beams, Jennifer L.; Rozen, Todd D.

    2011-01-01

    Head pain is the most common complaint in patients with giant cell arteritis but the headache has no distinct diagnostic features. There have been no published reports of giant cell arteritis presenting as a trigeminal autonomic cephalalgia. We describe a patient who developed a new onset headache in her fifties, which fit the diagnostic criteria for paroxysmal hemicrania and was completely responsive to corticosteroids. Removal of the steroid therapy brought a reemergence of her headaches. Giant cell arteritis should be considered in the evaluation of secondary causes of paroxysmal hemicrania; in addition giant cell arteritis needs to be ruled out in patients who are over the age of 50 years with a new onset trigeminal autonomic cephalalgia. PMID:24765352

  14. Spindle cell melanocytic lesions: part II--an approach to intradermal proliferations and horizontally oriented lesions.

    PubMed

    Sade, Shachar; Al Habeeb, Ayman; Ghazarian, Danny

    2010-05-01

    Melanocytic lesions show great morphological diversity in their architecture and the cytomorphological appearance of their composite cells. Whereas functional melanocytes show a dendritic cytomorphology and territorial isolation, lesional nevomelanocytes and melanoma cells typically show epithelioid, spindled or mixed cytomorphologies, and a range of architectural arrangements. Spindling is common to melanocytic lesions, and may either be a characteristic feature or a divergent appearance. The presence of spindle cells may mask the melanocytic nature of a lesion, and is often disconcerting, either due to its infrequent appearance in a particular lesion or its interpretation as a dedifferentiated phenotype. Spindle cell melanocytic lesions follow the full spectrum of potential biological outcomes, and difficulty may be experienced judging the nature of a lesion due to a lack of consistently reliable features to predict biological behaviour. Over time, recognition of numerous histomorphological features that may portend a more aggressive lesion have been identified; however, the translation of these features into a diagnostic entity requires a gestalt approach. Although most spindle cell melanocytic lesions may reliably be resolved through this standard approach, problem areas do exist for the surgical pathologist or dermatopathologist. With this review (part II of II), we complete our discussion of spindle cell melanocytic lesions, in order to: (1) model a systematic approach to such lesions; and (2) provide familiarity with those melanocytic lesions which either typically or occasionally display a spindled cytomorphology.

  15. Aggressive Metaplastic Carcinoma of the Breast with Osteoclastic Giant Cells.

    PubMed

    Khong, Kathleen; Zhang, Yanhong; Tomic, Mary; Lindfors, Karen; Aminololama-Shakeri, Shadi

    2015-09-01

    Metaplastic carcinoma of the breast is an uncommon type of malignancy that is aggressive but can mimic other benign breast neoplastic processes on imaging. We present a case of a young female patient who presented with a rapidly progressing metaplastic carcinoma with osteoclastic giant cells subtype. There have been only very rare published reports of this pathologic subtype of metaplastic carcinoma containing osteoclastic giant cells.

  16. Aggressive Metaplastic Carcinoma of the Breast with Osteoclastic Giant Cells

    PubMed Central

    Khong, Kathleen; Zhang, Yanhong; Tomic, Mary; Lindfors, Karen; Aminololama-Shakeri, Shadi

    2015-01-01

    Metaplastic carcinoma of the breast is an uncommon type of malignancy that is aggressive but can mimic other benign breast neoplastic processes on imaging. We present a case of a young female patient who presented with a rapidly progressing metaplastic carcinoma with osteoclastic giant cells subtype. There have been only very rare published reports of this pathologic subtype of metaplastic carcinoma containing osteoclastic giant cells. PMID:26629304

  17. Recurrent Giant Cell Tumor of Skull Combined with Multiple Aneurysms

    PubMed Central

    Kim, Dae Hwan

    2016-01-01

    Giant cell tumors are benign but locally invasive and frequently recur. Giant cell tumors of the skull are extremely rare. A patient underwent a surgery to remove a tumor, but the tumor recurred. Additionally, the patient developed multiple aneurysms. The patient underwent total tumor resection and trapping for the aneurysms, followed by radiotherapy. We report this rare case and suggest some possibilities for treating tumor growth combined with aneurysm development. PMID:27195256

  18. Giant cell arteritis: Current treatment and management

    PubMed Central

    Ponte, Cristina; Rodrigues, Ana Filipa; O’Neill, Lorraine; Luqmani, Raashid Ahmed

    2015-01-01

    Glucocorticoids remain the cornerstone of medical therapy in giant cell arteritis (GCA) and should be started immediately to prevent severe consequences of the disease, such as blindness. However, glucocorticoid therapy leads to significant toxicity in over 80% of the patients. Various steroid-sparing agents have been tried, but robust scientific evidence of their efficacy and safety is still lacking. Tocilizumab, a monoclonal IL-6 receptor blocker, has shown promising results in a number of case series and is now being tested in a multi-centre randomized controlled trial. Other targeted treatments, such as the use of abatacept, are also now under investigation in GCA. The need for surgical treatment is rare and should ideally be performed in a quiescent phase of the disease. Not all patients follow the same course, but there are no valid biomarkers to assess therapy response. Monitoring of disease progress still relies on assessing clinical features and measuring inflammatory markers (C-reactive protein and erythrocyte sedimentation rate). Imaging techniques (e.g., ultrasound) are clearly important screening tools for aortic aneurysms and assessing patients with large-vessel involvement, but may also have an important role as biomarkers of disease activity over time or in response to therapy. Although GCA is the most common form of primary vasculitis, the optimal strategies for treatment and monitoring remain uncertain. PMID:26090367

  19. Mediastinal epithelioid hemangioendothelioma with abundant spindle cells and osteoclast-like giant cells mimicking malignant fibrous histiocytoma

    PubMed Central

    2013-01-01

    Abstract Epithelioid hemangioendothelioma is a relatively uncommon lesion usually presenting in soft tissues. The occurrence in the mediastinum is exceptional rare. Histologically, this tumor is characterized by epithelioid cells with intracytoplasmic vacuoles in a hyalinized or mucinous stroma. Occasionally, spindle cells or osteoclast-like giant cells can be observed. Herein, we present a case of epithelioid hemangioendothelioma in a 38 year-old Chinese male. The tumor was predominantly composed of abundant spindle cells with marked atypia and scattered osteoclast-like giant cells reminiscent of malignant fibrous histiocytoma. The unusual histological appearance can pose a great diagnostic challenge. It may be easily misdiagnosed, especially if the specimen is limited or from fine-needle aspiration. Virtual slides http://www.diagnosticpathology.diagnomx.eu/vs/5804918529726307 PMID:23800015

  20. Denosumab and giant cell tumour of bone—a review and future management considerations

    PubMed Central

    Xu, S.F.; Adams, B.; Yu, X.C.; Xu, M.

    2013-01-01

    Giant cell tumour of bone (gctb) is one type of giant-cell-rich bone lesion characterized by the presence of numerous multinucleated osteoclast-type giant cells. Giant cells are known to express rankl (receptor activator of nuclear factor κB ligand) and are responsible for the aggressive osteolytic nature of the tumour. No available treatment option is definitively effective in curing this disease, especially in surgically unsalvageable cases. In recent years, several studies of denosumab in patients with advanced or unresectable gctb have shown objective changes in tumour composition, reduced bony destruction, and clinical benefit. Denosumab is a fully human monoclonal antibody that targets and binds with high affinity and specificity to rankl. Several large phase iii studies have shown that denosumab is more effective than bisphosphonates in reducing skeletal morbidity arising from a wide range of tumours and that it can delay bone metastasis. The relevant articles are reviewed here. The controversies related to the future use of denosumab in the treatment of gctb are discussed. PMID:24155640

  1. Tenosynovial giant cell tumor arising from the posterior cruciate ligament: a case report and literature review.

    PubMed

    Xu, Zhihong; Mao, Ping; Chen, Dongyang; Shi, Dongquan; Dai, Jin; Yao, Yao; Jiang, Qing

    2015-01-01

    The localized form of tenosynovial giant cell tumor or pigmented villonodular synovitis is rarely intraarticular in the knee. We reported a 40-year-old woman with a tenosynovial giant cell tumor arising from posterior cruciate ligament (PCL). She suffered sudden knee pain and locking without any reason for two days. A mass with a size of 1.7 × 0.8 × 0.7 cm in the fossa intercondyloidea was detected on the MRI. After one time hyperextension physical examination the patients felt sudden pain relief. During the arthroscopy examination, a loose soft tissue mass was found under the lateral meniscus. Only the synovium tissue lesion on the proximal PCL was detected. The mass had a conceivable thin pedicel and the shape matched well with the tumor bed on the PCL. The histopathology of the mass demonstrated a tenosynovial giant cell tumor. At six weeks follow-up, no clinical evidence of recurrence was noted. A Literature Review of tenosynovial giant cell tumor or pigmented villonodular synovitis arising from the PCL is present.

  2. Histogenetic Characterization of Giant Cell Tumor of Bone

    PubMed Central

    Salerno, Manuela; Avnet, Sofia; Alberghini, Marco; Giunti, Armando

    2008-01-01

    The unpredictable behavior of giant cell tumor (GCT) parallels its controversial histogenesis. Multinucleated giant cells, stromal cells, and CD68+ monocytes/macrophages are the three elements that interact in GCT. We compared the ability of stromal cells and normal mesenchymal stromal cells to differentiate into osteoblasts. Stromal cells and mesenchymal cells had similar proliferation rates and lifespans. Although stromal cells expressed early osteogenic markers, they were unable to differentiate into osteoblasts but they did express intracellular adhesion molecule-1, a marker of bone-lining cells. They were unable to form clones in a semisolid medium and unable to promote osteoclast differentiation, although they exerted a strong chemotactic effect on osteoclast precursors. Stromal cells may be either immature proliferating osteogenic elements or specialized osteoblast-like cells that fail to show neoplastic features but can induce the differentiation of osteoclast precursors. They might be secondarily induced to proliferate by a paracrine effect induced by monocyte-macrophages and/or giant cells. The increased number of giant cells in GCT may be secondary to an autocrine circuit mediated by the receptor activator of nuclear factor kB. PMID:18543051

  3. Giant multilocular prostatic cystadenoma: a distinctive lesion of the retroperitoneum in men. A report of two cases.

    PubMed

    Maluf, H M; King, M E; DeLuca, F R; Navarro, J; Talerman, A; Young, R H

    1991-02-01

    Two examples of large, multiloculated, cystic tumors that arose within the pelvis in men of 28 and 37 years of age are described. The tumors were composed of glands and cysts lined by prostatic-type epithelium lying in a hypocellular fibrous stroma. The prostatic nature of the lesions was confirmed by immunohistochemical staining of the epithelium for prostate-specific antigen and prostatic acid phosphatase. Two apparently similar lesions were found in the literature; one tumor was attached to the prostate by a pedicle, and the other arose in the retrovesical space. These tumors, for which we propose the designation "giant multilocular prostatic cystadenoma," appear to be benign, although they may recur if incompletely excised. They may pose considerable diagnostic difficulty if the prostatic nature of the epithelium is not appreciated, an error that is likely if a relationship to the prostate is not recognized. This lesion should be included in the differential diagnosis of retroperitoneal cystic tumors in men.

  4. Giant Cell Tumor of Bone: Documented Progression over 4 Years from Its Origin at the Metaphysis to the Articular Surface

    PubMed Central

    Link, Thomas; Cho, Soo-Jin; Motamedi, Daria

    2016-01-01

    The exact location of origin for giant cell tumors of bone (GCTB) remains controversial, as lesions are not routinely imaged early but rather late when the tumor is large and clinically symptomatic. At the time of diagnosis, GCTB are classically described as lucent, eccentric lesions with nonsclerotic margins, located within the epiphysis to a greater extent than the metaphysis. Here we present a case of a biopsy proven GCTB initially incidentally seen on MRI as a small strictly metaphyseal lesion, which over the course of several years expanded across a closed physis to involve the epiphysis and abut the articular surface/subchondral bone plate. PMID:27630783

  5. Giant Cell Tumor of Bone: Documented Progression over 4 Years from Its Origin at the Metaphysis to the Articular Surface.

    PubMed

    Burke, Colin; Link, Thomas; O'Donnell, Richard J; Cho, Soo-Jin; Motamedi, Daria

    2016-01-01

    The exact location of origin for giant cell tumors of bone (GCTB) remains controversial, as lesions are not routinely imaged early but rather late when the tumor is large and clinically symptomatic. At the time of diagnosis, GCTB are classically described as lucent, eccentric lesions with nonsclerotic margins, located within the epiphysis to a greater extent than the metaphysis. Here we present a case of a biopsy proven GCTB initially incidentally seen on MRI as a small strictly metaphyseal lesion, which over the course of several years expanded across a closed physis to involve the epiphysis and abut the articular surface/subchondral bone plate. PMID:27630783

  6. Giant Cell Tumor of Bone: Documented Progression over 4 Years from Its Origin at the Metaphysis to the Articular Surface

    PubMed Central

    Link, Thomas; Cho, Soo-Jin; Motamedi, Daria

    2016-01-01

    The exact location of origin for giant cell tumors of bone (GCTB) remains controversial, as lesions are not routinely imaged early but rather late when the tumor is large and clinically symptomatic. At the time of diagnosis, GCTB are classically described as lucent, eccentric lesions with nonsclerotic margins, located within the epiphysis to a greater extent than the metaphysis. Here we present a case of a biopsy proven GCTB initially incidentally seen on MRI as a small strictly metaphyseal lesion, which over the course of several years expanded across a closed physis to involve the epiphysis and abut the articular surface/subchondral bone plate.

  7. Giant-cell arteritis without cranial manifestations

    PubMed Central

    de Boysson, Hubert; Lambert, Marc; Liozon, Eric; Boutemy, Jonathan; Maigné, Gwénola; Ollivier, Yann; Ly, Kim; Manrique, Alain; Bienvenu, Boris; Aouba, Achille

    2016-01-01

    Abstract Diagnosis of giant-cell arteritis (GCA) is challenging in the absence of cardinal cranial symptoms/signs. We aimed to describe the clinical presentation, diagnostic process, and disease course of GCA patients without cranial symptoms, and to compare them to those of patients with typical cranial presentation. In this retrospective multicenter study, we enrolled patients with GCA who satisfied at least 3 of the 5 American College of Rheumatology criteria for GCA, or 2 criteria associated with contributory vascular biopsy other than temporal artery biopsy or with demonstration of large-vessel involvement; underwent iconographic evaluation of large arterial vessels (aortic CT scan or a positron emission tomography with 18F-fluorodeoxyglucose combined with computed tomography (FDG-PET/CT) scan or cardiac echography combined with a large-vessel Doppler) at diagnosis. We divided the cohort into 2 groups, distinguishing between patients without cranial symptoms/signs (i.e., headaches, clinical temporal artery anomaly, jaw claudication, ophthalmologic symptoms) and those with cranial symptoms/signs. In the entire cohort of 143 patients, all of whom underwent vascular biopsy and vascular imaging, we detected 31 (22%) patients with no cranial symptoms/signs. In the latter, diagnosis was biopsy proven in an arterial sample in 23 cases (74% of patients, on a temporal site in 20 cases and on an extratemporal site in 3). One-third of these 31 patients displayed extracranial symptoms/signs whereas the remaining two-thirds presented only with constitutional symptoms and/or inflammatory laboratory test results. Compared to the 112 patients with cardinal cranial clinical symptoms/signs, patients without cranial manifestations displayed lower levels of inflammatory laboratory parameters (C-reactive level: 68 [9–250] mg/L vs 120 [3–120] mg/L; P < 0.01), highest rate of aorta and aortic branch involvement identified (19/31 (61%) vs 42/112 (38%); P = 0.02) and also

  8. Bortezomib Inhibits Giant Cell Tumor of Bone through Induction of Cell Apoptosis and Inhibition of Osteoclast Recruitment, Giant Cell Formation, and Bone Resorption.

    PubMed

    Xu, Leqin; Luo, Jian; Jin, Rongrong; Yue, Zhiying; Sun, Peng; Yang, Zhengfeng; Yang, Xinghai; Wan, Wei; Zhang, Jishen; Li, Shichang; Liu, Mingyao; Xiao, Jianru

    2016-05-01

    Giant cell tumor of bone (GCTB) is a rare and highly osteolytic bone tumor that usually leads to an extensive bone lesion. The purpose of this study was to discover novel therapeutic targets and identify potential agents for treating GCTB. After screening the serum cytokine profiles in 52 GCTB patients and 10 normal individuals using the ELISA assay, we found that NF-κB signaling-related cytokines, including TNFα, MCP-1, IL1α, and IL17A, were significantly increased in GCTB patients. The results were confirmed by IHC that the expression and activity of p65 were significantly increased in GCTB patients. Moreover, all of the NF-κB inhibitors tested suppressed GCTB cell growth, and bortezomib (Velcade), a well-known proteasome inhibitor, was the most potent inhibitor in blocking GCTB cells growth. Our results showed that bortezomib not only induced GCTB neoplastic stromal cell (NSC) apoptosis, but also suppressed GCTB NSC-induced giant cell differentiation, formation, and resorption. Moreover, bortezomib specifically suppressed GCTB NSC-induced preosteoclast recruitment. Furthermore, bortezomib ameliorated GCTB cell-induced bone destruction in vivo As a result, bortezomib suppressed NF-κB-regulated gene expression in GCTB NSC apoptosis, monocyte migration, angiogenesis, and osteoclastogenesis. Particularly, the inhibitory effects of bortezomib were much better than zoledronic acid, a drug currently used in treating GCTB, in our in vitro experimental paradigms. Together, our results demonstrated that NF-κB signaling pathway is highly activated in GCTB, and bortezomib could suppress GCTB and osteolysis in vivo and in vitro, indicating that bortezomib is a potential agent in the treatment of GCTB. Mol Cancer Ther; 15(5); 854-65. ©2016 AACR.

  9. [Visual hallucinations and giant cell arteritis: the Charles Bonnet syndrome].

    PubMed

    Bloch, J; Morell-Dubois, S; Koch, E; Launay, D; Maillard-Lefebvre, H; Buchdahl, A-L; Hachulla, E; Rouland, J-F; Hatron, P-Y; Lambert, M

    2011-12-01

    In patients with visual hallucinations, diagnostic strategy is unclearly codified. In patients known to have giant cell arteritis, the main diagnostic assumption is disease relapse. Indeed, this should lead to rapid corticosteroid therapy. However, the Charles Bonnet syndrome, that is a poorly known etiology of visual hallucinations usually observed in elderly people, should be part of the differential diagnosis. We report a 87-year-old woman, with a 2-year history of giant cell arteritis who was admitted with an acute onset of visual hallucinations and who met all the criteria for Charles Bonnet syndrome.

  10. Spindle cell melanocytic lesions--part I: an approach to compound naevoidal pattern lesions with spindle cell morphology and Spitzoid pattern lesions.

    PubMed

    Sade, Shachar; Al Habeeb, Ayman; Ghazarian, Danny

    2010-04-01

    Melanocytic lesions show great morphological diversity in their architecture and the cytomorphological appearance of their composite cells. Whereas functional melanocytes reveal a dendritic cytomorphology and territorial isolation, lesional naevomelanocytes and melanoma cells typically show epithelioid, spindled or mixed cytomorphologies and a range of architectural arrangements. Spindling is common to melanocytic lesions, and may be either a characteristic feature or a divergent appearance. The presence of spindle cells may mask the melanocytic nature of a lesion, and is often disconcerting, either because of its infrequent appearance in a particular lesion or its interpretation as a dedifferentiated phenotype. Spindle cell melanocytic lesions follow the full spectrum of potential biological outcomes, and difficulty may be experienced judging the nature of a lesion because of a lack of consistently reliable features to predict biological behaviour. Over time, recognition of numerous histomorphological features that may portend a more aggressive lesion have been identified. However, the translation of these features into a diagnostic entity requires a gestalt approach. Although most spindle cell melanocytic lesions can reliably be resolved with this standard approach, problem areas do exist and cause no end of grief to the surgical pathologist or dermatopathologist. In this review, the authors present their algorithmic approach to spindle cell melanocytic lesions and discuss each entity in turn, in order to (1) model a systematic approach to such lesions, and (2) provide familiarity with those melanocytic lesions that either typically or occasionally display a spindled cytomorphology.

  11. Giant congenital melanocytic nevus.

    PubMed

    Viana, Ana Carolina Leite; Gontijo, Bernardo; Bittencourt, Flávia Vasques

    2013-01-01

    Giant congenital melanocytic nevus is usually defined as a melanocytic lesion present at birth that will reach a diameter ≥ 20 cm in adulthood. Its incidence is estimated in <1:20,000 newborns. Despite its rarity, this lesion is important because it may associate with severe complications such as malignant melanoma, affect the central nervous system (neurocutaneous melanosis), and have major psychosocial impact on the patient and his family due to its unsightly appearance. Giant congenital melanocytic nevus generally presents as a brown lesion, with flat or mammilated surface, well-demarcated borders and hypertrichosis. Congenital melanocytic nevus is primarily a clinical diagnosis. However, congenital nevi are histologically distinguished from acquired nevi mainly by their larger size, the spread of the nevus cells to the deep layers of the skin and by their more varied architecture and morphology. Although giant congenital melanocytic nevus is recognized as a risk factor for the development of melanoma, the precise magnitude of this risk is still controversial. The estimated lifetime risk of developing melanoma varies from 5 to 10%. On account of these uncertainties and the size of the lesions, the management of giant congenital melanocytic nevus needs individualization. Treatment may include surgical and non-surgical procedures, psychological intervention and/or clinical follow-up, with special attention to changes in color, texture or on the surface of the lesion. The only absolute indication for surgery in giant congenital melanocytic nevus is the development of a malignant neoplasm on the lesion.

  12. 'Salvage Treatment' of Aggressive Giant Cell Tumor of Bones with Denosumab

    PubMed Central

    Vaishya, Raju; Vijay, Vipul

    2015-01-01

    Giant cell tumor of the bone (GCTB) presents as a lytic lesion of epiphyseometaphyseal regions of the long bones usually during the second to the fourth decade with female predilection. Histologically, they are formed of neoplastic mononuclear cells with a higher receptor activator of nuclear factor kappa-B ligand (RANKL) expression responsible for the aggressive osteolytic nature of the tumour. RANKL helps in the formation and functioning of osteoclasts. A newer molecule, Denosumab, is a monoclonal antibody directed against RANKL and thus prevents the formation and function of osteoclasts. Management of refractory, multicentric, recurrent, or metastatic GCTB remains challenging as achieving a tumor-free margin surgically is not always possible. Denosumab may play a crucial role, especially in the management of such difficult lesions. We present three cases of locally aggressive GCTB (involving proximal humerus, sacrum, and proximal femur) that were treated and responded very well to Denosumab therapy. PMID:26251767

  13. Carpal tunnel syndrome caused by a giant cell tumour of the flexor tendon sheath.

    PubMed

    Meek, Marcel F; Sheikh, Zahid A; Quinton, David N

    2014-02-01

    A 76-year-old woman developed right carpal tunnel syndrome after being conservatively treated for tenosynovitis of the flexor tendons with associated mild carpal tunnel syndrome. A magnetic resonance imaging scan showed a tumour in the carpal tunnel. Re-exploration showed that the median nerve was being compressed by a giant cell tumour of the flexor tendon sheaths. Appropriate imaging is advised in patients with additional findings (such as swelling) or in patients with secondary carpal tunnel syndrome and incomplete response to conservative treatment, to exclude a space-occupying lesion.

  14. Primary hyperparathyroidism diagnosed after surgical ablation of a costal mass mistaken for giant-cell bone tumor: a case report

    PubMed Central

    2011-01-01

    Introduction Primary hyperparathyroidism is a common endocrine disorder characterized by elevated parathyroid hormone levels, which cause continuous osteoclastic bone resorption. Giant cell tumor of bone is an expansile osteolytic tumor that contains numerous osteoclast-like giant cells. There are many similarities in the radiological and histological features of giant cell tumor of bone and brown tumor. This is a rare benign focal osteolytic process most commonly caused by hyperparathyroidism. Case presentation We report the unusual case of a 40-year-old Caucasian woman in which primary hyperparathyroidism was diagnosed after surgical ablation of a costal mass. The mass was suspected of being neoplastic and histopathology was compatible with a giant cell tumor of bone. On the basis of the biochemical results (including serum calcium, phosphorous and intact parathyroid hormone levels) primary hyperparathyroidism was suspected and a brown tumor secondary to refractory hyperparathyroidism was diagnosed. Conclusions Since giant cell tumor is a bone neoplasm that has major implications for the patient, the standard laboratory tests in patients with bone lesions are important for a correct diagnosis. PMID:22204520

  15. Granulomatous giant cell submandibular sialadenitis in a dog.

    PubMed

    Pérez-Écija, Alejandro; Estepa, José Carlos; Mendoza, Francisco Javier

    2012-11-01

    A 4-month-old dog was presented with a progressive swelling of the submandibular area. The history, course, cytological, and sialographic findings were consistent with an aseptic pyogranulomatous sialadenitis with concurrent duct blockage. This rare entity, responsive to medical treatment, appears to be similar to the granulomatous giant cell sialadenitis of humans.

  16. The diagnosis and classification of giant cell arteritis.

    PubMed

    Nesher, Gideon

    2014-01-01

    Giant-cell arteritis (GCA) involves the major branches of the aorta with predilection for the extracranial branches of the carotid artery. It occurs in individuals older than 50 years and the incidence increases with age. The signs and symptoms of giant cell arteritis can be classified into four subsets: cranial arteritis, extracranial arteritis, systemic symptoms and polymyalgia rheumatica. Patients may develop any combination of these manifestations, associated with laboratory evidence of an acute-phase reaction. The only test that confirms GCA diagnosis is a temporal artery biopsy, showing vasculitis with mononuclear cell inflammatory infiltrates, often with giant cells. Due to the focal and segmental nature of the infiltrates, areas of inflammation may be missed by the biopsy and the histological examination is normal in about 15% of the cases. Some imaging modalities may aid in the diagnosis of GCA. Among those, color duplex ultrasonography of the temporal arteries is more commonly used. There are no independent validating criteria to determine whether giant cell arteritis is present when a temporal artery biopsy is negative. The American College of Rheumatology criteria for the classification of giant cell arteritis may assist in the diagnosis. However, meeting classification criteria is not equivalent to making the diagnosis in individual patients, and the final diagnosis should be based on all clinical, laboratory, imaging and histological findings. Glucocorticoids are the treatment of choice for GCA. The initial dose is 40-60 mg/day for most uncomplicated cases. Addition of low-dose aspirin (100 mg/d) has been shown to significantly decrease the rate of vision loss and stroke during the course of the disease. PMID:24461386

  17. Giant Cell Tumor of Bone in Skeletally Immature Patients - A Clinical Perspective

    PubMed Central

    Sharma, Vipin; Sharma, Seema; Mistry, Kewal A; Awasthi, Bhanu; Verma, Lucky; Singh, Uttam

    2015-01-01

    Introduction: Giant cell tumors of skeleton are very rare in pediatric and adolescent population. Here we report two cases-one a fifteen year old child with swelling distal humerus and another a case of a thirteen year old child with pain and swelling proximal tibia. Case Report: A fifteen year old child presented to department of orthopedics of our institute with complaint of difficulty in moving upper limb and swelling distal humerus. Another patient who was a 13 years old male had painful ambulation and swelling in upper tibia. MRI followed by core needle biopsy was done in both the patients confirming the mass to be giant cell tumor which is quite rare in this age group. First patient was managed by wide excision and total elbow replacement and second one by curettage, cementation and augmentation with plate-screw construct. Conclusion: Giant cell tumour of skeleton is highly uncommon in pediatric age group. It should be considered as one of the differential diagnosis of epiphyseo metaphyseal lesions in pediatric population in spite of its rarity. PMID:27299101

  18. Giant Cell Tumor of the Patella Tendon Sheath Presenting as a Painful Locked Knee

    PubMed Central

    Panagopoulos, Andreas; Tsoumpos, Pantelis; Tatani, Irini; Iliopoulos, Ilias; Papachristou, Dionysios

    2015-01-01

    Patient: Male, 26 Final Diagnosis: Giant cell tumor of the patella tendon seath Symptoms: Efusion • locking knee • pain Medication: None Clinical Procedure: Arthroscopy and open resection of the tumor Specialty: Orthopedics and Traumatology Objective: Rare disease Background: The giant cell tumor of the tendon sheath (GCT-TS) is a benign proliferative synovial tumor manifesting as an intra-articular solitary nodule. When it involves the infrapatellar fat pad it can present acutely as a painful locked knee. Case Report: A 26-year-old white male presented with a 2-week history of painful locking in his right knee. Clinical examination revealed lack of extension by approximately 20°. To help establish the diagnosis, an MRI scan of the right knee was performed, showing a large (5×4×2 cm), oval, well-circumscribed mass with a low-intensity homogenous signal. The size of the mass prohibited the removal by arthroscopy and we therefore proceeded with an open arthrotomy. Histological examination showed a tendosynovial giant cell tumor of the patella tendon sheath. At the latest follow-up, 2 years postoperatively, there was no local tumor recurrence. Conclusions: These rare tumorous lesions should be included in the differential diagnosis of painful locking knee, especially in the absence of definite traumatic history. PMID:26302970

  19. A Contemporary Approach to Classify Ghost Cells Comprising Oral Lesions

    PubMed Central

    Yadav, Sumit Kumar; Narwal, Anjali; Devi, Anju

    2015-01-01

    Ghost cells are swollen eosinophilic epithelial cells that have lost their nuclei but retain the cellular and nuclear outline. Pathologic ghost cell formation could be the process of aberrant keratinization or the result of coagulative necrosis. Ghost cells have been described in several odontogenic lesions, which include calcifying epithelial odontogenic cysts or tumours like odontomas, ameloblastic fibro-odontomas, and ameloblastomas. This article present a view on the formation of ghost cells with proposal/introduction of a classification for ghost cell lesions of the oral cavity in an attempt to organize these lesions for the better understanding and academic purpose. PMID:26501039

  20. A Contemporary Approach to Classify Ghost Cells Comprising Oral Lesions.

    PubMed

    Yadav, Achla Bharti; Yadav, Sumit Kumar; Narwal, Anjali; Devi, Anju

    2015-09-01

    Ghost cells are swollen eosinophilic epithelial cells that have lost their nuclei but retain the cellular and nuclear outline. Pathologic ghost cell formation could be the process of aberrant keratinization or the result of coagulative necrosis. Ghost cells have been described in several odontogenic lesions, which include calcifying epithelial odontogenic cysts or tumours like odontomas, ameloblastic fibro-odontomas, and ameloblastomas. This article present a view on the formation of ghost cells with proposal/introduction of a classification for ghost cell lesions of the oral cavity in an attempt to organize these lesions for the better understanding and academic purpose. PMID:26501039

  1. Rapidly growing giant cell tumor of bone in a skeletally immature girl.

    PubMed

    Akaike, Gensuke; Ueno, Teruko; Matsumoto, Seiichi; Motoi, Noriko; Matsueda, Kiyoshi

    2016-04-01

    Giant cell tumor of bone (GCTB) in skeletally immature patients is rare, and little is known regarding how fast GCTB can grow. We report a case of a 10-year-old skeletally immature girl with pathologically proven GCTB with obvious growth plate invasion that showed surprisingly rapid growth over only 14 days. A radiograph of the left knee revealed well-circumscribed, geographic bone destruction at the distal metaphysis of the femur with a focal cortical defect, suggesting a pathologic fracture. No abnormal mineralization or periosteal reaction was seen. A CT without contrast and an MRI demonstrated a homogeneous lesion with cortical disruption posteriorly and laterally with a slight soft tissue extension. Biopsy showed numerous multinucleated giant cells and spindle-shaped mononuclear cells without any sign of malignancy, suggesting GCTB. However, rapid lesion enlargement and destruction of the surrounding cortex were noted 14 days after biopsy. Considering the amount of bone destruction, traditional treatment of curettage and bone cement would not suffice to sustain structural strength. In addition, considering the patient's age, the tumor location, and the aggressive course, a malignant tumor, especially a giant cell-rich osteosarcoma, could not be excluded. Therefore, en bloc resection, including the growth plate and prosthetic replacement, were performed. Confirmation of GCTB was made from a pathologic evaluation, and a breach to the growth plate was identified. Since very little inflammatory reaction, degenerative change, or aneurysmal, bone, cyst-like change was found, the growth plate invasion was confirmed as due to GCTB extension, not due to the preoperative biopsy.

  2. Involvement of mast cells and microvessels density in reactive lesions of oral cavity: A comparative immunohistochemical study.

    PubMed

    Ferreira, Stephany Vasco; Xavier, Flávia Caló Aquino; Freitas, Maria da Conceição Andrade de; Nunes, Fábio Daumas; Gurgel, Clarissa Araújo; Cangussu, Maria Cristina Teixeira; Martins, Manoela Domingues; Freitas, Valéria Souza; Dos Santos, Jean Nunes

    2016-09-01

    In view of the similarity of clinicopathological features between reactive lesions of the oral cavity, the objective of the present study was to investigate the density of MCs (mast cells) and microvessels in a series of these lesions. Thirty-seven cases of reactive lesions including fibrous hyperplasia (FH, n=10), inflammatory fibrous hyperplasia (IFH, n=10), peripheral giant cell lesion (PGCL, n=10) and lobular capillary hemangioma (LCH, n=7) were investigated using immunohistochemistry for mast cell tryptase and CD34. For comparative purposes, central giant cell lesions (CGCL, n=5) were included. A higher MC density was observed in LCH (37.01), while CGCL exhibited the lowest density (n=8.14). There was a significant difference in MC density when all reactive lesions were compared to CGCL (p=0.001). The largest mean density of microvessels was observed in LCH (n=21.69). The smallest number was observed in CGCL (n=6.24). There was a significant difference in microvessel density when the reactive lesions were compared to CGCL (p=0.003). There was a significant and direct correlation between the density of MCs and microvessels only for IFH (p=0.048) and CGCL (p=0.005). A significant and direct correlation between the mean density of MCs and microvessels was observed when the reactive lesions were analyzed as a whole (p=0.005). Our results suggest that mast cells contribute to the connective tissue framework and angiogenic function, as well as the development, of reactive lesions of the oral cavity, including FH, IFH, LCH and PGCL. PMID:27493102

  3. Involvement of mast cells and microvessels density in reactive lesions of oral cavity: A comparative immunohistochemical study.

    PubMed

    Ferreira, Stephany Vasco; Xavier, Flávia Caló Aquino; Freitas, Maria da Conceição Andrade de; Nunes, Fábio Daumas; Gurgel, Clarissa Araújo; Cangussu, Maria Cristina Teixeira; Martins, Manoela Domingues; Freitas, Valéria Souza; Dos Santos, Jean Nunes

    2016-09-01

    In view of the similarity of clinicopathological features between reactive lesions of the oral cavity, the objective of the present study was to investigate the density of MCs (mast cells) and microvessels in a series of these lesions. Thirty-seven cases of reactive lesions including fibrous hyperplasia (FH, n=10), inflammatory fibrous hyperplasia (IFH, n=10), peripheral giant cell lesion (PGCL, n=10) and lobular capillary hemangioma (LCH, n=7) were investigated using immunohistochemistry for mast cell tryptase and CD34. For comparative purposes, central giant cell lesions (CGCL, n=5) were included. A higher MC density was observed in LCH (37.01), while CGCL exhibited the lowest density (n=8.14). There was a significant difference in MC density when all reactive lesions were compared to CGCL (p=0.001). The largest mean density of microvessels was observed in LCH (n=21.69). The smallest number was observed in CGCL (n=6.24). There was a significant difference in microvessel density when the reactive lesions were compared to CGCL (p=0.003). There was a significant and direct correlation between the density of MCs and microvessels only for IFH (p=0.048) and CGCL (p=0.005). A significant and direct correlation between the mean density of MCs and microvessels was observed when the reactive lesions were analyzed as a whole (p=0.005). Our results suggest that mast cells contribute to the connective tissue framework and angiogenic function, as well as the development, of reactive lesions of the oral cavity, including FH, IFH, LCH and PGCL.

  4. A case of thoracic giant cell tumor of bone and discussion of radiological features and current management practices.

    PubMed

    Kelly, Deirdre; Mc Erlean, Sarah; Byrne, Danielle; Mahon, Peter Mac; Mc Caffrey, John

    2016-09-01

    Giant cell tumor of bone (GCTB) is a rare condition with distinct radiological features that aid diagnosis. We present the case of an adult female patient, with locally invasive GCTB and review important radiological and management principles. Specific radiological features include locally aggressive, lytic radiolucent lesions, which can demonstrate cortical thinning and expansile remodeling of bone and typically involve the epiphysis and metaphysis. Management is primarily surgical, and denosumab has a role in the advanced setting. PMID:27594954

  5. A Rare Giant Cell Tumor of the Distal Fibula and its Management

    PubMed Central

    Vaishya, Raju; Kapoor, Chirag; Golwala, Paresh; Vijay, Vipul

    2016-01-01

    Giant Cell Tumour (GCT) of the distal fibula is extremely rare and poses challenges in the surgical management. Wide excision or intralesional curettage, along with adjuvant chemical cauterisation can prevent the recurrence of GCT. The excised bone gap needs reconstruction using tricortical iliac autograft and supportive plate fixation. In addition to wide excision, preservation of ankle mortise is advisable in locally aggressive and large lesions of the distal fibula. We report a GCT of the distal fibula in a young female patient. As part of the treatment, en bloc resection, chemical cauterisation with phenol, and distal fibula reconstruction with a tricortical iliac crest bone graft was done. Eighteen months after the treatment, the patient has no recurrence and her ankle is stable with full range of movement. We suggest this method to be worthwhile for the treatment of this uncommon lesion in quantifying recurrence and functional outcome. PMID:27493848

  6. A Rare Giant Cell Tumor of the Distal Fibula and its Management.

    PubMed

    Vaishya, Raju; Kapoor, Chirag; Golwala, Paresh; Agarwal, Amit Kumar; Vijay, Vipul

    2016-01-01

    Giant Cell Tumour (GCT) of the distal fibula is extremely rare and poses challenges in the surgical management. Wide excision or intralesional curettage, along with adjuvant chemical cauterisation can prevent the recurrence of GCT. The excised bone gap needs reconstruction using tricortical iliac autograft and supportive plate fixation. In addition to wide excision, preservation of ankle mortise is advisable in locally aggressive and large lesions of the distal fibula. We report a GCT of the distal fibula in a young female patient. As part of the treatment, en bloc resection, chemical cauterisation with phenol, and distal fibula reconstruction with a tricortical iliac crest bone graft was done. Eighteen months after the treatment, the patient has no recurrence and her ankle is stable with full range of movement. We suggest this method to be worthwhile for the treatment of this uncommon lesion in quantifying recurrence and functional outcome. PMID:27493848

  7. High-pressure paint-gun injury of the finger simulating giant cell tumor of tendon sheath.

    PubMed

    Stefanato, Catherine M; Turner, Matthew S; Bhawan, Jag

    2005-02-01

    High-pressure paint guns deliver paint at approximately 3000 pounds per square inch. At this pressure, paint will penetrate the skin and spread quickly through fascial planes and tendon sheaths. The present case is that of a lesion from the finger of a 35-year-old white male in whom a history was initially unavailable. Histologic examination revealed diffuse fibrohistiocytic proliferation and giant cells, with numerous darkly pigmented, uniformly small-sized particles throughout the lesion. The initial impression was that of a giant cell tumor of tendon sheath. However, the pigment particles were negative for Perls stain, and polariscopic examination revealed clear refractile fragments. These findings raised the possibility that the lesion was the result of a traumatic event. On further inquiry, it was revealed that the patient had sustained a high-pressure paint-gun injury 1 year earlier. The simulation, histopathologically, of a giant cell tumor of tendon sheath by a high-pressure paint-gun injury has not, to our knowledge, been reported previously, nor has the histologic finding of small, uniformly sized pigment particles and polarizable refractile fragments in this particular type of injury.

  8. Recurrent giant cell fibroblastoma: Malignancy predisposition in Kabuki syndrome revisited.

    PubMed

    Karagianni, Paraskevi; Lambropoulos, Vassilios; Stergidou, Dorothea; Fryssira, Helena; Chatziioannidis, Ilias; Spyridakis, Ioannis

    2016-05-01

    Kabuki syndrome is a genetic condition characterized by distinctive facial phenotype, mental retardation, and internal organ malformations. Mutations of the epigenetic genes KMT2D and KDM6A cause dysregulation of certain developmental genes and account for the multiple congenital anomalies of the syndrome. Eight cases of malignancies have been reported in young patients with Kabuki syndrome although a causative association to the syndrome has not been established. We report a case of a 12-year-old girl with Kabuki syndrome who developed a tumor on the right side of her neck. A relapsing tumor 19 months after initial excision, proved to be giant cell fibroblastoma. Τhis is the first report of giant cell fibroblastoma -a rare tumor of childhood- in a patient with Kabuki syndrome. PMID:26898171

  9. CTCFL (BORIS) mRNA Expression in a Peripheral Giant Cell Granuloma of the Oral Cavity

    PubMed Central

    Zambrano-Galván, Graciela; Reyes-Romero, Miguel; Bologna-Molina, Ronell; Almeda-Ojeda, Oscar Eduardo; Lemus-Rojero, Obed

    2014-01-01

    Peripheral giant cell granuloma (PGCG) is a relatively common benign reactive lesion of the oral cavity which can occur at any age. CTCFL/BORIS (CTCF like/Brother of the Regulator of Imprinted Sites) and CTCF (CCCTC-binding factor) are paralogous genes with an important role in the regulation of gene expression, genomic imprinting, and nuclear chromatin insulators regulation. BORIS expression promotes cell immortalization and growth while CTCF has tumor suppressor activity; the expression pattern may reflect the reverse transcription silencing of BORIS. The aim of this work was to describe a histopathological and molecular approach of an 8-year-old pediatric male patient with PGCG diagnosis. It was observed that the PGCG under study expressed CTCF as well as BORIS mRNAs alongside with the housekeeping gene GAPDH, which may be related to possible genetic and epigenetic changes in normal cells of oral cavity. PMID:25114808

  10. Trophoblast stem cells differentiate in vitro into invasive trophoblast giant cells.

    PubMed

    Hemberger, Myriam; Hughes, Martha; Cross, James C

    2004-07-15

    Trophoblast cells are characterized by an invasive behavior into the surrounding uterine tissue. In rodents, an early peri-/endovascular type of invasion exerted by trophoblast giant cells can be distinguished from a late interstitial type carried out by glycogen trophoblast cells. Analysis of the molecular mechanisms of trophoblast invasion has been hampered, however, by the complex temporal and spatial patterns of invasion. We utilized trophoblast stem (TS) cell lines to study trophoblast invasion in vitro and to establish a model that facilitates investigation of this process on the molecular level. Our results showed that trophoblast giant cells that differentiate from TS cells in vitro are capable of penetrating a reconstituted basement membrane matrix. Consequently, invasion rates were increased in various giant cell differentiation-promoting conditions. We also derived TS cell lines that are homozygous for a mutation of the Hand1 transcription factor. The Hand1-/- TS cells showed reduced levels of giant cell differentiation and exhibited an approximately 50% decrease in invasion rates. In summary, trophoblast giant cells that differentiate from TS cells in vitro recapitulate the invasive capacity of normal trophoblast cells in vivo. The TS cell system is a valuable tool to identify and quantitatively study regulators of trophoblast invasion.

  11. Asymmetric cell division in polyploid giant cancer cells and low eukaryotic cells.

    PubMed

    Zhang, Dan; Wang, Yijia; Zhang, Shiwu

    2014-01-01

    Asymmetric cell division is critical for generating cell diversity in low eukaryotic organisms. We previously have reported that polyploid giant cancer cells (PGCCs) induced by cobalt chloride demonstrate the ability to use an evolutionarily conserved process for renewal and fast reproduction, which is normally confined to simpler organisms. The budding yeast, Saccharomyces cerevisiae, which reproduces by asymmetric cell division, has long been a model for asymmetric cell division studies. PGCCs produce daughter cells asymmetrically in a manner similar to yeast, in that both use budding for cell polarization and cytokinesis. Here, we review the results of recent studies and discuss the similarities in the budding process between yeast and PGCCs.

  12. A Giant Intra Abdominal Mass Mimicking Renal Cell Carcinoma: A Rare Presentation of Renal Angiomyolipoma.

    PubMed

    Haque, M E; Rahman, M A; Kaisar, I; Islam, M F; Salam, M A

    2016-07-01

    Angiomyolipoma (AML) is a benign tumor commonly found in kidney than extra renal sites. Most of the small renal angiomyolipomas are diagnosed incidentally on ultrasound and other imaging studies. Some renal AMLs present clinically when become very big, giant renal angiomyolipoma. Although almost all cases are benign, a relatively rare variant of epitheloid angiomyolipoma has got malignant potential and can even metastasize. Ultrasonography, CT and MRI scan are usually used for diagnosis of angiomyolipoma with high level of accuracy; even though some lesions may be confused as renal cell carcinoma on imaging studies. Here, a 48 year old man presented with a large intra-abdominal mass preoperatively diagnosed as a case of right renal cell carcinoma and radical nephrectomy was performed. Histopathology revealed epitheloid angiomyolipoma (EAML). PMID:27612907

  13. Wheatstone bridge giant-magnetoresistance based cell counter.

    PubMed

    Lee, Chiun-Peng; Lai, Mei-Feng; Huang, Hao-Ting; Lin, Chi-Wen; Wei, Zung-Hang

    2014-07-15

    A Wheatstone bridge giant magnetoresistance (GMR) biosensor was proposed here for the detection and counting of magnetic cells. The biosensor was made of a top-pinned spin-valve layer structure, and it was integrated with a microchannel possessing the function of hydrodynamic focusing that allowed the cells to flow in series one by one and ensured the accuracy of detection. Through measuring the magnetoresistance variation caused by the stray field of the magnetic cells that flowed through the microchannel above the GMR biosensor, we can not only detect and count the cells but we can also recognize cells with different magnetic moments. In addition, a magnetic field gradient was applied for the separation of different cells into different channels. PMID:24534580

  14. Secondary malignant giant-cell tumor of bone. Clinicopathological assessment of nineteen patients

    SciTech Connect

    Rock, M.G.; Sim, F.H.; Unni, K.K.; Witrak, G.A.; Frassica, F.J.; Schray, M.F.; Beabout, J.W.; Dahlin, D.C.

    1986-09-01

    Twenty-six patients who had a malignant giant-cell tumor of bone--a sarcoma either juxtaposed to a zone of typical benign giant-cell tumor or occurring at the site of a previously documented benign giant-cell tumor--have been seen at the Mayo Clinic. Of the twenty-six tumors, nineteen were secondary to a previous attempt at local control of a benign giant-cell tumor. All but one of these nineteen patients with a secondary tumor had received therapeutic irradiation four to thirty-nine years earlier. The nature and duration of the symptoms and the sites of predilection of the malignant giant-cell tumors were the same as for benign giant-cell tumor. Fibrosarcoma occurred three times as frequently as osteosarcoma. The best results of treatment of the secondary sarcoma were obtained with early ablation.

  15. Intraoperative Squash Cytologic Features of Subependymal Giant Cell Astrocytoma.

    PubMed

    Nasit, Jitendra; Vaghsiya, Viren; Hiryur, Srilaxmi; Patel, Smita

    2016-01-01

    Subependymal giant cell astrocytoma (SEGA) is a low grade (WHO Grade I) tumor, usually seen in patients with tuberous sclerosis complex and commonly occurs at a lateral ventricular location. Intraoperative squash cytologic features can help in differentiating SEGA from gemistocytic astrocytoma (GA), giant cell glioblastoma and ependymoma, in proper clinical context and radiological findings, which may alter the surgical management. Here, we present a case of SEGA with squash cytologic findings and a review of cytology findings of SEGA presently available in the literature. Loose cohesive clusters of large polygonal cells containing an eccentric nucleus, evenly distributed granular chromatin, distinct to prominent nucleoli, and moderate to the abundant eosinophilic cytoplasm in a hair-like fibrillar background are the key cytologic features of SEGA. Other important features are moderate anisonucleosis and frequent binucleation and multinucleation. The absence of mitoses, necrosis, and vascular endothelial proliferation are important negative features. Other consistent features are cellular smears, few dispersed cells, few spindly strap-like cells, rare intranuclear cytoplasmic inclusion, and perivascular pseudorosettes. PMID:27013816

  16. Intraoperative Squash Cytologic Features of Subependymal Giant Cell Astrocytoma

    PubMed Central

    Nasit, Jitendra; Vaghsiya, Viren; Hiryur, Srilaxmi; Patel, Smita

    2016-01-01

    Subependymal giant cell astrocytoma (SEGA) is a low grade (WHO Grade I) tumor, usually seen in patients with tuberous sclerosis complex and commonly occurs at a lateral ventricular location. Intraoperative squash cytologic features can help in differentiating SEGA from gemistocytic astrocytoma (GA), giant cell glioblastoma and ependymoma, in proper clinical context and radiological findings, which may alter the surgical management. Here, we present a case of SEGA with squash cytologic findings and a review of cytology findings of SEGA presently available in the literature. Loose cohesive clusters of large polygonal cells containing an eccentric nucleus, evenly distributed granular chromatin, distinct to prominent nucleoli, and moderate to the abundant eosinophilic cytoplasm in a hair-like fibrillar background are the key cytologic features of SEGA. Other important features are moderate anisonucleosis and frequent binucleation and multinucleation. The absence of mitoses, necrosis, and vascular endothelial proliferation are important negative features. Other consistent features are cellular smears, few dispersed cells, few spindly strap-like cells, rare intranuclear cytoplasmic inclusion, and perivascular pseudorosettes. PMID:27013816

  17. EXCISION OF GIANT CELL TUMOR OF TENDON SHEATH WITH BONE INVOLVEMENT BY MEANS OF DOUBLE ACCESS APPROACH: CASE REPORT

    PubMed Central

    Alves, Marcelo de Pinho Teixeira

    2015-01-01

    Giant cell tumors of the tendon sheath are common lesions and are the second most frequent tumors in the hand, after synovial cysts. They are diagnosed by means of clinical examination and complementary examinations (simple radiography and magnetic resonance). Erosion and invasion of the phalangeal bone affected may be seen on radiological examination. Magnetic resonance may show a “fluorescent or radiant effect” may be observed, caused by the high quantity of hemosiderin inside the tumor. Surgical treatment is the commonest practice, and complete excision is important for avoiding recurrence of the tumor, especially when bone invasion is observed on imaging examinations, which is generally related to greater tumor recurrence. In this paper, a case of a giant cell tumor of the tendon sheath in the middle phalanx of the third finger of a 45-year-old female patient is presented. This was successfully treated by means of surgery using a double access approach (dorsal and volar). PMID:27026996

  18. Giant cell tumor of bone in children and adolescents.

    PubMed

    Hoeffel, J C; Galloy, M A; Grignon, Y; Chastagner, P; Floquet, J; Mainard, L; Kadiri, R

    1996-10-01

    Giant cell tumor of bone rarely affects children, in whom it is usually located in a metaphysis in contrast to the predominantly epiphyseal localization in adults. Five cases are reported, two at the femur, two at the fibula and one at the tibia. Plain film radiography and computed tomography are the most informative imaging studies. The differential diagnosis is with aneurysmal bone cyst and, in metaphyseal-epiphyseal forms, with chondroblastoma. Treatment usually consists in curettage of the tumor followed by filling of the cavity; however, more extensive resection is required in some cases. PMID:8938873

  19. Acute Myeloid Leukemia Complicated by Giant Cell Arteritis.

    PubMed

    Tsunemine, Hiroko; Umeda, Ryosuke; Nohda, Yasuhiro; Sakane, Emiko; Akasaka, Hiroshi; Itoh, Kiminari; Izumi, Mayuko; Tsuji, Goh; Kodaka, Taiichi; Itoh, Tomoo; Takahashi, Takayuki

    2016-01-01

    Giant cell arteritis (GCA), a type of systemic arteritis, is rare in Japan. We herein report a case of acute myeloid leukemia (AML) complicated by GCA that manifested during chemotherapy for AML. A 77-year-old woman with severe back pain was diagnosed with AML. She achieved complete remission with the resolution of her back pain following induction chemotherapy. However, she developed a headache and fever after consolidation chemotherapy. A diagnosis of GCA was made based on a biopsy of the temporal artery and arterial imaging. GCA should therefore be included in the differential diagnosis in AML patients complicated with a headache and fever of unknown origin. PMID:26831026

  20. [Giant cells undifferentiated parotid carcinoma. Report of two cases].

    PubMed

    Pino Rivero, V; González Palomino, A; Trinidad Ruiz, G; Pardo Romero, G; Montero García, C; Mogollón Cano-Cortés, T; Pando Pinto, J M; Blasco Huelva, A

    2005-01-01

    Tumours of the salivary glands represent a 5% of all head and neck neoplasms. Their origin is the parotid gland in about 80% of the cases. Most of them are benign. We are reporting two cases of patients diagnosed, by our ENT Department, as undifferentiated giant cells parotid carcinoma with cervical metastasis. They were operated by total parotidectomy and radical neck disection and later recieved treatment with radiotherapy. After two years-follow-up both patients are standing alive. The tumoral size is the most important pronostic factor in this histological type.

  1. Symplastic/pseudoanaplastic giant cell tumor of the bone

    PubMed Central

    Agaram, Narasimhan; Hwang, Sinchun; Lu, Chao; Wang, Lu; Healey, John; Hameed, Meera

    2016-01-01

    Objective Giant cell tumor of bone (GCTB) is a locally aggressive primary bone tumor. Its malignant counterpart is quite rare. Rarely, a conventional GCTB shows marked nuclear atypia, referred to as symplastic/pseudoanaplastic change, which can mimic sarcomatous transformation. Recently, somatic driver mutations of histone H3.3 exclusively in H3F3A have been described in GCTB. We report a series of 9 cases of GCTB with symplastic/pseudoanaplastic change, along with analysis of H3F3A variants. Materials and methods Nine cases of GCTB with symplastic change were identified. Clinico-radiological features, morphological features, and immunohistochemical stain for Ki-67 stain were reviewed. H3F3A variants were also analyzed using Sanger sequencing. Results Histologically, conventional giant cell tumor areas with scattered foci of markedly atypical cells were seen in all of the cases and all showed rare if any Ki-67 labeling. One patient had received denosumab treatment and another radiation therapy. Radiological features were characteristic of conventional GCTB. Mutation in H3F3A (p.Gly34Trp [G34W]) was found in 6 of the 7 cases. Clinical follow-up ranged from 6 to 208 months. Local recurrences were seen in 4 cases (44 %). Conclusions GCTB with symplastic/pseudoanaplastic change is an uncommon variant of conventional GCTB, which can mimic primary sarcoma or sarcomatous transformation. These tumors possess the same missense mutation in histone H3.3 as conventional GCTB. PMID:27020452

  2. Molecular Characterization of Clear Cell Lesions of Head and Neck.

    PubMed

    Jain, Anshi; Shetty, Devi Charan; Juneja, Saurabh; Narwal, Nidhi

    2016-05-01

    The salivary glands, oral mucosa and jaws constitute a group of lesions which are heterogeneous in nature and are odontogenic, salivary or metastatic in origin. This group of tumours is termed as Clear Cell Tumours. Fixation artifacts are one of the most important reasons for the cell to appear clear but clearing of cells may also result from cytoplasmic accumulation of water, presence of glycogen within the cell, intermediate filaments, immature zymogen granules, or a paucity of cellular organelles. Clear cell Odontogenic neoplasms predominantly include odontogenic carcinoma, ameloblastoma and calcifying epithelial odontogenic tumour. Clear cell tumours of salivary gland origin are almost invariably malignant in nature but they do include two benign lesions. Very frequently, surgical pathologist encounters clear cells in many malignant neoplasms, the nature and sources of which are undetermined on the basis of conventional histopathology. This review will selectively discuss the clinicopathological features of neoplasms which at times may pose a diagnostic challenge and dilemma due to clear cell changes.

  3. Estrogen Stimulates Homing of Endothelial Progenitor Cells to Endometriotic Lesions.

    PubMed

    Rudzitis-Auth, Jeannette; Nenicu, Anca; Nickels, Ruth M; Menger, Michael D; Laschke, Matthias W

    2016-08-01

    The incorporation of endothelial progenitor cells (EPCs) into microvessels contributes to the vascularization of endometriotic lesions. Herein, we analyzed whether this vasculogenic process is regulated by estrogen. Estrogen- and vehicle-treated human EPCs were analyzed for migration and tube formation. Endometriotic lesions were induced in irradiated FVB/N mice, which were reconstituted with bone marrow from FVB/N-TgN (Tie2/green fluorescent protein) 287 Sato mice. The animals were treated with 100 μg/kg β-estradiol 17-valerate or vehicle (control) over 7 and 28 days. Lesion growth, cyst formation, homing of green fluorescent protein(+)/Tie2(+) EPCs, vascularization, cell proliferation, and apoptosis were analyzed by high-resolution ultrasonography, caliper measurements, histology, and immunohistochemistry. Numbers of blood circulating EPCs were assessed by flow cytometry. In vitro, estrogen-treated EPCs exhibited a higher migratory and tube-forming capacity when compared with controls. In vivo, numbers of circulating EPCs were not affected by estrogen. However, estrogen significantly increased the number of EPCs incorporated into the lesions' microvasculature, resulting in an improved early vascularization. Estrogen further stimulated the growth of lesions, which exhibited massively dilated glands with a flattened layer of stroma. This was mainly because of an increased glandular secretory activity, whereas cell proliferation and apoptosis were not markedly affected. These findings indicate that vasculogenesis in endometriotic lesions is dependent on estrogen, which adds a novel hormonally regulated mechanism to the complex pathophysiology of endometriosis. PMID:27315780

  4. Central Giant Cell Granuloma of the Mandible Requiring Multiple Treatment Modalities: A Case Report.

    PubMed

    Jerkins, David; Malotky, Maximilian; Miremadi, Reza; Dole, Mukund

    2016-08-01

    Central giant cell granuloma (CGCG) is a relatively rare non-neoplastic, intraosseous lesion that exhibits a wide spectrum of clinical behavior, and its management can be particularly challenging even for experienced clinicians. The etiopathogenesis of this disease process remains unclear, although factors such as trauma, inflammatory foci, and a genetic predisposition have been implicated. Although multiple treatment modalities have been used with varying degrees of success, there is no accepted algorithm for therapeutic intervention and little is known about the reasons for success or failure of a given treatment. This article reviews the epidemiology, presentation, classification, and currently used therapies for CGCG while describing the clinical course and successful therapeutic outcome of a young female patient with an aggressive CGCG of the mandible.

  5. Donor-site giant cell reaction following backfill with synthetic bone material during osteochondral plug transfer.

    PubMed

    Fowler, Donald E; Hart, Joseph M; Hart, Jennifer A; Miller, Mark D

    2009-10-01

    Osteochondral defects are common in younger, active patients. Multiple strategies have been used to treat these lesions, including microfracture and osteochondral plug transfer. We describe a patient experiencing chronic knee pain and a full-thickness cartilage defect on the lateral femoral condyle. After failing conservative management and microfracture surgery, the patient underwent osteochondral autograft plug transfer, with backfilling of the donor sites using synthetic bone graft substitute. Initial recovery was uncomplicated until the patient experienced pain following a twist of the knee. Magnetic resonance imaging for the subsequent knee injury revealed poor healing at the donor sites. The donor sites were debrided, and specimens revealed a foreign body giant cell reaction. Donor-site morbidity is of primary concern during osteochondral plug transfer; however, insufficient data exist to support the use of synthetic bone graft material. Our results indicate that off-label use of synthetic bone graft substitute during a primary procedure requires further investigation.

  6. Multinuclear giant cell formation is enhanced by down-regulation of Wnt signaling in gastric cancer cell line, AGS

    SciTech Connect

    Kim, Shi-Mun; Kim, Rockki; Ryu, Jae-Hyun; Jho, Eek-Hoon; Song, Ki-Joon; Jang, Shyh-Ing; Kee, Sun-Ho . E-mail: keesh@korea.ac.kr

    2005-08-01

    AGS cells, which were derived from malignant gastric adenocarcinoma tissue, lack E-cadherin-mediated cell adhesion but have a high level of nuclear {beta}-catenin, which suggests altered Wnt signal. In addition, approximately 5% of AGS cells form multinuclear giant cells in the routine culture conditions, while taxol treatment causes most AGS cells to become giant cells. The observation of reduced nuclear {beta}-catenin levels in giant cells induced by taxol treatment prompted us to investigate the relationship between Wnt signaling and giant cell formation. After overnight serum starvation, the shape of AGS cells became flattened, and this morphological change was accompanied by decrease in Myc expression and an increase in the giant cell population. Lithium chloride treatment, which inhibits GSK3{beta} activity, reversed these serum starvation effects, which suggests an inverse relationship between Wnt signaling and giant cell formation. Furthermore, the down-regulation of Wnt signaling caused by the over-expression of ICAT, E-cadherin, and Axin enhanced giant cell formation. Therefore, down-regulation of Wnt signaling may be related to giant cell formation, which is considered to be a survival mechanism against induced cell death.

  7. Management of Giant Cell Tumour Radius in a Three Year old Child with an Improvised Technique

    PubMed Central

    Puri, Ajay; Gulia, Ashish; Sharma, Seema; Verma, Amit K

    2014-01-01

    Giant cell tumours of immature skeleton have a very low incidence and epi-metaphyseal location. We are presenting giant cell tumour distal radius in a skeletally immature patient; an uncontained defect with a large soft tissue component which was managed by wide excision and reconstruction with an improvised technique. PMID:25654002

  8. Histological Regression of Giant Cell Tumor of Bone Following RANK Ligand Inhibition

    PubMed Central

    Dietrich, Martin F.; Cavuoti, Dominick; Landay, Michael

    2014-01-01

    Lung metastases are a rare complication of giant cell tumors of bone. We herein describe an interesting case of histological regression and size reduction of lung metastases originating from a primary giant cell tumor of bone in response to the RANK ligand inhibitor denosumab. PMID:26425630

  9. Alternative surgical treatment for giant-cell reparative granuloma in the metacarpal, using phenol and ethanol adjuvant therapy.

    PubMed

    Yoshida, Tatsuya; Sakamoto, Akio; Tanaka, Kazuhiro; Matsuda, Shuichi; Oda, Yoshinao; Iwamoto, Yukihide

    2007-01-01

    Giant-cell reparative granuloma (GCRG) or a solid variant of an aneurysmal bone cyst (ABC) is an uncommon benign reactive lesion with a predilection for the small tubular bones of the hands and feet. Treatment usually involves wide resection or amputation because of unacceptable high recurrence rates after curettage. Adjuvant therapy usually is applied to reduce the recurrence of locally aggressive bone tumors. We report 2 cases of GCRG that were treated successfully with curettage, adjuvant phenol and ethanol, and autogenous bone grafting.

  10. Quantification and Localization of Mast Cells in Periapical Lesions

    PubMed Central

    Mahita, VN; Manjunatha, BS; Shah, R; Astekar, M; Purohit, S; Kovvuru, S

    2015-01-01

    Background: Periapical lesions occur in response to chronic irritation in periapical tissue, generally resulting from an infected root canal. Specific etiological agents of induction, participating cell population and growth factors associated with maintenance and resolution of periapical lesions are incompletely understood. Among the cells found in periapical lesions, mast cells have been implicated in the inflammatory mechanism. Aim: Quantifications and the possible role played by mast cells in the periapical granuloma and radicular cyst. Hence, this study is to emphasize the presence (localization) and quantification of mast cells in periapical granuloma and radicular cyst. Materials and Methods: A total of 30 cases and out of which 15 of periapical granuloma and 15 radicular cyst, each along with the case details from the previously diagnosed cases in the department of oral pathology were selected for the study. The gender distribution showed male 8 (53.3%) and females 7 (46.7%) in periapical granuloma cases and male 10 (66.7%) and females 5 (33.3%) in radicular cyst cases. The statistical analysis used was unpaired t-test. Results: Mean mast cell count in periapical granuloma subepithelial and deeper connective tissue, was 12.40 (0.99%) and 7.13 (0.83%), respectively. The mean mast cell counts in subepithelial and deeper connective tissue of radicular cyst were 17.64 (1.59%) and 12.06 (1.33%) respectively, which was statistically significant. No statistical significant difference was noted among males and females. Conclusion: Mast cells were more in number in radicular cyst. Based on the concept that mast cells play a critical role in the induction of inflammation, it is logical to use therapeutic agents to alter mast cell function and secretion, to thwart inflammation at its earliest phases. These findings may suggest the possible role of mast cells in the pathogenesis of periapical lesions. PMID:25861530

  11. Extensive DNA fragmentation in oxyphilic cell lesions of the thyroid.

    PubMed

    Volante, M; Papotti, M; Gugliotta, P; Migheli, A; Bussolati, G

    2001-08-01

    The in situ end-labeling (ISEL) method demonstrates DNA fragmentation, commonly regarded as a marker of apoptosis. We investigated by the ISEL procedure a series of 52 thyroid lesions, including 24 lesions of mitochondrion-rich oxyphilic cells, both benign and malignant, and 28 non-oxyphilic control tumors. A high percentage of nuclear ISEL staining (approximating to 100% in most cases) was observed in the vast majority of oxyphilic cells from both adenomas and carcinomas, in the absence of morphological apoptotic changes and with no immunocytochemical evidence of caspase activation. This pattern of DNA fragmentation was not observed in non-oxyphilic lesions and was confirmed in total extracted DNA. Moreover, a peculiar cytoplasmic staining was also observed in oxyphilic cells from both benign and malignant lesions, probably related to abnormal fragmentation of mitochondrial DNA. Similar staining patterns were detected in oxyphilic cell tumors of other organs (parathyroids, salivary glands, and kidneys). These findings are consistent with an extensive DNA fragmentation peculiar to oxyphilic cells, which is not directly related to apoptosis and whose origin and biological significance are presently unknown.

  12. Mycobacterium-Host Cell Relationships in Granulomatous Lesions in a Mouse Model of Latent Tuberculous Infection.

    PubMed

    Ufimtseva, Elena

    2015-01-01

    Tuberculosis (TB) is a dangerous infectious disease characterized by a tight interplay between mycobacteria and host cells in granulomatous lesions (granulomas) during the latent, asymptomatic stage of infection. Mycobacterium-host cell relationships were analyzed in granulomas obtained from various organs of BALB/c mice with chronic TB infection caused by in vivo exposure to the Bacillus Calmette-Guérin (BCG) vaccine. Acid-fast BCG-mycobacteria were found to be morphologically and functionally heterogeneous (in size, shape, and replication rates in colonies) in granuloma macrophages, dendritic cells, and multinucleate Langhans giant cells. Cord formation by BCG-mycobacteria in granuloma cells has been observed. Granuloma macrophages retained their ability to ingest damaged lymphocytes and thrombocytes in the phagosomes; however, their ability to destroy BCG-mycobacteria contained in these cells was compromised. No colocalization of BCG-mycobacteria and the LysoTracker dye was observed in the mouse cells. Various relationships between granuloma cells and BCG-mycobacteria were observed in different mice belonging to the same line. Several mice totally eliminated mycobacterial infection. Granulomas in the other mice had mycobacteria actively replicating in cells of different types and forming cords, which is an indicator of mycobacterial virulence and, probably, a marker of the activation of tuberculous infection in animals.

  13. Mycobacterium-Host Cell Relationships in Granulomatous Lesions in a Mouse Model of Latent Tuberculous Infection.

    PubMed

    Ufimtseva, Elena

    2015-01-01

    Tuberculosis (TB) is a dangerous infectious disease characterized by a tight interplay between mycobacteria and host cells in granulomatous lesions (granulomas) during the latent, asymptomatic stage of infection. Mycobacterium-host cell relationships were analyzed in granulomas obtained from various organs of BALB/c mice with chronic TB infection caused by in vivo exposure to the Bacillus Calmette-Guérin (BCG) vaccine. Acid-fast BCG-mycobacteria were found to be morphologically and functionally heterogeneous (in size, shape, and replication rates in colonies) in granuloma macrophages, dendritic cells, and multinucleate Langhans giant cells. Cord formation by BCG-mycobacteria in granuloma cells has been observed. Granuloma macrophages retained their ability to ingest damaged lymphocytes and thrombocytes in the phagosomes; however, their ability to destroy BCG-mycobacteria contained in these cells was compromised. No colocalization of BCG-mycobacteria and the LysoTracker dye was observed in the mouse cells. Various relationships between granuloma cells and BCG-mycobacteria were observed in different mice belonging to the same line. Several mice totally eliminated mycobacterial infection. Granulomas in the other mice had mycobacteria actively replicating in cells of different types and forming cords, which is an indicator of mycobacterial virulence and, probably, a marker of the activation of tuberculous infection in animals. PMID:26064970

  14. Mycobacterium-Host Cell Relationships in Granulomatous Lesions in a Mouse Model of Latent Tuberculous Infection

    PubMed Central

    2015-01-01

    Tuberculosis (TB) is a dangerous infectious disease characterized by a tight interplay between mycobacteria and host cells in granulomatous lesions (granulomas) during the latent, asymptomatic stage of infection. Mycobacterium-host cell relationships were analyzed in granulomas obtained from various organs of BALB/c mice with chronic TB infection caused by in vivo exposure to the Bacillus Calmette-Guérin (BCG) vaccine. Acid-fast BCG-mycobacteria were found to be morphologically and functionally heterogeneous (in size, shape, and replication rates in colonies) in granuloma macrophages, dendritic cells, and multinucleate Langhans giant cells. Cord formation by BCG-mycobacteria in granuloma cells has been observed. Granuloma macrophages retained their ability to ingest damaged lymphocytes and thrombocytes in the phagosomes; however, their ability to destroy BCG-mycobacteria contained in these cells was compromised. No colocalization of BCG-mycobacteria and the LysoTracker dye was observed in the mouse cells. Various relationships between granuloma cells and BCG-mycobacteria were observed in different mice belonging to the same line. Several mice totally eliminated mycobacterial infection. Granulomas in the other mice had mycobacteria actively replicating in cells of different types and forming cords, which is an indicator of mycobacterial virulence and, probably, a marker of the activation of tuberculous infection in animals. PMID:26064970

  15. Increased TNF-α, IL-6 and decreased IL-1β immunohistochemical expression by the stromal spindle-shaped cells in the central giant cell granuloma of the jaws

    PubMed Central

    Chrysomali, Evanthia; Stylogianni, Evangelia; Donta, Catherine; Vlachodimitropoulos, Dimitris

    2012-01-01

    Objectives: the exp ress ion of the osteoclastogenic cytokines TNF-α, IL-6 and IL-1β were immunohistochemically evaluated in periph eral (PGCG) and central (CGCG) giant cell granulomas of the jaws in order to determine diff erences between these two lesions and between the two distinct tumor cell populations (multinucleated giant cells, MGCs and stromal sp indle-sh aped cells). Study Design: Paraffin-embedd ed tiss ue sections from 40 PGCG and 40 CGCG were immunohistochemically stained using antibodies against TNF-α, IL-6 and IL-1β. The percentage of positively stained cells and the staining intensity were ass ess ed to provide a combined immunoreactivity score value. Results: TNF-α, IL-6 and IL-1β were exp ress ed in all lesions. The CGCG compared to the PGCG sh owed significantly increased exp ress ion of TNF-α and IL-6 and decreased exp ress ion of IL-1β by the sp indle-sh aped cells and increased exp ress ion of IL-1β by the MGCs. The MGCs demonstrated in comparison to the stromal sp indlesh aped cells significantly increased exp ress ion of all three cytokines in both PGCG and CGCG. Conclusions: The proinflammatory cytokines TNF-α, IL-6 and IL-1β seem to be involved in the growth process of PGCG and CGCG of the jaws. A poss ible alteration in the sy nthesis or/and activity of these cytokines by the stromal sp indle cells in the CGCGs may enhance osteolys is through the stimulation of osteoclast progenitor cells, given the fact that the intraoss eous lesions cause bone resorption. Key words: Giant cell granuloma, giant cell tumor, multinucleated giant cells, jaw, TNF-alpha, IL-6, IL-1beta, immunohistochemistry. PMID:22157665

  16. Oxidative Stress and DNA Lesions: The Role of 8-Oxoguanine Lesions in Trypanosoma cruzi Cell Viability

    PubMed Central

    Aguiar, Pedro H. N.; Furtado, Carolina; Repolês, Bruno M.; Ribeiro, Grazielle A.; Mendes, Isabela C.; Peloso, Eduardo F.; Gadelha, Fernanda R.; Macedo, Andrea M.; Franco, Glória R.; Pena, Sérgio D. J.; Teixeira, Santuza M. R.; Vieira, Leda Q.; Guarneri, Alessandra A.; Andrade, Luciana O.; Machado, Carlos R.

    2013-01-01

    The main consequence of oxidative stress is the formation of DNA lesions, which can result in genomic instability and lead to cell death. Guanine is the base that is most susceptible to oxidation, due to its low redox potential, and 8-oxoguanine (8-oxoG) is the most common lesion. These characteristics make 8-oxoG a good cellular biomarker to indicate the extent of oxidative stress. If not repaired, 8-oxoG can pair with adenine and cause a G:C to T:A transversion. When 8-oxoG is inserted during DNA replication, it could generate double-strand breaks, which makes this lesion particularly deleterious. Trypanosoma cruzi needs to address various oxidative stress situations, such as the mammalian intracellular environment and the triatomine insect gut where it replicates. We focused on the MutT enzyme, which is responsible for removing 8-oxoG from the nucleotide pool. To investigate the importance of 8-oxoG during parasite infection of mammalian cells, we characterized the MutT gene in T. cruzi (TcMTH) and generated T. cruzi parasites heterologously expressing Escherichia coli MutT or overexpressing the TcMTH enzyme. In the epimastigote form, the recombinant and wild-type parasites displayed similar growth in normal conditions, but the MutT-expressing cells were more resistant to hydrogen peroxide treatment. The recombinant parasite also displayed significantly increased growth after 48 hours of infection in fibroblasts and macrophages when compared to wild-type cells, as well as increased parasitemia in Swiss mice. In addition, we demonstrated, using western blotting experiments, that MutT heterologous expression can influence the parasite antioxidant enzyme protein levels. These results indicate the importance of the 8-oxoG repair system for cell viability. PMID:23785540

  17. Protein Expression Profiling of Giant Cell Tumors of Bone Treated with Denosumab

    PubMed Central

    Mukaihara, Kenta; Suehara, Yoshiyuki; Kohsaka, Shinji; Akaike, Keisuke; Tanabe, Yu; Kubota, Daisuke; Ishii, Midori; Fujimura, Tsutomu; Kazuno, Saiko; Okubo, Taketo; Takagi, Tatsuya; Yao, Takashi; Kaneko, Kazuo; Saito, Tsuyoshi

    2016-01-01

    Giant cell tumors of bone (GCTB) are locally aggressive osteolytic bone tumors. Recently, some clinical trials have shown that denosumab is a novel and effective therapeutic option for aggressive and recurrent GCTB. This study was performed to investigate the molecular mechanism underlying the therapeutic effect of denosumab. Comparative proteomic analyses were performed using GCTB samples which were taken before and after denosumab treatment. Each expression profile was analyzed using the software program to further understand the affected biological network. One of identified proteins was further evaluated by gelatin zymography and an immunohistochemical analysis. We identified 13 consistently upregulated proteins and 19 consistently downregulated proteins in the pre- and post-denosumab samples. Using these profiles, the software program identified molecular interactions between the differentially expressed proteins that were indirectly involved in the RANK/RANKL pathway and in several non-canonical subpathways including the Matrix metalloproteinase pathway. The data analysis also suggested that the identified proteins play a critical functional role in the osteolytic process of GCTB. Among the most downregulated proteins, the activity of MMP-9 was significantly decreased in the denosumab-treated samples, although the residual stromal cells were found to express MMP-9 by an immunohistochemical analysis. The expression level of MMP-9 in the primary GCTB samples was not correlated with any clinicopathological factors, including patient outcomes. Although the replacement of tumors by fibro-osseous tissue or the diminishment of osteoclast-like giant cells have been shown as therapeutic effects of denosumab, the residual tumor after denosumab treatment, which is composed of only stromal cells, might be capable of causing bone destruction; thus the therapeutic application of denosumab would be still necessary for these lesions. We believe that the protein expression

  18. Vascular solitary fibrous tumor with "floret" cells or giant cell angiofibroma? A lingual example highlighting the overlapping characteristics of these entities and positive immunoreaction for estrogen and progesterone receptors.

    PubMed

    Piperi, Evangelia; Rohrer, Michael D; Pambuccian, Stefan E; Koutlas, Ioannis G

    2009-05-01

    Recent literature suggests that giant cell angiofibroma (GCAF) is a variant of solitary fibrous tumor (SFT) and not just a related lesion. Herein we present a case of apparent SFT with giant cells, including floret cells and focal pseudovascular areas, which are defining features of GCAF. The tumor occurred in the tongue of an 84-year-old female and depicted an encapsulated, patternless spindle cell proliferation in a fibromyxoid stroma with focal dense collagenous areas and scattered floret-type multinucleated giant cells seen primarily in the periphery, as well as pseudovascular spaces, numerous capillaries, and hemangiopericytomalike areas. Immunohistochemical investigation revealed positive staining for CD34 and positive immunoreaction for estrogen and progesterone receptors. We support the present notion that GCAF is a histologic subtype of SFT.

  19. Case Study: Giant Cell Arteritis with Vertebral Artery Stenosis.

    PubMed

    Daniel Chomlak, R; Ghazanfari, Farshad; Datta, Mineesh

    2016-01-01

    In giant cell arteritis (GCA), involvement of the vertebral arteries is rare with reported rates of 3%-4% for ischemic events secondary to vertebral artery stenosis or occlusion for those patients with GCA. This case study describes a patient who initially presented with acute onset of vertigo but was also found to have transient, side-alternating upper limb neurological findings. While initial imaging showed no vascular abnormalities, it was not until GCA was eventually confirmed with a temporal artery biopsy that the initial scans were shown to have bilateral narrowing of the vertebral arteries. While rare, vertebral artery involvement is an important complication to consider in the setting of GCA due to the high rate of associated mortality, despite immunosuppressive therapy. PMID:27279753

  20. Multiple Giant Cell Tumours of Tendon Sheath: A Rare Occurrence

    PubMed Central

    Pathade, Smita Charandas; Kurpad, Ramkumar; Tauheed, Mohammed

    2014-01-01

    Giant Cell Tumours Of Tendon Sheath (GCTTS) are the second most frequent soft tissue tumours affecting the hand with an overall incidence of 1 in 50,000 individuals. These tumours are usually localized and solitary, with multiple GCTTS occurring rarely. Multi-centric origin is considered unusual and very few cases of multiple GCTTS have been reported till date. Here, we report a rare case of a 26-year-old female who presented with multiple painless swellings on palmar aspect of little finger of right hand since six months. Clinical diagnosis of Dupuytren’s contracture was given. Intraoperative examination revealed multiple separate nodules, firmly attached to the flexor tendon synovial sheath. Histopathology showed features of GCTTS. PMID:24596760

  1. Multiple giant cell tumours of tendon sheath: a rare occurrence.

    PubMed

    Pathade, Smita Charandas; Kurpad, Ramkumar; Tauheed, Mohammed

    2014-01-01

    Giant Cell Tumours Of Tendon Sheath (GCTTS) are the second most frequent soft tissue tumours affecting the hand with an overall incidence of 1 in 50,000 individuals. These tumours are usually localized and solitary, with multiple GCTTS occurring rarely. Multi-centric origin is considered unusual and very few cases of multiple GCTTS have been reported till date. Here, we report a rare case of a 26-year-old female who presented with multiple painless swellings on palmar aspect of little finger of right hand since six months. Clinical diagnosis of Dupuytren's contracture was given. Intraoperative examination revealed multiple separate nodules, firmly attached to the flexor tendon synovial sheath. Histopathology showed features of GCTTS.

  2. Case Study: Giant Cell Arteritis with Vertebral Artery Stenosis

    PubMed Central

    Daniel Chomlak, R.; Ghazanfari, Farshad; Datta, Mineesh

    2016-01-01

    In giant cell arteritis (GCA), involvement of the vertebral arteries is rare with reported rates of 3%–4% for ischemic events secondary to vertebral artery stenosis or occlusion for those patients with GCA. This case study describes a patient who initially presented with acute onset of vertigo but was also found to have transient, side-alternating upper limb neurological findings. While initial imaging showed no vascular abnormalities, it was not until GCA was eventually confirmed with a temporal artery biopsy that the initial scans were shown to have bilateral narrowing of the vertebral arteries. While rare, vertebral artery involvement is an important complication to consider in the setting of GCA due to the high rate of associated mortality, despite immunosuppressive therapy. PMID:27279753

  3. Hippocampal place cell instability after lesions of the head direction cell network

    NASA Technical Reports Server (NTRS)

    Calton, Jeffrey L.; Stackman, Robert W.; Goodridge, Jeremy P.; Archey, William B.; Dudchenko, Paul A.; Taube, Jeffrey S.; Oman, C. M. (Principal Investigator)

    2003-01-01

    The occurrence of cells that encode spatial location (place cells) or head direction (HD cells) in the rat limbic system suggests that these cell types are important for spatial navigation. We sought to determine whether place fields of hippocampal CA1 place cells would be altered in animals receiving lesions of brain areas containing HD cells. Rats received bilateral lesions of anterodorsal thalamic nuclei (ADN), postsubiculum (PoS), or sham lesions, before place cell recording. Although place cells from lesioned animals did not differ from controls on many place-field characteristics, such as place-field size and infield firing rate, the signal was significantly degraded with respect to measures of outfield firing rate, spatial coherence, and information content. Surprisingly, place cells from lesioned animals were more likely modulated by the directional heading of the animal. Rotation of the landmark cue showed that place fields from PoS-lesioned animals were not controlled by the cue and shifted unpredictably between sessions. Although fields from ADN-lesioned animals tended to have less landmark control than fields from control animals, this impairment was mild compared with cells recorded from PoS-lesioned animals. Removal of the prominent visual cue also led to instability of place-field representations in PoS-lesioned, but not ADN-lesioned, animals. Together, these findings suggest that an intact HD system is not necessary for the maintenance of place fields, but lesions of brain areas that convey the HD signal can degrade this signal, and lesions of the PoS might lead to perceptual or mnemonic deficits, leading to place-field instability between sessions.

  4. Aneurysmal bone cyst secondary to a giant cell tumor of the patella: A case report

    PubMed Central

    YU, XIAOLONG; GUO, RUNSHENG; FAN, CONGLIANG; LIU, HUCHENG; ZHANG, BIN; NIE, TAO; TU, YI; DAI, MIN

    2016-01-01

    The patella is an unusual location for primary and metastatic bone tumors to develop. The most frequently encountered primary osteolytic lesions at the patella include giant cell tumors of the bone (GCT), chondroblastoma and aneurysmal bone cysts (ABC). However, the presentation of an ABC originating secondary to a GCT at the patella is rare. The present study describes such a case in a 46-year-old female. The differential diagnosis of the condition was extensive. The patient underwent curettage and the addition of bone cement to fill the defect. Pathological analysis of the resected tissue demonstrated that the lesion was consistent with an ABC forming secondary to a GCT. A 3-month follow-up was completed subsequent to the surgery, with a computed tomography scan demonstrating no evidence of recurrence. However, frequent and continuous observations of the patient following diagnosis are planned in order to evaluate the long-term efficacy of the surgical treatment. To the best of our knowledge, the present study describes the third reported case in the literature of this rare, double synchronous, benign tumor located at the patella. PMID:26893764

  5. Giant cell tumor of the patella with a secondary aneurysmal bone cyst: A case report

    PubMed Central

    SONG, MINGZHI; DAI, WEI; SUN, RAN; LIANG, HONGFENG; LIU, BINGWU; WU, YUXUAN; MA, KAI; LU, MING

    2016-01-01

    The substance of the patella is an uncommon location for tumor occurrence and development. The present study reports a case of giant cell tumor (GCT) of the patella, combined with an aneurysmal bone cyst (ABC). To the best of our knowledge, this is the second report of GCT with ABC published in English. GCT is the most common type of benign tumor. Secondary ABC is frequently associated with GCT, but this symbiotic tumor rarely occurs in the patella. A 27-year-old male patient was examined at the outpatient clinic, and clinicopathological characteristics of the tumor were observed. X-ray and computed tomography (CT) scans revealed a lytic lesion located in the center of the right patella. Curettage, followed by autogenic and allograft bone grafting, was performed. Histopathologically, the lesion was diagnosed as a GCT with secondary ABC. No recurrence or metastasis was identified during the 1-year follow-up period. The present study reports a case of GCT with secondary ABC, and discusses the rare location and histopathological type of this tumor, in order to improve diagnosis and treatment of patellar tumors in general. PMID:27313738

  6. Tenosynovial giant cell tumour (pigmented villonodular synovitis-)-like changes in periprosthetic interface membranes.

    PubMed

    Söder, Stephan; Sesselmann, Stefan; Aigner, Thomas; Oehler, Stephan; Agaimy, Abbas

    2016-02-01

    Tenosynovial giant cell tumour (TSGCT; synonym, pigmented villonodular synovitis (PVNS)) is a rare low-grade mesenchymal neoplasm of either intra-articular or extra-articular origin. The etiopathogenesis of TSGCT is still uncertain, but recent studies showed a translocation involving colony-stimulating factor 1 (CSF-1) gene in a subset of cases. Histological features mimicking TSGCT can sometimes be encountered in periprosthetic interface membranes. To investigate the frequency and morphologic spectrum of this phenomenon, we conducted a systematic analysis of 477 periprosthetic interface membranes and performed immunohistochemical analysis on a subset of lesions compared to genuine TSGCT. In 26 of 477 periprosthetic membrane samples (5 %), at least some TSGCT-like features were found and 18 cases (4 %) strongly resembled it. Wear particles were detected in 100 % of the TSGCT-like lesions but only in 63.3 % of the whole cohort of periprosthetic membranes (p value <0.001). Immunohistochemistry comparing true TSGCT and TSGCT-like membranes showed similar inflammatory infiltrates with slightly elevated CD3+/CD8+ T lymphocytes and a slightly higher proliferation index in TSGCT samples. In conclusion, TSGCT-like changes in periprosthetic membranes likely represent exuberant fibrohistiocytic inflammatory response induced by wear particles and should be distinguished from genuine (neoplastic) TSGCT. Although TSGCT and TSGCT-like periprosthetic membranes represent different entities, their comparable morphology might reflect analogous morphogenesis.

  7. Therapy-resistant foreign body giant cell granuloma at the periapex of a root-filled human tooth

    SciTech Connect

    Nair, P.N.; Sjoegren, U.K.; Krey, G.; Sundqvist, G. )

    1990-12-01

    Although the primary etiological factor of periapical lesions is microbial, there are other independent factors that can adversely affect the outcome of endodontic treatment. In this communication, we present morphological evidence in support of the role of a foreign body reaction of periapical tissue to root-filling materials. The specimen consisted of a surgical biopsy of an asymptomatic periapical lesion which persisted after a decade of postendodontic follow-up. The biopsy was processed for correlated light and electron microscopy and was analyzed by various microtechniques. The unique feature of the lesion was the presence of vast numbers of large multinucleated cells and their cytoplasmic inclusion bodies. Morphologically, these multinucleated cells resembled foreign body giant cells. They contained characteristic birefringent cytoplasmic inclusions which on electron-probe x-ray microanalysis consistently revealed the presence of magnesium and silicon. The magnesium and silicon are presumably the remnants of a root-filling excess which protruded into the periapex and had been resorbed during the follow-up period. These observations strongly suggest that in the absence of microbial factors, root-filling materials which contain irritating substances can evoke a foreign body reaction at the periapex, leading to the development of asymptomatic periapical lesions that may remain refractory to endodontic therapy for long periods of time.

  8. Advantages of Pressurized-Spray Cryosurgery in Giant Cell Tumors of the Bone

    PubMed Central

    Dabak, Nevzat; Göçer, Hasan; Çıraklı, Alper

    2016-01-01

    Background: Giant Cell Tumor is considered a benign, local and aggressive tumor. Although considered a benign bone tumor, it is still the subject of discussion and research because of the associated local bone destruction, as well as high rates of recurrence and distant metastases. Options are being developed for both surgical techniques and adjuvant therapies. Aims: The present study evaluated the administration of cryotherapy via a pressurized-spray technique in giant cell tumors of the bone. Study Design: Cross-sectional study. Methods: The study included 40 patients who were treated with extensive curettage and cryotherapy at various locations during the period from February 2006 to December 2013. Informed consent forms were obtained from the participants and ethics committee approval was taken from the local ethics committee of Ondokuz Mayıs University. The pressurized-spray technique was performed using liquid nitrogen. The patients were evaluated with respect to age, gender, radiological appearance, treatment modality, duration of follow-up, skin problems and recurrence. Results: Twenty-one patients were female; 19 were male. The average age of the patients was 33 years (range: 16–72 years), and the average duration of follow-up was 43 months (range: 12–80 months). The average time from the onset of the complaints to the diagnosis was 6 months (range: 2–12 months). Based on the Campanacci classification: 9 patients were Grade I; 25 patients were Grade II; six patients were Grade III. The lesion was located in the femur in 14 patients, in the tibia in 11 patients, in the radius in 5 patients, in the pelvis in 4 patients, in the fibula in 3 patients, in the metatarsal in 2 patients and in the phalanges of the hand in one patient. One patient had postoperative early fracture. None of the patients had skin problems and infection. Three (7.5%) of the patients had recurrence. Conclusion: It was found that cryotherapy was highly effective in the lesions

  9. Amelanotic Melanoma Masquerading as a Granular Cell Lesion

    PubMed Central

    Pandiar, Deepak; Basheer, Shaini; Shameena, P. M.; Sudha, S.; Dhana, Lakshmi J.

    2013-01-01

    Amelanotic melanoma (AM) presents a diagnostic challenge due to its wide clinical presentations, lack of pigmentation, and varied histological appearances. Immunohistochemistry plays a crucial role in the diagnosis of these lesions. Amelanotic melanoma of oral mucosa is an uncommon lesion. We report a case of a 50-year-old male patient with a growth on the anterior mandibular gingiva of seven-month duration. In the present case, histologically, the tumour resembled a granular cell lesion, which has not been reported previously in AM. Diagnosis was possible by a sequential panel of immunohistochemical markers, of which finally vimentin, S100, HMB45, and Melan-A were positive. The tumor was surgically excised, and postsurgical radiotherapy was given. PMID:23533832

  10. Gingival squamous cell carcinoma mimicking as a desquamative lesion

    PubMed Central

    Keshava, Abbayya; Gugwad, Sushma; Baad, Rajendra; Patel, Rufi

    2016-01-01

    Oral squamous cell carcinoma (SCC) is the most frequently encountered neoplasm in the oral cavity, which accounts for more than 90% of all cancers. Except for carcinoma of the lip vermilion, the most common sites of oral SCC are the tongue and floor of mouth, followed at a lower frequency by the soft palate, gingiva, and buccal mucosa. Clinically, it may be misdiagnosed because of its variable appearances. This case report presents a case of well-differentiated SCC of gingiva. A 48-year-old male patient reported to the Department of Periodontology, School of Dental Sciences, Karad, with a 1-year history of burning sensation and painful lesion on the gingiva from 35 to 37 (mandibular) regions. On clinical examination, desquamated gingival lesion was seen with no purulent exudation. Clinical characteristics and differential diagnosis indicated the lesion for an excisional biopsy. Histopathological examination confirmed the lesion to be a well-differentiated SCC. The patient was referred for the treatment consisting of surgical excision of the lesion. Since an early diagnosis and treatment was possible in this case, it resulted in a good prognosis. In these instances, dentist plays an important role in early detection of gingival SCC. PMID:27041843

  11. Establishment and cryopreservation of a giant panda skeletal muscle-derived cell line.

    PubMed

    Yu, Fang-Jian; Zeng, Chang-Jun; Zhang, Yan; Wang, Cheng-Dong; Xiong, Tie-Yi; Fang, Sheng-Guo; Zhang, He-Min

    2015-06-01

    The giant panda Ailuropoda melanoleuca is an endangered species and is a symbol for wildlife conservation. Although efforts have been made to protect this rare and endangered species through breeding and conservative biology, the long-term preservation of giant panda genome resources (gametes, tissues, organs, genomic libraries, etc.) is still a practical option. In this study, the giant panda skeletal muscle-derived cell line was successfully established via primary explants culture and cryopreservation techniques. The population doubling time of giant panda skeletal cells was approximately 33.8 h, and this population maintained a high cell viability before and after cryopreservation (95.6% and 90.7%, respectively). The two skeletal muscle-specific genes SMYD1 and MYF6 were expressed and detected by RT-PCR in the giant panda skeletal muscle-derived cell line. Karyotyping analysis revealed that the frequencies of giant panda skeletal muscle cells showing a chromosome number of 2n=42 ranged from 90.6∼94.2%. Thus, the giant panda skeletal muscle-derived cell line provides a vital resource and material platform for further studies and is likely to be useful for the protection of this rare and endangered species.

  12. Establishment and cryopreservation of a giant panda skeletal muscle-derived cell line.

    PubMed

    Yu, Fang-Jian; Zeng, Chang-Jun; Zhang, Yan; Wang, Cheng-Dong; Xiong, Tie-Yi; Fang, Sheng-Guo; Zhang, He-Min

    2015-06-01

    The giant panda Ailuropoda melanoleuca is an endangered species and is a symbol for wildlife conservation. Although efforts have been made to protect this rare and endangered species through breeding and conservative biology, the long-term preservation of giant panda genome resources (gametes, tissues, organs, genomic libraries, etc.) is still a practical option. In this study, the giant panda skeletal muscle-derived cell line was successfully established via primary explants culture and cryopreservation techniques. The population doubling time of giant panda skeletal cells was approximately 33.8 h, and this population maintained a high cell viability before and after cryopreservation (95.6% and 90.7%, respectively). The two skeletal muscle-specific genes SMYD1 and MYF6 were expressed and detected by RT-PCR in the giant panda skeletal muscle-derived cell line. Karyotyping analysis revealed that the frequencies of giant panda skeletal muscle cells showing a chromosome number of 2n=42 ranged from 90.6∼94.2%. Thus, the giant panda skeletal muscle-derived cell line provides a vital resource and material platform for further studies and is likely to be useful for the protection of this rare and endangered species. PMID:26035009

  13. Magnetic resonance imaging findings of undifferentiated carcinoma with osteoclast-like giant cells of pancreas.

    PubMed

    Yang, Kyung Yoon; Choi, Joon-Il; Choi, Moon Hyung; Park, Michael Yong; Rha, Sung Eun; Byun, Jae Young; Jung, Eun Sun; Lall, Chandana

    2016-01-01

    Undifferentiated carcinoma with osteoclast-like giant cells is a rare pancreatic and periampullary neoplasm with less than 50 cases reported in the literature. Pathologically, this tumor mimics a giant cell tumor in bones. We report a case of undifferentiated carcinoma with osteoclast-like giant cells in a 55-year-old man presenting as a pancreatic mass with associated regional and distant lymphadenopathy. On T1- and T2-weighted images, the mass shows dark signal intensity which was atypical for a pancreatic adenocarcinoma.

  14. Emergency Diagnosis of Giant Cell Tumour (GCT) of Spine by Image Guided Fine Needle Aspiration Cytology (FNAC)

    PubMed Central

    Chaudhry, Manish; Singh, Amitoj

    2014-01-01

    Giant cell tumour (GCT) of spine is an extremely rare neoplasm accounting 0.5% to 1.5% of all cases. The patient usually presents with weakness of lower limbs. We describe a case of 25-year-old male who presented with sudden onset of paraplegia. On plain radiograph there was an osteolytic lesion in T9 vertebra. Computed tomography (CT) scan revealed expansile lytic lesion in T9 vertebral body with involvement of posterior elements on right side with associated soft tissue mass in the extradural location extending into the spinal cord. Further Magnetic Resonance Imaging (MRI) scan (T1 contrast) showed the enhancing extradural mass involving spinal cord from D 8-10 levels. A provisional radiological diagnosis of GCT was made. A CT guided FNAC of the mass was performed which revealed typical cytological features of Giant cell tumour. Role of image guided Fine Needle Aspiration Cytology (FNAC) of vertebral mass and its role in emergency situations with clear emphasis on differential diagnosis is highlighted. PMID:25177571

  15. Molecular Characterization of Clear Cell Lesions of Head and Neck

    PubMed Central

    Shetty, Devi Charan; Juneja, Saurabh; Narwal, Nidhi

    2016-01-01

    The salivary glands, oral mucosa and jaws constitute a group of lesions which are heterogeneous in nature and are odontogenic, salivary or metastatic in origin. This group of tumours is termed as Clear Cell Tumours. Fixation artifacts are one of the most important reasons for the cell to appear clear but clearing of cells may also result from cytoplasmic accumulation of water, presence of glycogen within the cell, intermediate filaments, immature zymogen granules, or a paucity of cellular organelles. Clear cell Odontogenic neoplasms predominantly include odontogenic carcinoma, ameloblastoma and calcifying epithelial odontogenic tumour. Clear cell tumours of salivary gland origin are almost invariably malignant in nature but they do include two benign lesions. Very frequently, surgical pathologist encounters clear cells in many malignant neoplasms, the nature and sources of which are undetermined on the basis of conventional histopathology. This review will selectively discuss the clinicopathological features of neoplasms which at times may pose a diagnostic challenge and dilemma due to clear cell changes. PMID:27437379

  16. Molecular Characterization of Clear Cell Lesions of Head and Neck.

    PubMed

    Jain, Anshi; Shetty, Devi Charan; Juneja, Saurabh; Narwal, Nidhi

    2016-05-01

    The salivary glands, oral mucosa and jaws constitute a group of lesions which are heterogeneous in nature and are odontogenic, salivary or metastatic in origin. This group of tumours is termed as Clear Cell Tumours. Fixation artifacts are one of the most important reasons for the cell to appear clear but clearing of cells may also result from cytoplasmic accumulation of water, presence of glycogen within the cell, intermediate filaments, immature zymogen granules, or a paucity of cellular organelles. Clear cell Odontogenic neoplasms predominantly include odontogenic carcinoma, ameloblastoma and calcifying epithelial odontogenic tumour. Clear cell tumours of salivary gland origin are almost invariably malignant in nature but they do include two benign lesions. Very frequently, surgical pathologist encounters clear cells in many malignant neoplasms, the nature and sources of which are undetermined on the basis of conventional histopathology. This review will selectively discuss the clinicopathological features of neoplasms which at times may pose a diagnostic challenge and dilemma due to clear cell changes. PMID:27437379

  17. T cells stimulate catabolic gene expression by the stromal cells from giant cell tumor of bone

    SciTech Connect

    Cowan, Robert W.; Ghert, Michelle; Singh, Gurmit

    2012-03-23

    Highlights: Black-Right-Pointing-Pointer Two T cell lines stimulate PTHrP, RANKL, MMP13 gene expression in GCT cell cultures. Black-Right-Pointing-Pointer CD40 expressed by stromal cells; CD40L detected in whole tumor but not cultures. Black-Right-Pointing-Pointer Effect of CD40L treatment on GCT cells increased PTHrP and MMP13 gene expression. Black-Right-Pointing-Pointer PTHrP treatment increased MMP13 expression, while inhibition decreased expression. Black-Right-Pointing-Pointer T cells may stimulate GCT stromal cells and promote the osteolysis of the tumor. -- Abstract: The factors that promote the localized bone resorption by giant cell tumor of bone (GCT) are not fully understood. We investigated whether T cells could contribute to bone resorption by stimulating expression of genes for parathyroid hormone-related protein (PTHrP), matrix metalloproteinase (MMP)-13, and the receptor activator of nuclear-factor {kappa}B ligand (RANKL). Two cell lines, Jurkat clone E6-1 and D1.1, were co-cultured with isolated GCT stromal cells. Real-time PCR analyses demonstrated a significant increase of all three genes following 48 h incubation, and PTHrP and MMP-13 gene expression was also increased at 24 h. Further, we examined the expression of CD40 ligand (CD40L), a protein expressed by activated T cells, and its receptor, CD40, in GCT. Immunohistochemistry results revealed expression of the CD40 receptor in both the stromal cells and giant cells of the tumor. RNA collected from whole GCT tissues showed expression of CD40LG, which was absent in cultured stromal cells, and suggests that CD40L is expressed within GCT. Stimulation of GCT stromal cells with CD40L significantly increased expression of the PTHrP and MMP-13 genes. Moreover, we show that inhibition of PTHrP with neutralizing antibodies significantly decreased MMP13 expression by the stromal cells compared to IgG-matched controls, whereas stimulation with PTHrP (1-34) increased MMP-13 gene expression. These

  18. Evolution of microscopic colitis to giant cell colitis without significant intraepithelial lymphocytosis or thickened collagen plate.

    PubMed

    De Petris, Giovanni; Chen, Longwen

    2015-05-01

    Microscopic colitis (MC) is an umbrella term that encompasses lymphocytic colitis (LC) and collagenous colitis (CC). Several histological variants of these 2 entities exist; among them is the uncommon giant cell colitis (GCC), in which histiocytic giant cells (GCs) are present in background of CC or LC. We report the case of a 71-year-old woman complaining of watery diarrhea for several years that was diagnosed with CC. At follow-up, she developed giant cell colitis (GCC). Nine years later, a colectomy revealed a form of microscopic colitis in which significant intraepithelial lymphocytosis and collagen plate thickening have disappeared while GCs persisted with diffuse mononuclear cells inflammation of the lamina propria. Thinning of the collagen plate in association with GCs has been described previously. The case contributes the possibility of further evolution of MC into a pure giant cell colitis in which the prototypical manifestations of MC have all but disappeared.

  19. Heart Attacks, Strokes, and Peripheral Artery Disease in Patients With Giant-Cell Arteritis

    MedlinePlus

    Annals of Internal Medicine Summaries for Patients Heart Attacks, Strokes, and Peripheral Artery Disease in Patients With Giant-Cell Arteritis The full report is titled “Risk for Cardiovascular Disease Early and Late ...

  20. Nonconventional papillary thyroid carcinomas with pleomorphic tumor giant cells: a diagnostic pitfall with anaplastic carcinoma.

    PubMed

    Hommell-Fontaine, Juliette; Borda, Angela; Ragage, Florence; Berger, Nicole; Decaussin-Petrucci, Myriam

    2010-06-01

    The presence of pleomorphic tumor giant cells in thyroid carcinomas of follicular cell origin is always worrisome for the pathologist as they first of all refer to anaplastic carcinoma, one of the most aggressive human malignancies. However, non-anaplastic pleomorphic giant cells are well described in other thyroid diseases, most often benign. In this paper, we describe four cases of papillary thyroid carcinoma displaying pleomorphic tumor giant cells with features that differ from those of anaplastic carcinoma. Pleomorphic giant cells were admixed with the underlying thyroid carcinoma and constituted from 5% to 25% of the tumor. Cytologically, they had an abundant eosinophilic cytoplasm with large and irregular nuclei. Compared to pleomorphic giant cells of anaplastic carcinoma, they reproduced the growth pattern of the underlying carcinoma, had a low mitotic index without necrosis or inflammation, and were reactive with thyroglobulin and thyroid-specific transcription factor-1 and strongly and diffusely positive for cytokeratin AE1/AE3. After 16-84 months of follow-up, patients are relapse-free and still alive. These cases show that pleomorphic tumor giant cells arising in papillary thyroid carcinomas do not always represent dedifferentiation and progression to anaplastic carcinoma. Distinction among these processes is critical as their treatment and prognosis are very different.

  1. Affinity cytochemistry analysis of mast cells in skin lesions: a possible tool to assess the timing of lesions after death.

    PubMed

    Bonelli, A; Bacci, S; Norelli, G A

    2003-12-01

    The histamine content in vital wounds is known to increase, with a zenith after 3 h, and then decrease until 24 h after wounding. We addressed whether this biochemical alteration has a morphological counterpart. Since the main source of skin histamine are mast cells, the distribution and number of these cells was assessed upon labeling with fluorescent avidin and with antibodies to the mast cell specific enzymes, chymase and tryptase. Analyses were performed on skin from 15 healthy controls (from surgical biopsies), from 15 post-mortem lesions and 75 vital lesions, obtained at autopsy from subjects who had survived from a few seconds to 24 h. The number of mast cells per unit area of section surface increased progressively with survival time, up to a maximum in subjects who survived 1-3 h ( p<0.01), and decreased thereafter becoming less than in the controls if lesions had occurred earlier than 6 h before death ( p<0.01). Samples from post-mortem lesions had significantly fewer mast cells than those of any other groups of samples ( p<0.01). We suggest that in association to other histological and circumstantial evidence the analysis of mast cells by affinity cytochemistry can help to discriminate vital from post-mortem lesions and to estimate survival time after lesions.

  2. Culture of mature trophoblastic giant cells from bovine placentomes.

    PubMed

    Landim, L P; Miglino, M A; Pfarrer, C; Ambrosio, C E; Garcia, J M

    2007-04-01

    The mostly binucleate trophoblast giant cells (TGC) found in bovine placentomes, in addition to synthesizing and releasing hormones play an important role in fetal development and maternal adaptation to pregnancy. Placentomes from early gestation were collected, and for isolation of mature TGC, three cellular disaggregation methods, mechanical (MECH), enzymatic by trypsin (TRYP) or collagenase (COLL) were compared to each other. Further on, the cell survival in culture medium (DMEM) supplemented with either 10% fetal calf serum (FCS) or 10% serum replacement (SR) on culture plates free of any substrate was evaluated over a period of 90 days by trypan blue exclusion. The cells were further characterized by HOECHST 33342 nuclear staining, and immunocytochemical staining with monoclonal antibodies against vimentin and cytokeratin. A mean total rate of TGC survival of 82.56% was recorded. Statistical analysis showed significantly higher survival rates after enzymatic disaggregation with COLL (86.23%) than following MECH (80.38%) or TRYP (80.91%) treatment. Supplementation of DMEM with FCS resulted in significantly higher cellular survival rates (87.13%) when compared to the addition of SR (77.73%). Analysis of the influence of both, disaggregation method and medium supplementation on TGC survival revealed statistically significant differences between the following groups: MECH-SR (71.09%) was significantly lower than all other groups; TRYP-SR (78.03%) was significantly different from all other groups; TRYP-FCS (83.43%) and COLL-SR (84.08%) were significantly lower than MECH-FCS (89.98%) which together with COLL-FCS (88.25%) showed the highest cellular survival rate. In summary, our results show that TGC isolated from early gestation placentomes may be viable for more than 90 days of culture. However, whether these TGC produce placental lactogen throughout this period has yet to be determined.

  3. Culture of mature trophoblastic giant cells from bovine placentomes.

    PubMed

    Landim, L P; Miglino, M A; Pfarrer, C; Ambrosio, C E; Garcia, J M

    2007-04-01

    The mostly binucleate trophoblast giant cells (TGC) found in bovine placentomes, in addition to synthesizing and releasing hormones play an important role in fetal development and maternal adaptation to pregnancy. Placentomes from early gestation were collected, and for isolation of mature TGC, three cellular disaggregation methods, mechanical (MECH), enzymatic by trypsin (TRYP) or collagenase (COLL) were compared to each other. Further on, the cell survival in culture medium (DMEM) supplemented with either 10% fetal calf serum (FCS) or 10% serum replacement (SR) on culture plates free of any substrate was evaluated over a period of 90 days by trypan blue exclusion. The cells were further characterized by HOECHST 33342 nuclear staining, and immunocytochemical staining with monoclonal antibodies against vimentin and cytokeratin. A mean total rate of TGC survival of 82.56% was recorded. Statistical analysis showed significantly higher survival rates after enzymatic disaggregation with COLL (86.23%) than following MECH (80.38%) or TRYP (80.91%) treatment. Supplementation of DMEM with FCS resulted in significantly higher cellular survival rates (87.13%) when compared to the addition of SR (77.73%). Analysis of the influence of both, disaggregation method and medium supplementation on TGC survival revealed statistically significant differences between the following groups: MECH-SR (71.09%) was significantly lower than all other groups; TRYP-SR (78.03%) was significantly different from all other groups; TRYP-FCS (83.43%) and COLL-SR (84.08%) were significantly lower than MECH-FCS (89.98%) which together with COLL-FCS (88.25%) showed the highest cellular survival rate. In summary, our results show that TGC isolated from early gestation placentomes may be viable for more than 90 days of culture. However, whether these TGC produce placental lactogen throughout this period has yet to be determined. PMID:16716544

  4. Polyclonal T-Cells Express CD1a in Langerhans Cell Histiocytosis (LCH) Lesions

    PubMed Central

    West, Jennifer A.; Olsen, Sharon L.; Mitchell, Jenée M.; Priddle, Ross E.; Luke, Jennifer M.; Åkefeldt, Selma Olsson; Henter, Jan-Inge; Turville, Christopher; Kannourakis, George

    2014-01-01

    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. PMID:25343480

  5. The cytology of giant solitary trichoepithelioma

    PubMed Central

    Krishnamurthy, Jayashree; Divya, KN

    2010-01-01

    Giant solitary trichoepithelioma (GST) is a rare trichogenic tumor, which may present as a pigmented lesion. An 80-year-old man was diagnosed to have giant solitary trichoepithelioma on fine-needle aspiration cytology. The cytological findings represented the histological features. The recognition of GST is important because of its close resemblance to basal cell carcinoma and other skin adnexal tumors – clinically, cytologically and histologically. PMID:21187885

  6. Premalignant Oral Lesion Cells Elicit Increased Cytokine Production and Activation of T-cells

    PubMed Central

    JOHNSON, SARA D.; LEVINGSTON, CORINNE; YOUNG, M. RITA I.

    2016-01-01

    Background Head and neck squamous cell carcinomas (HNSCC) are known to evade the host immune response. How premalignant oral lesions modulate the immune response, however, has yet to be elucidated. Materials and Methods A mouse model of oral carcinogenesis was used to determine how mediators from premalignant oral lesion cells vs. HNSCC cells impact on immune cytokine production and activation. Results Media conditioned by premalignant lesion cells elicited an increased production of T cell-associated cytokines and proinflammatory mediators from cervical lymph node cells compared to media conditioned by HNSCC cells or media alone. In the presence of premalignant lesion cell-conditioned media, CD4+ T cell expression of the IL-2 receptor CD25 and CD8+ T cell expression of the activation marker CD69 was greater, compared to what was induced in HNSCC cell-conditioned media or media alone. Conclusion Premalignant lesion cells promote a proinflammatory environment and induce immune changes before HNSCC tumors are established. PMID:27354582

  7. Clear cell renal cell carcinoma with a syncytial-type multinucleated giant tumor cell component: implications for differential diagnosis.

    PubMed

    Williamson, Sean R; Kum, Jennifer B; Goheen, Michael P; Cheng, Liang; Grignon, David J; Idrees, Muhammad T

    2014-04-01

    A component of syncytial-type multinucleated tumor giant cells is uncommon in clear cell renal cell carcinoma, and the histogenesis, incidence, and clinical implications of this finding are not well understood. We retrieved 13 such tumors from our pathology archives in patients with a median age of 60years, comprising 1.5% of clear cell renal cell carcinomas. Stage was typically pT4 or pT3 (each 38%). Microscopically, all tumors included a component of low-grade clear cell renal cell carcinoma with usual features. Syncytial-type giant tumor cells possessed voluminous cytoplasm, usually granular and eosinophilic, and numerous nuclei similar to those of the mononuclear tumor cells. Transition between areas of mononuclear and multinucleated cells was sometimes abrupt. Other findings included necrosis (77%), hyaline globules (46%), emperipolesis (46%), and intranuclear cytoplasmic invaginations (23%). Immunohistochemical staining typically revealed both mononuclear and multinucleated cells to be positive for carbonic anhydrase IX, CD10, epithelial membrane antigen, vimentin, and cytokeratin AE1/AE3 and negative for β human chorionic gonadotropin, TFE3, cathepsin K, cytokeratin 7, cytokeratin 20, HMB45, CD68, smooth muscle actin, and S100. Most patients with available information (7/9) were alive with metastatic disease at the most recent follow-up. Syncytial-type giant cells are an uncommon finding associated with aggressive clear cell renal cell carcinomas. Despite the unusual appearance of this tumor component, its immunoprofile supports an epithelial lineage and argues against trophoblastic, osteoclast-like, or histiocytic differentiation. Reactivity for typical clear cell renal cell carcinoma antigens facilitates discrimination from giant cells of epithelioid angiomyolipoma or other tumors, particularly in a biopsy specimen or a metastatic tumor. PMID:24499686

  8. In search of a candidate pathogen for giant cell arteritis: sequencing based characterization of the giant cell arteritis microbiome

    PubMed Central

    Bhatt, Ami S.; Manzo, Veronica E.; Pedamallu, Chandra Sekhar; Duke, Fujiko; Cai, Diana; Bienfang, Don C.; Padera, Robert F.; Meyerson, Matthew; Docken, William P.

    2014-01-01

    Objective The objectives of this study were (1) to characterize the microbiome of the temporal artery in patients with giant cell arteritis and (2) to apply an unbiased and comprehensive shotgun sequencing-based approach to determine if there is an enrichment of candidate pathogens in affected tissues. Methods We performed unbiased DNA sequencing of 17 formalin-fixed, paraffin-embedded temporal artery biopsy specimens collected at a single institution over a period of four years. Twelve cases fulfilled clinical and histopathological criteria for GCA. Five cases served as controls. Using PathSeq software, human sequences were computationally subtracted and the remaining non-human sequences taxonomically classified using a comprehensive microbial sequence database. The relative abundance of microbes was inferred based on read counts assigned to each organism. Comparison of the microbial diversity in cases versus controls was carried out using hierarchical clustering and linear discriminant analysis effect size. Results Propionibacterium acnes and Escherichia coli were the most abundant microorganisms in 16 of the 17 samples and Moraxella catarrhalis was the most abundant organism in one control. Pathogens previously described to be correlated with GCA were not differentially abundant in cases, compared to controls. There was not a significant burden of likely pathogenic viruses. Conclusion DNA sequencing of temporal artery biopsies from GCA cases and controls showed no evidence of previously identified candidate GCA pathogens. A single pathogen was not clearly and consistently associated with GCA in this case series. PMID:24644069

  9. Giant cell glioblastoma in the cerebrum of a Pembroke Welsh corgi.

    PubMed

    Giri, D K; Aloisio, F; Alosio, F; Ajithdoss, D K; Ambrus, A; Lidbury, J A; Hein, H E; Porter, B F

    2011-05-01

    A 6-year-old, neutered female Pembroke Welsh corgi was presented with a 1-month history of ataxia and panting. The clinical signs progressed until the dog became anorexic, obtunded and exhibited circling to the left. At necropsy examination, a mass was detected in the left forebrain, impinging on the cribriform plate. Microscopically, the mass was composed of sheets of round to pleomorphic neoplastic cells with vacuolated cytoplasm. Nuclear atypia, anisocytosis and anisokaryosis were common. Numerous bizarre, multinucleated giant cells containing 60 or more nuclei and giant mononuclear cells were present. The matrix contained abundant reticulin. Immunohistochemistry revealed the neoplastic cells uniformly to express vimentin, and a small number of neoplastic cells expressed glial fibrillary acid protein. A diagnosis of giant cell glioblastoma was made. Although well recognized in man, this tumour has been documented rarely in the veterinary literature.

  10. Genetic lesions in diffuse large B-cell lymphomas

    PubMed Central

    Testoni, M.; Zucca, E.; Young, K. H.; Bertoni, F.

    2015-01-01

    Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma in adults, accounting for 35%–40% of all cases. The combination of the anti-CD20 monoclonal antibody rituximab with anthracycline-based combination chemotherapy (R-CHOP, rituximab with cyclophosphamide, doxorubicin, vincristine and prednisone) lead to complete remission in most and can cure more than half of patients with DLBCL. The diversity in clinical presentation, as well as the pathologic and biologic heterogeneity, suggests that DLBCL comprises several disease entities that might ultimately benefit from different therapeutic approaches. In this review, we summarize the current literature focusing on the genetic lesions identified in DLBCL. PMID:25605746

  11. Tumor-induced rickets in a child with a central giant cell granuloma: a case report.

    PubMed

    Fernández-Cooke, Elisa; Cruz-Rojo, Jaime; Gallego, Carmen; Romance, Ana Isabel; Mosqueda-Peña, Rocio; Almaden, Yolanda; Sánchez del Pozo, Jaime

    2015-06-01

    Tumor-induced osteomalacia/rickets is a rare paraneoplastic disorder associated with a tumor-producing fibroblast growth factor 23 (FGF23). We present a child with symptoms of rickets as the first clinical sign of a central giant cell granuloma (CGCG) with high serum levels of FGF23, a hormone associated with decreased phosphate resorption. A 3-year-old boy presented with a limp and 6 months later with painless growth of the jaw. On examination gingival hypertrophy and genu varum were observed. Investigations revealed hypophosphatemia, normal 1,25 and 25 (OH) vitamin D, and high alkaline phosphatase. An MRI showed an osteolytic lesion of the maxilla. Radiographs revealed typical rachitic findings. Incisional biopsy of the tumor revealed a CGCG with mesenchymal matrix. The CGCG was initially treated with calcitonin, but the lesions continued to grow, making it necessary to perform tracheostomy and gastrostomy. One year after onset the hyperphosphaturia worsened, necessitating increasing oral phosphate supplements up to 100 mg/kg per day of elemental phosphorus. FGF23 levels were extremely high. Total removal of the tumor was impossible, and partial reduction was achieved after percutaneous computed tomography-guided radiofrequency, local instillation of triamcinolone, and oral propranolol. Compassionate use of cinacalcet was unsuccessful in preventing phosphaturia. The tumor slowly regressed after the third year of disease; phosphaturia improved, allowing the tapering of phosphate supplements, and FGF23 levels normalized. Tumor-induced osteomalacia/rickets is uncommon in children and is challenging for physicians to diagnose. It should be suspected in patients with intractable osteomalacia or rickets. A tumor should be ruled out if FGF23 levels are high.

  12. Tumor-induced rickets in a child with a central giant cell granuloma: a case report.

    PubMed

    Fernández-Cooke, Elisa; Cruz-Rojo, Jaime; Gallego, Carmen; Romance, Ana Isabel; Mosqueda-Peña, Rocio; Almaden, Yolanda; Sánchez del Pozo, Jaime

    2015-06-01

    Tumor-induced osteomalacia/rickets is a rare paraneoplastic disorder associated with a tumor-producing fibroblast growth factor 23 (FGF23). We present a child with symptoms of rickets as the first clinical sign of a central giant cell granuloma (CGCG) with high serum levels of FGF23, a hormone associated with decreased phosphate resorption. A 3-year-old boy presented with a limp and 6 months later with painless growth of the jaw. On examination gingival hypertrophy and genu varum were observed. Investigations revealed hypophosphatemia, normal 1,25 and 25 (OH) vitamin D, and high alkaline phosphatase. An MRI showed an osteolytic lesion of the maxilla. Radiographs revealed typical rachitic findings. Incisional biopsy of the tumor revealed a CGCG with mesenchymal matrix. The CGCG was initially treated with calcitonin, but the lesions continued to grow, making it necessary to perform tracheostomy and gastrostomy. One year after onset the hyperphosphaturia worsened, necessitating increasing oral phosphate supplements up to 100 mg/kg per day of elemental phosphorus. FGF23 levels were extremely high. Total removal of the tumor was impossible, and partial reduction was achieved after percutaneous computed tomography-guided radiofrequency, local instillation of triamcinolone, and oral propranolol. Compassionate use of cinacalcet was unsuccessful in preventing phosphaturia. The tumor slowly regressed after the third year of disease; phosphaturia improved, allowing the tapering of phosphate supplements, and FGF23 levels normalized. Tumor-induced osteomalacia/rickets is uncommon in children and is challenging for physicians to diagnose. It should be suspected in patients with intractable osteomalacia or rickets. A tumor should be ruled out if FGF23 levels are high. PMID:26009620

  13. Giant-cell tumor: analysis on the importance of early diagnosis and the epidemiological profile☆

    PubMed Central

    de Carvalho Diniz Ferraz, Diego Firmino; Torres dos Santos, César Augusto; Farias Costa, Victor Hugo; Gonçalves Souza, Antônio Marcelo; Gomes Lima, Paulo Rogerio

    2016-01-01

    Objective This study aimed to ascertain the relationship between early diagnosis of giant-cell tumors (GCT) and their prognosis, by correlating the time of symptom onset with the staging of the injury (through the Campanacci classification at the time of diagnosis), and with the type of treatment. The secondary objective of the study was to outline the epidemiological profile of patients with GCT in the region where the data were gathered, and to compare them with data in the literature. Methods The authors present an evaluation on 61 patients diagnosed with bone GCT, with regard to the site of involvement, age, initial symptoms, time of symptom onset, classification and type of treatment, among patients attended between May 1994 and August 2009. Results The threshold indicated as the limit for Campanacci stage I tumors to be the commonest diagnosis, with a 98.2% chance that the treatment would be non-aggressive, was 2 months after symptom onset. This finding was statistically significant (p = 0.017). Every additional month increased the chance that a patient would be diagnosed with an advanced-stage tumor by 10.94%, in relation to the chances of having the other two stages of the tumor. Conclusion The study result not only suggests that the alternative hypothesis that the earlier the diagnosis of GCT is, the less severe the lesion will be, has been confirmed; but also especially predicts the relationship between the time of symptom appearance and the severity of the tumor. PMID:26962501

  14. Treating giant cell tumours with curettage, electrocautery, burring, phenol irrigation, and cementation.

    PubMed

    Moon, Myung-Sang; Kim, Sung-SooS S; Moon, Jeong-Lim; Kim, Sung-Sim; Moon, Hanlim

    2013-08-01

    PURPOSE. To report on 23 patients with giant cell tumour (GCT) of the femur or tibia treated with curettage, electrocautery, burring, phenol irrigation, and cementation. METHODS. Records of these 14 men and 9 women aged 22 to 38 (mean, 31) years were reviewed. The most common site involved was the distal femur (n=13), followed by proximal tibia (n=8), proximal femur (n=1), and distal tibia (n=1). The lesions were classified as grade I (n=3), grade II (n=18), and grade III (n=2). Based on histology, the tumour stage was classified as grade I (n=5) and grade II (n=18). Two of these patients had recurrences, which were initially treated with simple curettage and bone grafting of the distal femur and distal tibia. RESULTS. The mean follow-up period was 5.7 (range, 2.5-10.1) years. 14 of the 23 patients were followed up for over 10 years. No patient developed any local recurrence, remote metastasis, or complication related to surgery or adjuvant therapy. CONCLUSION. Combined treatment entailing curettage, electrocautery, burring, phenol irrigation, and cementation was effective in treating GCT of bone.

  15. Malignant giant cell tumor in the carpal tunnel: a case report and review of literature.

    PubMed

    Theunissen, Carla I J M; Bras, Johannes; Lienden, Krijn P van; Obdeijn, Miryam C

    2013-08-01

    Background Malignant tenosynovial giant cell tumors (GCTs) are extremely rare, and their etiology is unknown. However, this type of malignancy is associated with high metastasis and mortality rates. Therefore, the treatment of choice is wide excision. Case Description A 66-year-old man complained of tingling and loss of sensation in the left hand, caused by a tumor that compressed the median nerve. The tumor was excised. Histopathologic examination revealed a ganglion cyst. Two years later, the patient visited our clinic with recurrent and similar complaints of the left hand. This time, however, the lesion turned out to be a malignant tenosynovial GCT and was treated by amputation of the forearm. Literature Review Since 1979, only 37 malignant tenosynovial GCTs have been reported in literature. Follow-up of these patients showed that 11 patients died of the disease, 4 patients were still living with the disease, and 14 patients had no evidence of disease after treatment. The other seven patients were lost to follow-up, and one patient died of other causes. In these 37 patients, a high incidence of lymph node metastasis (41%) and a high mortality rate (30%) were seen. Clinical Relevance Although this malignant tenosynovial GCT is very rare, high mortality rates have been observed because of the high incidence of lymph node metastases. Therefore, more awareness has to be created, to recognize and treat this tumor timely. PMID:24436827

  16. Bilateral scalp necrosis as a rare but devastating complication of giant cell arteritis.

    PubMed

    Akram, Q; Knight, S; Saravanan, R

    2015-01-01

    Giant cell arteritis (GCA) is a medium to large vessel vasculitis of unknown aetiology. Commonly, it affects the temporal arteries and is known as temporal arteritis. It has an association with polymyalgia rheumatica and can result in severe complications such as loss of vision and rarely scalp necrosis. There are approximately 100 cases of scalp necrosis in patients with GCA published in the literature to date. We report a case of a man who presented with a 4-week history of bilateral scalp necrosis associated with headache, jaw claudication, temporal artery tenderness, and raised inflammatory markers. He did not have any visual loss. A diagnosis of GCA was made and he was started on high-dose steroids immediately. The scalp lesions did improve and his symptoms resolved without any visual loss but, sadly he died due to severe sepsis. This case report is important as it describes a rare but severe complication of a common large vessel vasculitis seen by both primary care physicians and rheumatologists. Prompt recognition and early treatment by the physician are crucial to the patient to prevent visual loss or a fatal stroke. It also highlights complications associated with steroids which are the mainstay of treatment for this condition. PMID:25318611

  17. Pyogenic Granuloma/Peripheral Giant-Cell Granuloma Associated with Implants.

    PubMed

    Jané-Salas, Enric; Albuquerque, Rui; Font-Muñoz, Aura; González-Navarro, Beatríz; Estrugo Devesa, Albert; López-López, Jose

    2015-01-01

    Introduction. Pyogenic granuloma (PG) and peripheral giant-cell granuloma (PGCG) are two of the most common inflammatory lesions associated with implants; however, there is no established pathway for treatment of these conditions. This paper aims to illustrate the successful treatment of PG and PGCG and also report a systematic review of the literature regarding the various treatments proposed. Methods. To collect relevant information about previous treatments for PG and PGCG involving implants we carried out electronic searches of publications with the key words "granuloma", "oral", and "implants" from the last 15 years on the databases Pubmed, National Library of Medicine's Medline, Scielo, Scopus, and Cochrane Library. Results. From the electronic search 16 case reports were found showing excision and curettage as the main successful treatment. As no clinical trials or observational studies were identified the authors agreed to present results from a review perspective. Conclusion. This is the largest analysis of PG and PGCG associated with implants published to date. Our review would suggest that PGCG associated with implants appears to have a more aggressive nature; however the level of evidence is very limited. Further cohort studies with representative sample sizes and standard outcome measures are necessary for better understanding of these conditions. PMID:26697068

  18. Pyogenic Granuloma/Peripheral Giant-Cell Granuloma Associated with Implants

    PubMed Central

    Jané-Salas, Enric; Albuquerque, Rui; Font-Muñoz, Aura; González-Navarro, Beatríz; Estrugo Devesa, Albert; López-López, Jose

    2015-01-01

    Introduction. Pyogenic granuloma (PG) and peripheral giant-cell granuloma (PGCG) are two of the most common inflammatory lesions associated with implants; however, there is no established pathway for treatment of these conditions. This paper aims to illustrate the successful treatment of PG and PGCG and also report a systematic review of the literature regarding the various treatments proposed. Methods. To collect relevant information about previous treatments for PG and PGCG involving implants we carried out electronic searches of publications with the key words “granuloma”, “oral”, and “implants” from the last 15 years on the databases Pubmed, National Library of Medicine's Medline, Scielo, Scopus, and Cochrane Library. Results. From the electronic search 16 case reports were found showing excision and curettage as the main successful treatment. As no clinical trials or observational studies were identified the authors agreed to present results from a review perspective. Conclusion. This is the largest analysis of PG and PGCG associated with implants published to date. Our review would suggest that PGCG associated with implants appears to have a more aggressive nature; however the level of evidence is very limited. Further cohort studies with representative sample sizes and standard outcome measures are necessary for better understanding of these conditions. PMID:26697068

  19. A hidden giant: Wallenberg syndrome and aortal wall thickening as an atypical presentation of a giant cell arteritis

    PubMed Central

    Stengl, Katharina Luisa; Buchert, Ralph; Bauknecht, Hans; Sobesky, Jan

    2013-01-01

    We report a case of a 73-year-old woman with a brainstem stroke presenting as Wallenberg syndrome. By transoesophageal echocardiography and combined 18F-fluordeoxyglucose positron emission and CT (18F-FDG PET/CT), the diagnosis of large artery vasculitis owing to giant cell arteritis was confirmed. In the absence of classical clinical signs, the examination of the large extracranial vessels by ultrasound and 18F-FDG PET/CT played the key role in detecting a widespread vasculitis. PMID:23456154

  20. Impaired elastic properties of ascending aorta in patients with giant cell arteritis

    PubMed Central

    Margos, P; Moyssakis, I; Tzioufas, A; Zintzaras, E; Moutsopoulos, H

    2005-01-01

    Objective: To investigate the elastic properties of the ascending aorta in untreated patients with giant cell arteritis compared with age and sex matched normal controls. Methods: Distensibility of the ascending aorta and aortic strain were measured in 22 patients with a recent diagnosis of giant cell arteritis (documented by a positive temporal artery biopsy) before initiation corticosteroid treatment, and in 44 age and sex matched healthy subjects. Aortic distensibility was calculated as 2x[pulsatile change in aortic diameter]/[(diastolic aortic diameter)x(aortic pulse pressure)], and aortic strain as [pulsatile change in aortic diameter]/[diastolic aortic diameter]. Aortic diameters were measured by echocardiography. Aortic pressures were obtained by external sphygmomanometry. Results: Distensibility of the ascending aorta and aortic strain were both lower in patients with giant cell arteritis than in the controls (p<0.01). In the patients with giant cell arteritis, aortic distensibility was inversely correlated with white blood cell count (p<0.05), but not with erythrocyte sedimentation rate or C reactive protein. Conclusions: Compared with healthy subjects, aortic distensibility and aortic strain are decreased in patients with giant cell arteritis before initiation of corticosteroid treatment. There was an association between the degree of reduction of aortic distensibility and the white blood cell count in the patient group. PMID:15231510

  1. [Denosumab may be a supplement to the surgical treatment of giant cell tumours of bone].

    PubMed

    Sørensen, Anna Lynge; Hansen, Rehne Lessmann; Jørgensen, Peter Holmberg

    2016-09-01

    Giant cell tumour of bone (GCTB) is an aggressive bone tumour causing bone destruction. GCTB requires surgical treatment, and severe cases have a high risk of functional morbidity. GCTB consists of receptor activator of nuclear factor kappa-B (RANK)-positive osteoclast-like giant cells. The formation and activity of these cells are mediated by the interaction with RANK ligand (RANKL) released from neoplastic stromal cells. Denosumab is a human monoclonal antibody which inhibits RANKL and impairs the growth of the GCTB. Several studies have described the ability of denosumab to downgrade the extent of surgical treatment and improve the functional outcome. PMID:27593237

  2. Biological characteristics of a novel giant cell tumor cell line derived from spine.

    PubMed

    Zhou, Zhenhua; Li, Yan; Xu, Leqin; Wang, Xudong; Chen, Su; Yang, Cheng; Xiao, Jianru

    2016-07-01

    Giant cell tumor of bone(GCTB) is a special bone tumor for it consists of various cell types, and its biological characteristics is different from common benign or malignant neoplasm. In the present study, we report the biological features of a primary Asian GCTB cell line named GCTB28. We analyzed extensive properties of the GCTB28 cells including morphological observations, growth, cell cycle, karyotype, proliferation, proteins expression, surface biomarker verification, and tumorigenicity in nude mice. We found that the stromal cells of GCTB were endowed with self-renewal capacity and played dominant roles in GCTB development. Moreover, we confirmed that GCTB cells can be CD33(-)CD14(-) phenotype which was not in accord with previous study. This study provides an in vitro model system to investigate pathogenic mechanisms and molecular characteristics of GCTB and also provides a useful tool for researching the therapeutic targeting of GCTB.

  3. Syncytial giant cell hepatitis in a patient with chronic lymphocytic leukemia

    PubMed Central

    GUPTA, Neil; NJEI, Basile

    2016-01-01

    While it commonly occurs in the pediatric population, syncytial giant cell hepatitis is rare in adults, which is diagnosed histologically by the presence of multinucleated cells in the liver. The literature has recorded only approximately one hundred cases in adults during the past two decades in whom malignancy is rarely associated with giant cell hepatitis. Our patient is a 66-year-old woman who was diagnosed with chronic lymphocytic leukemia (CLL) and subsequently developed syncytial giant cell hepatitis. This disease is usually linked to virus infection, autoimmune diseases, and drug medications. The association between CLL and giant cell hepatitis is rare, with only three cases reported. In most cases viral particles on electron microscopy are reported and the patients usually have a history of chemotherapy and hypogammaglobulinemia. Unlike such cases, our patient developed giant cell hepatitis in the absence of such confounding variables. The treatment for our patient was a high-dose corticosteroid and rituxan, with improvement in liver enzymes. PMID:26147671

  4. Prognostic Impact of Reduced Connexin43 Expression and Gap Junction Coupling of Neoplastic Stromal Cells in Giant Cell Tumor of Bone

    PubMed Central

    Balla, Peter; Maros, Mate Elod; Barna, Gabor; Antal, Imre; Papp, Gergo; Sapi, Zoltan; Athanasou, Nicholas Anthony; Benassi, Maria Serena; Picci, Pierro; Krenacs, Tibor

    2015-01-01

    Missense mutations of the GJA1 gene encoding the gap junction channel protein connexin43 (Cx43) cause bone malformations resulting in oculodentodigital dysplasia (ODDD), while GJA1 null and ODDD mutant mice develop osteopenia. In this study we investigated Cx43 expression and channel functions in giant cell tumor of bone (GCTB), a locally aggressive osteolytic lesion with uncertain progression. Cx43 protein levels assessed by immunohistochemistry were correlated with GCTB cell types, clinico-radiological stages and progression free survival in tissue microarrays of 89 primary and 34 recurrent GCTB cases. Cx43 expression, phosphorylation, subcellular distribution and gap junction coupling was also investigated and compared between cultured neoplastic GCTB stromal cells and bone marow stromal cells or HDFa fibroblasts as a control. In GCTB tissues, most Cx43 was produced by CD163 negative neoplastic stromal cells and less by CD163 positive reactive monocytes/macrophages or by giant cells. Significantly less Cx43 was detected in α-smooth muscle actin positive than α-smooth muscle actin negative stromal cells and in osteoclast-rich tumor nests than in the adjacent reactive stroma. Progressively reduced Cx43 production in GCTB was significantly linked to advanced clinico-radiological stages and worse progression free survival. In neoplastic GCTB stromal cell cultures most Cx43 protein was localized in the paranuclear-Golgi region, while it was concentrated in the cell membranes both in bone marrow stromal cells and HDFa fibroblasts. In Western blots, alkaline phosphatase sensitive bands, linked to serine residues (Ser369, Ser372 or Ser373) detected in control cells, were missing in GCTB stromal cells. Defective cell membrane localization of Cx43 channels was in line with the significantly reduced transfer of the 622 Da fluorescing calcein dye between GCTB stromal cells. Our results show that significant downregulation of Cx43 expression and gap junction coupling in

  5. The riddle of multinucleated “floret-like” giant cells and their detection in an extensive gluteal neurofibroma: a case report

    PubMed Central

    2013-01-01

    Introduction The neurofibromatoses are inherited tumor predisposition syndromes involving two major clinical phenotypes: neurofibromatosis type 1 (von Recklinghausen's disease) is linked to chromosome 17q, and tends to occur seven times more frequently than neurofibromatosis type 2. Neurofibromatosis type 1 entails a distinctive cutaneous manifestation prevailed upon by benign neurofibromas, which may vary in size, number and distribution. On the histological level, neurofibromas are composed of an admixture of neurilemmal cells, including Schwann cells, fibroblasts, and – to a lesser extent – perineurial cells. Case presentation The case of a 39-year-old Caucasian man with a voluminous recurrent neurofibroma of 27×15cm extending from the left gluteal region to thoraco-lumbar levels Th6 through L4 is reported. Within the soft tissue tumor a pseudocyst of 7.3×9.3cm was found preoperatively. Conclusion Histopathological study of the excised mass was conspicuous for revealing a large number of multinucleated floret-like giant cells within an otherwise classical soft tissue neurofibroma. Previous reports on neurofibromas with multinucleated floret-like giant cells are distinctly scant. Available evidence from the literature does not suggest any consistent correlation of multinucleated floret-like giant cells in neurofibromas with gender, age, traumatic antecedents, size of the lesion, recurrence, or malignant transformation. Furthermore, the presence of such cells may not be specific for neurofibromatosis type 1, as they occasionally are encountered in some unrelated mesenchymal neoplasms as well. PMID:23890233

  6. Biophysical characterisation of electrofused giant HEK293-cells as a novel electrophysiological expression system

    SciTech Connect

    Zimmermann, D.; Terpitz, U.; Zhou, A.; Reuss, R.; Mueller, K.; Sukhorukov, V.L.; Gessner, P.; Nagel, G.; Zimmermann, U.; Bamberg, E. . E-mail: ernst.bamberg@mpibp-frankfurt.mpg.de

    2006-09-22

    Giant HEK293 cells of 30-65 {mu}m in diameter were produced by three-dimensional multi-cell electrofusion in 75 mOsm sorbitol media. These strong hypotonic conditions facilitated fusion because of the spherical shape and smooth membrane surface of the swollen cells. A regulatory volume decrease (RVD), as observed at higher osmolalities, did not occur at 75 mOsm. In contrast to field-treated, but unfused cells, the increase in volume induced by hypotonic shock was only partly reversible in the case of fused giant cells after their transfer into isotonic medium. The large size of the electrofused cells allowed the study of their electrophysiological properties by application of both whole-cell and giant excised patch-clamp techniques. Recordings on giant cells yielded a value of 1.1 {+-} 0.1 {mu}F/cm{sup 2} for the area-specific membrane capacitance. This value was consistent with that of the parental cells. The area-specific conductivity of giant cells (diameter > 50 {mu}m) was found to be between 12.8 and 16.1 {mu}S/cm{sup 2}, which is in the range of that of the parental cells. Measurements with patch-pipettes containing fluorescein showed uniform dye uptake in the whole-cell configuration, but not in the cell-attached configuration. The diffusion-controlled uniform uptake of the dye into the cell interior excludes internal compartmentalisation. The finding of a homogeneous fusion was also supported by expression of the yellow fluorescent protein YFP (as part of the fusion-protein ChR2-YFP) in giant cells since no plasma-membrane bound YFP-mediated fluorescence was detected in the interior of the electrofused cells. Functional expression and the electrophysiological characterisation of the light-activated cation channel Channelrhodopsin 2 (ChR2) yielded similar results as for parental cells. Most importantly, the giant cells exhibited a comparable expression density of the channel protein in the plasma membrane as observed in parental cells. This demonstrates that

  7. Respiration characteristics of mitochondria in parental and giant transformed cells of the murine Nemeth-Kellner lymphoma.

    PubMed

    Horbay, Rostyslav O; Manko, Bohdan O; Manko, Volodymyr V; Lootsik, Maxim D; Stoika, Rostyslav S

    2012-01-01

    Respiration characteristics of mitochondria of the parental and giant cells of murine NK/Ly (Nemeth-Kellner lymphoma) were studied. The giant cell-enriched ascites were obtained by serial intraperitoneal injections of vinblastine in tumour-bearing mice. Ascites containing >70% giant cells were used. Their diameter of was over 17 μm (~2800 μm(3)), while the diameter of the parental cells was 12.7 μm (1100 μm(3)). The respiration rate of mitochondria in situ was measured by oxygen consumption in intact and digitonin-permeabilized NK/Ly cells. Endogenous respiration of intact giant NK/Ly cells was three times higher compared to the parental ones, roughly in agreement with the volume change. The giant NK/Ly cells were far more resistant to permeabilization with digitonin than the parental cells, as shown by Trypan Blue and LDH (lactate dehydrogenase) release tests. After digitonin permeabilization, oxygen consumption was reduced to a minimal level (0.06 ng atom O/(s × 106 cells) in both types of cells. Addition of α-ketoglutarate or succinate to the incubation medium increased oxygen consumption in the parental cells by 46 and 164% respectively. In the giant NK/Ly cells, the corresponding increases were 164 and 276%. Addition of ADP to α-ketoglutarate- or succinate-supplemented medium further stimulated oxygen consumption of the permeabilized NK/Ly cells; however, the effect of ADP was more pronounced in the giant cells. In addition, indices of respiratory control were significantly higher in the giant cells. Oligomycin suppressed considerably the respiration of the intact giant cells but had a much weaker effect on parental cells. Thus, giant NK/Ly cells possess much higher respiration rates and show tighter coupling between the respiration and oxidative phosphorylation compared with parental cells.

  8. Aggregatibacter actinomycetemcomitans induces Th17 cells in atherosclerotic lesions.

    PubMed

    Jia, Ru; Hashizume-Takizawa, Tomomi; Du, Yuan; Yamamoto, Masafumi; Kurita-Ochiai, Tomoko

    2015-04-01

    Th17 cells have been linked to the pathogenesis of several chronic inflammatory and autoimmune diseases. However, the role of Th17 cells and IL-17 in atherosclerosis remains poorly understood. We previously reported that Aggregatibacter actinomycetemcomitans (Aa) bacteremia accelerated atherosclerosis accompanied by inflammation in apolipoprotein E-deficient spontaneously hyperlipidemic (Apoe(shl)) mice. In this study, we investigated whether Aa promotes the Th17 inducing pathway in Aa-challenged Apoe(shl) mice. Mice were intravenously injected with live Aa HK1651 or vehicles. Time-course analysis of splenic IL-17(+)CD4(+) cell frequencies, the proximal aorta lesion area, serum IL-17, IL-6, TGF-β and IL-1β levels, the mRNA expression of Th17-related molecules such as IL-1β, IL-6, IL17RA, STAT3, IL-21, IL-23, TGF-β and RORγt, Th17-related microRNA levels and the levels of AIM-2, Mincle and NLRP3 were examined. Challenge with Aa time dependently induced tropism of Th17 cells in the spleen and increase in atheromatous lesions in the aortic sinus of Apoe(shl) mice. Serum IL-17, IL-6, TGF-β and IL-1β levels were significantly enhanced by Aa. The gene expression of IL-1β, IL-6, IL-17RA, IL-21, IL-23, TGF-β, STAT3, RORγt, AIM-2, Mincle and NLRP3 was also time dependently stimulated in the aorta of Aa-challenged mice. Furthermore, Aa challenge significantly increased the expression of miR-146b and miR-155 in the aorta. Based on the results, it seems that Aa stimulates Th17 induction that affects the progression of Aa-accelerated atherosclerosis. PMID:25743474

  9. Transcriptional analysis through RNA sequencing of giant cells induced by Meloidogyne graminicola in rice roots

    PubMed Central

    Ji, Hongli; Gheysen, Godelieve; Denil, Simon; Lindsey, Keith; Topping, Jennifer F.; Nahar, Kamrun; Haegeman, Annelies; De Vos, Winnok H.; Trooskens, Geert; Van Criekinge, Wim; De Meyer, Tim; Kyndt, Tina

    2013-01-01

    One of the reasons for the progressive yield decline observed in aerobic rice production is the rapid build-up of populations of the rice root knot nematode Meloidogyne graminicola. These nematodes induce specialized feeding cells inside root tissue, called giant cells. By injecting effectors in and sipping metabolites out of these cells, they reprogramme normal cell development and deprive the plant of its nutrients. In this research we have studied the transcriptome of giant cells in rice, after isolation of these cells by laser-capture microdissection. The expression profiles revealed a general induction of primary metabolism inside the giant cells. Although the roots were shielded from light induction, we detected a remarkable induction of genes involved in chloroplast biogenesis and tetrapyrrole synthesis. The presence of chloroplast-like structures inside these dark-grown cells was confirmed by confocal microscopy. On the other hand, genes involved in secondary metabolism and more specifically, the majority of defence-related genes were strongly suppressed in the giant cells. In addition, significant induction of transcripts involved in epigenetic processes was detected inside these cells 7 days after infection. PMID:23881398

  10. Synthesis of sodium channels in the cell bodies of squid giant axons.

    PubMed Central

    Brismar, T; Gilly, W F

    1987-01-01

    Giant axons in squid are formed by fusion of axons from many small cell bodies in the giant fiber lobe (GFL) of the stellate ganglion. Somata of GFL cells in vivo are inexcitable and do not have measurable sodium current (INa) when studied with microelectrode or patch-electrode voltage-clamp techniques. If GFL cells are separated from the giant axons and maintained in primary culture, axon-like INa can be recorded from the somata after several days. Incorporation of Na channels into GFL cell bodies requires protein synthesis, intracellular microtubule-based transport, and the lack of a morphologically defined axon to serve as a sink for channels synthesized in culture. PMID:3469679

  11. Inactivated autograft–prosthesis composite have a role for grade III giant cell tumor of bone around the knee

    PubMed Central

    2013-01-01

    Background Giant cell tumors (GCT) around the knee are common and pose a special problem of reconstruction after tumor excision, especially for grade III GCT. We questioned whether en bloc resection and reconstruction with alcohol inactivated autograft-prosthesis composite would provide (1) local control and long-term survival and (2) useful limb function in patients who had grade III GCT around the knee. Methods We retrospectively reviewed eight patients (5 males and 3 females) treated with this procedure with mean age of 31 years (range 20 to 43 years) from Jan 2007 to Oct 2008. 5 lesions were located in distal femur and 3 in proximal tibia. 4 patients were with primary tumor and the other 4 with recurrence. 2 patients showed pathological fracture. Results Mean Follow-up is 54 months ranging from 38 to 47 months. No recurrence, metastasis, prosthesis loosening were found. The mean healing time between autograft and host bone was 5.5 months. The mean MSTS score was 26.3 (88%) ranging from 25 to 29. The mean ISOLS composite graft score was 32.8 (88.5%) ranging from 28 to 35. Creeping substitution is possibly the main way in bony junction. The healing time in femoral lesion is faster than that in tibial lesion. Conclusions The technique of alcohol inactivated autograft-prosthesis composite could be able to achieve satisfactory oncological and functional outcomes in Grade III GCT. PMID:24209887

  12. A case of osteoclast-like giant cell-rich epithelioid glioblastoma with BRAF V600E mutation.

    PubMed

    Funata, Nobuaki; Nobusawa, Sumihito; Yamada, Ryoji; Shinoura, Nobusada

    2016-01-01

    Epithelioid glioblastomas (E-GBMs) are rare, highly aggressive tumors consisting of closely packed tumor cells with smooth, round cell borders and abundant eosinophilic cytoplasm. They tend to affect younger patients compared with conventional GBM. BRAF V600E mutation is characteristically found in approximately 50% of all E-GBMs, compared with a low frequency of this mutation in conventional GBM. Here, we report an unusual case of glioma involving the right frontal lobe, basal ganglia and thalamus in an HIV-positive 30-year-old man on antiretroviral therapy. The lesion was composed of abundant discohesive, monotonous epithelioid cells with extensive necrosis, spindle and polyhedral cells, low-grade oligoastrocytoma-like areas, sarcomatous components, and numerous osteoclast-like giant cells (OLGCs) intermingled with epithelioid tumor cells. As the epithelioid cells accounted for more than one-third of the tumor, a pathological diagnosis of E-GBM was made. BRAF V600E mutation was detected in both oligoastrocytoma-like and epithelioid cell components. Similar to previously reported findings on E-GBM associated with low-grade glioma, this case suggested that low-grade astrocytic glioma with BRAF V600E mutation progressed to E-GBM. OLGCs are rarely observed in gliomas, and this is the first case report of E-GBM associated with abundant OLGC infiltration.

  13. Leukemic manifestation of blastic plasmacytoid dendritic cell neoplasm lacking skin lesion : a borderline case between acute monocytic leukemia.

    PubMed

    Takiuchi, Yoko; Maruoka, Hayato; Aoki, Kazunari; Kato, Aiko; Ono, Yuichiro; Nagano, Seiji; Arima, Hiroshi; Inoue, Daichi; Mori, Minako; Tabata, Sumie; Yanagita, Soshi; Matsushita, Akiko; Nishio, Mari; Imai, Yukihiro; Imai, Yukihiro; Ito, Kiminari; Fujita, Haruyuki; Kadowaki, Norimitsu; Ishikawa, Takayuki; Takahashi, Takayuki

    2012-01-01

    Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy with a poor prognosis. We encountered a unique case of BPDCN that was leukemic at presentation without skin lesion and expressed CD33 antigen. A 74-year-old man was admitted because of dyspnea. Physically, hepatosplenomegaly, but not skin lesions and superficial lymph node swelling, was noted. The white blood count was 33.6 × 10(9)/L with 19% giant abnormal cells. These cells were positive for CD4, CD86, CD123 (bright), BDCA-2, and HLA-DR, but negative for CD1a, CD3, CD11b, CD11c, CD13, CD14, CD19, CD64, and CD68. From these findings, a diagnosis of BPDCN was made. In terms of unusual expression, these tumor cells were positive for CD33 but negative for CD56. The karyotype was 47, XY, t(6;8) (p21;q24), + r. We performed combination chemotherapy (Ara-C + VP-16 + MIT), which resulted in a marked reduction of tumor cells and improvement of the dyspnea. On day 16, however, he died of sepsis due to Bacillus cereus. The clinical picture of this patient is unusual and may provide new information on the clinicopathology of BPDCN. PMID:23037626

  14. Treatment with Doxycycline of Generalized Annular Elastolytic Giant Cell Granuloma Associated with Borrelia burgdorferi Infection

    PubMed Central

    Tas, B; Caglar, A; Ozdemir, B

    2015-01-01

    ABSTRACT This is a case of generalized annular elastolytic giant cell granuloma (AEGCG) associated with borrelia infection and genes of p-30, p-31, p-39. A possible cross-mediated reaction from the T-cell type which might have induced the AEGCG is discussed from the concept of “heat-shock proteins (HSPs) and molecular mimicry”. PMID:26624605

  15. The suitability of the ultrasound biomicroscope for establishing texture in giant cell arteritis

    PubMed Central

    Roters, S.; Szurman, P.; Engels, B.; Brunner, R.

    2001-01-01

    AIM—To establish whether ultrasound biomicroscope (UBM) is a helpful tool in locating the arterial segment responsible in patients with segmental attacks in giant cell arteritis
METHODS—The superficial temporal arteries of 19 patients with suspected giant cell arteritis were examined with the UBM before biopsy.
RESULTS—20 specimens provided the histological proof of giant cell arteritis in five patients. Side differences, a dark perivascular halo, and high reflexivity of the intra-arterial space were found.
CONCLUSION—it is assumed that there are two types of arteritic inflammation: (1) the occlusion of intra-arterial space due to intimal fibrosis (UBM: high reflexive "filling"), and (2) inflammation of the perivascular zone with oedematous thickening and infiltration of the media (UBM: dark halo) and its combination. UBM is helpful in obtaining an indication of the side and segment for biopsy.

 PMID:11466252

  16. Infantile disseminated visceral giant cell arteritis presenting as sudden infant death.

    PubMed

    Kagata, Y; Matsubara, O; Ogata, S; Lie, J T; Mark, E J

    1999-03-01

    The rare clinicopathological entity 'disseminated visceral giant cell arteritis' (DVGCA) was first described in 1978. It is characterized by widespread small-vessel giant cell angitis and extravascular granulomas. A normal and healthy 7-month-old boy who presented unexpectedly with sudden infant death syndrome (SIDS) is reported. Histological examination at autopsy revealed giant cell angitis of the aorta, common carotid, coronary, pulmonary, celiac, mesenteric and common iliac arteries. There were also granulomas in the tracheal wall and liver. To our knowledge, this is the first documented case of DVGCA occurring in an infant younger than 12 months of age. A review of the literature on DVGCA is presented in this report, and the differential diagnosis is discussed.

  17. Coevolution of neoplastic epithelial cells and multilineage stroma via polyploid giant cells during immortalization and transformation of mullerian epithelial cells

    PubMed Central

    Zhang, Shiwu; Mercado-Uribe, Imelda; Sood, Anil; Bast, Robert C.; Liu, Jinsong

    2016-01-01

    Stromal cells are generally considered to be derived primarily from the host's normal mesenchymal stromal cells or bone marrow. However, the origins of stromal cells have been quite controversial. To determine the role of polyploidy in tumor development, we examined the fate of normal mullerian epithelial cells during the immortalization and transformation process by tracing the expression of SV40 large T antigen. Here we show that immortalized or HRAS-transformed mullerian epithelial cells contain a subpopulation of polyploid giant cells that grow as multicellular spheroids expressing hematopoietic markers in response to treatment with CoCl2. The immortalized or transformed epithelial cells can transdifferentiate into stromal cells when transplanted into nude mice. Immunofluorescent staining revealed expression of stem cell factors OCT4, Nanog, and SOX-2 in spheroid, whereas expression of embryonic stem cell marker SSEA1 was increased in HRAS-transformed cells compared with their immortalized isogenic counterparts. These results suggest that normal mullerian epithelial cells are intrinsically highly plastic, via the formation of polyploid giant cells and activation of embryonic stem-like program, which work together to promote the coevolution of neoplastic epithelial cells and multiple lineage stromal cells. PMID:27382431

  18. Coevolution of neoplastic epithelial cells and multilineage stroma via polyploid giant cells during immortalization and transformation of mullerian epithelial cells.

    PubMed

    Zhang, Shiwu; Mercado-Uribe, Imelda; Sood, Anil; Bast, Robert C; Liu, Jinsong

    2016-03-01

    Stromal cells are generally considered to be derived primarily from the host's normal mesenchymal stromal cells or bone marrow. However, the origins of stromal cells have been quite controversial. To determine the role of polyploidy in tumor development, we examined the fate of normal mullerian epithelial cells during the immortalization and transformation process by tracing the expression of SV40 large T antigen. Here we show that immortalized or HRAS-transformed mullerian epithelial cells contain a subpopulation of polyploid giant cells that grow as multicellular spheroids expressing hematopoietic markers in response to treatment with CoCl2. The immortalized or transformed epithelial cells can transdifferentiate into stromal cells when transplanted into nude mice. Immunofluorescent staining revealed expression of stem cell factors OCT4, Nanog, and SOX-2 in spheroid, whereas expression of embryonic stem cell marker SSEA1 was increased in HRAS-transformed cells compared with their immortalized isogenic counterparts. These results suggest that normal mullerian epithelial cells are intrinsically highly plastic, via the formation of polyploid giant cells and activation of embryonic stem-like program, which work together to promote the coevolution of neoplastic epithelial cells and multiple lineage stromal cells. PMID:27382431

  19. Vascular endothelial cell participation in formation of lymphoepithelial lesions (epi-myoepithelial islands) in lymphoepithelial sialadenitis (benign lymphoepithelial lesion).

    PubMed

    Metwaly, Hamdy; Cheng, Jun; Ida-Yonemochi, Hiroko; Ohshiro, Kazufumi; Jen, Kai Yu; Liu, Ai Ru; Saku, Takashi

    2003-07-01

    Lymphoepithelial lesions (LELs, or epi-myoepithelial islands) in lymphoepithelial sialadenitis (LESA, or benign lymphoepithelial lesion) of the salivary gland are known to be mainly composed of duct epithelial cells. However, other constituent cells are poorly characterized. Formalin-fixed paraffin sections obtained from six surgical specimens of LESA were examined using immunohistochemistry for cytoskeletal proteins, inflammatory cells, vascular endothelial cells, and extracellular matrix (ECM) molecules as well as by in situ hybridization for ECM molecules. In addition to keratin-immunopositive (+) duct-like epithelial cells, there were CD31/CD34+ vascular endothelial cells-which were either scattered in a singular fashion, in formed sheets, or in tubular structures-, CD20+ B lymphocytes, CD45RO+ T lymphocytes, and CD68 macrophages in the LELs. ECM molecules, such as heparan sulfate proteoglycan and tenascin, were immunolocalized in hyaline materials in the LELs. Their mRNAs were demonstrated mainly in endothelial cells and, to a lesser extent, in lympho-monocytic cells around hyaline materials, but were not as evident in epithelial constituent cells of LELs. The results indicate that endothelial cells as well as inflammatory cells are important constituents of the LELs, and the hyaline ECM cores mainly result from the intra-LEL angiogenesis by endothelial cells with the assistance of inflammatory cells. This intra-LEL vasculature seems to support regeneration and proliferation of salivary epithelial remnant cells.

  20. DNA sequence and expression analysis of root-knot nematode-elicited giant cell transcripts.

    PubMed

    Bird, D M; Wilson, M A

    1994-01-01

    Fifty-eight cDNA clones isolated from a library of transcripts exhibiting up regulation in tomato root giant cells induced by infection with the parasitic nematode Meloidogyne incognita were characterized. A survey of plant tissues identified 31 transcripts present in tissues other than root, including actively dividing and expanding tissues and mature leaf tissues. The identities of approximately 20% of the giant cell transcripts were inferred from DNA sequence data; they include sequences encoding a plasmalemma proton ATPase, a putative Myb-type transcription factor, and the largest subunit of RNA polymerase II.

  1. Extra-Articular Diffuse Giant Cell Tumor of the Tendon Sheath: A Report of 2 Cases.

    PubMed

    Savvidou, Olga D; Mavrogenis, Andreas F; Sakellariou, Vasilios I; Chloros, George D; Sarlikiotis, Thomas; Papagelopoulos, Panayiotis J

    2016-06-01

    Two rare cases of extra-articular diffuse variant giant cell tumor of the tendon sheath are presented, at the elbow of a 68-year-old female and the foot of a 56-year-old male. Both patients presented with a palpable masses and marginal excision was performed; histological sections confirmed the diagnosis of extra-articular giant cell tumor. No adjuvant therapy was administered. At the latest follow-up, minimum 24 months after excision both patients were disease-free. PMID:27517076

  2. Extra-Articular Diffuse Giant Cell Tumor of the Tendon Sheath: A Report of 2 Cases

    PubMed Central

    Savvidou, Olga D.; Mavrogenis, Andreas F.; Sakellariou, Vasilios I.; Chloros, George D.; Sarlikiotis, Thomas; Papagelopoulos, Panayiotis J.

    2016-01-01

    Two rare cases of extra-articular diffuse variant giant cell tumor of the tendon sheath are presented, at the elbow of a 68-year-old female and the foot of a 56-year-old male. Both patients presented with a palpable masses and marginal excision was performed; histological sections confirmed the diagnosis of extra-articular giant cell tumor. No adjuvant therapy was administered. At the latest follow-up, minimum 24 months after excision both patients were disease-free. PMID:27517076

  3. Characteristics of mesenchymal stem cells isolated from bone marrow of giant panda.

    PubMed

    Liu, Yuliang; Liu, Yang; Yie, Shangmian; Lan, Jingchao; Pi, Jinkui; Zhang, Zhihe; Huang, He; Cai, Zhigang; Zhang, Ming; Cai, Kailai; Wang, Hairui; Hou, Rong

    2013-09-01

    In present study, we report on bone marrow (BM) mesenchymal stem cells (MSCs) that are isolated from giant pandas. Cells were collected from the BM of two stillborn giant pandas. The cells were cultured and expanded in 10% fetal bovine serum medium. Cell morphology was observed under an inverted microscopy, and the proliferation potential of the cells was evaluated by counting cell numbers for eight consecutive days. Differentiation potentials of the cells were determined by using a variety of differentiation protocols for osteocytes, adipocytes, neuron cells, and cardiomyocytes. Meanwhile, the specific gene expressions for MSCs or differentiated cells were analyzed by RT-PCR. The isolated cells exhibited a fibroblast-like morphology; expressed mesenchymal specific markers such as cluster of differentiation 73 (CD73), SRY (sex determining region Y)-box 2 (SOX-2), guanine nucleotide-binding protein-like 3 (GNL3), and stem cell factor receptor (SCFR); and could be differentiated into osteocytes and adipocytes that were characterized by Alizarin Red and Oil Red O staining. Under appropriate induction conditions, these cells were also able to differentiate into neuroglial-like or myocardial-like cells that expressed specific myocardial markers such as GATA transcription factors 4 (GATA-4), cardiac troponin T (cTnT), and myosin heavy chain 7B (MYH7B), or neural specific markers such as Nestin and glial fibrillary acidic protein (GFAP). This study demonstrated stem cells recovery and growth from giant pandas. The findings suggest that cells isolated from the BM of giant pandas have a high proliferative capacity and multiple differentiation potential in vitro which might aid conservation efforts.

  4. Characteristics of mesenchymal stem cells isolated from bone marrow of giant panda.

    PubMed

    Liu, Yuliang; Liu, Yang; Yie, Shangmian; Lan, Jingchao; Pi, Jinkui; Zhang, Zhihe; Huang, He; Cai, Zhigang; Zhang, Ming; Cai, Kailai; Wang, Hairui; Hou, Rong

    2013-09-01

    In present study, we report on bone marrow (BM) mesenchymal stem cells (MSCs) that are isolated from giant pandas. Cells were collected from the BM of two stillborn giant pandas. The cells were cultured and expanded in 10% fetal bovine serum medium. Cell morphology was observed under an inverted microscopy, and the proliferation potential of the cells was evaluated by counting cell numbers for eight consecutive days. Differentiation potentials of the cells were determined by using a variety of differentiation protocols for osteocytes, adipocytes, neuron cells, and cardiomyocytes. Meanwhile, the specific gene expressions for MSCs or differentiated cells were analyzed by RT-PCR. The isolated cells exhibited a fibroblast-like morphology; expressed mesenchymal specific markers such as cluster of differentiation 73 (CD73), SRY (sex determining region Y)-box 2 (SOX-2), guanine nucleotide-binding protein-like 3 (GNL3), and stem cell factor receptor (SCFR); and could be differentiated into osteocytes and adipocytes that were characterized by Alizarin Red and Oil Red O staining. Under appropriate induction conditions, these cells were also able to differentiate into neuroglial-like or myocardial-like cells that expressed specific myocardial markers such as GATA transcription factors 4 (GATA-4), cardiac troponin T (cTnT), and myosin heavy chain 7B (MYH7B), or neural specific markers such as Nestin and glial fibrillary acidic protein (GFAP). This study demonstrated stem cells recovery and growth from giant pandas. The findings suggest that cells isolated from the BM of giant pandas have a high proliferative capacity and multiple differentiation potential in vitro which might aid conservation efforts. PMID:23557186

  5. Heterogeneous vesicles in mucous epithelial cells of posterior esophagus of Chinese giant salamander (Andrias davidianus).

    PubMed

    Zhang, H; Guo, X; Zhong, S; Ge, T; Peng, S; Yu, P; Zhou, Z

    2015-08-25

    The Chinese giant salamander belongs to an old lineage of salamanders and endangered species. Many studies of breeding and disease regarding this amphibian had been implemented. However, the studies on the ultrastructure of this amphibian are rare. In this work, we provide a histological and ultrastructural investigation on posterior esophagus of Chinese giant salamander. The sections of amphibian esophagus were stained by hematoxylin & eosin (H&E). Moreover, the esophageal epithelium was observed by transmission electron microscopy (TEM). The results showed that esophageal epithelium was a single layer epithelium, which consisted of mucous cells and columnar cells. The esophageal glands were present in submucosa. The columnar cells were ciliated. According to the diverging ultrastructure of mucous vesicles, three types of mucous cells could be identified in the esophageal mucosa: i) electron-lucent vesicles mucous cell (ELV-MC); ii) electron-dense vesicles mucous cell (EDV-MC); and iii) mixed vesicles mucous cell (MV-MC).

  6. Heterogeneous Vesicles in Mucous Epithelial Cells of Posterior Esophagus of Chinese Giant Salamander (Andrias Davidianus)

    PubMed Central

    Zhang, H.; Zhong, S.; Ge, T.; Peng, S.; Yu, P.; Zhou, Z.; Guo, X.

    2015-01-01

    The Chinese giant salamander belongs to an old lineage of salamanders and endangered species. Many studies of breeding and disease regarding this amphibian had been implemented. However, the studies on the ultrastructure of this amphibian are rare. In this work, we provide a histological and ultra-structural investigation on posterior esophagus of Chinese giant salamander. The sections of amphibian esophagus were stained by hematoxylin & eosin (H&E). Moreover, the esophageal epithelium was observed by transmission electron microscopy (TEM). The results showed that esophageal epithelium was a single layer epithelium, which consisted of mucous cells and columnar cells. The esophageal glands were present in submucosa. The columnar cells were ciliated. According to the diverging ultrastructure of mucous vesicles, three types of mucous cells could be identified in the esophageal mucosa: i) electron-lucent vesicles mucous cell (ELV-MC); ii) electron-dense vesicles mucous cell (EDV-MC); and iii) mixed vesicles mucous cell (MV-MC). PMID:26428885

  7. Giant Septic Lymphadenitis with Marked Gas Formation Caused by Bacteroides fragilis in a Patient with Adult T-cell Leukemia/lymphoma.

    PubMed

    Tomoyose, Takeaki; Nakachi, Sawako; Nishi, Yukiko; Morichika, Kazuho; Tedokon, Iori; Tamaki, Keita; Shimabukuro, Natsuki; Hanashiro, Taeko; Samura, Hironori; Fukushima, Takuya; Masuzaki, Hiroaki

    2015-01-01

    Adult T-cell leukemia/lymphoma (ATL) sometimes causes opportunistic infections. A 53-year-old woman with systemic lymphadenopathies was diagnosed with ATL by inguinal lymph node biopsies and underwent oral chemotherapy. Two months later, high grade fever, lower abdominal pain and lymphadenopathy recurred. Computed tomography revealed the presence of lymphadenopathy with marked gas formation in the pelvic lesion. Blood cultures were suggestive of septic lymphadenitis by Bacteroides fragilis (BF). This represents the first demonstration of giant lymphadenitis with gas formation caused by BF in a patient with ATL. Notably, septic lymphadenitis is pivotal in the differential diagnosis of systemic lymphadenopathy in ATL.

  8. Granulomatous slack skin T-cell lymphoma: an important differential diagnosis with giant cell tumor of soft tissue.

    PubMed

    Adriano, André Ricardo; Lima, Tiago Silveira; Battistella, Maxime; Bagot, Martine

    2015-01-01

    Granulomatous slack skin is an indolent T-cell lymphoma, considered to be a variant of mycosis fungoides. Clinically it is characterized by areas of redundant skin, wrinkled, inelastic, with variable erythema and infiltration besides a poikilodermic surface. A differential diagnosis unknown to most dermatologists is the giant cell tumor of soft tissue, which is an extremely rare low-grade sarcoma. The authors report a patient who had undergone extensive surgery because of a primary diagnosis of giant cell tumor of soft tissue, but which proved to be granulomatous slack skin after a second interventional procedure with confirmatory histopathology. PMID:26734874

  9. Granulomatous slack skin T-cell lymphoma: an important differential diagnosis with giant cell tumor of soft tissue*

    PubMed Central

    Adriano, André Ricardo; Lima, Tiago Silveira; Battistella, Maxime; Bagot, Martine

    2015-01-01

    Granulomatous slack skin is an indolent T-cell lymphoma, considered to be a variant of mycosis fungoides. Clinically it is characterized by areas of redundant skin, wrinkled, inelastic, with variable erythema and infiltration besides a poikilodermic surface. A differential diagnosis unknown to most dermatologists is the giant cell tumor of soft tissue, which is an extremely rare low-grade sarcoma. The authors report a patient who had undergone extensive surgery because of a primary diagnosis of giant cell tumor of soft tissue, but which proved to be granulomatous slack skin after a second interventional procedure with confirmatory histopathology. PMID:26734874

  10. Giant cell tumor of bone arising in long bones possibly originates from the metaphyseal region

    PubMed Central

    FUTAMURA, NAOHISA; URAKAWA, HIROSHI; TSUKUSHI, SATOSHI; ARAI, EISUKE; KOZAWA, EIJI; ISHIGURO, NAOKI; NISHIDA, YOSHIHIRO

    2016-01-01

    Giant cell tumor of bone (GCTB) is a primary benign bone tumor with a locally aggressive character. Definitive descriptions of the site of origin for this type of tumor are not available. The aim of the present study was to evaluate the site of origin of GCTB of long bones with regards to epiphyseal lines by means of radiographic examination. For that purpose, plain X-ray scans of 71 GCTBs arising in long bones were retrospectively reviewed. The tumor locations were the distal femur in 31 cases, proximal femur in 11 cases, proximal tibia in 13 cases, distal radius in 6 cases, proximal humerus in 5 cases and proximal fibula in 5 cases. The vertical center (VC) of the tumor was determined with X-ray anteroposterior view, and the correlation between the VC and the epiphyseal line, and between the distance from the epiphyseal line to the VC and tumor area or volume were analyzed using a regression model equation based on scatter plot diagrams. The VC of the tumor was located in the metaphyseal region in 57 cases, in the epiphyseal line in 11 cases and in the epiphyseal region in 3 cases. In cases of GCTB located in the distal femur or proximal tibia, significant correlations between the distance from the VC to the epiphyseal line and tumor area or volume were identified. The site of origin of GCTB was estimated to be located in the metaphyseal region. GCTB often occurs in mature patients, which renders it challenging to estimate the true site of origin of this lesion, since the metaphyseal line has disappeared in mature patients. The results of the present study suggest that GCTB possibly originates in the metaphyseal region. PMID:27073530

  11. Everolimus for subependymal giant cell astrocytoma: 5‐year final analysis

    PubMed Central

    Agricola, Karen; Mays, Maxwell; Tudor, Cindy; Care, Marguerite M.; Holland‐Bouley, Katherine; Berkowitz, Noah; Miao, Sara; Peyrard, Séverine; Krueger, Darcy A.

    2015-01-01

    Objective To analyze the cumulative efficacy and safety of everolimus in treating subependymal giant cell astrocytomas (SEGA) associated with tuberous sclerosis complex (TSC) from an open‐label phase II study (NCT00411619). Updated data became available from the conclusion of the extension phase and are presented in this ≥5‐year analysis. Methods Patients aged ≥ 3 years with a definite diagnosis of TSC and increasing SEGA lesion size (≥2 magnetic resonance imaging scans) received everolimus starting at 3mg/m2/day (titrated to target blood trough levels of 5–15ng/ml). The primary efficacy endpoint was reduction from baseline in primary SEGA volume. Results As of the study completion date (January 28, 2014), 22 of 28 (78.6%) initially enrolled patients finished the study per protocol. Median (range) duration of exposure to everolimus was 67.8 (4.7–83.2) months; 12 (52.2%) and 14 (60.9%) of 23 patients experienced SEGA volume reductions of ≥50% and ≥30% relative to baseline, respectively, after 60 months of treatment. The proportion of patients experiencing daily seizures was reduced from 7 of 26 (26.9%) patients at baseline to 2 of 18 (11.1%) patients at month 60. Most commonly reported adverse events (AEs) were upper respiratory tract infection and stomatitis of mostly grade 1 or 2 severity. No patient discontinued treatment due to AEs. The frequency of emergence of most AEs decreased over the course of the study. Interpretation Everolimus continues to demonstrate a sustained effect on SEGA tumor reduction over ≥5 years of treatment. Everolimus remained well‐tolerated, and no new safety concerns were noted. Ann Neurol 2015;78:929–938 PMID:26381530

  12. GIANT-CELL RICH ATRIAL MYXOMA: REPORT OF TWO CASES AND REVIEW OF LITERATURE.

    PubMed

    Tariq, Hina; Mamoon, Nadira

    2016-01-01

    The cases of two middle age males are presented who were incidentally diagnosed to have atrial myxoma. Both of them underwent successful surgical interventions. Histologically, both myxomas showed abundant multinucleated giant cells, in addition to typical myxoid stroma with stellate and cord-like structures. PMID:27323595

  13. Plasmacytoid dendritic cells in skin lesions of classic Kaposi's sarcoma.

    PubMed

    Karouni, Mirna; Kurban, Mazen; Abbas, Ossama

    2016-09-01

    Plasmacytoid dendritic cells (pDCs) are the most potent producers of type I interferons (IFNs), which allows them to provide anti-viral resistance and to link the innate and adaptive immunity by controlling the function of myeloid DCs, lymphocytes, and natural killer cells. pDCs are involved in the pathogenesis of several infectious [especially viral, such as Molluscum contagiosum (MC)], inflammatory/autoimmune, and neoplastic entities. Kaposi's sarcoma (KS) is a multifocal, systemic lympho-angioproliferative tumor associated with Kaposi's sarcoma-associated herpesvirus (KSHV) infection. Microscopy typically exhibits a chronic inflammatory lymphoplasmacytic infiltrate in addition to the vascular changes and spindle cell proliferation. Despite the extensive research done on the immune evasion strategies employed by KSHV, pDCs role in relation to KS has only rarely been investigated. Given this, we intend to investigate pDC occurrence and activity in the skin lesions of KS. Immunohistochemical staining for BDCA-2 (specific pDC marker) and MxA (surrogate marker for local type I IFN production) was performed on classic KS (n = 20) with the control group comprising inflamed MC (n = 20). As expected, BDCA-2+ pDCs were present in abundance with diffuse and intense MxA expression (indicative of local type I IFN production) in all inflamed MC cases (20 of 20, 100 %). Though present in all the KS cases, pDCs were significantly less abundant in KS than in inflamed MC cases, and MxA expression was patchy/weak in most KS cases. In summary, pDCs are part of the inflammatory host response in KS; however, they were generally low in number with decreased type I IFN production which is probably related to KSHV's ability to evade the immune system through the production of different viral proteins capable of suppressing IFN production as well as pDC function.

  14. Lethal Giant Larvae 1 Tumour Suppressor Activity Is Not Conserved in Models of Mammalian T and B Cell Leukaemia

    PubMed Central

    Hawkins, Edwin D.; Oliaro, Jane; Ramsbottom, Kelly M.; Ting, Stephen B.; Sacirbegovic, Faruk; Harvey, Michael; Kinwell, Tanja; Ghysdael, Jacques; Johnstone, Ricky W.; Humbert, Patrick O.; Russell, Sarah M.

    2014-01-01

    In epithelial and stem cells, lethal giant larvae (Lgl) is a potent tumour suppressor, a regulator of Notch signalling, and a mediator of cell fate via asymmetric cell division. Recent evidence suggests that the function of Lgl is conserved in mammalian haematopoietic stem cells and implies a contribution to haematological malignancies. To date, direct measurement of the effect of Lgl expression on malignancies of the haematopoietic lineage has not been tested. In Lgl1−/− mice, we analysed the development of haematopoietic malignancies either alone, or in the presence of common oncogenic lesions. We show that in the absence of Lgl1, production of mature white blood cell lineages and long-term survival of mice are not affected. Additionally, loss of Lgl1 does not alter leukaemia driven by constitutive Notch, c-Myc or Jak2 signalling. These results suggest that the role of Lgl1 in the haematopoietic lineage might be restricted to specific co-operating mutations and a limited number of cellular contexts. PMID:24475281

  15. Osteoclastic giant cell rich squamous cell carcinoma of the uterine cervix: a case report and review of the literature.

    PubMed

    Alemán-Meza, Lucía; Gómez-Macías, Gabriela Sofía; Barboza-Quintana, Oralia; Garza-Guajardo, Raquel; Loya-Solis, Abelardo

    2014-01-01

    Cervical carcinoma is the most common malignancy of the female genital tract and represents the second most common malignancy in women worldwide. Histologically 85 to 90% of cervical cancers are squamous cell carcinoma. Osteoclastic giant cell rich squamous cell carcinoma is an unusual histological variant of which only 4 cases have been reported. We present the case of a 49-year-old woman with a 6-month history of irregular vaginal bleeding. Examination revealed a 2.7 cm polypoid mass in the anterior lip of the uterine cervix. The patient underwent hysterectomy with bilateral salpingo-oophorectomy. Microscopically the tumor was composed of infiltrative nests of poorly differentiated nonkeratinizing squamous cell carcinoma. Interspersed in between these tumor cells were numerous osteoclastic giant cells with abundant eosinophilic cytoplasm devoid of nuclear atypia, hyperchromatism, or mitotic activity. Immunohistochemistry was performed; CK and P63 were strongly positive in the squamous component and negative in the osteoclastic giant cells, while CD68 and Vimentin were strongly positive in the giant cell population and negative in the squamous component. The patient received chemo- and radiotherapy for recurrent disease identified 3 months later on a follow-up CT scan; 7 months after the surgical procedure the patient is clinically and radiologically disease-free.

  16. Osteoclastic Giant Cell Rich Squamous Cell Carcinoma of the Uterine Cervix: A Case Report and Review of the Literature

    PubMed Central

    Alemán-Meza, Lucía; Gómez-Macías, Gabriela Sofía; Barboza-Quintana, Oralia; Garza-Guajardo, Raquel; Loya-Solis, Abelardo

    2014-01-01

    Cervical carcinoma is the most common malignancy of the female genital tract and represents the second most common malignancy in women worldwide. Histologically 85 to 90% of cervical cancers are squamous cell carcinoma. Osteoclastic giant cell rich squamous cell carcinoma is an unusual histological variant of which only 4 cases have been reported. We present the case of a 49-year-old woman with a 6-month history of irregular vaginal bleeding. Examination revealed a 2.7 cm polypoid mass in the anterior lip of the uterine cervix. The patient underwent hysterectomy with bilateral salpingo-oophorectomy. Microscopically the tumor was composed of infiltrative nests of poorly differentiated nonkeratinizing squamous cell carcinoma. Interspersed in between these tumor cells were numerous osteoclastic giant cells with abundant eosinophilic cytoplasm devoid of nuclear atypia, hyperchromatism, or mitotic activity. Immunohistochemistry was performed; CK and P63 were strongly positive in the squamous component and negative in the osteoclastic giant cells, while CD68 and Vimentin were strongly positive in the giant cell population and negative in the squamous component. The patient received chemo- and radiotherapy for recurrent disease identified 3 months later on a follow-up CT scan; 7 months after the surgical procedure the patient is clinically and radiologically disease-free. PMID:25587478

  17. Giant Cell Tumor of the Uterus: A Report of 3 Cases With a Spectrum of Morphologic Features.

    PubMed

    Bennett, Jennifer A; Sanada, Sakiko; Selig, Martin K; Hariri, Lida P; Nielsen, Gunnlaugur P; Oliva, Esther

    2015-07-01

    Giant cell tumors, a well-recognized neoplasm of bone, can rarely be found in the uterus. Such tumors are characterized by a dual population of mononuclear and osteoclast-like giant cells that lack epithelial and specific mesenchymal differentiation. In this study, the clinicopathologic features of 3 giant cell tumors of the uterus were reviewed. Immunohistochemistry for CD68, CD163, h-caldesmon, desmin, SMA, AE1/AE3, CD10, ER, PR, cyclin D1, CD1a, CD34, CD30, S100, myogenin/myoglobin, and Ki-67 was performed in all tumors, along with ultrastructural analysis in one. The patients were 47, 57, and 59 yr and the tumors measured 2.5, 7.5, and 16.0 cm. One neoplasm was confined to the endometrium, whereas the other 2 were myometrial. All 3 tumors showed a nodular growth comprised of mononuclear and osteoclast-like giant cells. The endometrial-confined tumor consisted of histologically benign mononuclear cells, whereas the others exhibited marked atypia. Mitotic activity was up to 5/10 HPF in the benign tumor and up to 22/10 HPF in the malignant. No cytologic atypia or mitoses were observed in the giant cells. CD68 and CD10 were strongly and diffusely expressed in both components of 3 and 2 neoplasms, respectively. Cyclin D1 was focal in the mononuclear cells and focal to diffuse in the giant cells. CD163 was diffuse in the mononuclear cells, but absent to focal in the giant cells. Ultrastructural analysis lacked diagnostic features of epithelial or specific mesenchymal differentiation. Both malignant tumors demonstrated an aggressive behavior. In summary, although rare, giant cell tumor of the uterus should be included in the differential diagnosis of benign or malignant tumors containing osteoclast-like giant cells. PMID:25851705

  18. A mouse model of luciferase-transfected stromal cells of giant cell tumor of bone.

    PubMed

    Lau, Carol P Y; Wong, Kwok Chuen; Huang, Lin; Li, Gang; Tsui, Stephen K W; Kumta, Shekhar Madhukar

    2015-11-01

    A major barrier towards the study of the effects of drugs on Giant Cell Tumor of Bone (GCT) has been the lack of an animal model. In this study, we created an animal model in which GCT stromal cells survived and functioned as proliferating neoplastic cells. A proliferative cell line of GCT stromal cells was used to create a stable and luciferase-transduced cell line, Luc-G33. The cell line was characterized and was found that there were no significant differences on cell proliferation rate and recruitment of monocytes when compared with the wild type GCT stromal cells. We delivered the Luc-G33 cells either subcutaneously on the back or to the tibiae of the nude mice. The presence of viable Luc-G33 cells was assessed using real-time live imaging by the IVIS 200 bioluminescent imaging (BLI) system. The tumor cells initially propagated and remained viable on site for 7 weeks in the subcutaneous tumor model. We also tested in vivo antitumor effects of Zoledronate (ZOL) and Geranylgeranyl transferase-I inhibitor (GGTI-298) alone or their combinations in Luc-G33-transplanted nude mice. ZOL alone at 400 µg/kg and the co-treatment of ZOL at 400 µg/kg and GGTI-298 at 1.16 mg/kg reduced tumor cell viability in the model. Furthermore, the anti-tumor effects by ZOL, GGTI-298 and the co-treatment in subcutaneous tumor model were also confirmed by immunohistochemical (IHC) staining. In conclusion, we established a nude mice model of GCT stromal cells which allows non-invasive, real-time assessments of tumor development and testing the in vivo effects of different adjuvants for treating GCT.

  19. Cell-to-cell transfer of glial proteins to the squid giant axon. The glia-neuron protein trnasfer hypothesis.

    PubMed

    Lasek, R J; Gainer, H; Barker, J L

    1977-08-01

    The hypothesis that glial cells synthesize proteins which are transferred to adjacent neurons was evaluated in the giant fiber of the squid (Loligo pealei). When giant fibers are separated from their neuron cell bodies and incubated in the presence of radioactive amino acids, labeled proteins appear in the glial cells and axoplasm. Labeled axonal proteins were detected by three methods: extrusion of the axoplasm from the giant fiber, autoradiography, and perfusion of the giant fiber. This protein synthesis is completely inhibited by puromycin but is not affected by chloramphenicol. The following evidence indicates that the labeled axonal proteins are not synthesized within the axon itself. (a) The axon does not contain a significant amount of ribosomes or ribosomal RNA. (b) Isolated axoplasm did not incorporate [(3)H]leucine into proteins. (c) Injection of Rnase into the giant axon did not reduce the appearance of newly synthesized proteins in the axoplasm of the giant fiber. These findings, coupled with other evidence, have led us to conclude that the adaxonal glial cells synthesize a class of proteins which are transferred to the giant axon. Analysis of the kinetics of this phenomenon indicates that some proteins are transferred to the axon within minutes of their synthesis in the glial cells. One or more of the steps in the transfer process appear to involve Ca++, since replacement of extracellular Ca++ by either Mg++ or Co++ significantly reduces the appearance of labeled proteins in the axon. A substantial fraction of newly synthesized glial proteins, possibly as much as 40 percent, are transferred to the giant axon. These proteins are heterogeneous and range in size from 12,000 to greater than 200,000 daltons. Comparisons of the amount of amino acid incorporation in glia cells and neuron cell bodies raise the possibility that the adaxonal glial cells may provide an important source of axonal proteins which is supplemental to that provided by axonal transport

  20. Osteoclasts derive from hematopoietic stem cells according to marker, giant lysosomes of beige mice.

    PubMed

    Ash, P; Loutit, J F; Townsend, K M

    1981-01-01

    To ascertain the origin of multinucleated osteoclasts from hematopoietic stem cells, giant lysosomes peculiar to cells of beige mice (bg bg) were used as marker cells of that provenance. Radiation chimeras were established reciprocally between bg bg mice and osteopetrotic mi mi mice with defective osteoclasts. As a result, all the derivative cells of the hematopoietic stem cell would depend on the donor's cell line, whereas osteogenesis would remain the province of the host. It was affirmed in the chimeras mi mi/bg bg that the osteopetrosis was cured within six weeks. Thereafter the definitive osteoclasts of the chimeras contained giant lysosomes attributable to the beige cell line. However, the cure was well advanced before donor osteoclasts were prominent, for which several reasons are offered. In the mouse chimeras, bg bg/mi mi, there was a delay of some six weeks before osteopetrosis became evident, histologically before radiologically, at the major metaphyseal growth centers. During the period one to two months after establishment, osteoclasts appeared to be a mixture of two cell lines according to quantitative assessments for giant lysosomes. Assessments consisted of measurements of the percentage area of osteoclasts occupied by lysosomes over 1 micrometer diameter. The means were 0.018% +/- 0.008% for nonbeige stock and 2.09% +/- 0.58% for beige stock.

  1. The activation pattern of macrophages in giant cell (temporal) arteritis and primary angiitis of the central nervous system.

    PubMed

    Mihm, Bernhard; Bergmann, Markus; Brück, Wolfgang; Probst-Cousin, Stefan

    2014-06-01

    To determine if the pattern of macrophage activation reflects differences in the pathogenesis and clinical presentation of giant cell arteritis and primary angiitis of the central nervous system, specimens of 10 patients with giant cell arteritis and five with primary angiitis of the central nervous system were immunohistochemically studied and the expression of the macrophage activation markers 27E10, MRP14, MRP8 and 25F9 was determined in the vasculitic infiltrates. Thus, a partly different expression pattern of macrophage activation markers in giant cell arteritis and primary angiitis of the central nervous system was observed. The group comparison revealed that giant cell arteritis cases had significantly higher numbers of acute activated MRP14-positive macrophages, whereas primary angiitis of the central nervous system is characterized by a tendency toward more MRP8-positive intermediate/late activated macrophages. Furthermore, in giant cell arteritis comparably fewer CD8-positive lymphocytes were observed. These observations suggest, that despite their histopathological similarities, giant cell arteritis and primary angiitis of the central nervous system appear to represent either distinct entities within the spectrum of granulomatous vasculitides or different stages of similar disease processes. Their discrete clinical presentation is reflected by different activation patterns of macrophages, which may characterize giant cell arteritis as a more acute process and primary angiitis of the central nervous system as a more advanced inflammatory process.

  2. What role for radiobiphosphonates bone scintigraphy in the monitoring of an unusual bone giant cell tumor: a case report and literature review

    PubMed Central

    Oueriagli, Salah Nabih; Ghfir, Imad; Guerrouj, Hassna El; Raïs, Nouzha Ben

    2016-01-01

    We report the case of 24 years old female patient, followed since ten years ago for bone giant cell tumor (GCT) of the right knee, which was complicated by pulmonary metastases. Surgical treatment and pulmonary metastasectomies have not allowed definitive cure of this disease with the appearance of metachronous bone lesions after eight years of evolution. The literature review confirms the originality of this observation: the age of the patient, the initial and metastasis locations and the occurrence of lung metastases with unfavorable prognosis. Through this clinical case, the authors highlight the role of radiobiphosphonates bone scintigraphy in detecting synchronous or metachronous bone lesions, and in monitoring of these locations under medical treatment. PMID:27186440

  3. Spontaneous Resolution of a Central Giant Cell Granuloma in a Child After an Incisional Biopsy: A Five-year Follow-up.

    PubMed

    Franco, Ademir; Segato, André V K; Couto, Soraya A B; Rodrigues Johann, Aline Cristina Batista; Friedlander, Arthur H; Couto Souza, Paulo H

    2016-01-01

    A central giant cell granuloma (CGCG) is typically regarded as a benign lesion with osteoclastic activity. Treatment often involves surgical procedures that may cause deformities; however, minimally invasive approaches have been suggested for treating pediatric patients. We report a case of CGCG of the mandible in a 13-year-old boy who presented with a well-defined radiolucent area in the anterior mandible that was initially detected in a radiographic examination for orthodontic purposes. An incisional biopsy was performed and diagnosed histologically as a CGCG. The patient underwent clinical and radiographic follow-up only after the biopsy, eventually showing signs of bone healing. Five years later, complete resolution of the lesion was observed radiographically. Considering this optimal outcome, similar cases of CGCG should be carefully analyzed for appropriateness of this conservative approach. PMID:27620523

  4. What role for radiobiphosphonates bone scintigraphy in the monitoring of an unusual bone giant cell tumor: a case report and literature review.

    PubMed

    Oueriagli, Salah Nabih; Ghfir, Imad; Guerrouj, Hassna El; Raïs, Nouzha Ben

    2016-01-01

    We report the case of 24 years old female patient, followed since ten years ago for bone giant cell tumor (GCT) of the right knee, which was complicated by pulmonary metastases. Surgical treatment and pulmonary metastasectomies have not allowed definitive cure of this disease with the appearance of metachronous bone lesions after eight years of evolution. The literature review confirms the originality of this observation: the age of the patient, the initial and metastasis locations and the occurrence of lung metastases with unfavorable prognosis. Through this clinical case, the authors highlight the role of radiobiphosphonates bone scintigraphy in detecting synchronous or metachronous bone lesions, and in monitoring of these locations under medical treatment. PMID:27186440

  5. Giant Panda (Ailuropoda melanoleuca) Buccal Mucosa Tissue as a Source of Multipotent Progenitor Cells.

    PubMed

    Prescott, Hilary M A; Manning, Craig; Gardner, Aaron; Ritchie, William A; Pizzi, Romain; Girling, Simon; Valentine, Iain; Wang, Chengdong; Jahoda, Colin A B

    2015-01-01

    Since the first mammal was cloned, the idea of using this technique to help endangered species has aroused considerable interest. However, several issues limit this possibility, including the relatively low success rate at every stage of the cloning process, and the dearth of usable tissues from these rare animals. iPS cells have been produced from cells from a number of rare mammalian species and this is the method of choice for strategies to improve cloning efficiency and create new gametes by directed differentiation. Nevertheless information about other stem cell/progenitor capabilities of cells from endangered species could prove important for future conservation approaches and adds to the knowledge base about cellular material that can be extremely limited. Multipotent progenitor cells, termed skin-derived precursor (SKP) cells, can be isolated directly from mammalian skin dermis, and human cheek tissue has also been shown to be a good source of SKP-like cells. Recently we showed that structures identical to SKPs termed m-SKPs could be obtained from monolayer/ two dimensional (2D) skin fibroblast cultures. Here we aimed to isolate m-SKPs from cultured cells of three endangered species; giant panda (Ailuropoda melanoleuca); red panda (Ailurus fulgens); and Asiatic lion (Panthera leo persica). m-SKP-like spheres were formed from the giant panda buccal mucosa fibroblasts; whereas dermal fibroblast (DF) cells cultured from abdominal skin of the other two species were unable to generate spheres. Under specific differentiation culture conditions giant panda spheres expressed neural, Schwann, adipogenic and osteogenic cell markers. Furthermore, these buccal mucosa derived spheres were shown to maintain expression of SKP markers: nestin, versican, fibronectin, and P75 and switch on expression of the stem cell marker ABCG2. These results demonstrate that giant panda cheek skin can be a useful source of m-SKP multipotent progenitors. At present lack of sample numbers

  6. Giant Panda (Ailuropoda melanoleuca) Buccal Mucosa Tissue as a Source of Multipotent Progenitor Cells.

    PubMed

    Prescott, Hilary M A; Manning, Craig; Gardner, Aaron; Ritchie, William A; Pizzi, Romain; Girling, Simon; Valentine, Iain; Wang, Chengdong; Jahoda, Colin A B

    2015-01-01

    Since the first mammal was cloned, the idea of using this technique to help endangered species has aroused considerable interest. However, several issues limit this possibility, including the relatively low success rate at every stage of the cloning process, and the dearth of usable tissues from these rare animals. iPS cells have been produced from cells from a number of rare mammalian species and this is the method of choice for strategies to improve cloning efficiency and create new gametes by directed differentiation. Nevertheless information about other stem cell/progenitor capabilities of cells from endangered species could prove important for future conservation approaches and adds to the knowledge base about cellular material that can be extremely limited. Multipotent progenitor cells, termed skin-derived precursor (SKP) cells, can be isolated directly from mammalian skin dermis, and human cheek tissue has also been shown to be a good source of SKP-like cells. Recently we showed that structures identical to SKPs termed m-SKPs could be obtained from monolayer/ two dimensional (2D) skin fibroblast cultures. Here we aimed to isolate m-SKPs from cultured cells of three endangered species; giant panda (Ailuropoda melanoleuca); red panda (Ailurus fulgens); and Asiatic lion (Panthera leo persica). m-SKP-like spheres were formed from the giant panda buccal mucosa fibroblasts; whereas dermal fibroblast (DF) cells cultured from abdominal skin of the other two species were unable to generate spheres. Under specific differentiation culture conditions giant panda spheres expressed neural, Schwann, adipogenic and osteogenic cell markers. Furthermore, these buccal mucosa derived spheres were shown to maintain expression of SKP markers: nestin, versican, fibronectin, and P75 and switch on expression of the stem cell marker ABCG2. These results demonstrate that giant panda cheek skin can be a useful source of m-SKP multipotent progenitors. At present lack of sample numbers

  7. Giant Panda (Ailuropoda melanoleuca) Buccal Mucosa Tissue as a Source of Multipotent Progenitor Cells

    PubMed Central

    Prescott, Hilary M. A.; Manning, Craig; Gardner, Aaron; Ritchie, William A.; Pizzi, Romain; Girling, Simon; Valentine, Iain; Wang, Chengdong; Jahoda, Colin A. B.

    2015-01-01

    Since the first mammal was cloned, the idea of using this technique to help endangered species has aroused considerable interest. However, several issues limit this possibility, including the relatively low success rate at every stage of the cloning process, and the dearth of usable tissues from these rare animals. iPS cells have been produced from cells from a number of rare mammalian species and this is the method of choice for strategies to improve cloning efficiency and create new gametes by directed differentiation. Nevertheless information about other stem cell/progenitor capabilities of cells from endangered species could prove important for future conservation approaches and adds to the knowledge base about cellular material that can be extremely limited. Multipotent progenitor cells, termed skin-derived precursor (SKP) cells, can be isolated directly from mammalian skin dermis, and human cheek tissue has also been shown to be a good source of SKP-like cells. Recently we showed that structures identical to SKPs termed m-SKPs could be obtained from monolayer/ two dimensional (2D) skin fibroblast cultures. Here we aimed to isolate m-SKPs from cultured cells of three endangered species; giant panda (Ailuropoda melanoleuca); red panda (Ailurus fulgens); and Asiatic lion (Panthera leo persica). m-SKP-like spheres were formed from the giant panda buccal mucosa fibroblasts; whereas dermal fibroblast (DF) cells cultured from abdominal skin of the other two species were unable to generate spheres. Under specific differentiation culture conditions giant panda spheres expressed neural, Schwann, adipogenic and osteogenic cell markers. Furthermore, these buccal mucosa derived spheres were shown to maintain expression of SKP markers: nestin, versican, fibronectin, and P75 and switch on expression of the stem cell marker ABCG2. These results demonstrate that giant panda cheek skin can be a useful source of m-SKP multipotent progenitors. At present lack of sample numbers

  8. Sox15 enhances trophoblast giant cell differentiation induced by Hand1 in mouse placenta.

    PubMed

    Yamada, Kayo; Kanda, Hiromi; Tanaka, Satoshi; Takamatsu, Nobuhiko; Shiba, Tadayoshi; Ito, Michihiko

    2006-06-01

    Some members of the Sry-type HMG box (Sox) protein family play important roles in embryogenesis as transcription factors. Here, we report that Sox15 transcripts were much more abundant in mouse placenta than in the fetus, the yolk sac, or several adult tissues. In situ hybridization analysis of the mouse E8.0 conceptus indicated that Sox15 mRNA was predominantly expressed in the trophoblast giant cells of the placenta. We also observed that the amount of Sox15 mRNA dramatically increased during the differentiation of mouse trophoblast stem cells. Ectopic expression of Sox15 in Rat choriocarcinoma cells enhanced the giant cell differentiation induced by a bHLH transcription factor, Hand1. Binding experiments in cotransfected 293 T cells and in vitro revealed that Sox15 interacted with Hand1. We next examined the effects of this interaction on the transcriptional activity of Hand1 and Sox15 using the luciferase reporter assay. Overexpression of Hand1 repressed the Sox15-driven reporter expression, but Sox15 enhanced the Hand1-driven transcription. This enhancement required both the Hand1-binding region and the transactivation domain of Sox15. These results may suggest that the increased transcriptional activity of Hand1 caused by Sox15 might promote the transcription of the target gene resulting in the trophoblast giant cell differentiation in the mouse placenta.

  9. Jejunal intussusception caused by metastasis of a giant cell carcinoma of the lung

    PubMed Central

    Fujii, Yuki; Homma, Shigenori; Yoshida, Tadashi; Taketomi, Akinobu

    2016-01-01

    A 55-year-old woman was admitted to our hospital reporting of nausea, vomiting and anorexia. One month before admission, she had been diagnosed with lung cancer with intestinal metastasis. A CT scan confirmed intussusception due to intestinal metastasis and she underwent emergency laparoscopic surgery followed by resection of the primary lung cancer. Histopathological findings of the intestinal specimen suggested the metastasis was from a giant cell carcinoma of the lung, which had extensive necrosis. She was still alive without recurrence 11 months after the first surgery. Giant cell carcinoma of the lung is a rare type of non-small cell carcinoma and intestinal metastasis is one of the unique features. This type of tumour has such aggressive characteristics that oncological prognosis is reported to be extremely poor. In our case, however, complete surgical resection of both primary and metastatic tumours might result in a better outcome than has been reported. PMID:27485876

  10. Jejunal intussusception caused by metastasis of a giant cell carcinoma of the lung.

    PubMed

    Fujii, Yuki; Homma, Shigenori; Yoshida, Tadashi; Taketomi, Akinobu

    2016-01-01

    A 55-year-old woman was admitted to our hospital reporting of nausea, vomiting and anorexia. One month before admission, she had been diagnosed with lung cancer with intestinal metastasis. A CT scan confirmed intussusception due to intestinal metastasis and she underwent emergency laparoscopic surgery followed by resection of the primary lung cancer. Histopathological findings of the intestinal specimen suggested the metastasis was from a giant cell carcinoma of the lung, which had extensive necrosis. She was still alive without recurrence 11 months after the first surgery. Giant cell carcinoma of the lung is a rare type of non-small cell carcinoma and intestinal metastasis is one of the unique features. This type of tumour has such aggressive characteristics that oncological prognosis is reported to be extremely poor. In our case, however, complete surgical resection of both primary and metastatic tumours might result in a better outcome than has been reported. PMID:27485876

  11. Omental leiomyosarcoma with unusual giant cells in a Beagle dog - Short communication.

    PubMed

    Sasaki, Jun; Toyoshima, Megumi; Okamura, Yasuhiko; Goryo, Masanobu

    2016-06-01

    A 10-year-old castrated male Beagle dog was presented with a 2-month history of intermittent vomiting and abdominal pain. The dog was referred to the Veterinary Teaching Hospital at Iwate University for further evaluation, and a splenic tumour was suspected on the basis of ultrasonography and computed tomography. Surgery identified a large, solid, light-pink mass on the greater omentum with blood-coloured ascites in the abdominal cavity, and resection was performed. Microscopically, the mass comprised spindle-shaped tumour cells and scattered osteoclast-like giant cells. Most spindle-shaped cells were positive for vimentin, desmin, and smooth muscle actin (α-SMA), whereas osteoclast-like giant cells were positive only for vimentin. On the basis of histopathological and immunohistochemical findings, a diagnosis of leiomyosarcoma was made. To the best of our knowledge, this represents the first report of leiomyosarcoma associated with osteoclast-like giant cells developing from the greater omentum in a dog. PMID:27342093

  12. Patterns of hippocampal cell loss based on subregional lesions of the hippocampus.

    PubMed

    Jerman, Taylor S; Kesner, Raymond P; Lee, Inah; Berman, Robert F

    2005-12-14

    It is widely accepted that the hippocampus plays an essential role in memory. Furthermore, studies have suggested that subregions within the hippocampus contribute differentially to specific behavioral components of memory. These studies typically rely on lesions produced by localized injections of neurotoxins (e.g., ibotenic acid or colchicine) into targeted subregions of the hippocampus. In the present study, the specificity of ibotenic acid lesions into areas CA1 and CA3 and colchicine lesions into the dorsal dentate gyrus (DG) was tested. Specifically, the effects of lesions within the dorsal hippocampus, the ventral hippocampus, and areas outside the hippocampus (e.g., lateral septum and entorhinal cortex) were evaluated using Fluoro-Jade, a histofluorescent stain for degenerating neurons. The results show that cell loss is relatively uniform after ibotenic acid injections into areas CA1 and CA3 and variable after colchicine injections into DG. CA1 and CA3 lesions appeared mostly localized to those relative subregions, and DG lesions appeared highly localized to the DG. Using these lesion procedures, little cell loss was apparent in the ventral hippocampus, and no cell loss was apparent in the entorhinal cortex. It is suggested that the lesion procedures described in this study produce relatively selective lesions of neurons within specific subregions of the hippocampus and should be useful for studies examining possible differential contributions of hippocampal subregions to memory processes. PMID:16307731

  13. [Basal cell carcinoma, squamous cell carcinoma and premalignant skin lesions--how to treat?].

    PubMed

    Pitkänen, Sari; Jeskanen, Leila; Ylitalo, Leea

    2014-01-01

    Increasing exposure to UV radiation is considered the most important etiologic factor of nonmelanoma skin cancers. Consequently, exposed areas such as the scalp and face, are the primary areas for developing non-melanoma skin cancers. Once a patient has presented with one tumor, additional lesions are common. The diagnosis is based on typical clinical picture and biopsy or excision for histopathological analysis. Various non-surgical treatment options have been established. Superficial basal cell carcinoma, superficial carcinoma in situ and all actinic keratoses are preferentially treated non-surgically. Most other basal cell and squamous cell carcinomas should be surgically removed. PMID:24724463

  14. Transcription bypass of DNA lesions enhances cell survival but attenuates transcription coupled DNA repair

    PubMed Central

    Li, Wentao; Selvam, Kathiresan; Ko, Tengyu; Li, Shisheng

    2014-01-01

    Transcription-coupled DNA repair (TCR) is a subpathway of nucleotide excision repair (NER) dedicated to rapid removal of DNA lesions in the transcribed strand of actively transcribed genes. The precise nature of the TCR signal and how the repair machinery gains access to lesions imbedded in stalled RNA polymerase II (RNAP II) complexes in eukaryotic cells are still enigmatic. RNAP II has an intrinsic capacity for transcription bypass of DNA lesions by incorporation or misincorporation of nucleotides across the lesions. It has been suggested that transcription bypass of lesions, which exposes the lesions, may be required for TCR. Here, we show that E1103G mutation of Rpb1, the largest subunit of RNAP II, which promotes transcription bypass of UV-induced cyclobutane pyrimidine dimers (CPDs), increases survival of UV irradiated yeast cells but attenuates TCR. The increased cell survival is independent of any NER subpathways. In contrast, G730D mutation of Rpb1, which impairs transcription bypass of CPDs, enhances TCR. Our results suggest that transcription bypass of lesions attenuates TCR but enhances cell tolerance to DNA lesions. Efficient stalling of RNAP II is essential for efficient TCR. PMID:25389266

  15. Langerhans cell histiocytosis: recurrent lesions affecting mandible in a 10-year-old patient.

    PubMed

    Loducca, S V; Mantesso, A; Araújo, N S; Magalhães, M H

    2001-01-01

    Hand-Schuller-Christian disease is a multifocal variant of eosinophilic granuloma, characterised by the classical triad of bony lesions, exophthalmos and diabetes insipidus. This case relates recurrent Langerhans' cell histiocytosis lesions presented as destruction of periodontal support associated with diabetes in a 10-year-old patient. Medical history suggests that the case represents a case of Hand-Schuller Christian disease.

  16. A solitary fibrous tumor with giant cells in the lacrimal gland: a case study.

    PubMed

    Son, Da Hye; Yoo, Su Hyun; Sa, Ho-Seok; Cho, Kyung-Ja

    2013-04-01

    Orbital solitary fibrous tumor (SFT) has recently been proposed as the encompassing terminology for hemangiopericytoma, giant cell angiofibroma (GCAF), and fibrous histiocytoma of the orbit. The lacrimal gland is a very rare location for both SFT and GCAF. A 39-year-old man presented with a painless left upper eyelid mass. An orbital computed tomography scan identified a 1.1 cm-sized well-defined nodule located in the left lacrimal gland. He underwent a mass excision. Histopathologic examination showed a proliferation of relatively uniform spindle cells with a patternless or focally storiform pattern. Dilated vessels were prominent, but angiectoid spaces lined with giant cells were absent. Floret-type giant cells were mostly scattered in the periphery. The tumor was immunoreactive for CD34 and CD99, but negative for smooth muscle actin and S-100 protein. This is the first Korean case of SFT of the lacrimal gland with overlapping features of GCAF, suggesting a close relationship between the two entities.

  17. Cardiac Sarcoidosis or Giant Cell Myocarditis? On Treatment Improvement of Fulminant Myocarditis as Demonstrated by Cardiovascular Magnetic Resonance Imaging

    PubMed Central

    Bogabathina, Hari; Olson, Peter; Rathi, Vikas K.; Biederman, Robert W. W.

    2012-01-01

    Giant cell myocarditis, but not cardiac sarcoidosis, is known to cause fulminant myocarditis resulting in severe heart failure. However, giant cell myocarditis and cardiac sarcoidosis are pathologically similar, and attempts at pathological differentiation between the two remain difficult. We are presenting a case of fulminant myocarditis that has pathological features suggestive of cardiac sarcoidosis, but clinically mimicking giant cell myocarditis. This patient was treated with cyclosporine and prednisone and recovered well. This case we believe challenges our current understanding of these intertwined conditions. By obtaining a sense of severity of cardiac involvement via delayed hyperenhancement of cardiac magnetic resonance imaging, we were more inclined to treat this patient as giant cell myocarditis with cyclosporine. This resulted in excellent improvement of patient's cardiac function as shown by delayed hyperenhancement images, early perfusion images, and SSFP videos. PMID:24826266

  18. Malignant fibrous histiocytoma (giant cell type) associated with a malignant mixed tumor in the salivary gland of a dog.

    PubMed

    Pérez-Martínez, C; García Fernández, R A; Reyes Avila, L E; Pérez-Pérez, V; González, N; García-Iglesias, M J

    2000-07-01

    A 12-year-old male Boxer dog presented with a 5 x 5 x 7-cm partially encapsulated mass in the right mandibular salivary gland. Histologically, the mass was composed of neoplastic epithelial and mesenchymal cells. The mesenchymal component consisted of two cell populations arranged in different patterns: coalescing nodules of neoplastic mononuclear cells with rare osteoid and numerous osteoclastlike giant cells; and sheets of neoplastic spindle cells intermingled with neoplastic epithelial cells and containing osteoid and well-formed bone trabeculae lined by osteoblasts and few osteoclastlike giant cells. On the basis of these histological features, two malignant salivary tumors were diagnosed: a malignant fibrous histiocytoma (giant cell type) and a malignant mixed tumor. Immunohistochemical studies demonstrated keratin 5 and 8 expression by the neoplastic epithelial cells, indicating a probable salivary ductal origin, and vimentin expression by all mesenchymal elements, suggesting a fibroblastic line of differentiation.

  19. CEMENTLESS ENDOPROSTHESIS IN THE TREATMENT OF GIANT CELL TUMOR OF THE TIBIA: EIGHTEEN YEARS OF EVOLUTION

    PubMed Central

    Mello, Glauco Pauka; Sonehara, Helio Ayabe; Neto, Mario Armani

    2015-01-01

    This is a case report on a giant cell tumor of the juxta-articular proximal tibia with a pathological fracture. A female patient presented pain and increased local volume after falling from her own height. She underwent clinical examination, radiographic examination and puncture biopsy. A diagnosis of giant cell tumor was made. The patient was then treated with tumor resection and use of an unconventional partial endoprosthesis of the tibia with preservation of the joint surface of the tibial plateau. The patient evolved with improvement of symptoms and maintenance of joint function of the operated limb, absence of recurrence and complications, without any need for reoperation over 18 years of follow-up. PMID:27026973

  20. Orbital solitary fibrous tumor with multinucleate giant cells: case report of an unusual finding in an uncommon tumor.

    PubMed

    Mulay, Kaustubh; Honavar, Santosh G

    2013-01-01

    Solitary fibrous tumor (SFT) is a rare soft-tissue neoplasm which may occur at any site although it is more frequent in the pleura, mediastinum and lung. Orbital involvement by SFT is uncommon. Giant cells are extremely rare to be seen in a SFT and have been described to be immunoreactive for CD34. We present a case of orbital SFT with multinucleate giant cells expressing CD68 and lacking immunoreactivity for CD34. The differential diagnosis is discussed.

  1. Fine Needle Aspiration Cytology of Chondroid Tenosynovial Giant Cell Tumor of the Hand

    PubMed Central

    Abdou, Asmaa Gaber; Aiad, Hayam; Youssef Asaad, Nancy

    2015-01-01

    Giant cell tumor (GCT) of tendon sheath is a localized form of tenosynovial GCT, which preferentially affects the joints of hands and feet. Chondroid metaplasia is a rare phenomenon in tenosynovial GCT either in localized or diffuse types. The current case investigates the cytological and histopathological features of chondroid GCT of tendon sheath in a 22-year-old female presenting with wrist swelling. PMID:26266013

  2. Giant oral tumor in a child with malnutrition and sickle cell trait: Anesthetic challenges

    PubMed Central

    Singh, Preet Mohinder; Borle, Anuradha; Trikha, Anjan

    2013-01-01

    Pediatric oral tumors have always been challenging for the even most skilled anesthesiologists. The conventional method of awake intubation is not realistic in this age group. The management is to chart out a plan to intubate the child post induction. We describe successful management of a case of giant of ossifying fibroma in a child with sickle cell trait where non-conventional innovate approach helped us to secure the airway pre-operatively and avoid possible medical complications. PMID:24106366

  3. Two Cases of Sarcoma Arising in Giant Cell Tumor of Bone Treated with Denosumab

    PubMed Central

    Broehm, Cory Julian; Garbrecht, Erika L.; Wood, Jeff; Bocklage, Therese

    2015-01-01

    Giant cell tumor (GCT) of bone is a generally benign, but often locally aggressive, neoplasm of bone, with a propensity for recurrence. Sarcomatous transformation is rare and typically occurs with a history of recurrences and radiation treatment. Denosumab, an inhibitor of the RANK ligand involved in bone resorption in GCT, is increasingly used in treatment of recurrent or unresectable giant cell tumor of bone. We report two cases of sarcomatous transformation of GCT to osteosarcoma in patients receiving denosumab. One was a 59-year-old male with a 12-year history of GCT and multiple recurrences taking denosumab for 2.5 years. The second case was in a 56-year-old male with a seven-year history of GCT taking denosumab for six months. Review of the literature shows one case report of malignant transformation of GCT in a patient being treated with denosumab. As the use of denosumab for treatment of GCT will likely increase, larger, controlled studies are needed to ascertain whether denosumab may play a role in malignant transformation of giant cell tumor of bone. PMID:26798348

  4. Giant Mediastinal Germ Cell Tumour: An Enigma of Surgical Consideration

    PubMed Central

    Ali, Nurayub Mohd; Azizan, Nornazirah; Zakaria, Andee Dzulkarnaen; Rahman, Mohd Ramzisham Abdul

    2016-01-01

    We present a case of 16-year-old male, who was referred from private centre for dyspnoea, fatigue, and orthopnea. The chest radiograph revealed complete opacification of left chest which was confirmed by computed tomography as a large left mediastinal mass measuring 14 × 15 × 18 cm. The diagnostic needle core biopsy revealed mixed germ cell tumour with possible combination of embryonal carcinoma, yolk sac, and teratoma. After 4 cycles of neoadjuvant BEP regime, there was initial response of tumour markers but not tumour bulk. Instead of classic median sternotomy or clamshell incision, posterolateral approach with piecemeal manner was chosen. Histology confirmed mixed germ cell tumour with residual teratomatous component without yolk sac or embryonal carcinoma component. Weighing 3.5 kg, it is one of the largest mediastinal germ cell tumours ever reported. We describe this rare and gigantic intrathoracic tumour and discuss the spectrum of surgical approach and treatment of this exceptional tumour. PMID:27807495

  5. Differentiation of Trophoblast Giant Cells and Their Metabolic Functions Are Dependent on Peroxisome Proliferator-Activated Receptor β/δ

    PubMed Central

    Nadra, Karim; Anghel, Silvia I.; Joye, Elisabeth; Tan, Nguan Soon; Basu-Modak, Sharmila; Trono, Didier; Wahli, Walter; Desvergne, Béatrice

    2006-01-01

    Mutation of the nuclear receptor peroxisome proliferator-activated receptor β/δ (PPARβ/δ) severely affects placenta development, leading to embryonic death at embryonic day 9.5 (E9.5) to E10.5 of most, but not all, PPARβ/δ-null mutant embryos. While very little is known at present about the pathway governed by PPARβ/δ in the developing placenta, this paper demonstrates that the main alteration of the placenta of PPARβ/δ-null embryos is found in the giant cell layer. PPARβ/δ activity is in fact essential for the differentiation of the Rcho-1 cells in giant cells, as shown by the severe inhibition of differentiation once PPARβ/δ is silenced. Conversely, exposure of Rcho-1 cells to a PPARβ/δ agonist triggers a massive differentiation via increased expression of 3-phosphoinositide-dependent kinase 1 and integrin-linked kinase and subsequent phosphorylation of Akt. The links between PPARβ/δ activity in giant cells and its role on Akt activity are further strengthened by the remarkable pattern of phospho-Akt expression in vivo at E9.5, specifically in the nucleus of the giant cells. In addition to this phosphatidylinositol 3-kinase/Akt main pathway, PPARβ/δ also induced giant cell differentiation via increased expression of I-mfa, an inhibitor of Mash-2 activity. Finally, giant cell differentiation at E9.5 is accompanied by a PPARβ/δ-dependent accumulation of lipid droplets and an increased expression of the adipose differentiation-related protein (also called adipophilin), which may participate to lipid metabolism and/or steroidogenesis. Altogether, this important role of PPARβ/δ in placenta development and giant cell differentiation should be considered when contemplating the potency of PPARβ/δ agonist as therapeutic agents of broad application. PMID:16581799

  6. Establishment of three cell lines from Chinese giant salamander and their sensitivities to the wild-type and recombinant ranavirus.

    PubMed

    Yuan, Jiang-Di; Chen, Zhong-Yuan; Huang, Xing; Gao, Xiao-Chan; Zhang, Qi-Ya

    2015-06-12

    Known as lethal pathogens, Ranaviruses have been identified in diseased fish, amphibians (including Chinese giant salamander Andrias davidianus, the world's largest amphibian) and reptiles, causing organ necrosis and systemic hemorrhage. Here, three Chinese giant salamander cell lines, thymus cell line (GSTC), spleen cell line (GSSC) and kidney cell line (GSKC) were initially established. Their sensitivities to ranaviruses, wild-type Andrias davidianus ranavirus (ADRV) and recombinant Rana grylio virus carrying EGFP gene (rRGV-EGFP) were tested. Temporal transcription pattern of ranavirus major capsid protein (MCP), fluorescence and electron microscopy observations showed that both the wild-type and recombinant ranavirus could replicate in the cell lines.

  7. Apoptosis triggered by pyropheophorbide-α methyl ester-mediated photodynamic therapy in a giant cell tumor in bone

    NASA Astrophysics Data System (ADS)

    Li, K.-T.; Zhang, J.; Duan, Q.-Q.; Bi, Y.; Bai, D.-Q.; Ou, Y.-S.

    2014-06-01

    A giant cell tumor in bone is the common primary bone tumor with aggressive features, occurring mainly in young adults. Photodynamic therapy is a new therapeutic technique for tumors. In this study, we investigated the effects of Pyropheophorbide-α methyl ester (MPPa)-mediated photodynamic therapy on the proliferation of giant cell tumor cells and its mechanism of action. Cell proliferation was evaluated using an MTT assay. Cellular apoptosis was detected by Hoechst nuclear staining, and flow cytometric assay. Mitochondrial membrane potential changes and cytochrome c, caspase-9, caspase-3, and Bcl-2 expression was assessed. Finally, we found that MPPa-mediated photodynamic therapy could effectively suppress the proliferation of human giant cell tumor cells and induce apoptosis. The mitochondrial pathway was involved in the MPPa-photodynamic therapy-induced apoptosis.

  8. Foreign body giant cells selectively covering haptics of intraocular lens implants: indicators of poor toleration?

    PubMed

    Wolter, J R

    1983-10-01

    A Sputnik lens implant removed after five years because of bullous keratopathy exhibits a dense covering of its Supramid anterior staves with large foreign body giant cells, while its Prolene loops and Polymethylmethacrylate optics have attracted only few of these cell units. The glass-membrane-like component of the reactive membrane also shows significant differences on the different parts of this implant. The use of observation of the components of reactive membranes on lens implants as indicators of toleration in the eye is suggested. PMID:6364004

  9. Phosphoinositides: Tiny Lipids With Giant Impact on Cell Regulation

    PubMed Central

    2013-01-01

    Phosphoinositides (PIs) make up only a small fraction of cellular phospholipids, yet they control almost all aspects of a cell's life and death. These lipids gained tremendous research interest as plasma membrane signaling molecules when discovered in the 1970s and 1980s. Research in the last 15 years has added a wide range of biological processes regulated by PIs, turning these lipids into one of the most universal signaling entities in eukaryotic cells. PIs control organelle biology by regulating vesicular trafficking, but they also modulate lipid distribution and metabolism via their close relationship with lipid transfer proteins. PIs regulate ion channels, pumps, and transporters and control both endocytic and exocytic processes. The nuclear phosphoinositides have grown from being an epiphenomenon to a research area of its own. As expected from such pleiotropic regulators, derangements of phosphoinositide metabolism are responsible for a number of human diseases ranging from rare genetic disorders to the most common ones such as cancer, obesity, and diabetes. Moreover, it is increasingly evident that a number of infectious agents hijack the PI regulatory systems of host cells for their intracellular movements, replication, and assembly. As a result, PI converting enzymes began to be noticed by pharmaceutical companies as potential therapeutic targets. This review is an attempt to give an overview of this enormous research field focusing on major developments in diverse areas of basic science linked to cellular physiology and disease. PMID:23899561

  10. Giant Cell Tumor of the Temporal Bone with Direct Invasion into the Middle Ear and Skull Base: A Case Report

    PubMed Central

    Iizuka, Takashi; Furukawa, Masayuki; Ishii, Hisato; Kasai, Misato; Hayashi, Chieri; Arai, Hajime; Ikeda, Katsuhisa

    2012-01-01

    Giant cell tumor (GCT) is classified as a benign bone tumor, and it is frequently identified at the epiphysis of long bones and relatively rare in the temporal bone. For orthopedists expert at recognizing bone and soft tissue tumors, the diagnosis of GCT is relatively easy; however, since head and neck surgeons experience few cases of GCT, it may be difficult to diagnose when it occurs in the temporal bone. A 32-year-old man complained of left hearing loss, aural fullness, and tinnitus. Examination of the ear revealed a bulging tumor. Audiologic examination demonstrated conductive hearing loss of the left ear. Computer tomograph of the temporal bone showed a soft-tissue-density specification indicating bone destruction at the left temporal bone. The tumor invaded the skull base. Imaging examinations using magnetic resonance imaging revealed a nonhomogenous isosignal intensity area on T1 at the left temporal bone. After intravenous gadolinium, the mass showed unequal enhancement. This patient subsequently underwent surgery to remove the lesion using transmastoid and middle fossa approach. Pathological examinations from specimens of the tumor revealed characteristic of GCT. No clinical or radiological evidence of tumor recurrence was detected for 4 years. PMID:22953120

  11. Fast Inactivation of Delayed Rectifier K Conductance in Squid Giant Axon and Its Cell Bodies

    PubMed Central

    Mathes, Chris; Rosenthal, Joshua J.C.; Armstrong, Clay M.; Gilly, William F.

    1997-01-01

    Inactivation of delayed rectifier K conductance (gK) was studied in squid giant axons and in the somata of giant fiber lobe (GFL) neurons. Axon measurements were made with an axial wire voltage clamp by pulsing to VK (∼−10 mV in 50–70 mM external K) for a variable time and then assaying available gK with a strong, brief test pulse. GFL cells were studied with whole-cell patch clamp using the same prepulse procedure as well as with long depolarizations. Under our experimental conditions (12–18°C, 4 mM internal MgATP) a large fraction of gK inactivates within 250 ms at −10 mV in both cell bodies and axons, although inactivation tends to be more complete in cell bodies. Inactivation in both preparations shows two kinetic components. The faster component is more temperature-sensitive and becomes very prominent above 12°C. Contribution of the fast component to inactivation shows a similar voltage dependence to that of gK, suggesting a strong coupling of this inactivation path to the open state. Omission of internal MgATP or application of internal protease reduces the amount of fast inactivation. High external K decreases the amount of rapidly inactivating IK but does not greatly alter inactivation kinetics. Neither external nor internal tetraethylammonium has a marked effect on inactivation kinetics. Squid delayed rectifier K channels in GFL cell bodies and giant axons thus share complex fast inactivation properties that do not closely resemble those associated with either C-type or N-type inactivation of cloned Kv1 channels studied in heterologous expression systems. PMID:9101403

  12. Fast inactivation of delayed rectifier K conductance in squid giant axon and its cell bodies.

    PubMed

    Mathes, C; Rosenthal, J J; Armstrong, G M; Gilly, W F

    1997-04-01

    Inactivation of delayed rectifier K conductance (gk) was studied in squid giant axons and in the somata of giant fiber lobe (GFL) neurons. Axon measurements were made with an axial wire voltage clamp by pulsing to VK (approximately -10 mV in 50-70 mM external K) for a variable time and then assaying available gK with a strong, brief test pulse. GFL cells were studied with whole-cell patch clamp using the same prepulse procedure as well as with long depolarizations. Under our experimental conditions (12-18 degrees C, 4 mM internal MgATP) a large fraction of gK inactivates within 250 ms at -10 mV in both cell bodies and axons, although inactivation tends to be more complete in cell bodies. Inactivation in both preparations shows two kinetic components. The faster component is more temperature-sensitive and becomes very prominent above 12 degrees C. Contribution of the fast component to inactivation shows a similar voltage dependence to that of gK, suggesting a strong coupling of this inactivation path to the open state. Omission of internal MgATP or application of internal protease reduces the amount of fast inactivation. High external K decreases the amount of rapidly inactivating IK but does not greatly alter inactivation kinetics. Neither external nor internal tetraethylammonium has a marked effect on inactivation kinetics. Squid delayed rectifier K channels in GFL cell bodies and giant axons thus share complex fast inactivation properties that do not closely resemble those associated with either C-type or N-type inactivation of cloned Kvl channels studied in heterologous expression systems.

  13. A giant cell surface protein in Synechococcus WH8102 inhibits feeding by a dinoflagellate predator.

    PubMed

    Strom, Suzanne L; Brahamsha, Bianca; Fredrickson, Kerri A; Apple, Jude K; Rodríguez, Andres Gutiérrez

    2012-03-01

    Diverse strains of the marine planktonic cyanobacterium Synechococcus sp. show consistent differences in their susceptibility to predation. We used mutants of Sargasso Sea strain WH8102 (clade III) to test the hypothesis that cell surface proteins play a role in defence against predation by protists. Predation rates by the heterotrophic dinoflagellate Oxyrrhis marina on mutants lacking the giant SwmB protein were always higher (by 1.6 to 3.9×) than those on wild-type WH8102 cells, and equalled predation rates on a clade I strain (CC9311). In contrast, absence of the SwmA protein, which comprises the S-layer (surface layer of the cell envelope that is external to the outer membrane), had no effect on predation by O. marina. Reductions in predation rate were not due to dissolved substances in Synechococcus cultures, and could not be accounted for by variations in cell hydrophobicity. We hypothesize that SwmB defends Synechococcus WH8102 by interfering with attachment of dinoflagellate prey capture organelles or cell surface receptors. Giant proteins are predicted in the genomes of multiple Synechococcus isolates, suggesting that this defence strategy may be more general. Strategies for resisting predation will contribute to the differential competitive success of different Synechococcus groups, and to the diversity of natural picophytoplankton assemblages.

  14. A giant cell surface protein in Synechococcus WH8102 inhibits feeding by a dinoflagellate predator.

    PubMed

    Strom, Suzanne L; Brahamsha, Bianca; Fredrickson, Kerri A; Apple, Jude K; Rodríguez, Andres Gutiérrez

    2012-03-01

    Diverse strains of the marine planktonic cyanobacterium Synechococcus sp. show consistent differences in their susceptibility to predation. We used mutants of Sargasso Sea strain WH8102 (clade III) to test the hypothesis that cell surface proteins play a role in defence against predation by protists. Predation rates by the heterotrophic dinoflagellate Oxyrrhis marina on mutants lacking the giant SwmB protein were always higher (by 1.6 to 3.9×) than those on wild-type WH8102 cells, and equalled predation rates on a clade I strain (CC9311). In contrast, absence of the SwmA protein, which comprises the S-layer (surface layer of the cell envelope that is external to the outer membrane), had no effect on predation by O. marina. Reductions in predation rate were not due to dissolved substances in Synechococcus cultures, and could not be accounted for by variations in cell hydrophobicity. We hypothesize that SwmB defends Synechococcus WH8102 by interfering with attachment of dinoflagellate prey capture organelles or cell surface receptors. Giant proteins are predicted in the genomes of multiple Synechococcus isolates, suggesting that this defence strategy may be more general. Strategies for resisting predation will contribute to the differential competitive success of different Synechococcus groups, and to the diversity of natural picophytoplankton assemblages. PMID:22103339

  15. Apoptotic Index and Proliferative Index in Premalignant and Malignant Squamous Cell Lesions of the Oral Cavity

    PubMed Central

    Viswanathan, Vidya; Juluri, Ravichandra; Goel, Seema; Madan, Jyotsna; Mitra, Subir K; Gopalakrishnan, Dharmarajan

    2015-01-01

    Background: Oral squamous cell lesions are most commonly diagnosed lesions in India. Both premalignant and malignant lesions are frequently encountered. In this study, we evaluated the role and significance of apoptotic indices (AI) and proliferative indices (PI) in premalignant and malignant squamous cell lesions of the oral cavity. Materials and Methods: A total of 62 histologically proven cases of premalignant and malignant oral squamous cell lesions were analyzed. The biopsies were stained with hematoxylin and eosin and also with monoclonal antibody Ki-67. AI and PI were assessed using a light microscope. Results: AI was found to increase gradually from normal to dysplasia to carcinoma. The highest AI was seen in well-differentiated squamous cell carcinomas (SCCs). PI also was found to increase significantly from normal to dysplasia to carcinoma. The highest PI was seen in poorly differentiated SCC. Conclusion: AI in conjunction with the PI offers an accurate idea as to the nature and course of the lesion and may help to plan timely surgical intervention that results in better clinical prognosis and outcome. PMID:25709366

  16. DNA lesions in hyperthermic cell killing: effects of thermotolerance, procaine, and erythritol

    SciTech Connect

    Jorritsma, J.B.; Konings, A.W.

    1986-04-01

    When HeLa S3 cells were subjected to 45 degrees C hyperthermia, DNA lesions were detected by the use of the alkaline unwinding/hydroxylapatite method. The number of lesions formed was not affected when the cells were made thermotolerant by either an acute (15 min 44 degrees C + 5 h 37 degrees C) or a chronic (5 h 42 degrees C) pretreatment before 45 degrees C hyperthermia. The presence of 10 mM procaine (heat sensitizer) or 0.5 M erythritol (heat protector) during hyperthermia also had no effect on the rate of formation of heat-induced alkali labile DNA lesions. These observations do not support a concept where DNA lesions are considered to be the ultimate cause of hyperthermic cell killing. Both drugs, however, influenced the rate of repair of radiation-induced strand breaks when present during preirradiation heat treatment. We conclude that the initial number of heat-induced alkali labile DNA lesions is not directly related to cell survival. It cannot be excluded, however, that differences in posthyperthermic repair of these lesions may lead to a positive correlation between residual DNA damage and survival after the different experimental conditions.

  17. Identification of a novel RNA giant nuclear body in cancer cells.

    PubMed

    Zhou, Hong; Zhang, Jiawei; Gu, Ying; Gan, Xiaoxian; Gan, Yichao; Zheng, Weiwei; Kim, Byung-Wook; Xu, Xiaohua; Lu, Xiaoya; Dong, Qi; Zheng, Shu; Huang, Wendong; Xu, Rongzhen

    2016-01-26

    Constitutive synthesis of oncogenic mRNAs is essential for maintaining the uncontrolled growth of cancer cells. However, little is known about how these mRNAs are exported from the nucleus to the cytoplasm. Here, we report the identification of a RNA giant nuclear body (RNA-GNB) that is abundant in cancer cells but rare in normal cells. The RNA-GNB contains a RNA core surrounded by a protein shell. We identify 782 proteins from cancer-associated RNA-GNBs, 40% of which are involved in the nuclear mRNA trafficking. RNA-GNB is required for cell proliferation, and its abundance is positively associated with tumor burden and outcome of therapies. Our findings suggest that the RNA-GNB is a novel nuclear RNA trafficking organelle that may contribute to the nuclear mRNA exporting and proliferation of cancer cells. PMID:26678034

  18. Identification of a novel RNA giant nuclear body in cancer cells.

    PubMed

    Zhou, Hong; Zhang, Jiawei; Gu, Ying; Gan, Xiaoxian; Gan, Yichao; Zheng, Weiwei; Kim, Byung-Wook; Xu, Xiaohua; Lu, Xiaoya; Dong, Qi; Zheng, Shu; Huang, Wendong; Xu, Rongzhen

    2016-01-26

    Constitutive synthesis of oncogenic mRNAs is essential for maintaining the uncontrolled growth of cancer cells. However, little is known about how these mRNAs are exported from the nucleus to the cytoplasm. Here, we report the identification of a RNA giant nuclear body (RNA-GNB) that is abundant in cancer cells but rare in normal cells. The RNA-GNB contains a RNA core surrounded by a protein shell. We identify 782 proteins from cancer-associated RNA-GNBs, 40% of which are involved in the nuclear mRNA trafficking. RNA-GNB is required for cell proliferation, and its abundance is positively associated with tumor burden and outcome of therapies. Our findings suggest that the RNA-GNB is a novel nuclear RNA trafficking organelle that may contribute to the nuclear mRNA exporting and proliferation of cancer cells.

  19. Characteristics of Multipotent Mesenchymal Stromal Cells Isolated from Human Endometrium and Endometriosis Lesions.

    PubMed

    Savilova, A M; Yushina, M N; Rudimova, Yu V; Khabas, G N; Chuprynin, V D; Sukhikh, G T

    2016-08-01

    Cell cultures isolated from endometriosis lesions by enzymatic dissociation consisted of fibroblast-like cells expressing CD90, CD73, and CD105; cell viability in these cultures was >90%, but this parameter decreased by passage 3. Zero passage cultures contained 10-25% epithelial cells expressing cytokeratin-7, but by passage 2, the cultures became more homogeneous and epithelial cells disappeared. The proportion of proliferating cells and population doubling level increased from passage 1 to passage 3. The cultures from the endometrium were induced to adipogenic and osteogenic differentiation in vitro. The cultures derived from ectopic endometrium have properties of multipotent mesenchymal stromal cells that exhibited in vitro similarities and differences from cell cultures from eutopic endometrium, which allows using this cell model for the search and testing of new drugs and technologies aimed at suppression of the growth and spread of endometriosis lesions. PMID:27590769

  20. Adult Human Nasal Mesenchymal-Like Stem Cells Restore Cochlear Spiral Ganglion Neurons After Experimental Lesion

    PubMed Central

    Bas, Esperanza; Van De Water, Thomas R.; Lumbreras, Vicente; Rajguru, Suhrud; Goss, Garrett; Hare, Joshua M.

    2014-01-01

    A loss of sensory hair cells or spiral ganglion neurons from the inner ear causes deafness, affecting millions of people. Currently, there is no effective therapy to repair the inner ear sensory structures in humans. Cochlear implantation can restore input, but only if auditory neurons remain intact. Efforts to develop stem cell-based treatments for deafness have demonstrated progress, most notably utilizing embryonic-derived cells. In an effort to bypass limitations of embryonic or induced pluripotent stem cells that may impede the translation to clinical applications, we sought to utilize an alternative cell source. Here, we show that adult human mesenchymal-like stem cells (MSCs) obtained from nasal tissue can repair spiral ganglion loss in experimentally lesioned cochlear cultures from neonatal rats. Stem cells engraft into gentamicin-lesioned organotypic cultures and orchestrate the restoration of the spiral ganglion neuronal population, involving both direct neuronal differentiation and secondary effects on endogenous cells. As a physiologic assay, nasal MSC-derived cells engrafted into lesioned spiral ganglia demonstrate responses to infrared laser stimulus that are consistent with those typical of excitable cells. The addition of a pharmacologic activator of the canonical Wnt/β-catenin pathway concurrent with stem cell treatment promoted robust neuronal differentiation. The availability of an effective adult autologous cell source for inner ear tissue repair should contribute to efforts to translate cell-based strategies to the clinic. PMID:24172073

  1. The plant cell inhibitor KRP6 is involved in multinucleation and cytokinesis disruption in giant-feeding cells induced by root-knot nematodes.

    PubMed

    Vieira, Paulo; de Almeida Engler, Janice

    2015-01-01

    The plant cell cycle inhibitor gene KRP6 has been investigated in roots infected by plant-parasitic root-knot nematodes (Meloidogyne spp.). Unexpectedly, KRP6 overexpressing lines revealed a distinct role for this specific KRP as an activator of the mitotic cell cycle. This function was confirmed in Arabidopsis thaliana suspension cultures ectopically expressing KRP6. A blockage in the mitotic exit was observed in cell suspensions and in giant cells resulted in the appearance of multi-nucleated cells. KRP6 expression during nematode infection and the similarity in phenotypes among KRP6 overexpressing cell cultures and giant-cell morphology strongly suggest that KRP6 is involved in multinucleation and acytokinesis occurring in giant-cells. Once again nematodes have been shown to manipulate the plant cell cycle machinery in order to promote gall establishment.

  2. The plant cell inhibitor KRP6 is involved in multinucleation and cytokinesis disruption in giant-feeding cells induced by root-knot nematodes

    PubMed Central

    Vieira, Paulo; Engler, Janice de Almeida

    2015-01-01

    The plant cell cycle inhibitor gene KRP6 has been investigated in roots infected by plant-parasitic root-knot nematodes (Meloidogyne spp.). Unexpectedly, KRP6 overexpressing lines revealed a distinct role for this specific KRP as an activator of the mitotic cell cycle. This function was confirmed in Arabidopsis thaliana suspension cultures ectopically expressing KRP6. A blockage in the mitotic exit was observed in cell suspensions and in giant cells resulted in the appearance of multi-nucleated cells. KRP6 expression during nematode infection and the similarity in phenotypes among KRP6 overexpressing cell cultures and giant-cell morphology strongly suggest that KRP6 is involved in multinucleation and acytokinesis occurring in giant-cells. Once again nematodes have been shown to manipulate the plant cell cycle machinery in order to promote gall establishment. PMID:25915833

  3. Aneurysmal Lesions of Patients with Abdominal Aortic Aneurysm Contain Clonally Expanded T Cells

    PubMed Central

    Lu, Song; White, John V.; Lin, Wan Lu; Zhang, Xiaoying; Solomides, Charalambos; Evans, Kyle; Ntaoula, Nectaria; Nwaneshiudu, Ifeyinwa; Gaughan, John; Monos, Dimitri S.; Oleszak, Emilia L.

    2014-01-01

    Abdominal aortic aneurysm (AAA) is a common disease with often life-threatening consequences. This vascular disorder is responsible for 1–2% of all deaths in men aged 65 years or older. Autoimmunity may be responsible for the pathogenesis of AAA. Although it is well documented that infiltrating T cells are essentially always present in AAA lesions, little is known about their role in the initiation and/or progression of the disease. To determine whether T cells infiltrating AAA lesions contain clonally expanded populations of T cells, we amplified β-chain TCR transcripts by the nonpalindromic adaptor–PCR/Vβ-specific PCR and/or Vβ-specific PCR, followed by cloning and sequencing. We report in this article that aortic abdominal aneurysmal lesions from 8 of 10 patients with AAA contained oligoclonal populations of T cells. Multiple identical copies of β-chain TCR transcripts were identified in these patients. These clonal expansions are statistically significant. These results demonstrate that αβ TCR+ T lymphocytes infiltrating aneurysmal lesions of patients with AAA have undergone proliferation and clonal expansion in vivo at the site of the aneurysmal lesion, in response to unidentified self- or nonself Ags. This evidence supports the hypothesis that AAA is a specific Ag–driven T cell disease. PMID:24752442

  4. Fine-needle aspiration of spindle cell and mesenchymal lesions of the salivary glands.

    PubMed

    Chhieng, D C; Cohen, J M; Cangiarella, J F

    2000-10-01

    Fine-needle aspiration (FNA) biopsy can accurately diagnose epithelial lesions of the salivary gland. Its role in the evaluation of salivary gland lesions containing a significant spindle cell component is less clear. We describe the cytologic features of 25 spindle cell lesions of the salivary gland and discuss the differential diagnosis and potential diagnostic pitfalls. Twenty-five aspiration smears (3.0%) containing a significant spindle cell or mesenchymal component were identified out of 844 salivary gland FNAs performed over a 5-year period. These aspiration smears were from 25 patients. The smears were classified into three categories: 1) reactive or inflammatory conditions, including one granulation tissue and four granulomatous sialoadenitis; 2) benign neoplasms, including one schwannoma, one fibromatosis, four lipomas, and nine pleomorphic adenomas; 3) malignant neoplasms, including one recurrent malignant fibrous histiocytoma (MFH), two metastatic melanomas, and two metastatic osteosarcomas. There was one false-negative biopsy. The metastatic desmoplastic malignant melanoma was initially interpreted as a reactive lymph node with fibrosis. A specific diagnosis was rendered in 21 (84%) cases. The schwannoma was diagnosed cytologically as benign spindle cell lesion, not otherwise specified (NOS), fibromatosis as an atypical cellular proliferation, and MFH as poorly differentiated malignant neoplasm. Salivary gland lesions with a significant spindle cell component are rarely encountered on FNA and constitute a heterogeneous group. A specific diagnosis can be rendered in the majority of cases by correlating clinical and cytologic findings.

  5. Stem cell therapy: A novel treatment approach for oral mucosal lesions.

    PubMed

    Suma, G N; Arora, Madhu Pruthi; Lakhanpal, Manisha

    2015-01-01

    Stem cells have enormous potential to alleviate sufferings of many diseases that currently have no effective therapy. The research in this field is growing at an exponential rate. Stem cells are master cells that have specialized capability for self-renewal, potency and capability to differentiate to many cell types. At present, the adult mesenchymal stem cells are being used in the head and neck region for orofacial regeneration (including enamel, dentin, pulp and alveolar bone) in lieu of their proliferative and regenerative properties, their use in the treatment of oral mucosal lesions is still in budding stages. Moreover, there is scanty literature available regarding role of stem cell therapy in the treatment of commonly seen oral mucosal lesions like oral submucous fibrosis, oral lichen planus, oral ulcers and oral mucositis. The present review will focus on the current knowledge about the role of stem cell therapies in oral mucosal lesions and could facilitate new advancements in this area (articles were obtained from electronic media like PubMed, EBSCO, Cochrane and Medline etc., from year 2000 to 2014 to review the role of stem cell therapy in oral mucosal lesions). PMID:25709329

  6. Late ipsilateral recurrence of ischemic optic neuropathy in giant cell arteritis.

    PubMed

    Kim, Nancy; Trobe, Jonathan D; Flint, Andrew; Keoleian, Gary

    2003-06-01

    A patient with arteriosclerosis, diabetes mellitus, and giant cell arteritis (GCA) treated continuously with low-dose prednisone developed anterior ischemic optic neuropathy (AION) at 5 and 13 months after clinical diagnosis of GCA. At the time of late recurrent AION, there were no systemic symptoms or elevations in acute phase reactants to signal active arteritis, yet temporal artery biopsy disclosed dramatic inflammation, forcing the presumption that the infarct was arteritic. Recurrent systemic symptoms and elevation of acute phase reactants are not reliable warning signs of reactivated GCA. In patients at high risk for corticosteroid complications, late biopsy may be a reasonable guide to corticosteroid weaning.

  7. Giant cell tumor of the upper cervical spine: transmandibular-translingual access. Clinical case.

    PubMed

    Cappuccio, M; Bandiera, S; Gasbarrini, A; De Iure, F; Barbanti Bròdano, G; Scimeca, G B; Presutti, L; Cocchi, R; Boriani, S

    2004-01-01

    The authors describe the clinical case of a patient aged 18 years affected with giant cell tumor (GCT) at C3 who came to the surgical unit of Orthopaedics and Traumatology at the Ospedale Maggiore in Bologna after being treated by surgery elsewhere. Particular attention is paid to surgical access by means of median transmandibuloglossotomy used in order to obtain a sufficiently wide surgical field that can adequately expose the vertebral segment affected by neoplastic disease. In particular, possible complications that may be observed postsurgery can be compared to other surgical approaches to the upper cervical spine and above all that there are no permanent clinical sequelae.

  8. Fatal recurrence of fulminant giant cell myocarditis and recovery after initialisation of an alternative immunosuppressive regime

    PubMed Central

    Fluschnik, Nina; Escher, Felicitas; Blankenberg, Stefan; Westermann, Dirk

    2014-01-01

    We report on a challenging case of a 34-year-old male patient with giant cell myocarditis (GCM) and fulminant relapse after discontinuing immunomodulatory therapy 2 years after the initial event. Specific combined immunosuppressive therapy with antithymocyte globulin (ATG), cyclosporine and high-dose glucocorticoids combined with guideline-based heart failure medication led to the recovery of GCM, improvement of systolic left ventricular function and clinical remission. This case report emphasises the importance of an immunosuppressive therapy for the prognosis and outcome and the risk of discontinuation. Most importantly, ATG seems to be one new possible potential treatment option for patients with acute GCM. PMID:25246472

  9. Increased Sensitivity of DNA Damage Response-Deficient Cells to Stimulated Microgravity-Induced DNA Lesions

    PubMed Central

    Li, Nan; An, Lili; Hang, Haiying

    2015-01-01

    Microgravity is a major stress factor that astronauts have to face in space. In the past, the effects of microgravity on genomic DNA damage were studied, and it seems that the effect on genomic DNA depends on cell types and the length of exposure time to microgravity or simulated microgravity (SMG). In this study we used mouse embryonic stem (MES) and mouse embryonic fibroblast (MEF) cells to assess the effects of SMG on DNA lesions. To acquire the insight into potential mechanisms by which cells resist and/or adapt to SMG, we also included Rad9-deleted MES and Mdc1-deleted MEF cells in addition to wild type cells in this study. We observed significant SMG-induced DNA double strand breaks (DSBs) in Rad9-/- MES and Mdc1-/- MEF cells but not in their corresponding wild type cells. A similar pattern of DNA single strand break or modifications was also observed in Rad9-/- MES. As the exposure to SMG was prolonged, Rad9-/- MES cells adapted to the SMG disturbance by reducing the induced DNA lesions. The induced DNA lesions in Rad9-/- MES were due to SMG-induced reactive oxygen species (ROS). Interestingly, Mdc1-/- MEF cells were only partially adapted to the SMG disturbance. That is, the induced DNA lesions were reduced over time, but did not return to the control level while ROS returned to a control level. In addition, ROS was only partially responsible for the induced DNA lesions in Mdc1-/- MEF cells. Taken together, these data suggest that SMG is a weak genomic DNA stress and can aggravate genomic instability in cells with DNA damage response (DDR) defects. PMID:25915950

  10. Increased sensitivity of DNA damage response-deficient cells to stimulated microgravity-induced DNA lesions.

    PubMed

    Li, Nan; An, Lili; Hang, Haiying

    2015-01-01

    Microgravity is a major stress factor that astronauts have to face in space. In the past, the effects of microgravity on genomic DNA damage were studied, and it seems that the effect on genomic DNA depends on cell types and the length of exposure time to microgravity or simulated microgravity (SMG). In this study we used mouse embryonic stem (MES) and mouse embryonic fibroblast (MEF) cells to assess the effects of SMG on DNA lesions. To acquire the insight into potential mechanisms by which cells resist and/or adapt to SMG, we also included Rad9-deleted MES and Mdc1-deleted MEF cells in addition to wild type cells in this study. We observed significant SMG-induced DNA double strand breaks (DSBs) in Rad9-/- MES and Mdc1-/- MEF cells but not in their corresponding wild type cells. A similar pattern of DNA single strand break or modifications was also observed in Rad9-/- MES. As the exposure to SMG was prolonged, Rad9-/- MES cells adapted to the SMG disturbance by reducing the induced DNA lesions. The induced DNA lesions in Rad9-/- MES were due to SMG-induced reactive oxygen species (ROS). Interestingly, Mdc1-/- MEF cells were only partially adapted to the SMG disturbance. That is, the induced DNA lesions were reduced over time, but did not return to the control level while ROS returned to a control level. In addition, ROS was only partially responsible for the induced DNA lesions in Mdc1-/- MEF cells. Taken together, these data suggest that SMG is a weak genomic DNA stress and can aggravate genomic instability in cells with DNA damage response (DDR) defects.

  11. Medication Management of Jaw Lesions for Dental Patients.

    PubMed

    Ogle, Orrett E; Santosh, Arvind Babu Rajendra

    2016-04-01

    Most pathologic lesions of the jaws or of oral mucosa are treated successfully by surgical interventions. For treatment of the central giant cell lesion, aneurysmal bone cysts, histiocytosis of the mandible, hemangioma, odontogenic keratocyst, Paget disease, oral submucous fibrosis, and oral lichen planus, medical management consisting of intralesional injections, sclerosing agents, and systemic bisphosphonates is as successful as surgical procedures with fewer complications. Pharmacology of agents used and protocols are presented. PMID:27040297

  12. Peptidergic modulation of the membrane potential of the Schwann cell of the squid giant nerve fibre.

    PubMed Central

    Evans, P D; Reale, V; Villegas, J

    1986-01-01

    The effects of a range of neuropeptides were investigated on the membrane potential of the Schwann cells of the giant nerve fibre of the tropical squid. Vasoactive intestinal peptide (VIP) produced a dose-dependent, long-lasting hyperpolarization of the Schwann-cell membrane potential. Among peptides structurally related to VIP, similar effects were produced by peptide histidine isoleucine (PHI) but not by secretin and glucagon. Substance P and somatostatin also hyperpolarized the Schwann-cell membrane potential but via receptor systems distinct from those activated by VIP. Methionine enkephalin ([Met]-enkephalin) blocked the actions of all the above peptides as well as the effects of DL-octopamine and carbachol. The actions of [Met]-enkephalin upon the VIP responses were antagonized by naloxone. VIP produces its effects on the Schwann-cell membrane potential via a receptor system that is independent from those described previously which mediate the effects of carbachol and DL-octopamine. However, VIP can potentiate the effects of the latter systems. The actions of VIP on the Schwann cell are unlikely to be mediated via changes in adenosine 3',5'-cyclic monophosphate (cyclic AMP) levels and are insensitive to changes in the level of extracellular calcium in the superfusate. The actions of VIP are, however, potentiated in the presence of low concentrations of lithium ions suggesting that the VIP receptor may mediate its effects by inducing the hydrolysis of polyphosphatidylinositols in the Schwann-cell membrane. Evidence is presented for the existence of an endogenous VIP-like component in the normal hyperpolarizing action of giant-axon activity on the membrane potential of the Schwann cell. PMID:2435897

  13. DNA lesion identity drives choice of damage tolerance pathway in murine cell chromosomes.

    PubMed

    Cohen, Isadora S; Bar, Carmit; Paz-Elizur, Tamar; Ainbinder, Elena; Leopold, Karoline; de Wind, Niels; Geacintov, Nicholas; Livneh, Zvi

    2015-02-18

    DNA-damage tolerance (DDT) via translesion DNA synthesis (TLS) or homology-dependent repair (HDR) functions to bypass DNA lesions encountered during replication, and is critical for maintaining genome stability. Here, we present piggyBlock, a new chromosomal assay that, using piggyBac transposition of DNA containing a known lesion, measures the division of labor between the two DDT pathways. We show that in the absence of DNA damage response, tolerance of the most common sunlight-induced DNA lesion, TT-CPD, is achieved by TLS in mouse embryo fibroblasts. Meanwhile, BP-G, a major smoke-induced DNA lesion, is bypassed primarily by HDR, providing the first evidence for this mechanism being the main tolerance pathway for a biologically important lesion in a mammalian genome. We also show that, far from being a last-resort strategy as it is sometimes portrayed, TLS operates alongside nucleotide excision repair, handling 40% of TT-CPDs in repair-proficient cells. Finally, DDT acts in mouse embryonic stem cells, exhibiting the same pattern—mutagenic TLS included—despite the risk of propagating mutations along all cell lineages. The new method highlights the importance of HDR, and provides an effective tool for studying DDT in mammalian cells. PMID:25589543

  14. DNA lesion identity drives choice of damage tolerance pathway in murine cell chromosomes

    PubMed Central

    Cohen, Isadora S.; Bar, Carmit; Paz-Elizur, Tamar; Ainbinder, Elena; Leopold, Karoline; de Wind, Niels; Geacintov, Nicholas; Livneh, Zvi

    2015-01-01

    DNA-damage tolerance (DDT) via translesion DNA synthesis (TLS) or homology-dependent repair (HDR) functions to bypass DNA lesions encountered during replication, and is critical for maintaining genome stability. Here, we present piggyBlock, a new chromosomal assay that, using piggyBac transposition of DNA containing a known lesion, measures the division of labor between the two DDT pathways. We show that in the absence of DNA damage response, tolerance of the most common sunlight-induced DNA lesion, TT-CPD, is achieved by TLS in mouse embryo fibroblasts. Meanwhile, BP-G, a major smoke-induced DNA lesion, is bypassed primarily by HDR, providing the first evidence for this mechanism being the main tolerance pathway for a biologically important lesion in a mammalian genome. We also show that, far from being a last-resort strategy as it is sometimes portrayed, TLS operates alongside nucleotide excision repair, handling 40% of TT-CPDs in repair-proficient cells. Finally, DDT acts in mouse embryonic stem cells, exhibiting the same pattern—mutagenic TLS included—despite the risk of propagating mutations along all cell lineages. The new method highlights the importance of HDR, and provides an effective tool for studying DDT in mammalian cells. PMID:25589543

  15. Identification of Mesenchymal Stem Cell Marker STRO-1 in Oral Reactive Lesions by Immunofluorescence Method

    PubMed Central

    Dehghani Nazhvani, Ali; Hosseini, Seyed-Mojtaba; Tahoori, Bita; Tavangar, Maryam-Sadat; Attar, Armin

    2015-01-01

    Statement of the Problem Stem cells are considered as new implement for tissue regeneration. Several niches in adult human body are colonized by multipotent stem cells but access to these potential reservoirs is often limited. Although human dental pulp stem cells isolated from healthy teeth have been extensively characterized, it is still unknown whether stem cells also exist in reactive lesions of oral cavity such as pyogenic granuloma and peripheral ossifying fibroma which are deliberated as inflammatory proliferation of different cell families. Purpose The aim of this study was to explore for clues to see whether pyogenic granuloma or peripheral ossifying fibroma contain dental mesenchymal stem cell (DMSC). Materials and Method Four pyogenic granuloma and four peripheral ossifying fibroma specimens were collected by excisional biopsy and preserved in PBS-EDTA at -86 °C. Then we cut them in 5µm diameter using Cryostat. Having been rinsed with PBS, the samples were stained with a primary mouse anti-human STRO-1 monoclonal IgM antibody. Afterward, a secondary goat anti-mouse IgM-FITC antibody was applied to detect STRO-1+ cells as probable stem cells by immunofluorescence technique. Results Immunofluorescence microscopy revealed presence of STRO-1+ cells in these lesions, particularly localized on perivascular zone. The negative control group was not glowing. Conclusion Based on these results, it was found that reactive lesions of pyogenic granuloma and peripheral ossifying fibroma have STRO-1 positive cells, which raises the possibility that these cells may be DMSCs. PMID:26535404

  16. Conversions of excision-repairable DNA lesions to micronuclei within one cell cycle in human lymphocytes

    SciTech Connect

    Fenech, M.; Neville, S. )

    1992-01-01

    The human lymphocyte micronucleus (MN) assay is relatively insensitive to genotoxic agents that predominantly induce excision-repairable lesions such as adducts and abasic sites. In this study the authors have explored the possibility of using cytosine arabinoside (ARA) to convert excision-repairable DNA lesions to micronuclei (MN) within one cell cycle. The system consisted of human lymphocytes as target cells, the cytokinesis-block (CB) method for identifying cells that had completed one nuclear division only, and X-rays, methylnitrosourea (MNU), and ultraviolet light (UV) as mutagens. With each mutagen they have observed significant increments induced MN in the cultures that had also been treated with ARA during G{sub 1}. These observations suggested that the combined ARA and cytokinesis-block micronucleus (CBMN) method may enhance the detection of exposure to genotoxic agents that predominantly induce excision-repairable lesions.

  17. Binucleate trophoblast giant cells in the water buffalo (Bubalus bubalis) placenta.

    PubMed

    Carvalho, A F; Klisch, K; Miglino, M A; Pereira, F T V; Bevilacqua, E

    2006-01-01

    The binucleate trophoblast giant cells (BNC) of the water buffalo, Bubalus bubalis, placenta were studied, with emphasis on the synthesis of BNC-specific proteins. Placentomal tissues of 27 water buffalos (2-10 months of pregnancy) were processed for light and electron microscopy. The frequency of BNCs was 20% of the trophoblastic cells in 2-3-month placentas and increased to 27% in the later stages. Ultrastructurally, binucleate cells displayed a prominent granular endoplasmic reticulum and Golgi apparatus, typical of cells involved with protein synthesis and exportation. The buffalo BNCs contained periodic acid-Schiff (PAS)-positive granules and reacted with antisera against bovine placental lactogen, prolactin-related protein-I, and pregnancy-associated glycoproteins. Lectin histochemistry with Dolichos biflorus agglutinin, Vicia villosa agglutinin, and Phaseolus vulgaris leucoagglutinin showed specific staining of BNCs. Different stages of BNC migration and fusion with uterine epithelial cells were observed. Trinucleate feto-maternal hybrid cells were the typical outcome of cell fusions. These cells underwent degeneration, with typical morphological features of apoptosis. The results revealed a strong homology between water buffalo and cattle BNCs concerning cell morphology, protein expression, glycosylation pattern, and characteristics of cell migration and fusion.

  18. Local immunological reactivity in oral squamous cell lesions of possible HPV (human papillomavirus) origin.

    PubMed

    Syrjänen, K J; Syrjänen, S M; Lamberg, M A; Happonen, R P

    1983-01-01

    The immunocompetent cells (B and T lymphocytes, mononuclear phagocytes, MPS cells) known to be responsible for the rejection of the HPV- (Human Papillomavirus) induced tumors in the skin (warts) were analyzed in the infiltrates of 63 oral squamous cell lesions of suspected HPV origin (Condyloma, CA; Focal Epithelial Hyperplasia, FEH; Squamous Cell Papilloma, SQP) as well as in tumors thought to be unrelated to HPV (Fibrous Hyperplasia, FH; Papillary Hyperplasia, PH; True Fibroma, TF; Keratoacanthoma, KA), using the ANAE (acid alpha-naphthyl acetate esterase) technique. All tumors were also stained by the indirect immunoperoxidase-PAP method for the demonstration of HPV antigens. Of the SQP's, 60% were HPV-positive, as were 80% of CA's and one third of FEH's. In addition, 1/18 FH's and 2/14 PH's stained HPV-positive. On electron microscopy, viral particles could be disclosed within the nuclei of HPV-lesions. The highest proportions of the T and MPS cells (the elements of cell-mediated immunity) were found in CA's and SQP's (15-17%), as compared with the values of less than 10% in all others. The infiltrates in FEH's also showed low values of MPS and T cells, interpreted to suggest an etiology of the HPV type (determining the type of immune reaction) different from that of CA and SQP. HPV-positivity in the lesions did not influence the distribution of the immunocompetent cells. The results indicate that immunological mechanisms are involved in HPV lesions of the oral cavity as they are at other sites. The role of HPV in the etiology of these (and possibly of the oral squamous cell carcinoma) was discussed. Further analyses of the lymphocyte subsets are needed to establish the role of host reactions in the development and eradication of HPV lesions in oral cavity.

  19. Basic Fibroblast Growth Factor Stimulates the Proliferation of Bone Marrow Mesenchymal Stem Cells in Giant Panda (Ailuropoda melanoleuca).

    PubMed

    Wang, Jun-Jie; Liu, Yu-Liang; Sun, Yuan-Chao; Ge, Wei; Wang, Yong-Yong; Dyce, Paul W; Hou, Rong; Shen, Wei

    2015-01-01

    It has been widely known that the giant panda (Ailuropoda melanoleuca) is one of the most endangered species in the world. An optimized platform for maintaining the proliferation of giant panda mesenchymal stem cells (MSCs) is very necessary for current giant panda protection strategies. Basic fibroblast growth factor (bFGF), a member of the FGF family, is widely considered as a growth factor and differentiation inducer within the stem cell research field. However, the role of bFGF on promoting the proliferation of MSCs derived from giant panda bone marrow (BM) has not been reported. In this study, we aimed to investigate the role of bFGF on the proliferation of BM-MSCs derived from giant panda. MSCs were cultured for cell proliferation analysis at 24, 48 and 72 hrs following the addition of bFGF. With increasing concentrations of bFGF, cell numbers gradually increased. This was further demonstrated by performing 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) cell proliferation assay, 5-Bromo-2-deoxyUridine (BrdU) labeling and cell cycle testing. Furthermore, the percentage of MSCs that were OCT4 positive increased slightly following treatment with 5 ng/ml bFGF. Moreover, we demonstrated that the extracellular signal-regulated kinase (ERK) signaling pathway may play an important role in the proliferation of panda MSCs stimulated by bFGF. In conclusion, this study suggests that giant panda BM-MSCs have a high proliferative capacity with the addition of 5 ng/ml bFGF in vitro.

  20. Basic Fibroblast Growth Factor Stimulates the Proliferation of Bone Marrow Mesenchymal Stem Cells in Giant Panda (Ailuropoda melanoleuca)

    PubMed Central

    Wang, Jun-Jie; Liu, Yu-Liang; Sun, Yuan-Chao; Ge, Wei; Wang, Yong-Yong; Dyce, Paul W.; Hou, Rong; Shen, Wei

    2015-01-01

    It has been widely known that the giant panda (Ailuropoda melanoleuca) is one of the most endangered species in the world. An optimized platform for maintaining the proliferation of giant panda mesenchymal stem cells (MSCs) is very necessary for current giant panda protection strategies. Basic fibroblast growth factor (bFGF), a member of the FGF family, is widely considered as a growth factor and differentiation inducer within the stem cell research field. However, the role of bFGF on promoting the proliferation of MSCs derived from giant panda bone marrow (BM) has not been reported. In this study, we aimed to investigate the role of bFGF on the proliferation of BM-MSCs derived from giant panda. MSCs were cultured for cell proliferation analysis at 24, 48 and 72 hrs following the addition of bFGF. With increasing concentrations of bFGF, cell numbers gradually increased. This was further demonstrated by performing 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) cell proliferation assay, 5-Bromo-2-deoxyUridine (BrdU) labeling and cell cycle testing. Furthermore, the percentage of MSCs that were OCT4 positive increased slightly following treatment with 5 ng/ml bFGF. Moreover, we demonstrated that the extracellular signal-regulated kinase (ERK) signaling pathway may play an important role in the proliferation of panda MSCs stimulated by bFGF. In conclusion, this study suggests that giant panda BM-MSCs have a high proliferative capacity with the addition of 5 ng/ml bFGF in vitro. PMID:26375397

  1. Basic Fibroblast Growth Factor Stimulates the Proliferation of Bone Marrow Mesenchymal Stem Cells in Giant Panda (Ailuropoda melanoleuca).

    PubMed

    Wang, Jun-Jie; Liu, Yu-Liang; Sun, Yuan-Chao; Ge, Wei; Wang, Yong-Yong; Dyce, Paul W; Hou, Rong; Shen, Wei

    2015-01-01

    It has been widely known that the giant panda (Ailuropoda melanoleuca) is one of the most endangered species in the world. An optimized platform for maintaining the proliferation of giant panda mesenchymal stem cells (MSCs) is very necessary for current giant panda protection strategies. Basic fibroblast growth factor (bFGF), a member of the FGF family, is widely considered as a growth factor and differentiation inducer within the stem cell research field. However, the role of bFGF on promoting the proliferation of MSCs derived from giant panda bone marrow (BM) has not been reported. In this study, we aimed to investigate the role of bFGF on the proliferation of BM-MSCs derived from giant panda. MSCs were cultured for cell proliferation analysis at 24, 48 and 72 hrs following the addition of bFGF. With increasing concentrations of bFGF, cell numbers gradually increased. This was further demonstrated by performing 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) cell proliferation assay, 5-Bromo-2-deoxyUridine (BrdU) labeling and cell cycle testing. Furthermore, the percentage of MSCs that were OCT4 positive increased slightly following treatment with 5 ng/ml bFGF. Moreover, we demonstrated that the extracellular signal-regulated kinase (ERK) signaling pathway may play an important role in the proliferation of panda MSCs stimulated by bFGF. In conclusion, this study suggests that giant panda BM-MSCs have a high proliferative capacity with the addition of 5 ng/ml bFGF in vitro. PMID:26375397

  2. Immunohistochemical demonstration of human papilloma virus (HPV) antigens in oral squamous cell lesions.

    PubMed

    Syrjänen, K J; Pyrhönen, S; Syrjänen, S M; Lamberg, M A

    1983-06-01

    Six oral squamous cell tumours classified as focal epithelial hyperplasia (FEH), Condyloma acuminatum (CA) and squamous cell papilloma (SQP) were subjected to indirect immunoperoxidase staining with anti-human papillomavirus (anti-HPV) antiserum to demonstrate the possible presence of HPV antigens in these lesions. The results are discussed in the light of the observations on HPV-lesions elsewhere in the body (in uterine cervix), and a suggestion is made to adopt the name condyloma for all those tumours where HPV aetiology can be established by ultrastructural or immunohistochemical means.

  3. Macrophage fusion, giant cell formation, and the foreign body response require matrix metalloproteinase 9

    PubMed Central

    MacLauchlan, Susan; Skokos, Eleni A.; Meznarich, Norman; Zhu, Dana H.; Raoof, Sana; Shipley, J. Michael; Senior, Robert M.; Bornstein, Paul; Kyriakides, Themis R.

    2009-01-01

    Macrophages undergo fusion to form multinucleated giant cells in several pathologic conditions, including the foreign body response (FBR). We detected high levels of matrix metalloproteinase (MMP)-9 during macrophage fusion in vitro and in foreign body giant cells (FBGCs) in vivo. Wild-type (WT) bone marrow-derived macrophages were induced to fuse with IL-4 in the presence of MMP-9 function-blocking antibodies and displayed reduced fusion. A similar defect, characterized by delayed shape change and abnormal morphology, was observed in MMP-9 null macrophages. Analysis of the FBR in MMP-9 null mice was then pursued to evaluate the significance of these findings. Specifically, mixed cellulose ester disks and polyvinyl alcohol sponges were implanted s.c. in MMP-9 null and WT mice and excised 2–4 weeks later. Histochemical and immunohistochemical analyses indicated equal macrophage recruitment between MMP-9 null and WT mice, but FBGC formation was compromised in the former. In addition, MMP-9 null mice displayed abnormalities in extracellular matrix assembly and angiogenesis. Consistent with a requirement for MMP-9 in fusion, we also observed reduced MMP-9 levels in MCP-1 null macrophages, previously shown to be defective in FBGC formation. Collectively, our studies show abnormalities in MMP-9 null mice during the FBR and suggest a role for MMP-9 in macrophage fusion. PMID:19141565

  4. Giant cell arteritis: the importance of immediate and appropriate diagnosis and treatment for better prognosis

    PubMed Central

    Pacella, Fernanda; Mazzeo, Francesco; Giorgi, Dario; Cerutti, Francesco; Impallara, David; Cuozzo, Giovanni; Soldini, Maurizio; Pacella, Elena

    2012-01-01

    This article describes the case of a 68-year-old patient suffering from giant cell arteritis (also known as Horton’s arteritis or temporal arteritis). The patient came to our attention due to a large and sudden visual loss caused by the occlusion of major retinal arteries. The patient had neuralgic pain in the face. The next day, for a thorough examination, the patient went to the day hospital with a further worsening of the visual loss which required immediate admission to the ophthalmological ward for hospitalization lasting 10 days. During the observation period it was difficult to make an instant diagnosis due to the absence of clinical signs or diagnostic tests for Horton’s arteritis. Only after the third day of hospitalization, when corticosteroid therapy was undertaken following the appearance of significant systemic symptoms, did the patient begin to show a gradual improvement in overall clinical status. The case highlights the difficulty in making a rapid diagnosis of giant cell arteritis and the efficacy of early steroid therapy in this vascular autoimmune disease that otherwise may result in irreversible functional and debilitating systemic damage. PMID:22791971

  5. Giant cell arteritis: the importance of immediate and appropriate diagnosis and treatment for better prognosis.

    PubMed

    Pacella, Fernanda; Mazzeo, Francesco; Giorgi, Dario; Cerutti, Francesco; Impallara, David; Cuozzo, Giovanni; Soldini, Maurizio; Pacella, Elena

    2012-01-01

    This article describes the case of a 68-year-old patient suffering from giant cell arteritis (also known as Horton's arteritis or temporal arteritis). The patient came to our attention due to a large and sudden visual loss caused by the occlusion of major retinal arteries. The patient had neuralgic pain in the face. The next day, for a thorough examination, the patient went to the day hospital with a further worsening of the visual loss which required immediate admission to the ophthalmological ward for hospitalization lasting 10 days. During the observation period it was difficult to make an instant diagnosis due to the absence of clinical signs or diagnostic tests for Horton's arteritis. Only after the third day of hospitalization, when corticosteroid therapy was undertaken following the appearance of significant systemic symptoms, did the patient begin to show a gradual improvement in overall clinical status. The case highlights the difficulty in making a rapid diagnosis of giant cell arteritis and the efficacy of early steroid therapy in this vascular autoimmune disease that otherwise may result in irreversible functional and debilitating systemic damage. PMID:22791971

  6. Giant cell interstitial pneumonia in a 15-year-old boy.

    PubMed

    Kakugawa, Tomoyuki; Mukae, Hiroshi; Nagata, Towako; Ishii, Hiroshi; Kaida, Hideyuki; Hayashi, Tomayoshi; Suematsu, Takashi; Kadota, Jun-ichi; Kohno, Shigeru

    2002-11-01

    Giant cell interstitial pneumonia (GIP) is a very uncommon respiratory disease. We report a juvenile patient with GIP aged 15 years. Although he has a negative past history of direct exposure to hard metals, we could not exclude possible exposure in very small amounts through his parents. Microscopic examination of lung biopsy specimen obtained by video-assisted thoracoscopy revealed marked cellular interstitial infiltrates and prominent intraalveolar macrophages as well as giant cells showing cellular cannibalism. Analysis of the biopsied lung tissue for cobalt and tungsten was negative. Clinical symptoms, laboratory, and radiological findings improved markedly after treatment with corticosteroids. To our knowledge, only eleven cases of GIP have been reported in Japan. Although possible exposure to hard metals was identified in 9 of the 11 reported cases, there is no clear dose-dependent relationship with onset and prognosis. The average age at onset was 46.2+/-15.0 years. Our patient is the youngest case of GIP reported in the world. PMID:12487179

  7. Expression of Stem Cell Markers in Preinvasive Tubal Lesions of Ovarian Carcinoma

    PubMed Central

    Chene, G.; Ouellet, V.; Rahimi, K.; Barres, V.; Meunier, L.; De Ladurantaye, M.; Provencher, D.; Mes-Masson, A. M.

    2015-01-01

    In order to better understand the ovarian serous carcinogenic process with tubal origin, we investigated the expression of stem cell markers in premalignant tubal lesions (serous tubal intraepithelial carcinoma or STIC). We found an increased stem cell marker density in the normal fallopian tube followed by a high CD117 and a low ALDH and CD44 expression in STICs raising the question of the role of the stem cell markers in the serous carcinogenic process. PMID:26504831

  8. [Failure of initial surgical treatment of a giant cell tumor of the capitate and its salvage: a case report].

    PubMed

    Moreel, P; Le Viet, D

    2006-12-01

    Giant Cell Tumors are rare tumors in the young adult and localisation in the hand is even more exceptional. In the absence of adjuvant treatment, the literature reports a strong potential for local recurrence of between 75 and 86%. These tumours also have a risk of sarcomatosis degeneration and pulmonary metastasis. The case report concerns a 24-year-old patient, with a Giant Cell Tumour of the capitate initially diagnosed on simple curettage, and we describe her treatment together with the treatment of a subsequent reccurrence. A literature review will also highlight the current knowledge of this disease.

  9. Quantitative analysis of disturbed cell maturation in dysplastic lesions of the respiratory tract epithelium

    SciTech Connect

    Klein-Szanto, A.J.P.; Nettesheim, P.; Topping, D.C.; Olson, A.C.

    1980-01-01

    Autoradiographic patterns of (/sup 3/H)thymidine incorporation, nuclear/cytoplasmic ratios (N/C), and the percentage of dark epithelial cells were analyzed in a group of epithelial lesions induced by 7,12-dimethylbenz(a)anthracene (DMBA) in rat tracheal transplants. It was found that similar lesions of different age exhibit the same labeling indices (LIs), therefore the lesions of different age were subsequently pooled in the following groups and studied by high resolution light microscopic autoradiography: squamous metaplasia without or with only mild atypia, squamous metaplasia with moderate atypia, squamous metaplasia with severe atypia, carcinoma in situ, and microinvasive carcinoma. Normal tracheal and esophageal epithelia were also analyzed. Gradients of increasing N/C (nucleus-cytoplasm ratios) values could be observed as the lesions increased in severity, especially in the middle and surface layers (e.g., in the surface layer regular metaplasia N/C = 0.08, squamous metaplasia with moderate atypia N/C = 0.26, and carcinoma in situ N/C = 0.50). Dark cells were absent in the normal esophageal epithelium, were present in moderate numbers in the basal layer of regular squamous metaplasia (18%), and increased markedly in the atypical epithelial lesions (approximately 50% in the atypical squamous metaplasias and 70% in carcinoma in situ). In the suprabasal layer dark cells increased from 3% in squamous metaplasia with moderate atypia to 28% in metaplasia with severe atypia and 56% in carcinoma in situ. The results confirm in a quantitative fashion that disturbances of cell maturation and cell proliferation are key features of dysplastic lesions induced by chemical carcinogens, and suggest the use of objective parameters for evaluation and classification of preneoplastic alterations.

  10. Roe Protein Hydrolysates of Giant Grouper (Epinephelus lanceolatus) Inhibit Cell Proliferation of Oral Cancer Cells Involving Apoptosis and Oxidative Stress

    PubMed Central

    Yang, Jing-Iong; Tang, Jen-Yang; Liu, Ya-Sin; Wang, Hui-Ru; Lee, Sheng-Yang; Yen, Ching-Yu

    2016-01-01

    Roe protein hydrolysates were reported to have antioxidant property but the anticancer effects were less addressed, especially for oral cancer. In this study, we firstly used the ultrafiltrated roe hydrolysates (URH) derived from giant grouper (Epinephelus lanceolatus) to evaluate the impact of URH on proliferation against oral cancer cells. We found that URH dose-responsively reduced cell viability of two oral cancer cells (Ca9-22 and CAL 27) in terms of ATP assay. Using flow cytometry, URH-induced apoptosis of Ca9-22 cells was validated by morphological features of apoptosis, sub-G1 accumulation, and annexin V staining in dose-responsive manners. URH also induced oxidative stress in Ca9-22 cells in terms of reactive oxygen species (ROS)/superoxide generations and mitochondrial depolarization. Taken together, these data suggest that URH is a potential natural product for antioral cancer therapy. PMID:27195297

  11. Mesenchymal Stem Cells Ameliorate Atherosclerotic Lesions via Restoring Endothelial Function

    PubMed Central

    Lin, Yu-Ling; Yet, Shaw-Fang; Hsu, Yuan-Tong

    2015-01-01

    Transplantation of mesenchymal stem cells (MSCs) is beneficial in myocardial infarction and hind limb ischemia, but its ability to ameliorate atherosclerosis remains unknown. Here, the effects of MSCs on inhibiting endothelial dysfunction and atherosclerosis were investigated in human/mouse endothelial cells treated with oxidized low-density lipoprotein (oxLDL) and in apolipoprotein E-deficient (apoE−/−) mice fed a high-fat diet. Treatment with oxLDL inactivated the Akt/endothelial nitric-oxide synthase (eNOS) pathway, induced eNOS degradation, and inhibited nitric oxide (NO) production in endothelial cells. Coculture with human MSCs reversed the effects of oxLDL on endothelial cells and restored Akt/eNOS activity, eNOS level, and NO production. Reduction of endothelium-dependent relaxation and subsequent plaque formation were developed in apoE−/− mice fed a high-fat diet. Systemic infusion with mouse MSCs ameliorated endothelial dysfunction and plaque formation in high-fat diet-fed apoE−/− mice. Interestingly, treatment with interleukin-8 (IL8)/macrophage inflammatory protein-2 (MIP-2) alone induced the similar effects of human/mouse MSCs on oxLDL-treated human/mouse endothelial cells. Neutralization antibodies (Abs) against IL8/MIP-2 also blocked the effects of human/mouse MSCs on oxLDL-treated human/mouse endothelial cells. Consistently, MIP-2 injection alone induced the similar effect of MSCs on the endothelial function in high-fat diet-fed apoE−/− mice. The improvement in endothelial dysfunction by mouse MSCs was also blocked when pretreating MSCs with anti-MIP-2 Abs. In conclusion, MSC transplantation improved endothelial function and plaque formation in high-fat diet-fed apoE−/− mice. Activation of the Akt/eNOS pathway in endothelium by IL8/MIP-2 is involved in the protective effect of MSCs. The study helps support the use and clarify the mechanism of MSCs for ameliorating atherosclerosis. PMID:25504897

  12. Early transcriptomic events in microdissected Arabidopsis nematode-induced giant cells.

    PubMed

    Barcala, Marta; García, Alejandra; Cabrera, Javier; Casson, Stuart; Lindsey, Keith; Favery, Bruno; García-Casado, Gloria; Solano, Roberto; Fenoll, Carmen; Escobar, Carolina

    2010-02-01

    Root-knot nematodes differentiate highly specialized feeding cells in roots (giant cells, GCs), through poorly characterized mechanisms that include extensive transcriptional changes. While global transcriptome analyses have used galls, which are complex root structures that include GCs and surrounding tissues, no global gene expression changes specific to GCs have been described. We report on the differential transcriptome of GCs versus root vascular cells, induced in Arabidopsis by Meloidogyne javanica at a very early stage of their development, 3 days after infection (d.p.i.). Laser microdissection was used to capture GCs and root vascular cells for microarray analysis, which was validated through qPCR and by a promoter-GUS fusion study. Results show that by 3 d.p.i., GCs exhibit major gene repression. Although some genes showed similar regulation in both galls and GCs, the majority had different expression patterns, confirming the molecular distinctiveness of the GCs within the gall. Most of the differentially regulated genes in GCs have no previously assigned function. Comparisons with other transcriptome analyses revealed similarities between GCs and cell suspensions differentiating into xylem cells. This suggests a molecular link between GCs and developing vascular cells, which represent putative GC stem cells. Gene expression in GCs at 3 d.p.i. was also found to be similar to crown galls induced by Agrobacterium tumefaciens, a specialized root biotroph. PMID:20003167

  13. Endothelial cell proliferation associated with lesions of murine systemic candidiasis.

    PubMed Central

    Ashman, R B; Papadimitriou, J M

    1994-01-01

    Neovascularization is associated with tumor growth and some inflammatory diseases but has not been reported to be induced by infectious agents. In a mouse model of systemic Candida albicans infection, extensive endothelial cell proliferation was seen in the periphery of brain abscesses and in the areas of fungal pyelonephritis in the kidney. This finding is important for an understanding of the pathogenesis of fungal infections and may contribute to an analysis of the mechanisms of angiogenesis. Images PMID:7523305

  14. Undifferentiated Carcinoma With Osteoclastic Giant Cells of the Pancreas: Clinicopathologic Analysis of 38 Cases Highlights a More Protracted Clinical Course Than Currently Appreciated.

    PubMed

    Muraki, Takashi; Reid, Michelle D; Basturk, Olca; Jang, Kee-Taek; Bedolla, Gabriela; Bagci, Pelin; Mittal, Pardeep; Memis, Bahar; Katabi, Nora; Bandyopadhyay, Sudeshna; Sarmiento, Juan M; Krasinskas, Alyssa; Klimstra, David S; Adsay, Volkan

    2016-09-01

    Undifferentiated carcinomas with osteoclastic giant cells of the pancreas (OGC) are rare tumors. The current impression in the literature is that they are highly aggressive tumors similar in prognosis to ductal adenocarcinomas. In this study, the clinicopathologic characteristics of 38 resected OGCs were investigated and contrasted with 725 resected pancreatic ductal adenocarcinomas without osteoclastic cells (PDCs). The frequency among systematically reviewed pancreatic cancers was 1.4%. OGCs showed a slight female predominance (62.9%, vs. 51.4% in PDCs). The mean age was 57.9 years (vs. 65.0). The mean size of invasive cancer was 5.3 cm (vs. 3.2). They were characterized by nodular, pushing-border growth, and 8 arose in tumoral intraepithelial neoplasms (4 in mucinous cystic neoplasms, 4 in intraductal papillary mucinous neoplasms type lesions), and 23 (61%) also showed prominent intraductal/intracystic growth. Twenty-nine (76%) had an invasive ductal/tubular adenocarcinoma component. Osteoid was seen in 12. Despite their larger size, perineural invasion and nodal metastasis were uncommon (31.6% and 22.6%, vs. 85.5% and 64.0%, respectively). Immunohistochemistry performed on 24 cases revealed that osteoclastic cells expressed the histiocytic marker CD68, and background spindle cells and pleomorphic/giant carcinoma cells often showed p53 and often lacked cytokeratin. Survival of OGCs was significantly better than that of PDCs (5 yr, 59.1% vs. 15.7%, respectively, P=0.0009). In conclusion, pancreatic OGCs present with larger tumor size and in slightly younger patients than PDC, 21% arise in mucinous cystic neoplasms/intraductal papillary mucinous neoplasms, and 61% show intraductal/intracystic polypoid growth. OGCs have a significantly better prognosis than is currently believed in the literature. PMID:27508975

  15. Cathepsin K expression in the spectrum of perivascular epithelioid cell (PEC) lesions of the kidney.

    PubMed

    Martignoni, Guido; Bonetti, Franco; Chilosi, Marco; Brunelli, Matteo; Segala, Diego; Amin, Mahul B; Argani, Pedram; Eble, John N; Gobbo, Stefano; Pea, Maurizio

    2012-01-01

    The perivascular epithelioid cell (PEC) is a unique cell type coexpressing contractile proteins (mainly α-smooth muscle actin), melanocytic markers, including microphthalmia-associated transcription factor (MITF), and estrogen and progesterone receptors. It is constantly present in a group of tumors called PEComas. Renal PEComas include the common angiomyolipoma as well as less common lesions such as microscopic angiomyolipoma, intraglomerular lesions, angiomyolipoma with epithelial cysts, epithelioid angiomyolipoma, oncocytoma-like angiomyolipoma and lymphangioleiomyomatosis of the renal sinus. It has been demonstrated that most of these lesions are determined by mutations affecting genes of the tuberous sclerosis complex, tuberous sclerosis 1 (TSC1) and tuberous sclerosis 2 (TSC2), with eventual deregulation of the RHEB/MTOR/RPS6KB2 pathway, and it has been observed that some PEComas regressed during sirolimus therapy, an MTOR inhibitor. Recently, overexpression of MITF has been related to the expression of the papain-like cysteine protease cathepsin K in osteoclasts where it has inhibited MTOR. The aim of this study is to evaluate cathepsin K immunohistochemically in the entire spectrum of PEComa lesions in the kidney. The study population consisted of 84 renal PEComa lesions, including 5 composed predominantly of fat (lipoma-like angiomyolipoma), 15 almost exclusively composed of spindle-shaped smooth muscle cells (leiomyoma-like angiomyolipoma) and 31 common angiomyolipomas composed of a mixture of fat, spindle and epithelioid smooth muscle cells, and abnormal thick-walled blood vessels, 15 microscopic angiomyolipomas, 5 intraglomerular lesions, 2 oncocytoma-like angiomyolipomas, 8 epithelioid angiomyolipomas, 2 angiomyolipomas with epithelial cysts and 1 example of lymphangioleiomyomatosis of the renal sinus. In all of the renal PEComas, cathepsin K was found to be constantly and strongly expressed and seems to be a more powerful marker than other commonly

  16. Giant-cell interstitial pneumonia and hard-metal pneumoconiosis. A clinicopathologic study of four cases and review of the literature

    SciTech Connect

    Ohori, N.P.; Sciurba, F.C.; Owens, G.R.; Hodgson, M.J.; Yousem, S.A.

    1989-07-01

    We report four cases of giant-cell interstitial pneumonia that occurred in association with exposure to hard metals. All patients presented with chronic interstitial lung disease and had open-lung biopsies that revealed marked interstitial fibrosis, cellular interstitial infiltrates, and prominent intraalveolar macrophages as well as giant cells displaying cellular cannibalism. We also review the literature to determine the sensitivity and specificity of giant-cell interstitial pneumonia for hard-metal pneumoconiosis. Although hard-metal pneumoconiosis may take the form of usual interstitial pneumonia, desquamative interstitial pneumonia, and giant-cell interstitial pneumonia, the finding of giant-cell interstitial pneumonia is almost pathognomonic of hard-metal disease and should provoke an investigation of occupational exposure. 25 references.

  17. Giant Host Red Blood Cell Membrane Mimicking Polymersomes Bind Parasite Proteins and Malaria Parasites.

    PubMed

    Najer, Adrian; Thamboo, Sagana; Palivan, Cornelia G; Beck, Hans-Peter; Meier, Wolfgang

    2016-01-01

    Malaria is an infectious disease that needs to be addressed using innovative approaches to counteract spread of drug resistance and to establish or optimize vaccination strategies. With our approach, we aim for a dual action with drug- and 'vaccine-like' activity against malaria. By inhibiting entry of malaria parasites into host red blood cells (RBCs) - using polymer vesicle-based (polymersome) nanomimics of RBC membranes - the life cycle of the parasite is interrupted and the exposed parasites are accessible to the host immune system. Here, we describe how host cell-sized RBC membrane mimics, formed with the same block copolymers as nanomimics, also bind the corresponding malaria parasite ligand and whole malaria parasites, similar to nanomimics. This was demonstrated using fluorescence imaging techniques and confirms the suitability of giant polymersomes (GUVs) as simple mimics for RBC membranes.

  18. Paucity of natural killer and cytotoxic T cells in human neuromyelitis optica lesions.

    PubMed

    Saadoun, Samira; Bridges, Leslie R; Verkman, A S; Papadopoulos, Marios C

    2012-12-19

    Neuromyelitis optica is a severe inflammatory demyelinating disease of the central nervous system. Most patients with neuromyelitis optica have circulating immunoglobulin G (IgG) antibodies against the astrocytic water channel protein aquaporin-4 (AQP4), which are pathogenic. Anti-AQP4 IgG-mediated complement-dependent astrocyte toxicity is a key mechanism of central nervous system damage in neuromyelitis optica, but the role of natural killer and cytotoxic T cells is unknown. Our objective was to determine whether natural killer and cytotoxic T cells play a role in human neuromyelitis optica lesions. We immunostained four actively demyelinating lesions, obtained from patients with anti-AQP4 IgG positive neuromyelitis optica, for Granzyme B and Perforin. The inflammatory cells were perivascular neutrophils, eosinophils and macrophages, with only occasional Granzyme B+ or Perforin+ cells. Greater than 95% of inflamed vessels in each lesion had no surrounding Granzyme B+ or Perforin+ cells. Granzyme B+ or Perforin+ cells were abundant in human spleen (positive control). Although natural killer cells produce central nervous system damage in mice injected with anti-AQP4 IgG, our findings here indicate that natural killer-mediated and T cell-mediated cytotoxicity are probably not involved in central nervous system damage in human neuromyelitis optica.

  19. Location and Density of Immune Cells in Precursor Lesions and Cervical Cancer.

    PubMed

    Bedoya, Astrid M; Jaramillo, Roberto; Baena, Armando; Castaño, Jorge; Olaya, Natalia; Zea, Arnold H; Herrero, Rolando; Sanchez, Gloria I

    2013-04-01

    Only a small proportion of women infected with Human Papillomavirus (HPV) develop cervical cancer. Host immune response seems to play a role eliminating the viral infection and preventing progression to cancer. Characterization of tumor infiltrating lymphocytes (TILs) in cervical pre-neoplastic lesions and cervical cancer may be helpful to understand the mechanisms that mediate this protection. The aim of this study was to determine if there are differences in the localization and density (cells/mm(2)) of CD8+ T-cells, CD4+ T-cells and Tregs (CD25 + Foxp3+) in cervical pre-neoplastic lesions and cervical cancer. Immunohistochemical analysis of sections of 96 (26 CIN1, 21 CIN2, 25 CIN3, and 24 SCC) samples revealed that regardless of CIN grades, CD8+ T-cells are more abundant than CD4+, CD25+ and Foxp3+ cells in both the stroma and epithelium. There was a higher density of CD8+ cells in the stroma of cervical cancer compared to CIN3 (OR = 4.20, 95% CI 1.2-15), CIN2 (OR = 7.86, 95% CI 1.7-36.4) and CIN1 (OR = 4.25, 95% CI 1.1-17). Studies evaluating whether these cells are recruited before or after cancer progression will be helpful to understand the role of these cells in the natural history of HPV-induced lesions.

  20. Lethal (2) giant larvae: an indispensable regulator of cell polarity and cancer development.

    PubMed

    Cao, Fang; Miao, Yi; Xu, Kedong; Liu, Peijun

    2015-01-01

    Cell polarity is one of the most basic properties of all normal cells and is essential for regulating numerous biological processes. Loss of polarity is considered a hallmark for cancer. Multiple polarity proteins are implicated in maintenance of cell polarity. Lethal (2) giant larvae (Lgl) is one of polarity proteins that plays an important role in regulating cell polarity, asymmetric division as well as tumorigenesis. Lgl proteins in different species have similar structures and conserved functions. Lgl acts as an indispensable regulator of cell biological function, including cell polarity and asymmetric division, through interplaying with other polarity proteins, regulating exocytosis, mediating cytoskeleton and being involved in signaling pathways. Furthermore, Lgl plays a role of a tumor suppressor, and the aberrant expression of Hugl, a human homologue of Lgl, contributes to multiple cancers. However, the exact functions of Lgl and the underlying mechanisms remain enigmatic. In this review, we will give an overview of the Lgl functions in cell polarity and cancer development, discuss the potential mechanisms underlying these functions, and raise our conclusion of previous studies and points of view about the future studies.

  1. Multisystem Langerhans Cell Histiocytosis in Adults Revealed by Skin Lesions.

    PubMed

    Atarguine, Hanane; Hocar, Ouafa; Oussmane, Samia; Mouafik, Sara Batoul; Hamdaoui, Abderrachid; Hafiane, Hanan; Belbaraka, Rhizlane; Akhdari, Nadia; Amal, Said

    2016-01-01

    A 37-year-old woman with no remarkable medical or family history presented with papules and vesicles on an erythematous background involving the neck, sacrum, and folds (postauricular, axillary, inguinal, and under the breasts) (Figure 1). During the previous year, she was treated with local and systemic antifungals without improvement. Her history included a secondary amenorrhea, polydipsia, and polyuria (6 L/d) that started 2 years prior. Physical examination revealed chronic bilateral purulent otorrhea with thick eardrums. Histologic examination of skin biopsy revealed a highly suggestive appearance of multisystem Langerhans cell histiocytosis (LCH) with immunohistochemistry (anti-PS100 and anti-CD1a), which were positive (Figure 2A and 2B). Pituitary magnetic resonance imaging showed a thickening of the pituitary stalk in relation to a location histiocytic (Figure 3). Bone gaps were objectified on two radiographic tibial diaphyseal. Results from computed tomography (CT) scan showed a magma coelio mesenteric, axillary, and inguinal lymph nodes. PMID:27319965

  2. Differentiation of trophoblast stem cells into giant cells is triggered by p57/Kip2 inhibition of CDK1 activity

    PubMed Central

    Ullah, Zakir; Kohn, Matthew J.; Yagi, Rieko; Vassilev, Lyubomir T.; DePamphilis, Melvin L.

    2008-01-01

    Genome endoreduplication during mammalian development is a rare event for which the mechanism is unknown. It first appears when fibroblast growth factor 4 (FGF4) deprivation induces differentiation of trophoblast stem (TS) cells into the nonproliferating trophoblast giant (TG) cells required for embryo implantation. Here we show that RO3306 inhibition of cyclin-dependent protein kinase 1 (CDK1), the enzyme required to enter mitosis, induced differentiation of TS cells into TG cells. In contrast, RO3306 induced abortive endoreduplication and apoptosis in embryonic stem cells, revealing that inactivation of CDK1 triggers endoreduplication only in cells programmed to differentiate into polyploid cells. Similarly, FGF4 deprivation resulted in CDK1 inhibition by overexpressing two CDK-specific inhibitors, p57/KIP2 and p21/CIP1. TS cell mutants revealed that p57 was required to trigger endoreduplication by inhibiting CDK1, while p21 suppressed expression of the checkpoint protein kinase CHK1, thereby preventing induction of apoptosis. Furthermore, Cdk2−/− TS cells revealed that CDK2 is required for endoreduplication when CDK1 is inhibited. Expression of p57 in TG cells was restricted to G-phase nuclei to allow CDK activation of S phase. Thus, endoreduplication in TS cells is triggered by p57 inhibition of CDK1 with concomitant suppression of the DNA damage response by p21. PMID:18981479

  3. Inactivation of the MAPK signaling pathway by Listeria monocytogenes infection promotes trophoblast giant cell death

    PubMed Central

    Hashino, Masanori; Tachibana, Masato; Nishida, Takashi; Hara, Hideki; Tsuchiya, Kohsuke; Mitsuyama, Masao; Watanabe, Kenta; Shimizu, Takashi; Watarai, Masahisa

    2015-01-01

    Listeria monocytogenes has a well-characterized ability to cross the placental barrier, resulting in spontaneous abortion and fetal infections. However, the mechanisms resulting in infection-associated abortion are not fully understood. In this study, we demonstrate that the dephosphorylation of MAPK family proteins caused by L. monocytogenes infection of trophoblast giant (TG) cells, which are placental immune cells, contributes to infectious abortion. Dephosphorylation of c-Jun, p38, and ERK1/2 was observed in infected TG cells, causing the downregulation of cytoprotective heme oxygenase (HO)-1. Blocking the dephosphorylation of proteins, including MAPK family proteins, inhibited the decrease in HO-1 expression. Treatment with MAPK inhibitors inhibited bacterial internalization into TG cells. Moreover, Toll-like receptor 2 involved in the expression of MAPK family proteins. Infection with a listeriolysin O-deleted mutant impaired dephosphorylation of MAPK family proteins in TG cells and did not induce infectious abortion in a mouse model. These results suggest that inactivation of the MAPK pathway by L. monocytogenes induces TG cell death and causes infectious abortion. PMID:26528279

  4. Distribution and immunophenotype of the inflammatory cell population in the benign lymphoepithelial lesion (Mikulicz's disease).

    PubMed

    Andrade, R E; Hagen, K A; Manivel, J C

    1988-08-01

    Benign lymphoepithelial lesion (BLL) is an autoimmune process characterized by swelling and diffuse inflammation of the major salivary glands. Autoantibodies have been isolated from lymphocyte cultures obtained from affected salivary glands, but the pathogenesis is still unknown. Previous studies have shown that the predominant population of inflammatory cells is represented by helper T cells, with only brief mention of the B cell population. Twenty-five surgical specimens from patients with BLL were studied immunohistochemically. Antisera used included monoclonal antibodies LN-1 and LN-2 for B cells, LN-3 for cells expressing human leukocyte antigen-DR (HLA-DR) antigens, UCHL-1 for T cells, Leu-7 for natural killer (NK) cells, and T suppressor lymphocytes and the polyclonal antibody to S100 protein for dendritic cells. A peculiar distribution of the inflammatory infiltrate was observed in all cases, characterized by the presence of very irregular "germinal centers" with pseudopod-like extensions surrounding epimyoepithelial islands. Lymphoid cells in this location were reactive with LN-1 and LN-2 antibodies. These structures were surrounded by a "mantle" of mixed small B and T lymphocytes. A well-defined "interfollicular" zone was composed of cells strongly reactive with UCHL-1 and LN-3 antibodies, indicating the presence and activation of T cells. Dendritic cells defined by S100 and LN-2 reactivity were intermixed with epimyoepithelial cells, and were identified in 18 cases. Epithelial expression of HLA-DR antigens was restricted to inflamed areas. In contrast to previous reports denying the presence of Leu-7-positive cells in these lesions, cells reactive for this antibody were identified in 13 of 20 cases, predominantly within germinal centers. The presence of dendritic cells, complex organization of the inflammatory infiltrate into well-defined B cell proliferation centers and activated interfollicular T areas, and the abnormal expression of HLA-DR antigens in

  5. Systemic therapy for selected skull base sarcomas: Chondrosarcoma, chordoma, giant cell tumour and solitary fibrous tumour/hemangiopericytoma.

    PubMed

    Colia, Vittoria; Provenzano, Salvatore; Hindi, Nadia; Casali, Paolo G; Stacchiotti, Silvia

    2016-01-01

    This review highlights the data currently available on the activity of systemic therapy in chondrosarcoma, chordoma, giant cell tumour of the bone (GCTB) and solitary fibrous tumour, i.e., four rare sarcomas amongst mesenchymal malignancy arising from the skull base.

  6. Metacarpal resection with a contoured iliac bone graft and silicone rubber implant for metacarpal giant cell tumor: a case report.

    PubMed

    Carlow, S B; Khuri, S M

    1985-03-01

    A definitive surgical procedure for a giant cell tumor that combines metacarpal resection with an iliac bone graft and arthroplasty with a silicone rubber implant is proposed for the elderly patient. The results were encouraging in one patient who had a cosmetically and functionally acceptable hand and no evidence of recurrence.

  7. Systemic therapy for selected skull base sarcomas: Chondrosarcoma, chordoma, giant cell tumour and solitary fibrous tumour/hemangiopericytoma.

    PubMed

    Colia, Vittoria; Provenzano, Salvatore; Hindi, Nadia; Casali, Paolo G; Stacchiotti, Silvia

    2016-01-01

    This review highlights the data currently available on the activity of systemic therapy in chondrosarcoma, chordoma, giant cell tumour of the bone (GCTB) and solitary fibrous tumour, i.e., four rare sarcomas amongst mesenchymal malignancy arising from the skull base. PMID:27330421

  8. Surgical treatment of multifocal giant cell tumor of carpal bones with preservation of wrist function: case report.

    PubMed

    Tarng, Yih-Wen; Yang, Shan-Wei; Hsu, Chien-Jen

    2009-02-01

    We report a rare case of multifocal giant cell tumor of bone involving the trapezium, trapezoid, capitate, and scaphoid with soft tissue extension. Following intralesional resection, an autogenous corticocancellous iliac crest bone graft was used to fill the resultant defect and preserve carpal height and radiocarpal motion. Successful union with no recurrence was noted at 1-year follow-up.

  9. Giant cell interstitial pneumonia in a hard-metal worker. Cytologic, histologic and analytical electron microscopic investigation

    SciTech Connect

    Tabatowski, K.; Roggli, V.L.; Fulkerson, W.J.; Langley, R.L.; Benning, T.; Johnston, W.W.

    1988-03-01

    A case of biopsy-proven giant cell interstitial pneumonia in a patient with occupational exposure to hard-metal dust is reported. Bronchial washings performed several days prior to open-lung biopsy yielded an almost exclusive population of nonpigmented alveolar macrophages and pleomorphic, phagocytic multinucleated giant cells. Microorganisms, viral inclusions in the giant cells, epithelioid histiocytes and well-formed granulomas were not seen. This cytologic picture strongly suggests the presence of giant cell interstitial pneumonia in a patient with restrictive lung disease, particularly when exposure to hard-metal dust is known or suspected. A specific diagnosis early in the course of the disease may facilitate removal of the individual from the workplace and forestall the development of end-stage interstitial fibrosis. Additionally, the working environment may be modified to minimize inhalational exposure. Recognition of this entity by the cytopathologist may direct diagnostic efforts toward accurate histologic evaluation and the identification of particulates by microprobe analysis of either cellular or biopsy material.

  10. Impaired Head Direction Cell Representation in the Anterodorsal Thalamus after Lesions of the Retrosplenial Cortex

    PubMed Central

    Clark, Benjamin J.; Bassett, Joshua P.; Wang, Sarah S.; Taube, Jeffrey S.

    2010-01-01

    The retrosplenial cortex (RSP), a brain region frequently linked to processes of spatial navigation, contains neurons that discharge as a function of a rat’s head direction (HD). HD cells have been identified throughout the limbic system including the anterodorsal thalamus (ADN) and postsubiculum (PoS), both of which are reciprocally connected to the RSP. The functional relationship between HD cells in the RSP and those found in other limbic regions is presently unknown, but given the intimate connectivity between the RSP and regions such as the ADN and PoS, and the reported loss of spatial orientation in rodents and humans with RSP damage, it is likely that the RSP plays an important role in processing the limbic HD signal. To test this hypothesis, we produced neurotoxic or electrolytic lesions of the RSP and recorded HD cells in the ADN of female Long-Evans rats. HD cells remained present in the ADN after RSP lesions, but the stability of their preferred firing directions was significantly reduced even in the presence of a salient visual landmark. Subsequent tests revealed that lesions of the RSP moderately impaired landmark control over the cells’ preferred firing directions, but spared the cells directional stability when animals were required to update their orientation using self-movement cues. Taken together, these results suggest that the RSP plays a prominent role in processing landmark information for accurate HD cell orientation and may explain the poor directional sense in humans that follows damage to the RSP. PMID:20392951

  11. Introducing micrometer-sized artificial objects into live cells: a method for cell-giant unilamellar vesicle electrofusion.

    PubMed

    Saito, Akira C; Ogura, Toshihiko; Fujiwara, Kei; Murata, Satoshi; Nomura, Shin-ichiro M

    2014-01-01

    Here, we report a method for introducing large objects of up to a micrometer in diameter into cultured mammalian cells by electrofusion of giant unilamellar vesicles. We prepared GUVs containing various artificial objects using a water-in-oil (w/o) emulsion centrifugation method. GUVs and dispersed HeLa cells were exposed to an alternating current (AC) field to induce a linear cell-GUV alignment, and then a direct current (DC) pulse was applied to facilitate transient electrofusion. With uniformly sized fluorescent beads as size indexes, we successfully and efficiently introduced beads of 1 µm in diameter into living cells along with a plasmid mammalian expression vector. Our electrofusion did not affect cell viability. After the electrofusion, cells proliferated normally until confluence was reached, and the introduced fluorescent beads were inherited during cell division. Analysis by both confocal microscopy and flow cytometry supported these findings. As an alternative approach, we also introduced a designed nanostructure (DNA origami) into live cells. The results we report here represent a milestone for designing artificial symbiosis of functionally active objects (such as micro-machines) in living cells. Moreover, our technique can be used for drug delivery, tissue engineering, and cell manipulation.

  12. The role of cyclic nucleotides in modulation of the membrane potential of the Schwann cell of squid giant nerve fibre.

    PubMed Central

    Evans, P D; Reale, V; Villegas, J

    1985-01-01

    The role of cyclic nucleotides in mediating the effects of nicotine cholinergic receptors has been investigated in Schwann cells of the giant nerve fibre of the squid. Elevation of cyclic AMP levels in this preparation by means of the phosphodiesterase inhibitor, theophylline, by the diterpene adenylate cyclase activator, forskolin, and by cyclic nucleotide analogues mimics the action of activating the nicotinic cholinergic receptors in producing a long-lasting hyperpolarization of the membrane potential of the Schwann cell. Theophylline and forskolin also potentiate the effects of carbachol and of neural stimulation on the Schwann cell. The results suggest that the nicotinic receptor of the squid Schwann cell is likely to mediate its effects via a mechanism that activates adenylate cyclase. The results are discussed in terms of the role of cyclic AMP in the complex multistep interaction between the giant axon of the squid and its surrounding Schwann-cell layer. PMID:2991504

  13. The role of cyclic nucleotides in modulation of the membrane potential of the Schwann cell of squid giant nerve fibre.

    PubMed

    Evans, P D; Reale, V; Villegas, J

    1985-06-01

    The role of cyclic nucleotides in mediating the effects of nicotine cholinergic receptors has been investigated in Schwann cells of the giant nerve fibre of the squid. Elevation of cyclic AMP levels in this preparation by means of the phosphodiesterase inhibitor, theophylline, by the diterpene adenylate cyclase activator, forskolin, and by cyclic nucleotide analogues mimics the action of activating the nicotinic cholinergic receptors in producing a long-lasting hyperpolarization of the membrane potential of the Schwann cell. Theophylline and forskolin also potentiate the effects of carbachol and of neural stimulation on the Schwann cell. The results suggest that the nicotinic receptor of the squid Schwann cell is likely to mediate its effects via a mechanism that activates adenylate cyclase. The results are discussed in terms of the role of cyclic AMP in the complex multistep interaction between the giant axon of the squid and its surrounding Schwann-cell layer.

  14. Modern Interpretation of Giant Cell Tumor of Bone: Predominantly Osteoclastogenic Stromal Tumor

    PubMed Central

    Kim, Yuhree; Nizami, Saqib; Goto, Hana

    2012-01-01

    Owing to striking features of numerous multinucleated cells and bone destruction, giant cell tumor (GCT) of bone, often called as osteoclastoma, has drawn major attractions from orthopaedic surgeons, pathologists, and radiologists. The name GCT or osteoclastoma gives a false impression of a tumor comprising of proliferating osteoclasts or osteoclast precursors. The underlying mechanisms for excessive osteoclastogenesis are intriguing and GCT has served as an exciting disease model representing a paradigm of osteoclastogenesis for bone biologists. The modern interpretation of GCT is predominantly osteoclastogenic stromal cell tumors of mesenchymal origin. A diverse array of inflammatory cytokines and chemokines disrupts osteoblastic differentiation and promotes the formation of excessive multi-nucleated osteoclastic cells. Pro-osteoclastogenic cytokines such as receptor activator of nuclear factor kappa-B ligand (RANKL), interleukin (IL)-6, and tumor necrosis factor (TNF) as well as monocyte-recruiting chemokines such as stromal cell-derived factor-1 (SDF-1) and monocyte chemoattractant protein (MCP)-1 participate in unfavorable osteoclastogenesis and bone destruction. This model represents a self-sufficient osteoclastogenic paracrine loop in a localized area. Consistent with this paradigm, a recombinant RANK-Fc protein and bisphosphonates are currently being tried for GCT treatment in addition to surgical excision and conventional topical adjuvant therapies. PMID:22662295

  15. Cytoplasmic localization of p21 protects trophoblast giant cells from DNA damage induced apoptosis.

    PubMed

    de Renty, Christelle; DePamphilis, Melvin L; Ullah, Zakir

    2014-01-01

    Proliferating trophoblast stem cells (TSCs) can differentiate into nonproliferating but viable trophoblast giant cells (TGCs) that are resistant to DNA damage induced apoptosis. Differentiation is associated with selective up-regulation of the Cip/Kip cyclin-dependent kinase inhibitors p57 and p21; expression of p27 remains constant. Previous studies showed that p57 localizes to the nucleus in TGCs where it is essential for endoreplication. Here we show that p27 also remains localized to the nucleus during TSC differentiation where it complements the role of p57. Unexpectedly, p21 localized to the cytoplasm where it was maintained throughout both the G- and S-phases of endocycles, and where it prevented DNA damage induced apoptosis. This unusual status for a Cip/Kip protein was dependent on site-specific phosphorylation of p21 by the Akt1 kinase that is also up-regulated in TGCs. Although cytoplasmic p21 is widespread among cancer cells, among normal cells it has been observed only in monocytes. The fact that it also occurs in TGCs reveals that p57 and p21 serve nonredundant functions, and suggests that the role of p21 in suppressing apoptosis is restricted to terminally differentiated cells.

  16. The use of giant cell tumor conditioned media in cytogenetic studies of hematologic malignancies.

    PubMed

    Wason, D; Richkind, K E

    1992-07-15

    The use of conditioned media produced from solid tumor cell lines has been beneficial in the study of hematologic malignancies. Conditioned media from giant cell tumors (GCT), human lung adenocarcinoma, and human bladder carcinoma express growth factors that have been used to stimulate growth of bone marrow cells and improve the quality of the preparations. It has been reported that addition of Lu-CSF1-conditioned media from a lung adenocarcinoma cell line masks abnormalities in cases of acute leukemia [1.] Because we routinely use GCT-CM in bone marrow and leukemic blood cultures for chromosome analysis in our lab, we investigated this potential effect on our case analysis. We have performed a serial study of a 100 cases of hematologic malignancies received for analysis in our lab to determine the effect of the addition of GCT-CM to our culture media with respect to 1) mitotic index, 2) quality of preparation, and 3) differential selection of either chromosomally normal or abnormal cell lines. Our results indicate that the mitotic index and quality of metaphases is enhanced with the addition of GCT media and that there is no difference in the rate of abnormality detection with or without the addition of GCT media.

  17. Differentiation of focal intrahepatic lesions with 99mTc-red blood cell imaging

    SciTech Connect

    Engel, M.A.; Marks, D.S.; Sandler, M.A.; Shetty, P.

    1983-03-01

    The appearance of focal hepatic lesions on 99mTc-sulfur colloid images is nonspecific. As it is important to distinguish hemangiomas from other lesions prior to biopsy, a prospective study was performed using 99mTc-labeled red blood cells. Dynamic perfusion and delayed blood-pool images (1-2 hours) were obtained and lesion activity categorized as increased, equal, or decreased compared with the liver. Of 21 patients studied, 9 (43%) had one or more hepatic hemangiomas, and 8 of these 9 patients (89%) demonstrated increased blood-pool activity. The 12 nonhemangiomatous lesions consisted of 7 metastatic tumors, 2 hepatomas, 1 cirrhotic nodule, and 2 hepatic cysts. None of these 12 patients had increased activity on delayed blood-pool images. Early dynamic images of hepatic hemangiomas demonstrated variable activity (vascularity) and were not useful in differentiating hemangiomas from other lesions. Sensitivity was 89% and specificity 100%. Although liver enzymes are usually normal with hepatic hemangiomas, they may also be normal in metastatic disease. The authors recommend that delayed blood-pool imaging be performed prior to biopsy, particularly in patients without a known primary tumor or those with normal liver enzyme levels.

  18. Differentiation of focal intrahepatic lesions with /sup 99m/Tc-red blood cell imaging

    SciTech Connect

    Engel, M.A.; Marks, D.S.; Sandler, M.A.; Shetty, P.

    1983-03-01

    The appearance of focal hepatic lesions on /sup 99m/Tc-sulfur colloid images is nonspecific. As it is important to distinguish hemangiomas from other lesions prior to biopsy, a prospective study was performed using /sup 99m/Tc-labeled red blood cells. Dynamic perfusion and delayed blood-pool images (1-2 hours) were obtained and lesion activity categorized as increased, equal, or decreased compared with the liver. Of 21 patients studied, 9 (43%) had one or more hepatic hemangiomas, and 8 of these 9 patients (89%) demonstrated increased blood-pool activity. The 12 nonhemangiomatous lesions consisted of 7 metastatic tumors, 2 hepatomas, 1 cirrhotic nodule, and 2 hepatic cysts. None of these 12 patients had increased activity on delayed blood-pool images. Early dynamic images of hepatic hemangiomas demonstrated variable activity (vascularity) and were not useful in differentiating hemangiomas from other lesions. Sensitivity was 89% and specificity 100%. Although liver enzymes are usually normal with hepatic hemangiomas, they may also be normal in metastatic disease. The authors recommend that delayed blood-pool imaging be performed prior to biopsy, particularly in patients without a known primary tumor or those with normal liver enzyme levels.

  19. Denosumab for Treatment of a Recurrent Cervical Giant-Cell Tumor

    PubMed Central

    Kajiwara, Daisuke; Yonemoto, Tsukasa; Iwata, Shintaro; Ishii, Takeshi; Tsukanishi, Toshinori; Ohtori, Seiji; Yamazaki, Masashi; Okawa, Akihiko

    2016-01-01

    A 43-year-old male patient with C5 giant cell tumor (GCT) underwent tumor resection and anterior bone fusion of C4–C6. The tumor recurred locally 9 months after surgery with the patient complaining of neck and shoulder pain similar to his preoperative symptoms. Denosumab was administered and his pain disappeared after a two-month administration, with a sclerotic rim formation seen at the tumor site on computed tomography. He has been followed for 18 months with no evidence of tumor recurrence. Complete resection is generally recommended, but is not easy for many patients with cervical GCT because of the existence of neurovascular structures. Some patients suffer from recurrence and treatment becomes more difficult. As such, denosumab may be an efficacious option for treatment of recurrent GCT of the cervical spine, although long-term follow-up is required to monitor for presence or absence of recurrence. PMID:27340537

  20. Spinal giant cell tumor in tuberous sclerosis: Case report and review of the literature

    PubMed Central

    Fraioli, Mario Francesco; Lecce, Mario; Fraioli, Chiara; Paolo, Curatolo

    2013-01-01

    Background Patients affected by tuberous sclerosis (TS) have a greater incidence of tumors than the healthy population. Spinal tumours in TS are reported very rarely and consist mainly of sacrococcygeal and cervical chordomas. Method Case report. Findings A 21-year-old man, affected by TS, presented a spinal dorsal T2 tumor that caused medullary compression. He underwent decompressive laminectomy and microsurgical excision of a giant cell tumor and an associated aneurysmal bone cyst. Postoperative hypofractionated radiotherapy was performed on the surgical field. At 2.4 years of follow-up the patient reported total recovery of neurological deficits and was free from tumor recurrence. Conclusion Considering this association, which is the first reported in the literature, spinal magnetic resonance imaging with gadolinium should be performed at the onset of spinal pain in patients affected by TS. PMID:23809532

  1. Differentiating giant cell tumor of bone from patellofemoral syndrome: a case study.

    PubMed

    Bonar, Jason; Carr, Shannon Clutton; De Carvalho, Diana; Wunder, Jay S

    2016-03-01

    Balancing the assessment of musculoskeletal dysfunctions with a high level of suspicion for non-mechanical origins can be a challenge for the clinician examining a sports injury. Without timely diagnosis, non-mechanical complaints could result in surgery or loss of limb. This case describes the discovery of a Giant Cell Tumor of Bone (GCTB) following the re-evaluation of an athlete who had undergone five years of conservative management for patellofemoral pain syndrome (PFPS). Knee injuries account for 32.6% of sports injuries with PFPS being the most common and most likely diagnosis for anterior knee pain. GCTB is a benign aggressive bone tumor with a predilection for the juxta-articular region of the knee, comprising up to 23% of all benign bone tumors, and commonly occurs in the second to fourth decades. This case report illustrates the difficulty in accurately diagnosing healthy athletes, reviews common differentials for knee complaints and explores helpful diagnostic procedures. PMID:27069267

  2. Giant Cell Arteritis: An Atypical Presentation Diagnosed with the Use of MRI Imaging

    PubMed Central

    2016-01-01

    Giant cell arteritis (GCA) is the most common primary systemic vasculitis in western countries in individuals over the age of 50. It is typically characterised by the granulomatous involvement of large and medium sized blood vessels branching of the aorta with particular tendencies for involving the extracranial branches of the carotid artery. Generally the diagnosis is straightforward when characteristic symptoms such as headache, jaw claudication, or other ischemic complications are present. Atypical presentations of GCA without “overt” cranial ischemic manifestations have become increasingly recognised but we report for the first time a case of GCA presenting as mild upper abdominal pain and generalized weakness in the context of hyponatremia as the presenting manifestation of vasculitis that was subsequently diagnosed by MRI scanning. This case adds to the literature and emphasises the importance of MRI in the evaluation of GCA patients without “classic” cranial ischemic symptoms. PMID:27493825

  3. Subtotal tongue necrosis in delayed diagnosed giant-cell arteritis: a case report.

    PubMed

    Biebl, Matthias Oliver; Hugl, Beate; Posch, Lydia; Tzankov, Alexandar; Weber, Florian; Perkmann, Reinhold; Fraedrich, Gustav

    2004-01-01

    Giant-cell arteritis (GCA) is a chronic systemic vasculitis of large- and medium-sized vessels, mainly affecting elderly patients. Headache, vision impairment, jaw claudication, and scalp tenderness are common symptoms. However, diagnosis can be difficult because GCA can affect almost every vascular pathway and lead to a variety of possible manifestations. We report the case of a belated diagnosed GCA, resulting in nearly complete necrosis of the mobile part of the tongue, visual impairment, and neurologic as well as intestinal ischemic symptoms. Aggressive immunosuppressive treatment resolved the symptoms, but the patient remained severely morbid because of bilateral necrosis of the mobile part of the tongue. In any case of unclear ischemic symptoms in an elderly patient, one must keep GCA in mind as the possible culprit disease.

  4. Current status and unanswered questions on the use of Denosumab in giant cell tumor of bone.

    PubMed

    Gaston, Czar Louie; Grimer, Robert J; Parry, Michael; Stacchiotti, Silvia; Dei Tos, Angelo Paolo; Gelderblom, Hans; Ferrari, Stefano; Baldi, Giacomo G; Jones, Robin L; Chawla, Sant; Casali, Paolo; LeCesne, Axel; Blay, Jean-Yves; Dijkstra, Sander P D; Thomas, David M; Rutkowski, Piotr

    2016-01-01

    Denosumab is a monoclonal antibody to RANK ligand approved for use in giant cell tumour (GCT) of bone. Due to its efficacy, Denosumab is recommended as the first option in inoperable or metastatic GCT. Denosumab has also been used pre-operatively to downstage tumours with large soft tissue extension to allow for less morbid surgery. The role of Denosumab for conventional limb GCT of bone is yet to be defined. Further studies are required to determine whether local recurrence rates will be decreased with the adjuvant use of Denosumab along with surgery. The long term use and toxicity of this agent is unknown as is the proportion of patients with primary or secondary resistance. It is advised that complicated cases of GCT requiring Denosumab treatment should be referred and followed up at expert centres. Collaborative studies involving further clinical trials and rigorous data collection are strongly recommended to identify the optimum use of this drug. PMID:27651889

  5. GIANT CELL TUMOR IN THE PROXIMAL PHALANX WITH PULMONARY METASTASIS: CASE REPORT AND LITERATURE REVIEW

    PubMed Central

    de Medeiros, Frederico Carvalho; de Medeiros, Fernando Carvalho; de Campos Carvalho Lopes, Izabella; de Medeiros, Guilherme Carvalho; de Medeiros, Eduardo Carvalho

    2015-01-01

    This is a case report on a giant cell tumor (GCT) in the proximal phalanx of the third finger of the left hand, with pulmonary metastasis. The patient presented pain in the finger without any previous history of trauma. Clinical examination, radiographic imaging and magnetic resonance imaging were carried out. A histological evaluation was carried out from an incisional biopsy, taking the hypothesis of GCT. The patient underwent amputation of the finger and the diagnosis was confirmed by means of microscopy on the specimen. The patient was followed up because of the risk of lung metastasis, which was shown by radiographic examination and computed tomography on the chest, and thoracotomy was performed. Since then, there has been an improvement in the symptoms that had been reported preoperatively, and no local recurrence or new metastasis has been found. PMID:27027012

  6. AL amyloidosis with temporal artery involvement simulates giant-cell arteritis.

    PubMed

    Audemard, Alexandra; Boutemy, Jonathan; Galateau-Salle, Françoise; Macro, Margaret; Bienvenu, Boris

    2012-03-01

    Light-chain (AL) amyloidosis may present with features suggesting vasculitis, including giant-cell arteritis (GCA). We describe a case of an 80-year-old man, who initially presented with bilateral jaw claudication, bi-temporal headache and arthralgia, however a temporal-artery biopsy then revealed AL amyloidosis. A diagnosis of AL amyloidosis complicating multiple myelome simulates GCA and polymyalgia rheumatica was established. The patient was successfully treated with melphalan and dexamethasone: the free kappa light chains decreased, the patient's jaw claudication and headache disappeared. Then we discuss similarities between GCA and AL amyloidosis and potential confusion in diagnosis. We suggest that, in patients with clinical features of GCA without any temporal-artery typical findings, specimens are stained with Congo red, which then results in a different diagnosis and treatment.

  7. Spinal cord infarction in giant cell arteritis associated with scalp necrosis.

    PubMed

    Mustafa, Khader N; Hadidy, Azmy; Joudeh, Anwar; Obeidat, Fatima Nouri; Abdulfattah, Khalid W

    2015-02-01

    Spinal cord infarction is extremely rare in patients with giant cell arteritis (GCA). There are only four case reports in the literature. We describe a 65-year-old man who presented with sudden paraplegia and back pain of 4-days duration with sensory loss below the umbilicus and bilateral scalp necrosis. Magnetic resonance imaging finding was consistent with dorsal spinal cord infarction. Biopsy of the temporal artery confirmed the diagnosis of GCA. The patient was treated with high dose of corticosteroids, which resulted in healing of the scalp ulcerations in 3 weeks, but the paraplegia was irreversible. To our knowledge, this is the first report of spinal cord infarction and simultaneous occurrence of bilateral scalp necrosis in a histopathologically proven GCA. Although literature about spinal cord involvement in GCA is very limited, cord infarction is associated with high mortality and therapeutic challenges since little is understood regarding the pathogenesis that leads to infarction.

  8. Osmometrically determined characteristics of the cell membrane of squid and lobster giant axons.

    PubMed

    Freeman, A R; Reuben, J P; Brandt, P W; Grundfest, H

    1966-11-01

    Lobster and squid giant nerve fibers respond differently when subjected to osmotic challenges. The axons proper, as distinct from the total (fiber) complex formed by the axon and connective sheath, both behave as "fast" osmometers for changes in the concentration of NaCl, but the maximum degree of swelling in hyposmotic media is by about 60% in lobster and only by 20% in squid. The relative volume intercepts of the van't Hoff relation are about 0.2 for lobster and 0.4 for squid. The sheaths of both axons undergo only small, apparently passive changes in volume. Lobster axons are permeable to Cl, but squid axons are impermeable to this anion. Lobster axons are also permeable to glycerol. The implications of the data as to the nature of volume regulation of cells are discussed.

  9. Denosumab for Treatment of a Recurrent Cervical Giant-Cell Tumor.

    PubMed

    Kajiwara, Daisuke; Kamoda, Hiroto; Yonemoto, Tsukasa; Iwata, Shintaro; Ishii, Takeshi; Tsukanishi, Toshinori; Ohtori, Seiji; Yamazaki, Masashi; Okawa, Akihiko

    2016-06-01

    A 43-year-old male patient with C5 giant cell tumor (GCT) underwent tumor resection and anterior bone fusion of C4-C6. The tumor recurred locally 9 months after surgery with the patient complaining of neck and shoulder pain similar to his preoperative symptoms. Denosumab was administered and his pain disappeared after a two-month administration, with a sclerotic rim formation seen at the tumor site on computed tomography. He has been followed for 18 months with no evidence of tumor recurrence. Complete resection is generally recommended, but is not easy for many patients with cervical GCT because of the existence of neurovascular structures. Some patients suffer from recurrence and treatment becomes more difficult. As such, denosumab may be an efficacious option for treatment of recurrent GCT of the cervical spine, although long-term follow-up is required to monitor for presence or absence of recurrence. PMID:27340537

  10. Large vessel vasculitis without temporal artery involvement: isolated form of giant cell arteritis?

    PubMed

    Lambert, M; Weber, A; Boland, B; De Plaen, J F; Donckier, J

    1996-03-01

    Diffuse arterial involvement in giant cell arteritis (GCA) is well recognized. By contrast, GCA clinically isolated to large vessels without cephalic, rheumatologic or systemic symptoms represents a much rarer manifestation of the disease. We report the cases of 4 elderly women presenting with a diffuse and symptomatic occlusive disease without the typical signs of temporal arteritis, in whom biological, angiographic or pathological findings were suggestive of GCA. Medium to high dose oral corticosteroids were given to the 4 patients, in combination with various revascularization procedures, allowing a fair clinical response. Large vessel arteritis should be considered in elderly women with diffuse non-atherosclerotic occlusive disease and elevated erythrocyte sedimentation rate, even if typical features of GCA are lacking. In those cases, a long-term treatment with corticosteroids is mandatory, but surgical or angioplastic revascularization is often required. PMID:8777852

  11. Differentiating giant cell tumor of bone from patellofemoral syndrome: a case study

    PubMed Central

    Bonar, Jason; Carr, Shannon Clutton; De Carvalho, Diana; Wunder, Jay S.

    2016-01-01

    Balancing the assessment of musculoskeletal dysfunctions with a high level of suspicion for non-mechanical origins can be a challenge for the clinician examining a sports injury. Without timely diagnosis, non-mechanical complaints could result in surgery or loss of limb. This case describes the discovery of a Giant Cell Tumor of Bone (GCTB) following the re-evaluation of an athlete who had undergone five years of conservative management for patellofemoral pain syndrome (PFPS). Knee injuries account for 32.6% of sports injuries with PFPS being the most common and most likely diagnosis for anterior knee pain. GCTB is a benign aggressive bone tumor with a predilection for the juxta-articular region of the knee, comprising up to 23% of all benign bone tumors, and commonly occurs in the second to fourth decades. This case report illustrates the difficulty in accurately diagnosing healthy athletes, reviews common differentials for knee complaints and explores helpful diagnostic procedures. PMID:27069267

  12. Giant cell myocarditis: a life-threatening disorder heralded by orbital myositis.

    PubMed

    Ali, Muhammad Sajawal; Mba, Benjamin I; Husain, Aliya Noor; Ciftci, Farah Diba

    2016-01-01

    A 40-year-old man with a history of orbital myositis (OM) presented to the emergency department with ventricular tachycardia requiring electrical cardioversion. Postcardioversion ECG showed right bundle branch block, while an echocardiogram revealed an ejection fraction of 20% and a dilated right ventricle. Cardiac MRI produced suboptimal images because the patient was having frequent arrhythmias. The rest of the work up, including coronary angiography, was unremarkable. Given the dilated right ventricle, we suspected arrhythmogenic right ventricular cardiomyopathy and discharged the patient with an implantable cardioverter-defibrillator. 1 week later, he was readmitted with cardiogenic shock; endomyocardial biopsy revealed giant cell myocarditis (GCM). To the best of our knowledge, this is the seventh case report of GCM described in a patient with OM. We recommend that clinicians maintain a high degree of suspicion for GCM in patients with OM presenting with cardiac problems. PMID:27009192

  13. p63 as a prognostic marker for giant cell tumor of bone

    PubMed Central

    kakizaki, Hiroshi; Okada, Kyoji; Torigoe, Tomoaki; Kusumi, Tomomi

    2013-01-01

    Background and purpose Giant cell tumor of bone (GCT) is sometimes difficult to distinguish from other giant-cell-rich tumors such as chondroblastoma (CHB) and aneurysmal bone cyst (ABC). The usefulness of p63 as a diagnostic marker for GCT is controversial. While there have been no reports about p63 as a prognostic marker for local recurrence, various p63-positive rates in GCT have been reported. The purpose of this study was to investigate retrospectively whether p63 is useful as a diagnostic marker and/or a prognostic marker for local recurrence of GCT. Methods This study included 36 patients diagnosed with either GCT (n = 16), CHB (n = 9), ABC (n = 7), or non-ossifying fibroma (NOF) (n = 4). p63 immunostaining was performed for all specimens. The mean p63-positive rate was compared with the four diseases and between the recurrent and non-recurrent cases of GCT. Results Although the mean p63-positive rate for GCT (36.3%) was statistically higher than that of all other diseases examined (CHB: 15.2%; ABC: 5.8%; NOF: 3.4%), p63 was not specific for GCT. The mean p63-positive rate for recurrent GCT cases (73.6%) was statistically higher than that for non-recurrent cases (29.1%). Conclusion In the diagnosis of GCT, p63 is a useful but not a conclusive marker. However, p63 did appear to indicate the biological aggressiveness of GCT. Therefore, p63 may help surgeons to estimate the risk of recurrence after surgery and help them to choose the best treatment for each GCT case. PMID:23033898

  14. Selective Amplification of the Genome Surrounding Key Placental Genes in Trophoblast Giant Cells.

    PubMed

    Hannibal, Roberta L; Baker, Julie C

    2016-01-25

    While most cells maintain a diploid state, polyploid cells exist in many organisms and are particularly prevalent within the mammalian placenta [1], where they can generate more than 900 copies of the genome [2]. Polyploidy is thought to be an efficient method of increasing the content of the genome by avoiding the costly and slow process of cytokinesis [1, 3, 4]. Polyploidy can also affect gene regulation by amplifying a subset of genomic regions required for specific cellular function [1, 3, 4]. This mechanism is found in the fruit fly Drosophila melanogaster, where polyploid ovarian follicle cells amplify genomic regions containing chorion genes, which facilitate secretion of eggshell proteins [5]. Here, we report that genomic amplification also occurs in mammals at selective regions of the genome in parietal trophoblast giant cells (p-TGCs) of the mouse placenta. Using whole-genome sequencing (WGS) and digital droplet PCR (ddPCR) of mouse p-TGCs, we identified five amplified regions, each containing a gene family known to be involved in mammalian placentation: the prolactins (two clusters), serpins, cathepsins, and the natural killer (NK)/C-type lectin (CLEC) complex [6-12]. We report here the first description of amplification at selective genomic regions in mammals and present evidence that this is an important mode of genome regulation in placental TGCs.

  15. Proteins of morula-like cells in hemolymph of the giant clam, Tridacna derasa.

    PubMed

    Nakayama, K; Ishikura, M; Maruyama, T

    1997-10-01

    The morula-like cell, a hemocyte packed with many large (about 3 microns in diameter) electron-dense granules, is found only in the hemolymph of giant clams belonging to the Tridacnidae. To clarify the function of the morula-like cell, we investigated its proteins, especially those found in the large granules. Proteins with molecular weights of 64 kDa, 17 kDa and 7.4 kDa were found to be specific to this type of hemocyte. N-terminal amino acid sequence analysis revealed that the 17-kDa and 7.4-kDa proteins were novel proteins rich in aromatic amino acids. Rabbit polyclonal antibody against a synthetic peptide of the 7.4-kDa protein reacted not only with that protein but also with a larger molecular weight (about 16-kDa) protein in the morula-like cell. Examination of the N-terminal amino acid sequences showed that the 16-kDa protein is distinct from the 17-kDa protein, and Western blot analysis suggested that it is a precursor of the 7.4-kDa protein. The zooxanthellate portion of clam mantle and kidney contained proteins immunoreactive to the antibody, but the azooxanthellate portion of the mantle did not contain any immunoreactive protein. These results suggest that the morula-like cells interact with the zooxanthellae.

  16. Chemical and physical effects on the adhesion, maturation, and survival of monocytes, macrophages, and foreign body giant cells

    NASA Astrophysics Data System (ADS)

    Collier, Terry Odell, III

    Injury caused by biomedical device implantation initiates inflammatory and wound healing responses. Cells migrate to the site of injury to degrade bacteria and toxins, create new vasculature, and form new and repair injured tissue. Blood-proteins rapidly adsorb onto the implanted material surface and express adhesive ligands which mediate cell adhesion on the material surface. Monocyte-derived macrophages and multi-nucleated foreign body giant cells adhere to the surface and degrade the surface of the material. Due to the role of macrophage and foreign body giant cell on material biocompatibility and biostability, the effects of surface chemistry, surface topography and specific proteins on the maturation and survival of monocytes, macrophages and foreign body giant cells has been investigated. Novel molecularly designed materials were used to elucidate the dynamic interactions which occur between inflammatory cells, proteins and surfaces. The effect of protein and protein adhesion was investigated using adhesive protein depleted serum conditions on RGD-modified and silane modified surfaces. The effects of surface chemistry were investigated using temperature responsive surfaces of poly (N-isopropylacrylamide) and micropatterned surfaces of N-(2 aminoethyl)-3-aminopropyltrimethoxysilane regions on an interpenetrating polymer network of polyacrylamide and poly(ethylene glycol). The physical effects were investigated using polyimide scaffold materials and polyurethane materials with surface modifying end groups. The depletion of immunoglobulin G caused decreased levels of macrophage adhesion, foreign body giant cell formation and increased levels of apoptosis. The temporal nature of macrophage adhesion was observed with changing effectiveness of adherent cell detachment with time, which correlated to increased expression of beta1 integrin receptors on detached macrophages with time. The limited ability of the micropatterned surface, polyimide scaffold and surface

  17. B regulatory cells are increased in hypercholesterolaemic mice and protect from lesion development via IL-10.

    PubMed

    Strom, Asa C; Cross, Amanda J; Cole, Jennifer E; Blair, Paul A; Leib, Christoph; Goddard, Michael E; Rosser, Elizabeth C; Park, Inhye; Hultgårdh Nilsson, Anna; Nilsson, Jan; Mauri, Claudia; Monaco, Claudia

    2015-10-01

    Whilst innate B1-B cells are atheroprotective, adaptive B2-B cells are considered pro-atherogenic. Different subsets of B regulatory cells (B(reg)) have been described. In experimental arthritis and lupus-like disease, B(reg) are contained within the CD21(hi)CD23(hi)CD24(hi) B cell pool. The existence and role of B(reg) in vascular disease is not known. We sought to investigate the existence, identity and location of B(reg) in vascular disease. The representation of B2-B cell subsets in the spleens and lymph nodes (LNs) of Apolipoprotein E(-/-) (ApoE(-/-)) mice compared to controls was characterised by flow cytometry. Additionally, we utilised a model of neointima formation based on the placement of a perivascular collar around the carotid artery in ApoE(-/-) mice to ascertain whether B cells and B cell subsets confer protection against lesion development. Adoptive transfer of B cells was performed from wild type or genetically modified mice. We showed that CD21(hi)CD23(hi)CD24(hi) B cells are unexpectedly increased in the draining LNs of ApoE(-/-) mice. Adoptive transfer of LN-derived B2-B cells or purified CD21(hi)CD23(hi)CD24(hi) B cells to syngeneic mice reduced lesion size and inflammation without changing serum cholesterol levels. Follicular B2-B cells did not confer protection. IL-10 blockade or transfer of IL10-deficient B cells prevented LN-derived B cell-mediated protection. This is the first identification of a specific LN-derived B2-B(reg) subset that confers IL-10 mediated protection from neointima formation. This may open the way for immune modulatory approaches in cardiovascular disease.

  18. Huge undifferentiated carcinoma of the pancreas with osteoclast-like giant cells.

    PubMed

    Jo, Sungho

    2014-03-14

    Undifferentiated carcinoma of the pancreas with osteoclast-like giant cells (OGCs) is very rare, less than 1% of all pancreatic malignancies, and shows worse prognosis than that of invasive ductal adenocarcinoma of the pancreas. We present a case of en bloc resection for a huge undifferentiated carcinoma with OGCs that invaded the stomach and transverse mesocolon. A 67-year female was admitted for left upper quadrant pain and computed tomography demonstrated a mass occupying the lesser sac and abutting the stomach and pancreas. There were no distant metastases and the patient underwent subtotal pancreatectomy with splenectomy, total gastrectomy, and segmental resection of the transverse colon. Histopathological examination confirmed an 11 cm-sized undifferentiated carcinoma of the pancreas with OGCs. Immunohistochemical staining revealed reactivity with pan-cytokeratin in adenocarcinoma component, with vimentin in neoplastic multi-nucleated cells, with CD45/CD68 in OGCs, and with p53 in tumor cells, respectively. The patient had suffered from multiple bone metastases and survived 9 mo after surgery. This case supports the ductal epithelial origin of undifferentiated carcinoma with OGCs and early diagnosis could result in favorable surgical outcomes. Investigations on the surgical role and prognostic factors need to be warranted in this tumor.

  19. Squamous Cell Carcinoma Arising from an Oral Lichenoid Lesion: A Case Report

    PubMed Central

    Taghavi Zenouz, Ali; Mehdipour, Masoumeh; Attaran, Rana; Bahramian, Ayla; Emamverdi Zadeh, Paria

    2012-01-01

    Lichenoid reactions represent a family of lesions with different etiologic factors and a common clinical and histologic ap-pearance. Lichen planus is included with lichenoid reactions and is a relatively common chronic mucocutaneous disorder. The most important complication of lichenoid reactions is the possibility of malignant transformation. That is why it has been considered a precancerous condition. Although the malignant transformation rate varies widely in the literature, from 0.4 to 6.5 percent, in most studies it does not exceed 1%. The aim of this paper is to report a rare case of squamous cell car-cinoma (SCC) arising within an oral lichenoid lesion in a 17-year-old woman, where SCC is very uncommon. The patient did not have any risk factors and was healthy. The lesion was located on the border of the tongue. In view of thecommon occurrence of OLP (oral lichen planus) and the unresolved issues regarding its premalignant potential, this case report illus-trates the need for histologic confirmation and a close follow-up of clinical lesions with lichenoid features. PMID:22991632

  20. Enrichment of c-Met+ tumorigenic stromal cells of giant cell tumor of bone and targeting by cabozantinib.

    PubMed

    Liu, L; Aleksandrowicz, E; Fan, P; Schönsiegel, F; Zhang, Y; Sähr, H; Gladkich, J; Mattern, J; Depeweg, D; Lehner, B; Fellenberg, J; Herr, I

    2014-10-16

    Giant cell tumor of bone (GCTB) is a very rare tumor entity, which is little examined owing to the lack of established cell lines and mouse models and the restriction of available primary cell lines. The stromal cells of GCTB have been made responsible for the aggressive growth and metastasis, emphasizing the presence of a cancer stem cell population. To identify and target such tumor-initiating cells, stromal cells were isolated from eight freshly resected GCTB tissues. Tumorigenic properties were examined by colony and spheroid formation, differentiation, migration, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, immunohistochemistry, antibody protein array, Alu in situ hybridization, FACS analysis and xenotransplantation into fertilized chicken eggs and mice. A sub-population of the neoplastic stromal cells formed spheroids and colonies, differentiated to osteoblasts, migrated to wounded regions and expressed the metastasis marker CXC-chemokine receptor type 4, indicating self-renewal, invasion and differentiation potential. Compared with adherent-growing cells, markers for pluripotency, stemness and cancer progression, including the CSC surface marker c-Met, were enhanced in spheroidal cells. This c-Met-enriched sub-population formed xenograft tumors in fertilized chicken eggs and mice. Cabozantinib, an inhibitor of c-Met in phase II trials, eliminated CSC features with a higher therapeutic effect than standard chemotherapy. This study identifies a c-Met(+) tumorigenic sub-population within stromal GCTB cells and suggests the c-Met inhibitor cabozantinib as a new therapeutic option for targeted elimination of unresectable or recurrent GCTB.

  1. Differential expression of chemokines, chemokine receptors and proteinases by foreign body giant cells (FBGCs) and osteoclasts.

    PubMed

    Khan, Usman A; Hashimi, Saeed M; Khan, Shershah; Quan, Jingjing; Bakr, Mahmoud M; Forwood, Mark R; Morrison, Nigel M

    2014-07-01

    Osteoclasts and foreign body giant cells (FBGCs) are both derived from the fusion of macropahges. These cells are seen in close proximity during foreign body reactions, therefore it was assumed that they might interact with each other. The aim was to identify important genes that are expressed by osteoclasts and FBGCs which can be used to understand peri-implantitis and predict the relationship of these cells during foreign body reactions. Bone marrow macrophages (BMM) were treated with receptor activator of nuclear factor kappa B ligand (RANKL) to produce osteoclasts. Quantitative PCR (qPCR) was used to identify the genes that were expressed by osteoclasts and FBGCs compared to macrophage controls. TRAP staining was used to visualise the cells while gelatine zymography and western blots were used for protein expression. Tartrate-resistant acid phosphatase (TRAP), matrix metallo proteinase 9 (MMP9), nuclear factor of activated T cells 1 (NFATc1), cathepsin K (CTSK) and RANK were significantly lower in FBGCs compared to osteoclasts. Inflammation specific chemokines such as monocyte chemotactic protein (MCP1 also called CCL2), macrophage inflammatory protein 1 alpha (MIP1α), MIP1β and MIP1γ, and their receptors CCR1, CCR3 and CCR5, were highly expressed by FBGCs. FBGCs were negative for osteoclast specific markers (RANK, NFATc1, CTSK). FBGCs expressed chemokines such as CCL2, 3, 5 and 9 while osteoclasts expressed the receptors for these chemokines i.e. CCR1, 2 and 3. Our findings show that osteoclast specific genes are not expressed by FBGCs and that FBGCs interact with osteoclasts during foreign body reaction through chemokines.

  2. Regulable neural progenitor-specific Tsc1 loss yields giant cells with organellar dysfunction in a model of tuberous sclerosis complex.

    PubMed

    Goto, June; Talos, Delia M; Klein, Peter; Qin, Wei; Chekaluk, Yvonne I; Anderl, Stefanie; Malinowska, Izabela A; Di Nardo, Alessia; Bronson, Roderick T; Chan, Jennifer A; Vinters, Harry V; Kernie, Steven G; Jensen, Frances E; Sahin, Mustafa; Kwiatkowski, David J

    2011-11-01

    Tuberous sclerosis complex (TSC) is a multiorgan genetic disease in which brain involvement causes epilepsy, intellectual disability, and autism. The hallmark pathological finding in TSC is the cerebral cortical tuber and its unique constituent, giant cells. However, an animal model that replicates giant cells has not yet been described. Here, we report that mosaic induction of Tsc1 loss in neural progenitor cells in Tsc1(cc) Nestin-rtTA(+) TetOp-cre(+) embryos by doxycycline leads to multiple neurological symptoms, including severe epilepsy and premature death. Strikingly, Tsc1-null neural progenitor cells develop into highly enlarged giant cells with enlarged vacuoles. We found that the vacuolated giant cells had multiple signs of organelle dysfunction, including markedly increased mitochondria, aberrant lysosomes, and elevated cellular stress. We found similar vacuolated giant cells in human tuber specimens. Postnatal rapamycin treatment completely reversed these phenotypes and rescued the mutants from epilepsy and premature death, despite prenatal onset of Tsc1 loss and mTOR complex 1 activation in the developing brain. This TSC brain model provides insights into the pathogenesis and organelle dysfunction of giant cells, as well as epilepsy control in patients with TSC.

  3. The Foreign Body Giant Cell Cannot Resorb Bone, But Dissolves Hydroxyapatite Like Osteoclasts

    PubMed Central

    ten Harkel, Bas; Schoenmaker, Ton; Picavet, Daisy I.; Davison, Noel L.; de Vries, Teun J.; Everts, Vincent

    2015-01-01

    Foreign body multinucleated giant cells (FBGCs) and osteoclasts share several characteristics, like a common myeloid precursor cell, multinuclearity, expression of tartrate-resistant acid phosphatase (TRAcP) and dendritic cell-specific transmembrane protein (DC-STAMP). However, there is an important difference: osteoclasts form and reside in the vicinity of bone, while FBGCs form only under pathological conditions or at the surface of foreign materials, like medical implants. Despite similarities, an important distinction between these cell types is that osteoclasts can resorb bone, but it is unknown whether FBGCs are capable of such an activity. To investigate this, we differentiated FBGCs and osteoclasts in vitro from their common CD14+ monocyte precursor cells, using different sets of cytokines. Both cell types were cultured on bovine bone slices and analyzed for typical osteoclast features, such as bone resorption, presence of actin rings, formation of a ruffled border, and characteristic gene expression over time. Additionally, both cell types were cultured on a biomimetic hydroxyapatite coating to discriminate between bone resorption and mineral dissolution independent of organic matrix proteolysis. Both cell types differentiated into multinucleated cells on bone, but FBGCs were larger and had a higher number of nuclei compared to osteoclasts. FBGCs were not able to resorb bone, yet they were able to dissolve the mineral fraction of bone at the surface. Remarkably, FBGCs also expressed actin rings, podosome belts and sealing zones—cytoskeletal organization that is considered to be osteoclast-specific. However, they did not form a ruffled border. At the gene expression level, FBGCs and osteoclasts expressed similar levels of mRNAs that are associated with the dissolution of mineral (e.g., anion exchange protein 2 (AE2), carbonic anhydrase 2 (CAII), chloride channel 7 (CIC7), and vacuolar-type H+-ATPase (v-ATPase)), in contrast the matrix degrading enzyme

  4. PTPN22 R620W minor allele is a genetic risk factor for giant cell arteritis

    PubMed Central

    Lester, Susan; Hewitt, Alex W; Ruediger, Carlee D; Bradbury, Linda; De Smit, Elisabeth; Wiese, Michael D; Black, Rachel; Harrison, Andrew; Jones, Graeme; Littlejohn, Geoffrey O; Merriman, Tony R; Shenstone, Bain; Smith, Malcolm D; Rischmueller, Maureen; Brown, Matthew A; Hill, Catherine L

    2016-01-01

    Giant cell arteritis (GCA) is one of the commonest forms of vasculitis in the elderly, and may result in blindness and stroke. The pathogenesis of GCA is not understood, although environmental, infectious and genetic risk factors are implicated. One gene of interest is PTPN22, encoding lymphoid protein tyrosine phosphatase (Lyp), expressed exclusively in immune cells, which is proposed to be an ‘archetypal non-HLA autoimmunity gene’. The minor allele of a functional PTPN22 single nucleotide polymorphism (rs2476601, R620W), which disrupts an interaction motif in the protein, was originally reported to be associated with biopsy-proven GCA in Spanish patients, with supporting data from three replicate Northern European studies. Recently, this observation was extended with additional patients and controls, and studies encompassing European, Scandinavian, UK and American patients. The aim of our study was to determine the association between PTPN22 rs2476601 (R620W) and biopsy-proven GCA in an Australian case cohort. PMID:27110387

  5. Solid variant of aneurysmal bone cyst presenting as a giant cervical mass: A clinical, radiological, histopathological dilemma

    PubMed Central

    Savardekar, Amey R.; Patra, Deviprasad; Chatterjee, Debajyoti; Ahuja, Chirag K.; Salunke, Pravin

    2015-01-01

    Background: Typical aneurysmal bone cysts (ABCs) are osteolytic, multicystic lesions with parietal sclerosis and blood-filled cysts. In rare instances, the cystic components may be completely absent. Such solid variants in ABC (s-ABC) exhibit a solid architecture; making the clinical, radiological, and histological differentiation from other solid bone tumors like osteosarcoma (especially giant cell rich osteosarcoma) and giant cell tumor, a difficult task. Case Report: We report the case of a 45–year-old male presenting with a giant solid cervical spine lesion. Histopathology revealed solid variant of ABC, even though the radiological and fine needle aspiration cytology studies pointed toward a giant cell tumor. Conclusion: We aim to discuss the clinical, radiological, and histological findings of solid ABC (a rare benign entity) vis-à-vis the common neoplastic entities of osteosarcoma and giant cell tumor. The histopathological nuisances in making the diagnosis of s-ABC are put forth, along with its impact on management of such giant bony spinal lesions. PMID:26005581

  6. The path of anti-tuberculosis drugs: from blood to lesions to mycobacterial cells

    PubMed Central

    Dartois, Véronique

    2015-01-01

    For the successful treatment of pulmonary tuberculosis, drugs need to penetrate complex lung lesions and permeate the mycobacterial cell wall in order to reach their intracellular targets. However, most currently used anti-tuberculosis drugs were introduced into clinical use without considering the pharmacokinetic and pharmacodynamic properties that influence drug distribution, and this has contributed to the long duration and limited success of current therapies. In this Progress article, I describe new methods to quantify and image drug distribution in infected lung tissue and in mycobacterial cells, and I explore how this technology could be used to design optimized multidrug regimens. PMID:24487820

  7. Co-expression of metalloproteinases 11 and 12 in cervical scrapes cells from cervical precursor lesions

    PubMed Central

    Valdivia, Alejandra; Peralta, Raúl; Matute-González, Manuel; García Cebada, Juan Manuel; Casasola, Ivonne; Jiménez-Medrano, Cristina; Aguado-Pérez, Rogelio; Villegas, Vanessa; González-Bonilla, Cesar; Manuel-Apolinar, Leticia; Ibáñez, Miguel; Salcedo, Mauricio

    2011-01-01

    The metalloproteinases (MMP) 11 and 12 have been shown to be expressed in cervical cancer (CC). In order to extend our previous results, these MMPs were evaluated in cervical precursor lesions. One hundred seventeen cervical scrapes: thirty-six normal, thirty-six Low grade squamous lesions (LSIL), thirty-six High grade (HSIL), nine CC; and, also ninety-nine paraffin-embedded cervical lesions: fifteen normal cervices, thirty eight LSIL, sixteen HSIL, and five CC were collected. The samples were analyzed for relative expression by real time RT-PCR or immunohistochemistry assay. We were able to identify a relative increased expression of MMP11 in 75% and 78% from LSIL and HSIL samples, respectively. While MMP12 expression was 64% and 75% in LSIL and HSIL, respectively. Positive samples for MMP11 expression were also positive for MMP12 expression and also increased according to illness progression. In the tissues, MMP11 or MMP12 expression was observed in the cytoplasm of the neoplastic cells, while in the normal epithelium was absent. The reaction was always stronger for MMP12 than MMP11. MMP11 expression was present in 77% and 66% of LSIL and HSIL, while MMP12 expression was 73% and 68%. There was a relationship between MMP11 or MMP12 expression and HPV infection. Our data are showing a relationship between diagnostic of precursor lesions and the MMP11 and 12 expressions, suggesting that their expression could be an early event in the neoplastic lesions of the cervix and could have clinical significance. PMID:22076168

  8. Co-expression of metalloproteinases 11 and 12 in cervical scrapes cells from cervical precursor lesions.

    PubMed

    Valdivia, Alejandra; Peralta, Raúl; Matute-González, Manuel; García Cebada, Juan Manuel; Casasola, Ivonne; Jiménez-Medrano, Cristina; Aguado-Pérez, Rogelio; Villegas, Vanessa; González-Bonilla, Cesar; Manuel-Apolinar, Leticia; Ibáñez, Miguel; Salcedo, Mauricio

    2011-01-01

    The metalloproteinases (MMP) 11 and 12 have been shown to be expressed in cervical cancer (CC). In order to extend our previous results, these MMPs were evaluated in cervical precursor lesions. One hundred seventeen cervical scrapes: thirty-six normal, thirty-six low grade squamous lesions (LSIL), thirty-six high grade (HSIL), nine CC; and, also ninety-nine paraffin-embedded cervical lesions: fifteen normal cervices, thirty eight LSIL, sixteen HSIL, and five CC were collected. The samples were analyzed for relative expression by real time RT-PCR or immunohistochemistry assay. We were able to identify a relative increased expression of MMP11 in 75% and 78% from LSIL and HSIL samples, respectively. While MMP12 expression was 64% and 75% in LSIL and HSIL, respectively. Positive samples for MMP11 expression were also positive for MMP12 expression and also increased according to illness progression. In the tissues, MMP11 or MMP12 expression was observed in the cytoplasm of the neoplastic cells, while in the normal epithelium was absent. The reaction was always stronger for MMP12 than MMP11. MMP11 expression was present in 77% and 66% of LSIL and HSIL, while MMP12 expression was 73% and 68%. There was a relationship between MMP11 or MMP12 expression and HPV infection. Our data are showing a relationship between diagnostic of precursor lesions and the MMP11 and 12 expressions, suggesting that their expression could be an early event in the neoplastic lesions of the cervix and could have clinical significance.

  9. Nuclear expression of Rac1 in cervical premalignant lesions and cervical cancer cells

    PubMed Central

    2012-01-01

    Background Abnormal expression of Rho-GTPases has been reported in several human cancers. However, the expression of these proteins in cervical cancer has been poorly investigated. In this study we analyzed the expression of the GTPases Rac1, RhoA, Cdc42, and the Rho-GEFs, Tiam1 and beta-Pix, in cervical pre-malignant lesions and cervical cancer cell lines. Methods Protein expression was analyzed by immunochemistry on 102 cervical paraffin-embedded biopsies: 20 without Squamous Intraepithelial Lesions (SIL), 51 Low- grade SIL, and 31 High-grade SIL; and in cervical cancer cell lines C33A and SiHa, and non-tumorigenic HaCat cells. Nuclear localization of Rac1 in HaCat, C33A and SiHa cells was assessed by cellular fractionation and Western blotting, in the presence or not of a chemical Rac1 inhibitor (NSC23766). Results Immunoreacivity for Rac1, RhoA, Tiam1 and beta-Pix was stronger in L-SIL and H-SIL, compared to samples without SIL, and it was significantly associated with the histological diagnosis. Nuclear expression of Rac1 was observed in 52.9% L-SIL and 48.4% H-SIL, but not in samples without SIL. Rac1 was found in the nucleus of C33A and SiHa cells but not in HaCat cells. Chemical inhibition of Rac1 resulted in reduced cell proliferation in HaCat, C33A and SiHa cells. Conclusion Rac1 is expressed in the nucleus of epithelial cells in SILs and cervical cancer cell lines, and chemical inhibition of Rac1 reduces cellular proliferation. Further studies are needed to better understand the role of Rho-GTPases in cervical cancer progression. PMID:22443139

  10. Giant repeater F-wave in patients with anterior horn cell disorders. Role of motor unit size.

    PubMed

    Ibrahim, I K; el-Abd, M A

    1997-01-01

    Conventional F-wave responses as well as single motor unit F-wave responses together with the volitionally recruited motor unit action potentials (MUAP) were studied in hand and feet muscles of 10 healthy subjects and 32 patients with anterior horn cell disorders. The amplitude of the largest F-wave (Fl) was significantly greater in the affected patients compared with healthy subjects. Giant repeater F-wave responses "up to 4 mV" were recorded in muscles having volitionally recruited giant MUAPs. Although, the group mean percentage of motor unit F-wave responses per stimulation in all tested orthodromic MUAPs was significantly decreased in amyotrophic lateral sclerosis patients, the group mean percentage of motor unit F-wave responses per stimulation in all tested orthodromic MUAPs that gave motor unit F-wave response was significantly increased compared with healthy subjects. The responding orthodromic MUAP gave identical motor unit F-wave response, even for complex polyphasic units. Enhanced monosynaptic (H-) reflex, proximal axon reflex (A-wave), and repetitive muscle response as possible explanations for the giant F-wave responses could be discounted. The electrophysiologic behavior of the giant late responses described here fits well with the criteria of F-waves modulated by newly formed distal (and or proximal) axonal branching.

  11. Iron porphyrinate Fe(TPPS) reduces brain cell damage in rats intrastriatally lesioned by quinolinate.

    PubMed

    González-Cortés, Carolina; Salinas-Lara, Citlaltepetl; Gómez-López, Marcos Artemio; Tena-Suck, Martha Lilia; Pérez-De La Cruz, Verónica; Rembao-Bojórquez, Daniel; Pedraza-Chaverrí, José; Gómez-Ruiz, Celedonio; Galván-Arzate, Sonia; Ali, Syed F; Santamaría, Abel

    2008-01-01

    It has been recently demonstrated that the reactive nitrogen species (RNS) peroxynitrite (ONOO(-)) is involved in the neurotoxic pattern produced by quinolinic acid in the rat brain [V. Pérez-De La Cruz, C. González-Cortés, S. Galván-Arzate, O.N. Medina-Campos, F. Pérez-Severiano, S.F. Ali, J. Pedraza-Chaverrí, A. Santamaría, Excitotoxic brain damage involves early peroxynitrite formation in a model of Huntington's disease in rats: protective role of iron porphyrinate 5,10,15,20-tetrakis (4-sulfonatophenyl)porphyrinate iron (III), Neuroscience 135 (2005) 463-474.]. The aim of this work was to investigate whether ONOO(-) can also be responsible for morphological alterations and inflammatory events in the same paradigm. For this purpose, we evaluated the effect of a pre-treatment with the iron porphyrinate Fe(TPPS), a well-known ONOO(-) decomposition catalyst (10 mg/kg, i.p., 120 min before lesion), on the quinolinate-induced striatal cell damage and immunoreactivities to glial-fibrilar acidic protein (GFAP), interleukin 6 (IL-6) and inducible nitric oxide synthase (iNOS), one and seven days after the intrastriatal infusion of quinolinate (240 nmol/microl) to rats. The striatal tissue from animals lesioned by quinolinate showed a significant degree of damage and enhanced immunoreactivities to GFAP, IL-6 and iNOS, both at 1 and 7 days post-lesion. Pre-treatment of rats with Fe(TPPS) significantly attenuated or prevented all these markers at both post-lesion times tested, except for GFAP immunoreactivity at 7 days post-lesion and iNOS immunoreactivity at 1 day post-lesion. Altogether, our results suggest that ONOO(-) is actively participating in triggering inflammatory events and morphological alterations in the toxic model produced by quinolinate, since the use of agents affecting its formation, such as Fe(TPPS), are effective experimental tools to reduce the brain lesions associated to excitotoxic and oxidative damage.

  12. 99mTc red blood cell scintigraphy in evaluating focal liver lesions

    SciTech Connect

    Rabinowitz, S.A.; McKusick, K.A.; Strauss, H.W.

    1984-07-01

    To determine the accuracy of blood-pool imaging in the diagnosis of hepatic hemangiomas, 39 patients with various focal hepatic lesions were studied. The diagnoses in these patients were made by biopsy, angiography, surgical exploration, or clinical stability for a minimum of 14 months. The diagnoses were: hemangiomas (13 patients), hepatoma (three), metastases (19), abscesses (two), and liver cysts (two). After modified in vivo labeling of red blood cells with 20 mCi (740 MBq) of 99mTc pertechnetate, an initial flow study and early (1-15 min) and delayed (1-2 hr) static images were obtained. Increased blood-pool activity with a discordant flow pattern was seen in 11 of 13 patients with hemangiomas. False-negative scans occurred in two hemangiomas with extensive fibrosis. Two of three hepatomas had increased blood-pool activity associated with increased flow in a pattern identical to the increased blood-pool activity. None of the metastatic, abscess, or cystic lesions had increased blood-pool activity at any time after injection. It is concluded that 99mTc red blood cell imaging can distinguish hemangiomas from other focal liver lesions.

  13. /sup 99m/Tc red blood cell scintigraphy in evaluating focal liver lesions

    SciTech Connect

    Rabinowitz, S.A.; McKusick, K.A.; Strauss, H.W.

    1984-07-01

    To determine the accuracy of blood-pool imaging in the diagnosis of hepatic hemangiomas, 39 patients with various focal hepatic lesions were studied. The diagnoses in these patients were made by biopsy, angiography, surgical exploration, or clinical stability for a minimum of 14 months. The diagnoses were: hemangiomas (13 patients), hepatoma (three), metastases (19), abscesses (two), and liver cysts (two). After modified in vivo labeling of red blood cells with 20 mCi (740 MBq) of /sup 99m/Tc pertechnetate, an initial flow study and early (1-15 min) and delayed (1-2 hr) static images were obtained. Increased blood-pool activity with a discordant flow pattern was seen in 11 of 13 patients with hemangiomas. False-negative scans occurred in two hemangiomas with extensive fibrosis. None of the metastatic, abscess, or cystic lesions had increased blood-pool activity at any time after injection. It is concluded that /sup 99m/Tc red blood cell imaging can distinguish hemangiomas from other focal liver lesions.

  14. Activated inflammatory T cells correlate with lesion size in human cutaneous leishmaniasis.

    PubMed

    Antonelli, Lis R V; Dutra, Walderez O; Almeida, Roque P; Bacellar, Olivia; Carvalho, Edgar M; Gollob, Kenneth J

    2005-11-15

    Leishmaniasis is an important parasitic disease affecting millions worldwide. In attempts to understand the clinical relevance of immunological measurements as determined using flow cytometry, several immunological phenotypes were determined for a group of well defined human leishmaniasis patients and correlated with clinical measurements of the disease (Montenegro skin test (MST) and lesion area). The analysis demonstrated a positive correlation between the MST size and the frequency of ex vivo recent activated CD4(+) T cells. In contrast, higher frequencies of recent activated CD8(+) T cells were correlated with a smaller MST size. Moreover, a positive correlation was observed between the lesion total area and the frequency of activated CD69(+) (ex vivo) and CD40L(+) (cultured with Leishmania soluble antigen (SLA)) T lymphocytes. Finally, larger lesions were also correlated with a higher frequency of SLA specific inflammatory cytokine (IFN-gamma or TNF-alpha) producing lymphocytes. These studies demonstrate that immunological markers are correlated with clinical indicators of human leishmaniasis and serve to better understand the evolution of this important parasitic disease.

  15. Human Embryonic Stem Cell Lines with Lesions in FOXP3 and NF1

    PubMed Central

    Zhu, Hui; Behr, Barry; Reddy, Vikrant V.; Hughes, Mark; Pan, Yuqiong; Baker, Julie

    2016-01-01

    Human embryonic stem cells (hESCs) are derived from the inner cell mass (ICM) of blastocyst staged embryos. Spare blastocyst staged embryos were obtained by in vitro fertilization (IVF) and donated for research purposes. hESCs carrying specific mutations can be used as a powerful cell system in modeling human genetic disorders. We obtained preimplantation genetic diagnosed (PGD) blastocyst staged embryos with genetic mutations that cause human disorders and derived hESCs from these embryos. We applied laser assisted micromanipulation to isolate the inner cell mass from the blastocysts and plated the ICM onto the mouse embryonic fibroblast cells. Two hESC lines with lesions in FOXP3 and NF1 were established. Both lines maintain a typical undifferentiated hESCs phenotype and present a normal karyotype. The two lines express a panel of pluripotency markers and have the potential to differentiate to the three germ layers in vitro and in vivo. The hESC lines with lesions in FOXP3 and NF1 are available for the scientific community and may serve as an important resource for research into these disease states. PMID:26990425

  16. Adhesion molecules on the endothelium and mononuclear cells in human atherosclerotic lesions.

    PubMed Central

    van der Wal, A. C.; Das, P. K.; Tigges, A. J.; Becker, A. E.

    1992-01-01

    Atherosclerotic lesions show features of a cell-mediated immune inflammatory process. From this viewpoint, the potential role of arterial endothelium in the recruitment of mononuclear cells (T lymphocytes and macrophages) was studied. The endothelium of diffuse intimal thickening (DIT) and atheromatous plaques (AP) in human coronary arteries and abdominal aortas was characterized for the expression of adhesion molecules ELAM-1, ICAM-1, and the major histocompatibility complex (MHC) class II antigens HLA-DR/DP. A marked increase in expression of ICAM-1 and ELAM-1, and to a lesser extent HLA-DR/DP was observed on endothelial cells that were adjacent to subendothelial infiltrates of T lymphocytes (CD3+, CD11a+, HLA-DR/DP+) and macrophages (CD14+, CD11a+, CD11c+, HLA-DR/DP+). This contrasted with a lower or absent expression of these activation markers at sites without prominent inflammatory cell infiltrates. These findings could be demonstrated in DIT as well as in AP. The observations suggest that cytokines produced by the subintimal infiltrates may activate the endothelium in a similar way as is observed in the microvasculature at sites of immune inflammation. The expression of these activation markers in the microvasculature is associated with enhanced leukocyte adhesion, permeability for macromolecules, and procoagulant activity, features known to occur also in early experimental atherosclerosis. The findings therefore support the concept that arterial endothelium plays an active role in the recruitment of mononuclear cells in atherosclerotic lesions. Images Figure 1 PMID:1281621

  17. Tenosynovial, Diffuse Type Giant Cell Tumor of the Temporomandibular Joint, Diagnosis and Management of a Rare Tumor

    PubMed Central

    Bredell, Marius; Schucknecht, Bernhard; Bode-Lesniewska, Baete

    2015-01-01

    The purpose of this paper was to describe a rare unusual case of primary mandibular condylar tenosynovial giant cell tumor of diffuse type with predominantly intraosseous growth and its management by resection and functional reconstruction with a vascularized costochondral graft. Clinical presentation was swelling in the right condylar area and limited mouth opening with radiological evidence of central bone destruction and magnetic resonance imaging showed central hemosiderin deposition. Fine needle aspiration did not lead to a diagnosis and an open biopsy had to be performed. Management consisted of tumor resection and reconstruction with a free vascularized costochondral graft. Tenosynovial diffuse type giant cell tumor of the temporomandibular joint is very rare. Complete resection leads to a low recurrence rate and reconstruction with a costochondral free vascularized flap leads to an excellent functional outcome. PMID:25699124

  18. Magnetic resonance imaging in the diagnosis and follow-up of giant cell arteritis: case report and review of literature

    PubMed Central

    Gračanin, Ana Gudelj; Ćurić, Josip; Lončarević, Jelena; Morović-Vergles, Jadranka

    2015-01-01

    A female patient with giant cell vasculitis of the abdominal aorta and its branches and strongly suspected of having extrapulmonary tuberculosis is presented. The diagnoses were based on the clinical picture, laboratory findings, and magnetic resonance imaging (MRI) findings. MRI is highly useful in cases where echosonography and/or vascular biopsy for histopathological analyses are not possible. A combination of giant cell vasculitis and extrapulmonary tuberculosis is extremely rare, and therefore, choosing the right treatment presents a considerable challenge. MRI performed after 6-month antituberculous therapy and 1-year glucocorticoid plus methotrexate therapy showed normal wall of the aorta and its branches, which was consistent with clinical and laboratory remission. Patients with large vessel vasculitis require regular follow-up by MRI.

  19. Development of poorly differentiated invasive squamous cell carcinoma in giant Bowen’s disease: a case report with dermatoscopy

    PubMed Central

    Akay, Bengu Nisa; Maden, Aysenur; Kocak, Oguzhan; Bostanci, Seher; Boyvat, Ayşe; Kocyigit, Pelin; Heper, Aylin Okcu

    2016-01-01

    Bowen’s disease (BD) is an in situ form of squamous cell carcinoma (SCC), often occurring in the chronically UV-damaged skin of elderly people. The risk of progression of BD to invasive SCC varies between 3% and 5%, and one-third of invasive tumors may metastasize. Herein we discuss the dermatoscopic findings of a case of giant Bowen’s disease, which progressed to poorly differentiated invasive SCC. PMID:27222765

  20. Description and Validation of Histological Patterns and Proposal of a Dynamic Model of Inflammatory Infiltration in Giant-cell Arteritis.

    PubMed

    Hernández-Rodríguez, José; Murgia, Giuseppe; Villar, Irama; Campo, Elías; Mackie, Sarah L; Chakrabarty, Aruna; Hensor, Elizabeth M A; Morgan, Ann W; Font, Carme; Prieto-González, Sergio; Espígol-Frigolé, Georgina; Grau, Josep M; Cid, Maria C

    2016-02-01

    The extent of inflammatory infiltrates in arteries from patients with giant-cell arteritis (GCA) have been described using different terms and definitions. Studies investigating the relationship between GCA histological features and clinical manifestations have produced controversial results. The aims of this study were to characterize and validate histological patterns in temporal artery biopsies (TABs) from GCA patients, to explore additional histological features, including the coexistence of different patterns, and also to investigate the relationship of the inflammatory patterns with clinical and laboratory features.We performed histological examination of TAB from patients with GCA consecutively diagnosed between 1992 and 2012. Patterns of inflammation were defined according to the extent and distribution of inflammatory infiltrates within the artery. Clinical and laboratory variables were recorded. Two external investigators underwent a focused, one-day training session and then independently scored 77 cases. Quadratic-weighted kappa was calculated.TAB from 285 patients (200 female/85 male) were evaluated. Four histological inflammatory patterns were distinguished: 1 - adventitial (n = 16); 2 - adventitial invasive: adventitial involvement with some extension to the muscular layer (n = 21); 3 - concentric bilayer: adventitial and intimal involvement with media layer preservation (n = 52); and 4 - panarteritic (n = 196). Skip lesions were observed in 10% and coexistence of various patterns in 43%. Raw agreement of each external scorer with the gold-standard was 82% and 77% (55% and 46% agreement expected from chance); kappa = 0.82 (95% confidence interval [CI] 0.70-0.95) and 0.79 (95% CI 0.68-0.91). Although abnormalities on temporal artery palpation and the presence of jaw claudication and scalp tenderness tended to occur more frequently in patients with arteries depicting more extensive inflammation, no statistically significant

  1. Description and Validation of Histological Patterns and Proposal of a Dynamic Model of Inflammatory Infiltration in Giant-cell Arteritis

    PubMed Central

    Hernández-Rodríguez, José; Murgia, Giuseppe; Villar, Irama; Campo, Elías; Mackie, Sarah L.; Chakrabarty, Aruna; Hensor, Elizabeth M.A.; Morgan, Ann W.; Font, Carme; Prieto-González, Sergio; Espígol-Frigolé, Georgina; Grau, Josep M.; Cid, Maria C.

    2016-01-01

    Abstract The extent of inflammatory infiltrates in arteries from patients with giant-cell arteritis (GCA) have been described using different terms and definitions. Studies investigating the relationship between GCA histological features and clinical manifestations have produced controversial results. The aims of this study were to characterize and validate histological patterns in temporal artery biopsies (TABs) from GCA patients, to explore additional histological features, including the coexistence of different patterns, and also to investigate the relationship of the inflammatory patterns with clinical and laboratory features. We performed histological examination of TAB from patients with GCA consecutively diagnosed between 1992 and 2012. Patterns of inflammation were defined according to the extent and distribution of inflammatory infiltrates within the artery. Clinical and laboratory variables were recorded. Two external investigators underwent a focused, one-day training session and then independently scored 77 cases. Quadratic-weighted kappa was calculated. TAB from 285 patients (200 female/85 male) were evaluated. Four histological inflammatory patterns were distinguished: 1 – adventitial (n = 16); 2 – adventitial invasive: adventitial involvement with some extension to the muscular layer (n = 21); 3 – concentric bilayer: adventitial and intimal involvement with media layer preservation (n = 52); and 4 – panarteritic (n = 196). Skip lesions were observed in 10% and coexistence of various patterns in 43%. Raw agreement of each external scorer with the gold-standard was 82% and 77% (55% and 46% agreement expected from chance); kappa = 0.82 (95% confidence interval [CI] 0.70–0.95) and 0.79 (95% CI 0.68–0.91). Although abnormalities on temporal artery palpation and the presence of jaw claudication and scalp tenderness tended to occur more frequently in patients with arteries depicting more extensive inflammation, no

  2. Histological lesions, cell cycle arrest, apoptosis and T cell subsets changes of spleen in chicken fed aflatoxin-contaminated corn.

    PubMed

    Peng, Xi; Zhang, Keying; Bai, Shiping; Ding, Xuemei; Zeng, Qiufeng; Yang, Jun; Fang, Jing; Chen, Kejie

    2014-08-20

    The purpose of this study was to evaluate the effects of corn naturally contaminated with aflatoxin B1 and aflatoxin B2 on pathological lesions, apoptosis, cell cycle phases and T lymphocyte subsets of spleen, and to provide an experimental basis for understanding the mechanism of aflatoxin-induced immunosuppression. A total of 900 COBB500 male broilers were randomly allocated into five groups with six replicates per group and 30 birds per replicate. The experiment lasted for 6 weeks and the five dietary treatments consisted of control, 25% contaminated corn, 50% contaminated corn, 75% contaminated corn and 100% contaminated corn groups. The histopathological spleen lesions from the contaminated corn groups was characterized as congestion of red pulp, increased necrotic cells and vacuoles in the splenic corpuscle and periarterial lymphatic sheath. The contaminated corn intake significantly increased relative weight of spleen, percentages of apoptotic splenocytes, induced cell cycle arrest of splenocytes, increased the percentages of CD3+CD8+ T cells and decreased the ratios of CD3+CD4+ to CD3+CD8+. The results suggest that AFB-induced immunosuppression maybe closely related to the lesions of spleen.

  3. Cerebral hemorrhagic lesions produced by Paragonimus mexicanus. Report of three cases in Costa Rica.

    PubMed

    Brenes Madrigal, R; Rodríguez-Ortiz, B; Vargas Solano, G; Ocamp Obando, E M; Ruiz Sotela, P J

    1982-05-01

    Three cases of cerebral lesions due to Paragonimus mexicanus in Costa Rica are reported, two of which were fatal. At autopsy a hemorrhagic, well circumscribed lesion was found in the hemispheres which microscopically consisted of a recent hemorrhage surrounded by a halo of eosinophils, with giant cell granulomas and Charcot-Leyden crystals. Eggs of P. mexicanus outside the brain were demonstrated in both fatal cases--in an eosinophilic pericarditis in one and in the other in multiple lesions of the liver and lungs. The third patient had a hemorrhagic cerebral lesion which was surgically evacuated; the patient recovered. Eggs were demonstrated in serial sections of the material resected.

  4. Unilateral non-pigmented palpebral conjunctival lesions due to cosmetics use.

    PubMed

    Pao, Kristina Y; Murchison, Ann P; Eagle, Ralph C

    2012-01-01

    A 62-year-old woman with a history of dry eyes was found to have unilateral pedunculated, nonpigmented palpebral conjunctival lesions. Excisional biopsy was performed, and the lesions were studied histopathologically. Microscopic examination of the lesions demonstrated exuberant granulation tissue with a granulomatous foreign body giant cell reaction surrounding pigmented and partially birefringent foreign material. Histopathologic examination of the patient's cosmetics revealed that the pigmented foreign bodies seen on the biopsy specimens were compatible with her mascara and/or eyeliner. While cosmetics have been reported to have ophthalmic sequelae, palpebral lesions such as these have not been reported to the authors' knowledge.

  5. Detection of circulating pancreas epithelial cells in patients with pancreatic cystic lesions.

    PubMed

    Rhim, Andrew D; Thege, Fredrik I; Santana, Steven M; Lannin, Timothy B; Saha, Trisha N; Tsai, Shannon; Maggs, Lara R; Kochman, Michael L; Ginsberg, Gregory G; Lieb, John G; Chandrasekhara, Vinay; Drebin, Jeffrey A; Ahmad, Nuzhat; Yang, Yu-Xiao; Kirby, Brian J; Stanger, Ben Z

    2014-03-01

    Hematogenous dissemination is thought to be a late event in cancer progression. We recently showed in a genetic model of pancreatic ductal adenocarcinoma that pancreas cells can be detected in the bloodstream before tumor formation. To confirm these findings in humans, we used microfluidic geometrically enhanced differential immunocapture to detect circulating pancreas epithelial cells in patient blood samples. We captured more than 3 circulating pancreas epithelial cells/mL in 7 of 21 (33%) patients with cystic lesions and no clinical diagnosis of cancer (Sendai criteria negative), 8 of 11 (73%) with pancreatic ductal adenocarcinoma, and in 0 of 19 patients without cysts or cancer (controls). These findings indicate that cancer cells are present in the circulation of patients before tumors are detected, which might be used in risk assessment. PMID:24333829

  6. Detection of circulating pancreas epithelial cells in patients with pancreatic cystic lesions.

    PubMed

    Rhim, Andrew D; Thege, Fredrik I; Santana, Steven M; Lannin, Timothy B; Saha, Trisha N; Tsai, Shannon; Maggs, Lara R; Kochman, Michael L; Ginsberg, Gregory G; Lieb, John G; Chandrasekhara, Vinay; Drebin, Jeffrey A; Ahmad, Nuzhat; Yang, Yu-Xiao; Kirby, Brian J; Stanger, Ben Z

    2014-03-01

    Hematogenous dissemination is thought to be a late event in cancer progression. We recently showed in a genetic model of pancreatic ductal adenocarcinoma that pancreas cells can be detected in the bloodstream before tumor formation. To confirm these findings in humans, we used microfluidic geometrically enhanced differential immunocapture to detect circulating pancreas epithelial cells in patient blood samples. We captured more than 3 circulating pancreas epithelial cells/mL in 7 of 21 (33%) patients with cystic lesions and no clinical diagnosis of cancer (Sendai criteria negative), 8 of 11 (73%) with pancreatic ductal adenocarcinoma, and in 0 of 19 patients without cysts or cancer (controls). These findings indicate that cancer cells are present in the circulation of patients before tumors are detected, which might be used in risk assessment.

  7. The interdisciplinary approach of an aggressive giant cell tumor of bone complicated with a fracture of the distal femur.

    PubMed

    Vîlcioiu, Iulian Daniel; Zamfirescu, Dragoş George; Cristescu, Ioan; Ursache, Andrei; Popescu, Şerban Arghir; Creangă, Cosmin Antoniu; Lascăr, Ioan

    2016-01-01

    Giant cell tumor of bone (GCTB) represents one of the commonest bone tumors encountered by an orthopedic surgeon. The giant-cell tumor is generally classified as benign but the fast growing rhythm and the aggressive soft-tissue invasion may in some cases demonstrate a malign potential of the tumor. We present the case of an aggressive giant cell tumor in a young patient that was first diagnosed in our emergency department with a fracture of the distal femur after a low energy trauma. With further examinations, we discovered that the tumor was invading the both femoral condyles and was vascularized by three major arterial pedicles. The onset of his problems was the femoral fracture and the changes on the major vessels, muscles and nerves. After an interdisciplinary approach of the patient and a meticulous preoperative planning, we decided to make an extensive total resection of the tumor followed by a complex reconstruction surgery for the bone. A very stable fixation of a vascularized graft allowed the bone to heal even if the surrounded soft-tissue was almost completely invaded by the tumor and removed during the excision. The follow-up of this case demonstrated that using an interdisciplinary approach of the patient with the Plastic Surgery team, we manage to remove the tumor within oncological limits and achieved bone healing with good stability of the distal femur. PMID:27516036

  8. Modified kraske procedure with mid-sacrectomy and coccygectomy for en bloc excision of sacral giant cell tumors.

    PubMed

    Gonçalves, Vítor M; Lima, Alvaro; Gíria, João; Carvalho, Nuno; Parreira, José; Cunha E Sá, Manuel

    2014-01-01

    Sacral giant cell tumors are rare neoplasms, histologically benign but potentially very aggressive due to the difficulty in achieving a complete resection, their high recurrence rate, and metastization capability. Although many treatment options have been proposed, en bloc excision with tumor-free margins seems to be the most effective, being associated with long term tumor control, improved outcome, and potential cure. An exemplifying case of a 29-year-old female with progressive complaints of pain and paresthesias in the sacral and perianal regions, constipation, and weight loss for 6 months is presented. The surgical technique for en bloc excision of a large sacral giant cell tumor through a modified Kraske procedure with mid-sacrectomy and coccygectomy is described. Complete resection with wide tumor-free margins was achieved. At 5 years of follow-up the patient is neurologically intact, without evidence of local recurrence on imaging studies. A multidisciplinary surgical procedure is mandatory to completely remove sacral tumors. In the particular case of giant cell tumors, it allows minimizing local recurrence preserving neurovascular function, through a single dorsal and definitive approach. PMID:25386379

  9. Laser-induced autofluorescence properties of base-cell lesions: analysis and algorithms for diagnosis and differentiation

    NASA Astrophysics Data System (ADS)

    Borisova, E.; Troyanova, P.; Avramov, L.

    2006-09-01

    The goals of this work were investigation of base-cell skin lesions by the method of laser-induced autofluorescence spectroscopy. Fluorescence spectra were obtained from benign base-cell papilloma and malignant base-cell carcinoma, as well as from healthy skin areas near to the lesions that were used posteriori to reveal changes between healthy and lesion skin spectra. Preliminarily lesions were classified by dermatoscopic method (MoleMax II, DERMA Instruments). All suspicious lesions were excised and were investigated histologically. The experimental set-up consists of a nitrogen laser (337 nm, 14 μJ, 10 Hz), lenses, filters, optical fibers, and a microspectrometer (PC2000, "Ocean Optics"). A computer controls this system. Spectrum of healthy skin consists of one main maximum at 470-500 nm spectral region and secondary maxima at in the regions around 400 and 440 nm. In cases of papilloma and base-cell carcinoma an intensity decrease was observed, related to accumulation of pigments in these cutaneous lesions. An relative increase of the fluorescence peak at 440 nm were registered in the case of base-cell carcinoma, related to metabolism activity increase, and appearance of green fluorescence, related to increase of keratin content in benign papilloma lesions were detected. The results, obtained were used to develop multispectral diagnostic algorithm of these base-cell lesions. An sensitivity of 89,4% and 91,0% and specificity of 99,6% and 97,4% for differentiation between normal skin and papilloma and carcinoma respectively were obtained. The capability of the human skin fluorescence spectroscopy for early diagnosis and differentiation of cutaneous lesions is shown.

  10. Lesion-induced accumulation of platelets promotes survival of adult neural stem / progenitor cells.

    PubMed

    Kazanis, Ilias; Feichtner, Martina; Lange, Simona; Rotheneichner, Peter; Hainzl, Stefan; Öller, Michaela; Schallmoser, Katharina; Rohde, Eva; Reitsamer, Herbert A; Couillard-Despres, Sebastien; Bauer, Hans-Christian; Franklin, Robin J M; Aigner, Ludwig; Rivera, Francisco J

    2015-07-01

    The presence of neural stem/progenitor cells (NSPCs) in specific areas of the central nervous system (CNS) supports tissue maintenance as well as regeneration. The subependymal zone (SEZ), located at the lateral ventricle's wall, represents a niche for NSPCs and in response to stroke or demyelination becomes activated with progenitors migrating towards the lesion and differentiating into neurons and glia. The mechanisms that underlie this phenomenon remain largely unknown. The vascular niche and in particular blood-derived elements such as platelets, has been shown to contribute to CNS regeneration in different pathological conditions. Indeed, intracerebroventricularly administrated platelet lysate (PL) stimulates angiogenesis, neurogenesis and neuroprotection in the damaged CNS. Here, we explored the presence of platelets in the activated SEZ after a focal demyelinating lesion in the corpus callosum of mice and we studied the effects of PL on proliferating SEZ-derived NSPCs in vitro. We showed that the lesion-induced increase in the size of the SEZ and in the number of proliferating SEZ-resident NSPCs correlates with the accumulation of platelets specifically along the activated SEZ vasculature. Expanding on this finding, we demonstrated that exposure of NSPCs to PL in vitro led to increased numbers of cells by enhanced cell survival and reduced apoptosis without differences in proliferation and in the differentiation potential of NSPCs. Finally, we demonstrate that the accumulation of platelets within the SEZ is spatially correlated with reduced numbers of apoptotic cells when compared to other periventricular areas. In conclusion, our results show that platelet-derived compounds specifically promote SEZ-derived NSPC survival and suggest that platelets might contribute to the enlargement of the pool of SEZ NSPCs that are available for CNS repair in response to injury.

  11. Lesion-induced accumulation of platelets promotes survival of adult neural stem / progenitor cells.

    PubMed

    Kazanis, Ilias; Feichtner, Martina; Lange, Simona; Rotheneichner, Peter; Hainzl, Stefan; Öller, Michaela; Schallmoser, Katharina; Rohde, Eva; Reitsamer, Herbert A; Couillard-Despres, Sebastien; Bauer, Hans-Christian; Franklin, Robin J M; Aigner, Ludwig; Rivera, Francisco J

    2015-07-01

    The presence of neural stem/progenitor cells (NSPCs) in specific areas of the central nervous system (CNS) supports tissue maintenance as well as regeneration. The subependymal zone (SEZ), located at the lateral ventricle's wall, represents a niche for NSPCs and in response to stroke or demyelination becomes activated with progenitors migrating towards the lesion and differentiating into neurons and glia. The mechanisms that underlie this phenomenon remain largely unknown. The vascular niche and in particular blood-derived elements such as platelets, has been shown to contribute to CNS regeneration in different pathological conditions. Indeed, intracerebroventricularly administrated platelet lysate (PL) stimulates angiogenesis, neurogenesis and neuroprotection in the damaged CNS. Here, we explored the presence of platelets in the activated SEZ after a focal demyelinating lesion in the corpus callosum of mice and we studied the effects of PL on proliferating SEZ-derived NSPCs in vitro. We showed that the lesion-induced increase in the size of the SEZ and in the number of proliferating SEZ-resident NSPCs correlates with the accumulation of platelets specifically along the activated SEZ vasculature. Expanding on this finding, we demonstrated that exposure of NSPCs to PL in vitro led to increased numbers of cells by enhanced cell survival and reduced apoptosis without differences in proliferation and in the differentiation potential of NSPCs. Finally, we demonstrate that the accumulation of platelets within the SEZ is spatially correlated with reduced numbers of apoptotic cells when compared to other periventricular areas. In conclusion, our results show that platelet-derived compounds specifically promote SEZ-derived NSPC survival and suggest that platelets might contribute to the enlargement of the pool of SEZ NSPCs that are available for CNS repair in response to injury. PMID:25819103

  12. Olig2-expressing progenitor cells preferentially differentiate into oligodendrocytes in cuprizone-induced demyelinated lesions.

    PubMed

    Islam, Mohammad Shyful; Tatsumi, Kouko; Okuda, Hiroaki; Shiosaka, Sadao; Wanaka, Akio

    2009-01-01

    Many oligodendrocyte progenitor cells (OPCs) are found in acute or chronic demyelinated area, but not all of them differentiate efficiently into mature oligodendrocytes in the demyelinated central nervous system (CNS). Recent studies have shown that the basic helix-loop-helix transcription factor Olig2, which stimulates OPCs to differentiate into oligodendrocyte, is strongly up-regulated in many pathological conditions including acute or chronic demyelinating lesions in the adult CNS. Despite their potential role in the treatment of demyelinating diseases, the long-term fate of these up-regulated Olig2 cells has not been identified due to the lack of stable labeling methods. To trace their fate we have used double-transgenic mice, in which we were able to label Olig2-positive cells conditionally with green fluorescent protein (GFP). Demyelination was induced in these mice by feeding cuprizone, a copper chelator. After 6 weeks of cuprizone exposure, GFP-positive (GFP(+)) cells were processed for a second labeling with antibodies to major neural cell markers APC (mature oligodendrocyte marker), GFAP (astrocyte marker), NeuN (neuron marker), Iba1 (microglia marker) and NG2 proteoglycan (oligodendrocyte progenitor marker). More than half of the GFP(+) cells in the external capsule showed co-localization with NG2 proteoglycan. While the percentages of NG2-positive (NG2(+)) and APC-positive (APC(+)) oligodendrocyte lineage cells in cuprizone-treated mice were significantly higher than those in the normal diet group, no significant difference was observed for GFAP-positive (GFAP(+)) astrocytic lineage cells. Our data therefore provide direct evidence that proliferation and differentiation of local and/or recruited Olig2 progenitors contribute to remyelination in demyelinated lesions. PMID:19070638

  13. Lethal giant larvae-1 deficiency enhances the CD8(+) effector T-cell response to antigen challenge in vivo.

    PubMed

    Ramsbottom, Kelly M; Sacirbegovic, Faruk; Hawkins, Edwin D; Kallies, Axel; Belz, Gabrielle T; Van Ham, Vanessa; Haynes, Nicole M; Durrant, Michael J; Humbert, Patrick O; Russell, Sarah M; Oliaro, Jane

    2016-03-01

    Lethal giant larvae-1 (Lgl-1) is an evolutionary conserved protein that regulates cell polarity in diverse lineages; however, the role of Lgl-1 in the polarity and function of immune cells remains to be elucidated. To assess the role of Lgl-1 in T cells, we generated chimeric mice with a hematopoietic system deficient for Lgl-1. Lgl-1 deficiency did not impair the activation or function of peripheral CD8(+) T cells in response to antigen presentation in vitro, but did skew effector and memory T-cell differentiation. When challenged with antigen-expressing virus or tumor, Lgl-1-deficient mice displayed altered T-cell responses. This manifested in a stronger antiviral and antitumor effector CD8(+) T-cell response, the latter resulting in enhanced control of MC38-OVA tumors. These results reveal a novel role for Lgl-1 in the regulation of virus-specific T-cell responses and antitumor immunity.

  14. Lethal giant larvae-1 deficiency enhances the CD8(+) effector T-cell response to antigen challenge in vivo.

    PubMed

    Ramsbottom, Kelly M; Sacirbegovic, Faruk; Hawkins, Edwin D; Kallies, Axel; Belz, Gabrielle T; Van Ham, Vanessa; Haynes, Nicole M; Durrant, Michael J; Humbert, Patrick O; Russell, Sarah M; Oliaro, Jane

    2016-03-01

    Lethal giant larvae-1 (Lgl-1) is an evolutionary conserved protein that regulates cell polarity in diverse lineages; however, the role of Lgl-1 in the polarity and function of immune cells remains to be elucidated. To assess the role of Lgl-1 in T cells, we generated chimeric mice with a hematopoietic system deficient for Lgl-1. Lgl-1 deficiency did not impair the activation or function of peripheral CD8(+) T cells in response to antigen presentation in vitro, but did skew effector and memory T-cell differentiation. When challenged with antigen-expressing virus or tumor, Lgl-1-deficient mice displayed altered T-cell responses. This manifested in a stronger antiviral and antitumor effector CD8(+) T-cell response, the latter resulting in enhanced control of MC38-OVA tumors. These results reveal a novel role for Lgl-1 in the regulation of virus-specific T-cell responses and antitumor immunity. PMID:26391810

  15. Behavioural consequences of oligodendrocyte progenitor cell transplantation into experimental demyelinating lesions in the rat spinal cord.

    PubMed

    Jeffery, N D; Crang, A J; O'leary, M T; Hodge, S J; Blakemore, W F

    1999-05-01

    Glial cell transplantation has the potential to be developed into a clinical treatment for human demyelinating diseases because of its demonstrated efficacy in remyelinating experimentally demyelinated axons. As a step towards clinical application it is necessary to demonstrate that the procedure is safe and efficacious in promoting behavioural recovery. In this study we transplanted glial cell progenitors into demyelinating lesions induced by intraspinal injection of ethidium bromide in the rat. Locomotor function after transplantation was assessed using a beam-walking test that has previously been shown able to detect deficits associated with demyelination in the dorsal funiculus of the rat spinal cord. Two groups of animals with transplants were examined. In one group, spontaneous remyelination was prevented by exposure of the lesion to 40 Gy of X-irradiation; in the other, male glial cells were transplanted into nonirradiated female recipients, permitting their identification by use of a probe specific to the rat Y chromosome. Following transplantation, there was severe axon loss in a large proportion of the irradiated animals and those affected did not recover normal behavioural function. In contrast, both the small proportion of the irradiated group that sustained only mild axon loss and the nonirradiated recipients of transplants recovered normal function on our behavioural test. We conclude that glial cell transplantation is able to reverse the functional deficits associated with demyelination, provided axonal loss is minimal. PMID:10215903

  16. Maternal nutrition modifies trophoblast giant cell phenotype and fetal growth in mice

    PubMed Central

    Watkins, Adam J; Lucas, Emma S; Marfy-Smith, Stephanie; Bates, Nicola; Kimber, Susan J; Fleming, Tom P

    2015-01-01

    Mammalian placentation is dependent upon the action of trophoblast cells at the time of implantation. Appropriate fetal growth, regulated by maternal nutrition and nutrient transport across the placenta, is a critical factor for adult offspring long-term health. We have demonstrated that a mouse maternal low-protein diet (LPD) fed exclusively during preimplantation development (Emb-LPD) increases offspring growth but programmes adult cardiovascular and metabolic disease. In this study, we investigate the impact of maternal nutrition on post-implantation trophoblast phenotype and fetal growth. Ectoplacental cone explants were isolated at day 8 of gestation from female mice fed either normal protein diet (NPD: 18% casein), LPD (9% casein) or Emb-LPD and cultured in vitro. We observed enhanced spreading and cell division within proliferative and secondary trophoblast giant cells (TGCs) emerging from explants isolated from LPD-fed females when compared with NPD and Emb-LPD explants after 24 and 48 h. Moreover, both LPD and Emb-LPD explants showed substantial expansion of TGC area during 24–48 h, not observed in NPD. No difference in invasive capacity was observed between treatments using Matrigel transwell migration assays. At day 17 of gestation, LPD- and Emb-LPD-fed conceptuses displayed smaller placentas and larger fetuses respectively, resulting in increased fetal:placental ratios in both groups compared with NPD conceptuses. Analysis of placental and yolk sac nutrient signalling within the mammalian target of rapamycin complex 1 pathway revealed similar levels of total and phosphorylated downstream targets across groups. These data demonstrate that early post-implantation embryos modify trophoblast phenotype to regulate fetal growth under conditions of poor maternal nutrition. PMID:25755287

  17. Long-term efficacy and safety of tocilizumab in giant cell arteritis and large vessel vasculitis

    PubMed Central

    Evans, Jobie; Steel, Lauren; Borg, Frances; Dasgupta, Bhaskar

    2016-01-01

    Giant cell arteritis (GCA) is a chronic systemic vasculitis affecting large-sized and medium-sized vessels. Glucocorticoids are currently the mainstay of treatment for GCA and associated large vessel vasculitis (LVV) but are associated with frequent adverse events. Methotrexate has only demonstrated a modest benefit while anti-TNF biological agents (infliximab and etanercept) have been inefficacious. Elevated levels of interleukin-6 (IL-6), a proinflammatory cytokine, has been associated with GCA. Tocilizumab (TCZ), a humanised antihuman IL-6 receptor antibody, has been used successfully in several reports as a treatment for GCA and LVV. We report the potentially long-term successful use of TCZ in 8 cases of refractory LVV. All of our patients achieved a good clinical response to TCZ and C reactive protein reduced from an average of 70.3 to 2.5. In all cases, the glucocorticoid dose was reduced, from an average of 24.6 mg prednisolone prior to TCZ treatment to 4.7 mg, indicating that TCZ may enable a reduction in glucocorticoid-associated adverse events. However, regular TCZ administration was needed for disease control in most cases. TCZ was discontinued in one case due to the development of an empyema indicating the need for careful monitoring of infection when using this treatment. PMID:26819753

  18. The Thromboembolic Risk in Giant Cell Arteritis: A Critical Review of the Literature

    PubMed Central

    Guida, A.; Tufano, A.; Perna, P.; Moscato, P.; De Donato, M. T.; Finelli, R.; Caputo, D.; Di Minno, M. N. D.

    2014-01-01

    Giant cell arteritis is a systemic vasculitis characterized by granulomatous inflammation of the aorta and its main vessels. Cardiovascular risk, both for arterial and venous thromboembolism, is increased in these patients, but the role of thromboprophylaxis is still debated. It should be suspected in elderly patients suffering from sudden onset severe headaches, jaw claudication, and visual disease. Early diagnosis is necessary because prognosis depends on the timeliness of treatment: this kind of arteritis can be complicated by vision loss and cerebrovascular strokes. Corticosteroids remain the cornerstone of the pharmacological treatment of GCA. Aspirin seems to be effective in cardiovascular prevention, while the use of anticoagulant therapy is controversial. Association with other rheumatological disease, particularly with polymyalgia rheumatica is well known, while possible association with antiphospholipid syndrome is not established. Large future trials may provide information about the optimal therapy. Other approaches with new drugs, such as TNF-alpha blockades, Il-6 and IL-1 blockade agents, need to be tested in larger trials. PMID:24963300

  19. Acute vision loss and choroidal filling delay in the absence of giant-cell arteritis

    PubMed Central

    Bei, Ling; Lee, Iris; Lee, Michael S; Van Stavern, Greg P; McClelland, Collin M

    2016-01-01

    Giant-cell arteritis (GCA) is a visually devastating disease that often progresses to severe bilateral vision loss if untreated. Diagnosis of GCA is made challenging by the protean nature of the disease and the lack of a simple test that is both highly sensitive and specific. Choroidal filling delay on fluorescein angiography (FA) has been touted as a highly characteristic feature of GCA-related vision loss, although knowledge of both the sensitivity and specificity of this finding remains unproven. We report our experience of delayed choroidal filling on FA in a series of seven patients referred to an academic neuro-ophthalmology practice due to concern for GCA. Despite the FA findings, our examination, diagnostic testing, and long-term follow-up excluded the diagnosis of GCA in all cases, suggesting that choroidal perfusion abnormalities may occur in the absence of GCA. When evaluating a patient for acute vision loss, the astute clinician must remain cognizant of the limitations of FA in the diagnosis of GCA.

  20. Epidemiologic and immunogenetic aspects of polymyalgia rheumatica and giant cell arteritis in northern Italy.

    PubMed

    Salvarani, C; Macchioni, P; Zizzi, F; Mantovani, W; Rossi, F; Castri, C; Capozzoli, N; Baricchi, R; Boiardi, L; Chiaravalloti, F

    1991-03-01

    We studied the epidemiology of giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) in a Mediterranean population. Ninety-nine patients with PMR and/or GCA were identified over a 9-year period (1980-1988) in Reggio Emilia, Italy. The average annual incidence of PMR and GCA was 12.7/100,000 and 6.9/100,000, respectively, in a population aged 50 years or older. Frequencies of HLA antigens were determined in 49 patients with PMR and/or GCA who were followed by staff at our rheumatology unit during the 1980-1988 period. When compared with HLA findings in 242 healthy controls, DR4 was not found to be significantly associated with PMR (24% in PMR patients versus 14% in controls). Patients with GCA also showed an increased frequency of DR4 compared with controls (36% versus 14%), but this difference was also not statistically significant. The immunogenetic features of PMR and GCA and the relationship between the immunogenetic and epidemiologic patterns in different populations are discussed.

  1. ZNF687 Mutations in Severe Paget Disease of Bone Associated with Giant Cell Tumor

    PubMed Central

    Divisato, Giuseppina; Formicola, Daniela; Esposito, Teresa; Merlotti, Daniela; Pazzaglia, Laura; Del Fattore, Andrea; Siris, Ethel; Orcel, Philippe; Brown, Jacques P.; Nuti, Ranuccio; Strazzullo, Pasquale; Benassi, Maria Serena; Cancela, M. Leonor; Michou, Laetitia; Rendina, Domenico; Gennari, Luigi; Gianfrancesco, Fernando

    2016-01-01

    Paget disease of bone (PDB) is a skeletal disorder characterized by focal abnormalities of bone remodeling, which result in enlarged and deformed bones in one or more regions of the skeleton. In some cases, the pagetic tissue undergoes neoplastic transformation, resulting in osteosarcoma and, less frequently, in giant cell tumor of bone (GCT). We performed whole-exome sequencing in a large family with 14 PDB-affected members, four of whom developed GCT at multiple pagetic skeletal sites, and we identified the c.2810C>G (p.Pro937Arg) missense mutation in the zinc finger protein 687 gene (ZNF687). The mutation precisely co-segregated with the clinical phenotype in all affected family members. The sequencing of seven unrelated individuals with GCT associated with PDB (GCT/PDB) identified the same mutation in all individuals, unravelling a founder effect. ZNF687 is highly expressed during osteoclastogenesis and osteoblastogenesis and is dramatically upregulated in the tumor tissue of individuals with GCT/PDB. Interestingly, our preliminary findings showed that ZNF687, indicated as a target gene of the NFkB transcription factor by ChIP-seq analysis, is also upregulated in the peripheral blood of PDB-affected individuals with (n = 5) or without (n = 6) mutations in SQSTM1, encouraging additional studies to investigate its potential role as a biomarker of PDB risk. PMID:26849110

  2. Acute vision loss and choroidal filling delay in the absence of giant-cell arteritis

    PubMed Central

    Bei, Ling; Lee, Iris; Lee, Michael S; Van Stavern, Greg P; McClelland, Collin M

    2016-01-01

    Giant-cell arteritis (GCA) is a visually devastating disease that often progresses to severe bilateral vision loss if untreated. Diagnosis of GCA is made challenging by the protean nature of the disease and the lack of a simple test that is both highly sensitive and specific. Choroidal filling delay on fluorescein angiography (FA) has been touted as a highly characteristic feature of GCA-related vision loss, although knowledge of both the sensitivity and specificity of this finding remains unproven. We report our experience of delayed choroidal filling on FA in a series of seven patients referred to an academic neuro-ophthalmology practice due to concern for GCA. Despite the FA findings, our examination, diagnostic testing, and long-term follow-up excluded the diagnosis of GCA in all cases, suggesting that choroidal perfusion abnormalities may occur in the absence of GCA. When evaluating a patient for acute vision loss, the astute clinician must remain cognizant of the limitations of FA in the diagnosis of GCA. PMID:27695279

  3. Complete response of giant desmoplastic small round cell tumor treated with chemoradiotherapy: A case report

    PubMed Central

    ZHANG, SHUO; ZHANG, YONG; YU, YONG-HUA; LI, JIA

    2016-01-01

    Desmoplastic small round cell tumor (DSRCT) is a rare tumor that mainly affects adolescents, and typically involves the abdominal and pelvic peritoneum. The present study reports one case of giant DSRCT, treated with concurrent chemoradiotherapy, and reviews the available medical literature. A 38-year-old man presented with a 3-month history of pain in the left lower abdomen and nausea, associated with decreased appetite and weight loss. Computed tomography (CT) showed a 12.3×7.9 cm confluent solid mass in the lower abdomen and pelvic cavity. The patient underwent exploratory laparotomy and the final pathological diagnosis was DSRCT. Following laparotomy, the patient was treated with external beam radiotherapy to the whole abdomen and pelvis to a dose of 40 Gy plus a 20 Gy boost to the residual disease. The results indicated that synchronous chemotherapy with cyclophosphamide, adriamycin and cisplatin combined with radiotherapy significantly improved locoregional control of DSRCT and a complete response, as measured by CT assessment 2 months subsequent to radiotherapy. In conclusion, DSRCT is a rare malignancy requiring multidisciplinary treatment, including surgery, chemotherapy and radiotherapy. The results of the present study confirm that radiotherapy has a significant role in the treatment of advanced abdominal DSRCT and may contribute to durable remission. PMID:26893693

  4. Obstructive hydrocephalus as a result of giant cell tumor of the thoracic spine: A case report

    PubMed Central

    WEI, CHENG-YU; CHEN, SHUO-TSUNG; TAI, HSU-CHIH; WANG, WEN-BING; CHANG, CHI-CHU; WANG, YAO-CHIN; WEI, LI; KUNG, WOON-MAN

    2016-01-01

    Giant cell tumors (GCTs) are rare bone tumors that account for ~5% of all primary bone tumors. When GCTs occur in the spine, patients usually present with localized pain and neurological symptoms, such as radiating pain or hyperesthesia. In the current report, an unusual case of a GCT of the thoracic spine associated with hydrocephalus is described. A 48-year-old male presented with urinary retention, loss of sensation in the lower limbs and inability to walk. The patient eventually developed hydrocephalus combined with altered consciousness, indicated by an inability to follow simple commands. Magnetic resonance (MR) imaging demonstrated the presence of a soft tissue mass at the T2 level, and biopsy examination of the tissue confirmed that it was a GCT. The patient experienced a sudden loss of consciousness due to an acute episode of obstructive hydrocephalus. A ventriculoperitoneal shunting procedure was performed to treat the hydrocephalus, and the patient regained normal consciousness, although the paraplegia persisted. An MR examination performed 30 months following surgery demonstrated that the tumor size was stable, consistent with the slow growth that is characteristic of GCTs. Diagnosis of GCTs may be challenging, and relies on radiographic and histopathologic findings. Although rare, acute hydrocephalus as a result of GCTs should not be excluded from a differential diagnosis. PMID:26870164

  5. Anti-CD20 treatment of giant cell hepatitis with autoimmune hemolytic anemia.

    PubMed

    Paganelli, Massimiliano; Patey, Natacha; Bass, Lee M; Alvarez, Fernando

    2014-10-01

    Giant cell hepatitis with autoimmune hemolytic anemia (GCH-AHA) is a rare autoimmune disease of infancy characterized by severe liver disease associated with Coombs-positive hemolytic anemia. We recently showed that GCH-AHA is probably caused by a humoral immune mechanism. Such data support the use of rituximab, an anti-CD-20 monoclonal antibody specifically targeting B lymphocytes, as a treatment for GCH-AHA. We describe here the detailed clinical evolution of 4 children with GCH-AHA who showed a complete response to rituximab. All patients shared a severe course of the disease with poor control on standard and aggressive immunosuppression. Rituximab was well tolerated, and no side effects or infections were registered. Several doses were needed to induce remission, and 5 to 11 additional maintenance injections were necessary in the 2 more severe cases. Weaning from corticosteroids was achieved in all subjects. A steroid-sparing effect was noted in the 3 children who started rituximab early in the course of the disease. Overall, we show here that there is a strong rationale for treating GCH-AHA with rituximab. Early treatment could reduce the use of corticosteroids. Nevertheless, short-term steroids should be initially associated with rituximab to account for autoantibodies' half-life. Repeated injections are needed to treat and prevent relapses, but the best frequency and duration of treatment remain to be defined.

  6. Acute upper limb ischemia, a rare presentation of giant cell arteritis.

    PubMed

    Almeida-Morais, Luís; Galego, Sofia; Marques, Nélia; Pack, Tiago; Rodrigues, Hugo; Abreu, Rodolfo; Vasconcelos, Leonor; Marques, Hugo; Sousa Guerreiro, António

    2016-04-01

    Giant cell arteritis (GCA) is a systemic large vessel vasculitis, with extracranial arterial involvement described in 10-15% of cases, usually affecting the aorta and its branches. Patients with GCA are more likely to develop aortic aneurysms, but these are rarely present at the time of the diagnosis. We report the case of an 80-year-old Caucasian woman, who reported proximal muscle pain in the arms with morning stiffness of the shoulders for eight months. In the previous two months, she had developed worsening bilateral arm claudication, severe pain, cold extremities and digital necrosis. She had no palpable radial pulses and no measurable blood pressure. The patient had normochromic anemia, erythrocyte sedimentation rate of 120 mm/h, and a negative infectious and autoimmune workup. Computed tomography angiography revealed concentric wall thickening of the aorta extending to the aortic arch branches, particularly the subclavian and axillary arteries, which were severely stenotic, with areas of bilateral occlusion and an aneurysm of the ascending aorta (47 mm). Despite corticosteroid therapy there was progression to acute critical ischemia. She accordingly underwent surgical revascularization using a bilateral carotid-humeral bypass. After surgery, corticosteroid therapy was maintained and at six-month follow-up she was clinically stable with reduced inflammatory markers. GCA, usually a chronic benign vasculitis, presented exceptionally in this case as acute critical upper limb ischemia, resulting from a massive inflammatory process of the subclavian and axillary arteries, treated with salvage surgical revascularization. PMID:27006059

  7. Endovascular embolization of a recurrent cervical giant cell neoplasm using N-butyl 2-cyanoacrylate.

    PubMed

    Mindea, Stefan A; Eddleman, Christopher S; Hage, Ziad A; Batjer, H Hunt; Ondra, Stephen L; Bendok, Bernard R

    2009-03-01

    Pre-operative endovascular embolization of spinal giant cell tumors (GCTs) has been an effective strategy to reduce blood loss during surgical resection. Traditionally, spinal GCTs have been embolized with polyvinyl acetate (PVA) particles. We present the pre-operative embolization of a recurrent cervical GCT with N-butyl 2-cyanoacrylate (NBCA) rather than PVA. The patient was a 17-year-old female who, 3 months prior, had undergone a surgical resection of a cervical GCT without pre-operative embolization. She returned with tumor recurrence in the approximate location. Resection was recommended, and pre-operative embolization was requested. The tumor was embolized with NBCA. Post-embolization angiography demonstrated significantly decreased tumor "blush" and a significant reduction of the vascular supply. This is the first reported use of NBCA for the pre-operative embolization of a cervical GCT. The benefits of NBCA over PVA particles include superior penetration, permanent tumor embolization and lower exposure to radiation due to shorter procedure time.

  8. HLA class II genes polymorphism in DR4 giant cell arteritis patients.

    PubMed

    Bignon, J D; Ferec, C; Barrier, J; Pennec, Y; Verlingue, C; Cheneau, M L; Lucas, V; Muller, J Y; Saleun, J P

    1988-11-01

    We have previously reported a significant increase of HLA-DR4 antigen frequency in giant cell arteritis (GCA). This finding suggested an important role of immunogenetic factors in this syndrome. Recent data suggest that inherited susceptibility to several autoimmune diseases was associated with specific DR4 associated DQ beta alleles. DNAs from 27 DR4 positive patients with GCA were digested with Taq I and Bam HI, analysed on 0.7% agarose gel and hybridized with DR beta, DQ alpha and DQ beta probes. DR beta hybridization produced no variant detectable within DR4. DQ beta probe confirmed two clusters among DR4 associated DQW3 alleles: DQW 3.1 (Bam HI 360 Kb) and DQw 3.2 (Taq I 1.9 Kb and Bam HI 11 Kb). Among our 27 DR4 positive patients, 34% were DQW 3.1 and 66% were DQW 3.2. These frequencies are the same as those observed in healthy controls. PMID:2906182

  9. Giant cell arteritis or tension-type headache?: A differential diagnostic dilemma

    PubMed Central

    Rana, Abdul Qayyum; Saeed, Usman; Khan, Osama A.; Qureshi, Abdul Rehman M.; Paul, Dion

    2014-01-01

    Giant cell arteritis (GCA) or Temporal arteritis (TA) is an autoimmune disease and the most common type of vasculitis in the elderly. It causes inflammation of the medium and large arteries in the upper part of the body. GCA is an under-recognized cause of  head aches in the elderly, especially when it presents itself with atypical features, resulting in delayed or incorrect diagnosis. Since GCA is a treatable condition, an accurate diagnosis is crucial to prevent the most serious complication of CGA, permanent vision loss. The diagnosis can be further complicated as GCA may present with features of other painful neurological conditions. The present case is an 81-year-old woman diagnosed with GCA, who initially presented with features similar to tension-type headache. Due to overlapping features of these conditions, the diagnosis of GCA was delayed, resulting in irreversible vision loss. Although previous research highlights diagnostic dilemmas featuring GCA and other disease states, this case is exclusive in describing a unique dilemma where tension-type headache mimics GCA. PMID:25288850

  10. Myelin-specific T cells induce interleukin-1beta expression in lesion-reactive microglial-like cells in zones of axonal degeneration.

    PubMed

    Grebing, Manuela; Nielsen, Helle H; Fenger, Christina D; T Jensen, Katrine; von Linstow, Christian U; Clausen, Bettina H; Söderman, Martin; Lambertsen, Kate L; Thomassen, Mads; Kruse, Torben A; Finsen, Bente

    2016-03-01

    Infiltration of myelin-specific T cells into the central nervous system induces the expression of proinflammatory cytokines in patients with multiple sclerosis (MS). We have previously shown that myelin-specific T cells are recruited into zones of axonal degeneration, where they stimulate lesion-reactive microglia. To gain mechanistic insight, we used RNA microarray analysis to compare the transcript profile in hippocampi from perforant pathway axonal-lesioned mice with and without adoptively transferred myelin-specific T cells 2 days postlesion, when microglia are clearly lesion reactive. Pathway analysis revealed that, among the 1,447 differently expressed transcripts, the interleukin (IL)-1 pathway including all IL-1 receptor ligands was upregulated in the presence of myelin-specific T cells. Quantitative polymerase chain reaction showed increased mRNA levels of IL-1β, IL-1α, and IL-1 receptor antagonist in the T-cell-infiltrated hippocampi from axonal-lesioned mice. In situ hybridization and immunohistochemistry showed a T-cell-enhanced lesion-specific expression of IL-1β mRNA and protein, respectively, and induction of the apoptosis-associated speck-like protein, ASC, in CD11b(+) cells. Double in situ hybridization showed colocalization of IL-1β mRNA in a subset of CD11b mRNA(+) cells, of which many were part of cellular doublets or clusters, characteristic of proliferating, lesion-reactive microglia. Double-immunofluorescence showed a T-cell-enhanced colocalization of IL-1β to CD11b(+) cells, including lesion-reactive CD11b(+) ramified microglia. These results suggest that myelin-specific T cells stimulate lesion-reactive microglial-like cells to produce IL-1β. These findings are relevant to understand the consequences of T-cell infiltration in white and gray matter lesions in patients with MS.

  11. Recurrent renal giant leiomyosarcoma.

    PubMed

    Öziş, Salih Erpulat; Gülpınar, Kamil; Şahlı, Zafer; Konak, Baha Burak; Keskin, Mete; Özdemir, Süleyman; Ataoğlu, Ömür

    2016-01-01

    Primary renal leiomyosarcomas are rare, aggressive tumors. They constitute 1-2% of adult malignant renal tumors. Although leiomyosarcomas are the most common histological type (50-60%) of renal sarcomas, information on renal leiomyosarcoma is limited. Local or systemic recurrences are common. The radiological appearance of renal leiomyosarcomas is not specific, therefore renal leiomyosarcoma cannot be distinguished from renal cell carcinoma by imaging methods in all patients. A 74-year-old female patient presented to our clinic complaining of a palpable mass on the right side of her abdomen in November 2012. The abdominal magnetic resonance imaging revealed a mass, 25 × 24 × 23 cm in size. Her past medical history revealed that she has undergone right radical nephrectomy in 2007, due to a 11 × 12 × 13 cm renal mass that was then reported as renal cell carcinoma on abdominal magnetic resonance imaging, but the pathological diagnosis was low-grade renal leiomyosarcoma. The most recent follow-up of the patient was in 2011, with no signs of local recurrence or distant metastases within this four-year period. The patient underwent laparotomy on November 2012, and a 35 cm retroperitoneal mass was excised. The pathological examination of the mass was reported as high-grade leiomyosarcoma. The formation of this giant retroperitoneal mass in 1 year can be explained by the transformation of the lesion's pathology from low-grade to a high-grade tumor. PMID:27436926

  12. Giant pleomorphic adenoma of the parotid gland.

    PubMed

    Takahama, Ademar; da Cruz Perez, Danyel Elias; Magrin, José; de Almeida, Oslei Paes; Kowalski, Luiz Paulo

    2008-01-01

    Pleomorphic adenoma is the most common type of all benign and malignant salivary gland tumors, involving more frequently the parotid gland. It is a benign tumor with a slow and continuous growth that without treatment can reach an enormous size. We present a case of a giant pleomorphic adenoma in a 78-year-old man with a history of more than 30 years of a growing lesion in the parotid gland. Clinical examination revealed a giant mass on the right side of the face, however without any sign of facial nerve damage. The tumor was completely resected by total parotidectomy and preservation of the facial nerve. Macroscopically, the tumor measured 28 cm and weighed 4.0 Kg. On the histological examination there was a predominance of epithelial and myoepithelial cells in a hyaline and myxoid stroma. It was not found any area of malignant transformation. In the post-operatory the aesthetic and functional results were excellent.

  13. Squamous Cell Carcinoma Developing in a Cutaneous Lichen Planus Lesion: A Rare Case

    PubMed Central

    Ghosh, Saptarshi; Kotne, Sivasankar; Ananda Rao, P. B.; Turlapati, S. P. V.; Kumar Soren, Dillip

    2014-01-01

    Lichen planus is a benign disorder characterized by an itchy, noninfectious skin rash. Though lichen planus is a common papulosquamous disorder affecting about 1-2% of the population, neoplastic transformation of cutaneous lichen planus lesions occurs very rarely and should be borne in mind while treating nonhealing longstanding lesions of lichen planus. Studies suggest an estimated 0.3–3% risk of malignancy in patients with oral lichen planus, however, cutaneous lichen planus does not carry an increased risk of malignant degeneration. We present a case of a 36-year-old male with a 10-year-long history of hypertrophic lichen planus who presented with a nonhealing ulcer in the left popliteal fossa. The patient underwent wide local excision with superficial skin grafting. Postoperative histopathological examination revealed verrucous squamous cell carcinoma complicating lichen planus. In view of underlying structure involvement, adjuvant radiation therapy was given. This case is being reported to emphasize the infrequent possibility of development of malignancy in cutaneous lichen planus, especially if it presents as a longstanding, nonhealing, itchy lesion with patchy areas of depigmentation in the lower limbs. PMID:24839562

  14. Dietary excess vanadium induces lesions and changes of cell cycle of spleen in broilers.

    PubMed

    Cui, Wei; Cui, Hengmin; Peng, Xi; Fang, Jing; Zuo, Zhicai; Liu, Xiaodong; Wu, Bangyuan

    2011-11-01

    The purpose of this 42-day study was to investigate the effects of dietary excess vanadium on spleen growth and lesions by determining morphological changes and cell cycle of spleen. Four hundred twenty 1-day-old avian broilers were divided into six groups and fed on a corn-soybean basal diet as control diet or the same diet amended to contain 5, 15, 30, 45, 60 ppm of vanadium supplied as ammonium metavanadate. When compared with that of control group, the relative weight of spleen was significantly raised in 5- and 15-ppm groups, but depressed in 45- and 60-ppm groups. The gross lesions of spleen showed obvious atrophy with decreased volume and pale color in 45- and 60-ppm groups. Histopathologically, lymphocytes in splenic corpuscle and periarterial lymphatic sheath were variously decreased in number in 30-, 45-, and 60-ppm groups. The percentage of static phase (G0/G1) was significantly decreased, and the percentage of synthesis period (S) phase and the proliferating index (PI) were significantly increased in 5- and 15-ppm groups. The percentage of G0/G1 phase was significantly increased, and the percentage of mitotic phase (G2+M), S phase, and PI significantly decreased in 45- and 60-ppm groups. These results suggested that dietary excess vanadium (45 and 60 ppm) could inhibit growth of spleen and induce lesions in spleen in chicken.

  15. [Giant condyloma of the penis with malignant transformation associated with lichen sclerosus et atrophicus].

    PubMed

    Wessendorf, U; Bruch-Gerharz, D; Braunstein, S; Braunstein, R; Schulte, K-W; Reifenberger, J

    2009-10-01

    A 72-year old patient presented with a 6 months history of a rapidly growing tumor of the glans and foreskin. He had a long history of phimosis with lichen sclerosus et atrophicus-like lesions on the foreskin which had not been treated. The rest of the personal, family and sexual history was unremarkable. Treatment consists of circumcision and tumor excision. Histopathology confirmed a squamous cell carcinoma within a giant condyloma with a concomitant lichen sclerosus et atrophicus. CT- and ultrasound scans showed no metastases. Giant condylomas are a rare sexually transmitted disease usually caused by human papilloma virus subtypes 6, 11, but also by 16 and 18 among others. They are expansive, cauliflower-like destructive lesions that most frequently affect the anogenital region. In about 30 percent a giant condyloma progresses into a squamous cell carcinoma. Therapy of choice is the histopathologically controlled excision. Recurrences are often seen, so the patients should be monitored frequently after therapy. PMID:19756435

  16. Predictive value of red blood cell distribution width for coronary artery lesions in patients with Kawasaki disease.

    PubMed

    Xu, Haiyan; Fu, Songling; Wang, Wei; Zhang, Qing; Hu, Jian; Gao, Lichao; Zhu, Weihua; Gong, Fangqi

    2016-08-01

    Recent studies have shown that elevated red blood cell distribution width is associated with poor outcome in cardiovascular diseases. In order to assess the predictive value of red blood cell distribution width, before treatment with intravenous immunoglobulins, for coronary artery lesions in patient with Kawasaki disease, we compared 83 patients with coronary artery lesions and 339 patients without coronary artery lesions before treatment with intravenous immunoglobulin. Clinical, echocardiographic, and biochemical values were evaluated along with red blood cell distribution width. A total of 422 consecutive patients with Kawasaki disease were enrolled into our study. According to receiver operating characteristic curve analysis, the optimal red blood cell distribution width cut-off value for predicting coronary artery lesions was 14.55% (area under the curve was 0.721; p=0.000); eighty-three patients (19.7%) had coronary artery lesions, and 70% of the patients with coronary artery lesions had red blood cell distribution width level >14.55%. Logistic regression analysis revealed that fever duration >14 days (odds ratio was 3.42, 95% confidence interval was 1.27-9.22; p=0.015), intravenous immunoglobulin resistance (odds ratio was 2.33, 95% confidence interval was 1.02-5.29; p=0.04), and red blood cell distribution width >14.55% (odds ratio was 3.49, 95% confidence interval was 2.01-6.05; p=0.000) were independent predictors of coronary artery lesions in patients with Kawasaki disease. In Conclusion, red blood cell distribution width may be helpful for predicting coronary artery lesions in patients with Kawasaki disease.

  17. Role of Liquid-based Cytology and Cell Block in the Diagnosis of Endometrial Lesions

    PubMed Central

    Zhang, Hui; Wen, Jia; Xu, Pi-Li; Chen, Rui; Yang, Xi; Zhou, Lian-Er; Jiang, Ping; Wan, An-Xia; Liao, Qin-Ping

    2016-01-01

    Background: Liquid-based cytology (LBC) offers an alternative method to biopsy in screening endometrial cancer. Cell block (CB), prepared by collecting residual cytological specimen, represents a novel method to supplement the diagnosis of endometrial cytology. This study aimed to compare the specimen adequacy and diagnostic accuracy of LBC and CB in the diagnosis of endometrial lesions. Methods: A total of 198 women with high risks of endometrial carcinoma (EC) from May 2014 to April 2015 were enrolled in this study. The cytological specimens were collected by the endometrial sampler (SAP-1) followed by histopathologic evaluation of dilatation and curettage or biopsy guided by hysteroscopy. The residual cytological specimens were processed into paraffin-embedded CB after LBC preparation. Diagnostic accuracies of LBC and CB for detecting endometrial lesions were correlated with histological diagnoses. Chi-square test was used to compare the specimen adequacies of LBC and CB. Results: The specimen inadequate rate of CB was significantly higher than that of LBC (22.2% versus 7.1%, P < 0.01). There were 144 cases with adequate specimens for LBC and CB preparation. Among them, 29 cases were atypical endometrial hyperplasia (11 cases) or carcinoma (18 cases) confirmed by histology evaluation. Taking atypical hyperplasia and carcinoma as positive, the diagnostic accuracy of CB was 95.1% while it was 93.8% in LBC. When combined LBC with CB, the diagnostic accuracy was improved to 95.8%, with a sensitivity of 89.7% and specificity of 97.4%. Conclusions: CB is a feasible and reproducible adjuvant method for screening endometrial lesions. A combination of CB and LBC can improve the diagnostic accuracy of endometrial lesions. PMID:27270542

  18. Processus and recessus adhaerentes: giant adherens cell junction systems connect and attract human mesenchymal stem cells.

    PubMed

    Wuchter, Patrick; Boda-Heggemann, Judit; Straub, Beate K; Grund, Christine; Kuhn, Caecilia; Krause, Ulf; Seckinger, Anja; Peitsch, Wiebke K; Spring, Herbert; Ho, Anthony D; Franke, Werner W

    2007-06-01

    Substrate-adherent cultured cells derived from human bone marrow or umbilical cord blood ("mesenchymal stem cells") are of special interest for regenerative medicine. We report that such cells, which can display considerable heterogeneity with respect to their cytoskeletal protein complement, are often interconnected by special tentacle-like cell processes contacting one or several other cells. These processus adhaerentes, studded with many (usually small) puncta adhaerentia and varying greatly in length (up to more than 400 microm long), either contact each other in the intercellular space ("ET touches") or insert in a tight-fitting manner into deep plasma membrane invaginations (recessus adhaerentes), thus forming a novel kind of long (up to 50 microm) continuous cuff-like junction (manubria adhaerentia). The cell processes contain an actin microfilament core that is stabilized with ezrin, alpha-actinin, and myosin and accompanied by microtubules, and their adhering junctions are characterized by a molecular complement comprising the transmembrane glycoproteins N-cadherin and cadherin-11, in combination with the cytoplasmic plaque proteins alpha- and beta-catenin, together with p120(ctn), plakoglobin, and afadin. The processes are also highly dynamic and rapidly foreshorten as cell colonies approach a denser state of cell packing. These structures are obviously able to establish cell-cell connections, even over long distances, and can form deep-rooted and tight cell-cell adhesions. The possible relationship to similar cell processes in the embryonic primary mesenchyme and their potential in cell sorting and tissue formation processes in the body are discussed. PMID:17372769

  19. An approach to the diagnosis of spindle cell lesions of the breast.

    PubMed

    Rakha, Emad A; Aleskandarany, Mohammed A; Lee, Andrew H S; Ellis, Ian O

    2016-01-01

    Although most breast spindle cell lesions (BSCLs) are rare, they constitute a wide spectrum of diseases, ranging from reactive processes to aggressive malignant tumours. Despite their varied histogenesis and behaviour, some lesions show an overlap of morphological features, making accurate diagnosis a challenging task, particularly in needle core biopsies. Clinical history and immunohistochemistry can help in making a correct diagnosis in morphologically challenging cases. To make an accurate diagnosis, it is important to maintain a wide differential diagnosis and be familiar with the diverse morphological appearances of these different entities. BSCLs can generally be classified into bland-looking and malignant-looking categories. In the former, the commonest diagnosis is scarring. However, it is important to distinguish low-grade spindle cell metaplastic breast carcinoma from other benign entities, as the management is clearly different. In the malignant category, it is important to differentiate metaplastic carcinoma from other malignant primary and metastatic malignant spindle cell tumours of the breast, such as malignant phyllodes tumour, angiosarcoma, and melanoma. This review focuses on the classification and histological and molecular diagnosis of various BSCLs, with an emphasis on the diagnostic approach, including in core biopsies. PMID:26768028

  20. Giant cell tumors of the spine: has denosumab changed the treatment paradigm?

    PubMed

    Goldschlager, Tony; Dea, Nicolas; Boyd, Michael; Reynolds, Jeremy; Patel, Shreyaskumar; Rhines, Laurence D; Mendel, Ehud; Pacheco, Marina; Ramos, Edwin; Mattei, Tobias A; Fisher, Charles G

    2015-05-01

    OBJECT Giant cell tumors (GCTs) of the spine are rare and complex to treat. They have a propensity for local recurrence and the potential to metastasize. Treatment is currently surgical and presents unique challenges due to the proximity of neural structures and the need for reconstruction. Denosumab has been shown in clinical trials to be an effective treatment for GCT, but has not yet been studied specifically in GCT of the spine or as a surgical adjunct. To the authors' knowledge this is the first such reported series. METHODS A multicenter, prospective series of 5 patients with GCT of the spine treated with denosumab were included. Patient demographic data, oncological history, neurological status, tumor staging, treatment details and adverse events, surgical procedure, complications, radiological and histological responses, and patient outcome were analyzed. RESULTS All patients were women, with a mean age of 38 years, and presented with pain; 2 patients had additional neurological signs and symptoms. The mean duration of symptoms was 62 weeks. No patient had a prior tumor or metastatic disease at presentation. All patients had Enneking Stage III tumors and were treated with monthly cycles of 120 mg of denosumab, with initial additional loading doses on Days 8 and 15. Patients were given daily supplements of calcium (500 mg) and vitamin D (400 IU). There were no denosumab-related adverse events. All patients had a radiological response to denosumab. One patient failed to have a histological response to denosumab, with > 90% of tumor cells found to be viable on histological investigation. CONCLUSIONS This study reports the early experience of using denosumab in the treatment of spinal GCT. The results demonstrate a clinically beneficial radiological response and an impressive histological response in most but not all patients. Further experience with denosumab and longer patient follow-up is required. Denosumab has the potential to change the treatment paradigm

  1. Diffuse-type tenosynovial giant cell tumour: Current treatment concepts and future perspectives.

    PubMed

    Staals, Eric L; Ferrari, Stefano; Donati, Davide M; Palmerini, Emanuela

    2016-08-01

    At present, the optimal treatment strategy in patients with diffuse-type tenosynovial giant cell tumour (D-TGCT) is unclear. The purpose of this review was to describe current treatment options, and to highlight recent developments in the knowledge of the molecular pathogenesis of D-TGCT as well as related therapeutic implications. Epidemiology, clinical features, and the pathogenesis of D-TGCT and the most widely used treatment modalities are described. D-TGCT is a benign clonal neoplastic proliferation arising from the synovium. Patients are often symptomatic and require multiple surgical procedures during their lifetime. Currently, surgery is the main treatment for patients with D-TGCT, with relapse rates ranging from 14% to 55%. Radiosynovectomy and external beam radiotherapy have been used in combination with surgical excision or as single modalities. The finding that D-TGCT cells overexpress colony-stimulating factor 1 (CSF1), resulting in recruitment of CSF1 receptor (CSF1R)-bearing macrophages that are polyclonal and make up the bulk of the tumour, has led to clinical trials with CSF1R inhibitors. These inhibitors include small molecules such as imatinib, nilotinib, PLX3397, and the monoclonal antibody RG7155. In conclusion, D-TGCT impairs patients' quality of life significantly. The evidence that the pathogenetic loop of D-TGCT can be inhibited could potentially change the therapeutic armamentarium for this condition. Clinical trials of agents that target D-TGCT are currently ongoing. In the meantime, international registries should be activated in order to provide useful information on this relatively rare tumour. PMID:27267143

  2. Fine-needle aspiration of pigmented villonodular synovitis of the temporomandibular joint masquerading as a primary parotid gland lesion.

    PubMed

    Yu, G H; Staerkel, G A; Kershisnik, M M; Varma, D G

    1997-01-01

    The fine-needle aspiration findings in a case of pigmented villonodular synovitis of the temporomandibular joint are presented. The characteristic cytomorphologic and clinical features of this uncommon, benign fibrohistiocytic lesion are discussed. In addition, due to the initial clinical impression of a primary parotid gland lesion, the differential diagnosis for the cytomorphologic features observed (histiocytoid cells admixed with osteoclast-like giant cells) are discussed within the context of a primary salivary gland mass.

  3. Differential Expression of Viral Bcl-2 Encoded by Kaposi's Sarcoma-Associated Herpesvirus and Human Bcl-2 in Primary Effusion Lymphoma Cells and Kaposi's Sarcoma Lesions

    PubMed Central

    Widmer, Isabelle; Wernli, Marion; Bachmann, Felix; Gudat, Fred; Cathomas, Gieri; Erb, Peter

    2002-01-01

    Expression of human herpesvirus 8 viral Bcl-2 protein was demonstrated in spindle cells of late-stage Kaposi's sarcoma lesions but not in primary effusion lymphoma cell lines. In contrast, strong expression of human Bcl-2 was found in stimulated primary effusion lymphoma cells, whereas in Kaposi's sarcoma lesions preferential mononuclear cells, and to a lesser extent spindle cells, stained positive. PMID:11836434

  4. Two rare entities in the same palate lesion: hyalinizing-type clear cell carcinoma and necrotizing sialometaplasia.

    PubMed

    Arpaci, Rabia Bozdoğan; Kara, Tuba; Porgali, Canan; Serinsoz, Ebru; Polat, Ayse; Vayisoglu, Yusuf; Ozcan, Cengiz

    2014-05-01

    Hyalinizing clear cell carcinoma is a low-grade malignant epithelial neoplasm of the salivary glands. The tumor has epithelial cells and lacks myoepithelial cells. Necrotizing sialometaplasia is a benign, self-limiting lesion of the salivary glands. The clinical and histologic features mimic those of mucoepidermoid carcinoma or squamous cell carcinoma. The importance of these entities are the rarity of both of them and their potential to be misdiagnosed as other lesions. Pathologists and clinicians should be aware of these entities to prevent misdiagnosis. This is the first clinical report of 2 rare and consecutive different entities of the same location on the hard palate to our knowledge.

  5. Whole-mount confocal imaging of nuclei in giant feeding cells induced by root-knot nematodes in Arabidopsis.

    PubMed

    Vieira, Paulo; Engler, Gilbert; de Almeida Engler, Janice

    2012-07-01

    • Excellent visualization of nuclei was obtained here using a whole-mount procedure adapted to provide high-resolution images of large, irregularly shaped nuclei. The procedure is based on tissue clearing, and fluorescent staining of nuclear DNA with the dye propidium iodide. • The method developed for standard confocal imaging was applied to large multicellular root swellings, named galls, induced in plant hosts by the root-knot nematode Meloidogyne incognita. • Here, we performed a functional analysis, and examined the nuclear structure in giant feeding cells overexpressing the cell cycle inhibitor Kip-related protein 4 (KRP4). Ectopic KRP4 expression in galls led to aberrant nuclear structure, disturbing giant cell expansion and nematode reproduction. In vivo live-cell imaging of GFP-KRP4 demonstrated that this protein co-localizes to chromosomes from prophase to late anaphase during cell cycle progression. • The data presented here suggest the involvement of KRP4 during mitotic progression in plant cells. The detailed results obtained using confocal analysis also demonstrate the potential utility of a rapid, easy-to-use clearing method for the analysis of the nuclei of certain Arabidopsis mutants and other complex plant nuclei.

  6. Predicting drug susceptibility of non–small cell lung cancers based on genetic lesions

    PubMed Central

    Sos, Martin L.; Michel, Kathrin; Zander, Thomas; Weiss, Jonathan; Frommolt, Peter; Peifer, Martin; Li, Danan; Ullrich, Roland; Koker, Mirjam; Fischer, Florian; Shimamura, Takeshi; Rauh, Daniel; Mermel, Craig; Fischer, Stefanie; Stückrath, Isabel; Heynck, Stefanie; Beroukhim, Rameen; Lin, William; Winckler, Wendy; Shah, Kinjal; LaFramboise, Thomas; Moriarty, Whei F.; Hanna, Megan; Tolosi, Laura; Rahnenführer, Jörg; Verhaak, Roel; Chiang, Derek; Getz, Gad; Hellmich, Martin; Wolf, Jürgen; Girard, Luc; Peyton, Michael; Weir, Barbara A.; Chen, Tzu-Hsiu; Greulich, Heidi; Barretina, Jordi; Shapiro, Geoffrey I.; Garraway, Levi A.; Gazdar, Adi F.; Minna, John D.; Meyerson, Matthew; Wong, Kwok-Kin; Thomas, Roman K.

    2009-01-01

    Somatic genetic alterations in cancers have been linked with response to targeted therapeutics by creation of specific dependency on activated oncogenic signaling pathways. However, no tools currently exist to systematically connect such genetic lesions to therapeutic vulnerability. We have therefore developed a genomics approach to identify lesions associated with therapeutically relevant oncogene dependency. Using integrated genomic profiling, we have demonstrated that the genomes of a large panel of human non–small cell lung cancer (NSCLC) cell lines are highly representative of those of primary NSCLC tumors. Using cell-based compound screening coupled with diverse computational approaches to integrate orthogonal genomic and biochemical data sets, we identified molecular and genomic predictors of therapeutic response to clinically relevant compounds. Using this approach, we showed that v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations confer enhanced Hsp90 dependency and validated this finding in mice with KRAS-driven lung adenocarcinoma, as these mice exhibited dramatic tumor regression when treated with an Hsp90 inhibitor. In addition, we found that cells with copy number enhancement of v-abl Abelson murine leukemia viral oncogene homolog 2 (ABL2) and ephrin receptor kinase and v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (avian) (SRC) kinase family genes were exquisitely sensitive to treatment with the SRC/ABL inhibitor dasatinib, both in vitro and when it xenografted into mice. Thus, genomically annotated cell-line collections may help translate cancer genomics information into clinical practice by defining critical pathway dependencies amenable to therapeutic inhibition. PMID:19451690

  7. Langerhans cells increase in the dermal lesions of adult T cell leukaemia in Japan

    PubMed Central

    Shamoto, M

    1983-01-01

    In cases of adult T cell leukaemia neoplastic T cell infiltration in the skin was accompanied by an increase in Langerhans cells. This is in keeping with the view that Langerhans cells may induce antigen-specific and allogenic T cell activation. Images PMID:6600750

  8. Nonsurgical options to treat giant-cell tumors of the head and neck: A case report and brief review of the literature.

    PubMed

    Rasband-Lindquist, Allison N; Lindquist, Jonathan D; Larsen, Christopher G; Thiessen, Aaron; Girod, Douglas

    2016-07-01

    Central giant-cell granulomas (CGCGs) are relatively uncommon. When they do occur, they typically arise in the mandible and maxilla. Some lesions are more destructive than others, and the destructive subtype has a tendency to recur. Unfortunately, there is no reproducible way to differentiate aggressive from nonaggressive subtypes. Treatment of CGCG has historically been based on surgical curettage or wide local excision. However, surgery has been associated with significant morbidity, disfigurement, and expense, as well as a high recurrence rate. Pharmacologic treatments-either as an alternative or an adjunct to surgery-have been shown to yield acceptable results. These agents include intralesional and/or systemic corticosteroids, bisphosphonates, calcitonin, and interferon alfa. These options are typically less expensive than surgery, and they are associated with few side effects, which makes them potentially more desirable. We report the case of a 36-year-old woman with a CGCG who was successfully treated with a combination of an intralesional steroid and an oral steroid over a period of 5 months. As evidenced by this case, medical management can be effective for tumor regression in treating CGCG of the head and neck, and it is ultimately associated with less morbidity and is less costly. To the best of our knowledge, no randomized controlled studies have been published on this topic. Such a study would be welcome, particularly considering the presence of both aggressive and nonaggressive subtypes of CGCG. We also briefly review the literature. PMID:27434482

  9. Gene therapy inhibiting neointimal vascular lesion: in vivo transfer of endothelial cell nitric oxide synthase gene.

    PubMed Central

    von der Leyen, H E; Gibbons, G H; Morishita, R; Lewis, N P; Zhang, L; Nakajima, M; Kaneda, Y; Cooke, J P; Dzau, V J

    1995-01-01

    It is postulated that vascular disease involves a disturbance in the homeostatic balance of factors regulating vascular tone and structure. Recent developments in gene transfer techniques have emerged as an exciting therapeutic option to treat vascular disease. Several studies have established the feasibility of direct in vivo gene transfer into the vasculature by using reporter genes such as beta-galactosidase or luciferase. To date no study has documented therapeutic effects with in vivo gene transfer of a cDNA encoding a functional enzyme. This study tests the hypothesis that endothelium-derived nitric oxide is an endogenous inhibitor of vascular lesion formation. After denudation by balloon injury of the endothelium of rat carotid arteries, we restored endothelial cell nitric oxide synthase (ec-NOS) expression in the vessel wall by using the highly efficient Sendai virus/liposome in vivo gene transfer technique. ec-NOS gene transfection not only restored NO production to levels seen in normal untreated vessels but also increased vascular reactivity of the injured vessels. Neointima formation at day 14 after balloon injury was inhibited by 70%. These findings provide direct evidence that NO is an endogenous inhibitor of vascular lesion formation in vivo (by inhibiting smooth muscle cell proliferation and migration) and suggest the possibility of ec-NOS transfection as a potential therapeutic approach to treat neointimal hyperplasia. Images Fig. 1 Fig. 2 Fig. 5 PMID:7532305

  10. Gene Therapy Inhibiting Neointimal Vascular Lesion: In vivo Transfer of Endothelial Cell Nitric Oxide Synthase Gene

    NASA Astrophysics Data System (ADS)

    von der Leyen, Heiko E.; Gibbons, Gary H.; Morishita, Ryuichi; Lewis, Neil P.; Zhang, Lunan; Nakajima, Masatoshi; Kaneda, Yasufumi; Cooke, John P.; Dzau, Victor J.

    1995-02-01

    It is postulated that vascular disease involves a disturbance in the homeostatic balance of factors regulating vascular tone and structure. Recent developments in gene transfer techniques have emerged as an exciting therapeutic option to treat vascular disease. Several studies have established the feasibility of direct in vivo gene transfer into the vasculature by using reporter genes such as β-galactosidase or luciferase. To date no study has documented therapeutic effects with in vivo gene transfer of a cDNA encoding a functional enzyme. This study tests the hypothesis that endothelium-derived nitric oxide is an endogenous inhibitor of vascular lesion formation. After denudation by balloon injury of the endothelium of rat carotid arteries, we restored endothelial cell nitric oxide synthase (ec-NOS) expression in the vessel wall by using the highly efficient Sendai virus/liposome in vivo gene transfer technique. ec-NOS gene transfection not only restored NO production to levels seen in normal untreated vessels but also increased vascular reactivity of the injured vessel. Neointima formation at day 14 after balloon injury was inhibited by 70%. These findings provide direct evidence that NO is an endogenous inhibitor of vascular lesion formation in vivo (by inhibiting smooth muscle cell proliferation and migration) and suggest the possibility of ec-NOS transfection as a potential therapeutic approach to treat neointimal hyperplasia.

  11. Step by step approach to rare breast lesions containing spindle cells.

    PubMed

    Ünal, Betül; Erdoğan, Gülgün; Karaveli, Fatma Şeyda

    2015-01-01

    Differential diagnosis of spindle cell lesions of breast is challenging for certain reasons. The most important reason is the presence of cytological atypia and mitosis in all three conditions: reactive, benign, and malignant. Patients diagnosed with benign and malignant tumor/tumor-like lesions that had spindle cell components following the histopathological examination were included in the study. The patients' medical records were accessed to obtain the clinical history, follow-up notes, and radiological findings. Following histopathological, immunohistochemical, and clinical evaluations, the patients were diagnosed as follows: pseudoangiomatous stromal hyperplasia (PASH), bilateral desmoid-type fibromatosis (FM), adenomyoepithelioma (AME), myofibroblastoma (MFB), malignant phyllodes tumor (MF), high-grade AS, post-chemotherapy osteosarcoma (OS) + Paget's disease, and metaplastic carcinoma (MC). An algorithmic approach should be used in the diagnosis; cellular structure, presence and grade of atypia, growth pattern, mitotic activity, immunohistochemical staining, and clinical and radiological features should be evaluated together. Detection of some molecular changes can be useful in differential diagnosis. PMID:26558181

  12. Incidence and predictive factors of benign renal lesions in Korean patients with preoperative imaging diagnoses of renal cell carcinoma.

    PubMed

    Park, Seo Yong; Jeon, Seong Soo; Lee, Seo Yeon; Jeong, Byong Chang; Seo, Seong Il; Lee, Hyun Moo; Choi, Han Yong

    2011-03-01

    The present study was performed to determine the incidence and predictive factors of benign renal lesions in Korean patients undergoing nephrectomy for presumed renal cell carcinoma on preoperative imaging. We analyzed the pathologic reports and medical records of 1,598 eligible patients with unilateral, nonmetastatic, and nonfamilial renal masses. Of the 1,598 renal masses, 114 (7.1%) were benign lesions, including angiomyolipoma in 47 (2.9%), oncocytoma in 23 (1.4%), and complicated cysts in 18 (1.1%) patients. On univariate analysis, the proportion of benign lesions was significantly higher in female patients, and in patients with smaller tumors, cystic renal masses, and without gross hematuria as a presenting symptom. When renal lesions were stratified by tumor size, the proportion of benign as opposed to malignant lesions decreased significantly as tumor size increased. On multivariate analysis, female gender, smaller tumor size, and cystic lesions were significantly associated with benign histological features. The findings in this large cohort of Korean patients show a lower incidence (7.1%) of benign renal lesions than those of previous Western reports. Female gender, cystic renal lesions, and smaller tumor size are independent predictors of benign histological features.

  13. Flares in Biopsy-Proven Giant Cell Arteritis in Northern Italy

    PubMed Central

    Restuccia, Giovanna; Boiardi, Luigi; Cavazza, Alberto; Catanoso, Mariagrazia; Macchioni, Pierluigi; Muratore, Francesco; Cimino, Luca; Aldigeri, Raffaella; Crescentini, Filippo; Pipitone, Nicolò; Salvarani, Carlo

    2016-01-01

    Abstract This study evaluated the frequency, timing, and characteristics of flares in a large cohort of Italian patients with biopsy-proven giant cell arteritis (GCA) and to identify factors at diagnosis able to predict the occurrence of flares. We evaluated 157 patients with biopsy-proven transmural GCA diagnosed and followed at the Rheumatology Unit of Reggio Emilia Hospital (Italy) for whom sufficient information was available from the time of diagnosis until at least 4 years of follow-up. Fifty-seven patients (36.5%) experienced ≥1 flares. Fifty-one (46.4%) of the 110 total flares (88 relapses and 22 recurrences) were experienced during the first 2 years after diagnosis. The majority of relapses occurred with doses of prednisone ≤ 10 mg/day (82.9%), whereas only 3.4% of relapses occurred for doses ≥ 25 mg/day. Polymyalgia rheumatica (46.5%) and cranial symptoms (41.9%) were the most frequent manifestations at the time of the first relapse. Cumulative prednisone dose during the first year and total cumulative prednisone dose were significantly higher in flaring patients compared with those without flares (7.8 ± 2.4 vs 6.7 ± 2.4 g, P = 0.02; 15.5 ± 8.9 vs 10.0 ± 9.2 g, P = 0.0001, respectively). The total duration of prednisone treatment was longer in flaring patients (58 ± 44 vs 30 ± 30 months, P = 0.0001). Patients with disease flares had at diagnosis more frequently systemic manifestations (P = 0.02) and fever ≥ 38°C (P = 0.02), significantly lower hemoglobin levels (P = 0.05), more frequent presence at temporal artery biopsy (TAB) specimens of giant cells (P = 0.04) and intraluminal acute thrombosis (P = 0.007), and more moderate/severe arterial inflammation (P = 0.009) compared with those without flares. In the multivariate model fever ≥ 38 °C (hazard ratio 2.14; 95% confidence interval, 1.06–4.32, P = 0.03) and the severity of inflammatory infiltrate

  14. A Retrospective Study of Chinese Patients With Giant Cell Arteritis (GCA)

    PubMed Central

    Sun, Fei; Ma, Sha; Zheng, Wenjie; Tian, Xinping; Zeng, Xiaofeng

    2016-01-01

    Abstract A retrospective study was performed on 70 giant cell arteritis (GCA) patients in Peking Union Medical College Hospital (PUMCH). The aim of this study was to describe the clinical features of these Chinese GCA patients and explore the possible associated factors for severe ischemic manifestations. Medical charts of all patients were reviewed, and the demographic, clinical, and laboratory data were analyzed. The mean age at disease onset was 65.2 years old, and the ratio of male to female was 1:1. Fever and headache were most prominent symptoms at onset, which occurred in 51.4% and 30.0% of patients, respectively. Common manifestations at diagnosis were constitutional symptoms (85.7%), headache (68.8%), visual impairment (38.6%), jaw claudication (30%), scalp tenderness (30%), and concurrent polymyalgia rheumatic (27.1%). No significant difference in clinical manifestations between genders was observed. Comparisons between patients with and without severe ischemic manifestations including jaw claudication, permanent visual loss, or cerebrovascular accident had shown that fever and asthenia were significantly less frequent in patients with severe ischemic manifestations (P = 0.006 and 0.023, respectively), and the mean value of erythrocyte sedimentation rate (ESR) was significantly lower in patients with severe ischemic manifestations than patients without (P = 0.001). History of smoking was more frequent in patients with severe ischemic manifestations (P = 0.038). This is the largest group of GCA patients from China so far. When compared our data with patients reported in the literature, this series of GCA patients were younger and without female predominance. The clinical manifestations of patients in this report were similar to other studies except for a higher prevalence of constitutional symptoms. The results of this study indicated that lower systemic inflammatory response and the history of smoking might be associated with severe ischemic

  15. Prevalence and distribution of VZV in temporal arteries of patients with giant cell arteritis

    PubMed Central

    White, Teresa; Khmeleva, Nelly; Heintzman, Anna; Choe, Alexander; Boyer, Philip J.; Grose, Charles; Carpenter, John E.; Rempel, April; Bos, Nathan; Kandasamy, Balasubramaniyam; Lear-Kaul, Kelly; Holmes, Dawn B.; Bennett, Jeffrey L.; Cohrs, Randall J.; Mahalingam, Ravi; Mandava, Naresh; Eberhart, Charles G.; Bockelman, Brian; Poppiti, Robert J.; Tamhankar, Madhura A.; Fogt, Franz; Amato, Malena; Wood, Edward; Durairaj, Vikram; Rasmussen, Steve; Petursdottir, Vigdis; Pollak, Lea; Mendlovic, Sonia; Chatelain, Denis; Keyvani, Kathy; Brueck, Wolfgang; Nagel, Maria A.

    2015-01-01

    Objective: Varicella-zoster virus (VZV) infection may trigger the inflammatory cascade that characterizes giant cell arteritis (GCA). Methods: Formalin-fixed, paraffin-embedded GCA-positive temporal artery (TA) biopsies (50 sections/TA) including adjacent skeletal muscle and normal TAs obtained postmortem from subjects >50 years of age were examined by immunohistochemistry for presence and distribution of VZV antigen and by ultrastructural examination for virions. Adjacent regions were examined by hematoxylin & eosin staining. VZV antigen–positive slides were analyzed by PCR for VZV DNA. Results: VZV antigen was found in 61/82 (74%) GCA-positive TAs compared with 1/13 (8%) normal TAs (p < 0.0001, relative risk 9.67, 95% confidence interval 1.46, 63.69). Most GCA-positive TAs contained viral antigen in skip areas. VZV antigen was present mostly in adventitia, followed by media and intima. VZV antigen was found in 12/32 (38%) skeletal muscles adjacent to VZV antigen–positive TAs. Despite formalin fixation, VZV DNA was detected in 18/45 (40%) GCA-positive VZV antigen–positive TAs, in 6/10 (60%) VZV antigen–positive skeletal muscles, and in one VZV antigen–positive normal TA. Varicella-zoster virions were found in a GCA-positive TA. In sections adjacent to those containing VZV, GCA pathology was seen in 89% of GCA-positive TAs but in none of 18 adjacent sections from normal TAs. Conclusions: Most GCA-positive TAs contained VZV in skip areas that correlated with adjacent GCA pathology, supporting the hypothesis that VZV triggers GCA immunopathology. Antiviral treatment may confer additional benefit to patients with GCA treated with corticosteroids, although the optimal antiviral regimen remains to be determined. PMID:25695965

  16. Surgical Outcomes in Patients with High Spinal Instability Neoplasm Score Secondary to Spinal Giant Cell Tumors

    PubMed Central

    Elder, Benjamin D.; Sankey, Eric W.; Goodwin, C. Rory; Kosztowski, Thomas A.; Lo, Sheng-Fu L.; Bydon, Ali; Wolinsky, Jean-Paul; Gokaslan, Ziya L.; Witham, Timothy F.; Sciubba, Daniel M.

    2015-01-01

    Study Design Retrospective review. Objective To describe the surgical outcomes in patients with high preoperative Spinal Instability Neoplastic Score (SINS) secondary to spinal giant cell tumors (GCT) and evaluate the impact of en bloc versus intralesional resection and preoperative embolization on postoperative outcomes. Methods A retrospective analysis was performed on 14 patients with GCTs of the spine who underwent surgical treatment prior to the use of denosumab. A univariate analysis was performed comparing the patient demographics, perioperative characteristics, and surgical outcomes between patients who underwent en bloc marginal (n = 6) compared with those who had intralesional (n = 8) resection. Results Six patients underwent en bloc resections and eight underwent intralesional resection. Preoperative embolization was performed in eight patients. All patients were alive at last follow-up, with a mean follow-up length of 43 months. Patients who underwent en bloc resection had longer average operative times (p = 0.0251), higher rates of early (p = 0.0182) and late (p = 0.0389) complications, and a higher rate of surgical revision (p = 0.0120). There was a 25% (2/8 patients) local recurrence rate for intralesional resection and a 0% (0/6 patients) local recurrence rate for en bloc resection (p = 0.0929). Conclusions Surgical excision of spinal GCTs causing significant instability, assessed by SINS, is associated with high intraoperative blood loss despite embolization and independent of resection method. En bloc resection requires a longer operative duration and is associated with a higher risk of complications when compared with intralesional resection. However, the increased morbidity associated with en bloc resection may be justified as it may minimize the risk of local recurrence. PMID:26835198

  17. Do solar cycles influence giant cell arteritis and rheumatoid arthritis incidence?

    SciTech Connect

    Wing, Simon; Rider, Lisa G.; Johnson, Jay R.; Miller, Federick W.; Matteson, Eric L.; Crowson, C. S.; Gabriel, S. E.

    2015-05-15

    Our objective was to examine the influence of solar cycle and geomagnetic effects on the incidence of giant cell arteritis (GCA) and rheumatoid arthritis (RA). Methods: We used data from patients with GCA (1950-2004) and RA (1955-2007) obtained from population-based cohorts. Yearly trends in age-adjusted and sex-adjusted incidence were correlated with the F10.7 index (solar radiation at 10.7 cm wavelength, a proxy for the solar extreme ultraviolet radiation) and AL index (a proxy for the westward auroral electrojet and a measure of geomagnetic activity). Fourier analysis was performed on AL, F10.7, and GCA and RA incidence rates. Results: The correlation of GCA incidence with AL is highly significant: GCA incidence peaks 0-1 year after the AL reaches its minimum (ie, auroral electrojet reaches a maximum). The correlation of RA incidence with AL is also highly significant. RA incidence rates are lowest 5-7 years after AL reaches maximum. AL, GCA and RA incidence power spectra are similar: they have a main peak (periodicity) at about 10 years and a minor peak at 4-5 years. However, the RA incidence power spectrum main peak is broader (8-11 years), which partly explains the lower correlation between RA onset and AL. The auroral electrojets may be linked to the decline of RA incidence more strongly than the onset of RA. The incidences of RA and GCA are aligned in geomagnetic latitude. Conclusions: AL and the incidences of GCA and RA all have a major periodicity of about 10 years and a secondary periodicity at 4-5 years. Geomagnetic activity may explain the temporal and spatial variations, including east-west skewness in geographic coordinates, in GCA and RA incidence, although the mechanism is unknown. Lastly, the link with solar, geospace and atmospheric parameters need to be investigated. These novel findings warrant examination in other populations and with other autoimmune diseases.

  18. Usefulness of Rabbit Anti-thymocyte Globulin in Patients With Giant Cell Myocarditis.

    PubMed

    Suarez-Barrientos, Aida; Wong, Joyce; Bell, Alexander; Lyster, Haifa; Karagiannis, Georgios; Banner, Nicholas R

    2015-08-01

    Giant cell myocarditis (GCM) is an aggressive inflammatory myocardial disease. Immunosuppression is an effective treatment for some cases. However, the duration of action of agents such as muromonab CD3 is short and others such as the calcineurin inhibitors may lead to renal failure. Here we describe the outcome of a novel approach to treatment using rabbit anti-thymocyte globulin (RATG). A retrospective analysis of 6 patients treated with RATG for GCM was performed. Diagnosis was confirmed by endomyocardial biopsy, and RATG was administered with a high dose of corticosteroids. None of the patients had cytokine release syndrome or leukopenia, and 5 had thrombocytopenia (2 of them severe). Only 1 had a serious bleeding event that occurred after implantation of mechanical circulatory support. None developed impaired renal function after the treatment. Five were successfully discharged home with an increase in global left ventricular ejection fraction of 29%. Four are currently alive without recurrent disease, 1 of them after heart transplantation, with a mean follow-up of 970 days (423 to 1,875 days), left ventricular ejection fraction of 53%, and all in current New York Heart Association Classification class ≤II. Only 1 case had GCM recurrence. There were 2 deaths: one because of intracranial bleeding after mechanical circulatory support implantation and the other caused by primary graft dysfunction. In conclusion, patients with GCM can be successfully immunosuppressed with RATG and corticosteroids, thereby avoiding renal impairment. Early thrombocytopenia is the main adverse event. Larger cohorts of patients are necessary to compare the different immunosuppressant strategies available for GCM in a randomized fashion. PMID:26048854

  19. Predicting malignant transformation of esophageal squamous cell lesions by combined biomarkers in an endoscopic screening program

    PubMed Central

    Zhang, Hao; Li, Hao; Ma, Qing; Yang, Fang-Yan; Diao, Tao-Yu

    2016-01-01

    AIM To determine the association of p53, carcinoembryonic antigen (CEA) and CA19-9 protein expression with esophageal carcinogenesis. METHODS An iodine staining endoscopic screening program of esophageal lesions was carried out in the high-incidence area of Feicheng County, China. Seventy-seven patients with basal cell hyperplasia (BCH), 247 with low-grade dysplasia (LGD), 51 with high-grade dysplasia (HGD), 134 with invasive cancer, and 80 normal controls diagnosed by mucous membrane biopsy pathology were enrolled. Immunohistochemical detection of p53, CEA and CA19-9 proteins was performed. In the ROC curve analysis, the expression of a single biomarker and the expression of a combination of biomarkers were used to predict the risk of these four esophageal lesions. RESULTS The positive rates of p53 protein expression in invasive cancer, HGD, LGD, BCH and the normal control groups were 53.0%, 52.9%, 35.6%, 27.3% and 20.0%, respectively; the positive rates of CA19-9 protein expression were 44.0%, 33.3%, 16.5%, 9.2% and 6.2%, respectively; the positive rates of CEA protein expression were 74.6%, 60.8%, 23.3%, 23.7% and 16.2%, respectively. The positive rates of the combined expression of the three biomarkers were 84.3%, 76.5%, 47.6%, 42.9% and 27.5%, respectively. In the receiver operating characteristic curves of the combination of the three biomarkers, the specificity was 88.8% for the normal controls, and the sensitivity was 58.2% for invasive cancer, 25.5% for HGD, 11.2% for LGD, and 6.5% for BCH. CONCLUSION p53, CEA and CA19-9 protein expression was correlated with esophageal carcinogenesis, and testing for the combination of these biomarkers is useful for identifying high-risk patients with precancerous lesions.

  20. Foreign Body Giant Cell Formation Is Preceded by Lamellipodia Formation and Can Be Attenuated by Inhibition of Rac1 Activation

    PubMed Central

    Jay, Steven M.; Skokos, Eleni; Laiwalla, Farah; Krady, Marie-Marthe; Kyriakides, Themis R.

    2007-01-01

    Macrophages that are recruited to the site of implanted biomaterials undergo fusion to form surface-damaging foreign body giant cells. Exposure of peripheral blood monocytes to interleukin-4 can recapitulate the fusion process in vitro. In this study, we used interleukin-4 to induce multinucleation of murine bone marrow-derived macrophages and observed changes in cell shape, including elongation and lamellipodia formation, before fusion. Because cytoskeletal rearrangements are regulated by small GTPases, we examined the effects of inhibitors of Rho kinase (Y-32885) and Rac activation (NSC23766) on fusion. Y-32885 did not prevent cytoskeletal changes or fusion but limited the extent of multinucleation. NSC23766, on the other hand, inhibited lamellipodia formation and fusion in a dose-dependent manner. In addition, we found that in control cells, these changes were preceded by Rac1 activation. However, NSC23766 did not block the uptake of polystyrene microspheres. Likewise, short interfering RNA knockdown of Rac1 limited fusion without limiting phagocytosis. Thus, phagocytosis and fusion can be partially decoupled based on their susceptibility to NSC23766. Furthermore, poly(ethylene-co-vinyl acetate) scaffolds containing NSC23766 attenuated foreign body giant cell formation in vivo. These observations suggest that targeting Rac1 activation could protect biomaterials without compromising the ability of macrophages to perform beneficial phagocytic functions at implantation sites. PMID:17556592

  1. Foreign body giant cell formation is preceded by lamellipodia formation and can be attenuated by inhibition of Rac1 activation.

    PubMed

    Jay, Steven M; Skokos, Eleni; Laiwalla, Farah; Krady, Marie-Marthe; Kyriakides, Themis R

    2007-08-01

    Macrophages that are recruited to the site of implanted biomaterials undergo fusion to form surface-damaging foreign body giant cells. Exposure of peripheral blood monocytes to interleukin-4 can recapitulate the fusion process in vitro. In this study, we used interleukin-4 to induce multinucleation of murine bone marrow-derived macrophages and observed changes in cell shape, including elongation and lamellipodia formation, before fusion. Because cytoskeletal rearrangements are regulated by small GTPases, we examined the effects of inhibitors of Rho kinase (Y-32885) and Rac activation (NSC23766) on fusion. Y-32885 did not prevent cytoskeletal changes or fusion but limited the extent of multinucleation. NSC23766, on the other hand, inhibited lamellipodia formation and fusion in a dose-dependent manner. In addition, we found that in control cells, these changes were preceded by Rac1 activation. However, NSC23766 did not block the uptake of polystyrene microspheres. Likewise, short interfering RNA knockdown of Rac1 limited fusion without limiting phagocytosis. Thus, phagocytosis and fusion can be partially decoupled based on their susceptibility to NSC23766. Furthermore, poly(ethylene-co-vinyl acetate) scaffolds containing NSC23766 attenuated foreign body giant cell formation in vivo. These observations suggest that targeting Rac1 activation could protect biomaterials without compromising the ability of macrophages to perform beneficial phagocytic functions at implantation sites.

  2. Erythropoietin reduces storage lesions and decreases apoptosis indices in blood bank red blood cells

    PubMed Central

    Penuela, Oscar Andrés; Palomino, Fernando; Gómez, Lina Andrea

    2015-01-01

    Background Recent evidence shows a selective destruction of the youngest circulating red blood cells (neocytolysis) trigged by a drop in erythropoietin levels. Objective The aim of this study was to evaluate the effect of recombinant human erythropoietin beta on the red blood cell storage lesion and apoptosis indices under blood bank conditions. Methods Each one of ten red blood cell units preserved in additive solution 5 was divided in two volumes of 100 mL and assigned to one of two groups: erythropoietin (addition of 665 IU of recombinant human erythropoietin) and control (isotonic buffer solution was added). The pharmacokinetic parameters of erythropoietin were estimated and the following parameters were measured weekly, for six weeks: Immunoreactive erythropoietin, hemolysis, percentage of non-discocytes, adenosine triphosphate, glucose, lactate, lactate dehydrogenase, and annexin-V/esterase activity. The t-test or Wilcoxon's test was used for statistical analysis with significance being set for a p-value <0.05. Results Erythropoietin, when added to red blood cell units, has a half-life >6 weeks under blood bank conditions, with persistent supernatant concentrations of erythropoietin during the entire storage period. Adenosine triphosphate was higher in the Erythropoietin Group in Week 6 (4.19 ± 0.05 μmol/L vs. 3.53 ± 0.02 μmol/L; p-value = 0.009). The number of viable cells in the Erythropoietin Group was higher than in the Control Group (77% ± 3.8% vs. 71% ± 2.3%; p-value <0.05), while the number of apoptotic cells was lower (9.4% ± 0.3% vs. 22% ± 0.8%; p-value <0.05). Conclusions Under standard blood bank conditions, an important proportion of red blood cells satisfy the criteria of apoptosis. Recombinant human erythropoietin beta seems to improve storage lesion parameters and mitigate apoptosis. PMID:26969770

  3. Pineal mixed germ cell tumor with a synchronous sellar lesion in the sixth decade.

    PubMed

    Bohara, Manoj; Hirano, Hirofumi; Tokimura, Hiroshi; Hanaya, Ryosuke; Yonezawa, Hajime; Campos, Francia; Sugiyama, Kazuhiko; Sugata, Sei; Arita, Kazunori

    2011-04-01

    Intracranial germ cell tumors (GCTs) typically affect children and adolescents. We here report on a 59-year-old male patient presenting with diplopia, polydipsia and polyuria. On clinical examination, slight restriction of the upward gaze was seen on the left side. Computed tomography demonstrated calcifications in the pineal region and enhanced neurohypophysis. Magnetic resonance imaging displayed a heterogeneous pineal mass of 3-cm diameter, which was multicystic with an enhanced cyst wall, and also swelling of the pituitary stalk. The pineal lesion of the tumor, which included calcifications and keratinaceous components, was totally excised using an occipital transtentorial approach. Histopathological examination showed it to be a mixed GCT with germinoma and mature teratoma components. Postoperative chemoradiotherapy provided complete disappearance of the suprasellar lesion. To our knowledge, this is the first case of mixed bifocal GCT in an older adult reported in the literature, although a few cases of tumors with a single histological component have been reported. Hence, our case further underlines the possibility of the occurrence of GCTs in older adults and advocates the consideration of GCTs in the differential diagnosis of such cases for appropriate management. PMID:21287366

  4. Disseminated Mycobacterium marinum Infection With a Destructive Nasal Lesion Mimicking Extranodal NK/T Cell Lymphoma

    PubMed Central

    Asakura, Takanori; Ishii, Makoto; Kikuchi, Taku; Kameyama, Kaori; Namkoong, Ho; Nakata, Noboru; Sugita, Kayoko; Tasaka, Sadatomo; Shimizu, Takayuki; Hoshino, Yoshihiko; Okamoto, Shinichiro; Betsuyaku, Tomoko; Hasegawa, Naoki

    2016-01-01

    Abstract Mycobacterium marinum is a ubiquitous waterborne organism that mainly causes skin infection in immunocompetent patients, and its disseminated infection is rare. Extranodal NK/T cell lymphoma, nasal type (ENKL) usually localizes at the nasal and/or paranasal area, but occasionally disseminates into the skin/soft tissue and gastrointestinal tract. Compromised immunity is a risk factor for developing nontuberculous mycobacterial (NTM) infection and malignant lymphoma, and the 2 diseases may share similar clinical presentation; however, only a few reports have described NTM infection mimicking malignant lymphoma. A 43-year-old Japanese man presented to our hospital complaining of multiple progressive skin nodules and purulent nasal discharge for 3 weeks. He was diagnosed with Crohn disease with refractory enteropathic arthritis and has been treated with anti-tumor necrosis factor alpha agents for 25 years. Fiberoptic nasal examination revealed septal perforation with hemorrhagic mucus and purulent rhinorrhea. Histological examination of the nasal septum revealed the infiltration of atypical medium-to-large-sized cells with erosion. The cells were positive for cytoplasmic CD3, granzyme B, and Epstein–Barr virus-encoded small RNA. Histological examination of the skin nodules and auricle also showed infiltration of atypical lymphocytes. The patient was tentatively diagnosed with ENKL, and chemotherapy was considered. However, the skin lesions decreased in size after discontinuation of immunosuppressive agents and minocycline administration. Two weeks later, nasal septum and lavage fluid and left leg skin cultures were positive for M marinum, and minocycline was discontinued. The skin and the nasal lesions improved after 2 months. To the best of our knowledge, this is the first case of disseminated M marinum infection with a destructive nasal lesion mimicking ENKL. The differentiation between M marinum infection and ENKL is clinically important because

  5. Salt tolerance at single cell level in giant-celled Characeae

    PubMed Central

    Beilby, Mary J.

    2015-01-01

    Characean plants provide an excellent experimental system for electrophysiology and physiology due to: (i) very large cell size, (ii) position on phylogenetic tree near the origin of land plants and (iii) continuous spectrum from very salt sensitive to very salt tolerant species. A range of experimental techniques is described, some unique to characean plants. Application of these methods provided electrical characteristics of membrane transporters, which dominate the membrane conductance under different outside conditions. With this considerable background knowledge the electrophysiology of salt sensitive and salt tolerant genera can be compared under salt and/or osmotic stress. Both salt tolerant and salt sensitive Characeae show a rise in membrane conductance and simultaneous increase in Na+ influx upon exposure to saline medium. Salt tolerant Chara longifolia and Lamprothamnium sp. exhibit proton pump stimulation upon both turgor decrease and salinity increase, allowing the membrane PD to remain negative. The turgor is regulated through the inward K+ rectifier and 2H+/Cl- symporter. Lamprothamnium plants can survive in hypersaline media up to twice seawater strength and withstand large sudden changes in salinity. Salt sensitive C. australis succumbs to 50–100 mM NaCl in few days. Cells exhibit no pump stimulation upon turgor decrease and at best transient pump stimulation upon salinity increase. Turgor is not regulated. The membrane PD exhibits characteristic noise upon exposure to salinity. Depolarization of membrane PD to excitation threshold sets off trains of action potentials, leading to further loses of K+ and Cl-. In final stages of salt damage the H+/OH- channels are thought to become the dominant transporter, dissipating the proton gradient and bringing the cell PD close to 0. The differences in transporter electrophysiology and their synergy under osmotic and/or saline stress in salt sensitive and salt tolerant characean cells are discussed in

  6. Central retinal artery occlusion as an iatrogenic complication of treatment of central giant cell granuloma of the mandible.

    PubMed

    Bhushan, Gauri; Gupta, Swati; Bhushan, Urvashi; Raina, Usha Kaul

    2015-05-01

    Although intralesional steroid injection as a management option for central giant cell granuloma (CGCG) of the mandible is considered safe, central retinal artery occlusion (CRAO) is a dreaded and previously unreported complication of this treatment modality. The present report discusses an iatrogenic case of CRAO that occurred during treatment of CGCG of the mandible. This complication occurred because of high injection pressure, which led to the opening of an anastomosis between the external and internal carotid arteries, leading to retrograde migration of steroid particles. This report also highlights the importance of being aware of such communications.

  7. Painless giant cell thyroiditis diagnosed by fine needle aspiration and associated with intense thyroidal uptake of gallium

    SciTech Connect

    Sanders, L.R.; Moreno, A.J.; Pittman, D.L.; Jones, J.D.; Spicer, M.J.; Tracy, K.P.

    1986-05-01

    A 52-year-old woman presented with fever, goiter, and no evidence of pain or tenderness in the thyroid. A diagnosis of silent thyroiditis was made after obtaining evidence of biochemical thyrotoxicosis, intense gallium-67 citrate thyroidal localization, and cytologic thyroiditis. Fine needle aspiration biopsy of the thyroid revealed numerous giant cells in all areas of the thyroid, typical of subacute thyroiditis. This is believed to be the first time painless thyroiditis is reported with the classic cytologic feature of painful subacute thyroiditis.

  8. Rare Presentation of Giant Cell Tumor in the Internal Auditory Canal: Case Report and Review of the Literature

    PubMed Central

    Jada, Ajit S.; Shrivastava, Raj K.; Mannan, Abul; Kobets, Andrew; Manolidis, Spiros

    2015-01-01

    Giant cell tumor (GCT) is a benign but locally aggressive bone tumor that usually involves the end of long bones. It is a relatively common neoplasm in patients, constituting 5 to 10% of all benign bone tumors. Approximately 2% of GCTs occur in the craniofacial skeleton with a predilection for the ethmoid, sphenoid, and temporal bones. The skull base location is unique and not commonly described. Hearing loss, headache, tinnitus, and subcutaneous masses are the most commonly reported symptoms in GCTs of the skull base. In this case report we present the first description of a GCT within the internal auditory canal causing cranial neuropathy and review the recent pertinent literature. PMID:26251814

  9. Cystic trophoblastic tumor: a nonaggressive lesion in postchemotherapy resections of patients with testicular germ cell tumors.

    PubMed

    Ulbright, Thomas M; Henley, John D; Cummings, Oscar W; Foster, Richard S; Cheng, Liang

    2004-09-01

    Cystic trophoblastic tumor (CTT) is an uncommon lesion that is usually seen after chemotherapy in patients with testicular germ cell tumors. Its clinical significance has not been well studied. We identified 17 patients with CTT in retroperitoneal lymph node dissections (RPLNDs) after cisplatin-based chemotherapy for testicular germ cell tumors. None had other forms of persistent germ cell tumor except for teratoma, and no patient received additional chemotherapy after RPLND. At the time of RPLND, 7 patients were known to have had normal serum levels of beta-subunit of human chorionic gonadotropin (beta-hCG), whereas 5 had relatively mild elevations (1.6-165 mIU/mL, median, 8.0 mIU/mL). The CTTs consisted of circumscribed, small cysts, usually multifocal, lined by mostly mononucleated trophoblast cells with abundant eosinophilic cytoplasm, often with smudged nuclei and showing only infrequent mitotic figures. Although the epithelial lining was often stratified to several layers in thickness or formed intracystic papillary tufts, solid proliferations of trophoblast cells within the stroma were absent, as were clearly biphasic admixtures of mononucleated and multinucleated trophoblast cells. The cysts were either empty or contained fibrinoid material and were set in a hypocellular, fibrous stroma with adjacent teratoma. Stains for hCG highlighted rare cells. On follow-up of 15 patients, 11 were disease free (mean, 80 months). Three recurred with serum alpha-fetoprotein elevations at 25, 31, and 107 months, respectively, and one with beta-hCG elevation at 2 months. The latter patient, however, also had unresected mediastinal tumor postchemotherapy. We conclude that the finding of CTT in postchemotherapy resections does not warrant additional chemotherapy. Its clinical significance appears similar to that of residual teratoma.

  10. αβ T-cell receptors from multiple sclerosis brain lesions show MAIT cell–related features

    PubMed Central

    Held, Kathrin; Bhonsle-Deeng, Latika; Siewert, Katherina; Sato, Wakiro; Beltrán, Eduardo; Schmidt, Stephan; Rühl, Geraldine; Ng, Judy K.M.; Engerer, Peter; Moser, Markus; Klinkert, Wolfgang E.F.; Babbe, Holger; Misgeld, Thomas; Wekerle, Hartmut; Laplaud, David-Axel; Hohlfeld, Reinhard

    2015-01-01

    Objectives: To characterize phenotypes of T cells that accumulated in multiple sclerosis (MS) lesions, to compare the lesional T-cell receptor (TCR) repertoire of T-cell subsets to peripheral blood, and to identify paired α and β chains from single CD8+ T cells from an index patient who we followed for 18 years. Methods: We combined immunohistochemistry, laser microdissection, and single-cell multiplex PCR to characterize T-cell subtypes and identify paired TCRα and TCRβ chains from individual brain-infiltrating T cells in frozen brain sections. The lesional and peripheral TCR repertoires were analyzed by pyrosequencing. Results: We found that a TCR Vβ1+ T-cell population that was strikingly expanded in active brain lesions at clinical onset comprises several subclones expressing distinct yet closely related Vα7.2+ α chains, including a canonical Vα7.2-Jα33 chain of mucosal-associated invariant T (MAIT) cells. Three other α chains bear striking similarities in their antigen-recognizing, hypervariable complementarity determining region 3. Longitudinal repertoire studies revealed that the TCR chains that were massively expanded in brain at onset persisted for several years in blood or CSF but subsequently disappeared except for the canonical Vα7.2+ MAIT cell and a few other TCR sequences that were still detectable in blood after 18 years. Conclusions: Our observation that a massively expanded TCR Vβ1-Jβ2.3 chain paired with distinct yet closely related canonical or atypical MAIT cell–related α chains strongly points to an antigen-driven process in early active MS brain lesions. PMID:25977934

  11. CD10 and CD138 can be expressed in giant cell tumor of bone: An immunohistochemical study.

    PubMed

    Al-Abbadi, Mousa A; Al-Yousef, Mohammed J; Yousef, Mohammad M; Sheikh, Salwa S; Almasri, Nidal M; Amr, Samir S

    2016-01-01

    Giant cell tumor of bone (GCTB) is a primary bone neoplasm which is characterized by the presence of mononuclear cells (MCs) and osteoclast-like multinucleated giant cells (MNGCs). Up to our knowledge, CD10 immunoreactivity in GCTB has not yet been studied, and only one study touched on CD138 immunoreactivity in GCTB. The objective of this study is to investigate the immunoreactivity of CD10 and CD138 in GCTB. We offer a discussion of our findings in the context of the differential diagnosis, particularly in small biopsy material. We retrieved and reviewed 15 well-documented cases of GCTB from January 2008 to December 2014. Well-controlled standard immunohistochemical satins were performed on these cases for CD10 and CD138 and few other selected antibodies. Immunoreactivity for CD10 was membranous and was found in 14 (93%) cases. This immunoreactivity was found only in the MCs, whereas the MNGC were all negative. CD138 showed variable positivity in 11 (73%) while 4 (37%) were completely negative. Similar to CD10, staining for CD138 was only seen in the MC; however, the immunoreactivity was predominantly concentrated in the peri-vascular areas. Most of GCTB cases can show variable immunoreactivity for CD10 and CD138. The aforementioned immune-expression raise the possibility of a role in the pathogenesis of GCTB. Paying attention to this immunoreactivity is recommended when considering the clinical and radiological differential diagnosis, especially in small biopsy specimens. PMID:27390668

  12. CD10 and CD138 can be expressed in giant cell tumor of bone: An immunohistochemical study

    PubMed Central

    Al-Abbadi, Mousa A.; Al-Yousef, Mohammed J.; Yousef, Mohammad M.; Sheikh, Salwa S.; Almasri, Nidal M.; Amr, Samir S.

    2016-01-01

    Giant cell tumor of bone (GCTB) is a primary bone neoplasm which is characterized by the presence of mononuclear cells (MCs) and osteoclast-like multinucleated giant cells (MNGCs). Up to our knowledge, CD10 immunoreactivity in GCTB has not yet been studied, and only one study touched on CD138 immunoreactivity in GCTB. The objective of this study is to investigate the immunoreactivity of CD10 and CD138 in GCTB. We offer a discussion of our findings in the context of the differential diagnosis, particularly in small biopsy material. We retrieved and reviewed 15 well-documented cases of GCTB from January 2008 to December 2014. Well-controlled standard immunohistochemical satins were performed on these cases for CD10 and CD138 and few other selected antibodies. Immunoreactivity for CD10 was membranous and was found in 14 (93%) cases. This immunoreactivity was found only in the MCs, whereas the MNGC were all negative. CD138 showed variable positivity in 11 (73%) while 4 (37%) were completely negative. Similar to CD10, staining for CD138 was only seen in the MC; however, the immunoreactivity was predominantly concentrated in the peri-vascular areas. Most of GCTB cases can show variable immunoreactivity for CD10 and CD138. The aforementioned immune-expression raise the possibility of a role in the pathogenesis of GCTB. Paying attention to this immunoreactivity is recommended when considering the clinical and radiological differential diagnosis, especially in small biopsy specimens. PMID:27390668

  13. Different Scoring Methods of FDG PET/CT in Giant Cell Arteritis

    PubMed Central

    Stellingwerff, Menno D.; Brouwer, Elisabeth; Lensen, Karel-Jan D.F.; Rutgers, Abraham; Arends, Suzanne; van der Geest, Kornelis S.M.; Glaudemans, Andor W.J.M.; Slart, Riemer H.J.A.

    2015-01-01

    Abstract Giant cell arteritis (GCA) is the most frequent form of vasculitis in persons older than 50 years. Cranial and systemic large vessels can be involved. [18F] fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) is increasingly used to diagnose inflammation of the large arteries in GCA. Unfortunately, no consensus exists on the preferred scoring method. In the present study, we aim to define the optimal FDG PET/CT scoring method for GCA diagnosis using temporal artery biopsy and clinical diagnosis as the reference method. FDG PET/CT scans of GCA patients (12 glucocorticoid-naive, 6 on glucocorticoid treatment) and 3 control groups (inflammatory, atherosclerotic, and normal controls) were evaluated. We compared 2 qualitative visual methods (i.e. (1a) first impression and (1b) vascular uptake versus liver uptake) and 4 semiquantitative methods ((2a) SUVmax aorta, (2b) SUVmax aorta-to-liver ratio, (2c) SUVmax aorta-to-superior-caval-vein ratio, and (2d) SUVmax aorta-to-inferior-caval-vein ratio). FDG uptake pattern (diffuse or focal) and presence of arterial calcifications were also scored. Diagnostic accuracy of the visual method vascular versus liver uptake (1b) was highest when the cut-off point “vascular uptake higher than liver uptake” (sensitivity 83%, specificity 91%) was used. Sensitivity increased to 92% when patients on glucocorticoids were excluded from the analysis. Regarding the semiquantitative methods, the aorta-to-liver ratio (2b) with a cutoff of 1.03 had the highest diagnostic accuracy, with a sensitivity and specificity of 69% and 92%, respectively. Sensitivity increased to 90% when patients on glucocorticoids were excluded. The number of vascular segments with diffuse FDG uptake pattern was significantly higher in GCA patients without glucocorticoid use compared with all control patient groups. CRP was not significantly different between positive and negative FDG PET scans in the GCA group. Visual vascular

  14. Steroid-sparing effect and toxicity of dapsone treatment in giant cell arteritis

    PubMed Central

    Ly, Kim Heang; Dalmay, François; Gondran, Guillaume; Palat, Sylvain; Bezanahary, Holy; Cypierre, Anne; Fauchais, Anne-Laure; Liozon, Eric

    2016-01-01

    Abstract Although a glucocorticoid (GC)-sparing strategy is needed for patients with giant cell arteritis (GCA) suffering from refractory disease or serious treatment-related complications, evidence of efficacy in this setting of immunosuppressive drugs and biotherapies is lacking. Herein, we evaluated the GC-sparing effects and tolerability of addition of dapsone (DDS) to prednisone therapy in patients with GCA. We retrospectively assessed data on 18 GCA patients who received DDS as a first-line treatment (DDS-1 group) and 52 patients who received it as a second- or third-line treatment for refractory GCA, with or without excessive GC-related toxicity (DDS-2 group). Of these 70 patients, 63 belonged to an inception cohort of 478 patients, whereas the remaining 7 were referred to our department for resistant GCA. In all, 52 patients were assessable for DDS efficacy. The baseline characteristics of the DDS-1 patients were similar to those of 395 GCA patients (control group) who received prednisone alone. DDS-1 patients had a more sustained decrease in GC dose with a lower mean prednisone dose at 12 months, and they comprised higher proportions who achieved GC withdrawal within the first year, who stopped prednisone treatment, and who recovered from GCA (P < 0.001 for each variable). Patients in the DDS-2 group achieved a mean rate of prednisone reduction of 65% and a prednisone dose reduction of 16.9 ± 13.3 mg/d. The monthly decreases in the prednisone dose were 2.4 and 1.25 mg in DDS-1 and DDS-2 patients, respectively. DDS-induced side effects were recorded in 44 (64%) assessable patients. These side effects led to lowering of the DDS dose by 25 mg/d in 11 (16%) patients and permanent cessation of DDS in 14 patients (20%), due to allergic skin rash in 7, agranulocytosis in 2, icteric hepatitis in 2, and excessive hemolysis in 2 patients. DDS is a potent GC-sparing agent in GCA that should be evaluated in prospective studies. However, DDS use should

  15. Do solar cycles influence giant cell arteritis and rheumatoid arthritis incidence?

    PubMed Central

    Wing, Simon; Rider, Lisa G; Johnson, Jay R; Miller, Federick W; Matteson, Eric L; Gabriel, Sherine E

    2015-01-01

    Objective To examine the influence of solar cycle and geomagnetic effects on the incidence of giant cell arteritis (GCA) and rheumatoid arthritis (RA). Methods We used data from patients with GCA (1950–2004) and RA (1955–2007) obtained from population-based cohorts. Yearly trends in age-adjusted and sex-adjusted incidence were correlated with the F10.7 index (solar radiation at 10.7 cm wavelength, a proxy for the solar extreme ultraviolet radiation) and AL index (a proxy for the westward auroral electrojet and a measure of geomagnetic activity). Fourier analysis was performed on AL, F10.7, and GCA and RA incidence rates. Results The correlation of GCA incidence with AL is highly significant: GCA incidence peaks 0–1 year after the AL reaches its minimum (ie, auroral electrojet reaches a maximum). The correlation of RA incidence with AL is also highly significant. RA incidence rates are lowest 5–7 years after AL reaches maximum. AL, GCA and RA incidence power spectra are similar: they have a main peak (periodicity) at about 10 years and a minor peak at 4–5 years. However, the RA incidence power spectrum main peak is broader (8–11 years), which partly explains the lower correlation between RA onset and AL. The auroral electrojets may be linked to the decline of RA incidence more strongly than the onset of RA. The incidences of RA and GCA are aligned in geomagnetic latitude. Conclusions AL and the incidences of GCA and RA all have a major periodicity of about 10 years and a secondary periodicity at 4–5 years. Geomagnetic activity may explain the temporal and spatial variations, including east-west skewness in geographic coordinates, in GCA and RA incidence, although the mechanism is unknown. The link with solar, geospace and atmospheric parameters need to be investigated. These novel findings warrant examination in other populations and with other autoimmune diseases. PMID:25979866

  16. Do solar cycles influence giant cell arteritis and rheumatoid arthritis incidence?

    DOE PAGESBeta

    Wing, Simon; Rider, Lisa G.; Johnson, Jay R.; Miller, Federick W.; Matteson, Eric L.; Crowson, C. S.; Gabriel, S. E.

    2015-05-15

    Our objective was to examine the influence of solar cycle and geomagnetic effects on the incidence of giant cell arteritis (GCA) and rheumatoid arthritis (RA). Methods: We used data from patients with GCA (1950-2004) and RA (1955-2007) obtained from population-based cohorts. Yearly trends in age-adjusted and sex-adjusted incidence were correlated with the F10.7 index (solar radiation at 10.7 cm wavelength, a proxy for the solar extreme ultraviolet radiation) and AL index (a proxy for the westward auroral electrojet and a measure of geomagnetic activity). Fourier analysis was performed on AL, F10.7, and GCA and RA incidence rates. Results: The correlationmore » of GCA incidence with AL is highly significant: GCA incidence peaks 0-1 year after the AL reaches its minimum (ie, auroral electrojet reaches a maximum). The correlation of RA incidence with AL is also highly significant. RA incidence rates are lowest 5-7 years after AL reaches maximum. AL, GCA and RA incidence power spectra are similar: they have a main peak (periodicity) at about 10 years and a minor peak at 4-5 years. However, the RA incidence power spectrum main peak is broader (8-11 years), which partly explains the lower correlation between RA onset and AL. The auroral electrojets may be linked to the decline of RA incidence more strongly than the onset of RA. The incidences of RA and GCA are aligned in geomagnetic latitude. Conclusions: AL and the incidences of GCA and RA all have a major periodicity of about 10 years and a secondary periodicity at 4-5 years. Geomagnetic activity may explain the temporal and spatial variations, including east-west skewness in geographic coordinates, in GCA and RA incidence, although the mechanism is unknown. Lastly, the link with solar, geospace and atmospheric parameters need to be investigated. These novel findings warrant examination in other populations and with other autoimmune diseases.« less

  17. The early history of odontogenic ghost cell lesions: from Thoma to Gorlin.

    PubMed

    Ide, Fumio; Kikuchi, Kentaro; Miyazaki, Yuji; Kusama, Kaoru; Saito, Ichiro; Muramatsu, Takashi

    2015-03-01

    To reappraise the early history of odontogenic ghost cell lesions (OGCL), the extensive world literature published from 1838 to 1962 was reviewed. In light of the long history of OGCL, the term "calcifying epithelioma of Malherbe" first appeared in a 1931 French report, and the term "ghost cells" had its origin in two American seminal articles by Thoma and Goldman in 1946. Although Gorlin et al. coined the term "calcifying odontogenic cyst" (COC) in 1962, this type of cyst was initially reported three decades earlier by Rywkind in Russia, and almost concurrently by Blood good in the United States and Sato in Japan. In 1948, Willis provided the initial histological evidence of a peripheral COC in his British pathology textbook. Credit for the earliest clinical presentation of odontoma associated calcifying cystic odontogenic tumor belongs to the American radiology textbook by Thoma in 1917. A Scandinavian journal report published in 1953 by Husted and Pindborg was the first to address a dentinogenic ghost cell tumor, and its peripheral counterpart was originally reported in the Swiss literature 7 years later. The current concept of COC was undoubtedly established by Gorlin et al. but the history of OGCL really started with Thoma's pioneering work about a century ago.

  18. Mutational spectrum of Barrett's stem cells suggests paths to initiation of a precancerous lesion

    PubMed Central

    Yamamoto, Yusuke; Wang, Xia; Bertrand, Denis; Kern, Florian; Zhang, Ting; Duleba, Marcin; Srivastava, Supriya; Khor, Chiea Chuen; Hu, Yuanyu; Wilson, Lane H.; Blaszyk, Hagen; Rolshud, Daniil; Teh, Ming; Liu, Jianjun; Howitt, Brooke E.; Vincent, Matthew; Crum, Christopher P.; Nagarajan, Niranjan; Ho, Khek Yu; McKeon, Frank; Xian, Wa

    2016-01-01

    The precancerous lesion known as Barrett's oesophagus can evolve to oesophageal adenocarcinoma in decades-long processes of regenerative growth. Here we report the isolation and propagation of distinct, patient-matched stem cells of Barrett's, gastric and oesophageal epithelia that yield divergent tumour types following in vitro transformation and xenografting. Genomic analyses reveal a broad mutational spectrum unique to Barrett's stem cells that likely reflects their risk for oncogenesis. Remarkably, 25% of cases show no cancer-related genomic changes, suggesting that Barrett's initiates without driver mutations. Most cases, however, sustain patterns of deletions almost identical to adenocarcinoma though tumour-associated gene amplifications were absent. Notably, those suspected of low-grade dysplasia have p53 mutations or undergo amplifications of proto-oncogenes and receptor tyrosine kinases, implicating these events in lethal transitions. Our findings suggest paths for the initiation and progression of Barrett's and define a discrete stem cell underlying its regenerative growth whose eradication could prevent oesophageal adenocarcinoma. PMID:26783136

  19. Reminiscences of work with Alex Hope: the movement of water and ions in giant algal cells, 1963-1967.

    PubMed

    Barry, Peter H

    2009-12-01

    This article, from the Tribute to Alex Hope Symposium at the 2008 Australian Society for Biophysics meeting, represents reminiscences of PhD studies done under my former supervisor, Professor Alex Hope. The studies demonstrated and quantified electroosmosis in giant algal cells of Chara and isolated segments of cell wall by measuring instantaneous current-induced volume flows. The studies also uncovered and modelled an unstirred-layer transport number effect that gave rise to an additional transiently increasing current-induced volume flow component, which could be mistaken for electroosmosis. In addition, action potential induced volume flows and pressure changes were measured in these cells and successfully modelled. An appreciation of the influence of Alex Hope and his laboratory environment, together with some of the further studies that resulted from this work, is also mentioned.

  20. Regulatory T-cells and IL17A(+) cells infiltrate oral lichen planus lesions.

    PubMed

    Javvadi, L R; Parachuru, V P B; Milne, T J; Seymour, G J; Rich, A M

    2016-10-01

    Oral lichen planus (OLP) is a complex immunological disorder, mediated in part by the release of cytokines from activated T-cells. Of late, two closely related T-helper (Th) cell subsets; regulatory T-cells (Tregs; FoxP3(+)) and Th17 cells (IL17(+)) have been described in various chronic inflammatory diseases. The aim of this study was to determine the expression of FoxP3 and IL17 in OLP using immunohistochemistry (IHC) and quantitative real-time reverse transcriptase polymerase chain reaction (qPCR). For IHC, formalin fixed, paraffin embedded archival specimens, an OLP group (n=10) and a non-specific inflammatory (NSI) control group (n=9) were used. In addition, 12 fresh tissue samples were used to determine gene expression of FoxP3 and IL17. Significantly more FoxP3(+) cells were present in OLP than in NSI. IL17(+) cells were significantly more frequent in the control tissues than in OLP. The gene expression experiments revealed a significantly higher expression of FoxP3 in OLP when compared to the controls. IL17 gene expression was not different between the groups. Double labelling immunofluorescence indicated co-localisation of IL17 with tryptase(+) mast cells. These findings suggest FoxP3(+) Tregs have a more prominent role in the pathogenesis of OLP when compared to IL17(+)cells. PMID:27594511

  1. Bacteria-reactive immune response may induce RANKL-expressing T-cells in the mouse periapical bone loss lesion

    PubMed Central

    Silva, Marcelo J.B.; Kajiya, Mikihito; AlShwaimi, Emad; Sasaki, Hajime; Hong, Jennifer; Ok, Peter; Rezende, Taia M.B.; Pagonis, Tom C.; White, Robert R.; Paster, Bruce J; Stashenko, Philip; Kawai, Toshihisa

    2012-01-01

    Introduction The present study investigated if T-cells infiltrating the periapical lesion produce RANKL and whether bacteria infecting the root canal can activate T-cells to produce RANKL. Methods Using a mouse model of periapical lesion induced by artificial dental pulp exposure, the presence of RANKL-positive T-cells and osteoclasts in the periapical lesion was examined by an immuno-histochemical approach. The bacteria colonizing the exposed root canal were identified by 16S ribosomal RNA (rRNA) sequence analysis. The isolated endodontic bacteria were further immunized to normal mice, and sRANKL production by the T-cells isolated from the immunized mice was evaluated by ex vivo culture system. Results RANKL-positive T-cells, along with TARP+ osteoclasts, were identified in periapical bone resorption lesions. The Gram-negative bacterium Pasterurella pnumotropica (P. pnumotropica), which was most frequently detected from root canal of exposed pulp, showed remarkably elevated serum IgG antibody response in pulp-exposed mice compared to control non-treated mice. Immunization of mice with P. pneumotropica induced not only serum IgG antibody but also primed bacteria reactive T-cells that produced sRANKL in response to ex vivo exposure to P. pneumotropica. Conclusion T-cells infiltrating the periapical region express RANKL, and the endodontic bacteria colonizing the root canal appear to induce RANKL expression from bacteria-reactive T-cells, suggesting the possible pathogenic engagement of immune response to endodontic bacteria in the context of developing boneresorptive periapical lesions. PMID:22341072

  2. Mesenchymal Stem Cell Alterations in Bone Marrow Lesions in Patients With Hip Osteoarthritis

    PubMed Central

    Campbell, T. Mark; Churchman, Sarah M.; Gomez, Alejandro; McGonagle, Dennis; Conaghan, Philip G.; Ponchel, Frederique

    2016-01-01

    Objective In patients with osteoarthritis (OA), bone marrow lesions (BMLs) are intimately linked to disease progression. We hypothesized that aberrant multipotential stromal cell (also known as mesenchymal stem cell [MSC]) responses within bone tissue contributes to BML pathophysiology. The aim of this study was to investigate BML and non‐BML native subchondral bone MSCs for numeric, topographic, in vitro functional, and gene expression differences. Methods Ex vivo 3T magnetic resonance imaging (MRI) of the femoral heads of 20 patients with hip OA was performed. MRI‐determined BML and non‐BML regions were excised and enzymatically treated to extract cells and quantify MSCs using flow cytometry and colony‐forming unit–fibroblast (CFU‐F) assay. Immunohistochemical analysis was performed to determine in vivo CD271+ MSC distribution. Culture‐expanded CD271+ cells were analyzed for tripotentiality and gene expression. Results BML regions were associated with greater trabecular bone area and cartilage damage compared with non‐BML regions. The proportion of CD45−CD271+ MSCs was higher in BML regions compared with non‐BML regions (median difference 5.6‐fold; P < 0.001); the CFU‐F assay showed a similar trend (median difference 4.3‐fold; P = 0.013). Immunohistochemistry revealed CD271+ cell accumulation in bone adjacent to cartilage defects and areas of osteochondral angiogenesis. BML MSCs had lower proliferation and mineralization capacities in vitro and altered expression of TNFSF11/RANKL and CXCR4/stromal cell–derived factor 1 receptor. OA MSCs showed up‐regulated transcripts for CXCR1 and CCR6 compared with MSCs derived from healthy or osteoporotic bone. Conclusion This study is the first to show numeric and topographic alterations in native MSCs in the diseased bone of patients with hip OA. Given the associated functional perturbation of MSCs, these data suggest that subchondral bone MSC manipulation may be an OA treatment target. PMID

  3. Introducing Micrometer-Sized Artificial Objects into Live Cells: A Method for Cell–Giant Unilamellar Vesicle Electrofusion

    PubMed Central

    Saito, Akira C.; Ogura, Toshihiko; Fujiwara, Kei; Murata, Satoshi; Nomura, Shin-ichiro M.

    2014-01-01

    Here, we report a method for introducing large objects of up to a micrometer in diameter into cultured mammalian cells by electrofusion of giant unilamellar vesicles. We prepared GUVs containing various artificial objects using a water-in-oil (w/o) emulsion centrifugation method. GUVs and dispersed HeLa cells were exposed to an alternating current (AC) field to induce a linear cell–GUV alignment, and then a direct current (DC) pulse was applied to facilitate transient electrofusion. With uniformly sized fluorescent beads as size indexes, we successfully and efficiently introduced beads of 1 µm in diameter into living cells along with a plasmid mammalian expression vector. Our electrofusion did not affect cell viability. After the electrofusion, cells proliferated normally until confluence was reached, and the introduced fluorescent beads were inherited during cell division. Analysis by both confocal microscopy and flow cytometry supported these findings. As an alternative approach, we also introduced a designed nanostructure (DNA origami) into live cells. The results we report here represent a milestone for designing artificial symbiosis of functionally active objects (such as micro-machines) in living cells. Moreover, our technique can be used for drug delivery, tissue engineering, and cell manipulation. PMID:25229561

  4. Constitutive activation of p38 MAPK in tumor cells contributes to osteolytic bone lesions in multiple myeloma.

    PubMed

    Yang, J; He, J; Wang, J; Cao, Y; Ling, J; Qian, J; Lu, Y; Li, H; Zheng, Y; Lan, Y; Hong, S; Matthews, J; Starbuck, M W; Navone, N M; Orlowski, R Z; Lin, P; Kwak, L W; Yi, Q

    2012-09-01

    Bone destruction is a hallmark of multiple myeloma and affects more than 80% of patients. However, current therapy is unable to completely cure and/or prevent bone lesions. Although it is accepted that myeloma cells mediate bone destruction by inhibition of osteoblasts and activation of osteoclasts, the underlying mechanism is still poorly understood. This study demonstrates that constitutive activation of p38 mitogen-activated protein kinase in myeloma cells is responsible for myeloma-induced osteolysis. Our results show that p38 is constitutively activated in most myeloma cell lines and primary myeloma cells from patients. Myeloma cells with high/detectable p38 activity, but not those with low/undetectable p38 activity, injected into severe combined immunodeficient (SCID) or SCID-hu mice caused bone destruction. Inhibition or knockdown of p38 in human myeloma reduced or prevented myeloma-induced osteolytic bone lesions without affecting tumor growth, survival, or homing to bone. Mechanistic studies showed that myeloma cell p38 activity inhibited osteoblastogenesis and bone formation and activated osteoclastogenesis and bone resorption in myeloma-bearing SCID mice. This study elucidates a novel molecular mechanism-activation of p38 signaling in myeloma cells-by which myeloma cells induce osteolytic bone lesions, and indicates that targeting myeloma cell p38 may be a viable approach to treating or preventing myeloma bone disease. PMID:22425892

  5. Fatal spontaneous subdural bleeding due to neonatal giant cell hepatitis: a rare differential diagnosis of shaken baby syndrome.

    PubMed

    Guddat, Saskia S; Ehrlich, Edwin; Martin, Hubert; Tsokos, Michael

    2011-09-01

    A 7-week-old girl showed vomiting after feeding, facial pallor, loss of muscle tone and respiratory depression. An emergency doctor performed successful resuscitation and after arrival in hospital, cranial ultrasound showed left-sided subdural hemorrhage, cerebral edema with a shift of the midline, and a decrease in cerebral perfusion. Ophthalmologic examination showed retinal hemorrhage. In view of this, the doctors suspected shaken baby syndrome and approached the parents with their suspicions, but they denied any shaking or trauma. Despite surgery for the subdural hemorrhage the girl died a few hours later with a severe coagulopathy. Autopsy verified subdural hemorrhage, cerebral edema and retinal hemorrhage, but also revealed intact bridging veins and a lack of optic nerve sheath hemorrhage, therefore shaken baby syndrome could not be proven by autopsy. Histological examination showed severe neonatal giant cell hepatitis as the cause of the severe coagulopathy and the associated spontaneous subdural bleeding. Neonatal giant cell hepatitis may be responsible for unexpected deaths in infancy and, although rarely associated with subdural bleeding, must be considered as a potential differential diagnosis of shaken baby syndrome.

  6. Hyalinizing Spindle Cell Tumor with Giant Rosettes with Pulmonary Metastasis After a Long Hiatus: A Case Report

    PubMed Central

    Chang, Eundeok; Lee, Eunjung; Shin, Okran; Kang, Changsuk; Kim, Joon Mee; Chu, Young Chae

    2004-01-01

    "Hyalinizing spindle cell tumor with giant rosettes" (HSCTGR) is a recently described tumor, which is regarded as an unusual variant of low-grade fibromyxoid sarcoma. Proof of a metastatic potential was lacking. The patient in the report was a 35-yr-old woman who showed multiple bilateral pulmonary nodules with massive pleural effusion in the right side. She had a history of a mass excision in the right thigh 11 yrs ago at another hospital, which was reported as a "leiomyoma". Two years before this presentation, the patient received a routine chest radiograph which demonstrated bilateral multiple pulmonary nodules. A lobectomy of the left upper lung was performed. The histological findings revealed a well-circumscribed nodule that was characterized by a spindle-shaped fibrous to hyalinized stroma with criss-crossing short fascicles and giant collagen rosettes surrounded by a rim of spindle-shaped cells. Electron microscopy confirmed the fibroblastic nature of the tumor. This case, in addition to at least two other cases reported in the literature, demonstrates that the HSCTGR is a malignant neoplasm with the capacity to metastasize after a long hiatus. PMID:15308860

  7. Primary Urinary Bladder Angiosarcoma with Osteoclast-Like Multinucleated Giant Cells: A Case Report and Literature Review

    PubMed Central

    Nawar, Nariman A.; Olsen, Jamie; Jelic, Tomislav M.; He, Chun

    2016-01-01

    Patient: Male, 68 Final Diagnosis: Urinary bladder angiosarcoma Symptoms: — Medication: — Clinical Procedure: TURBT Specialty: Diagnostics, Laboratory Objective: Rare co-existance of disease or pathology Background: Angiosarcoma is a fatal and aggressive mesenchymal tumor. It occurs in skin, breast, and parenchymal organs. It rarely arises primarily in the urinary bladder. Only 13 cases of primary urinary bladder angiosarcoma have been reported in the English literature. Case Report: The patient was a 68-year-old man who presented to the Emergency Department with inability to void. Computed tomography of the abdomen and pelvis showed a urinary bladder mass. Surgical excision of the mass was performed. Pathological examination results were consistent with angiosarcoma. In addition to the unusual location of this tumor, the pathology was different from the previously reported cases in that this case was rich with osteoclast-like multinucleated giant cells. Conclusions: The pathological diagnosis of primary urinary bladder angiosarcoma is challenging. Histological patterns and immunophenotypes are variable. Here, we review all reported cases of primary urinary bladder angiosarcoma, highlight the clinical and morphological features of this malignant neoplasm, and report a unique case of primary urinary bladder angiosarcoma with osteoclast-like multinucleated giant cells. PMID:26947436

  8. Multinucleated giant cell cytokine expression in pulmonary granulomas of cattle experimentally infected with Mycobacterium bovis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Pathogenic mycobacteria of the Mycobacterium tuberculosis complex such as Mycobacterium bovis, induce a characteristic lesion known as a granulomas. Granulomas represent a specific host response to chronic antigenic stimuli, such as foreign bodies, certain bacterial components, or persistent pathoge...

  9. Recurrent acute pancreatitis and persistent hyperamylasemia as a presentation of pancreatic osteoclastic giant cell tumor: an unusual presentation of a rare tumor.

    PubMed

    Rustagi, Tarun; Rampurwala, Murtuza; Rai, Mridula; Golioto, Michael

    2011-01-01

    Giant cell tumors of the pancreas are rare neoplasms divided into three forms: osteoclastic, pleomorphic, and mixed. We report an unusual case of a 62-year-old male presenting with recurrent acute pancreatitis and found to have a mass in the head of the pancreas on routine imaging. Endoscopic retrograde cholangiopancreatography showed a main pancreatic duct stricture, with brush cytology revealing the diagnosis of osteoclastic giant cell tumor of the pancreas. Whipple's procedure was successfully performed for resection of this tumor. and IAP.

  10. Constitutive activation of p38 MAPK in tumor cells contributes to osteolytic bone lesions in multiple myeloma

    PubMed Central

    Yang, Jing; He, Jin; Wang, Ji; Cao, Yabing; Ling, Jianhua; Qian, Jianfei; Lu, Yong; Li, Haiyan; Zheng, Yuhuan; Lan, Yongsheng; Hong, Sungyoul; Matthews, Jairo; Starbuck, Michael W; Navone, Nora M; Orlowski, Robert Z.; Lin, Pei; Kwak, Larry W.; Yi, Qing

    2012-01-01

    Bone destruction is a hallmark of multiple myeloma and affects more than 80% of patients. However, current therapy is unable to completely cure and/or prevent bone lesions. Although it is accepted that myeloma cells mediate bone destruction by inhibition of osteoblasts and activation of osteoclasts, the underlying mechanism is still poorly understood. This study demonstrates that constitutive activation of p38 mitogen-activated protein kinase in myeloma cells is responsible for myeloma-induced osteolysis. Our results show that p38 is constitutively activated in most myeloma cell lines and primary myeloma cells from patients. Myeloma cells with high/detectable p38 activity, but not those with low/undetectable p38 activity, injected into SCID or SCID-hu mice caused bone destruction. Inhibition or knockdown of p38 in human myeloma reduced or prevented myeloma-induced osteolytic bone lesions without affecting tumor growth, survival, or homing to bone. Mechanistic studies showed that myeloma cell p38 activity inhibited osteoblastogenesis and bone formation and activated osteoclastogenesis and bone resorption in myeloma-bearing SCID mice. This study elucidates a novel molecular mechanism—sactivation of p38 signaling in myeloma cells—by which myeloma cells induce osteolytic bone lesions and indicates that targeting myeloma cell p38 may be a viable approach to treating or preventing myeloma bone disease. PMID:22425892

  11. Cysts and cystic lesions of the mandible: clinical and radiologic-histopathologic review.

    PubMed

    Scholl, R J; Kellett, H M; Neumann, D P; Lurie, A G

    1999-01-01

    Many lesions that occur in the mandible have a cystlike radiographic appearance. These lesions are often difficult to differentiate on the basis of their radiographic features alone. Mandibular lesions may be odontogenic or nonodontogenic. Among odontogenic lesions without mineralization, ameloblastomas, odontogenic keratocysts, and dentigerous cysts can all appear as well-defined, unilocular, well-corticated, lucent lesions that are often associated with the crowns of impacted or unerupted teeth. Most radicular cysts appear as round or pear-shaped, unilocular, lucent lesions in the periapical region. Among odontogenic lesions with mineralization, complex odontomas contain multiple masses of dental tissue and compound odontomas contain multiple teeth or toothlike structures. Odontogenic myxomas are characterized by lytic osseous changes of varying size, which may be demarcated and expansile or exhibit ill-defined borders. Nonodontogenic lesions that mimic odontogenic lesions include benign fibro-osseous lesions (conventional or juvenile ossifying fibroma, focal or periapical cemento-osseous dysplasia, florid osseous dysplasia), traumatic bone cyst, lingual salivary gland inclusion defect, central giant cell granuloma, brown tumor of hyperparathyroidism, arteriovenous malformation, and mucoepidermoid carcinoma. The clinical and radiographic features of these mandibular lesions help establish a differential diagnosis, although microscopic tissue evaluation is generally necessary to accurately identify the lesion.

  12. Increased migration of olfactory ensheathing cells secreting the Nogo receptor ectodomain over inhibitory substrates and lesioned spinal cord.

    PubMed

    Reginensi, Diego; Carulla, Patricia; Nocentini, Sara; Seira, Oscar; Serra-Picamal, Xavier; Torres-Espín, Abel; Matamoros-Angles, Andreu; Gavín, Rosalina; Moreno-Flores, María Teresa; Wandosell, Francisco; Samitier, Josep; Trepat, Xavier; Navarro, Xavier; del Río, José Antonio

    2015-07-01

    Olfactory ensheathing cell (OEC) transplantation emerged some years ago as a promising therapeutic strategy to repair injured spinal cord. However, inhibitory molecules are present for long periods of time in lesioned spinal cord, inhibiting both OEC migration and axonal regrowth. Two families of these molecules, chondroitin sulphate proteoglycans (CSPG) and myelin-derived inhibitors (MAIs), are able to trigger inhibitory responses in lesioned axons. Mounting evidence suggests that OEC migration is inhibited by myelin. Here we demonstrate that OEC migration is largely inhibited by CSPGs and that inhibition can be overcome by the bacterial enzyme Chondroitinase ABC. In parallel, we have generated a stable OEC cell line overexpressing the Nogo receptor (NgR) ectodomain to reduce MAI-associated inhibition in vitro and in vivo. Results indicate that engineered cells migrate longer distances than unmodified OECs over myelin or oligodendrocyte-myelin glycoprotein (OMgp)-coated substrates. In addition, they also show improved migration in lesioned spinal cord. Our results provide new insights toward the improvement of the mechanisms of action and optimization of OEC-based cell therapy for spinal cord lesion.

  13. Diagnosis of a multifocal B cell lymphoma with preceding demyelinating central nervous system lesions by single voxel proton MR spectroscopy

    PubMed Central

    Kuhlmann, T; Schroter, A; Dechent, P; Weber, F; Rustenbeck, H; Fuzesi, L; Bruck, W; Ehrenreich, H; Frahm, J

    2001-01-01

    Single voxel proton magnetic resonance spectroscopy (MRS) provides a rapid non-invasive fingerprint of tissue chemistry. A case history is presented in which a B cell lymphoma with antecedent demyelinating lesions of the CNS was suspected by MRS and confirmed by neuropathological examination and immunoglobulin gene rearrangement.

 PMID:11160483

  14. Fibroblast growth factor signaling in oligodendrocyte-lineage cells facilitates recovery of chronically demyelinated lesions but is redundant in acute lesions.

    PubMed

    Furusho, Miki; Roulois, Aude J; Franklin, Robin J M; Bansal, Rashmi

    2015-10-01

    Remyelination is a potent regenerative process in demyelinating diseases, such as multiple sclerosis, the effective therapeutic promotion of which will fill an unmet clinical need. The development of proregenerative therapies requires the identification of key regulatory targets that are likely to be involved in the integration of multiple signaling mechanisms. Fibroblast growth factor (FGF) signaling system, which comprises multiple ligands and receptors, potentially provides one such target. Since the FGF/FGF receptor (FGFR) interactions are complex and regulate multiple diverse functions of oligodendrocyte lineage cells, it is difficult to predict their overall therapeutic potential in the regeneration of oligodendrocytes and myelin. Therefore, to assess the integrated effects of FGFR signaling on this process, we simultaneously inactivated both FGFR1 and FGFR2 in oligodendrocytes and their precursors using two Cre-driver mouse lines. Acute and chronic cuprizone-induced or lysolecithin-induced demyelination was established in Fgfr1/Fgfr2 double knockout mice (dKO). We found that in the acute cuprizone model, there was normal differentiation of oligodendrocytes and recovery of myelin in the corpus callosum of both control and dKO mice. Similarly, in the spinal cord, lysolecithin-induced demyelinated lesions regenerated similarly in the dKO and control mice. In contrast, in the chronic cuprizone model, fewer differentiated oligodendrocytes and less efficient myelin recovery were observed in the dKO compared to control mice. These data suggest that while cell-autonomous FGF signaling is redundant during recovery of acute demyelinated lesions, it facilitates regenerative processes in chronic demyelination. Thus, FGF-based therapies have potential value in stimulating oligodendrocyte and myelin regeneration in late-stage disease.

  15. Regulation and Biological Significance of Formation of Osteoclasts and Foreign Body Giant Cells in an Extraskeletal Implantation Model.

    PubMed

    Ahmed, Gazi Jased; Tatsukawa, Eri; Morishita, Kota; Shibata, Yasuaki; Suehiro, Fumio; Kamitakahara, Masanobu; Yokoi, Taishi; Koji, Takehiko; Umeda, Masahiro; Nishimura, Masahiro; Ikeda, Tohru

    2016-06-28

    The implantation of biomaterials induces a granulomatous reaction accompanied by foreign body giant cells (FBGCs). The characterization of multinucleated giant cells (MNGCs) around bone substitutes implanted in bone defects is more complicated because of healing with bone admixed with residual bone substitutes and their hybrid, and the appearance of two kinds of MNGCs, osteoclasts and FBGCs. Furthermore, the clinical significance of osteoclasts and FBGCs in the healing of implanted regions remains unclear. The aim of the present study was to characterize MNGCs around bone substitutes using an extraskeletal implantation model and evaluate the clinical significance of osteoclasts and FBGCs. Beta-tricalcium phosphate (β-TCP) granules were implanted into rat subcutaneous tissue with or without bone marrow mesenchymal cells (BMMCs), which include osteogenic progenitor cells. We also compared the biological significance of plasma and purified fibrin, which were used as binders for implants. Twelve weeks after implantation, osteogenesis was only detected in specimens implanted with BMMCs. The expression of two typical osteoclast markers, tartrate-resistant acid phosphatase (TRAP) and cathepsin-K (CTSK), was analyzed, and TRAP-positive and CTSK-positive osteoclasts were only detected beside bone. In contrast, most of the MNGCs in specimens without the implantation of BMMCs were FBGCs that were negative for TRAP, whereas the degradation of β-TCP was detected. In the region implanted with β-TCP granules with plasma, FBGCs tested positive for CTSK, and when β-TCP granules were implanted with purified fibrin, FBGCs tested negative for CTSK. These results showed that osteogenesis was essential to osteoclastogenesis, two kinds of FBGCs, CTSK-positive and CTSK-negative, were induced, and the expression of CTSK was plasma-dependent. In addition, the implantation of BMMCs was suggested to contribute to osteogenesis and the replacement of implanted β-TCP granules to bone. PMID

  16. Regulation and Biological Significance of Formation of Osteoclasts and Foreign Body Giant Cells in an Extraskeletal Implantation Model

    PubMed Central

    Ahmed, Gazi Jased; Tatsukawa, Eri; Morishita, Kota; Shibata, Yasuaki; Suehiro, Fumio; Kamitakahara, Masanobu; Yokoi, Taishi; Koji, Takehiko; Umeda, Masahiro; Nishimura, Masahiro; Ikeda, Tohru

    2016-01-01

    The implantation of biomaterials induces a granulomatous reaction accompanied by foreign body giant cells (FBGCs). The characterization of multinucleated giant cells (MNGCs) around bone substitutes implanted in bone defects is more complicated because of healing with bone admixed with residual bone substitutes and their hybrid, and the appearance of two kinds of MNGCs, osteoclasts and FBGCs. Furthermore, the clinical significance of osteoclasts and FBGCs in the healing of implanted regions remains unclear. The aim of the present study was to characterize MNGCs around bone substitutes using an extraskeletal implantation model and evaluate the clinical significance of osteoclasts and FBGCs. Beta-tricalcium phosphate (β-TCP) granules were implanted into rat subcutaneous tissue with or without bone marrow mesenchymal cells (BMMCs), which include osteogenic progenitor cells. We also compared the biological significance of plasma and purified fibrin, which were used as binders for implants. Twelve weeks after implantation, osteogenesis was only detected in specimens implanted with BMMCs. The expression of two typical osteoclast markers, tartrate-resistant acid phosphatase (TRAP) and cathepsin-K (CTSK), was analyzed, and TRAP-positive and CTSK-positive osteoclasts were only detected beside bone. In contrast, most of the MNGCs in specimens without the implantation of BMMCs were FBGCs that were negative for TRAP, whereas the degradation of β-TCP was detected. In the region implanted with β-TCP granules with plasma, FBGCs tested positive for CTSK, and when β-TCP granules were implanted with purified fibrin, FBGCs tested negative for CTSK. These results showed that osteogenesis was essential to osteoclastogenesis, two kinds of FBGCs, CTSK-positive and CTSK-negative, were induced, and the expression of CTSK was plasma-dependent. In addition, the implantation of BMMCs was suggested to contribute to osteogenesis and the replacement of implanted β-TCP granules to bone. PMID

  17. Polymyalgia rheumatica and giant cell arteritis in older patients: diagnosis and pharmacological management.

    PubMed

    Schmidt, Jean; Warrington, Kenneth J

    2011-08-01

    Giant cell arteritis (GCA) is an inflammatory vasculopathy that involves large- and medium-sized arteries and can cause vision loss, stroke and aneurysms. GCA occurs in people aged >50 years and is more common in women. A higher incidence of the disease is observed in populations from Northern European countries. Polymyalgia rheumatica (PMR) is a periarticular inflammatory process manifesting as pain and stiffness in the neck, shoulders and pelvic girdle. PMR shares the same pattern of age and sex distribution as GCA. The pathophysiology of PMR and GCA is not completely understood, but the two conditions may be related and often occur concurrently. A delay in the diagnosis should be avoided because of the risk of vascular ischaemic complications due to GCA. The diagnosis should be considered in patients aged >50 years presenting with symptoms such as new headache, visual disturbances, jaw claudication or symptoms of PMR. GCA can also present as a systemic inflammatory syndrome with fever of unknown origin. Marked elevation of acute-phase reactants, recognizable in higher erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels, is often seen in both PMR and GCA. However, some patients can present with a normal ESR. Confirmation of the diagnosis of GCA by temporal artery biopsy is important because clinical findings and laboratory tests are not specific, and because a diagnosis of GCA commits patients to long-term treatment with corticosteroids. The role of imaging techniques for the diagnosis of GCA remains unclear, but these modalities can be helpful in assessing the extent of vascular involvement, especially when extra-cranial disease is present. In PMR, subdeltoid and subacromial bursitis can be identified by imaging techniques, especially ultrasound or MRI. The clinical manifestations of GCA and PMR respond dramatically within 12-48 hours of starting corticosteroid treatment. The initial corticosteroid dosage commonly used in GCA is oral

  18. 2-Arachidonoylglycerol elicits neuroprotective effects on excitotoxically lesioned dentate gyrus granule cells via abnormal-cannabidiol-sensitive receptors on microglial cells.

    PubMed

    Kreutz, Susanne; Koch, Marco; Böttger, Charlotte; Ghadban, Chalid; Korf, Horst-Werner; Dehghani, Faramarz

    2009-02-01

    Endocannabinoids like 2-arachidonoylglycerol (2-AG) exert neuroprotective effects after brain injuries. According to current concepts, these neuroprotective effects are due to interactions between 2-AG and cannabinoid (CB)1 receptors on neurons. Moreover, 2-AG modulates migration and proliferation of microglial cells which are rapidly activated after brain lesion. This effect is mediated via CB2- and abnormal-cannabidiol (abn-CBD)-sensitive receptors. In the present study, we investigated whether the abn-CBD-sensitive receptor on microglial cells contributes to 2-AG-mediated neuroprotection in organotypic hippocampal slice cultures (OHSCs) after excitotoxic lesion induced by NMDA (50 microM) application for 4 h. This lesion caused neuronal damage and accumulation of microglial cells within the granule cell layer. To analyze the role of abn-CBD-sensitive receptors for neuroprotection and microglial cell accumulation, two agonists of the abn-CBD-sensitive receptor, abn-CBD or 2-AG, two antagonists, 1,3-dimethoxy-5-methyl-2-[(1R,6R)-3-methyl-6-(1-methylethenyl)-2-cyclohexen1-yl]-benzene (O-1918) or cannabidiol (CBD), and the CB1 receptor antagonist AM251, were applied to NMDA-lesioned OHSC. Propidium iodide (PI) labeling was used as a marker of degenerating neurons and isolectin B(4) (IB(4)) as a marker of microglial cells. Application of both, abn-CBD or 2-AG to lesioned OHSC significantly decreased the number of IB(4)(+) microglial cells and PI(+) neurons in the dentate gyrus. In contrast to AM251, application of O-1918 or CBD antagonized these effects. When microglial cells were depleted by preincubation of OHSC with the bisphosphonate clodronate (100 microg/mL) for 5 days before excitotoxic lesion, 2-AG and abn-CBD lost their neuroprotective effects. We therefore propose that the endocannabinoid 2-AG exerts its neuroprotective effects via activation of abn-CBD-sensitive receptors on microglial cells.

  19. How did bacterial ancestors reproduce? Lessons from L-form cells and giant lipid vesicles: multiplication similarities between lipid vesicles and L-form bacteria.

    PubMed

    Briers, Yves; Walde, Peter; Schuppler, Markus; Loessner, Martin J

    2012-12-01

    In possible scenarios on the origin of life, protocells represent the precursors of the first living cells. To study such hypothetical protocells, giant vesicles are being widely used as a simple model. Lipid vesicles can undergo complex morphological changes enabling self-reproduction such as growth, fission, and extra- and intravesicular budding. These properties of vesicular systems may in some way reflect the mechanism of reproduction used by protocells. Moreover, remarkable similarities exist between the morphological changes observed in giant vesicles and bacterial L-form cells, which represent bacteria that have lost their rigid cell wall, but retain the ability to reproduce. L-forms feature a dismantled cellular structure and are unable to carry out classical binary fission. We propose that the striking similarities in morphological transitions of L-forms and giant lipid vesicles may provide insights into primitive reproductive mechanisms and contribute to a better understanding of the origin and evolution of mechanisms of cell reproduction. Editor's suggested further reading in BioEssays Synthesizing artificial cells from giant unilamellar vesicles: State-of-the art in the development of microfluidic technology Abstract. PMID:23108858

  20. Breast Cancer Cells Induce Osteolytic Bone Lesions In vivo through a Reduction in Osteoblast Activity in Mice

    PubMed Central

    Gregory, Laura S.; Choi, Wilson; Burke, Leslie; Clements, Judith A.

    2013-01-01

    Bone metastases are severely debilitating and have a significant impact on the quality of life of women with metastatic breast cancer. Treatment options are limited and in order to develop more targeted therapies, improved understanding of the complex mechanisms that lead to bone lesion development are warranted. Interestingly, whilst prostate-derived bone metastases are characterised by mixed or osteoblastic lesions, breast-derived bone metastases are characterised by osteolytic lesions, suggesting unique regulatory patterns. This study aimed to measure the changes in bone formation and bone resorption activity at two time-points (18 and 36 days) during development of the bone lesion following intratibial injection of MDA-MB-231 human breast cancer cells into the left tibiae of Severely Combined Immuno-Deficient (SCID) mice. The contralateral tibia was used as a control. Tibiae were extracted and processed for undecalcified histomorphometric analysis. We provide evidence that the early bone loss observed following exposure to MDA-MB-231 cells was due to a significant reduction in mineral apposition rate, rather than increased levels of bone resorption. This suggests that osteoblast activity was impaired in the presence of breast cancer cells, contrary to previous reports of osteoclast-dependent bone loss. Furthermore mRNA expression of Dickkopf Homolog 1 (DKK-1) and Noggin were confirmed in the MDA-MB-231 cell line, both of which antagonise osteoblast regulatory pathways. The observed bone loss following injection of cancer cells was due to an overall thinning of the trabecular bone struts rather than perforation of the bone tissue matrix (as measured by trabecular width and trabecular separation, respectively), suggesting an opportunity to reverse the cancer-induced bone changes. These novel insights into the mechanisms through which osteolytic bone lesions develop may be important in the development of new treatment strategies for metastatic breast cancer

  1. Transplanted microvascular endothelial cells promote oligodendrocyte precursor cell survival in ischemic demyelinating lesions.

    PubMed

    Iijima, Keiya; Kurachi, Masashi; Shibasaki, Koji; Naruse, Masae; Puentes, Sandra; Imai, Hideaki; Yoshimoto, Yuhei; Mikuni, Masahiko; Ishizaki, Yasuki

    2015-11-01

    We previously showed that transplantation of brain microvascular endothelial cells (MVECs) greatly stimulated remyelination in the white matter infarct of the internal capsule (IC) induced by endothelin-1 injection and improved the behavioral outcome. In the present study, we examined the effect of MVEC transplantation on the infarct volume using intermittent magnetic resonance image and on the behavior of oligodendrocyte lineage cells histochemically. Our results in vivo show that MVEC transplantation reduced the infarct volume in IC and apoptotic death of oligodendrocyte precursor cells (OPCs). These results indicate that MVECs have a survival effect on OPCs, and this effect might contribute to the recovery of the white matter infarct. The conditioned-medium from cultured MVECs reduced apoptosis of cultured OPCs, while the conditioned medium from cultured fibroblasts did not show such effect. These results suggest a possibility that transplanted MVECs increased the number of OPCs through the release of humoral factors that prevent their apoptotic death. Identification of such humoral factors may lead to the new therapeutic strategy against ischemic demyelinating diseases.

  2. Transplanted microvascular endothelial cells promote oligodendrocyte precursor cell survival in ischemic demyelinating lesions.

    PubMed

    Iijima, Keiya; Kurachi, Masashi; Shibasaki, Koji; Naruse, Masae; Puentes, Sandra; Imai, Hideaki; Yoshimoto, Yuhei; Mikuni, Masahiko; Ishizaki, Yasuki

    2015-11-01

    We previously showed that transplantation of brain microvascular endothelial cells (MVECs) greatly stimulated remyelination in the white matter infarct of the internal capsule (IC) induced by endothelin-1 injection and improved the behavioral outcome. In the present study, we examined the effect of MVEC transplantation on the infarct volume using intermittent magnetic resonance image and on the behavior of oligodendrocyte lineage cells histochemically. Our results in vivo show that MVEC transplantation reduced the infarct volume in IC and apoptotic death of oligodendrocyte precursor cells (OPCs). These results indicate that MVECs have a survival effect on OPCs, and this effect might contribute to the recovery of the white matter infarct. The conditioned-medium from cultured MVECs reduced apoptosis of cultured OPCs, while the conditioned medium from cultured fibroblasts did not show such effect. These results suggest a possibility that transplanted MVECs increased the number of OPCs through the release of humoral factors that prevent their apoptotic death. Identification of such humoral factors may lead to the new therapeutic strategy against ischemic demyelinating diseases. PMID:26212499

  3. A novel germline mutation in a patient with nevoid basal cell carcinoma syndrome showing cystic lesion in the lung.

    PubMed

    Miyata, Ryo; Kurosawa, Manabu; Sato, Masaaki; Kono, Tomoya; Takubo, Yasutaka; Okai, Shinsaku; Yamada, Keisuke; Shinkura, Reiko; Date, Hiroshi; Matsuda, Fumihiko

    2015-01-01

    Nevoid basal cell carcinoma syndrome (NBCCS) manifests multiple defects involving the skin, endocrine and nervous systems, eyes and bones. Mutations in the patched homologue 1 (PTCH1) gene are the underlying causes of NBCCS, leading to aberrant cell proliferation through constitutive activation of the hedgehog signaling pathway. We identified a novel frameshift mutation (c.1207dupT) of PTCH1 in a NBCCS patient, which might explain multiple cystic lesions and neoplastic growth in the patient. PMID:27081528

  4. Signet-ring cell lymphoma of T-cell origin. An immunocytochemical and ultrastructural study relating giant vacuole formation to cytoplasmic sequestration of surface membrane.

    PubMed

    Grogan, T M; Richter, L C; Payne, C M; Rangel, C S

    1985-09-01

    In contrast to previous accounts of signet-ring lymphoma as a B-cell neoplasm, we report a case of signet-ring, large-cell lymphoma of T-cell lineage. Immunologic and ultrastructural studies were performed on a subcutaneous mass noted initially, as well as on an enlarged lymph node that developed later, in a 69-year-old man. Immunologic assessment indicated strong expression of T-helper antigen (Leu 3a + b), universal T-antigens (Leu 1, 5), and Ia. There was an absence of T-suppressor/cytotoxic antigen (Leu 2a), universal T-antigens (Leu 4, 9), and immunoglobulin light and heavy chains. Collectively, these findings indicate a mature T-cell lymphoma of T-helper type in an activated (Ia+) state. In contrast to previous reports of T-cell and Ia occurring solely as surface antigens, we demonstrated pools of cytoplasmic Leu 1, 3, 5 and Ia that displaced the nucleus. The ultrastructure of the giant cytoplasmic vacuoles was identical to the microvesicle-containing vacuoles reported in signet-ring cell lymphomas of B-cell lineage. In our case of T-cell lineage, we found substantial evidence of endocytosis by the neoplastic cells and numerous giant multivesicular bodies. The pools of cytoplasmic T and Ia antigens may result from abnormal internalization of surface T-antigens or the sequestration of T-antigen-containing Golgi-derived vesicles. Our combined immunologic and ultrastructural findings suggest that aberrant membrane recycling may be the common denominator of signet-ring formation in both B- and T-cell signet-ring lymphomas.

  5. Oxidative Glial Cell Damage Associated with White Matter Lesions in the Aging Human Brain.

    PubMed

    Al-Mashhadi, Sufana; Simpson, Julie E; Heath, Paul R; Dickman, Mark; Forster, Gillian; Matthews, Fiona E; Brayne, Carol; Ince, Paul G; Wharton, Stephen B

    2015-09-01

    White matter lesions (WML) are common in brain aging and are associated with dementia. We aimed to investigate whether oxidative DNA damage and occur in WML and in apparently normal white matter in cases with lesions. Tissue from WML and control white matter from brains with lesions (controls lesional) and without lesions (controls non-lesional) were obtained, using post-mortem magnetic resonance imaging-guided sampling, from the Medical Research Council Cognitive Function and Ageing Study. Oxidative damage was assessed by immunohistochemistry to 8-hydroxy-2'-deoxoguanosine (8-OHdG) and Western blotting for malondialdehyde. DNA response was assessed by phosphorylated histone H2AX (γH2AX), p53, senescence markers and by quantitative Reverse transcription polymerase chain reaction (RT-PCR) panel for candidate DNA damage-associated genes. 8-OHdG was expressed in glia and endothelium, with increased expression in both WML and controls lesional compared with controls non-lesional (P < 0.001). γH2Ax showed a similar, although attenuated difference among groups (P = 0.03). Expression of senescence-associated β-galactosidase and p16 suggested induction of senescence mechanisms in glia. Oxidative DNA damage and a DNA damage response are features of WML pathogenesis and suggest candidate mechanisms for glial dysfunction. Their expression in apparently normal white matter in cases with WML suggests that white matter dysfunction is not restricted to lesions. The role of this field-effect lesion pathogenesis and cognitive impairment are areas to be defined.

  6. Repositioning chloroquine and metformin to eliminate cancer stem cell traits in pre-malignant lesions

    PubMed Central

    Vazquez-Martin, Alejandro; López-Bonetc, Eugeni; Cufí, Sílvia; Oliveras-Ferraros, Cristina; Del Barco, Sonia; Martin-Castillo, Begoña; Menendez, Javier A.

    2013-01-01

    Ideal oncology drugs would be curative after a short treatment course if they could eliminate epithelium-originated carcinomas at their non-invasive, pre-malignant stages. Such ideal molecules, which are expected to molecularly abrogate all the instrumental mechanisms acquired by migrating cancer stem cells (CSCs) to by-pass tumour suppressor barriers, might already exist. We here illustrate how system biology strategies for repositioning existing FDA-approved drugs may accelerate our therapeutic capacity to eliminate CSC traits in pre-invasive intraepithelial neoplasias. First, we describe a signalling network signature that overrides bioenergetics stress- and oncogene-induced senescence (OIS) phenomena in CSCs residing at pre-invasive lesions. Second, we functionally map the anti-malarial chloroquine and the anti-diabetic metformin (“old drugs”) to their recently recognized CSC targets (“new uses”) within the network. By discussing the preclinical efficacy of chloroquine and metformin to inhibiting the genesis and self-renewal of CSCs we finally underscore the expected translational impact of the “old drugs–new uses” repurposing strategy to open a new CSC-targeted chemoprevention era. PMID:21600837

  7. Repositioning chloroquine and metformin to eliminate cancer stem cell traits in pre-malignant lesions.

    PubMed

    Vazquez-Martin, Alejandro; López-Bonetc, Eugeni; Cufí, Sílvia; Oliveras-Ferraros, Cristina; Del Barco, Sonia; Martin-Castillo, Begoña; Menendez, Javier A

    2011-01-01

    Ideal oncology drugs would be curative after a short treatment course if they could eliminate epithelium-originated carcinomas at their non-invasive, pre-malignant stages. Such ideal molecules, which are expected to molecularly abrogate all the instrumental mechanisms acquired by migrating cancer stem cells (CSCs) to by-pass tumour suppressor barriers, might already exist. We here illustrate how system biology strategies for repositioning existing FDA-approved drugs may accelerate our therapeutic capacity to eliminate CSC traits in pre-invasive intraepithelial neoplasias. First, we describe a signalling network signature that overrides bioenergetics stress- and oncogene-induced senescence (OIS) phenomena in CSCs residing at pre-invasive lesions. Second, we functionally map the anti-malarial chloroquine and the anti-diabetic metformin ("old drugs") to their recently recognized CSC targets ("new uses") within the network. By discussing the preclinical efficacy of chloroquine and metformin to inhibiting the genesis and self-renewal of CSCs we finally underscore the expected translational impact of the "old drugs-new uses" repurposing strategy to open a new CSC-targeted chemoprevention era. PMID:21600837

  8. Embryonic Cell Grafts in a Culture Model of Spinal Cord Lesion: Neuronal Relay Formation Is Essential for Functional Regeneration

    PubMed Central

    Tscherter, Anne; Heidemann, Martina; Kleinlogel, Sonja; Streit, Jürg

    2016-01-01

    Presently there exists no cure for spinal cord injury (SCI). However, transplantation of embryonic tissue into spinal cord (SC) lesions resulted in axon outgrowth across the lesion site and some functional recovery, fostering hope for future stem cell therapies. Although in vivo evidence for functional recovery is given, the exact cellular mechanism of the graft support remains elusive: either the grafted cells provide a permissive environment for the host tissue to regenerate itself or the grafts actually integrate functionally into the host neuronal network reconnecting the separated SC circuits. We tested the two hypotheses in an in vitro SC lesion model that is based on propagation of activity between two rat organotypic SC slices in culture. Transplantation of dissociated cells from E14 rat SC or forebrain (FB) re-established the relay of activity over the lesion site and thus, provoked functional regeneration. Combining patch-clamp recordings from transplanted cells with network activity measurements from the host tissue on multi-electrode arrays (MEAs) we here show that neurons differentiate from the grafted cells and integrate into the host circuits. Optogenetic silencing of neurons developed from transplanted embryonic mouse FB cells provides clear evidence that they replace the lost neuronal connections to relay and synchronize activity between the separated SC circuits. In contrast, transplantation of neurospheres (NS) induced neither the differentiation of mature neurons from the grafts nor an improvement of functional regeneration. Together these findings suggest, that the formation of neuronal relays from grafted embryonic cells is essential to re-connect segregated SC circuits. PMID:27708562

  9. Allelic deletion of the MEN1 gene in duodenal gastrin and somatostatin cell neoplasms and their precursor lesions

    PubMed Central

    Anlauf, M; Perren, A; Henopp, T; Rudolph, T; Garbrecht, N; Schmitt, A; Raffel, A; Gimm, O; Weihe, E; Knoefel, W T; Dralle, H; Heitz, Ph U; Komminoth, P; Klöppel, G

    2007-01-01

    Background Patients with a multiple endocrine neoplasia type 1 (MEN1)‐associated Zollinger–Ellison syndrome (ZES) show multifocal duodenal gastrinomas and precursor lesions. Aims To test these lesions for loss of heterozygosity (LOH) of the MEN1 gene locus on chromosome 11q13, and to investigate whether the MEN1‐related endocrine cell changes also involved somatostatin cells. Material and methods Tissue specimens from six patients with MEN1 and ZES were analysed by immunohistochemistry and immunofluorescence. LOH analysis was performed by fluorescence in situ hybridisation (FISH), using probes containing the MEN1 gene locus and the centromere 11 (C11) region. For simultaneous analysis of hormones and allelic deletions, a combined FISH/immunofluorescence protocol was established. Results 28 of a total of 33 duodenal neuroendocrine tumours (NETs) were gastrin‐producing tumours; 13/28 (46.4%) revealed LOH on 11q13 and/or C11. Five of the NETs were somatostatin‐expressing tumours, two revealing LOH. Allelic loss was detected in tumours as small as 300 μm (gastrin) and 400 μm (somatostatin) in diameter. The gastrin‐producing tumours showed different deletion/retention patterns. Hyperplastic somatostatin cell lesions, similar to those of the gastrin cells, were present in all patients. The hyperplastic lesions of both cell lines consistently retained both 11q13 alleles. Conclusions Allelic deletion of the MEN1 gene may reflect a pivotal event in the development of multifocal gastrin and somatostatin cell neoplasms in the duodenum of patients with MEN1. The observation of distinct deletion patterns in small synchronous tumours supports the concept that each gastrin‐producing tumour in an individual MEN1 patient arises from an independent cell clone. PMID:17135306

  10. Osteoclastome-like giant cell thyroid carcinoma controlled by intensive radiation and adriamycin, in a patient with meningioma and multiple myeloma treated by radiation and cytoxan

    SciTech Connect

    Vizel-Schwartz, M.

    1981-01-01

    The eighth cases of osteoclastome-like giant cell carcinoma of the thyroid, and the first one to be treated with adriamycin in addition to surgery and radiation, is reported. This rare variant of anaplastic thyroid carcinoma appeared in a patient operated on for meningioma and treated for multiple myeloma with cranial radiation and chronic administration of cytoxan.

  11. Crossed unilateral lesions of temporal lobe structures and cholinergic cell bodies impair visual conditional and object discrimination learning in monkeys.

    PubMed

    Barefoot, H C; Baker, H F; Ridley, R M

    2002-02-01

    Monkeys with excitotoxic lesions of the CA1/subiculum region in the right hemisphere and with immunotoxic lesions of the cholinergic cells of the diagonal band in the left hemisphere were impaired on a visual conditional task. In this task, correct choice of one of two objects depends on which of two background fields both objects are presented against, irrespective of the spatial positions of the objects. They were not impaired on simple object or shape discrimination tasks. The pattern of impairments is the same as that seen after bilateral excitotoxic lesions of CA1/subiculum, implying that the diagonal band lesion disables the ipsilateral CA1/subiculum. It also argues that CA1/subiculum, sustained by its cholinergic input, is necessary for some forms of nonspatial conditional learning. Addition of an inferotemporal (IT) cortical ablation to the left hemisphere did not affect simple visual discrimination learning, although all the monkeys then failed to learn a new visual conditional task. This demonstrates that intact IT cortex in only one hemisphere is sufficient to sustain simple visual discrimination learning but implies that the cholinergic input and the inferotemporal cortical input to the hippocampus both contribute to visual conditional learning. The subsequent addition of an immunotoxic lesion of the basal nucleus of Meynert in the right hemisphere resulted in an additional impairment on a difficult shape discrimination. This argues that it is the cholinergic projection to the inferotemporal cortex, rather than to the rest of the cortex, which contributes to visual discrimination learning and memory.

  12. Giant Planets

    NASA Astrophysics Data System (ADS)

    Lunine, J. I.

    Beyond the inner solar system's terrestrial planets, with their compact orbits and rock -metal compositions, lies the realm of the outer solar system and the giant planets. Here the distance between planets jumps by an order of magnitude relative to the spacing of the terrestrial planets, and the masses of the giants are one to two orders of magnitude greater than Venus and Earth - the largest terrestrial bodies. Composition changes as well, since the giant planets are largely gaseous, with inferred admixtures of ice, rock, and metal, while the terrestrial planets are essentially pure rock and metal. The giant planets have many more moons than do the terrestrial planets, and the range of magnetic field strengths is larger in the outer solar system. It is the giant planets that sport rings, ranging from the magnificent ones around Saturn to the variable ring arcs of Neptune. Were it not for the fact that only Earth supports abundant life (with life possibly existing, but not proved to exist, in the martian crust and liquid water regions underneath the ice of Jupiter's moon Europa), the terrestrial planets would pale in interest next to the giant planets for any extraterrestrial visitor.

  13. A novel method for monitoring functional lesion-specific recruitment of repair proteins in live cells

    PubMed Central

    Woodrick, Jordan; Gupta, Suhani; Khatkar, Pooja; Dave, Kalpana; Levashova, Darya; Choudhury, Sujata; Elias, Hadi; Saha, Tapas; Mueller, Susette; Roy, Rabindra

    2015-01-01

    DNA-protein relationships have been studied by numerous methods, but a particular gap in methodology lies in the study of DNA adduct-specific interactions with proteins in vivo, which particularly affects the field of DNA repair. Using the repair of a well-characterized and ubiquitous adduct, the abasic (AP) site, as a model, we have developed a comprehensive method of monitoring DNA lesion-specific recruitment of proteins in vivo over time. We utilized a surrogate system in which a Cy3-labeled plasmid containing a single AP-site was transfected into cells, and the interaction of the labeled DNA with BER enzymes, including APE1, Polβ, LIG1, and FEN1, was monitored by immunofluorescent staining of the enzymes by Alexafluor-488-conjugated secondary antibody. The recruitment of enzymes was characterized by quantification of Cy3-Alexafluor-488 co-localization. To validate the microscopy-based method, repair of the transfected AP-site DNA was also quantified at various time points post-transfection using a real time PCR-based method. Notably, the recruitment time kinetics for each enzyme were consistent with AP-site repair time kinetics. This microscopy-based methodology is reliable in detecting the recruitment of proteins to specific DNA substrates and can be extended to study other in vivo DNA-protein relationships in any DNA sequence and in the context of any DNA structure in transfectable proliferating or quiescent cells. The method may be applied to a variety of disciplines of nucleic acid transaction pathways, including repair, replication, transcription, and recombination. PMID:25879709

  14. A novel method for monitoring functional lesion-specific recruitment of repair proteins in live cells.

    PubMed

    Woodrick, Jordan; Gupta, Suhani; Khatkar, Pooja; Dave, Kalpana; Levashova, Darya; Choudhury, Sujata; Elias, Hadi; Saha, Tapas; Mueller, Susette; Roy, Rabindra

    2015-05-01

    DNA-protein relationships have been studied by numerous methods, but a particular gap in methodology lies in the study of DNA adduct-specific interactions with proteins in vivo, which particularly affects the field of DNA repair. Using the repair of a well-characterized and ubiquitous adduct, the abasic (AP) site, as a model, we have developed a comprehensive method of monitoring DNA lesion-specific recruitment of proteins in vivo over time. We utilized a surrogate system in which a Cy3-labeled plasmid containing a single AP-site was transfected into cells, and the interaction of the labeled DNA with BER enzymes, including APE1, Polβ, LIG1, and FEN1, was monitored by immunofluorescent staining of the enzymes by Alexafluor-488-conjugated secondary antibody. The recruitment of enzymes was characterized by quantification of Cy3-Alexafluor-488 co-localization. To validate the microscopy-based method, repair of the transfected AP-site DNA was also quantified at various time points post-transfection using a real time PCR-based method. Notably, the recruitment time kinetics for each enzyme were consistent with AP-site repair time kinetics. This microscopy-based methodology is reliable in detecting the recruitment of proteins to specific DNA substrates and can be extended to study other in vivo DNA-protein relationships in any DNA sequence and in the context of any DNA structure in transfectable proliferating or quiescent cells. The method may be applied to a variety of disciplines of nucleic acid transaction pathways, including repair, replication, transcription, and recombination. PMID:25879709

  15. Mutation Analysis of H3F3A and H3F3B as a Diagnostic Tool for Giant Cell Tumor of Bone and Chondroblastoma.

    PubMed

    Cleven, Arjen H G; Höcker, Saskia; Briaire-de Bruijn, Inge; Szuhai, Karoly; Cleton-Jansen, Anne-Marie; Bovée, Judith V M G

    2015-11-01

    Specific H3F3A driver mutations and IDH2 mutations were recently described in giant cell tumor of bone (GCTB) and H3F3B driver mutations in chondroblastoma; these may be helpful as a diagnostic tool for giant cell-containing tumors of the bone. Using Sanger sequencing, we determined the frequency of H3F3A, H3F3B, IDH1, and IDH2 mutations in GCTBs (n=60), chondroblastomas (n=12), and other giant cell-containing tumors (n=24), including aneurysmal bone cyst, chondromyxoid fibroma, and telangiectatic osteosarcoma. To find an easy applicable marker for H3F3A mutation status, H3K36 trimethylation and ATRX expression were correlated with H3F3A mutations. In total, 69% of all GCTBs harbored an H3F3A (G34W/V) mutation compared with 0% of all other giant cell-containing tumors (P<0.001), whereas 70% of chondroblastomas showed an H3F3B (K36M) mutation compared with 0% of other giant cell-containing tumors (P<0.001). Diffuse H3K36 trimethylation positivity was more often seen in mutated H3F3A GCTBs compared with other giant cell-containing tumors (P=0.005). ATRX protein expression was not correlated with H3F3A mutation status. Hotspot mutations in IDH1 or IDH2 were absent. Our results show that H3F3A and H3F3B mutation analysis appears to be a highly specific, although less sensitive, diagnostic tool for the distinction of GCTB and chondroblastoma from other giant cell-containing tumors. Although H3K36 trimethylation and ATRX immunohistochemistry cannot be used as surrogate markers for H3F3A mutation status, mutations in H3F3A are associated with increased H3K36 trimethylation, suggesting that methylation at this residue may play a role in the etiology of the disease.

  16. Mutation Analysis of H3F3A and H3F3B as a Diagnostic Tool for Giant Cell Tumor of Bone and Chondroblastoma.

    PubMed

    Cleven, Arjen H G; Höcker, Saskia; Briaire-de Bruijn, Inge; Szuhai, Karoly; Cleton-Jansen, Anne-Marie; Bovée, Judith V M G

    2015-11-01

    Specific H3F3A driver mutations and IDH2 mutations were recently described in giant cell tumor of bone (GCTB) and H3F3B driver mutations in chondroblastoma; these may be helpful as a diagnostic tool for giant cell-containing tumors of the bone. Using Sanger sequencing, we determined the frequency of H3F3A, H3F3B, IDH1, and IDH2 mutations in GCTBs (n=60), chondroblastomas (n=12), and other giant cell-containing tumors (n=24), including aneurysmal bone cyst, chondromyxoid fibroma, and telangiectatic osteosarcoma. To find an easy applicable marker for H3F3A mutation status, H3K36 trimethylation and ATRX expression were correlated with H3F3A mutations. In total, 69% of all GCTBs harbored an H3F3A (G34W/V) mutation compared with 0% of all other giant cell-containing tumors (P<0.001), whereas 70% of chondroblastomas showed an H3F3B (K36M) mutation compared with 0% of other giant cell-containing tumors (P<0.001). Diffuse H3K36 trimethylation positivity was more often seen in mutated H3F3A GCTBs compared with other giant cell-containing tumors (P=0.005). ATRX protein expression was not correlated with H3F3A mutation status. Hotspot mutations in IDH1 or IDH2 were absent. Our results show that H3F3A and H3F3B mutation analysis appears to be a highly specific, although less sensitive, diagnostic tool for the distinction of GCTB and chondroblastoma from other giant cell-containing tumors. Although H3K36 trimethylation and ATRX immunohistochemistry cannot be used as surrogate markers for H3F3A mutation status, mutations in H3F3A are associated with increased H3K36 trimethylation, suggesting that methylation at this residue may play a role in the etiology of the disease. PMID:26457357

  17. Effect of arsenic and cadmium on the persistence of mutagen-induced DNA lesions in human cells

    SciTech Connect

    Hartmann, A.; Speit, G.

    1996-12-31

    The alkaline single cell gel electrophoresis (SCG test or comet assay) was used to characterize the influence of sodium arsenite (NaAsO{sub 2}) and cadmium sulphate (CdSO{sub 4}) on the persistence of mutagen-induced DNA lesions. Human blood and SV40-transformed fibroblasts (MRC5CV1) were treated for 2 hr with methyl methanesulphonate (MMS) or benzo(a)pyrene (BaP). MMS induced concentration-related DNA damage in white blood cells (WBC) and fibroblasts in similar concentrations. For the induction of DNA damage by BaP, higher concentrations had to be applied to WBC than to the fibroblast cell line. To study the influence of metal ions on the persistence of DNA lesions, treated cells were further incubated for 2 hr in the absence (post-incubation) or presence (posttreatment) of NaAsO{sub 2} or CdSO{sub 4}, BaP- and MMS-induced DNA lesions persisted in both cell types, indicating an inhibition of DNA repair by these metals. The results suggest a strong interaction of arsenic and cadmium with BaP- and MMS-induced DNA repair processes. 34 refs., 5 figs., 2 tabs.

  18. Hemodynamic Transesophageal Echocardiography-Guided Venous-Arterial Extracorporeal Membrane Oxygenation Support in a Case of Giant Cell Myocarditis

    PubMed Central

    Ratzlaff, Robert A.; Menke, David M.; Olave, Maria C.; Maleszewski, Joseph J.

    2016-01-01

    Giant cell myocarditis (GCM) is a rare and commonly fatal form of fulminant myocarditis. During the acute phase, while immunosuppressive therapy is initiated, venoarterial extracorporeal membrane oxygenation (VA-ECMO) support is commonly used as a bridge to heart transplantation or recovery. Until recently, conventional transesophageal echocardiography and transthoracic echocardiography were the tools available for hemodynamic assessment of patients on this form of mechanical circulatory support. Nevertheless, both techniques have their limitations. We present a case of a 54-year-old man diagnosed with GCM requiring VA-ECMO support that was monitored under a novel miniaturized transesophageal echocardiography (hTEE) probe recently approved for 72 hours of continuous hemodynamic monitoring. Our case highlights the value of this novel, flexible, and disposable device for hemodynamic monitoring, accurate therapy guidance, and potential VA-ECMO weaning process of patients with this form of severe myocarditis.

  19. Giant Cell Arteritis which Developed after the Administration of Granulocyte-colony Stimulating Factor for Cyclic Neutropenia.

    PubMed

    Umeda, Masataka; Ikenaga, Jin; Koga, Tomohiro; Michitsuji, Toru; Shimizu, Toshimasa; Fukui, Shoichi; Nishino, Ayako; Nakasima, Yoshikazu; Kawashiri, Sin-Ya; Iwamoto, Naoki; Ichinose, Kunihiro; Hirai, Yasuko; Tamai, Mami; Nakamura, Hideki; Origuchi, Tomoki; Kawakami, Atsushi

    2016-01-01

    A 78-year-old woman diagnosed with cyclic neutropenia 5 years previously had been treated with recombinant granulocyte-colony stimulating factor (G-CSF). She developed fever, tenderness and distension of temporal arteries after the treatment with G-CSF. Magnetic resonance imaging and ultrasonography revealed wall thickening of the temporal arteries. She was therefore diagnosed with giant cell arteritis (GCA). Small vessel vasculitis has been reported as a complication of G-CSF. However, the development of large vessel vasculitis after G-CSF treatment is quite rare. To our knowledge, the present case is the first report of GCA suspected to be associated with coexisting cyclic neutropenia and G-CSF treatment. PMID:27523011

  20. The treatment of giant cell tumors by curettage and filling with acrylic cement. Long-term functional results.

    PubMed

    Segura, J; Albareda, J; Bueno, A L; Nuez, A; Palanca, D; Seral, F

    1997-01-01

    Curettage and filling with acrylic cement in the treatment of para-articular giant cell tumor (GCT) has multiple advantages as compared to other methods; nonetheless, the possibility of progression in arthrosis is still a drawback. The literature does not report long-term functional results when this method was used. Four cases are presented with a mean long-term follow-up of 13.5 years (minimum 11, maximum 18). Clinical results, evaluated by the Enneking system (18), were excellent, and there were no radiological modifications, so that we believe that this is the method to choose for Campanacci stage I and II GCT (1), and in some stage III cases, as joint function is not compromised in time.

  1. Hemodynamic Transesophageal Echocardiography-Guided Venous-Arterial Extracorporeal Membrane Oxygenation Support in a Case of Giant Cell Myocarditis

    PubMed Central

    Ratzlaff, Robert A.; Menke, David M.; Olave, Maria C.; Maleszewski, Joseph J.

    2016-01-01

    Giant cell myocarditis (GCM) is a rare and commonly fatal form of fulminant myocarditis. During the acute phase, while immunosuppressive therapy is initiated, venoarterial extracorporeal membrane oxygenation (VA-ECMO) support is commonly used as a bridge to heart transplantation or recovery. Until recently, conventional transesophageal echocardiography and transthoracic echocardiography were the tools available for hemodynamic assessment of patients on this form of mechanical circulatory support. Nevertheless, both techniques have their limitations. We present a case of a 54-year-old man diagnosed with GCM requiring VA-ECMO support that was monitored under a novel miniaturized transesophageal echocardiography (hTEE) probe recently approved for 72 hours of continuous hemodynamic monitoring. Our case highlights the value of this novel, flexible, and disposable device for hemodynamic monitoring, accurate therapy guidance, and potential VA-ECMO weaning process of patients with this form of severe myocarditis. PMID:27648312

  2. Hemodynamic Transesophageal Echocardiography-Guided Venous-Arterial Extracorporeal Membrane Oxygenation Support in a Case of Giant Cell Myocarditis.

    PubMed

    Ripoll, Juan G; Ratzlaff, Robert A; Menke, David M; Olave, Maria C; Maleszewski, Joseph J; Díaz-Gómez, José L

    2016-01-01

    Giant cell myocarditis (GCM) is a rare and commonly fatal form of fulminant myocarditis. During the acute phase, while immunosuppressive therapy is initiated, venoarterial extracorporeal membrane oxygenation (VA-ECMO) support is commonly used as a bridge to heart transplantation or recovery. Until recently, conventional transesophageal echocardiography and transthoracic echocardiography were the tools available for hemodynamic assessment of patients on this form of mechanical circulatory support. Nevertheless, both techniques have their limitations. We present a case of a 54-year-old man diagnosed with GCM requiring VA-ECMO support that was monitored under a novel miniaturized transesophageal echocardiography (hTEE) probe recently approved for 72 hours of continuous hemodynamic monitoring. Our case highlights the value of this novel, flexible, and disposable device for hemodynamic monitoring, accurate therapy guidance, and potential VA-ECMO weaning process of patients with this form of severe myocarditis. PMID:27648312

  3. 18F-fluorodeoxyglucose positron emission tomography and the risk of subsequent aortic complications in giant-cell arteritis

    PubMed Central

    de Boysson, Hubert; Liozon, Eric; Lambert, Marc; Parienti, Jean-Jacques; Artigues, Nicolas; Geffray, Loïk; Boutemy, Jonathan; Ollivier, Yann; Maigné, Gwénola; Ly, Kim; Huglo, Damien; Hachulla, Eric; Hatron, Pierre-Yves; Aouba, Achille; Manrique, Alain; Bienvenu, Boris

    2016-01-01

    Abstract Previous studies reported a 2- to 17-fold higher risk of aortic complications (dilation or dissection) in patients with giant-cell arteritis (GCA). We aimed to determine whether or not GCA patients with large-vessel involvement demonstrated by positron emission tomography with 18F-fluorodeoxyglucose combined with computed tomography (FDG-PET/CT) have a higher risk of aortic complications. We conducted a retrospective multicenter study between 1995 and 2014. Patients were included if they fulfilled at least 3 American College of Rheumatology criteria for GCA, or 2 criteria associated with extratemporal biopsy-proven giant-cell vasculitis; they underwent at least 1 FDG-PET/CT scan at diagnosis or during follow-up; and the morphology of the aorta was assessed by medical imaging at diagnosis. Patients with an aortic complication at the time of diagnosis were excluded. Of the 130 patients included [85 women (65%), median age 70 (50–86)], GCA was biopsy proven in 77 (59%). FDG-PET/CT was performed at diagnosis in 63 (48%) patients and during the follow-up period in the 67 (52%) remaining patients. FDG-PET/CT was positive in 38/63 (60%) patients at diagnosis and in 31/67 (46%) patients when performed during follow-up (P = NS). One hundred four patients (80%) underwent at least 1 morphological assessment of the aorta during follow-up. Nine (9%) patients developed aortic complications (dilation in all and dissection in 1) at a median time of 33 (6–129) months after diagnosis. All of them displayed large-vessel inflammation on previous FDG-PET/CT. A positive FDG-PET/CT was significantly associated with a higher risk of aortic complications (P = 0.004). In our study, a positive FDG-PET/CT was associated with an increased risk of aortic complications at 5 years. PMID:27367985

  4. Apoptosis is abundant in human atherosclerotic lesions, especially in inflammatory cells (macrophages and T cells), and may contribute to the accumulation of gruel and plaque instability.

    PubMed Central

    Björkerud, S.; Björkerud, B.

    1996-01-01

    Death of intimal tissue may lead to plaque rupture with thrombosis, which is the basis of the most severe clinical consequences of atherosclerosis. Little is known about the mechanisms that promote intimal cell death or its nature. This work was undertaken to elucidate the extent to which, the cell types in which, and where programmed cell death, apoptosis, might occur in atherosclerotic lesions. The material was fibrous or fibro-fatty non-ulcerated lesions from the human thoracic aorta and coronary arteries. Apoptosis was indicated by the in situ labeling of internucleosomally degraded DNA with the TUNEL technique, which has a preference for apoptosis as compared with cell necrosis and was combined with the immunohistochemical typing of cells. Apoptosis was corroborated by morphological criteria on the light and electron microscope levels and by the presence of an apoptosis-specific protein. It was common in the lesions and virtually absent in non-atherosclerotic regions. It occurred in smooth muscle cells subendothelially, in places of the fibrous cap, and in the underlying media, which may destabilize the plaque and promote rupture. Inflammatory cells, ie, macrophages and T cells, appeared abundantly subendothelially, in the fibrous cap, and in the shoulder regions, and apoptosis was common, maybe reflecting a means for quenching of the inflammatory reaction. Many macrophages contained abundant apoptotic material indicative of phagocytosis of apoptotic cells, but the occurrence of apoptosis, even in some of these cells, and of apoptotic material extracellularly and the very high numbers of apoptotic cells that were encountered may indicate insufficient mechanisms for the removal of apoptotic cells in the atherosclerotic lesion. It is not possible to decide as yet whether this is due to overloading with cellular material by inflammation and cell multiplication, to an increased frequency of apoptosis, to a reduction of the removal/degradation of apoptotic material

  5. Jaw Intraosseous Lesions Biopsied Extracted From 1998 to 2010 in an Iranian Population

    PubMed Central

    Jamshidi, Shokoofeh; Shojaei, Setareh; Roshanaei, Ghodratollah; Modabbernia, Shirin; Bakhtiary, Esmaeel

    2015-01-01

    Background: Jaw bones might be potential locations for different lesions. Differences in prevalence and the type of lesions can help in designing and programming prevention procedures in health care centers. Objectives: The aim of the present study was to evaluate the prevalence of intraosseous lesions in the jaws of patients referred to diagnostic and therapeutic centers in Hamadan during 1990-2010. Patients and Methods: This cross-sectional descriptive analytical study was carried out in Hamadan in 2011. Data sheets of the subjects were used to collect all the data of patients with intraosseous lesions, including their age, gender, location of the lesion, the radiographic view of lesions, and their type and histopathological diagnoses. Data were analyzed with SPSS, using means and frequencies. Results: A total of 284 intraosseous lesions were reported in our study. The mean age of the subjects was 28.8 ± 15.2 years. The lesions were distributed in males and females almost similarly. The most prevalent lesions were cystic lesions (54.58%), manifestations of systemic conditions in jaw bones (18.3%), benign tumors (15.5%), malignant lesions (6.7%), and inflammatory lesions (4.92%), in a descending order. The most common cystic lesion was radicular cyst; the most common manifestation of systemic conditions in jaw bones was central giant cell granuloma; the most common benign tumor was ameloblastoma; the most common malignant lesion was osteosarcoma; and the most common inflammatory lesion was periapical granuloma. Conclusions: Our data provided information on the prevalence and types of intraosseous lesions among an Iranian population. This study provided baseline information to help in designing and programming procedures in health care centers in every community so that preventive therapeutic measures can be adopted. PMID:26328061