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Sample records for central giant cell

  1. Central giant cell granuloma of the maxilla

    PubMed Central

    Gupta, Manish; Gupta, Monica; Singh, Sunder; Kaur, Rupinder

    2013-01-01

    Central giant cell granuloma (CGCG), formerly called giant cell reparative granuloma, is a non-neoplastic proliferative lesion of an unknown aetiology. It occurs most commonly in the mandible. The case reported here resembled a wide variety of conditions that led to a misdiagnosis both on clinical and radiographic examinations but was histopathologically diagnosed as CGCG. We managed this case by endoscopic excision and curettage via nasal route without producing external scar and avoiding damage to the un-erupted tooth. PMID:23475995

  2. Expression of CD34 and CD68 in peripheral giant cell granuloma and central giant cell granuloma: An immunohistochemical analysis

    PubMed Central

    VK, Varsha; Hallikeri, Kaveri; Girish, HC; Murgod, Sanjay

    2014-01-01

    Background: Central and Peripheral giant cell granulomas of jaws are uncommon, benign, reactive disorders that are characterized by the presence of numerous multinucleated giant cells and mononuclear cells within a stroma. The origin of the multinucleated giant cells is controversial; probably originating from fusion of histiocytes, endothelial cells and fibroblasts. Objective: To assess the expression of CD34 and CD68 in central and peripheral giant cell granulomas to understand the origin of these multinucleated giant cells. Materials and Methods: Twenty cases of Central and Peripheral giant cell granulomas were evaluated immunohistochemically for CD34 and CD68 proteins expression. Results: Immunopositivity for CD34 was seen only in cytoplasm of endothelial cells of blood vessels; whereas, consistent cytoplasmic immunopositivity for CD68 was seen in few stromal cells. Statistical significance was seen in mean number of multinucleated giant cells, mean number of nuclei in multinucleated giant cells, CD68 expression and ratio of macrophages to multinucleated giant cells among two lesions. Conclusion: Although the central giant cell granulomas share some clinical and histopathological similarities with peripheral giant cell granulomas, differences in mean number of nuclei in multinucleated giant cells and CD68 immunoreactivity may underlie the distinct clinical behavior. PMID:25948986

  3. 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

  4. 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

  5. Central Giant Cell Granuloma of Posterior Maxilla: First Expression of Primary Hyperparathyroidism

    PubMed Central

    Gulati, Deepanshu; Bansal, Vishal; Dubey, Prajesh; Pandey, Sanjay; Agrawal, Abhinav

    2015-01-01

    A case of 19-year-old male patient reported with the chief complaint of slowly growing diffuse painless swelling over the right part of the face from last 6 months. Intraoral examination revealed a swelling on right side of palate in relation to molar region with buccal cortical plate expansion. Radiographic examination (orthopantograph and 3DCT) showed large multilocular radiolucency in right maxilla with generalized loss of lamina dura. Incisional biopsy was done and specimen was sent for histopathological examination which showed multinucleated giant cells containing 15–30 nuclei. Based on clinical, radiological, and histopathological findings provisional diagnosis of central giant cell granuloma was made. Blood tests after histopathology demonstrated elevated serum calcium level and alkaline phosphatase level. Immunoassay of parathyroid hormone (PTH) level was found to be highly elevated. Radiographic examination of long bones like humerus and femur, mandible, and skull was also done which showed osteoclastic lesions. Considering the clinical, radiographic, histopathological, and blood investigation findings, final diagnosis of brown tumour of maxilla was made. The patient underwent partial parathyroidectomy under general anaesthesia to control primary hyperparathyroidism. Surgical removal of the bony lesion was done by curettage. The patient has been followed up for 1 year with no postoperative complications and the lesion healed uneventfully. PMID:25692050

  6. Surgical Management of Aggressive Central Giant Cell Granuloma of Maxilla through Le Fort I Access Osteotomy

    PubMed Central

    Reddy, G. V.; Reddy, G. Siva Prasad; Reddy, N. V. S. Sekhar; Kumar, Aswin

    2012-01-01

    Giant cell granuloma (GCG) is an uncommon bony lesion in the head and neck region, most commonly affecting the maxilla and mandible and has a female predilection. The clinical behavior of central GCG ranges from a slowly growing asymptomatic swelling to an aggressive lesion. The clinical, radiological, histological features and management of an aggressive GCG of maxilla in an 18-year-old female patient are described and discussed. It is emphasized that surgery is the traditional and still the most accepted treatment for GCG. Le Fort I osteotomy has been advocated as one of the access osteotomy for the surgical management of aggressive and extensive GCG involving the maxilla. The postoperative morbidity and recurrence have been discussed. PMID:22754742

  7. 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. PMID:27000410

  8. Quantification and Correlation of Angiogenesis with Macrophages by Histomorphometric Method in Central and Peripheral Giant Cell Granuloma: An Immunohistochemical Analysis

    PubMed Central

    Krishanappa, Savita Jangal; Prakash, Smitha Gowdra; Channabasaviah, Girish Hemdal; Murgod, Sanjay; Pujari, Ravikumar; Kamat, Mamata Sharad

    2016-01-01

    Introduction Angiogenesis is a fundamental process that affects physiologic reactions and pathological processes such as tumour development and metastasis. It is the process of formation of new microvessel from the preexisting vessels. Aim The purpose of this study was to evaluate angiogenesis, macrophage index and correlate the impact of macrophages on angiogenesis in the central and peripheral giant cell granulomas by evaluating immunohistochemically microvessel density, microvessel perimeter and macrophage index. Materials and Methods Immunohistochemical analysis was carried on 20 cases of central and peripheral giant cell granulomas each for CD34 and CD68 proteins expression. Inferential statistical analysis was performed using Independent student t-test to assess the microvessel density, microvessel perimeter and macrophage index on continuous scale between Group I and Group II. Level of significance was determined at 5%. Further bivariate analysis using Pearson correlation test was carried out to see the relationship between microvessel density and macrophage index in each group. Results Microvessel density, micro vessel perimeter and macrophage index was higher in central giant cell granuloma compared to that of peripheral giant cell granuloma. Correlation between microvessel density and macrophage index among these two lesions was statistically insignificant. Conclusion Angiogenesis as well as the number of macrophages appeared to increase in Central Giant Cell Granuloma in present study. These findings suggest that macrophages may up regulate the angiogenesis in these giant cell granulomas and angiogenesis do have a role in clinical behaviour. However, we could not establish a positive correlation between microvessel density and macrophage index as the values were statistically insignificant. This insignificance may be presumed due to fewer samples taken for study. PMID:27134990

  9. Incidence of central giant cell granuloma of the jaws with clinical and histological confirmation: an archival study in Northern India.

    PubMed

    Reddy, V; Saxena, S; Aggarwal, P; Sharma, P; Reddy, M

    2012-10-01

    To record the demographics, and correlate histological findings in central giant cell granulomas (CGCGs) of the jaws with their clinical behaviour, 30 paraffin-embedded samples of CGCG were retrieved from the archives of the Department of Oral Pathology and Microbiology, Subharti Dental College, Meerut, India. The diagnosis in each case was made on the basis of clinical, radiographic, and histological findings. Data about age, sex, anatomical site, presentation, radiological features, and laboratory investigations were analysed. Histomorphometric analyses were made in each case with respect to the number of giant cells, mean number of nuclei and giant cells, fractional surface area occupied by giant cells, index of relative size, and mitotic activity. The peak incidence of CGCG was during the second decade of life with a slight female predilection, and the mandible was the most common site. Of the 30 samples considered, 20 tumours were classified clinically as non-aggressive, and 10 as aggressive, based on their clinical behaviour. Histomorphometric analysis showed significant changes between the two groups with respect to the number of giant cells, the fractional surface area, and the mitotic activity. The data obtained showed clinical and histomorphometric features that may be reliable indicators for the differentiation between aggressive and non-aggressive CGCG. These data should be taken into consideration to improve planning of individual treatment and follow-up. PMID:22196146

  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. Mandibular central giant cell granuloma associated with sclerosing osteomyelitis of Garrè (periostitis ossificans). Case report.

    PubMed

    Toller, M O; Karaca, I

    1993-04-01

    Garrè's sclerosing osteomyelitis or periostitis ossificans with a radiographic 'onion skin' appearance is a separate clinical entity. The new bone formation underneath the periosteum is a response of periosteum to stimulation by low grade infection. This may occur in a variety of other developmental, metabolic, inflammatory and neoplastic diseases of bone. A case of mandibular giant cell granuloma of a central type associated with Garrè's sclerosing osteomyelitis is presented and the literature is reviewed. PMID:8494507

  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. Peripheral giant cell granuloma.

    PubMed

    Adlakha, V K; Chandna, P; Rehani, U; Rana, V; Malik, P

    2010-01-01

    Peripheral giant cell granuloma is a benign reactive lesion of gingiva. It manifests as a firm, soft, bright nodule or as a sessile or pedunculate mass. This article reports the management of peripheral giant cell granuloma in a 12-year-old boy by surgical excision. PMID:21273719

  14. 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)

  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. Peripheral Giant Cell Granuloma in a Dog.

    PubMed

    Hiscox, Lorraine A; Dumais, Yvan

    2015-01-01

    Peripheral giant cell granuloma is considered rare in the dog with little known about the clinicopathologic features. There are few reports in the veterinary literature concerning this benign, reactive lesion, formerly known as giant cell epulis. In humans, the four most commonly described reactive epulides are focal fibrous hyperplasia (fibrous epulis), pyogenic granuloma, peripheral ossifying fibroma, and peripheral giant cell granuloma. This case report describes the diagnosis and surgical management of a peripheral giant cell granuloma in a dog. PMID:26415387

  17. 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.

  18. Can calcitonin nasal spray reduce the risk of recurrence of central giant cell granuloma of the jaws? A double-blind clinical trial.

    PubMed

    Tabrizi, R; Fardisi, S; Zamiri, B; Amanpour, S; Karagah, T

    2016-06-01

    Recurrence is a major problem following the treatment of aggressive central giant cell granuloma (CGCG). The aim of this study was to compare the frequency of recurrence between patients who received calcitonin nasal spray after curettage of CGCGs and those who did not. A double-blind clinical trial was designed. Patients were allocated to one of two groups: those in the calcitonin group underwent curettage and received calcitonin salmon nasal spray 200IU/day once a day for 3 months after surgery; those in the control group underwent curettage of CGCGs and received a placebo once a day for 3 months after surgery. All patients were followed for 5 years after surgery. Twenty-four patients were treated in the two groups. There was no difference in age, sex, tumour size, or tumour location between the two groups (P>0.05). Eight of the 24 patients (33.3%) had recurrences during the follow-up period: one in the calcitonin group (9.1%) and seven in the control group (53.8%). Analysis of the data demonstrated a significant difference between the two study groups (P=0.033). It appears that calcitonin nasal spray may reduce the frequency of recurrence in aggressive CGCGs in the mandible and maxilla. PMID:26993105

  19. [Aortitis in giant cell arteritis].

    PubMed

    Schmidt, J; Duhaut, P

    2016-04-01

    Aortitis is a frequent complication of giant cell arteritis. Imaging techniques can reveal the inflammation of the aortic wall. CT-scan can show circumferential aortic wall thickening, or TEP-scan can show aortic FDG-uptake. Aortic aneurysm and dissection is a feared but probably rare complication of the inflammation of the aortic wall during GCA. Screening for aortitis could be proposed for patients with symptoms of aortic involvement, for patients with signs of large vessels involvement (limb claudication, bruit) or for patients with incomplete response to treatment. The best follow-up and treatment are to be determined for the patients with aortitis related to GCA. PMID:26781692

  20. SYNOVIAL GIANT CELL TUMOR OF THE KNEE

    PubMed Central

    Abdalla, Rene Jorge; Cohen, Moisés; Nóbrega, Jezimar; Forgas, Andrea

    2015-01-01

    Synovial giant cell tumor is a benign neoplasm, rarely reported in the form of malignant metastasis. Synovial giant cell tumor most frequently occurs on the hand, and, most uncommon, on the ankle and knee. In the present study, the authors describe a rare case of synovial giant cell tumor on the knee as well as the treatment approach. Arthroscopy has been shown, in this case, to be the optimal method for treating this kind of lesion, once it allowed a less aggressive approach, while providing good visualization of all compartments of knee joint and full tumor resection. PMID:27004193

  1. Giant cell arteritis presenting as scalp necrosis.

    PubMed

    Maidana, Daniel E; Muñoz, Silvia; Acebes, Xènia; Llatjós, Roger; Jucglà, Anna; Alvarez, Alba

    2011-01-01

    The differential of scalp ulceration in older patients should include several causes, such as herpes zoster, irritant contact dermatitis, ulcerated skin tumors, postirradiation ulcers, microbial infections, pyoderma gangrenosum, and giant cell arteritis. Scalp necrosis associated with giant cell arteritis was first described in the 1940s. The presence of this dermatological sign within giant cell arteritis represents a severity marker of this disease, with a higher mean age at diagnosis, an elevated risk of vision loss and tongue gangrene, as well as overall higher mortality rates, in comparison to patients not presenting this manifestation. Even though scalp necrosis due to giant cell arteritis is exceptional, a high level of suspicion must be held for this clinical finding, in order to initiate prompt and proper treatment and avoid blindness. PMID:21789466

  2. 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

  3. Osteoclastic giant cell tumor of the pancreas☆

    PubMed Central

    Temesgen, Wudneh M.; Wachtel, Mitchell; Dissanaike, Sharmila

    2014-01-01

    INTRODUCTION Pancreatic giant cell tumors are rare, with an incidence of less than 1% of all pancreatic tumors. Osteoclastic giant cell tumor (OGCT) of the pancreas is one of the three types of PGCT, which are now classified as undifferentiated carcinoma with osteoclast-like giant cells. PRESENTATION OF CASE The patient is a 57 year old woman who presented with a 3 week history of epigastric pain and a palpable abdominal mass. Imaging studies revealed an 18 cm × 15 cm soft tissue mass with cystic components which involved the pancreas, stomach and spleen. Exploratory laparotomy with distal pancreatectomy, partial gastrectomy and splenectomy was performed. Histology revealed undifferentiated pancreatic carcinoma with osteoclast-like giant cells with production of osteoid and glandular elements. DISCUSSION OGCT of the pancreas resembles benign-appearing giant cell tumors of bone, and contain osteoclastic-like multinucleated cells and mononuclear cells. OGCTs display a less aggressive course with slow metastasis and lymph node spread compared to pancreatic adenocarcinoma. Due to the rarity of the cancer, there is a lack of prospective studies on treatment options. Surgical en-bloc resection is currently considered first line treatment. The role of adjuvant therapy with radiotherapy or chemotherapy has not been established. CONCLUSION Pancreatic giant cell tumors are rare pancreatic neoplasms with unique clinical and pathological characteristics. Osteoclastic giant cell tumors are the most favorable sub-type. Surgical en bloc resection is the first line treatment. Long-term follow-up of patients with these tumors is essential to compile a body of literature to help guide treatment. PMID:24631915

  4. 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 ...

  5. 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.

  6. 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. PMID:17664921

  7. Polymyalgia rheumatica and giant cell arteritis.

    PubMed

    Subrahmanyan, Peddasomayajula; Dasgupta, Bhaskar

    2006-05-01

    Polymyalgia rheumatica and giant cell arteritis are the commonest inflammatory rheumatic conditions seen in the elderly. This review focuses on the diagnostic processes and complications of disease and treatment; and the safe management of these conditions with careful consideration of balance between benefits and long-term risks of glucocorticosteroid therapy. PMID:16729627

  8. Giant Cell Arteritis and Polymyalgia Rheumatica

    MedlinePlus

    ... symptoms of both GCA and PMR. Other Organizations Arthritis Foundation Questions to Ask Your Doctor What is the likely cause of my symptoms? Do I need any blood tests or biopsies? I have giant cell arteritis. Am I more likely to have polymyalgia rheumatica? I have polymyalgia ...

  9. Giant-cell granuloma of the sinuses

    SciTech Connect

    Rhea, J.T.; Weber, A.L.

    1983-04-01

    Three cases are presented which illustrate giant-cell granulomas in the maxillary, ethmoid, and sphenoid sinuses. The radiographic features are nonspecific, and the lesion can mimic carcinoma. Ossification can be demonstrated, especially with computed tomography, and may indicate a benign lesion.

  10. 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

  11. Identification of a giant cell fibroma.

    PubMed

    Lukes, Sherri M; Kuhnert, Joleen; Mangels, Mark A

    2005-01-01

    Fibrous hyperplastic connective tissue lesions are common in the oral cavity and may be similar both clinically and histologically. A giant cell fibroma, a type of fibrous hyperplasia, was discovered during a preventive patient visit in the dental hygiene clinic at a Midwestern university. The patient, a 19-year-old female, presented with a dome-shaped lesion of normal mucosal color on the attached gingiva apical to tooth number 11. She was referred to the dental school for biopsy, which revealed fibrocollagenous connective tissue exhibiting large stellate fibroblasts. She returned after 10 months and was referred to the graduate periodontal department, where the lesion was removed. Several fibrous hyperplastic lesions can be considered in the differential diagnosis of giant cell fibroma. Dental hygienists should be familiar with the different fibrous hyperplasias, noting lesions during the intra- and extra-oral examinations for further evaluation by the dentist. PMID:16197774

  12. Apical Orbital Aspergillosis Complicating Giant Cell Arteritis.

    PubMed

    Zhou, Yang; Morgan, Michael L; Almarzouqi, Sumayya J; Chevez-Barrios, Patricia; Lee, Andrew G

    2016-06-01

    A 75-year-old woman with new onset headaches and left vision loss, temporal scalp tenderness, and jaw claudication was found to have biopsy-proven giant cell arteritis (GCA). Despite treatment and improvement with prednisone, she later developed left orbital apex syndrome, and an orbital biopsy revealed aspergillosis. After antifungal treatment, extraocular motility improved although vision in the left eye remained no light perception. Clinicians should be aware that fungal orbital apex disease may mimic or complicate steroid-treated GCA. PMID:26835662

  13. 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

  14. Denosumab-treated Giant Cell Tumor of Bone Exhibits Morphologic Overlap With Malignant Giant Cell Tumor of Bone.

    PubMed

    Wojcik, John; Rosenberg, Andrew E; Bredella, Miriam A; Choy, Edwin; Hornicek, Francis J; Nielsen, G Petur; Deshpande, Vikram

    2016-01-01

    Giant cell tumor (GCT) of bone is a locally aggressive benign neoplasm characterized by an abundance of osteoclastic giant cells that are induced by the neoplastic mononuclear cells; the latter express high levels of receptor activator of nuclear factor κ-B ligand (RANKL). Denosumab, a RANKL inhibitor, which is clinically used to treat GCT, leads to a marked alteration in the histologic appearance of the tumor with giant cell depletion and new bone deposition, leading to substantial histologic overlap with other primary tumors of bone. Most significantly, denosumab-treated GCT (tGCT) with abundant bone deposition may mimic de novo osteosarcoma, or GCT that has undergone malignant transformation. To histologically characterize tGCT, we identified 9 cases of GCT biopsied or resected after denosumab treatment. tGCT cases included 16 specimens from 9 patients including 6 female and 3 male individuals aged 16 to 47 (median 32) years. Duration of treatment varied from 2 to 55 months. We compared these tumors with malignant neoplasms arising in GCTs (n=9). The histology of tGCT was variable but appeared to relate to the length of therapy. All tGCTs showed marked giant cell depletion. Early lesions were highly cellular, and the combination of cellularity, atypia, and haphazard bone deposition caused the lesion to resemble high-grade osteosarcoma. Unlike de novo high-grade osteosarcoma or malignancies arising in GCT, however, tGCT showed less severe atypia, reduced mitotic activity, and lack of infiltrative growth pattern. Tumor in patients on prolonged therapy showed decreased cellularity and abundant new bone, deposited as broad, rounded cords or long, curvilinear arrays. The latter morphology was reminiscent of low-grade central osteosarcoma, but, unlike low-grade central osteosarcoma, tGCT was negative for MDM2 and again lacked an infiltrative growth pattern. Overall, tGCT may have a wide range of morphologic appearances. Because the treated tumors bear little

  15. [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. PMID:26977631

  16. Annular elastolytic giant cell granuloma in association with Hashimoto's thyroiditis.

    PubMed

    Hassan, Rishi; Arunprasath, P; Padmavathy, L; Srivenkateswaran, K

    2016-01-01

    Annular elastolytic giant cell granuloma (AEGCG) is a rare granulomatous skin disease characterized clinically by annular plaques with elevated borders and atrophic centers found mainly on sun-exposed skin and histologically by diffuse granulomatous infiltrates composed of multinucleated giant cells, histiocytes and lymphocytes in the dermis along with phagocytosis of elastic fibers by multinucleated giant cells. We report a case of AEGCG in a 50-year-old woman and is highlighted for the classical clinical and histological findings of the disease and its rare co-existence with Hashimoto's thyroiditis. PMID:27057492

  17. Annular elastolytic giant cell granuloma in association with Hashimoto's thyroiditis

    PubMed Central

    Hassan, Rishi; Arunprasath, P.; Padmavathy, L.; Srivenkateswaran, K.

    2016-01-01

    Annular elastolytic giant cell granuloma (AEGCG) is a rare granulomatous skin disease characterized clinically by annular plaques with elevated borders and atrophic centers found mainly on sun-exposed skin and histologically by diffuse granulomatous infiltrates composed of multinucleated giant cells, histiocytes and lymphocytes in the dermis along with phagocytosis of elastic fibers by multinucleated giant cells. We report a case of AEGCG in a 50-year-old woman and is highlighted for the classical clinical and histological findings of the disease and its rare co-existence with Hashimoto's thyroiditis. PMID:27057492

  18. Giant Cell Tumor of the Peroneus Brevis Tendon Sheath

    PubMed Central

    Ch, Li; TH, Lui

    2015-01-01

    Introduction: Giant cell tumor of the tendon sheath is most commonly found in the flexor aspect of hand and wrist and is rare in the foot and ankle. Case report: A 49-year-old lady noticed a right lateral foot mass for 10 years. Magnetic resonance imaging suggested that the mass is originated from the peroneal tendons. The mass was excised and intra-operative findings showed that the tumor came from the peroneus brevis tendon sheath. Histological study confirmed the diagnosis of giant cell tumor. Conclusion: Giant cell tumor, although rare, should be one of the differential diagnoses of tendon sheath tumor of the foot and ankle. PMID:27299104

  19. Giant basal cell carcinoma of the forehead: a case report.

    PubMed

    Rudić, Milan; Kranjcec, Zoran; Lisica-Sikić, Natasa; Kovacić, Marijan

    2012-03-01

    Giant basal cell carcinoma (GBCC) is defined as a tumor 5cm or greater in diameter. They present less than 1% of all basal cell carcinomas. We present a case of an 85-year-old male patient with a giant ulcerating tumor of the left forehead (measuring 7x6 cm). Under local anesthesia tumor was surgically excised. No involvement of the underlying periostal or bone structure was noted. Pathohystological exam revealed the giant basal cell carcinoma, with free surgical margins. Giant basal cell carcinomas are rare tumors and are usually result of a long duration and patient neglect. In comparison to the ordinary basal cell carcinoma these tumors have a higher metastatic potential. Surgical resection with negative surgical margin is the best possible treatment option. PMID:22816239

  20. Annular elastolytic giant cell granuloma: A report of 10 cases

    PubMed Central

    Arora, Sandeep; Malik, Ajay; Patil, Chetan; Balki, Anil

    2015-01-01

    Annular elastolytic giant cell granuloma initially described by O’Brien in 1975 is a disorder of uncertain etiopathogenesis presenting with annular erythematous plaques predominantly on the sun-exposed areas. Hisptopathologically, it is characterized by elastin degenration, multinucleate giant cells, and elastophagocytosis. The authors came across 10 such cases, which were managed with hydroxychloroquine resulting in complete resolution in 4–6 months. PMID:26904442

  1. 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

  2. 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

  3. Genetic Alterations in Gliosarcoma and Giant Cell Glioblastoma.

    PubMed

    Oh, Ji Eun; Ohta, Takashi; Nonoguchi, Naosuke; Satomi, Kaishi; Capper, David; Pierscianek, Daniela; Sure, Ulrich; Vital, Anne; Paulus, Werner; Mittelbronn, Michel; Antonelli, Manila; Kleihues, Paul; Giangaspero, Felice; Ohgaki, Hiroko

    2016-07-01

    The majority of glioblastomas develop rapidly with a short clinical history (primary glioblastoma IDH wild-type), whereas secondary glioblastomas progress from diffuse astrocytoma or anaplastic astrocytoma. IDH mutations are the genetic hallmark of secondary glioblastomas. Gliosarcomas and giant cell glioblastomas are rare histological glioblastoma variants, which usually develop rapidly. We determined the genetic patterns of 36 gliosarcomas and 19 giant cell glioblastomas. IDH1 and IDH2 mutations were absent in all 36 gliosarcomas and in 18 of 19 giant cell glioblastomas analyzed, indicating that they are histological variants of primary glioblastoma. Furthermore, LOH 10q (88%) and TERT promoter mutations (83%) were frequent in gliosarcomas. Copy number profiling using the 450k methylome array in 5 gliosarcomas revealed CDKN2A homozygous deletion (3 cases), trisomy chromosome 7 (2 cases), and monosomy chromosome 10 (2 cases). Giant cell glioblastomas had LOH 10q in 50% and LOH 19q in 42% of cases. ATRX loss was detected immunohistochemically in 19% of giant cell glioblastomas, but absent in 17 gliosarcomas. These and previous results suggest that gliosarcomas are a variant of, and genetically similar to, primary glioblastomas, except for a lack of EGFR amplification, while giant cell glioblastoma occupies a hybrid position between primary and secondary glioblastomas. PMID:26443480

  4. New developments in giant cell arteritis.

    PubMed

    Frohman, Larry; Wong, Aaron B C; Matheos, Kaliopy; Leon-Alvarado, Luis G; Danesh-Meyer, Helen V

    2016-01-01

    Giant cell arteritis (GCA) is a medium-to-large vessel vasculitis with potentially sight- and life- threatening complications. Our understanding of the pathogenesis, diagnosis, and treatment of GCA has advanced rapidly in recent times. The validity of using the American College of Rheumatology guidelines for diagnosis of GCA in a clinical setting has been robustly challenged. Erythrocyte sedimentation rate, an important marker of inflammation, is lowered by the use of statins and nonsteroidal anti-inflammatory drugs. Conversely, it may be falsely elevated with a low hematocrit. Despite the emergence of new diagnostic modalities, temporal artery biopsy remains the gold standard. Evidence suggests that shorter biopsy lengths and biopsies done weeks to months after initiation of steroid therapy are still useful. New imaging techniques such as positron emission tomography have shown that vascular inflammation in GCA is more widespread than originally thought. GCA, Takayasu arteritis, and polymyalgia rheumatica are no longer thought to exist as distinct entities and are more likely parts of a spectrum of disease. A range of immunosuppressive drugs have been used in conjunction with corticosteroids to treat GCA. In particular, interleukin-6 inhibitors are showing promise as a therapy. PMID:26774550

  5. Giant Cell Tumors of the Axial Skeleton

    PubMed Central

    Balke, Maurice; Henrichs, Marcel P.; Gosheger, Georg; Ahrens, Helmut; Streitbuerger, Arne; Koehler, Michael; Bullmann, Viola; Hardes, Jendrik

    2012-01-01

    Background. We report on 19 cases of giant cell tumor of bone (GCT) affecting the spine or sacrum and evaluate the outcome of different treatment modalities. Methods. Nineteen patients with GCT of the spine (n = 6) or sacrum (n = 13) have been included in this study. The mean followup was 51.6 months. Ten sacral GCT were treated by intralesional procedures of which 4 also received embolization, and 3 with irradiation only. All spinal GCT were surgically treated. Results. Two (15.4%) patients with sacral and 4 (66.7%) with spinal tumors had a local recurrence, two of the letter developed pulmonary metastases. One local recurrence of the spine was successfully treated by serial arterial embolization, a procedure previously described only for sacral tumors. At last followup, 9 patients had no evidence of disease, 8 had stable disease, 1 had progressive disease, 1 died due to disease. Six patients had neurological deficits. Conclusions. GCT of the axial skeleton have a high local recurrence rate. Neurological deficits are common. En-bloc spondylectomy combined with embolization is the treatment of choice. In case of inoperability, serial arterial embolization seems to be an alternative not only for sacral but also for spinal tumors. PMID:22448122

  6. 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

  7. Giant Cell Tumor of Tendon Sheath

    PubMed Central

    Briët, Jan Paul; Becker, Stéphanie JE; Oosterhoff, Thijs CH; Ring, David

    2015-01-01

    Background: Giant cell tumor of tendon sheath (GCTTS) is often thought of as a volar finger mass. We hypothesized that GCTTS are equally common on the dorsal and volar aspects of the hand. In addition, we hypothesized that there are no factors associated with the location (volar versus dorsal) and largest measured dimension of a GCTTS. Methods: A total of 126 patients with a pathological diagnosis of a GCTTS of the hand or finger were reviewed. Basic demographic and GCTTS specific information was obtained. Bivariable analyses were used to assess predicting factors for location (volar or dorsal side) and largest measured diameter of a GCTTS. Results: Seventy-two tumors (57%) were on the volar side of the hand, 47 (37%) were dorsal, 6 (4.8%) were both dorsal and volar, and one was midaxial (0.79%). The most common site of a GCTTS was the index finger (30%). There were no factors significantly associated with the location (volar or dorsal, n=119) of the GCTTS. There were also no factors significantly associated with a larger diameter of a GCTTS. Conclusions: A GCTTS was more frequently seen on the volar aspect of the hand. No significant factors associated with the location or an increased size of a GCTTS were found in this study. PMID:25692164

  8. A cell line with multinucleated giant cell formation established from a human giant cell tumor of tendon sheath--preliminary report.

    PubMed

    Hosaka, M; Hatori, M; Smith, R A; Kokubun, S

    2001-01-01

    We first established a cell line with unique giant cell formation properties from a human giant cell tumor of tendon sheath (GCTTS) arising in the right ankle of a 7-year-old girl. The specimen for cell culture taken from the tumor was heterotransplanted into the back of a BALB/c (nu/nu) nude mouse. An in-vitro cell line was established from a tumor that grew after this heterotransplantation. Only mononuclear cells were observed in the primary culture, and these remained constant in growth. Multinucleated giant cells appeared at passage 3 and were constantly observed thereafter. The fusion of mononuclear cells into giant cells was verified by light and phase-contrast microscopy. This cell line was confirmed to be derived from a human by karyotype analysis and DNA fingerprinting. The cell-doubling time was 150 h. This cell line should be useful for studies of the mechanism of multinucleation in giant cell tumors. PMID:11845350

  9. Extracranial giant cell arteritis: A narrative review.

    PubMed

    Lensen, K D F; Voskuyl, A E; Comans, E F I; van der Laken, C J; Smulders, Y M

    2016-06-01

    A systematic literature search was performed to summarise current knowledge on extracranial giant cell arteritis (GCA), i.e. large-artery involvement in patients with or without clinically apparent temporal arteritis (cranial GCA). Extracranial GCA is increasingly recognised, both in patients with cranial GCA and with solitary extracranial GCA, due to increased awareness among physicians and development of modern imaging modalities. The literature on the pathogenesis and histopathology of extracranial GCA is scarce. It is considered to be similar to cranial GCA. Patients with solitary extracranial GCA often present with non-specific signs and symptoms, although vascular manifestations, mostly secondary to stenosis, may occur. Due to the non-specific clinical presentation and low sensitivity of temporal artery biopsies, extracranial GCA is usually diagnosed by imaging. 18F-FDG-PET, MRI, CT angiography and ultrasound are used for this purpose. At present, the optimal diagnostic strategy is undetermined. The choice for a particular modality can be guided by the clinical scenario that raises suspicion of extracranial GCA, in addition to local availability and expertise. Extracranial complications in GCA consist of aortic aneurysm or dissection (mainly the ascending aorta), aortic arch syndrome, arm claudication and posterior stroke (although this is technically a cranial complication, it often results from stenosis of the vertebrobasilar arteries). Mortality is generally not increased in patients with GCA. Treatment of patients with solitary extracranial and those with extracranial and cranial GCA has been debated in the recent literature. In general, the same strategy is applied as in patients with temporal arteritis, although criteria regarding who to treat are unclear. Surgical procedures may be indicated, in which case optimal medical treatment prior to surgery is important. PMID:27323671

  10. 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

  11. Malignant giant cell tumor of soft parts in a mare

    PubMed Central

    Marryatt, Paige A.

    2003-01-01

    Two subcutaneous masses were removed from the elbow of a mare. Histologically they were composed of islands of polygonal to plump spindlelioid cells with large nuclei, coarsely stippled chromatin, and eosinophilic cytoplasm. Findings were diagnostic for a malignant giant cell tumor of soft parts, a rare tumor with a fair prognosis. PMID:14524631

  12. Giant Cell Myocarditis: Not Always a Presentation of Cardiogenic Shock.

    PubMed

    Tompkins, Rose; Cole, William J; Rosenzweig, Barry P; Axel, Leon; Bangalore, Sripal; Lala, Anuradha

    2015-01-01

    Giant cell myocarditis is a rare and often fatal disease. The most obvious presentation often described in the literature is one of rapid hemodynamic deterioration due to cardiogenic shock necessitating urgent consideration of mechanical circulatory support and heart transplantation. We present the case of a 60-year-old man whose initial presentation was consistent with myopericarditis but who went on to develop a rapid decline in left ventricular systolic function without overt hemodynamic compromise or dramatic symptomatology. Giant cell myocarditis was confirmed via endomyocardial biopsy. Combined immunosuppression with corticosteroids and calcineurin inhibitor resulted in resolution of symptoms and sustained recovery of left ventricular function one year later. Our case highlights that giant cell myocarditis does not always present with cardiogenic shock and should be considered in the evaluation of new onset cardiomyopathy of uncertain etiology as a timely diagnosis has distinct clinical implications on management and prognosis. PMID:26257963

  13. Giant Cell Myocarditis: Not Always a Presentation of Cardiogenic Shock

    PubMed Central

    Tompkins, Rose; Cole, William J.; Rosenzweig, Barry P.; Axel, Leon; Bangalore, Sripal; Lala, Anuradha

    2015-01-01

    Giant cell myocarditis is a rare and often fatal disease. The most obvious presentation often described in the literature is one of rapid hemodynamic deterioration due to cardiogenic shock necessitating urgent consideration of mechanical circulatory support and heart transplantation. We present the case of a 60-year-old man whose initial presentation was consistent with myopericarditis but who went on to develop a rapid decline in left ventricular systolic function without overt hemodynamic compromise or dramatic symptomatology. Giant cell myocarditis was confirmed via endomyocardial biopsy. Combined immunosuppression with corticosteroids and calcineurin inhibitor resulted in resolution of symptoms and sustained recovery of left ventricular function one year later. Our case highlights that giant cell myocarditis does not always present with cardiogenic shock and should be considered in the evaluation of new onset cardiomyopathy of uncertain etiology as a timely diagnosis has distinct clinical implications on management and prognosis. PMID:26257963

  14. 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

  15. 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

  16. [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. PMID:21269738

  17. Giant cell glioblastoma in the frontal cortex of a dog.

    PubMed

    Uchida, K; Kuroki, K; Priosoeryanto, B P; Kato, K; Yano, Y; Murakami, T; Yamaguchi, R; Tateyama, S

    1995-03-01

    A dark gray mass 3 cm in diameter replacing the right frontal cortex was found in the brain of a 5-year-old male Doberman Pinscher dog at necropsy. Microscopic studies revealed that the mass consisted of a proliferation of pleomorphic tumor cells: large bizarre or plump eosinophilic cells, multinucleated giant cells, and small lymphocytic cells. These neoplastic cells at the margin of the necrotic area had a psuedopalisade arrangement and tended to proliferate around blood vessels. Immunohistochemically, the tumor cells reacted intensely with the antibody for vimentin and moderately with those for S-100 and glial fibrillary acidic protein. This canine tumor is placed in the category of glioblastoma or undifferentiated astrocytoma, which is analogous to human giant cell glioblastoma. PMID:7771064

  18. Giant evaporite belts of the Neogene central Andes

    NASA Astrophysics Data System (ADS)

    Alonso, Ricardo N.; Jordan, Teresa E.; Tabbutt, Kenneth T.; Vandervoort, Dirk S.

    1991-04-01

    Large volumes of continental evaporites accumulated within the central Andes during Neogene uplift of the Altiplano-Puna plateau and development of the Andean volcanic arc. Halite and gypsum are dominant minerals, along with local and economically important borates. Playa conditions have existed since ca. 15 Ma; halite and borate deposition has occurred for the past 7 to 8 m.y. Evaporites formed in salar environments (e.g., playa lakes) and are characterized by complex mineral assemblages, occurrence, zonation, and geochemistry. Evaporite deposition was controlled by volcanism, geothermal activity, closed drainage, and climate. These Andean deposits, and their controls, differ from evaporites in other continental and marine environments.

  19. Cell-free preparation of functional and triggerable giant proteoliposomes.

    PubMed

    Liu, Yan-Jun; Hansen, Gregory P R; Venancio-Marques, Anna; Baigl, Damien

    2013-11-25

    Heat, we leak: We express a membrane protein outside well-defined giant liposomes obtained by gravity-transferred sucrose-in-oil droplets into a cell-free, reconstituted expression system. We show that the presence of the liposome is necessary during expression for efficient protein insertion into the membrane and that temperature can trigger the resulting membrane function. PMID:24115581

  20. 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. © 2016 Wiley Periodicals, Inc. PMID:26898171

  1. Rare giant cell tumor involvement of the olecranon bone

    PubMed Central

    Yang, Chen; Gong, Yubao; Liu, Jianguo; Qi, Xin

    2014-01-01

    Giant cell tumor (GCT) of bone is a relatively common benign bone lesion and is usually located in long bones, but involvement of the olecranon is extremely rare. Here, we present a case of solitary GCT of bone in the olecranon that was confirmed by preoperative needle biopsy and postoperative histological examination. The treatment included intralesional curettage, allogeneic bone grafting, and plating. At 26 months follow-up, the patient had no local recurrence. PMID:25197303

  2. Pathogenic mechanisms in giant cell arteritis.

    PubMed

    Weyand, Cornelia M; Goronzy, Jörg J

    2002-01-01

    T lymphocytes, encountering stimulatory signals in the adventitia of medium-size arteries, emerge as the key players in inflammation-associated injury pathways. In GCA, all injury mechanisms have been related to effector macrophages. Regulated by IFN-gamma-producing T cells, macrophages commit to distinct avenues of differentiation and acquire a spectrum of potentially harmful capabilities (Figure 1). Macrophages in the adventitia focus on production of pro-inflammatory cytokines. Macrophages in the media specialize in oxidative damage with lipid peroxidation attacking smooth muscle cells and matrix components. These macrophages also supply reactive oxygen intermediates that, in combination with nitrogen intermediates, cause protein nitration of endothelial cells. Production of oxygen radicals is complemented by the production of metalloproteinases, likely essential in the breakdown of elastic membranes. With the fragmentation of the internal elastic lamina, the intimal layer becomes accessible to migratory myofibroblasts that, driven by PDGF, form a hyperplastic intimal layer and cause occlusion of the vessel lumen. Expansion of the hyperplastic intima is accompanied by intense neoangiogenesis, supported by angiogenesis factors that again derive from specialized macrophages. Similarities in injury pathways between GCA and another arterial disease, atherosclerosis, are beginning to be recognized. Specifically, activated T cells and macrophages are increasingly appreciated as key players in the process of instability and rupture of atherosclerotic plaque. A specialized subset of CD4 T cells, CD4+ CD28- T cells, are suspected to participate in tissue injury in the plaque. These T cells are equipped with cytolytic capabilities and release large amounts of IFN-gamma. Comparative studies between patients with GCA and those with acute coronary syndromes should enhance our ability to define the principles of arterial wall inflammation, the specifics of injury in that

  3. Giant cell hepatitis associated with systemic lupus erythematosus.

    PubMed Central

    Cairns, A; McMahon, R F

    1996-01-01

    Giant hepatocytes are commonly found in several neonatal and infantile liver diseases, but are rarely found in adult liver disease. A 42 year old white woman presented with a five month history of paraesthesia and numbness of both the upper and lower limbs and with vague abdominal pain. Abnormal liver function was noted on routine screening. Ultrasound scan of the abdomen showed gallstones; barium enema, ERCP and computed tomography scan were all normal. IgG antibodies to double stranded DNA were present at a titre of 40 units. Anti-cardiolipin antibodies, anti-mitochondrial antibodies and rheumatoid factor were not detected. Serology for hepatitis A, B, C, and paramyxoviruses was negative, as was the Paul Bunnell test. A clinical diagnosis of systemic lupus erythematosus (SLE) with an axonal sensory polyneuropathy was made, the latter confirmed on biopsy of the sural nerve. Giant cells were noted on liver biopsy. The patient was treated with corticosteroids; liver function had improved after two years of follow up. When extensive giant cell transformation is noted on liver biopsy, particularly when neuropathy is also a feature, the possibility of an association with SLE should be considered. Images PMID:8655694

  4. Asymmetric Cell Division in Polyploid Giant Cancer Cells and Low Eukaryotic Cells

    PubMed Central

    Zhang, Dan; Wang, Yijia

    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. PMID:25045675

  5. Unusual Presentation of Giant Cell Tumor in Skeletally Immature Patient in Diaphysis of Ulna

    PubMed Central

    Patel, Maulik T; Nayak, Maunil R

    2015-01-01

    Introduction: Giant cell tumor is a locally aggressive benign tumor. Giant cell tumor of bone is characteristically found in skeletally mature patient at the end of long bones in the epiphyseal region or epiphysio-metaphyseal region. Giant cell tumor is very rare in skeletally immature patient. But we are presenting a very rare case of giant cell tumor in skeletally immature patient in diaphyseal region which is very uncommon location for giant cell tumor. From this case we concluded that irrespective of the location and skeletal maturity, a giant cell tumor should be diagnosed based on its histology because classical clinical-radiological features are not always present. Index case strengthens this view. PMID:27299037

  6. 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.

  7. 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

  8. 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

  9. Supervoltage radiotherapy in the treatment of difficult giant cell tumors of bone

    SciTech Connect

    Bell, R.S.; Harwood, A.R.; Goodman, S.B.; Fornasier, V.L.

    1983-04-01

    Fifteen patients with giant cell tumor were treated by supervoltage radiotherapy. Each patient had been referred for therapy because adequate surgery would have been difficult or disfiguring. No patient who received appropriate therapy experienced a recurrence, and there were no cases of malignant transformation of a giant cell tumor after a mean follow-up period of 12 years. Radiotherapy is not recommended for primary treatment of giant cell tumor but may be indicated in exceptional circumstances.

  10. Mitochondrial Genomes of Giant Deers Suggest their Late Survival in Central Europe

    PubMed Central

    Immel, Alexander; Drucker, Dorothée G.; Bonazzi, Marion; Jahnke, Tina K.; Münzel, Susanne C.; Schuenemann, Verena J.; Herbig, Alexander; Kind, Claus-Joachim; Krause, Johannes

    2015-01-01

    The giant deer Megaloceros giganteus is among the most fascinating Late Pleistocene Eurasian megafauna that became extinct at the end of the last ice age. Important questions persist regarding its phylogenetic relationship to contemporary taxa and the reasons for its extinction. We analyzed two large ancient cervid bone fragments recovered from cave sites in the Swabian Jura (Baden-Württemberg, Germany) dated to 12,000 years ago. Using hybridization capture in combination with next generation sequencing, we were able to reconstruct nearly complete mitochondrial genomes from both specimens. Both mtDNAs cluster phylogenetically with fallow deer and show high similarity to previously studied partial Megaloceros giganteus DNA from Kamyshlov in western Siberia and Killavullen in Ireland. The unexpected presence of Megaloceros giganteus in Southern Germany after the Ice Age suggests a later survival in Central Europe than previously proposed. The complete mtDNAs provide strong phylogenetic support for a Dama-Megaloceros clade. Furthermore, isotope analyses support an increasing competition between giant deer, red deer, and reindeer after the Last Glacial Maximum, which might have contributed to the extinction of Megaloceros in Central Europe. PMID:26052672

  11. Mitochondrial Genomes of Giant Deers Suggest their Late Survival in Central Europe.

    PubMed

    Immel, Alexander; Drucker, Dorothée G; Bonazzi, Marion; Jahnke, Tina K; Münzel, Susanne C; Schuenemann, Verena J; Herbig, Alexander; Kind, Claus-Joachim; Krause, Johannes

    2015-01-01

    The giant deer Megaloceros giganteus is among the most fascinating Late Pleistocene Eurasian megafauna that became extinct at the end of the last ice age. Important questions persist regarding its phylogenetic relationship to contemporary taxa and the reasons for its extinction. We analyzed two large ancient cervid bone fragments recovered from cave sites in the Swabian Jura (Baden-Württemberg, Germany) dated to 12,000 years ago. Using hybridization capture in combination with next generation sequencing, we were able to reconstruct nearly complete mitochondrial genomes from both specimens. Both mtDNAs cluster phylogenetically with fallow deer and show high similarity to previously studied partial Megaloceros giganteus DNA from Kamyshlov in western Siberia and Killavullen in Ireland. The unexpected presence of Megaloceros giganteus in Southern Germany after the Ice Age suggests a later survival in Central Europe than previously proposed. The complete mtDNAs provide strong phylogenetic support for a Dama-Megaloceros clade. Furthermore, isotope analyses support an increasing competition between giant deer, red deer, and reindeer after the Last Glacial Maximum, which might have contributed to the extinction of Megaloceros in Central Europe. PMID:26052672

  12. Giant Cell Tumor of the Skull: Review of the Literature.

    PubMed

    Tamura, Ryota; Miwa, Tomoru; Shimizu, Kazuhiko; Mizutani, Katsuhiro; Tomita, Hideyuki; Yamane, Nobuo; Tominaga, Takehiro; Sasaki, Shunichi

    2016-05-01

    Background Giant cell tumors (GCTs) are rare in the skull. The present report describes a case with a primary GCT located in the temporal bone and reviews the relevant literature. We also propose a treatment strategy for GCT of the skull. Clinical Presentation A 41-year-old man presented with headache and auditory disturbance. Radiologic images showed a lytic expansive extradural lesion originating primarily from the right temporal bone and expanding into the middle cranial fossa and the infratemporal fossa. A biopsy specimen of the lesion was obtained from the external auditory meatus. Total removal was performed with temporal craniectomy, mandibular condylar process removal, tympanoplasty, and mastoidectomy. Discussion The rate of recurrence of GCTs is related to complete resection and location of the GCT rather than to the degree of invasiveness. Some of the mononuclear cells and stromal cells in GCT express receptor activator of nuclear factor κ-β ligand (RANKL). Because inhibition of RANKL and bisphosphonate therapy might eliminate giant cells, this approach might be useful for recurrent or unresectable GCTs of the skull. Conclusions Preoperative diagnosis by biopsy is important in determining the therapeutic strategy of GCTs. Complete resection is important to reduce the recurrence rate of GCTs in the skull. PMID:26091114

  13. Giant cell arteritis: a closer look at its ophthalmological manifestations.

    PubMed

    Pinto Ferreira, Nuno G; Menezes Falcão, Luiz; Alves, Antonio T; Campos, Fatima

    2015-01-01

    Giant cell arteritis with ocular involvement is an ocular emergency. Arteritic anterior ischaemic optic neuropathy (AAION) is the most common ophthalmological manifestation associated with this disease. Visual loss is usually permanent with rare cases showing visual recovery. Visual improvement, if it occurs, is generally limited, and the visual field defects are persistent and severe. The main goal of AAION treatment is the preservation of vision in the fellow eye. In patients with neurophthalmological manifestations, high-dose corticosteroids should be initiated immediately and aggressively, and maintained thereafter. We present a case of AAION and severe vision loss where significant visual recovery was seen after treatment. PMID:26416775

  14. Peripheral giant cell granuloma: a potentially aggressive lesion in children.

    PubMed

    Flaitz, C M

    2000-01-01

    A slowly enlarging gingival mass with a reddish-purple surface is observed in a school-age boy. The lesion was first noted 3 months ago during a routine oral examination but recently it has increased in size and interferes with eating. A periapical radiograph demonstrated focal loss of the alveolar crestal bone in the mandibular incisor region. The diagnosis of peripheral giant cell granuloma, a benign reactive gingival lesion, is confirmed by histopathologic examination. Early detection and excision of this hyperplastic nodule is important to minimize potential dentoalveolar complications. PMID:10846736

  15. Glucocorticoids for Management of Polymyalgia Rheumatica and Giant Cell Arteritis.

    PubMed

    Matteson, Eric L; Buttgereit, Frank; Dejaco, Christian; Dasgupta, Bhaskar

    2016-02-01

    Diagnosis of polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) is based on typical clinical, histologic, and laboratory features. Ultrasonographic imaging in PMR with assessment especially of subdeltoid bursitis can aid in diagnosis and in following response to treatment. In GCA, diagnosis and disease activity are supported with ultrasonographic, MRI, or [(18)F]fluorodeoxyglucose PET evaluation of large vessels. Glucocorticoids are the primary therapy for PMR and GCA. Methotrexate may be used in patients at high risk for glucocorticoid adverse effects and patients with frequent relapse or needing protracted therapy. Other therapeutic approaches including interleukin 6 antagonists are under evaluation. PMID:26611552

  16. 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

  17. 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

  18. 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

  19. Giant Cell Tumor Presenting as A Spindle Shaped Tumor Arising From the Costovertebral Junction at D7, d8, d9 Levels

    PubMed Central

    Upadhyaya, Mihir; Kale, Sachin; Chaudhary, Prasad; Dhar, Sanjay

    2016-01-01

    Introduction: Giant cell tumor accounts for 5 to 9 percent of all primary bony tumors. Giant cell tumors are usually found in the long bones, most often the distal femur, proximal tibia, distal radius and rarely arising from the ribs. In this paper, we describe a case of giant cell tumor presented at an unusual location of the costovertebral junction as a dumbbell shaped tumor. Case Report: Authors report a case of a 27 year old male patient with a giant cell tumor arising from the costovertebral junction at D7, D8, and D9 levels compressing the cord. Well-defined osteolysis with nonsclerotic borders were visualized on radiographs and CT scan images. Intermediate signal intensity on T1 sequences and central high signal and peripheral intermediate signal intensity on T2 sequences was visualized on MRI images. CT guided biopsy was reported as a moderately vascular lesion with spindle cell neoplasm suggestive of schwannoma. The cord was decompressed, tumor mass was surgically resected and stabilization with instrumentation was done. Histopatholgy was suggestive of giant cell tumor. Conclusion: Giant cell tumor may be included in the differential diagnosis in a well-defined lytic lesion when involving the costovertebral junction presenting as a spindle cell tumor on biopsy reports. PMID:27299118

  20. 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

  1. Clinical Management of a Peri-Implant Giant Cell Granuloma

    PubMed Central

    Pacifici, A.; Carbone, D.; Marini, R.; Sfasciotti, G. L.; Pacifici, L.

    2015-01-01

    Purpose. Implant therapy plays an important role in contemporary dentistry with high rates of long-term success. However, in recent years, the incidence of peri-implantitis and implant failures has significantly increased. The peripheral giant cell granuloma (PGCG) rarely occurs in peri-implant tissues and it is clinically comparable to the lesions associated with natural teeth. Therefore, the study of possible diseases associated with dental implants plays an important role in order to be able to diagnose and treat these conditions. Materials and Methods. This report described a 60-year-old Caucasian male who presented a reddish-purple pedunculated mass, of about 2 cm in diameter, associated with a dental implant and the adjacent natural tooth. Results. An excisional biopsy was performed and the dental implant was not removed. Histological examination provided the diagnosis of PGCG. After 19-month follow-up, there were no signs of recurrence of peri-implantitis around the implant. Conclusion. The correct diagnosis and appropriate surgical treatment of peri-implant giant cell granuloma are very important for a proper management of the lesion in order to preserve the implant prosthetic rehabilitation and prevent recurrences. PMID:26788379

  2. 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.

  3. 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

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

    PubMed

    Dietrich, Martin F; Cavuoti, Dominick; Landay, Michael; Arriaga, Yull E

    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

  5. Spin-dependent deprotonation induced giant magnetocurrent in electrochemical cells.

    PubMed

    Pan, Haiping; Shen, Yan; Duan, Jiashun; Lu, Kai; Hu, Bin

    2016-04-21

    A giant magnetocurrent (>100%) is observed in the electrochemical system based on tertiary amines at room temperature. This giant magnetocurrent is ascribed to spin-dependent deprotonation during the oxidation of tertiary amines. This presents a new approach of using spin-dependent deprotonation to generate giant magnetocurrent in electrochemical reactions. PMID:27009519

  6. The Hypermetabolic Giant: 18F-FDG avid Giant Cell Tumor identified on PET-CT

    PubMed Central

    O’Connor, Wendi; Quintana, Megan; Smith, Scott; Willis, Monte; Renner, Jordan

    2014-01-01

    An 87 year-old white female presented with a two-year history of intermittent discomfort in her left foot. PET-CT identified intense18F-fluorodeoxyglucose (FDG) uptake corresponding to the lesion. Histology of a fine needle aspiration and open biopsy were consistent with a benign giant cell tumor (GCT) of the bone. GCT of bone is an uncommon primary tumor typically presenting as a benign solitary lesion that arises in the end of the long bones. While GCT can occur throughout the axial and appendicular skeleton, it is exceedingly uncommon in the bone of the foot. While 18F-FDG has been established in detecting several malignant bone tumors, benign disease processes may also be identified. The degree of 18F-FDG activity in a benign GCT may be of an intensity that can be mistakenly interpreted as a malignant lesion. Therefore, GCT of the bone can be included in the differential diagnosis of an intensely 18F-FDG-avid neoplasm located within the tarsal bones. PMID:25426232

  7. Giant Cell Tumor (Osteoclastoma) of the Petrous Bone

    PubMed Central

    Spallone, Aldo; Flores, Gerardo Lopez; Zaldivar, Luis Ochoa; Estupinan, Barbara

    1999-01-01

    A case of a basal middle fossa giant cell tumor occurring in a 46-year-old man is described. The lesion appeared at the computed tomography (CT) scan examination as an hypodense mass with a peripheral “ring-like” enhancement, and no evident erosion of the skull base. The tumor, which infiltrated the basal temporal parenchyma, was removed via a temporal transzygomatic craniotomy, and extensive drilling of the petrous bone. Despite the occurrence, of significant postoperative complications, the patient ultimately showed a good clinical outcome, with no signs of recurrence at the 1-year follow-up CT scanning. The clinical and diageostic aspects and the management policy, of this rare lesion are discussed. Imagesp156-aFigure 1Figure 2Figure 3Figure 4 PMID:17171132

  8. 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

  9. Giant cell myocarditis in a patient with a spondyloarthropathy after a drug hypersensitivity reaction.

    PubMed

    Mitoff, Peter R; Mesana, Thierry G; Mielniczuk, Lisa M; Grenon, Jackie; Veinot, John P; Cooper, Leslie T; Davies, Ross A

    2013-09-01

    A young woman thought to have seronegative rheumatoid arthritis developed Stevens-Johnson syndrome after treatment with sulfasalazine; this resolved with prednisone. Later she was found to be HLA-B27-positive in keeping with a spondyloarthropathy. Soon afterward, she developed clinical myopericarditis and cardiogenic shock that responded initially to methylprednisolone and intravenous immunoglobulin, but recurred. An endomyocardial biopsy demonstrated active myocarditis with a mixed cell composition including rare giant cells, but not enough to classify it as giant cell myocarditis. Heart failure symptoms returned and she eventually required a heart transplant; the explanted heart showed giant cell myocarditis. PMID:23474137

  10. Ocular pneumoplethysmography can help in the diagnosis of giant-cell arteritis.

    PubMed

    Bosley, T M; Savino, P J; Sergott, R C; Eagle, R C; Sandy, R; Gee, W

    1989-03-01

    We compared the results of ocular pneumoplethysmography in nine patients who had a temporal artery biopsy (TAB) diagnostic of giant-cell arteritis with results of ocular pneumoplethysmography in nine patients with normal TAB results and 112 patients with anterior ischemic optic neuropathy or central retinal artery occlusion assumed to be nonarteritic. The mean +/- SD ocular pulse amplitude with ocular pneumoplethysmography was 3.9 +/- 1.8 mm in the group with abnormal TAB results and 10.6 +/- 4.0 mm in the group with normal TAB results. Every patient with abnormal TAB results had an average calculated ocular blood flow less than 0.60 mL/min, while only one patient with normal TAB results fell in this range. The average calculated ocular blood flow had a sensitivity of 100% and a specificity of 93.4% in the diagnosis of giant-cell arteritis, with a diagnostic accuracy of 93.9%. These results rival the diagnostic accuracy of the erythrocyte sedimentation rate and TAB results. PMID:2923561

  11. Preserved Visual Acuity in Anterior Ischemic Optic Neuropathy Secondary to Giant Cell (temporal) Arteritis

    PubMed Central

    Antonio-Santos, Aileen A.; Murad-Kejbou, Sally J.; Foroozan, Rod; Yedavally, Sunita; Kaufman, David I.; Eggenberger, Eric R.

    2016-01-01

    OBJECTIVE To evaluate the prevalence and clinical profile of patients with biopsy-proven arteritic anterior ischemic optic neuropathy presenting with preserved visual acuity of 20/40 or better and those with an initial poor visual acuity of 20/50 or worse through a retrospective chart review RESULTS Nine of 37 patients with arteritic anterior ischemic optic neuropathy presented with a preserved visual acuity of 20/40 or better in the affected eye. All patients with preserved visual acuity had initial visual field defects that spared the central field. All 37 patients immediately received high-dose corticosteroid therapy. Visual acuity worsened by > 2 lines in one of nine patients (11%) with preserved visual acuity, with a corresponding progression of visual field constriction. CONCLUSION Although preserved visual acuity of 20/40 or better has traditionally been associated with the nonarteritic form of anterior ischemic optic neuropathy, giant cell arteritis should still be strongly considered, especially if they have giant cell arteritis systemic symptoms. PMID:26958148

  12. Multinucleate Giant Cells in FNAC of Benign Breast Lesions: Its Significance

    PubMed Central

    R, Kalyani; Murthy V, Srinivasa

    2014-01-01

    Background: Multinucleate giant cells are described in breast aspirates. However, due to its rarity very few cases have been described cytologically. Hence recognition and correct interpretation of their presence is difficult, yet crucial for accurate diagnosis. Materials and Methods: The prospective study of FNAC (fine needle aspirate cytology) of breast lumps was conducted for a period of six months. Direct smears were prepared from the material aspirated. In case of fluid aspirates, centrifuge done and cell sediment was used for making smears. Smears were alcohol fixed and stained with PAP/H&E or air dried smears were stained with Leishman stain. Further smears were subjected to immunocytochemistry using vimentin and CD34 markers to know the origin of multinucleate giant cells. Results: We have reported 11 cases of breast lesions, which showed multinucleate giant cells on FNAC. Out of the 11 cases, Cytologically six cases showed granuloma debris with relative proportion of epithelioid histiocytes, lymphocytes, neutrophils and multinucleate giant cells. Two cases were diagnosed as acute suppurative granulomatous mastitis. Two cases of fibroadenoma and one case of fat necrosis showed multinucleate giant cells. Immunocytochemistry showed vimentin positivity in both stromal and histiocytic type of multinucleate giant cells and in isolated histiocytes. CD34 was focally positive in histiocytic type of giant cells. Conclusion: An effort is made to distinguish between the stromal and histiocytic type giant cells in non-neoplastic breast lesions. Further molecular studies have to be done to know the exact histogenesis and role of these multinucleate giant cells in benign lesions. PMID:25653953

  13. Recurrent giant earthquakes in South-Central Chile revealed by lacustrine sedimentary records

    NASA Astrophysics Data System (ADS)

    Moernaut, J.; de Batist, M. A.; Heirman, K.; van Daele, M.; Brümmer, R.; Pino, M.; Urrutia, R.; Wolff, C.; Brauer, A.; Roberts, S.; Kilian, R.

    2009-12-01

    Megathrust (‘giant’) earthquakes in the South-Central Chilean subduction zone (e.g. 1960 earthquake; Mw: 9.5) cause landslides, tsunamis, soil liquefaction, coastal uplift/subsidence, volcanic eruptions, all of which pose a major threat to society. A reliable seismic hazard assessment requires establishing if such mega-events occurred in the past and determining their recurrence pattern. The Lake District (39-42°S) in South-Central Chile, located in the northern half of the 1960 earthquake rupture zone, contains several large, steep-sloped glacigenic lakes with high sedimentation rates, and whose sedimentary deposits are highly susceptible to earthquake-triggered slope instability. To establish the reoccurrence interval of earthquakes during the Late Holocene, we mapped the spatial distribution of seismically-induced sedimentary ‘event’ deposits and structures in each lake using very-high resolution seismic data, and collected a series of short gravity cores and long piston cores. Multi-proxy sedimentary analyses (color, magnetic susceptibility, density, geochemistry, grain size), radiocarbon dating, varve-counting, and tephro-stratigraphy were used to identify ‘event’ deposits in each core and correlate paleoseismic horizons across basins. The sediment sequences investigated contain four main types of earthquake-induced structures: 1) multiple mass-wasting deposits on a single stratigraphic level, which are relicts of a basin-wide, subaqueous slope instability ‘event’; 2) homogenite deposits in the deepest parts of steep basins indicative of lake seiches and tsunamis; 3) fluid-escape structures (e.g. sediment volcanoes), which reflect sudden liquefaction in buried mass-wasting deposits and subsequent vertical fluidization flow; 4) in-situ deformed units (e.g., contorted bedding) in nearly-flat layers, which reflect strong horizontal ground acceleration events. Comparison with historical earthquakes suggests the spatial extent, thickness, nature of

  14. 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

  15. Giant cell tumor of the humeral head treated by denosumab: Implication to shoulder surgeons

    PubMed Central

    Leung, Ka Hei; Lam, Albert Ying Lee; Ho, Kenneth Wai Yip; Shek, Tony Wai Hung

    2015-01-01

    Giant cell tumor is a benign bone tumor that is commonly encountered. The optimal treatment of a giant cell tumor which causes extensive bony destruction is controversial. Recent studies on the receptor activator of nuclear factor κB ligand antagonist denosumab may offer a new treatment option for these patients. We presented a patient with giant cell tumor of the humeral head. He was initially treated with denosumab and subsequently with the operation. The shoulder joint was successfully salvaged. But there are potential difficulties that surgeons may face in patients treated with denosumab. PMID:26622131

  16. 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. PMID:25745294

  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. The Role of Central and Enteric Nervous Systems in the Control of the Retrograde Giant Contraction

    PubMed Central

    Lang, Ivan M

    2016-01-01

    Background/Aims The role of the enteric (ENS) and central (CNS) nervous systems in the control of the retrograde giant contraction (RGC) associated with vomiting is unknown. Methods The effects of myotomy or mesenteric nerve transection (MNT) on apomorphine-induced emesis were investigated in 18 chronically instrumented dogs Results Neither surgery affected the RGC orad of the surgical site or the velocity of the RGC over the entire small intestine. Myotomy blocked the RGC for 17 ± 5 cm aborad of the myotomy, and the velocity of the RGC from 100 to 70 cm from the pylorus slowed (18.1 ± 3.0 to 9.0 ± 0.8 cm/sec) such that the RGC orad and aborad of the myotomy occurred simultaneously. After MNT, the RGC was unchanged up to 66 ± 6 cm from the pylorus, and the sequence of the RGC across the denervated intestine was unaltered. The velocity of the RGC from 100 to 70 cm from the pylorus increased from 12.8 ± 1.6 to 196 ± 116 cm/sec. After myotomy or MNT, the percent occurrence and magnitude of the RGC across the intestine 100 to 70 cm from the pylorus decreased. Conclusions The CNS activates the RGC 10 to 20 cm aborad of its innervation of the intestine and controls the RGC sequence. On the other hand, the ENS plays a role in initiation and generation of the RGC. PMID:26645249

  19. Induction of giant cells by the synthetic food colorants viz. lemon yellow and orange red.

    PubMed

    Prajitha, V; Thoppil, John E

    2016-05-01

    Cytotoxicity and giant cell formation induced by lemon yellow and orange red synthetic food colorants were evaluated in the present study. The aqueous solutions of both the dye solutions were tested for cytotoxicity using Allium cepa assay. Frequency of giant cells were determined after treating the root tips with different concentrations of both food colorant solutions viz., 0.005, 0.01, 0.05, 0.1 % for varying time durations (1/2, 1, 2, 3 h). These colorants may cause giant cell formation primarily by interfering with the normal course of mitosis. Giant cells showing multiple aberrations viz. bridged and binucleate condition, cellular fragmentation, nuclear lesion, double and multiple nuclear lesions, double nuclear peaks and cellular breakage, elongated nucleus, nuclear budding, hyperchromasia, micronucleus, nuclear erosion, pulverized nucleus etc. were induced in root tips treated with both of the colorants. The synthetic food colorant treated cells showed inhibition of cell division and induction of giant cells. A dose dependant decrease in the mitotic index [88.20 % (c(-ve), 3h) to 81.54 % (Lx4, 3h) and 88.20 % (c(-ve), 3h) to 73.17 % (Ox4, 3h)] was observed. All mitotic phases show significant induction of giant cells when treated with both food colorants. Interphase stage shows higher percentage of giant cells, whereas in cytokinesis it was negligible. The orange red food colorant is observed to be more toxic because it recorded higher percentage of giant cell induction when compared with lemon yellow [27.93 % (Lx4, 3h) and 28.07 % (Ox4, 3h)]. PMID:25366067

  20. 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 ...

  1. Fluid-fluid levels in giant cell tumors of bone: report of two cases.

    PubMed

    Kaplan, P A; Murphey, M; Greenway, G; Resnick, D; Sartoris, D J; Harms, S

    1987-04-01

    Fluid-fluid levels have been described in association with aneurysmal bone cysts, telangiectatic osteosarcoma, and a chondroblastoma. We report two cases of giant cell tumors of bone with fluid-fluid levels identified by computed tomography and, in one case, by magnetic resonance imaging. This finding has not previously been associated with giant cell tumors. The radiographic features of the fluid-fluid levels cannot be distinguished from those reported in other osseous neoplasms. PMID:3581850

  2. Giant cell tumor of the flexor tendon of the wrist: US and MRI evaluation. Case report

    PubMed Central

    Bassetti, E.; Candreva, R.; Santucci, E.

    2011-01-01

    Giant cell tumor of the tendon sheath (GCTTS) is a benign proliferative lesion of synovial origin that may affect the joints, bursae and tendon sheaths. We report the case of a giant cell tumor of the tendon sheath arising from the carpal tunnel of the wrist in a 47-year-old woman. The patient underwent ultrasound (US) examination and subsequently magnetic resonance imaging (MRI). PMID:23396659

  3. MRI of giant cell turmor of the tendon sheath in the cervical spine

    SciTech Connect

    Bui-Mansfield, L.T.; Youngberg, R.A.; Coughlin, W.; Choolijian, D.

    1996-01-01

    The authors present a case of giant cell tumor of the tendon sheath (GCTTS) in the cervical spine, not previously described in the radiologic literature. Diagnostic imaging includes plain film radiographs, bone scintigraphy, CT, and MRI. Only one case of tenosynoviaI giant cell tumor of the cervical spine has been reported. The radiological features of this tumor are described along with a brief review of GCTTS. 6 refs., 3 figs.

  4. 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

  5. Post Asymptotic Giant Branch and Central Stars of Planetary Nebulae in the Galactic Halo

    NASA Astrophysics Data System (ADS)

    Weston, Simon

    2012-01-01

    Post asymptotic giant branch (post-AGB) stars, central stars of planetary nebulae (CSPNe) and planetary nebulae (PNe) are important phases of stellar evolution as the material they feedback is the seed of subsequent star formation in a galaxy. The majority of low and intermediate mass stars are expected to evolve through these channels, however, it is uncertain how many actually do, and at what rate. The Galactic halo, with its older population, provides a direct test of evolutionary models for low mass stars. Birthrate estimates of PNe are uncertain and worse still, are in contradiction with accepted white dwarf (WD) birthrate estimates. Much of the uncertainty stems from the lack of complete samples and poorly determined distance estimates. New surveys such as the Sloan Digital Sky Survey (SDSS), Galaxy Evolutionary Explorer (GALEX) and the INT Photometric Ha Survey (IPHAS) have discovered many new PNe and have observed the far edges of the Galaxy. Improved methods of determining distances to CSPNe are presented here, using model atmospheres, evolutionary tracks and high resolution reddening maps utilising these revolutionary surveys. Locating the CSPN is non-trivial particularly for evolved PNe, as they are extended with their central star often displaced from the centre of the nebula. Therefore, photometric criteria are required to locate the CSPN in the nebula's field. Synthetic photometry of the CSPNe is derived from spectral energy distributions (SEDs) computed from a grid of model atmospheres covering the parameter range of CSPNe. The SEDs are convolved with filter transmission curves to compute synthetic magnitudes for a given photometric system which are then calibrated with standard stars and WDs. A further project borne out of a search for luminous central stars of faint PNe, resulted in a systematic search for post-AGB stars in the Galactic halo. In this work, new candidate halo post-AGB stars are discovered from a search through the SDSS spectroscopic

  6. [Human papillomavirus, neonatal giant cell hepatitis and biliary duct atresia].

    PubMed

    Drut, R; Gómez, M A; Drut, R M; Cueto, R E; Lojo, M

    1998-01-01

    We previously recognized the presence of HPV-DNA in cases of idiopathic neonatal giant cell hepatitis (INGCH) and extrahepatic biliary duct atresia (EBDA) in archivated tissue using the PCR technique. In order to investigate a possible vertical transmission we looked for the presence of HPV-DNA in cervical swabs in the mothers along with formalin-fixed paraffin-embedded hepatic tissue from 3 infants with INGCH and 4 patients with EBDA by nested-PCR. Cervical smears showed koilocytosis consistent with HPV infection in 2 cases. Delivery was vaginal except for one that was by cesarean section. All infants were males. Amplification of HPV-DNA was demonstrated in all cases, the types being concordant in infants and mothers. Although this is a small group, the findings appear in line with previous data. The presence of the same type of HPV-DNA in the infants' livers and their mothers' cervical swabs is another argument supporting the possibility of vertical transmission of the virus. PMID:9607071

  7. Magnetic resonance imaging findings in giant cell arteritis.

    PubMed

    D'Souza, N M; Morgan, M L; Almarzouqi, S J; Lee, A G

    2016-05-01

    PurposeGiant cell arteritis (GCA) is a systemic vasculitis that affects medium-to-large-caliber arteries. Early diagnosis and treatment is essential as involvement of the ophthalmic artery or its branches may cause blindness. Radiographic findings may be variable and non-specific leading to delay in diagnosis. We conducted a review of the literature on neuroimaging findings in GCA and present a retrospective case series from tertiary-care ophthalmic referral centers of three patients with significant neuroimaging findings in biopsy-proven GCA.MethodsRetrospective case series of biopsy-proven GCA cases with neuroimaging findings at the Department of Ophthalmology, Blanton Eye Institute, Houston Methodist Hospital between 2010-2015 were included in this study. Literature search was conducted using Google Scholar and Medline search engines between the years 1970 and 2015.ResultsWe report findings of optic nerve enhancement, optic nerve sheath enhancement, and the first description in the English-language ophthalmic literature, to our knowledge, of chiasmal enhancement in biopsy-proven GCA. We describe four main categories of neuroimaging findings that may be seen in GCA from our series and from past cases in the literature.DiscussionIt is essential that clinicians be aware of the possible radiographic findings in GCA. Appropriate and prompt treatment should not be delayed based upon these findings. PMID:26915748

  8. The Effect of Diabetes Mellitus on Giant Cell Arteritis

    PubMed Central

    Abel, Anne S; Yashkin, Arseniy P; Sloan, Frank A; Lee, Michael S

    2015-01-01

    Objective To determine if type 2 diabetes mellitus (DM) is protective against giant cell arteritis (GCA) and to estimate the incidence of GCA diagnosis in the Medicare population. Methods Medicare 5% claims files from 1991-2011 were used to identify beneficiaries diagnosed with DM, but not GCA, within a three-year ascertainment period. Propensity score matching was used to define a control group of non-diabetics with comparable demographic covariates. Competing-risk regression was then used to assess the impact of DM diagnosis on GCA diagnosis. To allow for a three-year ascertainment period, the analysis sample was limited to beneficiaries over 68 years old at baseline. Results A total of 151,041 beneficiaries diagnosed with DM were matched to an equal number of controls. Mean study follow-up was 67.75 months. GCA was diagnosed among 1,116 beneficiaries with DM (0.73%) versus 465 (0.30%) controls. The risk of receiving a GCA diagnosis among patients with DM was increased by 100% (sub hazard ratio (SHR): 2.00; 95% confidence interval (CI): 1.78 2.25). The annual incidence of GCA diagnosis among U.S. Medicare beneficiaries over 68 was 93 in 100,000. Conclusion A DM diagnosis is not protective against a GCA diagnosis in the Medicare population. Our data suggests that a DM diagnosis increases the risk of GCA diagnosis within 5.7 years for Medicare beneficiaries over 68. PMID:25602744

  9. Giant magmatic water reservoir beneath Uturuncu volcano and Altiplano-Puna region (Central Andes)

    NASA Astrophysics Data System (ADS)

    Laumonier, Mickael; Gaillard, Fabrice; Muir, Duncan; Blundy, Jon; Unsworth, Martyn

    2016-04-01

    Volcanism at continental arcs is the surface manifestation of long-lived crustal magmatic processes whereby mantle-derived hydrous basalt magma differentiates to more silica-rich magmas by a combination of crystallization and crustal melting. What erupts is just a fraction of the total volume of magma produced by these processes; the unerupted, plutonic residues solidify and are inaccessible to direct study until millions of years of uplift and erosion bring them to the surface. In contrast, geophysical surveys, using electromagnetic and seismic waves, can provide real-time images of subduction zone magmatic systems. Several such studies have revealed that arc volcanoes are underlain by large partially molten regions at depths of >10 km, the largest known example being the Altiplano-Puna magma body (APMB) in central Andes. Interpreting such geophysical images in terms of amount, composition and distribution of partial melts is limited by our lack of knowledge of the physical properties of silicate melts at elevated pressures and temperatures. Here we present high-pressure, in situ experimental data showing that the electrical conductivity of andesitic melts is primarily controlled by their dissolved water contents. Linking our new measurements to petrological constraints from andesites erupted on the Altiplano, we show that the APMB is composed of 10-20% of an andesitic melt containing 8-10 wt% dissolved water. This implies that the APMB is a giant water anomaly in the global subduction system, with a total mass of dissolved magmatic water about half of the water contained within the Adriatic Sea. In addition to the controls on the physical properties of the melts, the abundance of dissolved water governs the structural levels of magma ponding, equivalent to the depth of water saturation, where degassing and crystallisation promote partial melting and weakening of the upper crust. Unexpectedly, very high concentrations of water in andesite magmas shall impede their

  10. 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

  11. 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. PMID:21146179

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

    PubMed

    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

  13. [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

  14. 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. PMID:26801673

  15. 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

  16. 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

  17. 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

  18. Initial TMX central-cell ICRH experiments

    SciTech Connect

    Molvik, A.W.; Coffield, F.E.; Falabella, S.; Griffin, D.; McVey, B.; Pickles, W.; Poulsen, P.; Simonen, T.C.; Yugo, J.

    1980-12-09

    Four topics are discussed in this report: the feasibility of applying ion cyclotron resonance heating (ICRH) in the TMX central cell, some applications of heating, the results of preliminary experiments, and plans for further ICRH experiments.

  19. 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

  20. Giant cell granuloma of the maxilla. Global management, review of literature and case report

    PubMed Central

    Manzano-Solo de Zaldívar, Damián; González-García, Raúl; Ruíz-Laza, Luís; Villanueva-Alcojol, Laura; González-Ballester, David; Hernández Vila, Cristina; Monje-Gil, Florencio

    2012-01-01

    Giant cell granuloma is a relatively rare benign entity but can be locally aggressive. Histologically characterized by intense proliferation of multinucleated giant cells and fibroblasts. Affects bone supported tissues. Definitive diagnosis is given by biopsy. Clinically manifest as a mass or nodule of reddish color and fleshy, occasionally ulcerated surface. They can range from asymptomatic to destructive lesions that grow quickly. It is a lesion to be considered in the differential diagnosis of osteolytic lesions affecting the maxilla or jaw. Its management passed from conservative treatment with intralesional infiltration of corticosteroids, calcitonin or interferon, to the surgical resection and reconstruction, for example with microvascular free flaps. Key words:Giant cell granuloma, intralesional injection, microvascular free flap, fibula. PMID:24558538

  1. Giant-cell tumor of bone: treatment options and role of denosumab

    PubMed Central

    Singh, Arun S; Chawla, Neal S; Chawla, Sant P

    2015-01-01

    Giant-cell tumor of bone is a rare, locally aggressive tumor that typically occurs in the bones of skeletally mature young adults in their second to fourth decades. Traditionally, surgery has been the mainstay of therapy for this disease, but the disease can recur even with optimal procedures. Furthermore, it may occur in locations where a surgical approach would be morbid. The maturation of the understanding of the role of the receptor activator of nuclear factor-κB ligand (RANKL) in the pathophysiology of giant-cell tumor of bone has led to the use of denosumab, a monoclonal antibody against RANKL, in this disease. In 2013, the US Food and Drug Administration approved denosumab for use in patients with recurrent/unresectable/metastatic giant-cell tumor of bone or for patients in whom surgery would be morbid. PMID:26203221

  2. 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

  3. Giant cell tumor of bone involving the temporomandibular joint and temporal bone.

    PubMed

    Akyigit, Abdulvahap; Karlidag, Turgut; Sakallioglu, Öner; Polat, Cahit; Keles, Erol

    2014-07-01

    Giant cell tumor is a primary bone tumor that usually originates from the epiphysis of the long bones and is rarely seen in the cranial region. Most frequently, the tumor develops in the sphenoid and temporal bones in the middle cranial fossa. Giant cell tumor generally shows diversity with respect to benignity, local invasiveness, and histology. Although surgical excision with negative surgical margin may lead to cure, adjuvant radiotherapy is still debated. The patient was admitted with a humming in the left ear and hearing loss. After radiologic examination, a mass with temporomandibular joint involvement as well as temporal and sphenoid bone localization was detected. The patient was diagnosed with giant cell tumor after a biopsy specimen was taken from the mass extending to the middle ear and destroying the temporomandibular joint. The current study reviewed the patient's clinical features, diagnosis, and treatment in light of the literature. PMID:25006918

  4. Everolimus Treatment for an Early Infantile Subependymal Giant Cell Astrocytoma With Tuberous Sclerosis Complex.

    PubMed

    Fukumura, Shinobu; Watanabe, Toshihide; Takayama, Rumiko; Minagawa, Kimio; Tsutsumi, Hiroyuki

    2015-08-01

    Subependymal giant cell astrocytomas are benign tumors often observed with tuberous sclerosis complex. These tumors are rarely diagnosed during fetal life or early infancy. Until recently, the only available treatment has been surgical resection. Current clinical research has demonstrated that everolimus can induce these tumors' regression. We report a 19-month-old boy with tuberous sclerosis complex. At 2 months of age, he presented with congenital subependymal giant cell astrocytoma that was complicated by refractory epilepsy and severe mental retardation. Treatment with everolimus was started when he was 10 months old. Three months after initiating everolimus, the tumor was significantly reduced in size, and the reduction was subsequently maintained. His seizures decreased and he showed cognitive and developmental improvement. No severe adverse events have been observed to date. Everolimus has promise as an effective alternative to surgery for subependymal giant cell astrocytomas during early infancy. PMID:25143481

  5. 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

  6. Giant Cell Tumor of Bone: A Neoplasm or a Reactive Condition?

    PubMed Central

    Haque, Anwar Ul; Moatasim, Ambreen

    2008-01-01

    Giant cell tumor of bone (GCTB) is a benign but locally aggressive bone tumor of young adults. It typically presents as a large lytic mass at the end of the epiphysis of long bones. Grossly it is comprised of cystic and hemorrhagic areas with little or no periosteal reaction. Microscopically areas of frank hemorrhage, numerous multinucleated giant cells and spindly stromal cells are present. Telomeric fusions, increased telomerase activity and karyotypic aberrations have been advanced as a proof of its neoplastic nature. However such findings are not universal and can be seen in rapidly proliferating normal cells as well as in several osseous lesions of developmental and/or reactive nature, and the true neoplastic nature of GCTB remains controversial. The ancillary studies have generally not reached to the point where these alone can be taken as sole diagnostic and discriminatory criteria. While giant cells and stromal cells have been extensively studied, little attention has been paid to the overwhelming hemorrhagic component. If examined carefully intact and partially degenerated red blood cells are almost invariably seen in many giant cells as well as in the stroma. While hemorrhage in many patients may be resolved without leaving any trace over time, in some it gives rise to giant cell formation, and in others it may lead to proliferation of fibroblasts and histiocytes. At times one sees xanthomatous cells due to intracytoplasmic cholesterol deposits and sharp cholesterol clefts. Individual genetic makeup, local tissue factors as well as the amount of hemorrhage may play a key role in the final effects and outcome. Malignancy usually does not occur in GCTB and when discover, it usually represents primary bone sarcomas missed at original diagnosis. Embolization therapy to curtail hemorrhage and insertion of cement substance to support matrix are helpful in reducing recurrences. Aneurysmal bone cyst (ABC) shares many features with GCTB. There had been unique

  7. Epidermal multinucleated giant cells are not always a histopathologic clue to a herpes virus infection: multinucleated epithelial giant cells in the epidermis of lesional skin biopsies from patients with acantholytic dermatoses can histologically mimic a herpes virus infection

    PubMed Central

    Cohen, Philip R.; Paravar, Taraneh; Lee, Robert A.

    2014-01-01

    Background: Multinucleated giant cells in the epidermis can either be epithelial or histiocytic. Epithelial multinucleated giant cells are most often associated with herpes virus infections. Purpose: To review the histologic differential diagnosis of conditions with epithelial and histiocytic multinucleated giant cells—since multinucleated giant cells in the epidermis are not always pathognomonic of a cutaneous herpes virus infection—and to summarize dermatoses in which herpes virus infection has been observed to coexist. Methods: Two individuals with acantholytic dermatoses whose initial lesional skin biopsies showed multinucleated epithelial giant cells suggestive of a herpes virus infection are reported. Using the PubMed database, an extensive literature search was performed on multinucleated giant cell (and epidermis, epithelial, and histiocytic) and herpes virus infection. Relevant papers were reviewed to discover the skin conditions with either multinucleated giant cells in the epidermis or coincident cutaneous herpes virus infection. Results: Initial skin biopsies from patients with either pemphigus vulgaris or transient acantholytic dermatosis mimicked herpes virus infection; however, laboratory studies and repeat biopsies established the correct diagnosis of their acantholytic dermatosis. Hence, epidermal multinucleated giant cells are not always a histopathologic clue to a herpes virus infection. Indeed, epithelial multinucleated giant cells in the epidermis can be observed not only in the presence of infection (herpes virus), but also acantholytic dermatoses and tumors (trichoepithelioma and pleomorphic basal cell carcinoma). Histiocytic multinucleated giant cells in the epidermis can be observed in patients with either giant cell lichenoid dermatitis or lichen nitidus of the palms. Conclusions: Epithelial and histiocytic multinucleated giant cell can occur in the epidermis. Keratinocyte-derived multinucleated giant cells are most commonly associated

  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. PMID:26861247

  9. 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

  10. 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

  11. OCULOECTODERMAL SYNDROME: A NEW CASE WITH GIANT CELL GRANULOMAS AND NON-OSSIFYING FIBROMAS.

    PubMed

    Mermer, S; Kayhan, G; Karacelebi, E; Percin, F E

    2016-01-01

    Oculoectodermal syndrome (OES) is a very rare disorder with an unknown etiology and characterized by aplasia cutis congenita, epibulbar dermoid and hyperpigmentation areas on the skin. To the best of our knowledge, two cases of OES have been reported to date with recurrent giant cell granuloma in the jaw and one of them also had a non-ossified fibroma in the long bones. Herein, we report the second case with aplasia cutis congenita, epibulbar dermoid, hyperpigmentation along Blaschko lines and also giant cell granuloma in the jaw and non-ossified fibromas in the bones. PMID:27192894

  12. Giant Cell Fibroma in a Paediatric Patient: A Rare Case Report

    PubMed Central

    Reddy, Veera Kishore Kumar; Kumar, Naveen; Battepati, Prashant; Samyuktha, Lalitha; Nanga, Swapna Priya

    2015-01-01

    Giant cell fibroma is a form of fibrous tumour affecting the oral mucosa. Its occurrence is relatively rare in paediatric patients. Clinically it is presented as a painless, sessile, or pedunculated growth which is usually confused with other fibrous lesions like irritation fibromas. Here we are presenting a case where a seven-year-old male patient reported with a painless nodular growth in relation to lingual surface of 41 and 42. Considering the size and location of the lesion, excisional biopsy was performed and sent for histopathological analysis which confirmed the lesion as giant cell fibroma. PMID:26693359

  13. Giant cell tumour of peroneus brevis tendon sheath – a case report and review of literature

    PubMed Central

    Goni, Vijay; Gopinathan, Nirmal Raj; Radotra, B D; Viswanathan, Vibhu Krishnan; Logithasan, Rajesh Kumar; S, Balaji

    2012-01-01

    Giant cell tumour of tendon sheath is a benign soft tissue lesion most commonly found in the flexor aspect of hand and wrist. Being rare in foot and ankle, the unusual presentation of this lesion may sometimes mimic other lesions like lipoma, synovial sarcoma, malignant fibrous histiocytoma, synovial cyst and ganglion. Hence it is important to include this lesion in differential diagnoses especially if the lesion is found to be anchored to any of the surrounding tendons. This article describes the unusual occurrence of giant cell tumour of the tendon sheath of peroneus brevis which is rarely described in literature. PMID:22802558

  14. 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

  15. 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

  16. Giant cell tumor of the pancreas arising in the ovarian-like stroma of a mucinous cystadenocarcinoma.

    PubMed

    Bergman, S; Medeiros, L J; Radr, T; Mangham, D C; Lewandrowski, K B

    1995-08-01

    We describe a malignant mucinous cystic neoplasm of the pancreas with ovarian-like stroma within which an osteoclast-like giant cell rich tumor arose. This rare tumor had a unique immunohistochemical profile with the giant cells staining for vimentin, leukocyte common antigen, and the monocyte/macrophage marker CD68, whereas the mucinous epithelium stained for epithelial membrane antigen and cytokeratin. The immunohistochemical findings are consistent with two lines of differentiation, one epithelial and the other suggesting mesenchymal differentiation of the giant cell tumor with an immunophenotype similar to giant cell tumor of bone. The coexistence of these two rare tumors suggests that they are histogenetically related. The findings of a giant cell tumor arising in the ovarian stroma indicates that the stroma of mucinous tumors is not always an innocuous component of the tumor. PMID:7594774

  17. [Giant cell tumor of the C2 colonized by an aneurismal bone cyst. Report of case].

    PubMed

    Cebula, H; Boujan, F; Beaujeux, R; Boyer, P; Froelich, S

    2012-12-01

    Giant cell tumor is colonized by aneurismal bone cyst in only 15% of cases and cervical localisation accounts for less than 1% of giant cell tumors. We are reporting a rare case of a C2 hypervascularized giant cell tumor colonized by an aneurismal bone cyst treated with an effective preoperative Onyx embolization followed by a full tumor resection. The patient experienced a moderate cervical spine injury 2 months prior admission followed by a progressive stiff neck and cervicalgia. CT and MRI identified a lytic lesion of the body and lateral masses of the C2 with encasement of both vertebral arteries. The angiography showed a hypervascularization of the lesion from the vertebral and external carotid arteries as well as a thrombosis of the V3 segment of the right vertebral artery at the C1 level. A posterior occipito-C3/C4 fixation and a tumor biopsy were performed. Histopathological examination concluded to a giant cell tumor colonized by an aneurismal bone cyst. Three weeks later, the patient developed a right upper extremity deficit. The MRI showed an increased C1-C2 stenosis and an increase of the hypervascularization. Three sessions of embolization by the onyx were performed. During surgery a near total tumor devascularisation was observed and a complete resection of the tumor was achieved through an anterolateral approach. Reconstruction consisted of a cementoplasty of the C2 body and odontoïd process with an anterior C3-prosthesis plate. The postoperative course was uneventful. PMID:22695034

  18. 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

  19. 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

  20. Involvement and prognosis value of CD8(+) T cells in giant cell arteritis.

    PubMed

    Samson, Maxime; Ly, Kim Heang; Tournier, Benjamin; Janikashvili, Nona; Trad, Malika; Ciudad, Marion; Gautheron, Alexandrine; Devilliers, Hervé; Quipourt, Valérie; Maurier, François; Meaux-Ruault, Nadine; Magy-Bertrand, Nadine; Manckoundia, Patrick; Ornetti, Paul; Maillefert, Jean-Francis; Besancenot, Jean-François; Ferrand, Christophe; Mesturoux, Laura; Labrousse, François; Fauchais, Anne-Laure; Saas, Philippe; Martin, Laurent; Audia, Sylvain; Bonnotte, Bernard

    2016-08-01

    CD8(+) T cells participate in the pathogenesis of some vasculitides. However, little is known about their role in Giant Cell Arteritis (GCA). This study was conducted to investigate CD8(+) T cell involvement in the pathogenesis of GCA. Analyses were performed at diagnosis and after 3 months of glucocorticoid treatment in 34 GCA patients and 26 age-matched healthy volunteers. Percentages of CD8(+) T-cell subsets, spectratype analysis of the TCR Vβ families of CD8(+) T cells, levels of cytokines and chemokines and immunohistochemistry of temporal artery biopsies (TAB) were assessed. Among total CD8(+) T cells, percentages of circulating cytotoxic CD8 T lymphocytes (CTL, CD3(+)CD8(+)perforin(+)granzymeB(+)), Tc17 (CD3(+)CD8(+)IL-17(+)), CD63(+)CD8(+) T cells and levels of soluble granzymes A and B were higher in patients than in controls, whereas the percentage of Tc1 cells (CD3(+)CD8(+)IFN-γ(+)) was similar. Moreover, CD8(+) T cells displayed a restricted TCR repertoire in GCA patients. Percentages of circulating CTL, Tc17 and soluble levels of granzymes A and B decreased after treatment. CXCR3 expression on CD8(+) T cells and its serum ligands (CXCL9, -10, -11) were higher in patients. Analyses of TAB revealed high expression of CXCL9 and -10 associated with infiltration by CXCR3(+)CD8(+) T cells expressing granzyme B and TiA1. The intensity of the CD8 T-cell infiltrate in TAB was predictive of the severity of the disease. This study demonstrates the implication and the prognostic value of CD8(+) T-cells in GCA and suggests that CD8(+) T-cells are recruited within the vascular wall through an interaction between CXCR3 and its ligands. PMID:27236507

  1. 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

  2. Drought frequency in central California since 101 B.C. recordered in giant sequoia tree rings

    SciTech Connect

    Hughes, M.K.; Brown, P.M.

    1992-01-01

    Well replicated tree-ring width index chronologies have been developed for giant sequoia at three sites in the Sierra Nevada, California. Extreme low-growth events in these chronologies correspond with regional drought events in the twentieth century in the San Joaquin drainage, in which the giant sequoia sites are located. This relationship is based upon comparison of tree-ring indices with August Palmer Drought Severity Indices for California Climate Division 5. Ring-width indices in the lowest decile from each site were compared. The frequency of low-growth events which occurred at all three sites in the same year is reconstructed from 101 B.C. to A.D. 1988. The inferred frequency of severe drought events changes through time, sometimes suddenly. The period from roughly 1850 to 1950 had one of the lowest frequencies of drought of any one hundred year period in the 2089 year record. The twentieth century so far has had a below-average frequency of extreme droughts. 26 refs., 6 figs., 1 tab.

  3. Drought frequency in central California since 101 B.C. recorded in giant sequoia tree rings

    NASA Astrophysics Data System (ADS)

    Hughes, Malcolm K.; Brown, Peter M.

    1992-01-01

    Well replicated tree-ring width index chronologies have been developed for giant sequoia at three sites in the Sierra Nevada, California. Extreme low-growth events in these chronologies correspond with regional drought events in the twentieth century in the San Joaquin drainage, in which the giant sequoia sites are located. This relationship is based upon comparison of tree-ring indices with August Palmer Drought Severity Indices for California Climate Division 5. Ring-width indices in the lowest decile from each site were compared. The frequency of low-growth events which occurred at all three sites in the same year is reconstructed from 101 B.C. to A.D. 1988. The inferred frequency of severe drought events changes through time, sometimes suddenly. The period from roughly 1850 to 1950 had one of the lowest frequencies of drought of any one hundred year period in the 2089 year record. The twentieth century so far has had a below-average frequency of extreme droughts.

  4. [Clinico-pathological study on giant cell fibroma of oral mucosa].

    PubMed

    Wang, Z; Levy, B

    1995-11-01

    The biopsy specimens of the Department of Oral Pathology, Dental School, UMBC, between 1985-1988 were reviewed in 1990 and. 124 cases of giant cell fibroma (GCF) of oral mucosa were found. GCF may develop at any age, but the highest incidence is middle adult life. GCF is slightly common in female than in male (1: 0.85). GCF occurs frequently in gingiva, tongue and cheek and is mistaken commonly for irritation fibroma, neurofibroma, papilloma and pyogenic granuloma, because there are no specific clinic features of it. The fusiform cells, star cells and multinucleated giant cells in the lesion are common histologic features of GCF. Local removal is usually successful. PMID:8762534

  5. A serially transplantable human giant cell glioblastoma that maintains a near-haploid stem line.

    PubMed

    Bigner, S H; Mark, J; Schold, S C; Eng, L F; Bigner, D D

    1985-10-01

    We have karyotyped a human giant cell glioblastoma removed from an 11-year-old girl and have established from it a subcutaneously transplantable line in athymic nude mice. The original tumor contained near-haploid cells with 25 or 26 chromosomes, including two copies of #1, (7 or 7p+) and #18. There were also hyperdiploid (49-52) cells that were tetraploid for these same three chromosome types; doubled versions of the hyperdiploid population were also seen. The stemline of the mouse-grown tumor was 26,X, +1, +7p+, +18 in the first passage and has remained consistently near-haploid through ten serial in vivo passages. Growth stabilization has occurred with an average latency of less than 3 months. This transplantable line is available for evaluating chemotherapeutic responsiveness of human giant cell glioblastoma and for studying near-haploidy in solid human tumors. PMID:3840409

  6. 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

  7. 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

  8. Laser Capture Microdissection and Real-Time PCR for Measuring mRNA in Giant Cells Induced by Meloidogyne javanica.

    PubMed

    He, Bin; Magill, C; Starr, J L

    2005-09-01

    The techniques of laser capture microdissection and quantitative RT-PCR were investigated as methods for measuring mRNA in giant cells induced by Meloidogyne javanica. Laser capture microdissection allowed precise sampling of giant cells at 1 to 3 weeks after inoculation. The expression of three genes (a water channel protein gene Rb7, a plasma membrane H(+)-ATPase (LHA4), and a hexose kinase (HXK1) was measured based on mRNA extracted from tissue samples and quantitated using reversetranscription real-time PCR. These genes were chosen arbitrarily to represent different aspects of primary metabolism. The amount of HXK1 mRNA in giant cells was not different from that in root meristem or cortical cells when compared on the basis of number of molecules per unit tissue volume, and was similar at all sample times. Amount of mRNA for LHA4 and Rb7 was much greater in giant cells than in cortical cells, but only Rb7 was also greater in giant cells than in root meristem cells. Numbers of mRNA molecules of LHA4 increased linearly in giant cells from 1 to 3 weeks after inoculation, whereas the amount of Rb7 mRNA was similar at 1 and 2 weeks after inoculation but increased at 3 weeks after inoculation. The amount of mRNA for these two genes was similar at all sample times in cortical and root-tip cells. Apparent up regulation of some genes in giant cells may be due primarily to the increased number of copies of the gene in giant cells, whereas for other genes up regulation may also involve increased transcription of the increased number of copies of the gene. PMID:19262878

  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. Transfer of newly synthesized proteins from Schwann cells to the squid giant axon.

    PubMed

    Lasek, R J; Gainer, H; Przybylski, R J

    1974-04-01

    The squid giant axon is presented as a model for the study of macromolecular interaction between cells in the nervous system. When the isolated giant axon was incubated in sea water containing [(3)H]leucine for 0.5-5 hr, newly synthesized proteins appeared in the sheath and axoplasm as demonstrated by: (i) radioautography, (ii) separation of the sheath and axoplasm by extrusion, and (iii) perfusion of electrically excitable axons. The absence of ribosomal RNA in the axoplasm [Lasek, R. J. et al. (1973) Nature 244, 162-165] coupled with other evidence indicates that the labeled proteins that are found in the axoplasm originate in the Schwann cells surrounding the axon. Approximately 50% of the newly synthesized Schwann cell proteins are transferred to the giant axon. These transferred proteins are soluble for the most part and range in molecular size from 12,000 to greater than 200,000 daltons. It is suggested that proteins transferred from the Schwann cell to the axon have a regulatory role in neuronal function. PMID:4524631

  13. Giant cell interstitial pneumonia: an unusual finding in a case of preoperative death.

    PubMed

    Sisodia, Shantilal M; Bendale, Kiran; Khan, Wasif Ali Zafarali; Sanklecha, Vandana

    2013-06-01

    Giant cell interstitial pneumonia (GIP) is an exceedingly rare, debatable, perplexing, occupational lung disease, which most commonly affects individuals exposed to hard metal dust. We report a case of GIP in a 60-year-old man, scheduled for coronary artery bypass graft surgery and died during induction of general anesthesia despite all efforts to resuscitate him. Patient's relatives lodged complaint with the police alleging the negligence by the attending physicians. Despite inaccessible data pertaining to the occupation, clinical history, and radiographic findings, the diagnosis was GIP due to the presence of intra-alveolar, bizarre, "cannibalistic" multinucleated giant cells-the histologic sine qua non of GIP. To the best of our knowledge, this is the first case report of GIP in the world literature that was diagnosed on histopathologic examination of lung tissue obtained at medicolegal autopsy. PMID:23629398

  14. 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

  15. Idiopathic neonatal giant cell hepatitis presenting with acute hepatic failure on postnatal day one.

    PubMed

    Correa, Kimberley K; Nanjundiah, Prathiba; Wirtschafter, David D; Alshak, Najeeb S

    2002-01-01

    We report a term male infant presenting on postnatal day 1 with fulminant hepatic failure. Described congenital infection, metabolic disorders, and cardiovascular etiologies of acute neonatal liver failure were assessed and eliminated. A liver biopsy on postnatal day 10 showed neonatal giant cell hepatitis (NGCH) with an unusual degree of fibrosis for this early postnatal age. NGCH is a clinical diagnosis of cholestatic disorders of unknown etiology in the newborn, and, to our knowledge, has not been previously associated with immediate neonatal hepatic failure. The giant cell transformation is a common response to a variety of insults and only rarely occurs beyond the neonatal period. Most cases present with cholestatic jaundice and varying degrees of coagulopathy, and, many, as in this case, show progressive resolution. PMID:11948391

  16. A Review and Report of Peripheral Giant Cell Granuloma in a 4-Year-Old Child

    PubMed Central

    Nekouei, Afsaneh; Eshghi, Alireza; Jafarnejadi, Parisa

    2016-01-01

    Peripheral giant cell granuloma is a common benign and reactive gingival epulis in oral cavity. It is often difficult to make a clinical diagnosis; thereby definitive diagnosis depends on histopathologic features. We report a case of a 4-year-old Caucasian boy presenting with a five-month history a 20 × 15 × 12 mm pedunculated, lobular soft tissue mass of the left anterior maxilla gingiva which was misdiagnosed and maltreated before his referral. An excisional biopsy of the lesion followed by histopathologic examination of the biopsy specimen revealed distinctive features of peripheral giant cell granuloma. Early detection and excision of this hyperplastic nodule especially in children are important to minimize potential dentoalveolar complications. PMID:27403351

  17. Anti-oxidative therapy with oral dapsone improved HCV antibody positive annular elastolytic giant cell granuloma.

    PubMed

    Igawa, K; Maruyama, R; Katayama, I; Nishioka, K

    1997-05-01

    A 72-year-old fisherman who was positive for the HCV antibody developed an annular, erythematous, infiltrated lesions on sun-exposed areas. The lesions were diagnosed as annular elastolytic giant cell granuloma both clinically and histologically. Topical corticosteroid and cryotherapy with liquid nitrogen for several months failed to improve the lesions. We then started dapsone, a known anti-oxidant, at 50 mg/day. A month later, the margins of the erythematous lesions faded, and the infiltration gradually decreased. No recurrence has been observed for one year after the start of the therapy. Anti-oxidative therapy appears to be effective for annular elastolytic giant cell granuloma and could be an alternate therapy for refractory granulomatous disease. PMID:9198323

  18. [A case report of phylloides tumor of the prostate: review of the literature and analysis of bizarre giant cell origin].

    PubMed

    Mishina, T; Shimada, N; Toki, J; Ikehara, S

    1990-10-01

    A case of phylloides tumor of the prostate in a 58-year-old male is presented. The tumor was composed of columnar cystic folds and pleomorphic stromal elements including bizarre giant cells. Electron microscopic examination, which was performed using specimens embedded in paraffin blocks, revealed that the bizarre giant cells originated from the smooth muscle. The postoperative course was uneventful, with no evidence of local recurrence or metastasis for more than 2 years after operation. PMID:2176059

  19. Selective infarction of the anterior genu fornices associated with giant cell arteritis.

    PubMed

    Murr, Najib; Thaisetthawatkul, Pariwat; Helvey, Jason; Fayad, Pierre

    2012-05-01

    We report a middle-aged woman presenting with acute confusion and anterograde amnesia. Magnetic resonance imaging revealed an acute infarction of the anterior genu fornices. Evaluation of an elevated erythrocyte sedimentation rate led to the diagnosis of giant cell arteritis (GCA). Cerebral infarction is a known complication of GCA; this is the first report of such an association with selective fornix infarction. PMID:20884244

  20. 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

  1. Primary giant cell malignant fibrous histiocytoma-associated with renal calculus

    PubMed Central

    Altunkol, Adem; Savas, Murat; Ciftci, Halil; Gulum, Mehmet; Yagmur, Ismail; Bitiren, Muharrem

    2014-01-01

    Malignant fibrous histiocytomas (MFH) are the most commonly seen soft tissue sarcomas in adults. It is rarely seen in some visceral organs. Kidneys are the parenchymal organs in which MFHs are most frequently seen. More than 50 cases of primary renal MFH have been reported. Among these cases, only 1 was reported as primary giant cell subtype in association with urolithiasis. This case report is the second such case with the these characteristics. PMID:24678364

  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. Imaging Manifestations of a Subependymal Giant Cell Astrocytoma in Tuberous Sclerosis

    PubMed Central

    Stein, Joseph R.; Reidman, Daniel A.

    2016-01-01

    Tuberous sclerosis is a rare genetic disorder resulting in benign tumor growth in various organs including the brain, heart, skin, eyes, kidney, and lung as well as systemic manifestations including seizures, cognitive impairment, and dermatologic abnormalities. This report shows the radiological findings and differentiation between a subependymal nodule and subependymal giant cell astrocytoma in a patient with tuberous sclerosis presenting with new onset seizures. PMID:26942030

  4. 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

  5. Arthroscopic Resection of a Tenosynovial Giant Cell Tumor in the Wrist

    PubMed Central

    Lee, Young-Keun; Han, Youngshin; Lee, Malrey

    2015-01-01

    Abstract The treatment for giant cell tumors of the tendon sheath is surgical therapy, but surgical recurrence rates were reported to be as high as 50% in some cases. Therefore, complete radical excision of the lesion is the treatment of choice. If the tumor originates from the joint, it is important to perform capsulotomy. Here, the authors report the first case of successful treatment of a localized intra-articular giant cell tumor in the wrist by arthroscopic resection. A 28-year-old right-handed woman visited the clinic because of left wrist ulnar-side pain, which had been aggravated during the previous 15 days. Vague ulnar-side wrist pain had begun 2 years ago. When the authors examined the patient, the wrist showed mild swelling on the volo-ulnar aspect and the distal radioulnar joint, as well as volar joint line tenderness. She showed a positive result on the ulnocarpal stress test and displayed limited range of motion. Magnetic resonance imaging revealed an intra-articular mass with synovitis in the ulnocarpal joint. Wrist arthroscopy was performed using standard portals under regional anesthesia. The arthroscopic findings revealed a large, well-encapsulated, yellow lobulated soft-tissue mass that was attached to the volar side of the ulnocarpal ligament and connected to the extra-articular side. The mass was completely excised piece by piece with a grasping forceps. Histopathologic examination revealed that the lesion was an intra-articular localized form of a tenosynovial giant cell tumor. At 24-month follow-up, the patient was completely asymptomatic and had full range of motion in her left wrist, and no recurrence was found in magnetic resonance imaging follow-up evaluations. The authors suggest that the arthroscopic excision of intra-articular giant cell tumors, as in this case, may be an alternative method to open excisions, with many advantages. PMID:26496348

  6. 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

  7. 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

  8. MRI sequence and characteristic features in 'giant cell tumor' of clivus.

    PubMed

    Mahale, Ajit; K V N, Dhananjaya; Pai, Muralidhar; Poornima, Vinaya; Sahu, Kausalya Kumari

    2013-06-01

    Giant cell tumours of the clivus are rare. These tumours present in the second and third decades of life and they are slightly more frequent in women than in men. We are presenting a case of a 20 years young patient who came with the complaints of headache, retro-orbital pain and recurrent transient bleeding from the nose since two and half months. MRI of the brain with contrast was done and its features were suggestive of a Giant cell tumour of the clivus. A transnasal endoscopic biopsy was done under general anaesthesia and the histopathology report suggested that the features were of a giant cell tumour. Excision of the mass was done by Transnasal endoscopy. Post operatively, the patient did not recover from the lateral rectus palsy which was there on the right side. The patient was discharged with an advice of a follow up and radiotherapy. Radiation therapy and chemotherapy may be effective as adjuvant treatments. Even though a recurrence usually occurs within 4 years of the initial treatment, these patients will need to be carefully followed for the remainder of their lives. PMID:23905141

  9. 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

  10. Giant Cell Tumor of the Tendon Sheath: Experience With 65 Cases

    PubMed Central

    Adams, Erin L.; Yoder, Eric M.; Kasdan, Morton L.

    2012-01-01

    Objective: No consensus exists on the etiology, prognostic factors, or recurrence rate of giant cell tumors of the tendon sheath. This article presents a series of 65 cases supplemented by a literature review that examines the epidemiology, presentation, gross and microscopic characteristics, and recurrence rate of giant cell tumor of the tendon sheath. Methods: The authors completed a retrospective review of one surgeon's practice from 1976 to 2001, evaluating 65 cases of giant cell tumor of the tendon sheath. The authors conducted a literature search and compared the case series with historical data. Results: The tumor most commonly presented as a firm, nontender mass in the dominant hand. Our cases showed a slight female predominance of 54%, compared with the literature average of 64%. A pseudocapsule was present in 51% of cases. Overall recurrence rate was 10%. No association was noted between recurrence and pseudocapsule presence, rheumatoid arthritis, or osteoarthritis. Satellite lesions at the first excision were noted in 80% of recurrent cases; however, satellite lesions were not a risk factor for recurrence per se. Conclusions: Our study shows similar findings to the literature, with the notable addition of satellite lesions in recurrent tumors. Marginal excision is the treatment of choice, but may be complicated when the tumor is attached to vital structures. Therefore, an appropriate balance between resection of tumor and maintenance of function must be achieved due to the possibility of recurrence. PMID:23185646

  11. A Fraction of CD133+ CNE2 Cells Is Made of Giant Cancer Cells with Morphological Evidence of Asymmetric Mitosis

    PubMed Central

    Jiang, Qingping; Zhang, Qianbing; Wang, Shuang; Xie, Siming; Fang, Weiyi; Liu, Zhen; Liu, Jinsong; Yao, Kaitai

    2015-01-01

    CD133 has been suggested as a broad-spectrum marker for cancer stem cells(CSCs). The present study investigated the expression of CD133 in biopsy tissues of nasopharyngeal carcinoma (NPC), NPC cell lines and the immortalized cell line NP69 by immunohistochemistry, flow cytometry and qRT-PCR. CD133+ cancer cells were isolated using magnetic-activated cell sorting technology. The study demonstrated that CD133+ cells are rare in NPC tissues and cell lines and that their self-renewal and proliferation abilities are stronger than those of CD133- cells and suggested that CD133+ NPC cells have characteristics of cancer stem cells. We further observed CD133+ cancer cells using a light microscope and scanning electron microscope. Generally, CD133+ cells are small, regular and round with small microvilli. On the other hand, CD133- cells are more polymorphic and larger with long micromicrovilli. Additionally, in some fields, several giant cancer cells (GCCs) in the CD133+ cell group were identified under the light microscope. Most of them were polynuclear cells. Under the scanning electron microscope, we found indefinite regular small bodies on the surface of or surrounding the giant cancer cells, some of which appeared to be creeping out the parental cells. This phenomenon was not observed in the CD133- cell groups. Through comparison with descriptions of apoptotic bodies in the literature and from the results of the acridine orange test, we propose that some of the small bodies are daughter cells of the GCCs. This phenomenon is a mode of division of cancer cells called neosis, or budding, which is a form of reproduction for simple organisms. Budding is satisfied with the rapid speed of tumor development. GCCs could be isolated by CD133 beads because the daughter cells have stem-cell characteristics and express stem-cell markers. PMID:26535065

  12. Thymic B Cells and Central T Cell Tolerance

    PubMed Central

    Yamano, Tomoyoshi; Steinert, Madlen; Klein, Ludger

    2015-01-01

    Central T cell tolerance is believed to be mainly induced by thymic dendritic cells and medullary thymic epithelial cells. The thymus also harbors substantial numbers of B cells. These may arise though intrathymic B lymphopoiesis or immigration from the bloodstream. Importantly, and in contrast to resting “mainstream” B cells in the periphery, thymic B cells display elevated levels of MHC class II and constitutively express CD80. Arguably, their most unexpected feature is the expression of autoimmune regulator. These unique features of thymic B cells result from a licensing process that involves cross-talk with CD4 single-positive T cells and CD40 signaling. Together, these recent findings suggest that B cells play a more prominent role as thymic APCs than previously appreciated. PMID:26257742

  13. Giant cell tumour of the sacrum: a suggested algorithm for treatment

    PubMed Central

    Grimer, R. J.; Carter, S. R.; Stirling, A. J.; Spilsbury, J.; Spooner, D.

    2010-01-01

    To investigate the outcome of our management of patients with giant cell tumour of the sacrum and draw lessons from this. A retrospective review of medical records and scans for all patients treated at our unit over the past 20 years with a giant cell tumour of the sacrum. Of the 517 patients treated at our unit for giant cell tumour over the past 20 years, only 9 (1.7%) had a giant cell tumour in the sacrum. Six were female, three male with a mean age of 34 (range 15–52). All, but two tumours involved the entire sacrum and there was only one purely distal to S3. The mean size was 10 cm and the most common symptom was back or buttock pain. Five had abnormal neurology at diagnosis, but only one presented with cauda equina syndrome. The first four patients were treated by curettage alone, but two patients had intraoperative cardiac arrests and although both survived all subsequent curettages were preceded by embolisation of the feeding vessels. Of the seven patients who had curettage, three developed local recurrence, but all were controlled with a combination of further embolisation, surgery or radiotherapy. One patient elected for treatment with radiotherapy and another had excision of the tumour distal to S3. All the patients are alive and only two patients have worse neurology than at presentation, one being impotent and one with stress incontinence. Three patients required spinopelvic fusion for sacral collapse. All patients are mobile and active at a follow-up between 2 and 21 years. Giant cell tumour of the sacrum can be controlled with conservative surgery rather than subtotal sacrectomy. The excision of small distal tumours is the preferred option, but for larger and more extensive tumours conservative management may well avoid morbidity whilst still controlling the tumour. Embolisation and curettage are the preferred first option with radiotherapy as a possible adjunct. Spinopelvic fusion may be needed when the sacrum collapses. PMID:20076978

  14. Giant Cell Tumor of Bone With Pseudosarcomatous Changes Leading to Premature Denosumab Therapy Interruption: A Case Report With Review of the Literature.

    PubMed

    Sanchez-Pareja, Andrea; Larousserie, Frédérique; Boudabbous, Sana; Beaulieu, Jean-Yves; Mach, Nicolas; Saiji, Essia; Rougemont, Anne-Laure

    2016-06-01

    Denosumab has shown promising results in the management of giant cell tumor of bone, a primary bone tumor with locally aggressive behaviour. We report a case of premature denosumab interruption due to radiological and clinical tumor expansion of a giant cell tumor of the distal ulna. Although denosumab is known to induce tumor regression, with progressive ossification and loss of the characteristic morphology of giant cell tumor of bone, the ulnar tumor specimen showed a moderately to highly cellular proliferation of short spindle-shaped cells, and no osteoclast-like giant cells. There were no abnormal mitotic figures. We considered the surgical specimen as a giant cell tumor of bone with partial regression after prematurely interrupted denosumab treatment. This case illustrates the diagnostic issues of an initially unfavourable evolution raising concern for malignancy, and the difficulties in histological assessment of a partially treated giant cell tumor of bone, that may mimic osteosarcoma. PMID:26842345

  15. Coalbed methane, Cook Inlet, south-central Alaska: A potential giant gas resource

    USGS Publications Warehouse

    Montgomery, S.L.; Barker, C.E.

    2003-01-01

    Cook Inlet Basin of south-central Alaska is a forearc basin containing voluminous Tertiary coal deposits with sufficient methane content to suggest a major coalbed gas resource. Coals ranging in thickness from 2 to 50 ft (0.6 to 15 m) and in gas content from 50 to 250 scf/ton (1.6 to 7.8 cm2/g) occur in Miocene-Oligocene fluvial deposits of the Kenai Group. These coals have been identified as the probable source of more than 8 tcf gas that has been produced from conventional sandstone reservoirs in the basin. Cook Inlet coals can be divided into two main groups: (1) those of bituminous rank in the Tyonek Formation that contain mainly thermogenic methane and are confined to the northeastern part of the basin (Matanuska Valley) and to deep levels elsewhere; and (2) subbituminous coals at shallow depths (<5000 ft [1524 m]) in the Tyonek and overlying Beluga formations, which contain mainly biogenic methane and cover most of the central and southern basin. Based on core and corrected cuttings-desorption analyses, gas contents average 230 scf/ton (7.2 cm2/g) for bituminous coals and 80 scf/ton (2.5 cm2/g) for subbituminous coals. Isotherms constructed for samples of both coal ranks suggest that bituminous coals are saturated with respect to methane, whereas subbituminous coals at shallow depths along the eroded west-central basin margin are locally unsaturated. A preliminary estimate of 140 tcf gas in place is derived for the basin.

  16. Magmatic origin of giant ‘Kiruna-type’ apatite-iron-oxide ores in Central Sweden

    PubMed Central

    Jonsson, Erik; Troll, Valentin R.; Högdahl, Karin; Harris, Chris; Weis, Franz; Nilsson, Katarina P.; Skelton, Alasdair

    2013-01-01

    Iron is the most important metal for modern industry and Sweden is by far the largest iron-producer in Europe, yet the genesis of Sweden's main iron-source, the ‘Kiruna-type’ apatite-iron-oxide ores, remains enigmatic. We show that magnetites from the largest central Swedish ‘Kiruna-type’ deposit at Grängesberg have δ18O values between −0.4 and +3.7‰, while the 1.90−1.88 Ga meta-volcanic host rocks have δ18O values between +4.9 and +9‰. Over 90% of the magnetite data are consistent with direct precipitation from intermediate to felsic magmas or magmatic fluids at high-temperature (δ18Omgt > +0.9‰, i.e. ortho-magmatic). A smaller group of magnetites (δ18Omgt ≤ +0.9‰), in turn, equilibrated with high-δ18O, likely meteoric, hydrothermal fluids at low temperatures. The central Swedish ‘Kiruna-type’ ores thus formed dominantly through magmatic iron-oxide precipitation within a larger volcanic superstructure, while local hydrothermal activity resulted from low-temperature fluid circulation in the shallower parts of this system. PMID:23571605

  17. Giant Lysosomes as a Chemotherapy Resistance Mechanism in Hepatocellular Carcinoma Cells

    PubMed Central

    Colombo, Federico; Trombetta, Elena; Cetrangolo, Paola; Maggioni, Marco; Razini, Paola; De Santis, Francesca; Torrente, Yvan; Prati, Daniele; Torresani, Erminio; Porretti, Laura

    2014-01-01

    Despite continuous improvements in therapeutic protocols, cancer-related mortality is still one of the main problems facing public health. The main cause of treatment failure is multi-drug resistance (MDR: simultaneous insensitivity to different anti-cancer agents), the underlying molecular and biological mechanisms of which include the activity of ATP binding cassette (ABC) proteins and drug compartmentalisation in cell organelles. We investigated the expression of the main ABC proteins and the role of cytoplasmic vacuoles in the MDR of six hepatocellular carcinoma (HCC) cell lines, and confirmed the accumulation of the yellow anti-cancer drug sunitinib in giant (four lines) and small cytoplasmic vacuoles of lysosomal origin (two lines). ABC expression analyses showed that the main ABC protein harboured by all of the cell lines was PGP, whose expression was not limited to the cell membrane but was also found on lysosomes. MTT assays showed that the cell lines with giant lysosomes were more resistant to sorafenib treatment than those with small lysosomes (p<0.01), and that verapamil incubation can revert this resistance, especially if it is administered after drug pre-incubation. The findings of this study demonstrate the involvement of PGP-positive lysosomes in drug sequestration and MDR in HCC cell lines. The possibility of modulating this mechanism using PGP inhibitors could lead to the development of new targeted strategies to enhance HCC treatment. PMID:25493932

  18. 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

  19. 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

  20. Giant cell interstitial pneumonia in patients without hard metal exposure: analysis of 3 cases and review of the literature.

    PubMed

    Khoor, Andras; Roden, Anja C; Colby, Thomas V; Roggli, Victor L; Elrefaei, Mohamed; Alvarez, Francisco; Erasmus, David B; Mallea, Jorge M; Murray, David L; Keller, Cesar A

    2016-04-01

    Giant cell interstitial pneumonia is a rare lung disease and is considered pathognomonic for hard metal lung disease, although some cases with no apparent hard metal (tungsten carbide cobalt) exposure have been reported. We aimed to explore the association between giant cell interstitial pneumonia and hard metal exposure. Surgical pathology files from 2001 to 2004 were searched for explanted lungs with the histopathologic diagnosis of giant cell interstitial pneumonia, and we reviewed the associated clinical histories. Mass spectrometry, energy-dispersive x-ray analysis, and human leukocyte antigen typing data were evaluated. Of the 455 lung transplants, 3 met the histologic criteria for giant cell interstitial pneumonia. Patient 1 was a 36-year-old firefighter, patient 2 was a 58-year-old welder, and patient 3 was a 45-year-old environmental inspector. None reported exposure to hard metal or cobalt dust. Patients 1 and 2 received double lung transplants; patient 3 received a left single-lung transplant. Histologically, giant cell interstitial pneumonia presented as chronic interstitial pneumonia with fibrosis, alveolar macrophage accumulation, and multinucleated giant cells of both alveolar macrophage and type 2 cell origin. Energy-dispersive x-ray analysis revealed no cobalt or tungsten particles in samples from the explanted lungs. None of the samples had detectable tungsten levels, and only patient 2 had elevated cobalt levels. The lack of appropriate inhalation history and negative analytical findings in the tissue from 2 of the 3 patients suggests that giant cell interstitial pneumonia is not limited to individuals with hard metal exposure, and other environmental factors may elicit the same histologic reaction. PMID:26997453

  1. The transition to endoreduplication in trophoblast giant cells is regulated by the mSNA zinc finger transcription factor.

    PubMed

    Nakayama, H; Scott, I C; Cross, J C

    1998-07-01

    Terminal cell differentiation is usually associated with cell cycle exit. In some lineages, however, cells undergo continued rounds of DNA synthesis without intervening mitoses (endoreduplication) resulting in polyploid nuclei. This is striking in rodent trophoblast giant cells which contain up to 1000N of DNA. In Drosophila, the Escargot gene has been implicated in regulating the transition from mitotic cell cycles to endocycles during development. We found that a murine homologue, mSna, was expressed in mouse trophoblast and was downregulated during giant cell differentiation. The mSNA zinc finger protein bound to E-box DNA elements and, in transfected C3H10T1/2 fibroblasts, acted as a transcriptional repressor. The maximal repressive effect was dependent on both the zinc finger DNA-binding domain and the N-terminal, seven-amino-acid SNAG domain. Misexpression experiments in Rcho-1 trophoblast cells revealed that mSna regulates the transition from replicating precursor cells to committed giant cells: overexpression blocked, whereas antisense RNA-mediated underexpression promoted trophoblast giant cell differentiation. Overexpression of mSna in precursor cells had no effect on cell cycle kinetics, but did increase cyclin A and B levels, implying actions during G2. These effects were dependent on both the zinc finger and SNAG domains. Together, these data suggest that mSNA has an ESCARGOT-like function to repress the transcription of genes that promote the transition from mitotic to endoreduplicative cell cycles in rodent trophoblast. PMID:9676199

  2. 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

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

    PubMed Central

    Gan, Xiaoxian; Gan, Yichao; Zheng, Weiwei; Kim, Byung-Wook; Xu, Xiaohua; Lu, Xiaoya; Dong, Qi; Zheng, Shu; Huang, Wendong; Xu, Rongzhen

    2016-01-01

    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

  4. An unusual case of desmoplastic melanoma containing an osteoclast-like giant cell-rich nodule.

    PubMed

    Houang, Michelle; Castillo, Christine; La Marca, Sophie; Combemale, Patrick; Wang, Qing; Paindavoine, Sandrine; Pissaloux, Daniel; de la Fouchardiere, Arnaud

    2015-04-01

    The authors describe a case of a 5 cm mixed desmoplastic melanoma occurring on the cheek of an 88-year-old white woman. The epidermis showed the features of lentigo maligna. Within the dermis, there was a mixed desmoplastic melanoma with 2 components. The first component consisted of infiltrative malignant spindled cells with prominent stromal fibrosis and had the typical appearance of desmoplastic melanoma. The second component was within the deep half of the tumor and consisted of a densely cellular nodule composed of spindled melanocytes admixed with many osteoclast-like giant cells. There was a peripheral neurotropism and tumor invaded bone. The Breslow thickness was 14 mm. On followup, a sacral metastasis was discovered, which had a similar morphology to the deep cellular nodule. Immunohistochemistry of spindled cells both inside and outside the nodule showed S100 positivity with the absence of other melanocytic markers (HMB-45, Melan-A). Smooth muscle actin and p63 were focally positive. The osteoclast-like giant cells expressed CD68 and MiTF. Array comparative genomic hybridization of the typical desmoplastic melanoma region had a flat profile, whereas the cellular osteoclast-like giant cell–rich region displayed important cytogenetic anomalies, some of which have been previously described in melanomas. The main array comparative genomic hybridization findings were confirmed by fluorescence in situ hybridization using specific probes. The differences in morphology and molecular cytogenetics between the 2 areas suggest that these might represent the progression or emergence of a more aggressive clone within the tumor. Subsequent metastatic spread to the bone may be a result of accumulated cytogenetic abnormalities. PMID:24999544

  5. 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. PMID:26585568

  6. Environmental controls on spatial patterns in the long-term persistence of giant kelp in central California

    USGS Publications Warehouse

    Young, Mary Alida; Cavanaugh, Kyle C.; Bell, Tom W.; Raimondi, Peter T.; Edwards, Christopher A.; Drake, Patrick T.; Erikson, Li H.; Storlazzi, Curt

    2016-01-01

    As marine management is moving towards the practice of protecting static areas, it is 44 important to make sure protected areas capture and protect persistent populations. Rocky reefs in 45 many temperate areas worldwide serve as habitat for canopy forming macroalgae and these 46 structure forming species of kelps (order Laminariales) often serve as important habitat for a great 47 diversity of species. Macrocystis pyrifera is the most common canopy forming kelp species found 48 along the coast of California but the distribution and abundance of M. pyrifera varies in space and 49 time. The purpose of this study is to determine what environmental parameters are correlated with 50 the spatial and temporal persistence of M. pyrifera along the central coast of California and how 51 well those environmental parameters can be used to predict areas where M. pyrifera is more likely 52 to persist. Nine environmental variables considered in this study included depth of the seafloor, 53 structure of the rocky reef, proportion of rocky reef, size of kelp patch, biomass of kelp within a 54 patch, distance from the edge of a kelp patch, sea surface temperature, wave orbital velocities, and 55 population connectivity of individual kelp patches. Using a generalized linear mixed effects model 56 (GLMM), the persistence of M. pyrifera was significantly associated with seven of the nine 57 variables considered: depth, complexity of the rocky reef, proportion of rock, patch biomass, 58 distance from the edge of a patch, population connectivity, and wave-orbital velocities. These 59 seven environmental variables were then used to predict the persistence of kelp across the central 60 coast and these predictions were compared to a reserved dataset of M. pyrifera persistence, which 61 was not used in the creation of the GLMM. The environmental variables were shown to accurately 62 predict the persistence of M. pyrifera within the central coast of California (r = 0.71, P<0.001). 63 Because

  7. Electron microscopy and computational studies of Ebh, a giant cell-wall-associated protein from Staphylococcus aureus

    SciTech Connect

    Sakamoto, Sou; Tanaka, Yoshikazu; Tanaka, Isao; Takei, Toshiaki; Yu, Jian; Kuroda, Makoto; Yao Min; Ohta, Toshiko; Tsumoto, Kouhei

    2008-11-14

    Ebh, a giant protein found in staphylococci, contains several domains, including a large central region with 52 imperfect repeats of a domain composed of 126 amino acids. We used electron microscopy to observe the rod-like structure of a partial Ebh protein containing 10 repeating units. This is the first report of the direct observation of an Ebh structure containing a large number of repeating units, although structures containing one, two, or four repeating units have been reported. The observed structure of the partial Ebh protein was distorted and had a length of ca. 520 A and a width of ca. 21 A. The observed structures were consistent with those deduced from crystal structure analysis, suggesting that the Ebh domains are connected to form a rod-like structure. The crystal structure data revealed distorted, string-like features in the simulated structure of the whole-length Ebh protein. Superposition of fragments of the simulated whole-length structure of the Ebh protein onto each electron micrograph showed a high level of correlation between the observed and calculated structures. These results suggest that Ebh is composed of highly flexible filate molecules. The highly repetitive structure and the associated unique structural flexibility of Ebh support the proposed function of this protein, i.e. binding to sugars in the cell wall. This binding might result in intra-cell-wall cross-linking that contributes to the rigidity of bacterial cells.

  8. Coastal evolution between two giant rivers: The Chan May embayment in central Vietnam

    NASA Astrophysics Data System (ADS)

    Gouramanis, C.; Switzer, A.; Bristow, C.; Pham, D. T.; Mauz, B.; Pile, J.; Doan, L. D.; Hoang, Q. D.; Ngo, C. K.; Dao, N.; Polivka, P.; Soria, L.; Lee, Y.; Sloss, C.; Hoang, L. V.

    2015-12-01

    The coastal landscapes of Vietnam are dominated in the north and south by the very large Red and Mekong rivers. Central Vietnam, in contrast, has few large rivers that flow to the coastal zone. This coupled with the high relief (>1500 m) of the granitic Truong Son Range and shallow gradient continental shelf, has produced two different coastal geomorphologies. The first is a shallow basin infilled with a sequence of parallel, arcuate beach ridges, and the second includes the development of shore-parallel spits and coastal lagoons. All systems are Holocene in age and we present evidence of the Holocene evolution of the northward-facing, beach ridge strandplain located in the Chan May embayment, approximately 35 km north of Danang. This embayment is relatively small (5 km long at the beach and with a beach ridge sequence that spans 11 km from the modern beach to the base of the Truong Son Range) compared to other beach ridge strandplains to the north and south and serves as an analogue for the evolution of these larger systems. The Holocene evolution of the embayment was resolved using Ground Penetrating Radar (GPR), high-resolution sedimentological analysis and quartz Optically Stimulated Luminescence were used to investigate the internal stratigraphy and chronological development of the beach ridges at Chan May. The strandplain contains uniform, clean quartz-rich sediment interspersed by thin heavy mineral rich bands forming shallow-gradient beach ridges that have steadily prograded seaward during the regression after the mid-Holocene sea level highstand. As the beach ridges prograded seaward, a small river feeding directly from the Truong Son Range meandered across the strandplain and significantly modified the embayment. Recently, the river has become much reduced due to anthropogenic modification of the river and landscape. Prior to the Holocene marine highstand, the area was similarly characterized by a surface of prograding beach ridges that were eroded by

  9. 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

  10. Giant Cell Tumour of Distal Fibula Managed by En Block Resection and Reconstruction with Ipsilateral Proximal Fibula.

    PubMed Central

    Nadkarni, Sambprasad; Punit, Abhinanadan S; Nair, Rohit V

    2015-01-01

    Introduction: Giant cell tumour is the commonest benign bone tumour arising at the epiphyseometaphyseal regions of long bones. Around the knee is commonest site followed by distal radius. A giant cell tumour of the distal fibula is extremely rare. We report here a case of giant cell tumour of distal fibula. There are very few similar cases reported worldwide and it is the purpose of this report to describe the management of such a case. Case Report: A 17 year old girl presented with swelling of ankle and pain while walking for six months. Radiographs were suggestive of a giant cell tumour, computerised tomography revealed cortical break, en block resection was done with ipsilateral proximal fibula used in reconstruction of ankle mortise. Conclusion: Giant cell tumour of long bones are common but those involving the distal fibula are exceedingly rare. The management of such tumours with high recurrence rates can be easily accomplished by en block resection and reconstruction of the ankle mortise with proximal fibula ensuring good range of motion of the joint post operatively.

  11. A solitary pleural metastasis of benign giant cell tumor of bone

    PubMed Central

    Mitsui, Ai; Doi, Masatomo; Hoshikawa, Masahiro; Hayashi, Akinobu; Nakamura, Haruhiko

    2016-01-01

    Abstract Giant cell tumor of bone (GCTB) usually appears as a benign tumor. We describe an extremely rare case of a metastatic pleural tumor arising from a benign GCTB. The patient had undergone radial resection of a GCTB in his left wrist. After 6 years, he was sent to us for diagnosis of a large mass detected upon routine radiographic screening. We resected the tumor, which was found to be a solitary pleural metastasis of GCTB and had evidently spread arterially. To our knowledge, this is the first report of its kind. PMID:27516881

  12. Multiple metastases from histologically benign intraarticular diffuse-type tenosynovial giant cell tumor: a case report.

    PubMed

    Asano, Naofumi; Yoshida, Akihiko; Kobayashi, Eisuke; Yamaguchi, Takehiko; Kawai, Akira

    2014-11-01

    Diffuse-type tenosynovial giant cell tumor (D-TGCT) is a relatively rare mesenchymal tumor. It is a locally aggressive but virtually nonmetastasizing neoplasm and thus regarded as benign. Only a few D-TGCTs with benign histology have been reported to metastasize. We report an extremely rare case of benign D-TGCT in which multiple metastases developed 9 years after surgery for the primary tumor. The present case suggests that conventional D-TGCT has the potential to form distant metastases, albeit exceptionally rarely, and that this probable implantation phenomenon can be managed conservatively. PMID:25130396

  13. Forehead necrosis, one of the many facades of giant cell arteritis.

    PubMed

    Palmer, Vanessa Elizabeth; Young-Zvandasara, Tafadzwa; Vusirikala, Bharati

    2015-01-01

    Giant cell arteritis (GCA) is known to be a potentially blinding condition. Swift diagnosis can aid in preventing permanent visual loss and, more importantly, protect the contralateral eye. Classical symptoms include jaw claudication, myalgia and new-onset headache. We present two cases of GCA with scalp necrosis, a rare feature associated with this condition. In the first case, forehead necrosis preceded the visual symptoms by 2 days. In the second case it was noted a few weeks after the patient presented with profound unilateral loss of vision. Scalp necrosis is an important sign that should prompt those approached by these patients to consider GCA. PMID:25953578

  14. Pseudoangiomatous stromal hyperplasia with giant cells in the female breast. No association with neurofibromatosis?

    PubMed

    Zámecník, M; Dubac, V

    2011-04-01

    A simultaneous finding of pseudoangiomatous stromal hyperplasia (PASH) and stromal multinucleated giant cells (MGC) in mammary tissue was previously observed in patients with type-1 neurofibromatosis, indicating that it can represent a morphologic marker for this syndrome. Here, we present PASH with MGC occurring in the left breast of a 39-years-old woman who does not have neurofibromatosis. This case, along with two additional ones reported previously, indicates that PASH with MGC in the female breast may not be associated with neurofibromatosis. PMID:21598761

  15. 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

  16. 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

  17. A giant protein associated with the anterior pole of a trypanosomatid cell body skeleton.

    PubMed

    Baqui, M M; Takata, C S; Milder, R V; Pudles, J

    1996-07-01

    A megadalton protein was found to be a cytoskeleton component of the promastigote forms of the flagellate Phytomonas serpens. This protein migrated on sodium dodecyl sulfate polyacrylamide gel electrophoresis as a doublet of polypeptides with a molecular mass similar to muscle beta-connectin (titin) 2500-3000 kDa. A polyclonal antibody raised against this protein reacts, by immunoblot analysis, with Phytomonas serpens and two others Phytomonas species. In addition, the Phytomonas serpens protein was immunoprecipitated after being metabolically labeled with [35S]methionine. This antibody did not cross-react with the cytoskeletal proteins of Trypanosoma cruzi, Crithidia luciliae thermophila, Crithidia fasciculata and Leptomonas samueli or with beta-connectin (titin). Indirect immunofluorescence microscopy analysis revealed a punctate fluorescence staining at the anterior region of the parasite's body skeleton. Moreover, immunogold electron microscopy of cytoskeletal preparations and of thin sections of whole cells indicates that the giant protein appears to cap the anterior end of the cell body microtubules at the level of the junctional complex. We suggest that this giant protein may serve as a linker between the cell body skeleton and the flagellum membrane. PMID:8832208

  18. Long segmental hyperplasia of interstitial cells of Cajal with giant diverticulum formation.

    PubMed

    Xue, Liyan; Qiu, Tian; Song, Ying; Shan, Ling; Liu, Xiuyun; Guo, Lei; Ying, Jianming; Zou, Shuangmei; Shi, Susheng; Polydorides, Alexandros D; Zhao, Xinming; Lu, Ning; Lin, Dongmei

    2013-01-01

    Sporadic gastrointestinal stromal tumors (GISTs) usually form a well-circumscribed mass. In contrast, diffuse interstitial cell of Cajal (ICC) hyperplasia along the Auerbach plexus without a discrete mass may occur in patients with germline mutations in the NF1, c-KIT or PDGFRA genes. However, sporadic, diffuse ICC hyperplasia without c-KIT or PDGFRA mutations has not been reported. We describe herein one such case, forming a giant diverticulum. A 63-year-old woman with no features of Neurofibromatosis 1 (NF1) presented with increasing abdominal pain for more than 30 years. A large, diverticulum-like mass in the ileum was resected. Microscopically, a diffuse proliferation of bland spindle cells was seen extending for 12 cm, replacing the muscularis propria and lined by intact mucosa. The spindle cells were CD117+/CD34+/DOG1+/SMA+/Desmin-/S100-. Mutation analyses did not reveal any mutations in c-KIT or PDGFRA. The lesion had two silent mutations in the NF1 gene. It is rare of the diffuse form of sporadic ICC hyperplasia showing diffuse longitudinal microscopic growth completely replacing the muscularis propria, mimicking diffuse ICC hyperplasia in hereditary GIST syndromes, but without solid components and no c-KIT or PDGFRA gene mutations. This peculiar form of sporadic ICC hyperplasia may be related to intestinal dysmotility in this ileal segment and giant diverticulum formation. PMID:24294389

  19. 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

  20. 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. PMID:16240388

  1. 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

  2. Including MIR of a primary bone leiomyosarcoma that radiologically mimics a giant cell tumor.

    PubMed

    Sirikulchayanonta, Vorachai; Jaovisidh, Suphaneewan

    2008-02-01

    The authors present a case of a 42-year-old female who developed a leiomyosarcoma of the right proximal tibia that appeared radiologically similar to a giant cell tumor Histology revealed spindle cells running in whorl-like fashion with focal atypia and low mitotic figures. The immuno-stains revealed positive reactivity for alpha-smooth muscle (SMA), muscle actin and cytokeratin (AE1/AE3). The authors rendered a diagnosis of low-grade leiomyosarcoma of bone. The lesion was considered a primary lesion since the patient did not have other leiomyomatous tumors. The MRI showed hypo- to iso- signal intensity on T1-weighted imaging and heterogeneous intensity on T2-weighted imaging. This was likely due to admixed fibrotic tissue in the lesion. The tumor cells were not positive for Ebstein-Barr virus by in-situ hybridization as seen in leiomyomatous tumors in immunodeficiency patients. PMID:18389991

  3. Endopolyploidy in irradiated p53-deficient tumour cell lines: Persistence of cell division activity in giant cells expressing Aurora B- kinase

    PubMed Central

    Erenpreisa, Jekaterina; Ivanov, Andrei; Wheatley, Sally P; Kosmacek, Elizabeth A; Ianzini, Fiorenza; Anisimov, Alim P; Mackey, Michael; Davis, Paul J; Plakhins, Grigorijs; Illidge, Timothy M

    2008-01-01

    Recent findings including computerized live imaging suggest that polyploidy cells transiently emerging after severe genotoxic stress (and named ‘endopolyploid cells’) may have a role in tumour regrowth after anti-cancer treatment. Until now, mostly the factors enabling metaphase were studied in them. Here we investigate the mitotic activities and the role of Aurora B, in view of potential de-polyploidisation of these cells, because Aurora B- kinase is responsible for coordination and completion of mitosis. We observed that endopolyploid giant cells are formed in irradiated p53 tumours in several ways: (1) by division/fusion of daughter cells creating early multi-nucleated cells; (2) by asynchronous division/fusion of sub-nuclei of these multinucleated cells; (3) by a series of polyploidising mitoses reverting replicative interphase from aborted metaphase and forming giant cells with a single nucleus; (4) by micronucleation of arrested metaphases enclosing genome fragments; or (5) by incomplete division in the multipolar mitoses forming late multi-nucleated giant cells. We also observed that these activities are able to release para-diploid cells, although they do so infrequently. Although after a substantial delay, apoptosis typically occurs in these cells, we also found that roughly 2% of endopolyploid cells evade apoptosis and senescence arrest and continue mitotic activities. In this article we describe that catalytically active aurora B-kinase is expressed in the nuclei of many interphase endopolyploid cells, as well as being present at the centromeres, mitotic spindle and cleavage furrow during their mitotic efforts. The totally micronucleated giant cells (containing subgenomic fragments in multiple micronuclei) represented the only minor fraction, which failed to undergo mitosis and Aurora B was absent from it. These observations suggest that most endopolyploid tumour cells are not reproductively inert and that aurora B may contribute to the establishment

  4. 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

  5. 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

  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. 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

  8. 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

  9. An Explanation of the Photoinduced Giant Dielectric Constant of Lead Halide Perovskite Solar Cells.

    PubMed

    Almond, Darryl P; Bowen, Chris R

    2015-05-01

    A photoinduced giant dielectric constant of ~10(6) has been found in impedance spectroscopy measurements of lead halide perovskite solar cells. We report similar effects in measurements of a porous lead zirconate titanate (PZT) sample saturated with water. The principal effect of the illumination of the solar cell and of the introduction of water into the pore volume of the PZT sample is a significant increase in conductivity and dielectric loss. This is shown to exhibit low frequency power law dispersion. Application of the Kramers-Kronig relationships show the large measured values of permittivity to be related to the power law changes in conductivity and dielectric loss. The power law dispersions in the electrical responses are consistent with an electrical network model of microstructure. It is concluded that the high apparent values of permittivity are features of the microstructural networks and not fundamental effects in the two perovskite materials. PMID:26263342

  10. 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

  11. Giant Basal Cell Carcinoma: A 12-Year Follow-up Case Report.

    PubMed

    Jiménez-Hernández, Fabiola; Caballero-Centeno, Ana M; Barrera-Pérez, María; Ramos-Garibay, José A

    2016-01-01

    Giant basal cell carcinomas (GBCCs) are a strange and aggressive variety of basal cell carcinomas (BCCs); they are characterized by deep tissue invasion, rapid growth, high risk of metastasis, and a poor prognosis. GBCCs represent 0.4%-1% of all BCCs. The pathogenesis of GBCC is sometimes linked to a spontaneous mutation in the PTCH gene, mapped to the q22.33 locus of chromosome 9. The key factor in the development of GBCC, in at least 30% of the cases, is the delay in seeking medical attention (7.5 ± 3.1 years). This is associated to a poor socioeconomic level, deficient hygiene, mental illness, advanced age, and the fact that BCCs are painless lesions. The authors present a Mexican female with a 2-year ulcer diagnosed as a GBCC in the year 2000, its initial therapeutic approach, and her follow-up during the next 12 years. PMID:26332533

  12. The Giant Protein Ebh Is a Determinant of Staphylococcus aureus Cell Size and Complement Resistance

    PubMed Central

    Cheng, Alice G.; Missiakas, Dominique

    2014-01-01

    Staphylococcus aureus USA300, the clonal type associated with epidemic community-acquired methicillin-resistant S. aureus (MRSA) infections, displays the giant protein Ebh on its surface. Mutations that disrupt the ebh reading frame increase the volume of staphylococcal cells and alter the cross wall, a membrane-enclosed peptidoglycan synthesis and assembly compartment. S. aureus ebh variants display increased sensitivity to oxacillin (methicillin) as well as susceptibility to complement-mediated killing. Mutations in ebh are associated with reduced survival of mutant staphylococci in blood and diminished virulence in mice. We propose that Ebh, following its secretion into the cross wall, contributes to the characteristic cell growth and envelope assembly pathways of S. aureus, thereby enabling complement resistance and the pathogenesis of staphylococcal infections. PMID:24363342

  13. 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.

  14. Interferon γ-induced GTPase promotes invasion of Listeria monocytogenes into trophoblast giant cells

    PubMed Central

    Tachibana, Masato; Hashino, Masanori; Watanabe, Kenta; Shimizu, Takashi; Watarai, Masahisa

    2015-01-01

    Listeria monocytogenes is well known for having the ability to cross the placental barrier, leading to fetal infections and abortion. However, the mechanisms leading to infectious abortion are poorly understood. In this study, we demonstrate that interferon γ-induced GTPase (IGTP) contributes to the invasion of L. monocytogenes into trophoblast giant (TG) cells, which are placental immune cells. Knockdown of IGTP in TG cells decreased the relative efficiencies of L. monocytogenes invasion. Moreover, IGTP accumulated around infected L. monocytogenes in TG cells. Treatment of TG cells with phosphatidylinositol 3-kinase (PI3K)/Akt inhibitors also reduced bacterial invasion. PI3K/Akt inhibitor or IGTP knockdown reduced the amount of phosphorylated Akt. Monosialotetrahexosylganglioside (GM1) gangliosides, lipid raft markers, accumulated in the membrane of L. monocytogenes-containing vacuoles in TG cells. Furthermore, treatment with a lipid raft inhibitor reduced bacterial invasion. These results suggest that IGTP-induced activation of the PI3K/Akt signaling pathway promotes bacterial invasion into TG cells. PMID:25645570

  15. 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

  16. 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

  17. Gynecomastia in type-1 neurofibromatosis with features of pseudoangiomatous stromal hyperplasia with giant cells. Report of two cases.

    PubMed

    Damiani, S; Eusebi, V

    2001-05-01

    We describe the histological finding in two cases of gynecomastia in patients with von Recklinghausen's disease. The histological and immunohistochemical features of the two cases were reviewed and compared with those of five cases of gynecomastia in men without clinical evidence of neurofibromatosis. In both patients bearing von Recklinghausen's disease, the breast stroma showed features consistent with pseudoangiomatous stromal hyperplasia (PASH). It was characterised by anastomosing empty spaces lined by spindle and multinucleated giant cells which were positive with CD34 and anti-vimentin antisera and negative with anti-FVIII and CD31 antisera. In two of five of the control cases without neurofibromatosis, the mammary stroma showed focal areas with features of PASH, but no multinucleated giant cells were present in any case. PASH with giant cells should be recognised as a feature of gynecomastia in von Recklinghausen's disease. The presence of multinucleated giant cells is very unusual and, although more cases have to be studied, these cells seem to be a feature of PASH occurring in patients with von Recklinghausen's disease. PMID:11407482

  18. 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

  19. 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

  20. 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.

  1. Inferior Vena Caval Tumor Thrombus in Giant Cell Tumor of Sacrum – An Unusual Complication Treated with Multimodality Management

    PubMed Central

    Gulia, Ashish; Puri, Ajay; Byregowda, Suman; Rekhi, Bharat; Laskar, Siddhartha; Shetty, Nitin

    2015-01-01

    Introduction: Giant cell tumor is the most common benign lesion encountered. It accounts for 5 % of all skeletal tumors. It mainly affects the epiphysis of long bones and rarely axial bones. In axial bones, sacrum is the most common site to be affected. Case report: A 23 year old female with giant cell tumor of sacrum was treated initially with conservative treatment (serial angioembolisation and bisphosphonates). Later intralesional curettage was done as the patient started developing bladder and bowel disturbances after two sessions of angioembolisation. Six months later patient again presented with pain at the primary lesion site and bilateral limb swelling. Imaging revealed recurrence of the disease and tumor thrombus extending into the inferior vena cava up to the subhepatic region. Conclusion: Treatment of sacral GCT (Giant Cell Tumor) poses a unique challenge to the treating surgeon because of the close proximity of vital neurovascular structures, viscera and associated complications related to the disease. Tumor thrombi are a very rare phenomenon associated with giant cell tumors of the bone. High index of suspicion and multimodality approach is the key in treating such challenging tumors and their complications. PMID:27299100

  2. 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. PMID:25229561

  3. Multinucleated Giant Cells Are Specialized for Complement-Mediated Phagocytosis and Large Target Destruction

    PubMed Central

    Milde, Ronny; Ritter, Julia; Tennent, Glenys A.; Loesch, Andrzej; Martinez, Fernando O.; Gordon, Siamon; Pepys, Mark B.; Verschoor, Admar; Helming, Laura

    2015-01-01

    Summary Multinucleated giant cells (MGCs) form by fusion of macrophages and are presumed to contribute to the removal of debris from tissues. In a systematic in vitro analysis, we show that IL-4-induced MGCs phagocytosed large and complement-opsonized materials more effectively than their unfused M2 macrophage precursors. MGC expression of complement receptor 4 (CR4) was increased, but it functioned primarily as an adhesion integrin. In contrast, although expression of CR3 was not increased, it became functionally activated during fusion and was located on the extensive membrane ruffles created by excess plasma membrane arising from macrophage fusion. The combination of increased membrane area and activated CR3 specifically equips MGCs to engulf large complement-coated targets. Moreover, we demonstrate these features in vivo in the recently described complement-dependent therapeutic elimination of systemic amyloid deposits by MGCs. MGCs are evidently more than the sum of their macrophage parts. PMID:26628365

  4. Intracranial internal carotid artery angioplasthy and stenting in giant cell arteritis.

    PubMed

    Guerrero, Antonio Méndez; Sierra-Hidalgo, Fernando; Calleja, Patricia; Navia, Pedro; Campollo, Jorge; Díaz-Guzmán, Jaime

    2015-01-01

    We report the case of a 59-year-old woman who presented with several episodes of transient ischemic attack (TIA) caused by pathologically confirmed giant cell arteritis. She continued suffering from TIAs during admission despite immunosuppressant and antithrombotic therapy. Sudden neurological deterioration with paraparesis and cognitive impairment developed. A brain magnetic resonance (MR) imaging showed bilateral watershed ischemic lesions. MR angiography demonstrated severe stenosis of both intracranial internal carotid arteries (ICAs). Angioplasty and stenting on the left ICA were performed, with evident clinical improvement occurring within 24 hours. Endovascular therapy may be an alternative option to treat severe GCA with symptomatic intracranial large vessel disease not responsive to intensive conventional medical treatment. PMID:24707958

  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. 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

  7. 3-T MRI detects inflammatory stenosis of the vertebral artery in giant cell arteritis.

    PubMed

    Geiger, J; Uhl, M; Peter, H H; Langer, M; Bley, T A

    2008-05-01

    Giant cell arteritis (GCA) is a granulomatous vasculitis. Early diagnosis is important for the initiation of corticosteroid treatment because the arteritis can result in blindness. In most of the cases, the superficial cranial arteries are affected. However, extracranial involvement of various arteries is known. Here, we report a case of histologically proven GCA with an inflammatory stenosis of the right vertebral artery. For complete evaluation of the extension of the disease, an optimized protocol of high-resolution magnetic resonance imaging at 3 T in combination with contrast-enhanced magnetic resonance angiography was performed. This non-invasive method facilitates the differentiation of inflamed and healthy segments of small cranial arteries, may help to find appropriate sites for biopsy, and allows the assessment of affected extracranial vessels. In this patient case, even the cause of vertebral stenosis--inflammatory versus arteriosclerotic--could be elucidated. PMID:18172573

  8. Bilateral vertebral artery occlusion with retrograde basilary flow in three cases of giant cell arteritis

    PubMed Central

    Boettinger, Markus Robert; Sebastian, Schreglmann Robert; Gamulescu, Maria-Andreea Robert; Grauer, Oliver; Ritzka, Markus; Schuierer, Gerhard Robert; Bogdahn, Ulrich Robert; Steinbrecher, Andreas; Schlachetzki, Felix

    2009-01-01

    Vertebrobasilar ischaemia is a rare life-threatening complication in giant cell arteritis (GCA). We report three patients with bilateral vertebral artery occlusion. Neurovascular imaging, including CT-angiography, MR-angiography and colour-coded duplex sonography revealed flow reversal in the basilar artery as well as inflammation of the vertebral vessel wall. The first patient died from massive brainstem infarction, the other two patients survived the initial inflammatory phase of GCA. No stroke recurrence at 12 months’ follow-up on warfarin and steroid treatment was observed. Bilateral distal vertebral artery occlusion and retrograde basilar artery flow persisted. Outcome in these patients is dependant on potent immunosuppression, concurrent atherosclerotic steno-occlusive disease and presence and/or rapid development of sufficient collateral pathways into the vertebrobasilar circulation. The identification of patients with high risk of ischaemia due to compromised vertebrobasilar flow may be important to select adjunct treatment to immunosuppression, such as anticoagulation in GCA. PMID:21691390

  9. Postoperative irrigation with bisphosphonates may reduce the recurrence of giant cell tumor of bone.

    PubMed

    Yang, Tao; Zheng, Xiao-Fei; Lin, Xi; Yin, Qing-Shui

    2013-11-01

    Giant cell tumor of bone (GCTB) is a common benign bone tumor characterized by local osteolysis and high proclivity for recurrence. Surgical excision is the preferred treatment. However, simple wide resection may cause functional and cosmetic deformities of the skeleton. Currently, intralesional curettage with adjuvant therapy is a popular treatment. Bisphosphonates are recommended as an effective adjuvant treatment, and their antitumor effects have been proved in laboratory studies. During clinical treatment, intravenous and peroral administration of bisphosphonates has been attempted and has been successful in reducing the tumor recurrence rate. However, the use of bisphosphonates in GCTB adjuvant therapy requires additional study. Irrigation is a classic method for focal clearance after surgery. Therefore, we hypothesize that postoperative irrigation with bisphosphonates may be a safe and effective treatment for GCTB. The efficacy and safety of this method are worthy of further investigation. PMID:23968573

  10. 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

  11. 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

  12. [ANEURYSMAL TYPE RENAL ARTERIOVENOUS FISTULA WITH GIANT VENOUS ANEURYSM, MIMICKING RENAL CELL CARCINOMA: A CASE REPORT].

    PubMed

    Nagumo, Yoshiyuki; Komori, Hiroka; Rii, Jyunryo; Ochi, Atsuhiko; Suzuki, Koichiro; Shiga, Naoki; Ota, Tomonori

    2015-04-01

    A 39-year-old man was referred to our clinic for a 7 cm tumor in the right kidney, found by simple CT scan. It was suspected as renal cell carcinoma accompanying tumor emboli in the inferior vena cava by enhanced CT scan. For further evaluation of the tumor emboli, color Doppler ultrasound and enhanced MRI was performed. They showed a large cystic lesion with high velocity turbulent flow and flow voids in T2-weighted imaging, it seemed as giant venous aneurysm of the right renal vein. Subsequently, angiography revealed aneurysmal type renal arteriovenous fistula (AVF), transarterial embolization (TAE) of the arterial feeder with coils was performed on the same day. After 6 months from embolization, there was no recurrences or reinterventions. Color Doppler ultrasound and MRI are beneficial in distinguishing vascular disease from neoplastic disease which may sometimes mimick in other diagnostic imaging studies. In addition TAE seems to be an effective treatment for the AVF. PMID:26415363

  13. 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

  14. 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

  15. New models for the evolution of post-asymptotic giant branch stars and central stars of planetary nebulae

    NASA Astrophysics Data System (ADS)

    Miller Bertolami, Marcelo Miguel

    2016-04-01

    Context. The post-asymptotic giant branch (AGB) phase is arguably one of the least understood phases of the evolution of low- and intermediate- mass stars. The two grids of models presently available are based on outdated micro- and macrophysics and do not agree with each other. Studies of the central stars of planetary nebulae (CSPNe) and post-AGB stars in different stellar populations point to significant discrepancies with the theoretical predictions of post-AGB models. Aims: We study the timescales of post-AGB and CSPNe in the context of our present understanding of the micro- and macrophysics of stars. We want to assess whether new post-AGB models, based on the latter improvements in TP-AGB modeling, can help us to understand the discrepancies between observation and theory and within theory itself. In addition, we aim to understand the impact of the previous AGB evolution for post-AGB phases. Methods: We computed a grid of post-AGB full evolutionary sequences that include all previous evolutionary stages from the zero age main sequence to the white dwarf phase. We computed models for initial masses between 0.8 and 4 M⊙ and for a wide range of initial metallicities (Z0 = 0.02, 0.01, 0.001, 0.0001). This allowed us to provide post-AGB timescales and properties for H-burning post-AGB objects with masses in the relevant range for the formation of planetary nebulae (~0.5-0.8 M⊙). We included an updated treatment of the constitutive microphysics and included an updated description of the mixing processes and winds that play a key role during the thermal pulses (TP) on the AGB phase. Results: We present a new grid of models for post-AGB stars that take into account the improvements in the modeling of AGB stars in recent decades. These new models are particularly suited to be inputs in studies of the formation of planetary nebulae and for the determination of the properties of CSPNe from their observational parameters. We find post-AGB timescales that are at

  16. Retrobulbar blood flow and visual organ function disturbance in the course of giant cell arteritis coexisting with optic disc drusen – a case report

    PubMed Central

    Post, Michał; Milchert, Marcin

    2013-01-01

    The review presented ophthalmologic syndrome connected with visual organ function disorder in giant cell arteritis patient concomitant with optic nerve disc drusen. Diagnostic difficulties were shown in relation to incidence of both similar ophthalmic symptoms as well as interpretation of specialists examinations results (pattern visual evoked potential test, scanning laser polarimetry, and perimetric tests – kinetic and static). Apart from ophthalmic investigations, significant role of radiological examinations was considered, especially color Doppler ultrasonography of retrobulbar circulation – optic artery, central retinal artery, long posterior ciliary arteries. Adequate interpretation of results seems to be crucial to establish scheme and timing of treatment in case of co-occurrence of the abovementioned disorders. In the presented case early implementation of steroid therapy resulted in improvement of blood flow parameters and the regression of ophthalmological complaints. Visual field deficiency in kinetic perimetry, reduced wave amplitude p100 in visual evoked potential test as well as decrease in number of optic nerve fibers in optic nerve disc region in scanning laser polarimetry exam can be diagnostic features in diagnosis of visual impairment in the course of giant cell arteritis and optic nerve disc drusen. Evaluation of blood flow velocity parameters in retrobulbar arteries in color Doppler ultrasonography is the most valuable screening in monitoring ophthalmic dysregulation in presented disorders. PMID:26673284

  17. 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. PMID:26774788

  18. Compared Experimental Studies of Giant Vesicles and Red Blood Cells in Shear Flow

    NASA Astrophysics Data System (ADS)

    Viallat, Annie; Faivre, Magalie; Leyrat, Anne; Abkarian, Manouk

    2003-11-01

    The motion and the deformation of soft shells in bounded shear flows is of biological importance since, for example, white or red blood cells (RBC) are submitted to strong shear stresses during circulation. The role of cell deformability and viscoelastic properties has not been yet quantitatively studied experimentally although it is important for understanding mobility, binding and rolling of cells on vascular walls. We quantitatively characterized the behaviour of giant lipid vesicles and RBC in a bounded linear shear flow by optical microscopy. The tank-treading motion (fixed cell orientation), the tumbling motion and the lift force experienced by deformable vesicles and RBC close to a substrate, are described as a function of the contrast of viscosity between the inner and the outer fluids, and as a function of the distance from the wall. Results are compared to models developed for ellipsoids of fixed shape. Finally, we showed that RBC oscillate while tank-treading and by increasing the shear rate, they pass from tank treading to tumbling, which discloses the existence of a characteristic time that is related to the visco-elasticity of their cytoskeleton.

  19. CCL2 and CCR2 are Essential for the Formation of Osteoclasts and Foreign Body Giant Cells.

    PubMed

    Khan, Usman A; Hashimi, Saeed M; Bakr, Mahmoud M; Forwood, Mark R; Morrison, Nigel A

    2016-02-01

    Osteoclasts are multinucleated cells responsible for bone resorption. They are derived from the fusion of cells in the monocyte/macrophage lineage. Monocytes and macrophages can also fuse to form foreign body giant cells (FBGC). Foreign body giant cells are observed at the interface between a host and a foreign body such as implants during a foreign body reaction. Macrophages are attracted to the site of bone resorption and foreign body reactions by different cytokines. Chemokine (C-C) ligand-2 (CCL2) is an important chemotactic factor and binds to a receptor CCR2. In this study we investigated the importance of CCL2 and the receptor CCR2 in the formation of osteoclasts and FBGC. CCL2 mRNA was more highly expressed in giant cell culture than macrophages, being 9-fold and 16-fold more abundant in osteoclasts and FBGC respectively. Significantly fewer osteoclasts and FBGC were cultured from the bone marrow of CCL2 and CCR2 knockout mice, when compared to wild type. Not only were the number of giant cells reduced but there was a significant reduction in the number of nuclei and the size of these cells in the cultures of CCL2 and CCR2 knockout mice. Formation of osteoclasts and FBGC were recovered in cultures by addition of exogenous CCL2 to the media containing marrow cells from CCL2-/- mice. We conclude that CCL2 and its receptor CCR2 are important for the formation of osteoclasts and FBGC and absence of these genes causes inhibition of osteoclast and FBGC formation. PMID:26205994

  20. 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

  1. The palaeoclimatic significance of Eurasian Giant Salamanders (Cryptobranchidae: Zaissanurus, Andrias) - indications for elevated humidity in Central Asia during global warm periods (Eocene, late Oligocene warming, Miocene Climate Optimum)

    NASA Astrophysics Data System (ADS)

    Vasilyan, Davit; Böhme, Madelaine; Winklhofer, Michael

    2010-05-01

    Cryptobranchids represent a group of large sized (up to 1.8 m) tailed amphibians known since the Middle Jurassic (Gao & Shubin 2003). Two species are living today in eastern Eurasia: Andrias davidianus (China) and A. japonicus (Japan). Cenozoic Eurasian fossil giant salamanders are known with two genera and two or three species from over 30 localities, ranging from the Late Eocene to the Early Pliocene (Böhme & Ilg 2003). The Late Eocene species Zaissanurus beliajevae is restricted to the Central Asian Zaissan Basin (SE-Kazakhstan, 50°N, 85°E), whereas the Late Oligocene to Early Pliocene species Andrias scheuchzeri is distributed from Central Europe to the Zaissan Basin. In the latter basin the species occur during two periods; the latest Oligocene and the late Early to early Middle Miocene (Chkhikvadse 1982). Andrias scheuchzeri is osteological indistinguishable from both recent species, indicating a similar ecology (Westfahl 1958). To investigate the palaeoclimatic significance of giant salamanders we analyzed the climate within the present-day distribution area and at selected fossil localities with independent palaeoclimate record. Our results indicate that fossil and recent Andrias species occur in humid areas where the mean annual precipitation reach over 900 mm (900 - 1.300 mm). As a working hypothesis (assuming a similar ecology of Andrias and Zaissanurus) we interpret occurrences of both fossil Eurasian giant salamanders as indicative for humid palaeoclimatic conditions. Based on this assumption the Late Eocene, the latest Oligocene (late Oligocene warming) and the late Early to early Middle Miocene (Miocene Climatic Optimum) of Central Asia (Zaissan Basin) are periods of elevated humidity, suggesting a direct (positive) relationship between global climate and Central Asian humidity evolution. Böhme M., Ilg A. 2003: fosFARbase, www.wahre-staerke.com/ Chkhikvadze V.M. 1982. On the finding of fossil Cryptobranchidae in the USSR and Mongolia. Vertebrata

  2. Enrichment of c-Met+ tumorigenic stromal cells of giant cell tumor of bone and targeting by cabozantinib

    PubMed Central

    Liu, L; Aleksandrowicz, E; Fan, P; Schönsiegel, F; Zhang, Y; Sähr, H; Gladkich, J; Mattern, J; Depeweg, D; Lehner, B; Fellenberg, J; Herr, I

    2014-01-01

    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. PMID:25321478

  3. 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. PMID:24500983

  4. 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

  5. PTPN22 R620W minor allele is a genetic risk factor for giant cell arteritis.

    PubMed

    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

  6. Foreign Body Giant Cell-Related Encapsulation of a Synthetic Material Three Years After Augmentation.

    PubMed

    Lorenz, Jonas; Barbeck, Mike; Sader, Robert A; Kirkpatrick, Charles J; Russe, Philippe; Choukroun, Joseph; Ghanaati, Shahram

    2016-06-01

    Bone substitute materials of different origin and chemical compositions are frequently used in augmentation procedures to enlarge the local bone amount. However, relatively little data exist on the long-term tissue reactions. The presented case reports for the first time histological and histomorphometrical analyses of a nanocrystaline hydroxyapatite-based bone substitute material implanted in the human sinus cavity after an integration period of 3 years. The extracted biopsy was analyzed histologically and histomorphometrically with focus on the tissue reactions, vascularization, new bone formation, and the induction of a foreign body reaction. A comparably high rate of connective tissue (48.25%) surrounding the remaining bone substitute granules (42.13%) was observed. Accordingly, the amount of bone tissue (9.62%) built the smallest fraction within the biopsy. Further, tartrate-resistant acid phosphatase-positive and -negative multinucleated giant cells (4.35 and 3.93 cells/mm(2), respectively) were detected on the material-tissue interfaces. The implantation bed showed a mild vascularization of 10.03 vessels/mm(2) and 0.78%. The present case report shows that after 3 years, a comparable small amount of bone tissue was observable. Thus, the foreign body response to the bone substitute seems to be folded without further degradation or regeneration. PMID:26824327

  7. 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

  8. Human T-cell lymphotropic virus type III infection of the central nervous system: a preliminary in situ analysis

    SciTech Connect

    Stoler, M.H.; Eskin, T.A.; Benn, S.; Angerer, R.C.; Angerer, L.M.

    1986-11-07

    Patients with acquired immunodeficiency syndrome (AIDS) are subject to a spectrum of central nervous system (CNS) disorders. Recent evidence implicates the human T-cell lymphotropic virus type III (HTLV-III) in the pathogenesis of some of these illnesses, although the cells infected by the virus have yet to be identified. Using in situ hybridization, the authors examined brain tissue from two patients with AIDS encephalopathy for the presence of HTLV-III RNA. In both cases, viral RNA was detected and concentrated in, though not limited to, the white matter. The CNS cells most frequently infected included macrophages, pleomorphic microglia, and multinucleated giant cells. Less frequently, cells morphologically consistent with astrocytes, oligodendroglia, and rarely neurons were also infected. The findings strengthen the association of HTLV-III with the pathogenesis of AIDS encephalopathy. In situ hybridization can be applied to routinely prepared biopsy tissue in the diagnosis of HTLV-III infection of the CNS.

  9. The development of large-cell carcinoma in the wall of a giant bulla complicated by hemorrhage.

    PubMed

    Nakamura, Shota; Kawaguchi, Koji; Fukui, Takayuki; Fukumoto, Koichi; Okasaka, Toshiki; Yokoi, Kohei

    2016-12-01

    There were a few reports of patients with lung cancer developing at the wall of giant bullae complicated with hemorrhage. A 40-year-old male with complaints of hemoptysis was referred to our hospital, and a solitary pulmonary mass was pointed out on his chest roentgenogram. Computed tomography (CT) demonstrated a well-circumscribed solid mass measuring 7.0 × 6.5 × 6.0 cm in the right upper lobe of the lung. At the chest CT 1 year before, only a giant bulla without mass was found. From the interval change of CT findings with his clinical course, the mass was suspected as acute hemorrhage in the giant bulla. A right upper lobectomy of the lung was performed to control his hemoptysis. The surgical specimen showed the giant bulla filled with blood clot, and a partial wall of the bulla was irregularly thickened. Pathological examination revealed that the thickened wall was composed of large-cell carcinoma. In patients with bullous diseases complicated with hemorrhage, we should be aware of a possibility of developing lung cancer in the bullae. PMID:26964998

  10. Giant scaffolding protein AHNAK1 interacts with β-dystroglycan and controls motility and mechanical properties of Schwann cells.

    PubMed

    von Boxberg, Ysander; Soares, Sylvia; Féréol, Sophie; Fodil, Redouane; Bartolami, Sylvain; Taxi, Jacques; Tricaud, Nicolas; Nothias, Fatiha

    2014-09-01

    The profound morphofunctional changes that Schwann cells (SCs) undergo during their migration and elongation on axons, as well as during axon sorting, ensheathment, and myelination, require their close interaction with the surrounding laminin-rich basal lamina. In contrast to myelinating central nervous system glia, SCs strongly and constitutively express the giant scaffolding protein AHNAK1, localized essentially underneath the outer, abaxonal plasma membrane. Using electron microscopy, we show here that in the sciatic nerve of ahnak1(-) (/) (-) mice the ultrastructure of myelinated, and unmyelinated (Remak) fibers is affected. The major SC laminin receptor β-dystroglycan co-immunoprecipitates with AHNAK1 shows reduced expression in ahnak1(-) (/) (-) SCs, and is no longer detectable in Cajal bands on myelinated fibers in ahnak1(-) (/) (-) sciatic nerve. Reduced migration velocity in a scratch wound assay of purified ahnak1(-) (/) (-) primary SCs cultured on a laminin substrate indicated a function of AHNAK1 in SC motility. This was corroborated by atomic force microscopy measurements, which revealed a greater mechanical rigidity of shaft and leading tip of ahnak1(-) (/) (-) SC processes. Internodal lengths of large fibers are decreased in ahnak1(-) (/) (-) sciatic nerve, and longitudinal extension of myelin segments is even more strongly reduced after acute knockdown of AHNAK1 in SCs of developing sciatic nerve. Together, our results suggest that by interfering in the cross-talk between the transmembrane form of the laminin receptor dystroglycan and F-actin, AHNAK1 influences the cytoskeleton organization of SCs, and thus plays a role in the regulation of their morphology and motility and lastly, the myelination process. PMID:24796807

  11. MGMT Promoter Methylation and BRAF V600E Mutations Are Helpful Markers to Discriminate Pleomorphic Xanthoastrocytoma from Giant Cell Glioblastoma.

    PubMed

    Lohkamp, Laura-Nanna; Schinz, Maren; Gehlhaar, Claire; Guse, Katrin; Thomale, Ulrich-Wilhelm; Vajkoczy, Peter; Heppner, Frank L; Koch, Arend

    2016-01-01

    Giant Cell Glioblastoma (gcGBM) and Pleomorphic Xanthoastrocytoma (PXA) are rare astroglial tumors of the central nervous system. Although they share certain histomorphological and immunohistochemical features, they are characterized by different clinical behavior and prognosis. Nevertheless, few cases remain uncertain, as their histomorphological hallmarks and immunophenotypes do correspond to the typical pattern neither of gcGBM nor PXA. Therefore, in addition to the routinely used diagnostic histochemical and immunohistochemical markers like Gömöri, p53 and CD34, we analyzed if genetic variations like MGMT promoter methylation, mutations in the IDH1/2 genes, or BRAF mutations, which are actually used as diagnostic, prognostic and predictive molecular markers in anaplastic glial tumors, could be helpful in the differential diagnostic of both tumor entities. We analyzed 34 gcGBM and 20 PXA for genetic variations in the above-named genes and found distinct distributions between both groups. MGMT promoter hypermethylation was observed in 3 out of 20 PXA compared to 14 out of 34 gcGBM (15% vs. 41.2%, p-value 0.09). BRAF V600E mutations were detected in 50% of the PXA but not in any of the gcGBM (50% vs. 0%, p-value < 0.001). IDH1 R132 and IDH R172 mutations were not present in any of the PXA and gcGBM cases. Our data indicate, that in addition to the histological and immunohistochemical evaluation, investigation of MGMT promoter methylation and in particular BRAF V600E mutations represent reliable additional tools to sustain differentiation of gcGBM from PXA on a molecular basis. Based on these data specific BRAF kinase inhibitors could represent a promising agent in the therapy of PXA and their use should be emphasized. PMID:27253461

  12. MGMT Promoter Methylation and BRAF V600E Mutations Are Helpful Markers to Discriminate Pleomorphic Xanthoastrocytoma from Giant Cell Glioblastoma

    PubMed Central

    Lohkamp, Laura-Nanna; Schinz, Maren; Gehlhaar, Claire; Guse, Katrin; Thomale, Ulrich-Wilhelm; Vajkoczy, Peter; Heppner, Frank L.; Koch, Arend

    2016-01-01

    Giant Cell Glioblastoma (gcGBM) and Pleomorphic Xanthoastrocytoma (PXA) are rare astroglial tumors of the central nervous system. Although they share certain histomorphological and immunohistochemical features, they are characterized by different clinical behavior and prognosis. Nevertheless, few cases remain uncertain, as their histomorphological hallmarks and immunophenotypes do correspond to the typical pattern neither of gcGBM nor PXA. Therefore, in addition to the routinely used diagnostic histochemical and immunohistochemical markers like Gömöri, p53 and CD34, we analyzed if genetic variations like MGMT promoter methylation, mutations in the IDH1/2 genes, or BRAF mutations, which are actually used as diagnostic, prognostic and predictive molecular markers in anaplastic glial tumors, could be helpful in the differential diagnostic of both tumor entities. We analyzed 34 gcGBM and 20 PXA for genetic variations in the above-named genes and found distinct distributions between both groups. MGMT promoter hypermethylation was observed in 3 out of 20 PXA compared to 14 out of 34 gcGBM (15% vs. 41.2%, p-value 0.09). BRAF V600E mutations were detected in 50% of the PXA but not in any of the gcGBM (50% vs. 0%, p-value < 0.001). IDH1 R132 and IDH R172 mutations were not present in any of the PXA and gcGBM cases. Our data indicate, that in addition to the histological and immunohistochemical evaluation, investigation of MGMT promoter methylation and in particular BRAF V600E mutations represent reliable additional tools to sustain differentiation of gcGBM from PXA on a molecular basis. Based on these data specific BRAF kinase inhibitors could represent a promising agent in the therapy of PXA and their use should be emphasized. PMID:27253461

  13. Reconstruction of the Midfoot Using a Free Vascularized Fibular Graft After En Bloc Excision for Giant Cell Tumor of the Tarsal Bones: A Case Report.

    PubMed

    Hara, Hitomi; Kawamoto, Teruya; Onishi, Yasuo; Fujioka, Hiroyuki; Nishida, Kotaro; Kuroda, Ryosuke; Kurosaka, Masahiro; Akisue, Toshihiro

    2016-01-01

    We report the case of a 32-year-old Japanese female with a giant cell tumor of bone involving multiple midfoot bones. Giant cell tumors of bone account for approximately 5% of all primary bone tumors and most often arise at the ends of long bones. The small bones, such as those of the hands and feet, are rare sites for giant cell tumors. Giant cell tumors of the small bones tend to exhibit more aggressive clinical behavior than those of the long bones. The present patient underwent en bloc tumor excision involving multiple tarsals and metatarsals. We reconstructed the longitudinal arch of the foot with a free vascularized fibular graft. At the 2-year follow-up visit, bony union had been achieved, with no tumor recurrence. PMID:26213165

  14. Long-term outcome of giant cell tumor of bone involving sacroiliac joint treated with selective arterial embolization and curettage: a case report and literature review

    PubMed Central

    2013-01-01

    Background Giant cell tumor of the sacrum, especially involving the sacroiliac joint, is rare, but is particularly challenging to treat. The long term outcome of a patient was studied with giant cell tumor involving the sacroiliac joint treated with selective arterial embolization and curretage. Method One patient with giant cell tumor involving the sacroiliac joint was treated with selective arterial embolization and curettage in our hospital in October 2002. The curettage and bone grafting was done after two times of selective arterial embolization;1600 ml of blood were transfused and no complications developed during the operation. Results At the final follow-up of 9 years after the operation, no local recurrence and metastasis developed and she retained normal activity in daily life. Conclusion We think it is an optimal treatment for giant cell tumor involving the sacroiliac joint, with repeated selective arterial embolization and curettage, which has the advantage of less injury, less blood loss and fewer complications. PMID:23497322

  15. Recurrent temporal bone tenosynovial giant cell tumor with chondroid metaplasia: the use of imaging to assess recurrence.

    PubMed

    Pina, Sofia; Fernandez, Maria; Maya, Silvia; Garcia, Roberto A; Noor, Ali; Pawha, Puneet S; Som, Peter M

    2014-02-01

    Tenosynovial giant cell tumor (TGCT) is a benign proliferative lesion of unclear etiology. It is predominantly monoarticular and involves the synovium of the joint, tendon sheath, and bursa. TGCT of the temporomandibular joint (TMJ) is rare and aggressive resulting in destruction of surrounding structures. The diagnosis may be suggested by imaging, mainly by the MR features and PET/CT, and confirmed by histopathology. We describe the case of a 50-year-old man who presented with right-sided hearing loss, tinnitus and TMJ pain. Pathology revealed tenosynovial giant cell tumor with chondroid metaplasia. Six years later he developed a recurrence, which was documented to our knowledge for the first time with CT, MR and FDG PET/CT imaging. PMID:24571839

  16. 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

  17. Congenital segmental lymphedema in tuberous sclerosis complex with associated subependymal giant cell astrocytomas treated with Mammalian target of rapamycin inhibitors.

    PubMed

    Prato, Giulia; Mancardi, Maria Margherita; Baglietto, Maria Giuseppina; Janis, Sara; Vercellino, Nadia; Rossi, Andrea; Consales, Alessandro; Raso, Alessandro; Garrè, Maria Luisa

    2014-09-01

    Tuberous sclerosis complex is a genetic, multisystemic disorder characterized by circumscribed benign lesions (hamartomas) in several organs, including brain. This is the result of defects in the TSC1 and/or TSC2 tumor suppressor genes, encoding the hamartin-tuberin complex that inhibits the mammalian target of rapamycin pathway. Specific inhibitors of this pathway have been shown to reduce the volume of subependymal giant cell astrocytomas associated with tuberous sclerosis. Congenital lymphedema is rarely seen in association with tuberous sclerosis, with only a few reported cases. Although this association can be coincidental, the dysgenetic lymphatic system can represent a hamartia as a consequence of gene mutation. We describe a child with congenital lymphedema in tuberous sclerosis and associated subependymal giant cell astrocytoma who experienced lymphangitis under treatment with mammalian target of rapamycin inhibitors. Because our patient did not show worsening of lymphedema, congenital lymphedema does not seem to be a contraindication for this therapy. PMID:24056156

  18. Skin Uptake of 99mTc-HDP in a Case of Annular Elastolytic Giant Cell Granuloma.

    PubMed

    Gomez, Maria Del Val; Theillac, Bernard; Rizkallal Monzon, Sebastian; Lorente Castro, Berta Covadonga; Castro-Beiras, Jose Manuel

    2016-06-01

    Sometimes unexpected extraosseous uptakes appear in a bone scintigraphy as a consequence of a wide spectrum of nonosseous disorders. Recognition of these findings is important to enhance the diagnostic value of bone scintigraphy. We report a case of intense bone scintigraphy cutaneous uptake due to elastolytic actinic giant cell granuloma (EAGCG). We present the case of a patient with intense extraosseous uptakes of Tc-HDP that appeared in a bone scintigraphy that was performed for lumbar pain. PMID:26975009

  19. 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

  20. 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

  1. Dramatic Resolution of an Unresectable Giant Basal Cell Carcinoma Treated with Intensity-Modulated Radiation Therapy (IMRT) - A Case Report

    PubMed Central

    Wandrey, Narine; Chen, Tiffany

    2015-01-01

    A 59-year-old man presented with an unresectable bulky giant basal cell carcinoma on his upper back. A trial of chemotherapy did not help relieve his symptoms or reduce the tumor. He was referred for and received definitive radiation therapy via IMRT with dramatic regression. The patient had been unable to lie on his back for many years but currently can sleep comfortably on his back without pain, which has dramatically improved his quality of life. PMID:26848409

  2. 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

  3. Nicotine Directly Induces Endoplasmic Reticulum Stress Response in Rat Placental Trophoblast Giant Cells.

    PubMed

    Wong, Michael K; Holloway, Alison C; Hardy, Daniel B

    2016-05-01

    Nicotine exposure during pregnancy leads to placental insufficiency impairing both fetal and neonatal development. Previous studies from our laboratory have demonstrated that in rats, nicotine augmented endoplasmic reticulum (ER) stress in association with placental insufficiency; however, the underlying mechanisms remain elusive. Therefore, we sought to investigate the possible direct effect of nicotine on ER stress in Rcho-1 rat placental trophoblast giant (TG) cells during differentiation. Protein and/or mRNA expression of markers involved in ER stress (eg, phosphorylated PERK, eIF2α, CHOP, and BiP/GRP78) and TG cell differentiation and function (eg, Pl-1, placental growth factor [Pgf], Hsd11b1, and Hsd11b2) were quantified via Western blot or real-time polymerase chain reaction. Nicotine treatment led to dose-dependent increases in the phosphorylation of PERK[Thr981] and eIF2α[Ser51], whereas pretreatment with a nicotinic acetylcholine receptor (nAChR) antagonist (mecamylamine hydrochloride) blocked the induction of PERK phosphorylation, verifying the direct involvement of nicotine and nAChR binding. We next investigated select target genes known to play essential roles in placental TG cell differentiation and function (Pl-1, Pgf, Hsd11b1, and Hsd11b2), and found that nicotine significantly augmented the mRNA levels of Hsd11b1 in a dose-dependent manner. Furthermore, using tauroursodeoxycholic acid, a safe bile acid known to improve protein chaperoning and folding, we were able to prevent nicotine-induced increases in both PERK phosphorylation and Hsd11b1 mRNA levels, revealing a potential novel therapeutic approach to reverse the deleterious effects of nicotine exposure in pregnancy. Collectively, these results implicate that nicotine, acting through its receptor, can directly augment ER stress and impair placental function. PMID:26803847

  4. Ultrastructural aspects of foreign body giant cells generated on different substrates.

    PubMed

    Ten Harkel, Bas; Koopsen, Jelle; van Putten, Sander M; van Veen, Henk; Picavet, Daisy I; de Vries, Teun J; Bank, Ruud A; Everts, Vincent

    2016-07-01

    Implantation of biomaterials into the body, e.g. for tissue engineering purposes, induces a material-dependent inflammatory response called the foreign body reaction (FBR). A hallmark feature of this response is the formation of large multinucleated cells: foreign body giant cells (FBGCs). Biomaterials like cross-linked and non-cross-linked collagen often induce the formation of FBGCs. It is unknown whether different biomaterials result in the formation of different FBGCs. To investigate this, we implanted cross-linked and non-cross-linked dermal sheep collagen subcutaneously in mice. After 21 days the implanted material was collected and prepared for ultrastructural analysis. More FBGCs formed on and between implants of cross-linked collagen compared to non-cross-linked material. The ultrastructural aspects of the FBGCs present on the two types of implants proved to be similar. On both materials, they formed long slender protrusions on the basolateral membrane, they were very rich in mitochondria, contained numerous nuclei, and showed signs of the presence of a clear zone facing the implanted material. Similar clear zones, that resemble osteoclastic features, were also seen in FBGCs generated in vitro on bone slices, but these cells did not form a ruffled border. However, similarities in ultrastructure such as the occurrence of slender protrusions and high mitochondrion content were also found in the FBGCs generated in vitro. These data indicate that FBGCs formed on different substrates share many morphological characteristics. The formation of long finger-like protrusions seemed typical for the FBGCs, in vivo as well as in vitro, however the function of these structures needs further analysis. PMID:27155321

  5. The cell polarity scaffold Lethal Giant Larvae regulates synapse morphology and function

    PubMed Central

    Staples, Jon; Broadie, Kendal

    2013-01-01

    Summary Lethal Giant Larvae (LGL) is a cytosolic cell polarity scaffold whose loss dominantly enhances neuromuscular junction (NMJ) synaptic overgrowth caused by loss of the Fragile X Mental Retardation Protein (FMRP). However, direct roles for LGL in NMJ morphological and functional development have not before been tested. Here, we use confocal imaging and two-electrode voltage-clamp electrophysiology at the Drosophila larval NMJ to define the synaptic requirements of LGL. We find that LGL is expressed both pre- and postsynaptically, where the scaffold localizes at the membrane on both sides of the synaptic interface. We show that LGL has a cell autonomous presynaptic role facilitating NMJ terminal branching and synaptic bouton formation. Moreover, loss of both pre- and postsynaptic LGL strongly decreases evoked neurotransmission strength, whereas the frequency and amplitude of spontaneous synaptic vesicle fusion events is increased. Cell-targeted RNAi and rescue reveals separable pre- and postsynaptic LGL roles mediating neurotransmission. We show that presynaptic LGL facilitates the assembly of active zone vesicle fusion sites, and that neuronally targeted rescue of LGL is sufficient to ameliorate increased synaptic vesicle cycling imaged with FM1-43 dye labeling. Postsynaptically, we show that loss of LGL results in a net increase in total glutamate receptor (GluR) expression, associated with the selective elevation of GluRIIB subunit-containing receptors. Taken together, these data indicate that the presynaptic LGL scaffold facilitates the assembly of active zone fusion sites to regulate synaptic vesicle cycling, and that the postsynaptic LGL scaffold modulates glutamate receptor composition and function. PMID:23444371

  6. 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

  7. Modified Kraske Procedure with Mid-Sacrectomy and Coccygectomy for En Bloc Excision of Sacral Giant Cell Tumors

    PubMed Central

    Lima, Álvaro; 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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. PMID:24014786

  18. 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

  19. Plasma viscosity or erythrocyte sedimentation rate in the diagnosis of giant cell arteritis?

    PubMed Central

    Brittain, G. P.; McIlwaine, G. G.; Bell, J. A.; Gibson, J. M.

    1991-01-01

    Plasma viscosity (PV) has replaced the erythrocyte sedimentation rate (ESR) as a routine laboratory test in many hospitals. The finding of a normal PV but raised ESR in a case of biopsy proved giant cell arteritis (GCA) cast doubt on this substitution in cases of suspected GCA. To assess the equivalence of PV and ESR in the diagnosis of this disease 40 suspected cases were prospectively investigated with both tests. The correlation between the two tests was good (r = 0.742, p less than 0.0001). The substitution of one test for the other would appear to be justified in most cases of suspected GCA. In the presence of biopsy proved disease, however, the PV and ESR each produced 13.3% false negatives. These occurred both in combination with and independently of the other test showing that, when in error, the two tests may not be equivalent. In cases of doubt the performing of both PV and ESR tests together improves but does not achieve complete diagnostic accuracy. Clinical judgment based on careful assessment of all available symptoms and signs must remain the foundation of diagnosis. PMID:1751458

  20. 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

  1. 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

  2. ZNF687 Mutations in Severe Paget Disease of Bone Associated with Giant Cell Tumor.

    PubMed

    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

    2016-02-01

    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

  3. 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. PMID:2003856

  4. Mega-aorta syndrome development in giant cell arteritis. A same entity?

    PubMed

    Rodríguez-Caulo, Emiliano A; Velázquez, Carlos J; García-Borbolla, Mariano; Barquero, José M

    2011-11-01

    Giant cell arteritis (GCA) is the most common form of large vessel arteritis. GCA typically involves the branches of the external carotid artery, but is the leading cause of inflammatory aortitis. However, involvement of the aorta often goes undetected. We present a case of an 81-year-old man, with headache and intense chest pain, who was previously given a diagnosis of GCA with a temporal artery biopsy 6 years ago. Owing to the suspicion of acute aortic syndrome, an emergent computed tomography (CT) was performed. CT showed the development of mega-aorta syndrome, with a diameter of 75.2 mm in the ascending aorta, 61.8 mm in the aortic arch, 76.1 mm in the descending thoracic aorta, and 45.1 mm in the abdominal aorta, presenting a chronic type B aortic dissection. Although there are reported cases secondary to Takayasu arteritis, this is the first case reported in the literature of mega-aorta syndrome associated with GCA in a patient previously diagnosed using temporal artery biopsy. PMID:22023949

  5. Giant cell tumor of tendon sheath: study of 64 cases and review of literature.

    PubMed

    Di Grazia, S; Succi, G; Fragetta, F; Perrotta, R E

    2013-01-01

    The giant cell tumor of tendon sheath (GCTTS) is the most common benign neoplasm in the hand after the ganglion cyst. Several hypotheses were formulated about the etiological factors of these tumors, but still there is not a common opinion on etiology, prognostic factors and recurrence rate. This article presents a review of literature of the last 15 years about GCTTS to assess the demographic, clinical and histological profile. We compared the information obtained from literature with our experience of 64 cases between 2000 and 2012. Our study showed similar results to those reported in literature, except for the recurrence rate: only 3 cases (4.7%) of 64 patients reported recurrence (versus about 15% on average in literature). Among the various possible factors that predispose to recurrence, it is necessary that the surgeon ensures complete excision of the tumor and removal of any residual satellite nodules. Although the marginal excision is the treatment of choice, it is often difficult to perform due to for the location and the strict adherence of the tumor to the tendon or neurovascular bundles. We used in all cases a magnifying loupe to help a careful research of satellite lesions and to respect surrounding structures. PMID:23837951

  6. Clinical Outcome of Treatment for Patients with Giant Cell Tumor in Spine

    PubMed Central

    Kim, Seon Chun; Cho, Wonik; Chang, Ung-Kyu

    2015-01-01

    Objective The treatment of giant cell tumor (GCT) is mainly performed surgically. However, GCT in spine seems difficult to treat because of the limited surgical accessibility and proximity. In this report, we analyzed the outcome of GCT treatment in spine. Methods Between 2000 and 2012, 19 patients received treatment for GCT in spine. Median age at their first diagnosis was 31 years, 10 patients were male, and 9 female. Fourteen tumors were located in the sacrum, 1 in cervical, 1 in thoracic and 3 in lumbar spine. As primary treatment, gross total removal (GTR) was done in 6 patients, and subtotal removal (STR) in 13 patients. Radiation therapy (RT) as an adjuvant therapy was performed in 2 cases in GTR group and 10 cases in STR group. Results During the follow-up, 7 patients had local recurrence (36.8%). The average period until recurrence after primary treatment was 14 months. No recurrence was detected in GTR group. Recurrence was noted in 7 out of 13 patients who underwent STR. These differences were statistically significant (p=0.024). A median of recurrence free period (RFP) was 84 months. Also average RFP of the RT group was 112 months, and non-RT group was 65 months. These differences were statistically significant (p=0.041). Conclusion Treatment of choice for GCT in spine is a complete removal of tumor without neurological deficits. In case of incomplete removal, radiation therapy may be a useful adjuvant treatment modality. PMID:26539269

  7. Tenosynovial Giant Cell Tumor in the Dermis of the External Auditory Meatus.

    PubMed

    Maghari, Amin; Zaleski, Theresa A; Jow, Tiffany; Lambert, W Clark

    2016-01-01

    A 26-year-old African American woman with a history of a recurring "oozing papule" in the right ear presented to the emergency department in July 2010 with a 2-month history of an enlarging, painful growth in the right ear canal. Physical examination revealed a 1-cm round cystic lesion along the right, anterior external auditory canal wall, just medial to the tragus. Initial diagnosis was an infected cyst of the external ear canal. The patient was instructed to follow-up with an ear, nose, and throat (ENT) office. Two months following the emergency department visit, inspection by ENT revealed a 3- to 4-mm round, firm subcutaneous nodule that did not extend into the ear canal or cartilage. According to the patient, this lesion had recurred with several infections. The lesion was biopsied in the outpatient setting and demonstrated ulceration with marked acute and chronic inflammation in addition to granulation tissue. Two months later, the lesion was surgically excised. The final diagnosis of giant cell tumor, tenosynovial type with lesion-free margins, and no involvement of the cartilage was made (Figures 1-3). No further treatment was recommended. Gross examination of the excised lesion revealed tan to white soft tissue measuring 1.0×0.7×0.3 cm. Results from factor XIII A immunostain was negative, confirming that the lesion did not represent an unusual variant of fibrous histiocytoma (Figure 4). To date, recurrence of this lesion has not been appreciated. PMID:27072732

  8. Cell fate control in the developing central nervous system

    SciTech Connect

    Guérout, Nicolas; Li, Xiaofei; Barnabé-Heider, Fanie

    2014-02-01

    The principal neural cell types forming the mature central nervous system (CNS) are now understood to be diverse. This cellular subtype diversity originates to a large extent from the specification of the earlier proliferating progenitor populations during development. Here, we review the processes governing the differentiation of a common neuroepithelial cell progenitor pool into mature neurons, astrocytes, oligodendrocytes, ependymal cells and adult stem cells. We focus on studies performed in mice and involving two distinct CNS structures: the spinal cord and the cerebral cortex. Understanding the origin, specification and developmental regulators of neural cells will ultimately impact comprehension and treatments of neurological disorders and diseases. - Highlights: • Similar mechanisms regulate cell fate in different CNS cell types and structures. • Cell fate regulators operate in a spatial–temporal manner. • Different neural cell types rely on the generation of a diversity of progenitor cells. • Cell fate decision is dictated by the integration of intrinsic and extrinsic signals.

  9. A central role for venom in predation by Varanus komodoensis (Komodo Dragon) and the extinct giant Varanus (Megalania) priscus

    PubMed Central

    Fry, Bryan G.; Wroe, Stephen; Teeuwisse, Wouter; van Osch, Matthias J. P.; Moreno, Karen; Ingle, Janette; McHenry, Colin; Ferrara, Toni; Clausen, Phillip; Scheib, Holger; Winter, Kelly L.; Greisman, Laura; Roelants, Kim; van der Weerd, Louise; Clemente, Christofer J.; Giannakis, Eleni; Hodgson, Wayne C.; Luz, Sonja; Martelli, Paolo; Krishnasamy, Karthiyani; Kochva, Elazar; Kwok, Hang Fai; Scanlon, Denis; Karas, John; Citron, Diane M.; Goldstein, Ellie J. C.; Mcnaughtan, Judith E.; Norman, Janette A.

    2009-01-01

    The predatory ecology of Varanus komodoensis (Komodo Dragon) has been a subject of long-standing interest and considerable conjecture. Here, we investigate the roles and potential interplay between cranial mechanics, toxic bacteria, and venom. Our analyses point to the presence of a sophisticated combined-arsenal killing apparatus. We find that the lightweight skull is relatively poorly adapted to generate high bite forces but better adapted to resist high pulling loads. We reject the popular notion regarding toxic bacteria utilization. Instead, we demonstrate that the effects of deep wounds inflicted are potentiated through venom with toxic activities including anticoagulation and shock induction. Anatomical comparisons of V. komodoensis with V. (Megalania) priscus fossils suggest that the closely related extinct giant was the largest venomous animal to have ever lived. PMID:19451641

  10. A central role for venom in predation by Varanus komodoensis (Komodo Dragon) and the extinct giant Varanus (Megalania) priscus.

    PubMed

    Fry, Bryan G; Wroe, Stephen; Teeuwisse, Wouter; van Osch, Matthias J P; Moreno, Karen; Ingle, Janette; McHenry, Colin; Ferrara, Toni; Clausen, Phillip; Scheib, Holger; Winter, Kelly L; Greisman, Laura; Roelants, Kim; van der Weerd, Louise; Clemente, Christofer J; Giannakis, Eleni; Hodgson, Wayne C; Luz, Sonja; Martelli, Paolo; Krishnasamy, Karthiyani; Kochva, Elazar; Kwok, Hang Fai; Scanlon, Denis; Karas, John; Citron, Diane M; Goldstein, Ellie J C; McNaughtan, Judith E; Norman, Janette A

    2009-06-01

    The predatory ecology of Varanus komodoensis (Komodo Dragon) has been a subject of long-standing interest and considerable conjecture. Here, we investigate the roles and potential interplay between cranial mechanics, toxic bacteria, and venom. Our analyses point to the presence of a sophisticated combined-arsenal killing apparatus. We find that the lightweight skull is relatively poorly adapted to generate high bite forces but better adapted to resist high pulling loads. We reject the popular notion regarding toxic bacteria utilization. Instead, we demonstrate that the effects of deep wounds inflicted are potentiated through venom with toxic activities including anticoagulation and shock induction. Anatomical comparisons of V. komodoensis with V. (Megalania) priscus fossils suggest that the closely related extinct giant was the largest venomous animal to have ever lived. PMID:19451641

  11. 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

  12. An observational study of giant cell interstitial pneumonia and lung fibrosis in hard metal lung disease

    PubMed Central

    Tanaka, Junichi; Moriyama, Hiroshi; Terada, Masaki; Takada, Toshinori; Suzuki, Eiichi; Narita, Ichiei; Kawabata, Yoshinori; Yamaguchi, Tetsuo; Hebisawa, Akira; Sakai, Fumikazu; Arakawa, Hiroaki

    2014-01-01

    Background Hard metal lung disease has various pathological patterns including giant cell interstitial pneumonia (GIP) and usual interstitial pneumonia (UIP). Although the UIP pattern is considered the prominent feature in advanced disease, it is unknown whether GIP finally progresses to the UIP pattern. Objectives To clarify clinical, pathological and elemental differences between the GIP and UIP patterns in hard metal lung disease. Methods A cross-sectional study of patients from 17 institutes participating in the 10th annual meeting of the Tokyo Research Group for Diffuse Parenchymal Lung Diseases, 2009. Nineteen patients (seven female) diagnosed with hard metal lung disease by the presence of tungsten in lung specimens were studied. Results Fourteen cases were pathologically diagnosed as GIP or centrilobular inflammation/fibrosing. The other five cases were the UIP pattern or upper lobe fibrosis. Elemental analyses of lung specimens of GIP showed tungsten throughout the centrilobular fibrotic areas. In the UIP pattern, tungsten was detected in the periarteriolar area with subpleural fibrosis, but no association with centrilobular fibrosis or inflammatory cell infiltration. The GIP group was younger (43.1 vs 58.6 years), with shorter exposure duration (73 vs 285 months; p<0.01), lower serum KL-6 (398 vs 710 U/mL) and higher lymphocyte percentage in bronchoalveolar lavage fluid (31.5% vs 3.22%; p<0.05) than the fibrosis group. Conclusions The UIP pattern or upper lobe fibrosis is remarkably different from GIP in distribution of hard metal elements, associated interstitial inflammation and fibrosis, and clinical features. In hard metal lung disease, the UIP pattern or upper lobe fibrosis may not be an advanced form of GIP. PMID:24674995

  13. GIANT CONVECTION CELL TURNOVER AS AN EXPLANATION OF THE LONG SECONDARY PERIODS IN SEMIREGULAR RED VARIABLE STARS

    SciTech Connect

    Stothers, Richard B.

    2010-12-10

    Giant convection cells in the envelopes of massive red supergiants turn over in a time comparable in order of magnitude with the observed long secondary periods in these stars, according to a theory proposed some years ago by Stothers and Leung. This idea is developed further here by using improved theoretical data, especially a more accurate convective mixing length and a simple calculation of the expected radial-velocity variations at the stellar surface. The theory is applied to the two best-observed red supergiants, Betelgeuse and Antares, with more success than in the earlier study. The theory can also explain the long secondary periods seen in the low-mass red giants, thus providing a uniform and coherent picture for all of the semiregular red variables. How the turnover of a giant convection cell might account for the observed slow light and radial-velocity variations, their relative phasing, and the absence of these variations in certain stars is discussed here in a qualitative way, but follows naturally from the theory.

  14. The central Onodi cell: A previously unreported anatomic variation

    PubMed Central

    Cherla, Deepa V.; Tomovic, Senja; Liu, James K.

    2013-01-01

    Preoperative recognition of the Onodi cell is necessary to avoid injury to closely associated structures, including the internal carotid artery and the optic nerve. This article describes the central Onodi cell, a variation in which a posterior ethmoid cell lies superior to the sphenoid sinus in a midline position with at least one optic canal bulge. To our knowledge, this anatomic variation has not been previously reported in the literature. Radiographic and endoscopic imaging of this unique variation is provided. PMID:23772328

  15. Giant cavernous hemangioma of the liver and multiple primary malignant tumors in a patient with suspected familial inhibition of natural killer cell activity--a case report.

    PubMed

    Tomiyama, T; Uchida, K; Yoshida, K; Muto, T; Saito, H; Nemoto, K; Inoue, Z; Morita, T; Miyakoshi, H; Tamura, K

    1989-03-01

    A woman was operated on for a nonepithelial malignant tumor of the left leg and subsequently, for an epithelial carcinoma of the right breast and a borderline malignant tumor of the right ovary. She also developed a giant cavernous hemangioma that caused disseminated intravascular coagulation syndrome, which necessitated a left trisegmentectomy of the liver. Her family history suggested a hereditary predisposition to diverse malignant neoplasms, and also to giant cavernous hemangioma of the liver. Immunological evaluation disclosed selective inhibition of natural killer cell activity. Hormonal and hereditary factors are discussed in relation to the development of multiple primary tumors and giant cavernous hemangioma of the liver. PMID:2724721

  16. 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

  17. 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

  18. 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

  19. 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.

  20. Disease Relapses among Patients with Giant Cell Arteritis: A Prospective, Longitudinal Cohort Study

    PubMed Central

    Kermani, Tanaz A.; Warrington, Kenneth J.; Cuthbertson, David; Carette, Simon; Hoffman, Gary S.; Khalidi, Nader A.; Koening, Curry L.; Langford, Carol A.; Maksimowicz-McKinnon, Kathleen; McAlear, Carol A.; Monach, Paul A.; Seo, Philip; Merkel, Peter A.; Ytterberg, Steven R.

    2015-01-01

    Objective To evaluate the frequency, timing, and clinical features of relapses in giant cell arteritis (GCA). Methods Patients with GCA enrolled in a prospective, multicenter, longitudinal study were included in the analysis. Relapse was defined as either new disease activity after a period of remission or worsening disease activity. Results The study included 128 subjects: 102 women (80%) and 26 men (20%). Mean ± SD age at diagnosis of GCA was 69.9 ± 8.6 years. Mean followup for the cohort was 21.4 ± 13.9 months. Median (interquartile range) duration of disease at study enrollment was 4.6 months (1.2, 16.8). During followup, 59 relapses were observed in 44 patients (34%). Ten patients (8%) experienced 2 or more relapses. The most common symptoms at relapse were headache (42%) and polymyalgia rheumatica (51%), but ischemic (some transient) manifestations (visual symptoms, tongue or jaw claudication, and/or limb claudication) occurred in 29% of relapses (12% cohort). Forty-three relapses (73%) occurred while patients were taking glucocorticoid therapy at a median (range) prednisone dose of 7.5 (0–35) mg. In 21% of relapses, both erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were normal. Among 69 patients enrolled in the cohort with newly diagnosed disease, 24% experienced a first relapse within 12 months after diagnosis. Conclusion Among patients with GCA, relapses are common, often occurring during treatment. ESR and CRP are frequently normal at times of clinical relapse, highlighting the need for better biomarkers to assess disease activity in GCA. There remains a need for effective therapeutic alternatives to glucocorticoids in GCA. PMID:25877501

  1. 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

  2. Giant cell tumours in fingers among the Inuit population in Greenland

    PubMed Central

    Duelund, Nick; Hougaard, Kjeld

    2016-01-01

    Objective Giant cell tumours (GCTs) of the tendon sheets in fingers are rare. We therefore find it of interest to report on 5 cases identified in the Inuit population in Greenland within 16 months prior to this study. Material and methods The Inuit account for 56,000 people of the total population in Greenland. From November 2010 to 16 months prior to this study, we diagnosed 5 cases (0.6% of all orthopaedic operations) with a GCT of the flexor tendon sheet of a finger. The patients were aged between 10 and 54 years, and 4 were women. All of them had noticed slow-growing tumours over 3 or more years and were referred for a suspected ganglion. Results In two cases, the tumour was located at the distal interphalangeal (DIP) joint in the thumb and in one case at the third finger. Two other patients had tumours at the metacarpophalangeal (MCP) joint of the third finger and the thumb, respectively; one of these two had a communicating tumour to the DIP joint. The last patient had two tumours on the same finger, one at the MCP joint and the other at the DIP joint. In one case, the tumour had also eroded the cortex of the first phalanx of the thumb, and the largest tumour measured 5 cm. Conclusion GCTs of the flexor tendon sheets in fingers are rare. It could be a coincidence that we have seen 5 cases within a short period of time. It is not possible to identify past cases through a register. A tumour in a finger is not the most common location for a ganglion, especially not at the DIP level. Therefore, a large tumour at this location is more likely to be a GCT. PMID:27052154

  3. 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

  4. Platelets Direct Monocyte Differentiation Into Epithelioid-Like Multinucleated Giant Foam Cells With Suppressive Capacity Upon Mycobacterial Stimulation

    PubMed Central

    Feng, Yonghong; Dorhoi, Anca; Mollenkopf, Hans-Joachim; Yin, Hongyun; Dong, Zhengwei; Mao, Ling; Zhou, Jun; Bi, Aixiao; Weber, Stephan; Maertzdorf, Jeroen; Chen, Gang; Chen, Yang; Kaufmann, Stefan H. E.

    2014-01-01

    Background. Epithelioid, foam, and multinucleated giant cells (MNGCs) are characteristics of tuberculosis granulomas, yet the precise genesis and functions of these transformed macrophages are unclear. We evaluated the role of platelets as drivers of macrophage transformation in mycobacterial infection. Methods. We employed flow cytometry and microscopy to assess cellular phenotype and phagocytosis. Immune assays allowed quantification of cytokines and chemokines, whereas gene microarray technology was applied to estimate global transcriptome alterations. Immunohistochemical investigations of tuberculosis granulomas substantiated our findings at the site of infection. Results. Monocytes differentiated in presence of platelets (MP-Macs) acquired a foamy, epithelioid appearance and gave rise to MNGCs (MP-MNGCs). MP-Macs up-regulated activation markers, phagocytosed mycobacteria, and released abundant interleukin 10. Upon extended culture, MP-Macs shared transcriptional features with epithelioid cells and M2 macrophages and up-regulated CXCL5 transcripts. In line with this, CXCL5 concentrations were significantly increased in airways of active tuberculosis patients. The platelet-specific CD42b antigen was detected in MP-Macs, likewise in macrophages, MNGCs, and epithelioid cells within tuberculosis granulomas, along with the platelet aggregation-inducing factor PDPN. Conclusions. Platelets drive macrophage differentiation into MNGCs with characteristics of epithelioid, foam, and giant cells observed in tuberculosis granulomas. Our data define platelets as novel participants in tuberculosis pathogenesis. PMID:24987031

  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. Osteoclast-Like Giant Cell Tumor of the Parotid Gland: Report of a Case Diagnosed on Fine-Needle Aspiration Cytology With Histological and Immunohistochemical Findings.

    PubMed

    Elhence, Poonam; Rao, Meenakshi; Goyal, Amit; Kumar, Amit; Khera, Pushpinder S; Bhattacharya, Shilajit

    2016-06-01

    Extraosseous giant cell tumors have been described in organs like larynx, thyroid, pancreas, heart, skin, lung, colon, kidney, and soft tissues (Wu et al., Oncol Lett 2013;6:829-832). Osteoclast-like giant cell tumor of the parotid gland has been reported only rarely with the first description of primary giant cell tumour of the parotid gland (GCTPs) given in 1984 by Eusebi et al. (Am J Clin Pathol. 1984;81:666-675). However, FNAC of osteoclast-like giant cell tumor of the parotid gland has not been well described, and only one case has been reported till date (Torabinezad et al., Acta Cytol. 2006;50:80-83). Two presentations have been observed in the form of either an isolated giant cell tumor (Eusebi et al., Am J Clin Pathol. 1984;81:666-675) or tumor associated with a carcinomatous component (Yang et al., Korean J Pathol 2012;46:297-301; Pasricha et al., J Can Res Ther 2013;9:314-316). GCTPs are uncommon benign soft tissue tumors with a malignant potential. Diagn. Cytopathol. 2016;44:548-551. © 2016 Wiley Periodicals, Inc. PMID:27079183

  7. Distal ulna giant cell tumor resection with reconstruction using distal ulna prosthesis and brachioradialis wrap soft tissue stabilization.

    PubMed

    Burke, Charity S; Gupta, Amit; Buecker, Peter

    2009-12-01

    This is a surgical technique report concerning the treatment of a 32-year-old male who had a giant cell tumor of distal ulna with suspected metastatic disease to the lungs. Three curettage procedures and a Darrach procedure were performed at an outlying facility. Upon the fourth reoccurrence, the patient was referred to our facility. It was established that the patient needed a distal ulna en bloc resection. To accommodate his activity requirements, reconstruction of the sigmoid notch and distal ulna was undertaken using a prosthesis. Soft tissue stabilization of the prosthesis was a challenge due to his previous procedures. This was accomplished using a brachioradialis tendon wrap. PMID:19370378

  8. Malignant Tenosynovial Giant Cell Tumor of the Leg: A Radiologic-Pathologic Correlation and Review of the Literature

    PubMed Central

    Richman, Danielle M; Bresler, Scott C; Rosenthal, Michael H; Howard, Stephanie Anne Holler

    2015-01-01

    Malignant tenosynovial giant cell tumor (TGCT) is a rare clinical entity that can arise as a recurrent lesion or can co-exist with a benign TGCT lesion. Malignant TGCT most commonly arises in the lower extremity and tends to be clinically aggressive, with most patients developing recurrent lesions or dying. Much of the literature describes the histopathologic features and classifies this broad group of tumors, with little description of the imaging characteristics of this disease. We present the multimodality appearance of a case of malignant diffuse-type TGCT that recurred 2 months after resection with subsequent rapid clinical progression. PMID:25861547

  9. Tenosynovial Giant Cell Tumor of Diffuse Type Mimicking Bony Metastasis Detected on F-18 FDG PET/CT.

    PubMed

    Chang, Kyoung Jin; Byun, Byung Hyun; Moon, Han Sol; Park, Jihyun; Koh, Jae Soo; Kim, Byung Il; Lim, Sang Moo

    2014-09-01

    Tenosynovial giant cell tumor of diffuse type (TGCT-D) is a locally aggressive neoplasm that arises in the tendon sheath, bursa, or synovium. It typically involves the appendicular skeleton and rarely involves the axial skeleton. Because there are no specific findings of TGCT-D based on imaging studies or clinical symptoms, TGCT-D can be confused with other primary or metastatic bone tumors. We report findings of TGCT-D involving the T9 vertebra incidentally detected on F-18 FDG PET/CT in a patient with papillary thyroid cancer. PMID:25177381

  10. Malignant tenosynovial giant cell tumor of the leg: a radiologic-pathologic correlation and review of the literature.

    PubMed

    Richman, Danielle M; Bresler, Scott C; Rosenthal, Michael H; Howard, Stephanie Anne Holler

    2015-01-01

    Malignant tenosynovial giant cell tumor (TGCT) is a rare clinical entity that can arise as a recurrent lesion or can co-exist with a benign TGCT lesion. Malignant TGCT most commonly arises in the lower extremity and tends to be clinically aggressive, with most patients developing recurrent lesions or dying. Much of the literature describes the histopathologic features and classifies this broad group of tumors, with little description of the imaging characteristics of this disease. We present the multimodality appearance of a case of malignant diffuse-type TGCT that recurred 2 months after resection with subsequent rapid clinical progression. PMID:25861547

  11. Challenges in imaging and histopathological assessment of a giant cell tumour with secondary aneurysmal cyst in the patella

    PubMed Central

    Low, Soo Fin; Hanafiah, Mohammad; Nurismah, Md Isa; Suraya, Aziz

    2013-01-01

    The patella is an uncommon site for all primary and metastatic bone tumours and primary intra-osseous tumours of the patella are very rare. A majority of the patella tumours are benign. We report a patient with a sudden onset swelling and pain of the right knee following a staircase fall. The plain radiograph showed an expansile multiseptated patella lesion and it was further assessed with an MRI. The radiological findings and the initial histopathological features from a limited sample were suggestive of a primary aneurysmal bone cyst. However, the final histopathological diagnosis from a more adequate specimen was a giant cell tumour with a secondary aneurysmal bone cyst. PMID:24057334

  12. 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.

  13. 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.

  14. Metabolism Is Central to Tolerogenic Dendritic Cell Function

    PubMed Central

    Sim, Wen Jing; Ahl, Patricia Jennifer; Connolly, John Edward

    2016-01-01

    Immunological tolerance is a fundamental tenant of immune homeostasis and overall health. Self-tolerance is a critical component of the immune system that allows for the recognition of self, resulting in hyporeactivity instead of immunogenicity. Dendritic cells are central to the establishment of dominant immune tolerance through the secretion of immunosuppressive cytokines and regulatory polarization of T cells. Cellular metabolism holds the key to determining DC immunogenic or tolerogenic cell fate. Recent studies have demonstrated that dendritic cell maturation leads to a shift toward a glycolytic metabolic state and preferred use of glucose as a carbon source. In contrast, tolerogenic dendritic cells favor oxidative phosphorylation and fatty acid oxidation. This dichotomous metabolic reprogramming of dendritic cells drives differential cellular function and plays a role in pathologies, such as autoimmune disease. Pharmacological alterations in metabolism have promising therapeutic potential. PMID:26980944

  15. Peripheral synapses and giant neurons in whip spiders.

    PubMed

    Foelix, Rainer; Troyer, David; Igelmund, Peter

    2002-08-15

    Among invertebrates the synapses between neurons are generally restricted to ganglia, i.e., to the central nervous system (CNS). As an exception, synapses occur in the sensory nerves of arachnid legs, indicating that some nervous integration is already taking place far out in the periphery. In the antenniform legs of whip spiders (Amblypygi), a very special synaptic circuit is present. These highly modified legs contain several large interneurons (giant neurons) that receive mechanosensory input from 700-1,500 tarsal bristles. Some of the sensory cell axons contact a giant neuron at its short, branched dendrite, a few at the soma, but most synapse onto the long giant axon. The fine structure of these synapses resembles that of typical chemical synapses in other arthropods. Although thousands of sensory fibers converge on a single giant neuron, there is no reduction in the actual number of sensory fibers, because these afferent fibers continue their course to the CNS after having made several en passant synapses onto the giant neuron. Touching a single tarsal bristle is sufficient to elicit action potentials in a giant neuron. Owing to the large diameter of the giant axon (10-20 microm), the action potentials reach the CNS within 55 ms, at conduction velocities of up to 7 m/s. However, mechanical stimulation of the tarsal bristles does not elicit a fast escape response, in contrast to giant fiber systems in earthworms, certain insects, and crayfishes. A quick escape is observed in whip spiders, but only after stimulation of the filiform hairs (trichobothria) on the regular walking legs. Although the giant fiber system in the antenniform legs undoubtedly provides a fast sensory pathway, its biological significance is not clearly understood at the moment. PMID:12214295

  16. 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

  17. Giant-cell arteritis without cranial manifestations: Working diagnosis of a distinct disease pattern.

    PubMed

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

    2016-06-01

    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 F-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 a lower rate of

  18. 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

  19. 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

  20. Associations between polymyalgia rheumatica and giant cell arteritis and 12 cardiovascular diseases

    PubMed Central

    Pujades-Rodriguez, Mar; Duyx, Bram; Thomas, Sara L; Stogiannis, Dimitris; Smeeth, Liam; Hemingway, Harry

    2016-01-01

    Objectives Evidence of the association of polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) with the full range of cardiovascular diseases (CVDs) is limited. We examined their relationship with the first clinical presentation of the 12 most common CVDs in an unselected population-based cohort of men and women. Methods We analysed CArdiovascular disease research using LInked Bespoke studies and Electronic health Records (CALIBER) data, which links primary care and hospital and mortality data in England, from 1997 to 2010. We assembled a cohort of men and women initially free from CVD at baseline and included all patients with PMR and/or GCA (PMR/GCA) diagnosis, matched by age, sex and general practice with up to 10 individuals without PMR/GCA. Random effects Poisson regression analysis was used to study the association between PMR/GCA and the initial presentation of 12 types of CVDs. Results The analysis included 9776 patients with PMR only, 1164 with GCA only, 627 with PMR and GCA and 105 504 without either condition. During a median of 3.14 years of follow-up 2787 (24.1%) individuals with PMR/GCA and 21 559 (20.4%) without PMR/GCA developed CVDs. Patients with PMR/GCA had lower rates of unheralded coronary death (3.18 vs 3.61/1000 person-years; adjusted incidence ratio 0.79, 95% CI 0.66 to 0.95), transient ischaemic attack (5.11 vs 5.61/1000 person-years; 0.67, 95% CI 0.54 to 0.84) and coronary and death composite (24.17 vs 25.80/1000 person-years; 0.90, 95% CI 0.82 to 0.98). No associations were observed for other CVDs or cerebrovascular diseases, and in patients with only PMR or GCA. No evidence of interaction by age or sex was found. Estimates decreased with longer PMR/GCA duration and findings were robust to multiple sensitivity analyses. Conclusions In this large contemporary population-based cohort the presence of PMR and/or GCA was not associated with an increased risk of CVDs or cerebrovascular diseases regardless of PMR/GCA duration. PMID

  1. Vision Loss due to Central Retinal Artery Occlusion Following Embolization in a Case of a Giant Juvenile Nasopharyngeal Angiofibroma.

    PubMed

    Trivedi, Mihir; Desai, Roshani J; Potdar, Nayana A; Shinde, Chhaya A; Ukirde, Vivek; Bhuta, Maunil; Nair, Akshay Gopinathan

    2015-07-01

    Juvenile nasopharyngeal angiofibroma (JNA) is a benign, vascular, and locally aggressive tumor that arises in the nasal cavity, extending into the nasopharynx and often in to the orbit. It may rarely present to the ophthalmologist with proptosis and optic neuropathy. Preoperative embolization of JNA is done before surgical resection. In this communication, the authors report a rare occurrence of ipsilateral central retinal artery occlusion (CRAO) following embolization with polyvinyl alcohol in a 13-year-old boy with right-sided JNA. Retrospective review of the angiograms pointed out to a suspicious communication between the external carotid artery and the ophthalmic vessels. Pre-embolization detailed study of the angiograms is necessary to avoid such devastating complications. Although rare, vision loss is a possible complication arising from embolization of nasopharyngeal and intracranial tumors, and all patients undergoing these procedures should be informed of the risk of visual loss because it has a lasting impact on the quality of life. PMID:26167999

  2. Inhibitory effect of bone morphogenetic protein-2 on the proliferation of giant cell tumor of bone stromal cells in vitro

    PubMed Central

    HE, BAOHUA; HE, GUANPING; ZHENG, XIAOFEI; LI, LIHUA; LI, MEI; XIA, HONG

    2016-01-01

    The inhibitory effect of bone morphogenetic protein-2 (BMP-2) on the proliferation of giant cell tumor of bone stromal cells (GCTSCs) has not been fully elucidated. Therefore, the aim of this study was to evaluate the role of recombinant human BMP-2 (rhBMP-2) in the growth of GCTSCs. The effects of exposure to different concentrations of rhBMP-2 (0, 10, 100 and 300 ng/ml) for 1, 3, 5 and 7 days on GCTSC proliferation were examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. In addition, the effect of treatment with rhBMP-2 (0 or 10 ng/ml) for 48 h on the cell cycle pattern of GCTSCs was examined by flow cytometry. The apoptosis-inducing effect of rhBMP-2 (0 or 10 ng/ml) in GCTSCs was also determined by flow cytometry after 48 and 72 h. In addition, western blot assays were conducted to determine whether rhBMP-2 acts on non-Smad mitogen-activated protein kinase (MAPK) signaling pathways, namely extracellular signal-regulated kinase (ERK1/2), p38 and c-jun-N-terminal kinase (JNK) pathways. The proliferation of GCTSCs treated with rhBMP-2 (10, 100 or 300 ng/ml) for 5 or 7 days was significantly inhibited in a non dose-dependent and non-time-dependent manner (P<0.05). The treatment of GCTSCs with rhBMP-2 (10 ng/ml) for 48 h had no effect on cell cycle distribution. The apoptosis of GCTSCs induced by exposure to rhBMP-2 (10 ng/ml) for 48 or 72 h was significant (P<0.05). Expression levels of phospho-ERK1/2, phospho-p38 and phospho-JNK increased significantly when GCTSCs were treated with rhBMP-2 (10 ng/ml) for 72 h (P<0.05). The results indicate that rhBMP-2 has no stimulatory effect on GCTSC growth. However, it may lead to the apoptosis of GCTSCs by non-Smad MAPK signaling pathways. PMID:26889259

  3. 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

  4. Giant cell tumor of the tendon sheath originating from the ankle capsule: A case report and literature review

    PubMed Central

    CHEN, YU; YU, XIU-CHUN; XU, SONG-FENG; WANG, BING

    2016-01-01

    Giant cell tumor of the tendon sheath (GCTTS), also termed tendosynovial giant cell tumor, is a benign, slow-growing tumor that originates from the tendon sheath or bursa. GCTTS of the foot and ankle is much less frequently reported compared with GCTTS of the hand and knee. However, GCTTS should be considered as a differential diagnosis of soft tissue tumors of the foot and ankle. The optimal treatment strategy for GCTTS in the foot and ankle is controversial due to a scarcity of cases. The present study reports the case of a patient that presented with localized intra-articular GCTTS originating from the capsule of the ankle, which is a rare anatomical location for this tumor. Considering the proximity of the tumor to the adjacent non-tumorous structures, a less radical but complete resection of the tumor was performed, followed by a hydrogen peroxide lavage. There was no evidence of recurrence during a follow-up period of 12 months, and adjuvant radiotherapy was not administered to the patient. A pre-operative diagnosis for GCTTS in the foot and ankle is mainly based on the findings of clinical examination and magnetic resonance imaging, which also facilitates the determination of a surgical strategy. For a localized tumor, an integral resection, as opposed to a radical resection, with a hydrogen peroxide lavage may result in a favorable prognosis. However, the optimal treatment for diffuse GCTTS remains to be identified. PMID:27123136

  5. 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

  6. Analysis of the B cell repertoire against autoantigens in patients with giant cell arteritis and polymyalgia rheumatica

    PubMed Central

    SCHMITS, R; KUBUSCHOK, B; SCHUSTER, S; PREUSS, K-D; PFREUNDSCHUH, M

    2002-01-01

    The analysis of the antibody repertoire of patients with giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) might identify target antigens of the autoimmune response with potential relevance to our understanding of the pathogenesis of the disease and to the development of serodiagnostic tests. To detect such antigens, we screened a cDNA library derived from normal human testis for antigens reacting with IgG antibodies in the 1:250 diluted sera of three patients with untreated GCA using SEREX, the serological identification of antigens by recombinant cDNA expression cloning. Of 100 000 clones screened with each serum, six, 28 and six clones, respectively, were positive, representing a total of 33 different antigens. Most of the antigens reacted only with the serum used for identification and/or at a similar frequency with normal control sera. However, lamin C and the nuclear antigen of 14 kD reacted specifically with 32% of GCA/PMR, but with none of the control sera, while human cytokeratin 15, mitochondrial cytochrome oxidase subunit II, and a new gene product were detected preferentially, but not exclusively by sera from GCA/PMR patients. We conclude that patients with GCA/PMR develop antibodies against a broad spectrum of human autoantigens. Antibodies against human lamin C, the nuclear autoantigen of 14 kD as well as human cytokeratin 15, mitochondrial cytochrome oxidase subunit II and the product of a new gene should be investigated further to determine their value as tools for the diagnosis and/or the definition of clinical subgroups of patients with GCA/PMR. PMID:11876765

  7. Human neural progenitor cells in central nervous system lesions.

    PubMed

    Åkesson, Elisabet; Sundström, Erik

    2016-02-01

    Various immature cells can be isolated from human embryonic and fetal central nervous system (CNS) residual tissue and potentially be used in cell therapy for a number of neurological diseases and CNS insults. Transplantation of neural stem and progenitor cells is essential for replacing lost cells, particularly in the CNS with very limited endogenous regenerative capacity. However, while dopamine released from transplanted cells can substitute the lost dopamine neurons in the experimental models of Parkinson's disease, stem and progenitor cells primarily have a neuroprotective effect, probably through the release of trophic factors. Understanding the therapeutic effects of transplanted cells is crucial to determine the design of clinical trials. During the last few years, a number of clinical trials for CNS diseases and insults such as amyotrophic lateral sclerosis (ALS), stroke, and spinal cord trauma using neural progenitor cells have been initiated. Data from these early studies will provide vital information on the safety of transplanting these cells, which still is a major concern. That the beneficial results observed in experimental models also can be repeated in the clinical setting is highly hoped for. PMID:26803559

  8. HMGB1: The Central Cytokine for All Lymphoid Cells

    PubMed Central

    Li, Guanqiao; Liang, Xiaoyan; Lotze, Michael T.

    2013-01-01

    High-mobility group box 1 (HMGB1) is a leaderless cytokine, like the IL-1 and FGF family members, that has primary roles within the nucleus and the cytosol. Within the nucleus, it serves as another guardian of the genome, protecting it from oxidant injury and promoting access to transcriptional complexes such as nuclear hormone/nuclear hormone receptors and p53/p73 complexes. Within the cytosol it promotes autophagy and recruitment of the myddosome to Toll-like receptor (TLR) 9 vesicular compartments. Outside of the cell, it can either bind to specific receptors itself, or with high affinity to DNA, nucleosomes, IL-1β, lipopolysaccharide, and lipoteichoic acid to mediate responses in specific physiological or pathological conditions. Currently identified receptors include TLR2, TLR4, the receptor for advanced glycation end products, CD24-Siglec G/10, chemokine CXC receptor 4, and TIM-3. In terms of its effects or functions within lymphoid cells, HMGB1 is principally secreted from mature dendritic cells (DCs) to promote T-cell and B-cell reactivity and expansion and from activated natural killer cells to promote DC maturation during the afferent immune response. Some studies suggest that its primary role in the setting of chronic inflammation is to promote immunosuppression. As such, HMGB1 is a central cytokine for all lymphoid cells playing a role complementary to its better studied role in myeloid cells. PMID:23519706

  9. 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

  10. 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

  11. Chronic Opioid Therapy and Central Sensitization in Sickle Cell Disease.

    PubMed

    Carroll, C Patrick; Lanzkron, Sophie; Haywood, Carlton; Kiley, Kasey; Pejsa, Megan; Moscou-Jackson, Gyasi; Haythornthwaite, Jennifer A; Campbell, Claudia M

    2016-07-01

    Chronic opioid therapy (COT) for chronic non-cancer pain is frequently debated, and its effectiveness is unproven in sickle cell disease (SCD). The authors conducted a descriptive study among 83 adult SCD patients and compared the severity of disease and pain symptoms among those who were prescribed COT (n=29) with those who were not using COT. All patients completed baseline laboratory pain assessment and questionnaires between January 2010 and June 2014. Thereafter, participants recorded daily pain, crises, function, and healthcare utilization for 90 days using electronic diaries. Analyses were conducted shortly after the final diary data collection period. Patients on COT did not differ on age, sex, or measures of disease severity. However, patients on COT exhibited greater levels of clinical pain (particularly non-crisis); central sensitization; and depression and increased diary measures of pain severity, function, and healthcare utilization on crisis and non-crisis diary days, as well as a greater proportion of days in crisis. Including depressive symptoms in multivariate models did not change the associations between COT and pain, interference, central sensitization, or utilization. Additionally, participants not on COT displayed the expected positive relationship between central sensitization and clinical pain, whereas those on COT demonstrated no such relationship, despite having both higher central sensitization and higher clinical pain. Overall, the results point out a high symptom burden in SCD patients on COT, including those on high-dose COT, and suggest that nociceptive processing in SCD patients on COT differs from those who are not. PMID:27320469

  12. 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

  13. Cannibalism in a benign soft tissue tumor (giant-cell tumor of the tendon sheath, localized type): a study of 66 cases.

    PubMed

    Fernandez-Flores, A

    2012-01-01

    Cellular cannibalism refers to a phenomenon where a living cell is phagocytosed into a tumoral cell, where it eventually dies. With the exception of cells in suspension, cellular cannibalism has only been observed with malignant tumors. The finding of occasional images of cannibalism in our daily biopsies of giant cell tumors of the tendon sheath led us to examine this phenomenon further in a retrospective study of 66 cases from our archives. In each case, four morphological features were evaluated: evidence of giant cells, cannibalism, xanthomatous cells, and hemosiderin deposits. Five cases were randomly selected for further immunohistochemical study with the following antibodies: CD68, vimentin, leukocytary common antigen (LCA), Bcl-2 oncoprotein, p53, caspase-3, and Bax. Patients included 35 (53.03%) females and 31 (46.97%) males. Mean age was 50.73 years (range from 14 to 75 years). Giant cells were found in all cases but one (98.48%). Cannibalism was found in 56 cases (84.34%) and this phenomenon was graded as 1 in 35 cases, 2 in 13 cases, and 3 in six cases. The internalized cells frequently appeared apoptotic. Immunohistochemical analysis revealed that the internalized cells as well as the cannibal cells expressed CD68. PMID:22395494

  14. Isolation of functional giant smooth muscle cells from an invertebrate: structural features of relaxed and contracted fibers.

    PubMed Central

    Hernandez-Nicaise, M L; Bilbaut, A; Malaval, L; Nicaise, G

    1982-01-01

    The giant smooth muscle fibers of a ctenophore were isolated by enzymatic digestion. These fibers are multinucleated cells, up to 50 micrometers in diameter and 2 cm in length. Their ultrastructure and membrane electrical properties are similar to those of in situ fibers. Relaxed, coiled (partially contracted), and fully shortened states were distinguished in isolated cells and studied by scanning and transmission electron microscopy. Calcium-containing mitochondrial granules were found in the coiled cells but not in either the relaxed or the fully shortened cells. The relaxed cell is characterized in cross section by the density of myosin filaments (457 +/- 15 per micrometer2) and the thin-to-thick filament ratio (5.2 +/- 0.2). In the coiled cell, the muscle lattice does not expand uniformly, as shown by the variability of myosin spacing, and the thin-to-thick filament ratio decreases. Both clockwise and counterclockwise coiling occur along the same fiber. The implications of these findings with respect to the structure of the contractile apparatus are discussed. Images PMID:6952237

  15. Giant Cell Tumour of the Tendon Sheath: Analysis of 35 Cases and their Ki-67 Proliferation Indexes

    PubMed Central

    Balik, Mehmet Sabri; Sehitoglu, Ibrahim; Güçer, Hasan; Yurdakul, Cüneyt

    2014-01-01

    Introduction: A giant cell Tumour of the tendon sheath (GCTTS) is a slow-growing benign Tumour originating from the synovial cells of the tendon sheath. It is the second most common Tumour of the hand. The aim of this study was to perform a retrospective clinicopathological evaluation of GCTTS cases and determine whether the proliferative activity of giant cell tumour of tendon sheath is related to its recurrence rate and local aggressiveness. Materials and Methods: The age, gender, Tumour location and diameter, treatment mode, Ki-67 proliferation index, mitotic rate, and recurrence were retrospectively evaluated in 35 patients diagnosed with GCTTS in the Department of Pathology, School of Medicine, Recep Tayyip Erdogan University between 2009 and 2014. Results: Of the 35 GCTTS cases, 23 were female, and 12 were male. The mean age was 45 y (range 10–70). Sixteen tumours were located in the right hand and 14 in the left hand, and five were in the feet. The mean Tumour diameter was 2.3 cm (0.6–6 cm). All patients underwent marginal excision. The mean postoperative follow-up period was 4 y (range 28 months–5 y). Only six patients showed recurrence. In these cases, the site of GCTTS recurrence was the phalanx of the hand. The mean Ki-67 index in the recurrence cases was 6.5%, whereas it was 2.3% in those without recurrence. Conclusion: The Ki-67 proliferation index and mitotic activity were increased in recurrent cases compared to nonrecurrent cases. Therefore, these parameters may be helpful in predicting recurrence of GCTTS. However, adequate surgical excision and complete removal of the Tumour are important steps to minimize the recurrence rate. PMID:25653956

  16. 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.

  17. 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

  18. Undifferentiated carcinoma of the pancreas with osteoclast-like giant cells: a rare case report and review of the literature

    PubMed Central

    Sah, Shambhu K; Li, Ying; Li, Yongmei

    2015-01-01

    Undifferentiated carcinoma of the pancreas with osteoclast-like giant cells (UCPOGC) is an extremely rare non-endocrine pancreatic tumor. To date, some cases have been reported, however, histogenesis and biologic behavior of UCPOGC remain controversial. We report a case of an UCPOGC in a 54-year-old female, who presented with a three-month history of recurrent abdominal pain without any incentive. Abdominal computed tomography (CT) revealed a large cystic mass of 10.5 × 9.3 cm in the body and tail of the pancreas compressing the adjacent bowel loop and stomach. The preliminary diagnosis was considered as a malignant tumor of body and tail of the pancreas. The patient had open distal pancreatic mass resection with splenectomy and according to the results of histopathological and immunohistochemical studies, the diagnosis of an UCPOGC was established. PMID:26617927

  19. Arthroscopic excision of giant cell tumor of the tendon sheath in the knee mimicking patellar tendinopathy: A case report

    PubMed Central

    GAO, KAI; CHEN, JIWU; CHEN, SHIYI; LI, YUNXIA

    2016-01-01

    Giant cell tumor of the tendon sheath (GCTTS) predominantly occurs in the tendon sheaths of the hand, but rarely in those of the knee. The current study reports the case of a 36-year-old male patient presenting with anterior knee pain. The patient was ultimately diagnosed with GCTTS in the knee mimicking patellar tendinopathy. To the best of our knowledge, this is the first case of its kind. Magnetic resonance imaging revealed a well-defined oval intra-articular lesion located at the proximal segment of the infrapatellar fat pad. The lesion was completely excised under arthroscopy and pathological examination confirmed the diagnosis of GCTTS. There was no evidence of recurrence at the 2-year follow-up examination. The findings of the present study suggest that, despite its rarity, GCTTS should be considered in the differential diagnosis of patellar tendinopathy. PMID:27123148

  20. Comparison of tumor curettage and resection for treatment of giant cell tumor of the bone around the knee joint

    PubMed Central

    Zhang, Sheng; Zhang, Jianhua; Wang, Xin

    2016-01-01

    Objective: To analyze the efficacies of tumor curettage and resection for treatment of giant cell tumor of the bone (GCTB) around the knee joint (KJ). Methods: A total of 126 KJ-GCTB cases were treated at our department from August 2011 to February 2015. These cases were divided into two groups (A and B) according to treatment methods. Group A underwent tumor curettage, while group B underwent tumor resection. Results: The relapse rates did not differ significantly between the groups (P>0.05), while the complication rate in group A was significantly lower than that in group B (P<0.05). In addition, the Enneking score for group A was significantly higher than that for group B (P<0.05); in addition, postoperative local recurrence, histopathological grading according to Jaffe, and radiographic imaging-based Campanacci’s staging positively correlated (P<0.05). Conclusion: Tumor curettage was the preferred surgical approach for patients with KJ-GCTB.

  1. Baseline clinical predictors of an ultimate giant cell arteritis diagnosis in patients referred to temporal artery biopsy.

    PubMed

    Grossman, Chagai; Barshack, Iris; Koren-Morag, Nira; Ben-Zvi, Ilan; Bornstein, Gil

    2016-07-01

    The diagnosis of giant cell arteritis (GCA) is based on clinical grounds and confirmed by characteristic histological findings on temporal artery biopsy (TAB). Patients may be diagnosed with GCA based on clinical grounds only, despite negative histological findings. We aimed to investigate which baseline clinical and laboratory features best predict an ultimate diagnosis of giant cell arteritis among patients referred to TAB. We retrospectively analyzed 224 patients who underwent TAB in our hospital between 2000 and 2014. Patients were diagnosed with GCA if TAB was positive for GCA, or by clinical grounds only despite a negative biopsy, provided they fulfilled the American College of Rheumatology 1990 criteria. Baseline clinical and laboratory features were obtained from medical records. Predictors of an ultimate GCA diagnosis were investigated. Overall, 82 patients were diagnosed with GCA-57 had histological evidence of GCA and 25 were diagnosed with GCA despite a negative biopsy. One hundred and forty-two patients were not diagnosed with GCA. Predictors of an eventual diagnosis of GCA in a multivariate logistic regression analysis were headache (OR = 6; p < 0.001), jaw claudication (OR 4.5; p = 0.007), erythrocyte sedimentation rate (ESR) (OR = 1.5; p = 0.032) and platelet count (OR = 1.74; p = 0.004). Among patients referred to TAB, headache, jaw claudication, ESR, and thrombocyte levels are predictors for an ultimate diagnosis of GCA. These clinical and laboratory features should be considered when contemplating the diagnosis and treatment of GCA. PMID:26925851

  2. 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

  3. Occupation and renal cell cancer in Central and Eastern Europe

    PubMed Central

    Heck, Julia E; Charbotel, Barbara; Moore, Lee E; Karami, Sara; Zaridze, David G; Matveev, Vsevolod; Janout, Vladimir; Kollárová, Helena; Foretova, Lenka; Bencko, Vladimir; Szeszenia-Dabrowska, Neonila; Lissowska, Jolanta; Mates, Dana; Ferro, Gilles; Chow, Wong-Ho; Rothman, Nathaniel; Stewart, Patricia; Brennan, Paul; Boffetta, Paolo

    2010-01-01

    Objective Central and Eastern Europe has among the highest rates of renal cell cancer worldwide. Few studies have been conducted in these areas to investigate the possible role of occupational exposures in renal cell cancer etiology. The purpose of this study was to examine the association of renal cell cancer with employment in specific occupations and industries. Methods From 1999–2003, we conducted a hospital-based case-control study in seven areas of the Czech Republic, Poland, Romania and Russia. A detailed occupational history was collected from renal cell cancer cases and controls, together with information on potential confounders. Odds ratios (OR) and 95% confidence intervals (CI) of cancer risk were calculated for having ever been employed in selected jobs and industries, with follow-up analyses examining duration of employment. Results A total of 992 histologically confirmed incident renal cell cancer cases and 1,465 controls were included in the analysis. An increased risk of renal cell cancer was observed for workers in agricultural labor and animal husbandry (OR=1.43, 95% CI 1.05, 1.93), particularly among women employed as general farm workers (OR=2.73, 95% CI 1.05, 7.13). Risk gradients for agricultural work increased with longer employment. An overall increased risk of renal cell cancer was seen among architects and engineers (OR=1.89, 95% CI 1.35, 2.65), and mechanical engineers (OR=1.71, 95% CI 1.03, 2.84). Conclusions Our data suggest an association between renal cell cancer and agricultural work, particularly among female workers. PMID:19737732

  4. Syn-volcanic cannibalisation of juvenile felsic crust: Superimposed giant 18O-depleted rhyolite systems in the hot and thinned crust of Mesoproterozoic central Australia

    NASA Astrophysics Data System (ADS)

    Smithies, R. H.; Kirkland, C. L.; Cliff, J. B.; Howard, H. M.; Quentin de Gromard, R.

    2015-08-01

    Eruptions of voluminous 18O-depleted rhyolite provide the best evidence that the extreme conditions required to produce and accumulate huge volumes of felsic magma can occur in the upper 10 km of the crust. Mesoproterozoic bimodal volcanic sequences from the Talbot Sub-basin in central Australia contain possibly the world's most voluminous accumulation of 18O-depleted rhyolite. This volcanic system differs from the better known, but geochemically similar, Miocene Snake River Plain - Yellowstone Plateau of North America. Both systems witnessed 'super' sized eruptions from shallow crustal chambers, and produced 18O-depleted rhyolite. The Talbot system, however, accumulated over a much longer period (>30 Ma), at a single depositional centre, and from a magma with mantle-like isotopic compositions that contrast strongly with the isotopically evolved basement and country-rock compositions. Nevertheless, although the Talbot rhyolites are exclusively 18O-depleted, the unavoidable inference of an 18O-undepleted precursor requires high-temperature rejuvenation of crust in an upper-crustal chamber, and in this respect the evolution of the Talbot rhyolites and 18O-depleted rhyolites of the Snake River Plain - Yellowstone Plateau is very similar. However, instead of older crustal material, the primary upper-crustal source recycled into Talbot rhyolites was comagmatic (or nearly so) felsic rock itself derived from a contemporaneous juvenile basement hot-zone. Whereas giant low δ18O volcanic systems show that voluminous melting of upper crust can occur, our studies indicate that felsic magmas generated at lower crustal depths can also contribute significantly to the thermal and material budget of these systems. The requirement that very high-temperatures be achieved and sustained in the upper crust means that voluminous low δ18O magmatism is rare, primarily restricted to bimodal tholeiitic, high-K rhyolite (A-type) magmatic associations in highly attenuated lithosphere. In the

  5. Compositional and fluorescence characteristics of the giant diatom Ethmodiscus along a 3000 km transect (28°N) in the central North Pacific gyre

    NASA Astrophysics Data System (ADS)

    Villareal, Tracy A.; McKay, R. M. L.; Al-Rshaidat, M. M. D.; Boyanapalli, R.; Sherrell, R. M.

    2007-08-01

    The giant diatom Ethmodiscus was examined along an east-west transect at 28-30°N during 2002 and 2003 to determine if abundance, chemical composition or physiological status of this largest of diatoms varied on the scale of 100's-1000's of km in North Pacific gyre. Abundance ranged from <0.1->2.0 cells m -3 and supported the notion of an abundance mosaic reported previously. However, there was only minimal support for the relationship between abundance and nutrient concentration at 125 m reported previously. Cellular chlorophyll varied little along the transect (7.3-10.9 ng chl cell -1) except at the westernmost station. Cellular N and P quotas co-varied 3-4.5 fold (mean=50.8±3.7 and 3.7±0.8 nmol N and P cell -1) and yielded N:P ratios that closely clustered around the Redfield ratio (average=14.6±1.1). Only low levels of chlorophyll-normalized alkaline phosphatase (APase) activity were observed (0.4-2.5 nmol P μg chl -1 h -1) with APase activity lower than that in either the bulk water, or co-occurring Trichodesmium spp. and Pyrocystis noctiluca. The active fluorescence parameter Fv: Fm, a property sensitive to Fe stress, was uniformly high at all stations (average=0.73±0.04 for 2003, and 0.69±0.05 for 2002), indicating sufficient Fe for optimum photosynthetic competence. These results contrasted sharply with results from Rhizosolenia mats reported along the same transect where there was a significant decline westward in Fv: Fm. Both ferredoxin (Fd) and flavodoxin accumulated in cells of Ethmodiscus, resulting in Fd Index values of<0.6. Iron cell quotas ranged from 0.7-5.1 pmol Fe cell -1. When normalized to cytoplasmic volume, the Fe μm -3 was comparable to that of Escherichia coli. We note that the disproportionate contribution of the vacuole (with its high organic content) to total volume typical of large diatoms is a potentially significant source of error in Fe:C ratios and suggest that Fe should be normalized to cytoplasmic volume whenever possible

  6. Aggressive giant cell lesion of the jaws: a review of management options and report of a mandibular lesion treated with denosumab.

    PubMed

    O'Connell, John Edward; Bowe, Conor; Murphy, Colm; Toner, Mary; Kearns, Gerard J

    2015-11-01

    Giant cell lesions (GCLs), previously referred to as giant cell granulomas, are benign tumors of the jaws of unknown etiology. Surgical management of aggressive GCLs is challenging, as these lesions demonstrate a tendency to recur following surgical removal. In addition, surgical treatment can be associated with significant morbidity. In an attempt to reduce both the extent of morbidity and the recurrence rate following surgery, a number of pharmacologic therapies have been advocated on the basis of assumptions about the predominant cell types and receptors, for the management of these lesions. This report describes the use of denosumab, an agent originally used for its anti-resorptive effects, in the management of an aggressive GCL of the mandible in an older patient, who was unsuitable for extensive surgery and in whom treatment with intralesional triamcinolone had proved unsuccessful. Denosumab may be a viable alternative or adjunct to surgery in the management of GCLs of the jaws. PMID:26340897

  7. Are astrocytes executive cells within the central nervous system?

    PubMed

    Sica, Roberto E; Caccuri, Roberto; Quarracino, Cecilia; Capani, Francisco

    2016-08-01

    Experimental evidence suggests that astrocytes play a crucial role in the physiology of the central nervous system (CNS) by modulating synaptic activity and plasticity. Based on what is currently known we postulate that astrocytes are fundamental, along with neurons, for the information processing that takes place within the CNS. On the other hand, experimental findings and human observations signal that some of the primary degenerative diseases of the CNS, like frontotemporal dementia, Parkinson's disease, Alzheimer's dementia, Huntington's dementia, primary cerebellar ataxias and amyotrophic lateral sclerosis, all of which affect the human species exclusively, may be due to astroglial dysfunction. This hypothesis is supported by observations that demonstrated that the killing of neurons by non-neural cells plays a major role in the pathogenesis of those diseases, at both their onset and their progression. Furthermore, recent findings suggest that astrocytes might be involved in the pathogenesis of some psychiatric disorders as well. PMID:27556379

  8. Spin-Glass Behavior in a Giant Unit Cell Compound Tb117Fe52Ge113.8(1)

    SciTech Connect

    Liu, Jing; Xie, Weiwei; Gschneidner, Karl A; Miller, Gordon J; Pecharsky, Vitalij K

    2014-10-15

    In this paper we demonstrate evidence of a cluster spin glass in Tb117Fe52Ge113.8(1) (a compound with a giant cubic unit cell) via ac and dc magnetic susceptibility, magnetization, magnetic relaxation and heat capacity measurements. The results clearly show that Tb117Fe52Ge113.8(1) undergoes a spin glass phase transition at the freezing temperature, ~38 K. The good fit of the frequency dependence of the freezing temperature to the critical slowing down model and Vogel-Fulcher law strongly suggest the formation of cluster glass in the Tb117Fe52Ge113.8(1) system. The heat capacity data exhibit no evidence for long-range magnetic order, and yield a large value of Sommerfeld coefficient. The spin glass behavior of Tb117Fe52Ge113.8(1) may be understood by assuming the presence of competing interactions among multiple non-equivalent Tb sites present in the highly complex unit cell.

  9. Brain architecture of the largest living land arthropod, the Giant Robber Crab Birgus latro (Crustacea, Anomura, Coenobitidae): evidence for a prominent central olfactory pathway?

    PubMed Central

    2010-01-01

    Background Several lineages within the Crustacea conquered land independently during evolution, thereby requiring physiological adaptations for a semi-terrestrial or even a fully terrestrial lifestyle. Birgus latro Linnaeus, 1767, the giant robber crab or coconut crab (Anomura, Coenobitidae), is the largest land-living arthropod and inhabits Indo-Pacific islands such as Christmas Island. B. latro has served as a model in numerous studies of physiological aspects related to the conquest of land by crustaceans. From an olfactory point of view, a transition from sea to land means that molecules need to be detected in gas phase instead of in water solution. Previous studies have provided physiological evidence that terrestrial hermit crabs (Coenobitidae) such as B. latro have a sensitive and well differentiated sense of smell. Here we analyze the brain, in particular the olfactory processing areas of B. latro, by morphological analysis followed by 3 D reconstruction and immunocytochemical studies of synaptic proteins and a neuropeptide. Results The primary and secondary olfactory centers dominate the brain of B. latro and together account for ca. 40% of the neuropil volume in its brain. The paired olfactory neuropils are tripartite and composed of more than 1,000 columnar olfactory glomeruli, which are radially arranged around the periphery of the olfactory neuropils. The glomeruli are innervated ca. 90,000 local interneurons and ca. 160,000 projection neurons per side. The secondary olfactory centers, the paired hemiellipsoid neuropils, are targeted by the axons of these olfactory projection neurons. The projection neuron axonal branches make contact to ca. 250.000 interneurons (per side) associated with the hemiellipsoid neuropils. The hemiellipsoid body neuropil is organized into parallel neuropil lamellae, a design that is quite unusual for decapod crustaceans. The architecture of the optic neuropils and areas associated with antenna two suggest that B. latro has

  10. The epidemiological and clinical features of primary giant cell tumor around the knee: A report from the multicenter retrospective study in china

    PubMed Central

    Lin, Fengsong; Hu, Yongcheng; Zhao, Liming; Zhang, Huilin; Yu, Xiuchun; Wang, Zhen; Ye, Zhaoming; Wu, Sujia; Guo, Shibing; Zhang, Guochuan; Wang, Jinghua

    2016-01-01

    Objectives We aimed to determine the demographic characteristics of giant cell tumor around the knee in China. Methods Between March 2000 and June 2014, patients with primary giant cell tumor around the knee were recruited from 6 institutions located in different regions of China, and were reviewed retrospectively the clinical features according to gender and age. Results 334 qualified patients were included in this study. The sex ratio was 1.14:1 (178/156), with mean ages of 36.9 years in men and 33.1 years in women, constituting a significant difference (P=0.007). The prevalence of pathological fracture was 32.9% overall (28.7% in men and 37.8% in women). The prevalence of simple fracture was significantly higher in women (26.3%) than in men (15.2%), P=0.042. Tumor location and staging did not differ significantly according to sex (P>0.05). However, comparing with >40 years old, those patients aged ≤40 were more likely to have a right knee tumor (56.7% vs. 44.7%, P=0.042), less likely to have Enneking stage 3 disease (18.6% vs. 35.0%, P=0.005), and less likely to have both soft-tissue extension and a mass (18.6% vs. 34.0%, P=0.009). Conclusions Giant cell tumor around the knee was more common in men than in women, although female patients were younger on average. Further, cases among patients ≤40 years old were observed to be milder than cases among older patients. The results suggest that efficient treatment and preservation of function should both be valued for young patients with giant cell tumor around the knee. PMID:26998425

  11. Segmental pairs of giant insect cells discharge presumptive immune proteins at each larval molt.

    PubMed

    Nardi, James B; Bee, Charles M; Miller, Lou Ann; Imai, Brian S; Yau, Peter M

    2016-05-15

    A pair of massive secretory cells exists within each thoracic and the nine abdominal segments of Manduca larvae. Each of these cells is nestled between the dorsal integument and underlying muscles. Contents of large vacuoles in these cells are abruptly discharged at each molt and have always been considered to contribute to shedding and/or formation of cuticle. Peanut agglutinin is a specific lectin label for these secretory vacuoles; vacuoles label intensely immediately before each molt as vacuoles attain their maximal size. Contents of vacuoles are restored after each molt and throughout most of each intermolt. During the molt cycle these cells secrete contents of their vacuoles into the interior hemocoel rather than onto the exterior cuticle. Vacuoles discharge via a distinctive mechanism involving partitioning of contents into numerous vesicles that move to the cell surface. Dermal secretory cells were dissected from larvae before and after the 4th-5th instar molt. Proteins from pre-molt and post-molt secretory cells were separated by two-dimensional electrophoresis to establish which proteins are discharged at the molt. While secreted proteins are novel, all have presumptive roles in immune responses. Dermal secretory cells may represent a new, unsuspected component of the innate immune system that release their proteins during the vulnerable molting period of an insect's life. PMID:27039264

  12. g-force induced giant efficiency of nanoparticles internalization into living cells.

    PubMed

    Ocampo, Sandra M; Rodriguez, Vanessa; de la Cueva, Leonor; Salas, Gorka; Carrascosa, Jose L; Rodríguez, María Josefa; García-Romero, Noemí; Cuñado, Jose Luis F; Camarero, Julio; Miranda, Rodolfo; Belda-Iniesta, Cristobal; Ayuso-Sacido, Angel

    2015-01-01

    Nanotechnology plays an increasingly important role in the biomedical arena. Iron oxide nanoparticles (IONPs)-labelled cells is one of the most promising approaches for a fast and reliable evaluation of grafted cells in both preclinical studies and clinical trials. Current procedures to label living cells with IONPs are based on direct incubation or physical approaches based on magnetic or electrical fields, which always display very low cellular uptake efficiencies. Here we show that centrifugation-mediated internalization (CMI) promotes a high uptake of IONPs in glioblastoma tumour cells, just in a few minutes, and via clathrin-independent endocytosis pathway. CMI results in controllable cellular uptake efficiencies at least three orders of magnitude larger than current procedures. Similar trends are found in human mesenchymal stem cells, thereby demonstrating the general feasibility of the methodology, which is easily transferable to any laboratory with great potential for the development of improved biomedical applications. PMID:26477718

  13. g-force induced giant efficiency of nanoparticles internalization into living cells

    PubMed Central

    Ocampo, Sandra M.; Rodriguez, Vanessa; de la Cueva, Leonor; Salas, Gorka; Carrascosa, Jose. L.; Josefa Rodríguez, María; García-Romero, Noemí; Luis, Jose; Cuñado, F.; Camarero, Julio; Miranda, Rodolfo; Belda-Iniesta, Cristobal; Ayuso-Sacido, Angel

    2015-01-01

    Nanotechnology plays an increasingly important role in the biomedical arena. Iron oxide nanoparticles (IONPs)-labelled cells is one of the most promising approaches for a fast and reliable evaluation of grafted cells in both preclinical studies and clinical trials. Current procedures to label living cells with IONPs are based on direct incubation or physical approaches based on magnetic or electrical fields, which always display very low cellular uptake efficiencies. Here we show that centrifugation-mediated internalization (CMI) promotes a high uptake of IONPs in glioblastoma tumour cells, just in a few minutes, and via clathrin-independent endocytosis pathway. CMI results in controllable cellular uptake efficiencies at least three orders of magnitude larger than current procedures. Similar trends are found in human mesenchymal stem cells, thereby demonstrating the general feasibility of the methodology, which is easily transferable to any laboratory with great potential for the development of improved biomedical applications. PMID:26477718

  14. g-force induced giant efficiency of nanoparticles internalization into living cells

    NASA Astrophysics Data System (ADS)

    Ocampo, Sandra M.; Rodriguez, Vanessa; de La Cueva, Leonor; Salas, Gorka; Carrascosa, Jose. L.; Josefa Rodríguez, María; García-Romero, Noemí; Luis, Jose; Cuñado, F.; Camarero, Julio; Miranda, Rodolfo; Belda-Iniesta, Cristobal; Ayuso-Sacido, Angel

    2015-10-01

    Nanotechnology plays an increasingly important role in the biomedical arena. Iron oxide nanoparticles (IONPs)-labelled cells is one of the most promising approaches for a fast and reliable evaluation of grafted cells in both preclinical studies and clinical trials. Current procedures to label living cells with IONPs are based on direct incubation or physical approaches based on magnetic or electrical fields, which always display very low cellular uptake efficiencies. Here we show that centrifugation-mediated internalization (CMI) promotes a high uptake of IONPs in glioblastoma tumour cells, just in a few minutes, and via clathrin-independent endocytosis pathway. CMI results in controllable cellular uptake efficiencies at least three orders of magnitude larger than current procedures. Similar trends are found in human mesenchymal stem cells, thereby demonstrating the general feasibility of the methodology, which is easily transferable to any laboratory with great potential for the development of improved biomedical applications.

  15. The clinical and radiological evaluation of the use of an allograft-prosthesis composite in the treatment of proximal femoral giant cell tumours.

    PubMed

    Malhotra, R; Kiran Kumar, G N; K Digge, V; Kumar, V

    2014-08-01

    Giant cell tumour is the most common aggressive benign tumour of the musculoskeletal system and has a high rate of local recurrence. When it occurs in proximity to the hip, reconstruction of the joint is a challenge. Options for reconstruction after wide resection include the use of a megaprosthesis or an allograft-prosthesis composite. We performed a clinical and radiological study to evaluate the functional results of a proximal femoral allograft-prosthesis composite in the treatment of proximal femoral giant cell tumour after wide resection. This was an observational study, between 2006 and 2012, of 18 patients with a mean age of 32 years (28 to 42) and a mean follow-up of 54 months (18 to 79). We achieved excellent outcomes using Harris Hip Score in 13 patients and a good outcome in five. All allografts united. There were no complications such as infection, failure, fracture or resorption of the graft, or recurrent tumour. Resection and reconstruction of giant cell tumours with proximal femoral allograft-prosthesis composite is a better option than using a prosthesis considering preservation of bone stock and excellent restoration of function. A good result requires demanding bone banking techniques, effective measures to prevent infection and stability at the allograft-host junction. PMID:25086128

  16. 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

  17. Venous Thromboembolism and Cerebrovascular Events in Patients with Giant Cell Arteritis: A Population-Based Retrospective Cohort Study

    PubMed Central

    Crowson, Cynthia S.; Makol, Ashima; Ytterberg, Steven R.; Saitta, Antonino; Salvarani, Carlo; Matteson, Eric L.; Warrington, Kenneth J.

    2016-01-01

    Objective To investigate the incidence of venous thromboembolism (VTE) and cerebrovascular events in a community-based incidence cohort of patients with giant cell arteritis (GCA) compared to the general population. Methods A population-based inception cohort of patients with incident GCA between January 1, 1950 and December 31, 2009 in Olmsted County, Minnesota and a cohort of non-GCA subjects from the same population were assembled and followed until December 31, 2013. Confirmed VTE and cerebrovascular events were identified through direct medical record review. Results The study population included 244 patients with GCA with a mean ± SD age at diagnosis of 76.2 ± 8.2 years (79% women) and an average length of follow-up of 10.2 ± 6.8 years. Compared to non-GCA subjects of similar age and sex, patients diagnosed with GCA had a higher incidence (%) of amaurosis fugax (cumulative incidence ± SE: 2.1 ± 0.9 versus 0, respectively; p = 0.014) but similar rates of stroke, transient ischemic attack (TIA), and VTE. Among patients with GCA, neither baseline characteristics nor laboratory parameters at diagnosis reliably predicted risk of VTE or cerebrovascular events. Conclusion In this population-based study, the incidence of VTE, stroke and TIA was similar in patients with GCA compared to non-GCA subjects. PMID:26901431

  18. Pseudoangiomatous stromal hyperplasia with multinucleated stromal giant cells is neither exceptional in gynecomastia nor characteristic of neurofibromatosis type 1.

    PubMed

    Pižem, Jože; Velikonja, Mojca; Matjašič, Alenka; Jerše, Maja; Glavač, Damjan

    2015-04-01

    Six cases of gynecomastia with pseudoangiomatous stromal hyperplasia (PASH) and multinucleated stromal giant cells (MSGC) associated with neurofibromatosis type 1 (NF1) have been reported, and finding MSGC within PASH in gynecomastia has been suggested as being a characteristic of NF1. The frequency of PASH with MSGC in gynecomastia and its specificity for NF1 have not, however, been systematically studied. A total of 337 gynecomastia specimens from 215 patients, aged from 8 to 78 years (median, 22 years) were reevaluated for the presence of PASH with MSGC. Breast tissue samples of 25 patients were analyzed for the presence of an NF1 gene mutation using next generation sequencing. Rare MSGC, usually in the background of PASH, were noted at least unilaterally in 27 (13 %) patients; and prominent MSGC, always in the background of PASH, were noted in 8 (4 %) patients. The NF1 gene was mutated in only 1 (an 8-year-old boy with known NF1 and prominent MSGC) of the 25 tested patients, including 6 patients with prominent MSGC and 19 patients with rare MSGC. MSGC, usually in the background of PASH, are not characteristic of NF1. PMID:25586494

  19. 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

  20. L4 and L5 Spondylectomy for En Bloc Resection of Giant Cell Tumor and Review of the Literature

    PubMed Central

    Santiago-Dieppa, David R.; Hwang, Lee S.; Bydon, Ali; Gokaslan, Ziya L.; McCarthy, Edward F.; Witham, Timothy F.

    2014-01-01

    Study Design Case report and review of the literature. Objective We present the case of a two-level lumbar spondylectomy at L4 and L5 for en bloc resection of a giant cell tumor (GCT) and lumbopelvic reconstruction. Methods A 58-year-old woman presented with a 7-month history of progressive intractable back and leg pain secondary to a biopsy-proven Enneking stage III GCT of the L4 and L5 vertebrae. The patient underwent a successful L4–L5 spondylectomy and lumbopelvic reconstruction using a combined posterior and anterior approach over two operative stages. Results Postoperative complications included a deep wound infection and a cerebrospinal fluid leak; however, following surgical debridement and long-term antibiotic treatment, the patient was neurologically intact with minimal pain and there was no evidence of tumor recurrence or instrumentation failure at more than 2 years of follow-up. Conclusion Spondylectomy that achieves en bloc resection is a viable and effective treatment option that can be curative for Enneking stage III GCTs involving the lower lumbar spine. The lumbosacral junction represents a challenging anatomic location for spinal reconstruction after spondylectomy with unique technical considerations. PMID:25364329

  1. Blinded search for varicella zoster virus in giant cell arteritis (GCA)-positive and GCA-negative temporal arteries.

    PubMed

    Gilden, Don; White, Teresa; Khmeleva, Nelly; Katz, Bradley J; Nagel, Maria A

    2016-05-15

    Recent analysis of archived temporal arteries (TAs) acquired from 13 pathology laboratories in the US, Canada, Iceland, France, Germany and Israel from patients with pathologically-verified giant cell arteritis (GCA-positive) and TAs from patients with clinical features and laboratory abnormalities of GCA but whose TAs were pathologically negative (GCA-negative) revealed VZV antigen in most TAs from both groups. Despite formalin-fixation, VZV DNA was also found in many VZV-antigen positive sections that were scraped, subjected to DNA extraction, and examined by PCR with VZV-specific primers. Importantly, in past studies, the pathological diagnosis (GCA-positive or -negative) was known to the neurovirology laboratory. Herein, GCA-positive and GCA-negative TAs were provided by an outside institution and examined by 4 investigators blinded to the pathological diagnoses. VZV antigen was found in 3/3 GCA-positive TAs and in 4/6 GCA-negative TAs, and VZV DNA in 1/3 VZV antigen-positive, GCA-positive TAs and in 3/4 VZV antigen-positive, GCA-negative TAs. VZV DNA was also detected in one GCA-negative, VZV-antigen negative TA. Overall, the detection of VZV antigen in 78% of GCA-positive and GCA-negative TAs is consistent with previous reports on the prevalence of VZV antigen in patients with clinically suspect GCA. PMID:27084233

  2. Sex Differences in the Recurrence Rate and Risk Factors for Primary Giant Cell Tumors Around the Knee in China

    PubMed Central

    Hu, Yongcheng; Zhao, Liming; Zhang, Huilin; Yu, Xiuchun; Wang, Zhen; Ye, Zhaoming; Wu, Sujia; Guo, Shibing; Zhang, Guochuan; Wang, Jinghua; Ning, Xianjia

    2016-01-01

    Although giant cell tumor of bone (GCTB) is more common in women in Western countries, it tends to be more common in men in Asian countries. We aimed to determine the sex differences in clinical characteristics, local recurrence rate, and relevant risk factors for local recurrence in primary GCTB around the knee. Between March 2000 and June 2014, patients with primary GCTB around the knee were recruited from 7 institutions in China, and 410 patients were included. The age at diagnosis was younger in women than in men (34.0 vs 37.2 years). The local recurrence rates were 23.4% overall, 25.8% in men, and 20.7% in women. Lower local recurrence rates were observed with en-bloc marginal resection in both men (6.9%) and women (3.1%). With tumors located in the distal femur, the local recurrence rate was higher for men than for women (29.1% vs 14.3%, P = 0.025). Local recurrence was significantly associated with the tumor location and surgical operation in men and only surgical operation in women. These findings suggest that more aggressive operations should be considered in men with GCTB in the proximal fibula. PMID:27321308

  3. Molecular Profiling of Giant Cell Tumor of Bone and the Osteoclastic Localization of Ligand for Receptor Activator of Nuclear Factor κB

    PubMed Central

    Morgan, Teresa; Atkins, Gerald J.; Trivett, Melanie K.; Johnson, Sandra A.; Kansara, Maya; Schlicht, Stephen L.; Slavin, John L.; Simmons, Paul; Dickinson, Ian; Powell, Gerald; Choong, Peter F.M.; Holloway, Andrew J.; Thomas, David M.

    2005-01-01

    Giant cell tumor of bone (GCT) is a generally benign, osteolytic neoplasm comprising stromal cells and osteoclast-like giant cells. The osteoclastic cells, which cause bony destruction, are thought to be recruited from normal monocytic pre-osteoclasts by stromal cell expression of the ligand for receptor activator of nuclear factor κB (RANKL). This model forms the foundation for clinical trials in GCTs of novel cancer therapeutics targeting RANKL. Using expression profiling, we identified both osteoblast and osteoclast signatures within GCTs, including key regulators of osteoclast differentiation and function such as RANKL, a C-type lectin, osteoprotegerin, and the wnt inhibitor SFRP4. After ex vivo generation of stromal- and osteoclast-enriched cultures, we unexpectedly found that RANKL mRNA and protein were more highly expressed in osteoclasts than in stromal cells, as determined by expression profiling, flow cytometry, immunohistochemistry, and reverse transcriptase-polymerase chain reaction. The expression patterns of molecules implicated in signaling between stromal cells and monocytic osteoclast precursors were analyzed in both primary and fractionated GCTs. Finally, using array-based comparative genomic hybridization, neither GCTs nor the derived stromal cells demonstrated significant genomic gains or losses. These data raise questions regarding the role of RANKL in GCTs that may be relevant to the development of molecularly targeted therapeutics for this disease. PMID:15972958

  4. Simultaneous Renal Cell Carcinoma and Giant Retroperitoneal Liposarcoma Involving Small Intestine.

    PubMed

    Reznichenko, Aleksandr A

    2016-01-01

    Background. The concomitant occurrence of a renal cell carcinoma and retroperitoneal sarcoma is extremely rare with only few cases being reported. Methods. We present a case of simultaneous renal cell carcinoma and exceptionally large size retroperitoneal sarcoma involving small intestine. Surgical resection of retroperitoneal sarcoma and simultaneous right nephrectomy were performed. Results. Patient developed recurrent and metastatic disease and underwent debulking surgery following by chemotherapy. Despite aggressive behavior of the retroperitoneal sarcomas, patient is currently (7 years after simultaneous resection and nephrectomy) recurrence-free. Conclusions. Complete surgical resection is the mainstay of therapy for both renal cell carcinoma and retroperitoneal sarcoma. We present a case of simultaneous renal cell carcinoma and exceptionally large size retroperitoneal sarcoma. Debulking surgery and chemotherapy were helpful in our case. PMID:27595033

  5. Simultaneous Renal Cell Carcinoma and Giant Retroperitoneal Liposarcoma Involving Small Intestine

    PubMed Central

    2016-01-01

    Background. The concomitant occurrence of a renal cell carcinoma and retroperitoneal sarcoma is extremely rare with only few cases being reported. Methods. We present a case of simultaneous renal cell carcinoma and exceptionally large size retroperitoneal sarcoma involving small intestine. Surgical resection of retroperitoneal sarcoma and simultaneous right nephrectomy were performed. Results. Patient developed recurrent and metastatic disease and underwent debulking surgery following by chemotherapy. Despite aggressive behavior of the retroperitoneal sarcomas, patient is currently (7 years after simultaneous resection and nephrectomy) recurrence-free. Conclusions. Complete surgical resection is the mainstay of therapy for both renal cell carcinoma and retroperitoneal sarcoma. We present a case of simultaneous renal cell carcinoma and exceptionally large size retroperitoneal sarcoma. Debulking surgery and chemotherapy were helpful in our case. PMID:27595033

  6. Tumor associated osteoclast-like giant cells promote tumor growth and lymphangiogenesis by secreting vascular endothelial growth factor-C

    SciTech Connect

    Hatano, Yu; Nakahama, Ken-ichi; Isobe, Mitsuaki; Morita, Ikuo

    2014-03-28

    Highlights: • M-CSF and RANKL expressing HeLa cells induced osteoclastogenesis in vitro. • We established OGC-containing tumor model in vivo. • OGC-containing tumor became larger independent of M-CSF or RANKL effect. • VEGF-C secreted from OGCs was a one of candidates for OGC-containing tumor growth. - Abstract: Tumors with osteoclast-like giant cells (OGCs) have been reported in a variety of organs and exert an invasive and prometastatic phenotype, but the functional role of OGCs in the tumor environment has not been fully clarified. We established tumors containing OGCs to clarify the role of OGCs in tumor phenotype. A mixture of HeLa cells expressing macrophage colony-stimulating factor (M-CSF, HeLa-M) and receptor activator of nuclear factor-κB ligand (RANKL, HeLa-R) effectively supported the differentiation of osteoclast-like cells from bone marrow macrophages in vitro. Moreover, a xenograft study showed OGC formation in a tumor composed of HeLa-M and HeLa-R. Surprisingly, the tumors containing OGCs were significantly larger than the tumors without OGCs, although the growth rates were not different in vitro. Histological analysis showed that lymphangiogenesis and macrophage infiltration in the tumor containing OGCs, but not in other tumors were accelerated. According to quantitative PCR analysis, vascular endothelial growth factor (VEGF)-C mRNA expression increased with differentiation of osteoclast-like cells. To investigate whether VEGF-C expression is responsible for tumor growth and macrophage infiltration, HeLa cells overexpressing VEGF-C (HeLa-VC) were established and transplanted into mice. Tumors composed of HeLa-VC mimicked the phenotype of the tumors containing OGCs. Furthermore, the vascular permeability of tumor microvessels also increased in tumors containing OGCs and to some extent in VEGF-C-expressing tumors. These results suggest that macrophage infiltration and vascular permeability are possible mediators in these tumors. These

  7. Cytogenetic analysis of 101 giant cell tumors of bone: nonrandom patterns of telomeric associations and other structural aberrations.

    PubMed

    Gorunova, Ludmila; Vult von Steyern, Fredrik; Storlazzi, Clelia Tiziana; Bjerkehagen, Bodil; Follerås, Gunnar; Heim, Sverre; Mandahl, Nils; Mertens, Fredrik

    2009-07-01

    Giant cell tumor of bone (GCTB) is a benign but locally aggressive tumor with metastatic potential. We performed cytogenetic analysis on 101 GCTB from 92 patients. Karyotypes were obtained from 95 tumors, 47 of which had clonal aberrations. The majority of the cytogenetically abnormal GCTB had multiple, up to 28 per tumor, clones. Clonal telomeric associations (tas) and other structural and numerical changes were found in about 70, 60, and 30%, respectively, of clonally abnormal tumors. Forty-seven aberrations were recurrent, of which 35 are novel. The vast majority of the recurrent aberrations were tas, confirming the important role of telomeric fusions in the development of GCTB. The frequency of tas in GCTB cultures increased with passaging, suggesting a selective advantage of tas-positive cells in vitro. The termini most frequently involved in tas were 22p, 13p, 15p, 21p, 14p, 19q, 1q, 12p, 11p, and 20q. The frequency of tas (irrespective of their clonality) was significantly higher in tumors carrying clonal changes, indicating that tas are precursors of other types of aberrations. In line with this assumption, the chromosomes preferentially involved in tas in a given tumor were also the ones most often affected by other rearrangements. We did not find the previously reported amplicon in 20q11.1, assessed by fluorescence in situ hybridization in 10 tumors. Nor did we find any association between cytogenetic features and adverse clinical outcome. Thus, local recurrences probably depend more on the adequacy of surgical treatment than on the intrinsic biology of the tumors. PMID:19396867

  8. Pregnancy associated glycoprotein-1, -6, -7, and -17 are major products of bovine binucleate trophoblast giant cells at midpregnancy.

    PubMed

    Klisch, Karl; De Sousa, Noelita Melo; Beckers, Jean-François; Leiser, Rudolf; Pich, Andreas

    2005-08-01

    Pregnancy associated glycoproteins (PAGs) are extensively glycosylated secretory proteins of ruminant trophoblast cells. In cattle placenta several PAG cDNAs are expressed, but the variety of correspondent proteins and their degree of glycosylation are not well characterized. Thus, we purified PAGs by using a protocol which included a lectin (Vicia villosa agglutinin) affinity chromatography. Due to their specific glycosylation pattern, PAGs derived from binucleate trophoblast giant cells were highly enriched by this protocol. PAGs were purified from cotyledons of 2 day 100 placentas and from a single placenta at day 155 and 180. In all samples three major bands (75; 66; 56 kDa) were detected by one-dimensional SDS-PAGE. Mass-spectrometric analysis identified the 75 kDa band as a mixture of PAG-7 and PAG-6, the 66 kDa band as PAG-1 and the 56 kDa band as PAG-17. N-terminal sequencing of the day 100 sample confirmed the mass spectrometric identifications. Enzymatic release of N-glycans with peptide-N-glycanase-F from PAGs reduced the molecular weight to approximately 37 kDa which corresponds to the theoretical molecular mass of PAGs. Limited peptide-N-glycanase-F treatment revealed that all four N-glycosylation sites are quantitatively occupied in PAG-1. Compared to PAG-1 the number of potential N-glycosylation sites is lower in PAG-17 (three sites) and higher in PAG-6 and -7 (five and six sites, respectively). This suggests that the number of attached N-glycans is the main determinant of molecular mass of bovine PAGs. The degree of glycosylation may be a major factor regulating the plasma half life of PAGs. PMID:15822115

  9. Giant Axonal Neuropathy

    MedlinePlus

    ... Diversity Find People About NINDS NINDS Giant Axonal Neuropathy Information Page Table of Contents (click to jump ... done? Clinical Trials Organizations What is Giant Axonal Neuropathy? Giant axonal neuropathy (GAN) is a rare inherited ...

  10. Giant axonal neuropathy: MRS findings.

    PubMed

    Alkan, Alpay; Kutlu, Ramazan; Sigirci, Ahmet; Baysal, Tamer; Altinok, Tayfun; Yakinci, Cengiz

    2003-10-01

    Giant axonal neuropathy (GAN) is a rare genetic disease of childhood involving the central and peripheral nervous systems. Axonal loss with several giant axons filled with neurofilaments is the main histopathological feature of peripheral nerve biopsies in this disease. Routine neuroimaging studies reveal diffuse hyperintensities in cerebral and cerebellar white matter. In this case report, the authors present the brain magnetic resonance spectroscopic features (normal N-acetylaspartate/creatine and increased choline/creatine and myoinositol/creatine ratios), which might indicate the absence of neuroaxonal loss and the presence of significant demyelination and glial proliferation in white matter, of an 11-year-old boy diagnosed with GAN. PMID:14569833

  11. Final steps in exocytosis observed in a cell with giant secretory granules.

    PubMed Central

    Breckenridge, L J; Almers, W

    1987-01-01

    Secretion by single mast cells was studied in normal and beige mice, a mutant with grossly enlarged secretory vesicles or granules. During degranulation, the membrane capacitance increased in steps, as single secretory vesicles fused with the cell membrane. The average step size was 10 times larger in beige than in normal mice, in agreement with the different granule sizes measured microscopically in the two preparations. Following individual capacitance steps in beige mice, individual granules of the appropriate size were observed to swell rapidly. Capacitance steps are frequently followed by the stepwise loss of a fluorescent dye loaded into the vesicles. Stepwise capacitance increases were occasionally intermittent before they became permanent, indicating the existence of an early, reversible, and incomplete state of vesicle fusion. During such "capacitance flicker," loss of fluorescent dye from vesicles did not occur, suggesting that the earliest aqueous connection between vesicle interior and cell exterior is a narrow channel. Our results support the view that the reversible formation of such a channel, which we term the fusion pore, is an early step in exocytosis. Images PMID:3470768

  12. Characterization of Haemaphysalis flava (Acari: Ixodidae) from Qingling subspecies of giant panda (Ailuropoda melanoleuca qinlingensis) in Qinling Mountains (Central China) by morphology and molecular markers.

    PubMed

    Cheng, Wen-yu; Zhao, Guang-hui; Jia, Yan-qing; Bian, Qing-qing; Du, Shuai-zhi; Fang, Yan-qing; Qi, Mao-zhen; Yu, San-ke

    2013-01-01

    Tick is one of important ectoparasites capable of causing direct damage to their hosts and also acts as vectors of relevant infectious agents. In the present study, the taxa of 10 ticks, collected from Qinling giant pandas (Ailuropoda melanoleuca qinlingensis) in Qinling Mountains of China in April 2010, were determined using morphology and molecular markers (nucleotide ITS2 rDNA and mitochondrial 16S). Microscopic observation demonstrated that the morphological features of these ticks were similar to Haemaphysalis flava. Compared with other Haemaphysalis species, genetic variations between Haemaphysalis collected from A. m. qinlingensis and H. flava were the lowest in ITS2 rDNA and mitochondrial 16S, with sequence differences of 2.06%-2.40% and 1.30%-4.70%, respectively. Phylogenetic relationships showed that all the Haemaphysalis collected from A. m. qinlingensis were grouped with H. flava, further confirmed that the Haemaphysalis sp. is H. flava. This is the first report of ticks in giant panda by combining with morphology and molecular markers. This study also provided evidence that combining morphology and molecular tools provide a valuable and efficient tool for tick identification. PMID:23894541

  13. Daunomycin triggers membrane blebbing and breakage of giant DNA encapsulated in a cell-sized liposome

    NASA Astrophysics Data System (ADS)

    Yoshikawa, Yuko; Kanbe, Toshio; Yoshikawa, Kenichi

    2002-12-01

    We studied the effect of daunomycin, a cancer chemotherapeutic agent, on a model cellular system in which folded compact DNA was encapsulated inside a cell-sized phospholipid liposome. Real-time observation with fluorescence microscopy revealed that, upon the addition of daunomycin, entrapped DNA was first elongated and then cut into fragments. A blebbing transition of the membrane was also observed. A theoretical model is proposed to explain the blebbing phenomenon induced by daunomycin, taking into account its effect on the asymmetry between the outer and inner layers of the membrane.

  14. Positron emission tomography and computed tomography angiography for the diagnosis of giant cell arteritis: A real-life prospective study.

    PubMed

    Lariviere, Delphine; Benali, Khadija; Coustet, Baptiste; Pasi, Nicoletta; Hyafil, Fabien; Klein, Isabelle; Chauchard, Maria; Alexandra, Jean-François; Goulenok, Tiphaine; Dossier, Antoine; Dieude, Philippe; Papo, Thomas; Sacre, Karim

    2016-07-01

    The use of 18F-fluoro-deoxyglucose positron emission tomography scan (FDG-PET) and computed tomography angiography (CTA) to improve accuracy of diagnosis of giant cell arteritis (GCA) is a very important clinical need. We aimed to compare the diagnostic performance of FDG-PET and CTA in patients with GCA.FDG-PET and CTA were acquired in all consecutive patients suspected for GCA. Results of FDG-PET and CTA were compared with the final diagnosis based on clinical judgment, temporal artery biopsy (TAB) findings, and ACR criteria. Sensitivity, specificity, and positive and negative predictive values (PPV, NPV) were calculated for each method.Twenty-four patients suspected for GCA were included. Fifteen (62.5%) were ultimately diagnosed as having GCA. Among them, all fulfilled ACR criteria and 6 had biopsy-proven GCA. Strong FDG uptake in large vessels was found in 10 patients who all had GCA. Mean maximal standard uptake values (SUVmax) per patient measured at all the arterial territories were of 3.7 (range: 2.8-4.7). FDG uptake was negative in 14 patients including 9 and 5 patients without and with GCA, respectively. Mural thickening suggestive of aortitis or branch vessel arteritis was observed on CTA in 11 patients with and 2 patients without GCA. No mural thickening was observed in 11 patients including 7 patients without and 4 patients with GCA. Overall, sensitivity was 66.7% and 73.3%, specificity was 100% and 84.6%, NPV was 64.3% and 64.6%, and PPV was 100% and 84.6% of FDG-PET and CTA, respectively.Both FDG-PET and CTA have a strong diagnostic yield for the diagnosis of GCA. FDG-PET appeared to have a higher PPV as compared to CTA and may be the preferred noninvasive technique to explore patients with suspected GCA. PMID:27472684

  15. The Megavoltage Radiation Therapy in Treatment of Patients With Advanced or Difficult Giant Cell Tumors of Bone

    SciTech Connect

    Ruka, Wlodzimierz; Ptaszynski, Konrad; Bylina, Elzbieta

    2010-10-01

    Purpose: To assess the outcomes of radiotherapy, in terms of local control and treatment complications, of advanced or difficult giant cell tumors of bone (GCTB) that could not be treated by surgery. Methods and Materials: Among 122 consecutive patients with confirmed GCTB from 1985 to 2007, 77 patients were treated by megavoltage radiotherapy because they were inappropriate candidates for surgery. We have performed analysis of all data in terms of progression-free survival (PFS) and treatment morbidity. Median follow-up time was 58 months. Results: In the irradiated group, maximal tumor size ranged from 5 to 18 cm (median, 8.5). Anatomic distribution was as follows: femur, 27 cases; tibia, 19; radial/ulnar bone, 12; sacrum, 9; pelvic bones, 5; other, 5. Twenty-one patients (27%) were referred for local recurrence after {>=}1 other treatment procedures. The radiation doses ranged from 26 to 89 Gy (median, 56; administered 1.8-2.0 Gy/fraction with average total duration of treatment of 5-7 weeks); 8 patients (10%) received <50 Gy. All patients tolerated treatment well without acute or late complications. All patients except two are alive. Local control was achieved in 65 patients (84%; bone recalcification/restitution of joint functions), 12 patients showed signs of local progression, all within irradiated fields (9 were treated successfully with salvage surgery). Five- and 10-year local PFS were 83% and 73%, respectively. Three patients developed lungs metastases. Malignant transformation of GCTB occurred in two patients. Conclusions: GCTB can be safely and effectively treated with megavoltage radiotherapy with local control rate >80% at 5 years. Our study confirms that radiotherapy of GCTB offers an alternative to difficult or complex surgery and may be an option of choice in the treatment of inoperable patients.

  16. Childhood Central Nervous System Germ Cell Tumors Treatment

    MedlinePlus

    ... cancer will come back, is called adjuvant therapy . High-dose chemotherapy with stem cell rescue High-dose chemotherapy with stem cell rescue is a way of giving high doses of chemotherapy and replacing blood -forming cells ...

  17. [Giant gastric neuroendocrine cell carcinoma with extraluminal growth and direct invasion: a case report].

    PubMed

    Okawa, Takaomi; Nogami, Hiromi; Kadota, Eiji

    2015-11-01

    A 68-year-old man presented to our hospital requesting an operation for an anal prolapse. However, because of appetite loss and general malaise, we performed screening gastroscopy that revealed a huge ulcerative lesion in the greater curvature of the middle stomach. Biopsy showed a solid tumor with marked dyskaryosis that was positive for synaptophysin on immunohistochemical staining. Abdominal computed tomography revealed a tumor measuring larger than 20 cm in diameter in the greater curvature of the stomach and two hepatic metastases. A preoperative diagnosis of neuroendocrine cell carcinoma (NEC) was made and the patient underwent surgery. The lesion displayed extraluminal growth and directly infiltrated the ileum and colon. We therefore performed distal gastrectomy with combined resection of the gallbladder, ileum, transverse colon, and sigmoid colon. However, despite transcatheter arterial chemoembolization for the liver metastases, the patient died 1 year 2 months after the initial surgery. Gastric NECs are rare and have poor outcomes, being associated with rapid progression of lymph node and liver metastases. Moreover, they rarely show extraluminal growth or invasion to other organs. We present a report of this case along with a review of the literature. PMID:26537329

  18. The use of the color Doppler ultrasonography in the diagnosis and monitoring of an atypical case of giant-cell arteritis.

    PubMed

    Martins, N; Polido-Pereira, J; Rodrigues, A M; Soares, F; Batista, P; Pereira da Silva, J A

    2016-01-01

    Giant Cell Arteritis (GCA) is a large vessels vasculitis that is typically characterised by headache, scalp tenderness, jaw claudication and visual disturbances. Temporal arteries color Doppler ultrasonography (CDUS) is a sensitive and non-invasive image technique used in the diagnosis of this disease. This work highlights the importance of CDUS in the diagnostic workup of GCA and also demonstrates it´s usefullness in the evaluation and documentation of the response to corticosteroids therapy in an atypical case of ACG. PMID:27606478

  19. Effective use of gemcitabine in the treatment of undifferentiated carcinoma with osteoclast-like giant cells of the pancreas with portal vein tumor thrombus.

    PubMed

    Yoshioka, Masato; Uchinami, Hiroshi; Watanabe, Go; Takahashi, Tomokazu; Nakagawa, Yasuhiko; Andoh, Hideaki; Yoshioka, Toshiaki; Nanjo, Hiroshi; Yamamoto, Yuzo

    2012-01-01

    A 74-year-old woman had an undifferentiated carcinoma with osteoclast-like giant cells (UCWOGC) in the body of the pancreas with massive portal vein tumor thrombus (PVTT). Because the PVTT progressed so rapidly into the right portal branch, the patient first underwent distal pancreatectomy and tumor thrombectomy to prevent life-threatening portal venous obstruction. Although a recurrent PVTT had developed early postoperatively, systemic gemcitabine treatment was so effective that it induced complete remission 5 months after the initiation of chemotherapy. The patient continued to be in complete response for 12 months, and has survived for 19 months since surgery. PMID:22892493

  20. Mammalian Target of Rapamycin Inhibitor Induced Complete Remission of a Recurrent Subependymal Giant Cell Astrocytoma in a Patient Without Features of Tuberous Sclerosis Complex.

    PubMed

    Appalla, Deepika; Depalma, Andres; Calderwood, Stanley

    2016-07-01

    The majority of patients with subependymal giant cell astrocytoma (SEGA) have tuberous sclerosis complex (TSC). In such patients, the mammalian target of rapamycin (mTOR) inhibitor everolimus has been shown to induce responses. Isolated SEGA have been reported in patients without clinical or genetic features of TSC. The treatment of these patients with everolimus has not previously been reported. We treated a patient with a recurrent isolated SEGA with an mTOR inhibitor. The patient tolerated therapy well and had a sustained complete remission. MTOR inhibitors may be useful for the treatment of isolated SEGA. Further study is warranted. PMID:26929034

  1. Propagation of the Israeli vaccine strain of Anaplasma centrale in tick cell lines.

    PubMed

    Bell-Sakyi, Lesley; Palomar, Ana M; Bradford, Emma L; Shkap, Varda

    2015-09-30

    Anaplasma centrale has been used in cattle as a live blood vaccine against the more pathogenic Anaplasma marginale for over 100 years. While A. marginale can be propagated in vitro in tick cell lines, facilitating studies on antigen production, immunisation and vector-pathogen interaction, to date there has been no in vitro culture system for A. centrale. In the present study, 25 cell lines derived from 13 ixodid tick species were inoculated with the Israeli vaccine strain of A. centrale and monitored for at least 12 weeks by microscopic examination of Giemsa-stained cytocentrifuge smears. Infection of 19 tick cell lines was subsequently attempted by transfer of cell-free supernate from vaccine-inoculated tick cells. In two separate experiments, rickettsial inclusions were detected in cultures of the Rhipicephalus appendiculatus cell line RAE25 28-32 days following inoculation with the vaccine. Presence of A. centrale in the RAE25 cells was confirmed by PCR assays targeting the 16S rRNA, groEL and msp4 genes; sequenced PCR products were 100% identical to published sequences of the respective genes in the Israeli vaccine strain of A. centrale. A. centrale was taken through three subcultures in RAE25 cells over a 30 week period. In a single experiment, the Dermacentor variabilis cell line DVE1 was also detectably infected with A. centrale 11 weeks after inoculation with the vaccine. Availability of an in vitro culture system for A. centrale in tick cells opens up the possibility of generating a safer and more ethical vaccine for bovine anaplasmosis. PMID:26210950

  2. Propagation of the Israeli vaccine strain of Anaplasma centrale in tick cell lines

    PubMed Central

    Bell-Sakyi, Lesley; Palomar, Ana M.; Bradford, Emma L.; Shkap, Varda

    2015-01-01

    Anaplasma centrale has been used in cattle as a live blood vaccine against the more pathogenic Anaplasma marginale for over 100 years. While A. marginale can be propagated in vitro in tick cell lines, facilitating studies on antigen production, immunisation and vector-pathogen interaction, to date there has been no in vitro culture system for A. centrale. In the present study, 25 cell lines derived from 13 ixodid tick species were inoculated with the Israeli vaccine strain of A. centrale and monitored for at least 12 weeks by microscopic examination of Giemsa-stained cytocentrifuge smears. Infection of 19 tick cell lines was subsequently attempted by transfer of cell-free supernate from vaccine-inoculated tick cells. In two separate experiments, rickettsial inclusions were detected in cultures of the Rhipicephalus appendiculatus cell line RAE25 28–32 days following inoculation with the vaccine. Presence of A. centrale in the RAE25 cells was confirmed by PCR assays targeting the 16S rRNA, groEL and msp4 genes; sequenced PCR products were 100% identical to published sequences of the respective genes in the Israeli vaccine strain of A. centrale. A. centrale was taken through three subcultures in RAE25 cells over a 30 week period. In a single experiment, the Dermacentor variabilis cell line DVE1 was also detectably infected with A. centrale 11 weeks after inoculation with the vaccine. Availability of an in vitro culture system for A. centrale in tick cells opens up the possibility of generating a safer and more ethical vaccine for bovine anaplasmosis. PMID:26210950

  3. Giant Magnons Meet Giant Gravitons

    SciTech Connect

    Hofman, Diego M.

    2008-07-28

    We study the worldsheet reflection matrix of a string attached to a D-brane in AdS{sub 5}xS{sup 5}. The D-brane corresponds to a maximal giant graviton that wraps an S{sup 3} inside S{sup 5}. In the gauge theory, the open string is described by a spin chain with boundaries. We focus on open strings with a large SO(6) charge and define an asymptotic boundary reflection matrix. Using the symmetries of the problem, we review the computation of the boundary reflection matrix, up to a phase. We also discuss weak and strong coupling computations where we obtain the overall phase factor and test our exact results.

  4. 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

  5. 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

  6. Giant Cell Arteritis

    MedlinePlus

    ... American College of Rheumatology Committee on Communications and Marketing. This information is provided for general education only. ... Lists Supporters About Us Leadership Careers at ACR Social Media Newsroom Annual Reports & Financial Statements Policies & Guidelines ...

  7. Analyzing cell fusion events within the central nervous system using bone marrow chimerism.

    PubMed

    Kemp, Kevin; Hares, Kelly

    2015-01-01

    It has emerged that cells which typically reside in the bone marrow have the capacity to cross the blood brain barrier and contribute genetic material to a range of neuronal cell types within the central nervous system. One such mechanism to account for this phenomenon is cellular fusion, occurring between migrating bone marrow-derived stem cells and neuronal cells in-situ. Biologically, the significance as to why cells from distinct lineages fuse with cells of the central nervous system is, as yet, unclear. Growing evidence however suggests that these cell fusion events could provide an efficient means of rescuing the highly complex and differentiated neuronal cell types that cannot be replaced in adulthood. To facilitate further understanding of cell fusion within the central nervous system, we describe here a technique to establish chimeric mice that are stably reconstituted with green fluorescent protein expressing sex-mismatched bone marrow. These chimeric mice are known to represent an excellent model for studying bone marrow cell migration and infiltration throughout the body, while in parallel, as will be described here, also provide a means to neatly analyze both bone marrow-derived cell fusion and trans-differentiation events within the central nervous system. PMID:25947664

  8. [Current cell therapy strategies for repairing the central nervous system].

    PubMed

    Féron, F

    2007-09-01

    One of the chief contemporary goals of neurologists and neuroscientists is to find a way to overcome the debilitating effects of brain diseases, especially neurodegenerative diseases. Since very few molecules have been found to be efficient in curing the patients and even halting the progression of the symptoms, cell therapy is now seen as an attractive alternative. Two therapeutic strategies are currently under investigation: i) the "substitution" strategy, based on grafts of cells capable of differentiating in the appropriate cells and restoring lost functions and ii) the "neuroprotective" or "conservative" strategy aiming to increase the resistance of spared cells to the toxicity of their environment and to reinforce the body's own mechanisms of healing. Twenty years ago, foetal neuroblasts were the first cells to be transplanted in the brains of patients with Parkinson's or Huntington disease. A phase II clinical trial is presently conducted in France for the latter disorder. However, the numerous ethical and technical issues raised by the use of embryonic and foetal cells have directed the focus of clinicians and researchers towards substitute cell types. In this review, we summarise the main findings of the most recent basic studies and clinical trials based on: i) the grafting of surrogate adult cells such as bone marrow mesenchymal stem cells and olfactory ensheathing cells; ii) the potential therapeutic applications of neuropoiesis - the persistent neurogenesis in the brain - as a source for tissue engraftment and as self-repair by a person's own indigenous population of pluripotent cells and iii) immune-based therapy (autologous activated macrophages and T cell vaccination) as well as administration of immunomodulatory molecules. Unexpectedly, it has been found that undifferentiated adult stem cells can display immune-like functions when they home in on an inflamed brain area while immune cells and immunosuppressors can improve functional and

  9. The Role of Dendritic Cells in Central Tolerance.

    PubMed

    Oh, Jaehak; Shin, Jeoung-Sook

    2015-06-01

    Dendritic cells (DCs) play a significant role in establishing self-tolerance through their ability to present self-antigens to developing T cells in the thymus. DCs are predominantly localized in the medullary region of thymus and present a broad range of self-antigens, which include tissue-restricted antigens expressed and transferred from medullary thymic epithelial cells, circulating antigens directly captured by thymic DCs through coticomedullary junction blood vessels, and peripheral tissue antigens captured and transported by peripheral tissue DCs homing to the thymus. When antigen-presenting DCs make a high affinity interaction with antigen-specific thymocytes, this interaction drives the interacting thymocytes to death, a process often referred to as negative selection, which fundamentally blocks the self-reactive thymocytes from differentiating into mature T cells. Alternatively, the interacting thymocytes differentiate into the regulatory T (Treg) cells, a distinct T cell subset with potent immune suppressive activities. The specific mechanisms by which thymic DCs differentiate Treg cells have been proposed by several laboratories. Here, we review the literatures that elucidate the contribution of thymic DCs to negative selection and Treg cell differentiation, and discusses its potential mechanisms and future directions. PMID:26140042

  10. Fibroblast and vascular endothelial growth factor coating of decellularized vascular grafts stimulates undesired giant cells and graft encapsulation in a rat model.

    PubMed

    Heidenhain, Christoph; Veeravoorn, Ariyakhagorn; Vachkov, Blagovest; Weichert, Wilko; Schmidmaier, Gerhard; Wildemann, Britt; Neuhaus, Peter; Heise, Michael

    2011-01-01

    Replacing an infected prosthesis with a bioimplant provides a hopeful alternative in septic vascular surgery. The objective of this study was to determine the effect of fibroblast endothelial growth factors (FGF) and vascular endothelial growth factors (VEGF) coating on a decellularized vascular graft in a rat model and the possible impact on recellularization processes. Rat aortas were decellularized, crosslinked with genipin, and coated with poly-(D, L) lactide containing either FGF or VEGF. Observation periods were 6 and 12 weeks. Surprisingly, we found moderate accumulation of giant cells around the grafts that contained poly-(D, L) lactide acid. FGF and VEGF grafts showed massive stimulation of giant cells and eosinophils leading to complete graft encapsulation (P < 0.05). Pseudointmal hyperplasia was significantly increased in the FGF group (P < 0.05). Both results can only be interpreted as very negative. We achieved a situation in diametric opposition to that which we had hoped for. These data demonstrate that the use of growth factors may produce harmful side effects. PMID:20883449

  11. Giant Cell Tumor of Tendon Sheath in Guyon's Canal Causing Ulnar Tunnel Syndrome A Case Report and Review of the Literature

    PubMed Central

    Francisco, Ben S.; Agarwal, Jayant P.

    2009-01-01

    Objective: Giant cell tumor of tendon sheath is a rare cause of ulnar tunnel syndrome. We present a case of a 37-year-old woman who presented with decreased sensation and weakness of grip of the right hand. Magnetic resonance imaging indicated the presence of a mass in the hypothenar eminence and showed that the mass was associated with the flexor carpi ulnaris tendon and displacing the ulnar neurovascular bundle. A differential diagnosis included desmoid tumor and sarcoma. Methods: Surgical examination showed a mass that was associated with the flexor carpi ulnaris tendon and flexor retinaculum located in the distal portion of Guyon's canal and intertwined with the ulnar nerve and displacing the ulnar artery. The mass was removed and Guyon's canal was released. Results: Histological examination indicated a diagnosis of giant cell tumor of tendon sheath (GCTTS). Postoperatively, the patient had fully restored sensory and motor function of the right hand. Conclusions: Although GCTTS is the most common solid, soft-tissue lesion of the hand, it is rarely diagnosed properly preoperatively. Therefore, it is imperative to always include GCTTS in the differential diagnosis of any mass of the hand. PMID:19252681

  12. Two giant stellar complexes

    NASA Astrophysics Data System (ADS)

    Efremov, Yu. N.; Efremov, E. Yu.

    Common star complexes are huge (0.3-1 kpc in diameter) groups of relatively young stars, associations and clusters. The complexes usually form regular chains along spiral arms of grand design galaxies, being evidently formed and supported by magneto- gravitational instability developing along an arm. Special attention is given to a few large complexes which have signatures of gravitational boundness, such as round shape and high central density. Concentrations of stars and clusters in such a complex in M51 galaxy were found in this paper; we concluded it is possible to suggest that the complex is gravitationally bound. It is also stressed that some properties of the giant complex in NGC 6946 (such as its semicircular and sharp Western edge) are still enigmatic.

  13. 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

  14. CCR4 promotes medullary entry and thymocyte-dendritic cell interactions required for central tolerance.

    PubMed

    Hu, Zicheng; Lancaster, Jessica N; Sasiponganan, Chayanit; Ehrlich, Lauren I R

    2015-10-19

    Autoimmunity results from a breakdown in central or peripheral tolerance. To establish central tolerance, developing T cells must enter the thymic medulla, where they scan antigen-presenting cells (APCs) displaying a diverse array of autoantigens. If a thymocyte is activated by a self-antigen, the cell undergoes either deletion or diversion into the regulatory T cell (T reg) lineage, thus maintaining self-tolerance. Mechanisms promoting thymocyte medullary entry and interactions with APCs are incompletely understood. CCR4 is poised to contribute to central tolerance due to its expression by post-positive selection thymocytes, and expression of its ligands by medullary thymic dendritic cells (DCs). Here, we use two-photon time-lapse microscopy to demonstrate that CCR4 promotes medullary entry of the earliest post-positive selection thymocytes, as well as efficient interactions between medullary thymocytes and DCs. In keeping with the contribution of thymic DCs to central tolerance, CCR4 is involved in regulating negative selection of polyclonal and T cell receptor (TCR) transgenic thymocytes. In the absence of CCR4, autoreactive T cells accumulate in secondary lymphoid organs and autoimmunity ensues. These studies reveal a previously unappreciated role for CCR4 in the establishment of central tolerance. PMID:26417005

  15. CCR4 promotes medullary entry and thymocyte–dendritic cell interactions required for central tolerance

    PubMed Central

    Hu, Zicheng; Lancaster, Jessica N.; Sasiponganan, Chayanit

    2015-01-01

    Autoimmunity results from a breakdown in central or peripheral tolerance. To establish central tolerance, developing T cells must enter the thymic medulla, where they scan antigen-presenting cells (APCs) displaying a diverse array of autoantigens. If a thymocyte is activated by a self-antigen, the cell undergoes either deletion or diversion into the regulatory T cell (T reg) lineage, thus maintaining self-tolerance. Mechanisms promoting thymocyte medullary entry and interactions with APCs are incompletely understood. CCR4 is poised to contribute to central tolerance due to its expression by post-positive selection thymocytes, and expression of its ligands by medullary thymic dendritic cells (DCs). Here, we use two-photon time-lapse microscopy to demonstrate that CCR4 promotes medullary entry of the earliest post-positive selection thymocytes, as well as efficient interactions between medullary thymocytes and DCs. In keeping with the contribution of thymic DCs to central tolerance, CCR4 is involved in regulating negative selection of polyclonal and T cell receptor (TCR) transgenic thymocytes. In the absence of CCR4, autoreactive T cells accumulate in secondary lymphoid organs and autoimmunity ensues. These studies reveal a previously unappreciated role for CCR4 in the establishment of central tolerance. PMID:26417005

  16. General Information About Childhood Central Nervous System Germ Cell Tumors

    MedlinePlus

    ... before the cancer is diagnosed and continue for months or years. Childhood CNS germ cell tumors may ... after treatment. Some cancer treatments cause side effects months or years after treatment has ended. Some cancer ...

  17. T-Cell/Histiocyte-Rich Large B-Cell Lymphoma Presenting as a Primary Central Nervous System Lymphoma

    PubMed Central

    Advani, Pooja; Starr, Jason; Swaika, Abhisek; Jiang, Liuyan; Qiu, Yushi; Li, Zhimin

    2015-01-01

    Primary central nervous system (PCNSL) lymphoma is an aggressive extranodal non-Hodgkin lymphoma, and most cases are classified as diffuse large B-cell lymphoma (DLBCL) by histology. T-cell/histiocyte-rich large B-cell lymphoma (TCRLBCL) represents a distinct subtype of diffuse large B-cell lymphoma and is characterized by the presence of scattered large neoplastic B-cells in a background of abundant T-cells and histiocytes. This is in contrast to the dense perivascular cuffing of neoplastic B-cells in classic DLBCL. T-cell/histiocyte-rich large B-cell lymphoma should be considered in PCNSL cases in which neoplastic B-cells are sparse and scattered. Immunohistochemistry will help identify the B-cells and surrounding infiltrate rich in Tlymphocytes and histiocytes. Future studies exploring the biology of TCRLBCL and the crosstalk between the neoplastic cells and the surrounding inflammatory infiltrate may provide exciting prospects for future therapies for TCRLBCL. PMID:26788280

  18. Characterization of a synaptiform transmission between a neuron and a glial cell in the leech central nervous system.

    PubMed

    Britz, Frank C; Lohr, Christian; Schmidt, Joachim; Deitmer, Joachim W

    2002-05-01

    The cross-talk between neurons and glial cells is receiving increased attention because of its potential role in information processing in nervous systems. Stimulation of a single identifiable neuron, the neurosecretory Leydig interneuron in segmental ganglia of the leech Hirudo medicinalis, which modulates specific behaviors in the leech, evokes membrane hyperpolarization directly in the giant glial cell (Schmidt and Deitmer. Eur J Neurosci 11:3125-3133, 1999). We have studied the neuron-to-glia signal transmission in the voltage-clamped giant glial cell to determine whether this interaction exhibits properties of a chemical synapse. The glial response had a mean latency of 4.9 s and was dependent on the action potential frequency; the glial cell responded to as few as five Leydig neuron action potentials in 50% of the trials. The glial current was sustained for minutes during repetitive Leydig neuron activity without any sign of desensitization. The current was sensitive to tetraethylammonium, and its reversal potential of -78 mV shifted with the external K+ concentration. The glial response increased with the duration of the neuronal action potentials and was sensitive to the external Ca2+/Mg2+ concentration ratio. The results suggest that Leydig neuron activity leads to a Ca2+-dependent release of transmitter from the neuronal dendrites, evoking an K+ outward current in the giant glial cell, implying a synapse-like transmission between a neuron and a glial cell. PMID:11968059

  19. Central Nervous System Stromal Cells Control Local CD8(+) T Cell Responses during Virus-Induced Neuroinflammation.

    PubMed

    Cupovic, Jovana; Onder, Lucas; Gil-Cruz, Cristina; Weiler, Elke; Caviezel-Firner, Sonja; Perez-Shibayama, Christian; Rülicke, Thomas; Bechmann, Ingo; Ludewig, Burkhard

    2016-03-15

    Stromal cells generate a complex cellular scaffold that provides specialized microenvironments for lymphocyte activation in secondary lymphoid organs. Here, we assessed whether local activation of stromal cells in the central nervous system (CNS) is mandatory to transfer immune recognition from secondary lymphoid organs into the infected tissue. We report that neurotropic virus infection in mice triggered the establishment of such stromal cell niches in the CNS. CNS stromal cell activation was dominated by a rapid and vigorous production of CC-motif chemokine receptor (CCR) 7 ligands CCL19 and CCL21 by vascular endothelial cells and adjacent fibroblastic reticular cell (FRC)-like cells in the perivascular space. Moreover, CCR7 ligands produced by CNS stromal cells were crucial to support recruitment and local re-activation of antiviral CD8(+) T cells and to protect the host from lethal neuroinflammatory disease, indicating that CNS stromal cells generate confined microenvironments that control protective T cell immunity. PMID:26921107

  20. T-cell-mediated clearance of mouse hepatitis virus strain JHM from the central nervous system.

    PubMed Central

    Sussman, M A; Shubin, R A; Kyuwa, S; Stohlman, S A

    1989-01-01

    Clearance of the neurotropic JHM strain of mouse hepatitis virus from the central nervous system was examined by the transfer of spleen cells from immunized donors. A T cell with the surface phenotype of Thy1.2+ CD4+ CD8- asialo-GM1+ Mac-1- was found to be necessary for viral clearance. The surface phenotype and adherence to nylon wool suggest that these cells are activated helper-inducer T cells. Adoptive transfer to congenic histocompatibility strains demonstrated the necessity for compatibility at the D locus of the major histocompatibility complex. The expression of the CD4 surface marker and the requirement for major histocompatibility complex class I were further studied by the transfer of cells to recipients treated with anti-CD4 or anti-CD8 monoclonal antibodies. Treatment of recipients with either the anti-CD8 or the anti-CD4 antibodies inhibited virus clearance from the central nervous system. This suggests that the CD4+ cell acts as a helper and that virus is cleared from the central nervous system. This suggests that the CD4+ cell acts as a helper and that virus is cleared from the central nervous system by CD8+ cells that recognize viral antigen in the context of the H-2Db gene product. PMID:2542613

  1. Bovine central memory T cells are highly proliferative in response to bovine tuberculosis infection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Long-term (i.e., 14 days) cultured IFN-gamma responses of peripheral blood mononuclear cells are used as a correlate of T cell central memory (Tcm) responses in both humans and cattle. With bovine tuberculosis, vaccine-elicited long-term IFN-gamma ELISPOT assays are a correlate of protection. Recent...

  2. Giant impacts on giant planets

    NASA Astrophysics Data System (ADS)

    de Pater, Imke

    2012-10-01

    The 2009 impact on Jupiter caught the world by surprise and cast doubt on impactor flux estimates for the outer solar system. Enhanced amateur planetary imaging techniques yield both high spatial resolution {enabling the 2009 impact debris field detection} and rapid frame rates {enabling the 2010 impact flash detections and lightcurve measurements}.We propose a Target of Opportunity program to image future impacts on Jupiter and Saturn. To remove the possibility of impact cloud non-detections, the program will be triggered only if an existing impact debris field is seen, an object on a collision course with Jupiter or Saturn is discovered, or an impact light curve is measured with an estimated total energy large enough to generate an impact cloud in a giant planet atmosphere.HST provides the only way to image these events in the ultraviolet, providing information on aerosol altitudes and on smaller particles that are less visible to ground-based infrared observations. High-resolution imaging with proper timing {not achievable from the ground} is required to measure precisely both the velocity fields of impact sites and the optical spectrum of impact debris. HST observations of past impacts on Jupiter have also served both as cornerstones of science investigations at other wavelengths and as vehicles for effective public outreach.Large outer solar system impacts are governed by the same physics as in the terrestrial events that dominate the impact threat to humans. Studying the behavior of impactors of various sizes and compositions, as they enter the atmosphere at varying angles and speeds, will better quantify terrestrial impact hazards.

  3. Giant impacts on giant planets

    NASA Astrophysics Data System (ADS)

    de Pater, Imke

    2014-10-01

    The 2009 impact and recent superbolides on Jupiter caught the world by surprise and cast doubt on impactor flux estimates for the outer solar system. Enhanced amateur planetary imaging techniques yield both high spatial resolution (enabling the 2009 impact debris field detection) and rapid frame rates (enabling the 2010/2012 impact flash detections and lightcurve measurements).We propose a ToO program to image future impacts on Jupiter and Saturn. To remove the possibility of impact cloud non-detections, the program will be triggered only if an existing impact debris field is seen, an object on a collision course with Jupiter or Saturn is discovered, or an impact light curve is measured with an estimated total energy large enough to generate an impact cloud in a giant planet atmosphere (10^20 J).HST provides the only way to image these events in the ultraviolet, providing information on aerosol altitudes and on smaller particles that are less visible to ground-based infrared observations. High-resolution imaging with proper timing (not achievable from the ground) is required to measure precisely both the velocity fields of impact sites and the optical spectrum of impact debris. HST observations of past impacts on Jupiter have also served both as cornerstones of science investigations at other wavelengths and as vehicles for effective public outreach.Large outer solar system impacts are governed by the same physics as in the terrestrial events that dominate the impact threat to humans. Studying the behavior of impactors of various sizes and compositions, as they enter the atmosphere at varying angles and speeds, will better quantify terrestrial impact hazards.

  4. Giant impacts on giant planets

    NASA Astrophysics Data System (ADS)

    de Pater, Imke

    2013-10-01

    The 2009 impact and recent superbolides on Jupiter caught the world by surprise and cast doubt on impactor flux estimates for the outer solar system. Enhanced amateur planetary imaging techniques yield both high spatial resolution {enabling the 2009 impact debris field detection} and rapid frame rates {enabling the 2010/2012 impact flash detections and lightcurve measurements}.We propose a ToO program to image future impacts on Jupiter and Saturn. To remove the possibility of impact cloud non-detections, the program will be triggered only if an existing impact debris field is seen, an object on a collision course with Jupiter or Saturn is discovered, or an impact light curve is measured with an estimated total energy large enough to generate an impact cloud in a giant planet atmosphere {10^20 J}.HST provides the only way to image these events in the ultraviolet, providing information on aerosol altitudes and on smaller particles that are less visible to ground-based infrared observations. High-resolution imaging with proper timing {not achievable from the ground} is required to measure precisely both the velocity fields of impact sites and the optical spectrum of impact debris. HST observations of past impacts on Jupiter have also served both as cornerstones of science investigations at other wavelengths and as vehicles for effective public outreach.Large outer solar system impacts are governed by the same physics as in the terrestrial events that dominate the impact threat to humans. Studying the behavior of impactors of various sizes and compositions, as they enter the atmosphere at varying angles and speeds, will better quantify terrestrial impact hazards.

  5. Specific central memory T cells in the bone marrow of patients immunized against tyrosinase peptides.

    PubMed

    Letsch, Anne; Keilholz, Ulrich; Kern, Florian; Asemissen, Anne Marie; Thiel, Eckhard; Scheibenbogen, Carmen

    2006-01-01

    The goal of vaccination against tumors is the induction of effector T cells mediating tumor destruction and memory T cells providing long-term immunity. Several previous studies in patients vaccinated with major histocompatibility complex (MHC) class I peptides failed to show induction of central memory T cells, which are considered important to provide long-term memory. This study examined the subset composition and function of specific T cells generated by immunization with MHC class I binding tyrosinase peptides in combination with the adjuvants granulocyte-macrophage colony-stimulating factor and keyhole limpet hemocyanin in peripheral blood (PB) and bone marrow (BM) of melanoma patients. Most of the tyrosinase-specific T cells in PB had a CD45RA(+)CCR7(-) effector phenotype. In contrast to this, a large subset of tyrosinase-specific T cells in BM were memory T cells, including CD45RA(+)CCR7(-) central and CD45RA(-)CCR7(-) effector memory T cells. BM tyrosinase-specific T cells were functional, because they produced interferon-gamma and had a high proliferative potential. This study suggests that peptide vaccination can generate a fully functional memory T-cell response characterized by central and effector memory phenotypes, proliferative potential, and BM tropism. PMID:16531820

  6. Wear particles derived from metal hip implants induce the generation of multinucleated giant cells in a 3-dimensional peripheral tissue-equivalent model.

    PubMed

    Dutta, Debargh K; Potnis, Pushya A; Rhodes, Kelly; Wood, Steven C

    2015-01-01

    Multinucleate giant cells (MGCs) are formed by the fusion of 5 to 15 monocytes or macrophages. MGCs can be generated by hip implants at the site where the metal surface of the device is in close contact with tissue. MGCs play a critical role in the inflammatory processes associated with adverse events such as aseptic loosening of the prosthetic joints and bone degeneration process called osteolysis. Upon interaction with metal wear particles, endothelial cells upregulate pro-inflammatory cytokines and other factors that enhance a localized immune response. However, the role of endothelial cells in the generation of MGCs has not been completely investigated. We developed a three-dimensional peripheral tissue-equivalent model (PTE) consisting of collagen gel, supporting a monolayer of endothelial cells and human peripheral blood mononuclear cells (PBMCs) on top, which mimics peripheral tissue under normal physiological conditions. The cultures were incubated for 14 days with Cobalt chromium alloy (CoCr ASTM F75, 1-5 micron) wear particles. PBMC were allowed to transit the endothelium and harvested cells were analyzed for MGC generation via flow cytometry. An increase in forward scatter (cell size) and in the propidium iodide (PI) uptake (DNA intercalating dye) was used to identify MGCs. Our results show that endothelial cells induce the generation of MGCs to a level 4 fold higher in 3-dimentional PTE system as compared to traditional 2-dimensional culture plates. Further characterization of MGCs showed upregulated expression of tartrate resistant alkaline phosphatase (TRAP) and dendritic cell specific transmembrane protein, (DC-STAMP), which are markers of bone degrading cells called osteoclasts. In sum, we have established a robust and relevant model to examine MGC and osteoclast formation in a tissue like environment using flow cytometry and RT-PCR. With endothelial cells help, we observed a consistent generation of metal wear particle- induced MGCs, which heralds

  7. Central Administration of Galanin Receptor 1 Agonist Boosted Insulin Sensitivity in Adipose Cells of Diabetic Rats

    PubMed Central

    Zhang, Zhenwen; Fang, Penghua; He, Biao; Guo, Lili; Runesson, Johan; Langel, Ülo; Shi, Mingyi; Zhu, Yan; Bo, Ping

    2016-01-01

    Our previous studies testified the beneficial effect of central galanin on insulin sensitivity of type 2 diabetic rats. The aim of the study was further to investigate whether central M617, a galanin receptor 1 agonist, can benefit insulin sensitivity. The effects of intracerebroventricular administration of M617 on insulin sensitivity and insulin signaling were evaluated in adipose tissues of type 2 diabetic rats. The results showed that central injection of M617 significantly increased plasma adiponectin contents, glucose infusion rates in hyperinsulinemic-euglycemic clamp tests, GLUT4 mRNA expression levels, GLUT4 contents in plasma membranes, and total cell membranes of the adipose cells but reduced the plasma C-reactive protein concentration in nondiabetic and diabetic rats. The ratios of GLUT4 contents were higher in plasma membranes to total cell membranes in both nondiabetic and diabetic M617 groups than each control. In addition, the central administration of M617 enhanced the ratios of pAkt/Akt and pAS160/AS160, but not phosphorylative cAMP response element-binding protein (pCREB)/CREB in the adipose cells of nondiabetic and diabetic rats. These results suggest that excitation of central galanin receptor 1 facilitates insulin sensitivity via activation of the Akt/AS160 signaling pathway in the fat cells of type 2 diabetic rats. PMID:27127795

  8. Group D Adenoviruses Infect Primary Central Nervous System Cells More Efficiently than Those from Group C

    PubMed Central

    Chillon, Miguel; Bosch, Assumpció; Zabner, Joseph; Law, Lane; Armentano, Donna; Welsh, Michael J.; Davidson, Beverly L.

    1999-01-01

    Group C adenovirus-mediated gene transfer to central nervous system cells is inefficient. We found that wild-type group D viruses, or recombinant adenovirus type 2 (Ad2) (group C) modified to contain Ad17 (group D) fiber, were more efficient in infecting primary cultures of neurons. Together with studies on primary vascular endothelial cells and tissue culture cell lines, our results indicate that there is not a universally applicable adenovirus serotype for use as a gene transfer vector. PMID:9971839

  9. Giant solitary trichoepithelioma

    PubMed Central

    Teli, Bhavuray; Thrishuli, P. B.; Santhosh, R.; Amar, D. N.; Rajpurohit, Shravan

    2015-01-01

    Adnexal tumors like giant solitary trichoepitheliomas are uncommon to most of us to permit a ready familiarity with them. Information regarding the genesis, clinical profile, behavior, and management options for this tumor is limited. There are 18 cases reported in the world literature till date. This review attempts to provide insight to this rare tumor. Our search included indexed literature from Pubmed, Directory of Open Access Journals, Health Inter Network Access to Research Initiative and Google databases in addition to standard dermatology texts. Giant solitary trichoepithelioma is a rare trichogenic tumor with potential for local recurrence. It has predilection for the older age, but may present at any age including at birth. It has close resemblance to basal cell carcinoma and other skin adnexal tumors - clinically, cytologically, and histologically. CD10, CD 34, PHLDA1 but not p75NTR are useful adjunct markers. Surgical excision is the standard treatment. Recurrence and possible transformation into BCC cautions follow up at regular intervals. PMID:25839021

  10. Giant solitary trichoepithelioma.

    PubMed

    Teli, Bhavuray; Thrishuli, P B; Santhosh, R; Amar, D N; Rajpurohit, Shravan

    2015-01-01

    Adnexal tumors like giant solitary trichoepitheliomas are uncommon to most of us to permit a ready familiarity with them. Information regarding the genesis, clinical profile, behavior, and management options for this tumor is limited. There are 18 cases reported in the world literature till date. This review attempts to provide insight to this rare tumor. Our search included indexed literature from Pubmed, Directory of Open Access Journals, Health Inter Network Access to Research Initiative and Google databases in addition to standard dermatology texts. Giant solitary trichoepithelioma is a rare trichogenic tumor with potential for local recurrence. It has predilection for the older age, but may present at any age including at birth. It has close resemblance to basal cell carcinoma and other skin adnexal tumors - clinically, cytologically, and histologically. CD10, CD 34, PHLDA1 but not p75NTR are useful adjunct markers. Surgical excision is the standard treatment. Recurrence and possible transformation into BCC cautions follow up at regular intervals. PMID:25839021

  11. Giant papillary conjunctivitis.

    PubMed Central

    Donshik, P C

    1994-01-01

    Giant papillary conjunctivitis is a syndrome found frequently as a complication of contact lenses. Many variables can affect the onset and severity of the presenting signs and symptoms. Rigid gas permeable contact lenses appear to result in less severe signs and symptoms, with a longer time before the development of giant papillary conjunctivitis. Nonionic, low-water-content soft contact lenses tend to produce less severe signs and symptoms than ionic, low-water-content soft contact lenses. Enzymatic treatment appears to lessen the severity of signs and symptoms. The association of an allergy appears to play a role in the onset of the severity of the signs and symptoms but does not appear to affect the final ability of the individual to wear contact lenses. Using multiple treatment options, such as changing the polymer to a glyceryl methyl methacrylate or a rigid lens, or utilizing a soft lens on a frequent-replacement basis, can result in a success rate of over 90%. In individuals who still have a return of symptoms, the use of topical mast cell stabilizers or a nonsteroidal anti-inflammatory drug as an adjunctive therapy offers the added possibility of keeping these patients in contact lenses. Images FIGURE 1 FIGURE 2 FIGURE 3 FIGURE 4 FIGURE 5 FIGURE 6 FIGURE 7 FIGURE 11 A FIGURE 11 B FIGURE 11 C FIGURE 11 D PMID:7886881

  12. ssiRNA Induced Gene Silencing is Transmitted Between Cells From the Mammalian Central Nervous System

    PubMed Central

    Zhao, Tian-Yong; Zou, Shi-Ping; Alimova, Yelena V.; Wang, Guoying; Hauser, Kurt F.; Ghandour, M. Said; Knapp, Pamela E.

    2014-01-01

    Although siRNA induced gene silencing can be transmitted between cells in plants and in C. elegans, this phenomenon has been barely studied in mammalian cells. Both immortalized oligodendrocytes and SNB-19 glioblastoma cells were transfected with siRNA constructs for PTEN (phosphatase and tensin homolog deleted on chromosome 10) or Akt (Akt/protein kinase B). Co-cultures were established between silenced cells and non-silenced cells which were hygromycin resistant and/or expressed green fluorescent protein (GFP). After fluorescence sorting or hygromycin selection to remove the silenced cells, the expression of PTEN or Akt genes in the originally unsilenced cells was in all cases significantly decreased. Importantly, silencing did not occur in transwell culture studies, suggesting that transmission of the silencing signal requires a close association between cells. These results provide the first direct demonstration that an siRNA induced silencing signal can be transmitted between mammalian central nervous system (CNS) cells. PMID:16923165

  13. Endothelial cells are a replicative niche for entry of Toxoplasma gondii to the central nervous system.

    PubMed

    Konradt, Christoph; Ueno, Norikiyo; Christian, David A; Delong, Jonathan H; Pritchard, Gretchen Harms; Herz, Jasmin; Bzik, David J; Koshy, Anita A; McGavern, Dorian B; Lodoen, Melissa B; Hunter, Christopher A

    2016-01-01

    An important function of the blood-brain barrier is to exclude pathogens from the central nervous system, but some microorganisms benefit from the ability to enter this site. It has been proposed that Toxoplasma gondii can cross biological barriers as a motile extracellular form that uses transcellular or paracellular migration, or by infecting a host cell that then crosses the blood-brain barrier. Unexpectedly, analysis of acutely infected mice revealed significant numbers of free parasites in the blood and the presence of infected endothelial cells in the brain vasculature. The use of diverse transgenic parasites combined with reporter mice and intravital imaging demonstrated that replication in and lysis of endothelial cells precedes invasion of the central nervous system, and highlight a novel mechanism for parasite entry to the central nervous system. PMID:27572166

  14. Endothelial cells are a replicative niche for entry of Toxoplasma gondii to the central nervous system

    PubMed Central

    Konradt, Christoph; Ueno, Norikiyo; Christian, David A.; Delong, Jonathan H.; Pritchard, Gretchen Harms; Herz, Jasmin; Bzik, David J.; Koshy, Anita A.; McGavern, Dorian B.; Lodoen, Melissa B.; Hunter, Christopher A.

    2016-01-01

    An important function of the blood–brain barrier is to exclude pathogens from the central nervous system, but some microorganisms benefit from the ability to enter this site. It has been proposed that Toxoplasma gondii can cross biological barriers as a motile extracellular form that uses transcellular or paracellular migration, or by infecting a host cell that then crosses the blood–brain barrier. Unexpectedly, analysis of acutely infected mice revealed significant numbers of free parasites in the blood and the presence of infected endothelial cells in the brain vasculature. The use of diverse transgenic parasites combined with reporter mice and intravital imaging demonstrated that replication in and lysis of endothelial cells precedes invasion of the central nervous system, and highlight a novel mechanism for parasite entry to the central nervous system. PMID:27478622

  15. Shadowing on Apollo 12 Solar Cells and Possible Movement of the ALSEP Central Station

    NASA Technical Reports Server (NTRS)

    Berman, Paul A.; Williams, David R.

    2014-01-01

    A fortuitous arrangement of a west-facing solar cell and a bracket on the Apollo 12 ALSEP (Apollo Lunar Surface Experiments Package) has allowed us to precisely determine the relative position of the Sun near sunset relative to the Apollo 12 central station over a period of nearly 8 years. The small bracket, mounted on the central station due west of the cell, casts a shadow on the cell near sunset, decreasing the output of the cell proportional to the area of shadow covering the cell. The pattern of shadowing by the bracket gives good agreement with the known change of solar azimuth on a yearly timescale, but the pattern gradually but constantly changed from year-to-year, in a manner inconsistent with the known and changing position of the Sun.

  16. Everolimus for the treatment of subependymal giant cell astrocytoma probably causing seizure aggravation in a child with tuberous sclerosis complex: a case report.

    PubMed

    Wiemer-Kruel, Adelheid; Woerle, H; Strobl, K; Bast, T

    2014-04-01

    We are reporting on a 13.5-year-old girl with tuberous sclerosis complex (TSC) who was treated with everolimus because of giant cell astrocytoma and bilateral angiomyolipoma. She suffered from pharmacoresistant partial epilepsy with clusters of tonic and tonic-clonic seizures. Treatment with carbamazepine and sulthiame had led to a stable situation for more than 2.5 years. The dosage of everolimus had to be increased and refractory status epilepticus followed after 12 days. In the absence of any other possible cause, we believe that the status epilepticus was provoked by everolimus. So far, only a few cases of possible seizure aggravation by everolimus have been reported. The clinical relevance of possible negative effects in epileptic patients remains unclear. Similar observations should be documented and reported. PMID:24293099

  17. Biological Reconstruction of the Knee Joint in a Case of Giant Cell Tumor of the Tibia of 15yrs Followup- A Case Report

    PubMed Central

    Ravindranath, V S; Sastri, V.R.K.

    2014-01-01

    Introduction: A 40 year old male patient presented to us with Giant Cell Tumor of upper end of Tibia involving both condyles with a breach in the posterior cortex. In this case report we tried to retain the joint function by biological reconstruction using the Patella after the wide excision of the tumor mass. Case Report: A radical excision of the upper end of the Tibia was done. The Patella was used as an articular surface supported by ipsilateral Fibula as struts, thus the joint was reconstructured biologically. The case was followed for 15years. Conclusion: The tumor was excised in toto, the knee joint was restored by the Patella and the Fibular struts. The results were discussed in details. PMID:27299004

  18. Clinical Practice: Giant Cell Tumour of the Jaw Mimicking Bone Malignancy on Three-Dimensional Computed Tomography (3D CT) Reconstruction

    PubMed Central

    Lanza, Alessandro; Laino, Luigi; Rossiello, Luigi; Perillo, Letizia; Ermo, Antonio Dell; Cirillo, Nicola

    2008-01-01

    A wide range of diseases may present with radiographic features of osteolysis. Periapical inflammation, cysts and benign tumours, bone malignancies, all of these conditions may show bone resorption on radiograph. Features of the surrounding bone, margins of the lesion, and biological behaviour including tendency to infiltration and root resorption, may represent important criteria for distinguishing benign tumours from their malign counterpart, although the radiographic aspect of the lesion is not always predictive. Therefore a critical differential diagnosis has to be reached to choose the best management. Here, we report a case of giant cell tumour (GCT) whose radiological features by computed tomography (CT) suggested the presence of bone malignancy, whereas the evaluation of a routine OPT scan comforted us about the benign nature of the lesion. A brief review of the literature on such a benign but locally aggressive neoplasm is also provided. PMID:19088886

  19. 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

  20. Effect of fluidics on corneal endothelial cell density, central corneal thickness, and central macular thickness after phacoemulsification with torsional ultrasound

    PubMed Central

    Das, Sudeep; Nanaiah, Soumya Ganesh; Kummelil, Mathew K; Nagappa, Somshekar; Shetty, Rohit; Shetty, Bhujang K

    2015-01-01

    Aim: To study the relative effects of high and low fluidic parameters on endothelial cell density (ECD), central corneal thickness (CCT), and central macular thickness (CMT) after phacoemulsification with torsional ultrasound. Settings and Design: Prospective, randomized clinical trial based on a tertiary eye hospital. Subjects and Methods: The study included 65 patients in each group. Patients were randomized to either the high or the low flow group using a computerized random number table. The study was patient and examiner masked. All patients underwent phacoemulsification with torsional ultrasound. Visual acuity, ECD, CCT, and CMT were measured for all patients preoperatively at 2 weeks and 6 weeks postoperatively. Statistical Analysis Used: The Shapiro–Wilks test was used to assess the normality of the data. Mann–Whitney U-test with the P value set at 0.05 was used to compare the two groups. Results: Cumulative dissipated energy was significantly higher in the low flow group (16.44 ± 9.07 vs. 11.74 ± 6.68; P = 0.002). No statistically significant difference was noted between the two groups in the ECD, CCT, CMT, or corrected distance visual acuity at the end of 6 weeks. Conclusions: No significant difference was noted in the postoperative outcome between high and low flow groups. Parameters can be modified to suit the surgeon's preference, as both high and low flow parameters were found to have comparable postoperative outcomes. PMID:26576520

  1. Diagnostic value of H3F3A mutations in giant cell tumour of bone compared to osteoclast‐rich mimics

    PubMed Central

    Presneau, Nadège; Baumhoer, Daniel; Behjati, Sam; Pillay, Nischalan; Tarpey, Patrick; Campbell, Peter J; Jundt, Gernot; Hamoudi, Rifat; Wedge, David C; Loo, Peter Van; Hassan, A Bassim; Khatri, Bhavisha; Ye, Hongtao; Tirabosco, Roberto; Amary, M Fernanda

    2015-01-01

    Abstract Driver mutations in the two histone 3.3 (H3.3) genes, H3F3A and H3F3B, were recently identified by whole genome sequencing in 95% of chondroblastoma (CB) and by targeted gene sequencing in 92% of giant cell tumour of bone (GCT). Given the high prevalence of these driver mutations, it may be possible to utilise these alterations as diagnostic adjuncts in clinical practice. Here, we explored the spectrum of H3.3 mutations in a wide range and large number of bone tumours (n = 412) to determine if these alterations could be used to distinguish GCT from other osteoclast‐rich tumours such as aneurysmal bone cyst, nonossifying fibroma, giant cell granuloma, and osteoclast‐rich malignant bone tumours and others. In addition, we explored the driver landscape of GCT through whole genome, exome and targeted sequencing (14 gene panel). We found that H3.3 mutations, namely mutations of glycine 34 in H3F3A, occur in 96% of GCT. We did not find additional driver mutations in GCT, including mutations in IDH1, IDH2, USP6, TP53. The genomes of GCT exhibited few somatic mutations, akin to the picture seen in CB. Overall our observations suggest that the presence of H3F3A p.Gly34 mutations does not entirely exclude malignancy in osteoclast‐rich tumours. However, H3F3A p.Gly34 mutations appear to be an almost essential feature of GCT that will aid pathological evaluation of bone tumours, especially when confronted with small needle core biopsies. In the absence of H3F3A p.Gly34 mutations, a diagnosis of GCT should be made with caution.

  2. Effects of diabetic keratopathy on corneal optical density, central corneal thickness, and corneal endothelial cell counts

    PubMed Central

    Gao, Feng; Lin, Tao; Pan, Yingzhe

    2016-01-01

    Diabetic keratopathy is an ocular complication that occurs with diabetes. In the present study, the effect of diabetic keratopathy on corneal optical density, central corneal thickness, and corneal endothelial cell count was investigated. One hundred and eighty diabetic patients (360 eyes) were enrolled in the study during the period from March, 2012 to March, 2013. The patients were divided into three age groups: <5, 5–10 and >10 years, with 60 patients per group (120 eyes). During the same period, 60 healthy cases (120 eyes) were selected and labeled as the normal control group. The Pentacam was used to measure the corneal optical density, and central corneal thickness. Specular microscopy was used to examine the corneal endothelial cell density. The coefficient of partial correlation was used to control age and correlate the analysis between the corneal optical density, corneal endothelial cell density, and central corneal thickness. The stage of the disease, the medial and intimal corneal optical density and central corneal thickness was analyzed in the diabetes group. The corneal optical density in the diabetes group increased compared with that of the normal control group. The medial and intimal corneal optical density and central corneal thickness were positively correlated with the course of the disease. However, the corneal endothelial cell density was not associated with the course of diabetes. There was a positive association between the medial and intimal corneal optical density and central corneal thickness of the diabetic patients. In conclusion, the results of the present study show that medial and intimal corneal optical density and central corneal thickness were sensitive indicators for early diabetic keratopathy.

  3. Giant Pumpkins

    NASA Astrophysics Data System (ADS)

    Hu, David; Alexeev, Alex

    2009-11-01

    In this combined experimental and theoretical study, we investigate the growth of pumpkins from 1 to 1000 pounds in weight. Time-lapse photography is used to document the growth of pumpkins. Data is presented on the relation between the pumpkins' weights and aspect ratios (height divided by width). We observe pumpkins tend to become squashed (up to 50%) as they increase in size. The lattice-spring method is used to numerically estimate the elasto-plastic forces resisting deformation of the pumpkin. Using levels of plasticity consistent with that of plant cell growth, we find pumpkins shapes consistent with those observed.

  4. Programmed cell death acts at different stages of Drosophila neurodevelopment to shape the central nervous system.

    PubMed

    Pinto-Teixeira, Filipe; Konstantinides, Nikolaos; Desplan, Claude

    2016-08-01

    Nervous system development is a process that integrates cell proliferation, differentiation, and programmed cell death (PCD). PCD is an evolutionary conserved mechanism and a fundamental developmental process by which the final cell number in a nervous system is established. In vertebrates and invertebrates, PCD can be determined intrinsically by cell lineage and age, as well as extrinsically by nutritional, metabolic, and hormonal states. Drosophila has been an instrumental model for understanding how this mechanism is regulated. We review the role of PCD in Drosophila central nervous system development from neural progenitors to neurons, its molecular mechanism and function, how it is regulated and implemented, and how it ultimately shapes the fly central nervous system from the embryo to the adult. Finally, we discuss ideas that emerged while integrating this information. PMID:27404003

  5. Establishment of an agamid cell line and isolation of adenoviruses from central bearded dragons (Pogona vitticeps).

    PubMed

    Ball, Inna; Hoferer, Marc; Marschang, Rachel E

    2014-03-01

    A cell line was established from whole 6-8-week-old central bearded dragon (Pogona vitticeps) embryos. Cells were mid-sized and showed an elongated and polymorphic form. The cell line grew in a monolayer and has been serially passaged for 17 passages at time of publication. This cell line has been used with samples from adenovirus polymerase chain reaction (PCR)-positive bearded dragons, and 2 virus isolates have been obtained so far. The isolates show a clear cytopathic effect in inoculated cells. Both virus isolates have been serially passaged on this cell line, and have been identified by PCR amplification and sequencing of a portion of the DNA-dependent DNA polymerase gene and show 100% nucleotide identity to the corresponding region of an agamid adenovirus. Electron microscopic examination of supernatant from infected cells demonstrated the presence of nonenveloped particles, with a diameter of approximately 80 nm in both virus isolates. PMID:24569225

  6. B cell VLA-4-deficiency reduces leukocyte recruitment and susceptibility to central nervous system autoimmunity

    PubMed Central

    Lehmann-Horn, Klaus; Sagan, Sharon A.; Bernard, Claude C.A.; Sobel, Raymond A.; Zamvil, Scott S.

    2015-01-01

    Natalizumab, which binds very late antigen-4 (VLA-4), is a potent therapy for multiple sclerosis (MS). Studies have focused primarily upon its capacity to interfere with T cell-migration into the central nervous system (CNS). B cells are important in MS pathogenesis and express high levels of VLA-4. Here, we report that the selective inhibition of VLA-4-expression on B cells impedes CNS accumulation of B cells, recruitment of Th17 cells and macrophages, and reduces susceptibility to experimental autoimmune encephalomyelitis (EAE). These results underscore the importance of B cell VLA-4-expression in pathogenesis of CNS autoimmunity and provide insight regarding mechanisms that may contribute to the benefit of natalizumab in MS, as well as candidate therapeutics that selectively target B cells. PMID:25712734

  7. Bovine central memory T cells are highly proliferative in response to bovine tuberculosis infection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Long-term (i.e., 14 days) cultured IFN-gamma ELISPOT assays measure central memory T cell (Tcm) responses in both humans and cattle. With bovine tuberculosis, vaccine-elicited long-term IFN-gamma ELISPOT responses correlate with protection. In other species, Tcm’s pose low activation threshold and a...

  8. Case Study: Fuel Cells Provide Combined Heat and Power at Verizon's Garden City Central Office

    SciTech Connect

    2010-12-01

    This case study describes how Verizon's Central Office in Garden City, NY, installed a 1.4-MW phosphoric acid fuel cell system as an alternative solution to bolster electric reliability, optimize the company's energy use, and reduce costs in an environmentally responsible manner.

  9. Primary central nervous system T-cell lymphoma mimicking meningoencephalomyelitis in a cat

    PubMed Central

    Guil-Luna, Silvia; Carrasco, Librado; Gómez-Laguna, Jaime; Hilbe, Monika; Mínguez, Juan J.; Köhler, Kernt; de las Mulas, Juana Martín

    2013-01-01

    A cat was presented with right head tilt and circling. The lack of expression of virus antigens did not support the postmortem diagnosis of encephalomyelitis pointing to a diffuse primary central nervous system T-cell lymphoma on the basis of CD3 and CD45R co-expression with absence of CD79α staining. PMID:24155454

  10. Primary central nervous system T-cell lymphoma mimicking meningoencephalomyelitis in a cat.

    PubMed

    Guil-Luna, Silvia; Carrasco, Librado; Gómez-Laguna, Jaime; Hilbe, Monika; Mínguez, Juan J; Köhler, Kernt; de las Mulas, Juana Martín

    2013-06-01

    A cat was presented with right head tilt and circling. The lack of expression of virus antigens did not support the postmortem diagnosis of encephalomyelitis pointing to a diffuse primary central nervous system T-cell lymphoma on the basis of CD3 and CD45R co-expression with absence of CD79α staining. PMID:24155454

  11. CEACAM1 mediates B cell aggregation in central nervous system autoimmunity

    PubMed Central

    Rovituso, Damiano M.; Scheffler, Laura; Wunsch, Marie; Dörck, Sebastian; Ulzheimer, Jochen; Bayas, Antonios; Steinman, Lawrence; Ergün, Süleyman; Kuerten, Stefanie

    2016-01-01

    B cell aggregates in the central nervous system (CNS) have been associated with rapid disease progression in patients with multiple sclerosis (MS). Here we demonstrate a key role of carcinoembryogenic antigen-related cell adhesion molecule1 (CEACAM1) in B cell aggregate formation in MS patients and a B cell-dependent mouse model of MS. CEACAM1 expression was increased on peripheral blood B cells and CEACAM1+ B cells were present in brain infiltrates of MS patients. Administration of the anti-CEACAM1 antibody T84.1 was efficient in blocking aggregation of B cells derived from MS patients. Along these lines, application of the monoclonal anti-CEACAM1 antibody mCC1 was able to inhibit CNS B cell aggregate formation and significantly attenuated established MS-like disease in mice in the absence of any adverse effects. CEACAM1 was co-expressed with the regulator molecule T cell immunoglobulin and mucin domain −3 (TIM-3) on B cells, a novel molecule that has recently been described to induce anergy in T cells. Interestingly, elevated coexpression on B cells coincided with an autoreactive T helper cell phenotype in MS patients. Overall, these data identify CEACAM1 as a clinically highly interesting target in MS pathogenesis and open new therapeutic avenues for the treatment of the disease. PMID:27435215

  12. CEACAM1 mediates B cell aggregation in central nervous system autoimmunity.

    PubMed

    Rovituso, Damiano M; Scheffler, Laura; Wunsch, Marie; Kleinschnitz, Christoph; Dörck, Sebastian; Ulzheimer, Jochen; Bayas, Antonios; Steinman, Lawrence; Ergün, Süleyman; Kuerten, Stefanie

    2016-01-01

    B cell aggregates in the central nervous system (CNS) have been associated with rapid disease progression in patients with multiple sclerosis (MS). Here we demonstrate a key role of carcinoembryogenic antigen-related cell adhesion molecule1 (CEACAM1) in B cell aggregate formation in MS patients and a B cell-dependent mouse model of MS. CEACAM1 expression was increased on peripheral blood B cells and CEACAM1(+) B cells were present in brain infiltrates of MS patients. Administration of the anti-CEACAM1 antibody T84.1 was efficient in blocking aggregation of B cells derived from MS patients. Along these lines, application of the monoclonal anti-CEACAM1 antibody mCC1 was able to inhibit CNS B cell aggregate formation and significantly attenuated established MS-like disease in mice in the absence of any adverse effects. CEACAM1 was co-expressed with the regulator molecule T cell immunoglobulin and mucin domain -3 (TIM-3) on B cells, a novel molecule that has recently been described to induce anergy in T cells. Interestingly, elevated coexpression on B cells coincided with an autoreactive T helper cell phenotype in MS patients. Overall, these data identify CEACAM1 as a clinically highly interesting target in MS pathogenesis and open new therapeutic avenues for the treatment of the disease. PMID:27435215

  13. [Giant cholesterol cysts of the petrous apex].

    PubMed

    Pellet, W; Valenzuela, S; Malca, S; Cannoni, M; Perez-Castillo, A M

    1992-01-01

    In connection with their two own cases, the authors deal about the giant cholesterol cysts of the petrous apex. The lesions which are to be differentiated from epidermoid cysts are cholesterol granulomas. Their petrous apex location explains their characteristic large appearance. As each cholesterol granuloma, they occur when a bony cell is obstructed. This chronic obstruction induces mucosal edema then bleedings which lead to the formation and, by the lack of drainage, to the accumulation of cholesterol crystals. These crystals initiate a non specific reaction to foreign bodies, a granuloma, which also can bleed. Thus, a continuous cycle perpetuates the growth of the lesion. This lesion, when it is localized in the petrous apex, can reach a big size before the appearance of some signs. Usually, these are otologic (sensorineural hearing loss, tinnitus, vertigo) and/or cranial nerve palsies (V, VI, VII). C.T. scan (well defined, sharply marginated bony expansible lesion with isodense to the brain central part) and M.R.I. (central region of increased intensity on both T1 and T2 weighted images and peripheral rim of markedly decreased signal intensity in all instances) features are characteristic enough to allow diagnose with other petrous apex lesions (cholesteatoma, mucocele, epithelial cyst, histiocytosis X, ...). Surgical treatment must try to evacuate and to aerate the cavity or perhaps to obliterate it with fatty pieces in order to prevent the recurrence. PMID:1299772

  14. A novel coculture model of porcine central neuroretina explants and retinal pigment epithelium cells

    PubMed Central

    Di Lauro, Salvatore; Rodriguez-Crespo, David; Gayoso, Manuel J.; Garcia-Gutierrez, Maria T.; Pastor, J. Carlos; Srivastava, Girish K.

    2016-01-01

    Purpose To develop and standardize a novel organ culture model using porcine central neuroretina explants and RPE cells separated by a cell culture membrane. Methods RPE cells were isolated from porcine eyes, expanded, and seeded on the bottom of cell culture inserts. Neuroretina explants were obtained from the area centralis and cultured alone (controls) on cell culture membranes or supplemented with RPE cells in the same wells but physically separated by the culture membrane. Finally, cellular and tissue specimens were processed for phase contrast, cyto-/histological, and immunochemical evaluation. Neuroretina thickness was also determined. Results Compared to the neuroretinas cultured alone, the neuroretinas cocultured with RPE cells maintained better tissue structure and cellular organization, displayed better preservation of photoreceptors containing rhodopsin, lower levels of glial fibrillary acidic protein immunoexpression, and preservation of cellular retinaldehyde binding protein both markers of reactive gliosis. Neuroretina thickness was significantly greater in the cocultures. Conclusions A coculture model of central porcine neuroretina and RPE cells was successfully developed and standardized. This model mimics a subretinal space and will be useful in studying interactions between the RPE and the neuroretina and to preclinically test potential therapies. PMID:27081295

  15. FUNCTIONAL CONNECTIONS ARE ESTABLISHED BETWEEN GIANT NERVE FIBERS IN GRAFTED EARTHWORMS

    EPA Science Inventory

    Giant fiber interconnections were examined in successful grafts between two posterior portions of earthworms (Eisenia foetida). Electrophysiological and histological results indicated that cell-specific interanimal connections were formed between the medial giant fibers (MGF) in ...

  16. Physiological, pathological, and engineered cell identity reprogramming in the central nervous system.

    PubMed

    Smith, Derek K; Wang, Lei-Lei; Zhang, Chun-Li

    2016-07-01

    Multipotent neural stem cells persist in restricted regions of the adult mammalian central nervous system. These proliferative cells differentiate into diverse neuron subtypes to maintain neural homeostasis. This endogenous process can be reprogrammed as a compensatory response to physiological cues, traumatic injury, and neurodegeneration. In addition to innate neurogenesis, recent research has demonstrated that new neurons can be engineered via cell identity reprogramming in non-neurogenic regions of the adult central nervous system. A comprehensive understanding of these reprogramming mechanisms will be essential to the development of therapeutic neural regeneration strategies that aim to improve functional recovery after injury and neurodegeneration. WIREs Dev Biol 2016, 5:499-517. doi: 10.1002/wdev.234 For further resources related to this article, please visit the WIREs website. PMID:27258392

  17. Neural Stem Cells: Implications for the Conventional Radiotherapy of Central Nervous System Malignancies

    SciTech Connect

    Barani, Igor J.; Benedict, Stanley H.; Lin, Peck-Sun . E-mail: plin@vcu.edu

    2007-06-01

    Advances in basic neuroscience related to neural stem cells and their malignant counterparts are challenging traditional models of central nervous system tumorigenesis and intrinsic brain repair. Neurogenesis persists into adulthood predominantly in two neurogenic centers: subventricular zone and subgranular zone. Subventricular zone is situated adjacent to lateral ventricles and subgranular zone is confined to the dentate gyrus of the hippocampus. Neural stem cells not only self-renew and differentiate along multiple lineages in these regions, but also contribute to intrinsic brain plasticity and repair. Ionizing radiation can depopulate these exquisitely sensitive regions directly or impair in situ neurogenesis by indirect, dose-dependent and inflammation-mediated mechanisms, even at doses <2 Gy. This review discusses the fundamental neural stem cell concepts within the framework of cumulative clinical experience with the treatment of central nervous system malignancies using conventional radiotherapy.

  18. Central Muscarinic Cholinergic Activation Alters Interaction between Splenic Dendritic Cell and CD4+CD25- T Cells in Experimental Colitis

    PubMed Central

    Pavlov, Valentin A.; Tracey, Kevin J.; Khafipour, Ehsan; Ghia, Jean-Eric

    2014-01-01

    Background The cholinergic anti-inflammatory pathway (CAP) is based on vagus nerve (VN) activity that regulates macrophage and dendritic cell responses in the spleen through alpha-7 nicotinic acetylcholine receptor (a7nAChR) signaling. Inflammatory bowel disease (IBD) patients present dysautonomia with decreased vagus nerve activity, dendritic cell and T cell over-activation. The aim of this study was to investigate whether central activation of the CAP alters the function of dendritic cells (DCs) and sequential CD4+/CD25−T cell activation in the context of experimental colitis. Methods The dinitrobenzene sulfonic acid model of experimental colitis in C57BL/6 mice was used. Central, intracerebroventricular infusion of the M1 muscarinic acetylcholine receptor agonist McN-A-343 was used to activate CAP and vagus nerve and/or splenic nerve transection were performed. In addition, the role of α7nAChR signaling and the NF-kB pathway was studied. Serum amyloid protein (SAP)-A, colonic tissue cytokines, IL-12p70 and IL-23 in isolated splenic DCs, and cytokines levels in DC-CD4+CD25−T cell co-culture were determined. Results McN-A-343 treatment reduced colonic inflammation associated with decreased pro-inflammatory Th1/Th17 colonic and splenic cytokine secretion. Splenic DCs cytokine release was modulated through α7nAChR and the NF-kB signaling pathways. Cholinergic activation resulted in decreased CD4+CD25−T cell priming. The anti-inflammatory efficacy of central cholinergic activation was abolished in mice with vagotomy or splenic neurectomy. Conclusions Suppression of splenic immune cell activation and altered interaction between DCs and T cells are important aspects of the beneficial effect of brain activation of the CAP in experimental colitis. These findings may lead to improved therapeutic strategies in the treatment of IBD. PMID:25295619

  19. Two distinct distribution patterns of sarcoplasmic reticulum in two functionally different giant smooth muscle cells of Beroe ovata.

    PubMed

    Cario, C; Malaval, L; Hernandez-Nicaise, M L

    1995-12-01

    The sarcoplasmic reticulum has been studied in radial and longitudinal giant smooth muscle fibres of the marine planktonic invertebrate Beroe. Impregnation with heavy metals has revealed that the smooth component is organised in a longitudinally oriented three-dimensional network of tubules running along the myofilaments. An ultrastructural morphometric analysis has shown that the relative volume of the sarcoplasmic reticulum is the same (1% of the myofilament volume) in both fibres but that the size, number and distribution of the sarcoplasmic reticulum tubules differ significantly. The longitudinal fibres are characterised physiologically by an action potential with a short calcium-dependent plateau that can trigger a short contraction; radial fibres produce action potentials without a plateau and their contraction requires a train of spikes. The sarcoplasmic reticulum tubules in longitudinal fibres are thinner (132 nm in diameter) and more numerous than those in radial fibres (160 nm in diameter). Moreover, the tubules are homogeneously distributed among the myofilaments in radial fibres, whereas they are more numerous in the centre of longitudinal muscles. PMID:8581937

  20. K+ accumulation in the space between giant axon and Schwann cell in the squid Alloteuthis. Effects of changes in osmolarity.

    PubMed Central

    Astion, M L; Coles, J A; Orkand, R K; Abbott, N J

    1988-01-01

    In a train of impulses in squid giant axon, accumulation of extracellular potassium causes successive afterhyperpolarizations to be progressively less negative. In Loligo, Frankenhaeuser and Hodgkin had satisfactorily accounted for the characteristics of this effect with a model in which the axon is surrounded by a space, width theta, and a barrier of permeability P. In axons isolated from Alloteuthis, we found that the model fitted the observations quite well. Superfusing the axon with hypotonic artificial seawater (ASW) caused theta and P to decrease, and, conversely, hypertonic ASW caused them to increase: this would be the case if both the space and the pathway through the barrier were extracellular. In some cases, in normal ASW, the afterhyperpolarizations in a train decreased very little, less than 0.7 mV. In these extreme cases, theta was estimated to be 190 nm and P to be 7 x 10(-4) cm s-1, both several times the values of 30 nm and 6 x 10(-5) cm s-1 estimated by Frankenhaeuser and Hodgkin. We suggest that in vivo the periaxonal space may be considerably wider than that seen in conventionally fixed squid tissue. PMID:3345336

  1. Impurity of stem cell graft by murine embryonic fibroblasts - implications for cell-based therapy of the central nervous system.

    PubMed

    Molcanyi, Marek; Mehrjardi, Narges Zare; Schäfer, Ute; Haj-Yasein, Nadia Nabil; Brockmann, Michael; Penner, Marina; Riess, Peter; Reinshagen, Clemens; Rieger, Bernhard; Hannes, Tobias; Hescheler, Jürgen; Bosche, Bert

    2014-01-01

    Stem cells have been demonstrated to possess a therapeutic potential in experimental models of various central nervous system disorders, including stroke. The types of implanted cells appear to play a crucial role. Previously, groups of the stem cell network NRW implemented a feeder-based cell line within the scope of their projects, examining the implantation of stem cells after ischemic stroke and traumatic brain injury. Retrospective evaluation indicated the presence of spindle-shaped cells in several grafts implanted in injured animals, which indicated potential contamination by co-cultured feeder cells (murine embryonic fibroblasts - MEFs). Because feeder-based cell lines have been previously exposed to a justified criticism with regard to contamination by animal glycans, we aimed to evaluate the effects of stem cell/MEF co-transplantation. MEFs accounted for 5.3 ± 2.8% of all cells in the primary FACS-evaluated co-culture. Depending on the culture conditions and subsequent purification procedure, the MEF-fraction ranged from 0.9 to 9.9% of the cell suspensions in vitro. MEF survival and related formation of extracellular substances in vivo were observed after implantation into the uninjured rat brain. Impurity of the stem cell graft by MEFs interferes with translational strategies, which represents a threat to the potential recipient and may affect the graft microenvironment. The implications of these findings are critically discussed. PMID:25249934

  2. IL-10-dependent Tr1 cells attenuate astrocyte activation and ameliorate chronic central nervous system inflammation.

    PubMed

    Mayo, Lior; Cunha, Andre Pires Da; Madi, Asaf; Beynon, Vanessa; Yang, Zhiping; Alvarez, Jorge I; Prat, Alexandre; Sobel, Raymond A; Kobzik, Lester; Lassmann, Hans; Quintana, Francisco J; Weiner, Howard L

    2016-07-01

    SEE WINGER AND ZAMVIL DOI101093/BRAIN/AWW121 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: The innate immune system plays a central role in the chronic central nervous system inflammation that drives neurological disability in progressive forms of multiple sclerosis, for which there are no effective treatments. The mucosal immune system is a unique tolerogenic organ that provides a physiological approach for the induction of regulatory T cells. Here we report that nasal administration of CD3-specific antibody ameliorates disease in a progressive animal model of multiple sclerosis. This effect is IL-10-dependent and is mediated by the induction of regulatory T cells that share a similar transcriptional profile to Tr1 regulatory cells and that suppress the astrocyte inflammatory transcriptional program. Treatment results in an attenuated inflammatory milieu in the central nervous system, decreased microglia activation, reduced recruitment of peripheral monocytes, stabilization of the blood-brain barrier and less neurodegeneration. These findings suggest a new therapeutic approach for the treatment of progressive forms of multiple sclerosis and potentially other types of chronic central nervous system inflammation. PMID:27246324

  3. IL-10-dependent Tr1 cells attenuate astrocyte activation and ameliorate chronic central nervous system inflammation

    PubMed Central

    Mayo, Lior; Cunha, Andre Pires Da; Madi, Asaf; Beynon, Vanessa; Yang, Zhiping; Alvarez, Jorge I.; Prat, Alexandre; Sobel, Raymond A.; Kobzik, Lester; Lassmann, Hans; Quintana, Francisco J.

    2016-01-01

    See Winger and Zamvil (doi:10.1093/brain/aww121) for a scientific commentary on this article. The innate immune system plays a central role in the chronic central nervous system inflammation that drives neurological disability in progressive forms of multiple sclerosis, for which there are no effective treatments. The mucosal immune system is a unique tolerogenic organ that provides a physiological approach for the induction of regulatory T cells. Here we report that nasal administration of CD3-specific antibody ameliorates disease in a progressive animal model of multiple sclerosis. This effect is IL-10-dependent and is mediated by the induction of regulatory T cells that share a similar transcriptional profile to Tr1 regulatory cells and that suppress the astrocyte inflammatory transcriptional program. Treatment results in an attenuated inflammatory milieu in the central nervous system, decreased microglia activation, reduced recruitment of peripheral monocytes, stabilization of the blood–brain barrier and less neurodegeneration. These findings suggest a new therapeutic approach for the treatment of progressive forms of multiple sclerosis and potentially other types of chronic central nervous system inflammation. PMID:27246324

  4. Epigenetic silencing of genes and microRNAs within the imprinted Dlk1-Dio3 region at human chromosome 14.32 in giant cell tumor of bone

    PubMed Central

    2014-01-01

    Background Growing evidence exists that the neoplastic stromal cell population (GCTSC) within giant cell tumors (GCT) originates from mesenchymal stem cells (MSC). In a previous study we identified a microRNA signature that differentiates between these cell types. Five differentially expressed microRNAs are located within the Dlk1-Dio3 region on chromosome 14. Aberrant regulation within this region is known to influence cell growth, differentiation and the development of cancer. The aim of this study was to elucidate the involvement of deregulations within the Dlk1-Dio3 region in GCT pathogenesis. Methods Quantitative gene and microRNA expression analyses were performed on GCTSCs and MSCs with or without treatment with epigenetic modifiers. Methylation analysis of differentially methylated regions was performed by bisulfite sequencing. Results In addition to microRNA silencing we detected a significant downregulation of Dlk1, Meg3 and Meg8 in GCTSCs compared to MSCs. DNA methylation analyses of the Meg3-DMR and IG-DMR revealed a frequent hypermethylation within the IG-DMR in GCTs. Epigenetic modification could restore expression of some but not all analyzed genes and microRNAs suggesting further regulatory mechanisms. Conclusion Epigenetic silencing of genes and microRNAs within the Dlk1-Dio3 region is a common event in GCTSCs, in part mediated by hypermethylation within the IG-DMR. The identified genes, micro RNAs and microRNA target genes might be valuable targets for the development of improved strategies for GCT diagnosis and therapy. PMID:25005035

  5. Psg22 expression in mouse trophoblast giant cells is associated with gene inversion and co-expression of antisense long non-coding RNAs.

    PubMed

    Williams, John M; Ball, Melanie; Ward, Andrew; Moore, Tom

    2015-01-01

    Pregnancy-specific glycoproteins (PSGs) are secreted carcinoembryonic antigen (CEA)-related cell adhesion molecules-related members of the immunoglobulin superfamily and are encoded by multigene families in species with haemochorial placentation. PSGs may be the most abundant trophoblast-derived proteins in human maternal blood in late pregnancy and there is evidence that dysregulation of PSG expression is associated with gestational pathology. PSGs are produced by syncytiotrophoblast in the human placenta and by trophoblast giant cells (TGCs) and spongiotrophoblast in rodents, and are implicated in immune regulation, angiogenesis and regulation of platelet function. PSGs are encoded by 17 genes in the mouse and ten genes in the human. While functions appear to be conserved, the typical protein domain organisation differs between species. We analysed the evolution of the mouse Psg genomic locus structure and report inversion of the Psg22 gene within the locus. Psg22 is the most abundant Psg transcript detected in the first half of mouse pregnancy and we identified antisense long non-coding RNA (lncRNA) transcripts adjacent to Psg22 associated with an active local chromatin conformation. This suggests that an epigenetic regulatory mechanism may underpin high Psg22 expression relative to the other Psg gene family members in TGCs. PMID:25359516

  6. Giant viruses come of age.

    PubMed

    Fischer, Matthias G

    2016-06-01

    Viruses with genomes up to a few megabases in length are a common occurrence in nature, even though they have escaped our notice until recently. These giant viruses infect mainly single-celled eukaryotes and isolation efforts concentrating on amoebal hosts alone have spawned hundreds of viral isolates, featuring viruses with previously unseen virion morphologies and the largest known viral genomes and particles. One of the challenges that lie ahead is to analyze and categorize the available data and to establish an approved classification system that reflects the evolutionary relationships and biological properties of these viruses. Extensive sampling of Acanthamoeba-infecting mimiviruses and initial characterization of their virophage parasites have provided a first blueprint of the genetic diversity and composition of a giant virus clade that will facilitate the taxonomic grouping of these fascinating microorganisms. PMID:26999382

  7. Proteorhodopsin genes in giant viruses

    PubMed Central

    2012-01-01

    Viruses with large genomes encode numerous proteins that do not directly participate in virus biogenesis but rather modify key functional systems of infected cells. We report that a distinct group of giant viruses infecting unicellular eukaryotes that includes Organic Lake Phycodnaviruses and Phaeocystis globosa virus encode predicted proteorhodopsins that have not been previously detected in viruses. Search of metagenomic sequence data shows that putative viral proteorhodopsins are extremely abundant in marine environments. Phylogenetic analysis suggests that giant viruses acquired proteorhodopsins via horizontal gene transfer from proteorhodopsin-encoding protists although the actual donor(s) could not be presently identified. The pattern of conservation of the predicted functionally important amino acid residues suggests that viral proteorhodopsin homologs function as sensory rhodopsins. We hypothesize that viral rhodopsins modulate light-dependent signaling, in particular phototaxis, in infected protists. This article was reviewed by Igor B. Zhulin and Laksminarayan M. Iyer. For the full reviews, see the Reviewers’ reports section. PMID:23036091

  8. Localization of beta-adrenergic receptors on differentiated cells of the central nervous system in culture.

    PubMed Central

    Ventimiglia, R; Greene, M I; Geller, H M

    1987-01-01

    Hypothalamic neurons and cortical protoplasmic (type 1) astrocytes in dissociated cultures of rat brain express binding sites for antibodies specific for epitopes related to the beta-adrenergic receptor. Undifferentiated glial progenitor cells of the rat optic nerve do not detectably bind these antibodies, but both of the progeny [oligodendroglia and process-bearing (type 2) astrocytes] express immunologically identified beta-adrenergic receptors. Levels of receptor expression are variable: not all cells of each type express receptors nor is expression uniform on a given cell. The data suggest that cells of the central nervous system express beta-adrenergic receptors but that levels of expression may be determined by the differentiated state of the cells. Images PMID:3037533

  9. A high-content imaging assay for the quantification of the Burkholderia pseudomallei induced multinucleated giant cell (MNGC) phenotype in murine macrophages

    PubMed Central

    2014-01-01

    Background Burkholderia pseudomallei (Bp), a Gram-negative, motile, facultative intracellular bacterium is the causative agent of melioidosis in humans and animals. The Bp genome encodes a repertoire of virulence factors, including the cluster 3 type III secretion system (T3SS-3), the cluster 1 type VI secretion system (T6SS-1), and the intracellular motility protein BimA, that enable the pathogen to invade both phagocytic and non-phagocytic cells. A unique hallmark of Bp infection both in vitro and in vivo is its ability to induce cell-to-cell fusion of macrophages to form multinucleated giant cells (MNGCs), which to date are semi-quantitatively reported following visual inspection. Results In this study we report the development of an automated high-content image acquisition and analysis assay to quantitate the Bp induced MNGC phenotype. Validation of the assay was performed using T6SS-1 (∆hcp1) and T3SS-3 (∆bsaZ) mutants of Bp that have been previously reported to exhibit defects in their ability to induce MNGCs. Finally, screening of a focused small molecule library identified several Histone Deacetylase (HDAC) inhibitors that inhibited Bp-induced MNGC formation of macrophages. Conclusions We have successfully developed an automated HCI assay to quantitate MNGCs induced by Bp in macrophages. This assay was then used to characterize the phenotype of the Bp mutants for their ability to induce MNGC formation and identify small molecules that interfere with this process. Successful application of chemical genetics and functional reverse genetics siRNA approaches in the MNGC assay will help gain a better understanding of the molecular targets and cellular mechanisms responsible for the MNGC phenotype induced by Bp, by other bacteria such as Mycobacterium tuberculosis, or by exogenously added cytokines. PMID:24750902

  10. Applications of human umbilical cord blood cells in central nervous system regeneration.

    PubMed

    Herranz, Antonio S; Gonzalo-Gobernado, Rafael; Reimers, Diana; Asensio, Maria J; Rodríguez-Serrano, Macarena; Bazán, Eulalia

    2010-03-01

    In recent decades, there has been considerable amount of information about embryonic stem cells (ES). The dilemma facing scientists interested in the development and use of human stem cells in replacement therapies is the source of these cells, i.e. the human embryo. There are many ethical and moral problems related to the use of these cells. Hematopoietic stem cells from umbilical cord blood have been proposed as an alternative source of embryonic stem cells. After exposure to different agents, these cells are able to express antigens of diverse cellular lineages, including the neural type. The In vitro manipulation of human umbilical cord blood (hUCB) cells has shown their stem capacity and plasticity. These cells are easily accessible, In vitro amplifiable, well tolerated by the host, and with more primitive molecular characteristics that give them great flexibility. Overall, these properties open a promising future for the use of hUCB in regenerative therapies for the Central Nervous System (CNS). This review will focus on the available literature concerning umbilical cord blood cells as a therapeutic tool for the treatment of neurodegenerative diseases. PMID:19807661

  11. Nonlesions, unusual cell types, and postmortem artifacts in the central nervous system of domestic animals.

    PubMed

    Wohlsein, P; Deschl, U; Baumgärtner, W

    2013-01-01

    In the central nervous system (CNS) of domestic animals, numerous specialized normal structures, unusual cell types, findings of uncertain or no significance, artifacts, and various postmortem alterations can be observed. They may cause confusion for inexperienced pathologists and those not specialized in neuropathology, leading to misinterpretations and wrong diagnoses. Alternatively, changes may mask underlying neuropathological processes. "Specialized structures" comprising the hippocampus and the circumventricular organs, including the vascular organ of the lamina terminalis, subfornical organ, subcommissural organ, pineal gland, median eminence/neurohypophyseal complex, choroid plexus, and area postrema, are displayed. Unusual cell types, including cerebellar external germinal cells, CNS progenitor cells, and Kolmer cells, are presented. In addition, some newly recognized cell types as of yet incompletely understood significance and functionality, such as synantocytes and aldynoglia, are introduced and described. Unusual reactive astrocytes in cats, central chromatolysis, neuronal vacuolation, spheroids, spongiosis, satellitosis, melanosis, neuromelanin, lipofuscin, polyglucosan bodies, and psammoma bodies may represent incidental findings of uncertain or no significance and should not be confused with significant microscopic changes. Auto- and heterolysis as well as handling and histotechnological processing may cause postmortem morphological changes of the CNS, including vacuolization, cerebellar conglutination, dark neurons, Buscaino bodies, freezing, and shrinkage artifacts, all of which have to be differentiated from genuine lesions. Postmortem invasion of micro-organisms should not be confused with intravital infections. Awareness of these different changes and their recognition are a prerequisite for identifying genuine lesions and may help to formulate a professional morphological and etiological diagnosis. PMID:22692622

  12. Recurrent renal giant leiomyosarcoma

    PubMed Central

    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.

  13. Newberry Volcano—Central Oregon's Sleeping Giant

    USGS Publications Warehouse

    Donnelly-Nolan, Julie M.; Stovall, Wendy K.; Ramsey, David W.; Ewert, John W.; Jensen, Robert A.

    2011-01-01

    Hidden in plain sight, Oregon's massive Newberry Volcano is the largest volcano in the Cascades volcanic arc and covers an area the size of Rhode Island. Unlike familiar cone-shaped Cascades volcanoes, Newberry was built into the shape of a broad shield by repeated eruptions over 400,000 years. About 75,000 years ago a major explosion and collapse event created a large volcanic depression (caldera) at its summit. Newberry last erupted about 1,300 years ago, and present-day hot springs and geologically young lava flows indicate that it could reawaken at any time. Because of its proximity to nearby communities, frequency and size of past eruptions, and geologic youthfulness, U.S. Geological Survey scientists are working to better understand volcanic activity at Newberry and closely monitor the volcano for signs of unrest.

  14. Giant cell tumour of tendon sheath with simultaneous two tendon involvement of the foot treated with excision of the tumour and reconstruction of the flexor retinaculum using tibialis posterior tendon in a paediatric patient: A rare case report.

    PubMed

    Tiwari, Vivek; Ansari, Tahir; Mittal, Samarth; Sharma, Pankaj; Nalwa, Aasma

    2015-12-01

    Giant cell tumour of tendon sheath is a benign soft tissue tumour arising from the tendon sheath. The involvement of foot and ankle by such tumours is relatively rare. Children are not commonly afflicted by this condition. All such tumours are reported to arise either from a single tendon sheath or one joint. We report a case of giant cell tumour of tendon sheath in a 12-year-old child, arising simultaneously from the tendon sheaths of tibialis posterior and flexor digitorum longus tendons, as well as extending into the ankle joint. It was treated by complete excision of the mass along with the tendon sheaths with reconstruction of the flexor retinaculum. The location of the tumour, age of the patient, diffuse nature of the tumour and novel technique of reconstruction of the flexor retinaculum make this case extremely rare and the first to be reported in literature. PMID:26564735

  15. Giant axonal neuropathy: visual and oculomotor deficits.

    PubMed

    Kirkham, T H; Guitton, D; Coupland, S G

    1980-08-01

    Giant axonal neuropathy, a generalised disorder or neurofilaments, presents as a chronic, progressive peripheral neuropathy in childhood. Evidence for central nervous system involvement is demonstrated in this study of four male patients with giant axonal neuropathy who had defective visual function and abnormal ocular motility. The visual system was studied by electroretinography, which showed normal retinal function, and by visual evoked potentials, which showed disease of both optic nerves and retrochiasmal visual pathways. The ocular motility disorder, studied by electrooculography, comprised defective pursuit, inability to maintain eccentric gaze with gaze paretic and rebound nystagmus, abnormal optokinetic responses and failure of suppression of the vestibulo-ocular reflex by fixation. These findings suggested involvement by giant axonal neuropathy of the cerebellar and brain stem pathways important in the control of ocular motility. PMID:7192592

  16. RAGE mediates a novel proinflammatory axis: a central cell surface receptor for S100/calgranulin polypeptides.

    PubMed

    Hofmann, M A; Drury, S; Fu, C; Qu, W; Taguchi, A; Lu, Y; Avila, C; Kambham, N; Bierhaus, A; Nawroth, P; Neurath, M F; Slattery, T; Beach, D; McClary, J; Nagashima, M; Morser, J; Stern, D; Schmidt, A M

    1999-06-25

    S100/calgranulin polypeptides are present at sites of inflammation, likely released by inflammatory cells targeted to such loci by a range of environmental cues. We report here that receptor for AGE (RAGE) is a central cell surface receptor for EN-RAGE (extracellular newly identified RAGE-binding protein) and related members of the S100/calgranulin superfamily. Interaction of EN-RAGEs with cellular RAGE on endothelium, mononuclear phagocytes, and lymphocytes triggers cellular activation, with generation of key proinflammatory mediators. Blockade of EN-RAGE/RAGE quenches delayed-type hypersensitivity and inflammatory colitis in murine models by arresting activation of central signaling pathways and expression of inflammatory gene mediators. These data highlight a novel paradigm in inflammation and identify roles for EN-RAGEs and RAGE in chronic cellular activation and tissue injury. PMID:10399917

  17. Metabolic profiling of breast cancer: Differences in central metabolism between subtypes of breast cancer cell lines.

    PubMed

    Willmann, Lucas; Schlimpert, Manuel; Halbach, Sebastian; Erbes, Thalia; Stickeler, Elmar; Kammerer, Bernd

    2015-09-01

    Although the concept of aerobic glycolysis in cancer was already reported in the 1930s by Otto Warburg, the understanding of metabolic pathways remains challenging especially due to the heterogeneity of cancer. In consideration of four different time points (1, 2, 4, and 7 days of incubation), GC-MS profiling of metabolites was performed on cell extracts and supernatants of breast cancer cell lines (MDA-MB-231, -453, BT-474) with different sub classification and the breast epithelial cell line MCF-10A. To the exclusion of trypsinization, direct methanolic extraction, cell scraping and cell disruption was executed to obtain central metabolites. Major differences in biochemical pathways have been observed in the breast cancer cell lines compared to the breast epithelial cell line, as well as between the breast cancer cell lines themselves. Characteristics of breast cancer subtypes could be correlated to their individual metabolic profiles. PLS-DA revealed the discrimination of breast cancer cell lines from MCF-10A based on elevated amino acid levels. The observed metabolic signatures have great potential as biomarker for breast cancer as well as an improved understanding of subtype specific phenomenons of breast cancer. PMID:26218769

  18. Central nervous system complications of sickle cell disease in children: an overview.

    PubMed

    Wang, Winfred C

    2007-03-01

    Complications involving the central nervous system are among the most devastating manifestations of sickle cell disease. Although overt stroke occurs in 1 in 10 children with Hemoglobin SS, "silent cerebral infarcts" are even more frequent. Both are associated with significant neuropsychological deficits. The end result of these effects on the CNS often is diminished school performance. The use of transcranial Doppler ultrasonography screening allows the identification of patients at high risk for clinical stroke as well as stroke prevention by chronic transfusion. However, definitive prophylaxis and treatment for most CNS complications of sickle cell disease have yet to be determined. PMID:17364568

  19. Oral cavity squamous cell carcinoma metastatic to central compartment (level 6) lymph nodes.

    PubMed

    Likhterov, Ilya; Rowe, Meghan E; Khorsandi, Azita S; Urken, Mark L

    2016-08-01

    Alterations to drainage pathways in the head and neck as a result of surgical manipulation are not well understood. We present two unusual cases of oral squamous cell carcinoma metastatic to the level 6 nodal compartment following extensive treatment. Both oral squamous cell carcinoma cases exhibited metastases to the central neck compartment following extensive surgery and radiation. Each patient had prior history of multifocal oral cavity disease and recurrent neck metastases requiring salvage lymphadenectomy. Surgical interventions may alter the usual lymphatic drainage patterns. In cases of extensive treatment, all levels of the neck should be monitored for lymph node recurrence. Laryngoscope, 126:1803-1805, 2016. PMID:26490846

  20. Primary central nervous system T-cell lymphoma in a common dolphin (Delphinus delphis).

    PubMed

    Arbelo, M; Espinosa de los Monteros, A; Herráez, P; Suárez-Bonnet, A; Andrada, M; Rivero, M; Grau-Bassas, E R; Fernández, A

    2014-01-01

    This report describes the pathological findings in an adult female short-beaked common dolphin (Delphinus delphis) stranded alive in the Canary Islands. Necropsy examination revealed the presence of a nodular neoplastic growth in the central nervous system (CNS) at the level of the thalamus. Microscopical examination revealed the mass to be a lymphoma and immunohistochemical labelling demonstrated a T-cell origin. No significant lesions were observed in other organs, including lymphoid organs. This is the first report of a primary T-cell lymphoma in the CNS in cetaceans. PMID:24650893

  1. Cell-Specific Survival Motor Neuron Gene Expression during Human Development of the Central Nervous System

    PubMed Central

    Tizzano, Eduardo F.; Cabot, Carmen; Baiget, Montserrat

    1998-01-01

    Spinal muscular atrophy is an autosomal recessive disorder characterized by the progressive loss or degeneration of the motor neurons. To investigate the expression of survival motor neuron (SMN), the spinal muscular atrophy-determining gene, and its relationship with the pathogenesis of the disease, we analyzed by means of in situ hybridization the location of SMN mRNA in fetal, newborn, infant, and adult human central nervous system tissues. The large motor neurons of the spinal cord are the main cells that express SMN together with the neurons of the medulla oblongata, the pyramidal cells of the cortex, and the Purkinje cells of the cerebellum. Some sensory neurons from the posterior horn and dorsal root ganglia express SMN to a lesser degree. Furthermore, strong SMN expression is detected in the ependymal cells of the central canal. The expression is present in the spinal cord at 8 weeks of fetal life throughout postnatal and adult life. The sharp expression of SMN in the motor neurons of the human spinal cord, the target cells in spinal muscular atrophy, suggests that this gene is implicated in neuronal development and in the pathogenesis of the disease. The location of the SMN gene expression in other neuronal structures not clearly or directly associated with clinical manifestations or pathological findings of spinal muscular atrophy may indicate a varying sensitivity to the absence or dysfunction of the SMN gene in motor neurons. PMID:9708795

  2. Role of Immune Cells in the Course of Central Nervous System Injury: Modulation with Natural Products.

    PubMed

    Magrone, Thea; Russo, Matteo Antonio; Jirillo, Emilio

    2016-01-01

    Immune cells actively participate to the central nervous system (CNS) injury either damaging or protecting neural tissue with release of various mediators. Residential microglia and monocyte-derived macrophages play a fundamental role within the injured CNS and, here, special emphasis will be placed on M1 and M2 macrophages for their different functional activities. On the other hand, peripheral T regulatory (Treg) cells exert antiinflammatory activities in the diseased host. In this respect, activation of Treg cells by nutraceuticals may represent a novel approach to treat neuroinflammation. Omega-3 fatty acids and polyphenols will be described as substances endowed with antioxidant and anti-inflammatory activities. However, taking into account that Treg cells act in the later phase of CNS injury, favoring immune suppression, manipulation of host immune system with both substances requires caution to avoid undesired side effects. PMID:26635268

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

    PubMed

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

    2015-01-01

    Langerhans cell histiocytosis (LCH) is a rare disease characterized by the accumulation within tissues of anomalous dendritic cells similar to Langerhans cells. The clinical presentation varies, ranging from the appearance of a single bone lesion to multisystemic involvement. Central nervous system (CNS) involvement, manifesting as diabetes insipidus secondary to pituitary involvement, has been known since the original description of the disease. Two types of CNS lesions are currently differentiated. The first, pseudotumoral lesions with infiltration by Langerhans cells, most commonly manifests as pituitary infiltration. The second, described more recently, consists of neurodegenerative lesions of the CNS associated with neurologic deterioration. This second type of lesion constitutes a complication of the disease; however, there is no consensus about the cause of this complication. Our objective was to describe the radiologic manifestations of LCH in the CNS in pediatric patients. PMID:24837565

  4. Cell wall composition profiling of parasitic giant dodder (Cuscuta reflexa) and its hosts: a priori differences and induced changes.

    PubMed

    Johnsen, Hanne R; Striberny, Bernd; Olsen, Stian; Vidal-Melgosa, Silvia; Fangel, Jonatan U; Willats, William G T; Rose, Jocelyn K C; Krause, Kirsten

    2015-08-01

    Host plant penetration is the gateway to survival for holoparasitic Cuscuta and requires host cell wall degradation. Compositional differences of cell walls may explain why some hosts are amenable to such degradation while others can resist infection. Antibody-based techniques for comprehensive profiling of cell wall epitopes and cell wall-modifying enzymes were applied to several susceptible hosts and a resistant host of Cuscuta reflexa and to the parasite itself. Infected tissue of Pelargonium zonale contained high concentrations of de-esterified homogalacturonans in the cell walls, particularly adjacent to the parasite's haustoria. High pectinolytic activity in haustorial extracts and high expression levels of pectate lyase genes suggest that the parasite contributes directly to wall remodeling. Mannan and xylan concentrations were low in P. zonale and in five susceptible tomato introgression lines, but high in the resistant Solanum lycopersicum cv M82, and in C. reflexa itself. Knowledge of the composition of resistant host cell walls and the parasite's own cell walls is useful in developing strategies to prevent infection by parasitic plants. PMID:25808919

  5. Giant photovoltaic effects driven by residual polar field within unit-cell-scale LaAlO3 films on SrTiO3

    PubMed Central

    Liang, Haixing; Cheng, Long; Zhai, Xiaofang; Pan, Nan; Guo, Hongli; Zhao, Jin; Zhang, Hui; Li, Lin; Zhang, Xiaoqiang; Wang, Xiaoping; Zeng, Changgan; Zhang, Zhenyu; Hou, J. G.

    2013-01-01

    For polar/nonpolar heterostructures, Maxwell's theory dictates that the electric potential in the polar components will increase divergently with the film thickness. For LaAlO3/SrTiO3, a conceptually intriguing route, termed charge reconstruction, has been proposed to avert such “polar catastrophe”. The existence of a polar potential in LaAlO3 is a prerequisite for the validity of the charge reconstruction picture, yet to date, its direct measurement remains a major challenge. Here we establish unambiguously the existence of the residual polar potential in ultrathin LaAlO3 films on SrTiO3, using a novel photovoltaic device design as an effective probe. The measured lower bound of the residual polar potential is 1.0 V. Such a direct observation of the giant residual polar potential within the unit-cell-scale LaAlO3 films amounts to a definitive experimental evidence for the charge reconstruction picture, and also points to new technological significance of oxide heterostructures in photovoltaic and sensing devices with atomic-scale control. PMID:23756918

  6. A case of long-term 24-month survival in pancreatic anaplastic carcinoma (giant cell type) after S1 postoperative adjuvant chemotherapy

    PubMed Central

    Nitta, Toshikatsu; Fujii, Kensuke; Kataoka, Jun; Tominaga, Tomo; Kawasaki, Hiroshi; Ishibashi, Takashi

    2016-01-01

    We herein describe the case of a 70-year-old female patient diagnosed with pancreatic carcinoma. An abdominal enhanced computed tomography scan revealed a poorly enhanced mass (17 mm × 15 mm in size) in the pancreatic head. Magnetic resonance cholangiopancreatography revealed stenosis of the main pancreatic and common bile ducts caused by a mass-neighboring cyst. Based on these findings, we performed subtotal stomach-preserving pancreaticoduodenectomy. The patient demonstrated a good postoperative course, and was discharged from our hospital in remission 49 days after the surgery. Pathological findings confirmed that it was anaplastic pancreas carcinoma (giant cell type). After the surgery, we performed S-1 adjuvant chemotherapy 100 mg/day for four weeks, repeated similarly every six weeks for a total of four courses. We have followed this case for over 2 years so far with adjuvant chemotherapy, and no recurrence or metastasis has been revealed. Adjuvant chemotherapy with S-1 in patients with resected anaplastic carcinoma of the pancreas is also recommended as a result of Japan Adjuvant Study Group of Pancreatic Cancer 01(JASPAC-01) like the ordinary pancreatic ductal carcinomas. There is a possibility to achieve long-term survival in cases in which multidisciplinary treatment such as a curative resection and adjuvant chemotherapy are performed. PMID:27111877

  7. Giant cell tumor of cervicothoracic region treated by triple corpectomy from posterior only approach: A case report with review of literature

    PubMed Central

    Mahajan, Rajat; Chhabra, Harvinder Singh; Tandon, Vikas; Venkatesh, Raghavendra

    2015-01-01

    Giant cell tumor (GCT) is a benign aggressive tumor, which affects axial as well as a peripheral skeleton. It affects epiphysis of long bones and can result in pathological fractures. GCT affects cervical spine rarely and has been known to affect almost all vertebra in the human body. It has a predilection for fixed spine, that is, sacrum though it can affect mobile spine as well. GCT of cervicothoracic region poses a challenge for the surgeon because of the difficulty in approaching this region anteriorly. This situation is further compounded when GCT involves multiple contiguous vertebral bodies in this region and has already spread beyond the confines of its capsule. We report a case of GCT involving three vertebral bodies C7, D1, and D2 at cervicothoracic region who presented to us and was treated with triple corpectomy from the posterior only approach. This is the first ever case report of triple corpectomy and anterior reconstruction by a posterior only approach for GCT at the cervicothoracic junction to the best of author's knowledge. PMID:26692702

  8. Interleukin-1 Receptor-associated Kinase-4 (IRAK4) Promotes Inflammatory Osteolysis by Activating Osteoclasts and Inhibiting Formation of Foreign Body Giant Cells*

    PubMed Central

    Katsuyama, Eri; Miyamoto, Hiroya; Kobayashi, Tami; Sato, Yuiko; Hao, Wu; Kanagawa, Hiroya; Fujie, Atsuhiro; Tando, Toshimi; Watanabe, Ryuichi; Morita, Mayu; Miyamoto, Kana; Niki, Yasuo; Morioka, Hideo; Matsumoto, Morio; Toyama, Yoshiaki; Miyamoto, Takeshi

    2015-01-01

    Formation of foreign body giant cells (FBGCs) occurs following implantation of medical devices such as artificial joints and is implicated in implant failure associated with inflammation or microbial infection. Two major macrophage subpopulations, M1 and M2, play different roles in inflammation and wound healing, respectively. Therefore, M1/M2 polarization is crucial for the development of various inflammation-related diseases. Here, we show that FBGCs do not resorb bone but rather express M2 macrophage-like wound healing and inflammation-terminating molecules in vitro. We also found that FBGC formation was significantly inhibited by inflammatory cytokines or infection mimetics in vitro. Interleukin-1 receptor-associated kinase-4 (IRAK4) deficiency did not alter osteoclast formation in vitro, and IRAK4-deficient mice showed normal bone mineral density in vivo. However, IRAK4-deficient mice were protected from excessive osteoclastogenesis induced by IL-1β in vitro or by LPS, an infection mimetic of Gram-negative bacteria, in vivo. Furthermore, IRAK4 deficiency restored FBGC formation and expression of M2 macrophage markers inhibited by inflammatory cytokines in vitro or by LPS in vivo. Our results demonstrate that osteoclasts and FBGCs are reciprocally regulated and identify IRAK4 as a potential therapeutic target to inhibit stimulated osteoclastogenesis and rescue inhibited FBGC formation under inflammatory and infectious conditions without altering physiological bone resorption. PMID:25404736

  9. Treatment for giant cell tumor of the spine metastasizing to the lung: A report of two cases and a literature review

    PubMed Central

    MUHEREMU, AIKEREMUJIANG; HUANG, ZHEN; NIU, XIAOHUI

    2015-01-01

    Giant cell tumors of the bone (GCTB) account for 5% of all primary skeletal tumors. Although the tumors are normally benign, recurrence and metastasis of GCTB does occur. The most usual sites of a primary GCTB lesion are the distal femur and proximal tibia, and ~3% of these metastasize to the lung. Primary GCTB lesions in the spine are rare, and there have been few cases reporting the pulmonary metastasis of GCTB in the spine. The present study reports two cases of thoracic and sacral spinal GCTB lesions with pulmonary metastasis. One of the patients was a 45-year-old male who presented to hospital with gradually worsening pain in the left buttock during the last two years and was diagnosed with GCTB of the sacrum. The other patient was a 30-year-old female who complained of persistent back pain for a year and was also diagnosed with GCTB of the sacrum. Arterial embolization was performed prior to surgery and computer navigation was used during the surgery, resulting in the two patients achieving en bloc resection of their respective tumors, with satisfactory rehabilitation to follow. PMID:25663906

  10. A central to peripheral progression of cell cycle exit and hair cell differentiation in the developing mouse cristae.

    PubMed

    Slowik, Amber D; Bermingham-McDonogh, Olivia

    2016-03-01

    The inner ear contains six distinct sensory organs that each maintains some ability to regenerate hair cells into adulthood. In the postnatal cochlea, there appears to be a relationship between the developmental maturity of a region and its ability to regenerate as postnatal regeneration largely occurs in the apical turn, which is the last region to differentiate and mature during development. In the mature cristae there are also regional differences in regenerative ability, which led us to hypothesize that there may be a general relationship between the relative maturity of a region and the regenerative competence of that region in all of the inner ear sensory organs. By analyzing adult mouse cristae labeled embryonically with BrdU, we found that hair cell birth starts in the central region and progresses to the periphery with age. Since the peripheral region of the adult cristae also maintains active Notch signaling and some regenerative competence, these results are consistent with the hypothesis that the last regions to develop retain some of their regenerative ability into adulthood. Further, by analyzing embryonic day 14.5 inner ears we provide evidence for a wave of hair cell birth along the longitudinal axis of the cristae from the central regions to the outer edges. Together with the data from the adult inner ears labeled with BrdU as embryos, these results suggest that hair cell differentiation closely follows cell cycle exit in the cristae, unlike in the cochlea where they are uncoupled. PMID:26826497

  11. Cell wall glycoproteins at interaction sites between parasitic giant dodder (Cuscuta reflexa) and its host Pelargonium zonale.

    PubMed

    Striberny, Bernd; Krause, Kirsten

    2015-01-01

    The process of host plant penetration by parasitic dodder (genus Cuscuta) is accompanied by molecular and structural changes at the host/parasite interface. Recently, changes in pectin methyl esterification levels in the host cell walls abutting parasitic cells in established infection sites were reported. In addition to that, we show here that the composition of cell wall glycoproteins in Cuscuta-infected Pelargonium zonale undergoes substantial changes. While several arabinogalactan protein epitopes exhibit decreased abundances in the vicinity of the Cuscuta reflexa haustorium, extensins tend to increase in the infected areas. PMID:26367804

  12. Cell wall glycoproteins at interaction sites between parasitic giant dodder (Cuscuta reflexa) and its host Pelargonium zonale

    PubMed Central

    Striberny, Bernd; Krause, Kirsten

    2015-01-01

    The process of host plant penetration by parasitic dodder (genus Cuscuta) is accompanied by molecular and structural changes at the host/parasite interface. Recently, changes in pectin methyl esterification levels in the host cell walls abutting parasitic cells in established infection sites were reported. In addition to that, we show here that the composition of cell wall glycoproteins in Cuscuta-infected Pelargonium zonale undergoes substantial changes. While several arabinogalactan protein epitopes exhibit decreased abundances in the vicinity of the Cuscuta reflexa haustorium, extensins tend to increase in the infected areas. PMID:26367804

  13. Nonlinear joint transmit-receive processing for coordinated multi-cell systems: centralized and decentralized

    NASA Astrophysics Data System (ADS)

    Hu, Zhirui; Feng, Chunyan; Zhang, Tiankui; Niu, Qin; Chen, Yue

    2015-12-01

    This paper proposes a nonlinear joint transmit-receive (tx-rx) processing scheme for downlink-coordinated multi-cell systems with multi-stream multi-antenna users. The nonlinear joint tx-rx processing is formulated as an optimization problem to maximize the minimum signal-to-interference noise ratio (SINR) of streams to guarantee the fairness among streams of each user. Nonlinear Tomlinson-Harashima precoding (THP) is applied at transmitters, and linear receive processing is applied at receivers, to eliminate the inter-user interference and inter-stream interference. We consider multi-cell systems under two coordinated modes: centralized and decentralized, corresponding to systems with high- and low-capacity backhaul links, respectively. For the centralized coordinated mode, transmit and receive processing matrices are jointly determined by the central processing unit based on the global channel state information (CSI) shared by base stations (BSs). For the decentralized coordinated mode, transmit and receive processing matrices are computed independently based on the local CSI at each BS. In correspondence, we propose both a centralized and a decentralized algorithm to solve the optimization problem under the two modes, respectively. Feasibility and computational complexity of the proposed algorithms are also analyzed. Simulation results prove that the proposed nonlinear joint tx-rx processing scheme can achieve user fairness by equalizing the bit error rate (BER) among streams of each user and the proposed scheme outperforms the existing linear joint tx-rx processing. Moreover, consistent with previous research results, performance of the proposed centralized nonlinear joint tx-rx processing scheme is proved to be better than that of the decentralized nonlinear joint tx-rx processing.

  14. Unstable giant gravitons

    SciTech Connect

    Mello Koch, Robert de; Ives, Norman; Smolic, Jelena; Smolic, Milena

    2006-03-15

    We find giant graviton solutions in Frolov's three parameter generalization of the Lunin-Maldacena background. The background we study has {gamma}-tilde{sub 1}=0 and {gamma}-tilde{sub 2}={gamma}-tilde{sub 3}={gamma}-tilde. This class of backgrounds provides a nonsupersymmetric example of the gauge theory/gravity correspondence that can be tested quantitatively, as recently shown by Frolov, Roiban, and Tseytlin. The giant graviton solutions we find have a greater energy than the point gravitons, making them unstable states. Despite this, we find striking quantitative agreement between the gauge theory and gravity descriptions of open strings attached to the giant.

  15. Common clonal origin of central and resident memory T cells following skin immunization

    PubMed Central

    Gaide, Olivier; Emerson, Ryan O.; Jiang, Xiaodong; Gulati, Nicholas; Nizza, Suzanne; Desmarais, Cindy; Robins, Harlan; Krueger, James G.; Clark, Rachael A.; Kupper, Thomas S.

    2015-01-01

    Central memory T (TCM) cells in lymph nodes (LN) and resident memory T (TRM) cells in peripheral tissues play distinct roles in protective immunity1-5. Both are generated after primary infections, but the clonal origin of TRM and TCM cells is unclear. To address this question, mice were immunized through the skin with either a protein antigen, a chemical hapten, or a non-replicating poxvirus. We then analyzed antigen activated T cells from different tissues using high-throughput sequencing (HTS) of the gene (Tcrbv) encoding T cell receptor gene β chain CDR3 region to simultaneously track thousands of unique T cells6. For every abundant TRM clone generated in the skin, an abundant TCM clone bearing the identical TCR was present in lymph nodes (LN). Thus antigen reactive skin TRM and LN TCM clones were derived from a common naive T cell precursor after skin immunization, generating overlapping TCR repertoires. Although they bore the same TCR, TRM mediated rapid contact hypersensitivity (CHS)7 responses in mice, whereas TCM mediated delayed and attenuated responses. Studies in human subjects confirmed the generation of skin TRM in allergic contact dermatitis. Thus, immunization through skin simultaneously generates skin TRM and LN TCM in similar numbers from the same naïve T cells. PMID:25962122

  16. How Does Transcranial Magnetic Stimulation Influence Glial Cells in the Central Nervous System?

    PubMed Central

    Cullen, Carlie L.; Young, Kaylene M.

    2016-01-01

    Transcranial magnetic stimulation (TMS) is widely used in the clinic, and while it has a direct effect on neuronal excitability, the beneficial effects experienced by patients are likely to include the indirect activation of other cell types. Research conducted over the past two decades has made it increasingly clear that a population of non-neuronal cells, collectively known as glia, respond to and facilitate neuronal signaling. Each glial cell type has the ability to respond to electrical activity directly or indirectly, making them likely cellular effectors of TMS. TMS has been shown to enhance adult neural stem and progenitor cell (NSPC) proliferation, but the effect on cell survival and differentiation is less certain. Furthermore there is limited information regarding the response of astrocytes and microglia to TMS, and a complete paucity of data relating to the response of oligodendrocyte-lineage cells to this treatment. However, due to the critical and yet multifaceted role of glial cells in the central nervous system (CNS), the influence that TMS has on glial cells is certainly an area that warrants careful examination. PMID:27092058

  17. Formation of giant planets

    NASA Astrophysics Data System (ADS)

    Magni, G.; Coradini, A.

    2003-04-01

    In this presentation we address the problem of the formation of giant planets and their regular satellites. We study in particular the problem of formation of the Jupiter System comparing the results of the model with the present characteristics of the system, in order to identify what are those better represented by our approach. In fact here, using a 3-D hydro-dynamical code, we study the modalities of gas accretion onto a solid core, believed to be the seed from which Jupiter started. To do that we have modelled three main regions: the central planet, a turbulent accretion disk surrounding it and an extended region from which the gas is collected. In the extended region we treat the gas as a frictionless fluid. Our main goal is to identify what are the characteristics of the planet during its growth and the physical parameters affecting its growth at the expenses of the nebular gas present in the feeding zone. Moreover we want to understand what are the thermodynamical parameters characterizing the gas captured by the planet and swirling around it. Finally, we check if a disk can be formed in prograde rotation around the planet and if this disk can survive the final phases of the planet formation. Due to the interaction between the accreting planet and the disk it has been necessary to develop a complete model of the Jupiter’s structure. In fact the radiation emitted by the growing planet heats up the surrounding gas. In turn the planet’s thermodynamic structure depend on the mass accretion rate onto it. When the accretion is rapid, shock waves in the gas are formed close to the planet. This region cannot be safely treated by a numerical code; for this reason we have developed a semi-analytically model of a a turbulent accretion disk to be considered as transition between the planet and the surrounding disk.

  18. Peripheral and central neuronal ATF3 precedes CD4+ T-cell infiltration in EAE.

    PubMed

    Frezel, Noémie; Sohet, Fabien; Daneman, Richard; Basbaum, Allan I; Braz, Joao M

    2016-09-01

    Experimental allergic encephalomyelitis (EAE), an animal model of multiple sclerosis produced by immunization with myelin oligodendrocyte glycoprotein (MOG) and adjuvants, results from profound T-cell mediated CNS demyelination. EAE is characterized by progressive, ascending motor dysfunction and symptoms of ongoing pain and hypersensitivity, in some cases preceding or concomitant with the motor deficits. In this regard, the EAE model mimics major features of multiple sclerosis, where a central neuropathic pain state is common. Although the latter condition is presumed to arise from a CNS loss of inhibitory controls secondary to the demyelination, dysfunction of sensory neurons may also contribute. Based on our previous studies that demonstrated the utility of monitoring expression of activating transcription factor 3 (ATF3), a sensitive marker of injured sensory neurons, here we followed both ATF3 and CD4+ T cells invasion of sensory ganglia (as well as the CNS) at different stages of the EAE model. We found that ATF3 is induced in peripheral sensory ganglia and brainstem well before the appearance of motor deficits. Unexpectedly, the ATF3 induction always preceded T cell infiltration, typically in adjacent, but non-overlapping regions. Surprisingly, control administration of the pertussis toxin and/or Complete Freund's adjuvants, without MOG, induced ATF3 in sensory neurons. In contrast, T cell infiltration only occurred with MOG. Taken together, our results suggest that the clinical manifestations in the EAE result not only from central demyelination but also from neuronal stress and subsequent pathophysiology of sensory neurons. PMID:27343802

  19. Enzymatic passaging of human embryonic stem cells alters central carbon metabolism and glycan abundance

    PubMed Central

    Badur, Mehmet G.; Zhang, Hui; Metallo, Christian M.

    2016-01-01

    To realize the potential of human embryonic stem cells (hESCs) in regenerative medicine and drug discovery applications, large numbers of cells that accurately recapitulate cell and tissue function must be robustly produced. Previous studies have suggested that genetic instability and epigenetic changes occur as a consequence of enzymatic passaging. However, the potential impacts of such passaging methods on the metabolism of hESCs have not been described. Using stable isotope tracing and mass spectrometry-based metabolomics, we have explored how different passaging reagents impact hESC metabolism. Enzymatic passaging caused significant decreases in glucose utilization throughout central carbon metabolism along with attenuated de novo lipogenesis. In addition, we developed and validated a method for rapidly quantifying glycan abundance and isotopic labeling in hydrolyzed biomass. Enzymatic passaging reagents significantly altered levels of glycans immediately after digestion but surprisingly glucose contribution to glycans was not affected. These results demonstrate that there is an immediate effect on hESC metabolism after enzymatic passaging in both central carbon metabolism and biosynthesis. HESCs subjected to enzymatic passaging are routinely placed in a state requiring re-synthesis of biomass components, subtly influencing their metabolic needs in a manner that may impact cell performance in regenerative medicine applications. PMID:26289220

  20. Melting the core of giant planets: impact on tidal dissipation

    NASA Astrophysics Data System (ADS)

    Mathis, S.

    2015-12-01

    Giant planets are believed to host central dense rocky/icy cores that are key actors in the core-accretion scenario for their formation. In the same time, some of their components are unstable in the temperature and pressure regimes of central regions of giant planets and only ab-initio EOS computations can address the question of the state of matter. In this framework, several works demonstrated that erosion and redistribution of core materials in the envelope must be taken into account. These complex mechanisms thus may deeply modify giant planet interiors for which signatures of strong tidal dissipation have been obtained for Jupiter and Saturn. The best candidates to explain this dissipation are the viscoelastic dissipation in the central dense core and turbulent friction acting on tidal inertial waves in their fluid convective envelope. In this work, we study the consequences of the possible melting of central regions for the efficiency of each of these mechanisms.

  1. Recognition of Linear B-Cell Epitope of Betanodavirus Coat Protein by RG-M18 Neutralizing mAB Inhibits Giant Grouper Nervous Necrosis Virus (GGNNV) Infection

    PubMed Central

    Chen, Chien-Wen; Wu, Ming-Shan; Huang, Yi-Jen; Cheng, Chao-An; Chang, Chi-Yao

    2015-01-01

    Betanodavirus is a causative agent of viral nervous necrosis syndrome in many important aquaculture marine fish larvae, resulting in high global mortality. The coat protein of Betanodavirus is the sole structural protein, and it can assemble the virion particle by itself. In this study, we used a high-titer neutralizing mAB, RG-M18, to identify the linear B-cell epitope on the viral coat protein. By mapping a series of recombinant proteins generated using the E. coli PET expression system, we demonstrated that the linear epitope recognized by RG-M18 is located at the C-terminus of the coat protein, between amino acid residues 195 and 338. To define the minimal epitope region, a set of overlapping peptides were synthesized and evaluated for RG-M18 binding. Such analysis identified the 195VNVSVLCR202 motif as the minimal epitope. Comparative analysis of Alanine scanning mutagenesis with dot-blotting and ELISA revealed that Valine197, Valine199, and Cysteine201 are critical for antibody binding. Substitution of Leucine200 in the RGNNV, BFNNV, and TPNNV genotypes with Methionine200 (thereby simulating the SJNNV genotype) did not affect binding affinity, implying that RG-M18 can recognize all genotypes of Betanodaviruses. In competition experiments, synthetic multiple antigen peptides of this epitope dramatically suppressed giant grouper nervous necrosis virus (GGNNV) propagation in grouper brain cells. The data provide new insights into the protective mechanism of this neutralizing mAB, with broader implications for Betanodavirus vaccinology and antiviral peptide drug development. PMID:25938761

  2. Giant distal humeral geode.

    PubMed

    Maher, M M; Kennedy, J; Hynes, D; Murray, J G; O'Connell, D

    2000-03-01

    We describe the imaging features of a giant geode of the distal humerus in a patient with rheumatoid arthritis, which presented initially as a pathological fracture. The value of magnetic resonance imaging in establishing this diagnosis is emphasized. PMID:10794554

  3. Giant Subclavian Artery Aneurysm.

    PubMed

    Counts, Sarah; Zeeshan, Ahmad; Elefteriades, John

    2016-06-01

    We report the case of a 37-year-old construction executive presenting with chest pain, shortness of breath, and dizziness on exertion secondary to a giant left subclavian artery aneurysm and aortic valvular disease. PMID:27231430

  4. The Next Giant Step

    NASA Video Gallery

    Artist Robert McCall painted "The Next Giant Step" in 1979 to commemorate the heroism and courage of spaceflight pioneers. Located in the lobby of Johnson's building 2, the mural depicts America's ...

  5. Vaccination Expands Antigen-Specific CD4+ Memory T Cells and Mobilizes Bystander Central Memory T Cells

    PubMed Central

    Li Causi, Eleonora; Parikh, Suraj C.; Chudley, Lindsey; Layfield, David M.; Ottensmeier, Christian H.; Stevenson, Freda K.; Di Genova, Gianfranco

    2015-01-01

    CD4+ T helper memory (Thmem) cells influence both natural and vaccine-boosted immunity, but mechanisms for their maintenance remain unclear. Pro-survival signals from the common gamma-chain cytokines, in particular IL-7, appear important. Previously we showed in healthy volunteers that a booster vaccination with tetanus toxoid (TT) expanded peripheral blood TT-specific Thmem cells as expected, but was accompanied by parallel increase of Thmem cells specific for two unrelated and non cross-reactive common recall antigens. Here, in a new cohort of healthy human subjects, we compare blood vaccine-specific and bystander Thmem cells in terms of differentiation stage, function, activation and proliferative status. Both responses peaked 1 week post-vaccination. Vaccine-specific cytokine-producing Thmem cells were predominantly effector memory, whereas bystander cells were mainly of central memory phenotype. Importantly, TT-specific Thmem cells were activated (CD38High HLA-DR+), cycling or recently divided (Ki-67+), and apparently vulnerable to death (IL-7RαLow and Bcl-2 Low). In contrast, bystander Thmem cells were resting (CD38Low HLA-DR- Ki-67-) with high expression of IL-7Rα and Bcl-2. These findings allow a clear distinction between vaccine-specific and bystander Thmem cells, suggesting the latter do not derive from recent proliferation but from cells mobilized from as yet undefined reservoirs. Furthermore, they reveal the interdependent dynamics of specific and bystander T-cell responses which will inform assessments of responses to vaccines. PMID:26332995

  6. CMV-specific central memory T cells reside in bone marrow.

    PubMed

    Letsch, Anne; Knoedler, Maren; Na, Il-Kang; Kern, Florian; Asemissen, Anne-Marie; Keilholz, Ulrich; Loesch, Michael; Thiel, Eckhard; Volk, Hans-Dieter; Scheibenbogen, Carmen

    2007-11-01

    CMV-specific CD8(+) T cell responses in peripheral blood (PB) are characterized by a preponderance of effector and effector memory T cells. CMV-specific central memory T cells (T(CM)), which are considered crucial in maintaining long-term immunity, are rarely detectable in PB. In this study we have analyzed differentiation and function of CMV pp65-specific CD8(+) T cells in paired samples of human PB and BM using intracellular cytokine and tetramer staining. Overall frequencies of CMV pp65-specific T cells were similar in PB compared to BM; however, CMV-specific CD45RA(-)CCR7(+) T(CM) were almost exclusively detectable in BM, which was not related to a general accumulation of T(CM) in BM. In vitro, CMV-specific T cells could be more efficiently expanded from BM (median 128-fold, n=6) than from PB (median 72-fold, p=0.01). Taken together, these data show that the BM is a compartment harboring CMV-specific T(CM) and underline the concept of the BM as a secondary immune organ. CMV specific BM-derived T(CM) might be a valuable source for generating T cells for adoptive transfer. PMID:17960663

  7. Fine-tuning the central nervous system: microglial modelling of cells and synapses

    PubMed Central

    Xavier, Anna L.; Menezes, João R. L.; Goldman, Steven A.; Nedergaard, Maiken

    2014-01-01

    Microglia constitute as much as 10–15% of all cells in the mammalian central nervous system (CNS) and are the only glial cells that do not arise from the neuroectoderm. As the principal CNS immune cells, microglial cells represent the first line of defence in response to exogenous threats. Past studies have largely been dedicated to defining the complex immune functions of microglial cells. However, our understanding of the roles of microglia has expanded radically over the past years. It is now clear that microglia are critically involved in shaping neural circuits in both the developing and adult CNS, and in modulating synaptic transmission in the adult brain. Intriguingly, microglial cells appear to use the same sets of tools, including cytokine and chemokine release as well as phagocytosis, whether modulating neural function or mediating the brain's innate immune responses. This review will discuss recent developments that have broadened our views of neuro-glial signalling to include the contribution of microglial cells. PMID:25225087

  8. Primary central nervous system gamma delta cytotoxic T-cell lymphoma.

    PubMed

    Mooney, Kelly L; Choy, Winward; Woodard, Joslyn; Xian, Rena R; Deal, Taylor M; Kendle, Ryan F; Said, Jonathan; Grody, Wayne; Yang, Isaac

    2016-04-01

    Primary T-cell lymphomas of the central nervous system (CNS) are uncommon, but aggressive and increasing in incidence. We describe a rare case of T-cell lymphoma in a cerebellar location, to our knowledge the first reported case demonstrating gamma/delta receptor expression. Additionally, we elaborate on key diagnostic features and review all nine patients with primary CNS lymphoma of cytotoxic T-cell phenotype reported in the literature. A 26-year-old female medical student presented with a 6week history of nausea, vomiting and dizziness. MRI revealed a 2cm cerebellar mass. The tumor was subtotally resected, and pathologic examination of a subtotal resection specimen demonstrated peripheral T-cell lymphoma, not otherwise specified, with a gamma/delta cytotoxic T-cell phenotype. She subsequently started high dose methotrexate and cytarabine. We report a unique case of primary CNS gamma delta CD8+ T-cell lymphoma lineage in a young female patient. While these are rare entities, it is an important differential diagnosis to consider. Therapy should be tailored to the patient, and involves resection with adjuvant chemotherapy, radiotherapy or autologous stem-cell based treatments. PMID:26804925

  9. IL-9 signaling affects central nervous system resident cells during inflammatory stimuli.

    PubMed

    Ding, Xiaoli; Cao, Fang; Cui, Langjun; Ciric, Bogoljub; Zhang, Guang-Xian; Rostami, Abdolmohamad

    2015-12-01

    Interleukin (IL) 9, a dominant cytokine in Th9 cells, has been proven to play a pathogenic role in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), by augmenting T cell activation and differentiation; however, whether IL-9 signaling affects central nervous system (CNS)-resident cells during CNS autoimmunity remains unknown. In the present study, we found that the IL-9 receptor (IL-9R) was highly expressed in astrocytes, oligodendrocyte progenitor cells (OPCs), oligodendrocytes and microglia cells, and that its expression was significantly upregulated in brain and spinal cord during EAE. In addition, IL-9 increased chemokine expression, including CXCL9, CCL20 and MMP3, in primary astrocytes. Although IL-9 had no effect on the proliferation of microglia cells, it decreased OPC proliferation and differentiation when in combination with other pro-inflammatory cytokines, but not with IFN-γ. IL-9 plus IFN-γ promoted OPC proliferation and differentiation. These findings indicate that CNS-restricted IL-9 signaling may be involved in the pathogenesis of MS/EAE, thus providing a potential therapeutic target for future MS/EAE treatment through disruption of CNS cell-specific IL-9 signaling. PMID:26216406

  10. Giant congenital melanocytic nevus in a bulgarian newborn.

    PubMed

    Chokoeva, A A; Fioranelli, M; Roccia, M G; Lotti, T; Wollina, U; Tchernev, G

    2016-01-01

    Giant congenital melanocytic nevus (GCMN) is a rare disorder affecting 1 in 200,000–500,000 live births. Central nervous system defects such as spina bifida, meningocele, Dandy Walker malformation may accompany it and thus cause significant morbidity. Despite the related risk for malignant transformation, GCMNs may be associated with neurocutaneous melanosis, a rare syndrome in which a giant CMN or multiple smaller CMNs are accompanied by melanocytic deposition in the brain and the spinal cord. We present a case of a 5-day-old newborn with giant congenital melanocytic nevus on his back, as we discuss the diagnostic and treatment approach. PMID:27373137

  11. Giant Piloleiomyoma of the Forehead

    PubMed Central

    Kim, Gun-Wook; Park, Hyun-Je; Kim, Hoon-Soo; Kim, Su-Han; Ko, Hyun-Chang; Kim, Byung-Soo

    2011-01-01

    Cutaneous piloleiomyomas are benign smooth muscle tumors arising from the arrector pili muscles. Piloleiomyomas appear as firm dermal papules of skin color or with a reddish to brown surface, and are commonly located on the extremities. Histologically, these lesions are composed of interlacing bundles of smooth muscle cells in the reticular dermis. Our case presented with an unusually large nodule on the forehead that was accompanied by intermittent pain. Histological analysis was compatible with piloleiomyoma and the lesion showed haphazardly arranged bundles of smooth muscle in the dermis. We describe herein an interesting case of a giant piloleiomyoma occurring on the forehead. PMID:22148036

  12. ERG is a novel and reliable marker for endothelial cells in central nervous system tumors.

    PubMed

    Haber, Matthew A; Iranmahboob, Amir; Thomas, Cheddhi; Liu, Mengling; Najjar, Amanda; Zagzag, David

    2015-01-01

    ETS-related gene (ERG) is a transcription factor that has been linked to angiogenesis. Very little research has been done to assess ERG expression in central nervous system (CNS) tumors. We evaluated 57 CNS tumors, including glioblastomas (GBMs) and hemangioblastomas (HBs), as well as two arteriovenous malformations and four samples of normal brain tissue with immunohistochemistry using a specific ERG rabbit monoclonal antibody. In addition, immunostains for CD31, CD34, and α-smooth muscle actin (α-SMA) were performed on all samples. CD31 demonstrated variable and sometimes weak immunoreactivity for endothelial cells. Furthermore, in 1 case of a GBM, CD34 stained not only endothelial cells, but also tumor cells. In contrast, we observed that ERG was only expressed in the nuclei of endothelial cells, for example, in the hyperplastic vascular complexes that comprise the glomeruloid microvascular proliferation seen in GBMs. Conversely, α-SMA immunoreactivity was identified in the abluminal cells of these hyperplastic vessels. Quantitative evaluation with automated methodology and custom Matlab 2008b software was used to calculate percent staining of ERG in each case. We observed significantly higher quantitative expression of ERG in HBs than in other CNS tumors. Our results show that ERG is a novel, reliable, and specific marker for endothelial cells within CNS tumors that can be used to better study the process of neovascularization. PMID:25881913

  13. ERG is a novel and reliable marker for endothelial cells in central nervous system tumors

    PubMed Central

    Haber, Matthew A.; Iranmahboob, Amir; Thomas, Cheddhi; Liu, Mengling; Najjar, Amanda; Zagzag, David

    2015-01-01

    ETS-related gene (ERG) is a transcription factor that has been linked to angiogenesis. Very little research has been done to assess ERG expression in central nervous system (CNS) tumors. We evaluated 57 CNS tumors, including glioblastomas (GBMs) and hemangioblastomas (HBs), as well as two arteriovenous malformations and four samples of normal brain tissue with immunohistochemistry using a specific ERG rabbit monoclonal antibody. In addition, immunostains for CD31, CD34, and α-smooth muscle actin (α-SMA) were performed on all samples. CD31 demonstrated variable and sometimes weak immunoreactivity for endothelial cells. Furthermore, in 1 case of a GBM, CD34 stained not only endothelial cells, but also tumor cells. In contrast, we observed that ERG was only expressed in the nuclei of endothelial cells, for example, in the hyperplastic vascular complexes that comprise the glomeruloid microvascular proliferation seen in GBMs. Conversely, α-SMA immunoreactivity was identified in the abluminal cells of these hyperplastic vessels. Quantitative evaluation with automated methodology and custom Matlab 2008b software was used to calculate percent staining of ERG in each case. We observed significantly higher quantitative expression of ERG in HBs than in other CNS tumors. Our results show that ERG is a novel, reliable, and specific marker for endothelial cells within CNS tumors that can be used to better study the process of neovascularization. PMID:25881913

  14. Neural Stem Cell Therapy and Rehabilitation in the Central Nervous System: Emerging Partnerships.

    PubMed

    Ross, Heather H; Ambrosio, Fabrisia; Trumbower, Randy D; Reier, Paul J; Behrman, Andrea L; Wolf, Steven L

    2016-05-01

    The goal of regenerative medicine is to restore function through therapy at levels such as the gene, cell, tissue, or organ. For many disorders, however, regenerative medicine approaches in isolation may not be optimally effective. Rehabilitation is a promising adjunct therapy given the beneficial impact that physical activity and other training modalities can offer. Accordingly, "regenerative rehabilitation" is an emerging concentration of study, with the specific goal of improving positive functional outcomes by enhancing tissue restoration following injury. This article focuses on one emerging example of regenerative rehabilitation-namely, the integration of clinically based protocols with stem cell technologies following central nervous system injury. For the purposes of this review, the state of stem cell technologies for the central nervous system is summarized, and a rationale for a synergistic benefit of carefully orchestrated rehabilitation protocols in conjunction with cellular therapies is provided. An overview of practical steps to increase the involvement of physical therapy in regenerative rehabilitation research also is provided. PMID:26847015

  15. Diffuse large B-cell lymphoma involving the central nervous system.

    PubMed

    Gualco, Gabriela; Weiss, Lawrence M; Barber, Glen N; Bacchi, Carlos E

    2011-02-01

    Lymphomas involving the central nervous system are recognized increasingly in immunocompetent as well as immunosuppressed individuals, and the majority of the cases are diffuse large B-cell lymphoma (DLBCL). The aim of this study was to compare the immunophenotype, clinicopathological features, and association with Epstein-Barr virus (EBV) of DLBCL of the central nervous system (CNS) in 3 different clinical situations: primary, in immunocompetent patients; "primary," in immunosuppressed patients; and in patients with secondary involvement by systemic lymphoma. The authors reviewed the clinicopathological features, morphology, immunophenotype (according to germinal-center B-cell-like and nongerminal B-cell-like subtypes), and association with EBV in 36 cases of DLBCL of the CNS, including 25 primary cases, 5 associated with immunosuppression, and 6 cases with secondary involvement. Survival was evaluated in 15 cases of primary CNS lymphomas. Of the 36 patients, 19 were male and 18 female. Only 2 cases of lymphomas were EBV-positive; both occurred in immunosuppressed patients. Separation into germinal-center and non-germinal center subtypes by an immunohistochemistry panel showed that 68% of primary, 80% of secondary, and 83% of the cases associated with immunosuppression were of non-germinal-center subtype, respectively. Patients with non-germinal-center immunophenotype showed significantly worse survival than those with CNS lymphomas of the germinal-center subtype. PMID:21087986

  16. Responses of precentral cells during cooling of post-central cortex in conscious monkeys.

    PubMed Central

    Brinkman, J; Colebatch, J G; Porter, R; York, D H

    1985-01-01

    A cooling plate was implanted over the forelimb representation in area 2 of the post-central region of cerebral cortex in two monkeys. Recordings were made of the discharges of thirty-seven movement-related neurones (thirty-four precentral and three post-central) in the forelimb motor representation of the cerebral cortex during active and passively imposed limb movements before, during and after cooling area 2 and local surrounding regions. Perfusion of the cooling plate with ice-cooled water for 3-5 min caused marked clumsiness of the conscious animal's forelimb movement and anaesthesia of the contralateral hand. Cooling of area 2 did not reduce the responses of area 4 cells to passive joint movements, nor did it alter the over-all pattern of activity of these cells during self-initiated lever pulling while that could still be performed. Cooling of area 2 did cause a significant increase in background cellular discharge in area 4 while the animal was at rest. Afferent impulses which are generated by passive joint movement and which have been shown to influence cells in area 4 of the conscious monkey at short latencies are probably not transmitted through cortico-cortical connexions from area 2. PMID:4078751

  17. Early effector cells survive the contraction phase in malaria infection and generate both central and effector memory T cells.

    PubMed

    Opata, Michael M; Carpio, Victor H; Ibitokou, Samad A; Dillon, Brian E; Obiero, Joshua M; Stephens, Robin

    2015-06-01

    CD4 T cells orchestrate immunity against blood-stage malaria. However, a major challenge in designing vaccines to the disease is poor understanding of the requirements for the generation of protective memory T cells (Tmem) from responding effector T cells (Teff) in chronic parasite infection. In this study, we use a transgenic mouse model with T cells specific for the merozoite surface protein (MSP)-1 of Plasmodium chabaudi to show that activated T cells generate three distinct Teff subsets with progressive activation phenotypes. The earliest observed Teff subsets (CD127(-)CD62L(hi)CD27(+)) are less divided than CD62L(lo) Teff and express memory genes. Intermediate (CD62L(lo)CD27(+)) effector subsets include the most multicytokine-producing T cells, whereas fully activated (CD62L(lo)CD27(-)) late effector cells have a terminal Teff phenotype (PD-1(+), Fas(hi), AnnexinV(+)). We show that although IL-2 promotes expansion, it actually slows terminal effector differentiation. Using adoptive transfer, we show that only early Teff survive the contraction phase and generate the terminal late Teff subsets, whereas in uninfected recipients, they become both central and effector Tmem. Furthermore, we show that progression toward full Teff activation is promoted by increased duration of infection, which in the long-term promotes Tem differentiation. Therefore, we have defined markers of progressive activation of CD4 Teff at the peak of malaria infection, including a subset that survives the contraction phase to make Tmem, and show that Ag and cytokine levels during CD4 T cell expansion influence the proportion of activated cells that can survive contraction and generate memory in malaria infection. PMID:25911759

  18. Cutting edge: neuronal recognition by CD8 T cells elicits central diabetes insipidus.

    PubMed

    Scheikl, Tanja; Pignolet, Béatrice; Dalard, Cécile; Desbois, Sabine; Raison, Danièle; Yamazaki, Masanori; Saoudi, Abdelhadi; Bauer, Jan; Lassmann, Hans; Hardin-Pouzet, Hélène; Liblau, Roland S

    2012-05-15

    An increasing number of neurologic diseases is associated with autoimmunity. The immune effectors contributing to the pathogenesis of such diseases are often unclear. To explore whether self-reactive CD8 T cells could attack CNS neurons in vivo, we generated a mouse model in which the influenza virus hemagglutinin (HA) is expressed specifically in CNS neurons. Transfer of cytotoxic anti-HA CD8 T cells induced an acute but reversible encephalomyelitis in HA-expressing recipient mice. Unexpectedly, diabetes insipidus developed in surviving animals. This robust phenotype was associated with preferential accumulation of cytotoxic CD8 T cells in the hypothalamus, upregulation of MHC class I molecules, and destruction of vasopressin-expressing neurons. IFN-γ production by the pathogenic CD8 T cells was necessary for MHC class I upregulation by hypothalamic neurons and their destruction. This novel mouse model, in combination with related human data, supports the concept that autoreactive CD8 T cells can trigger central diabetes insipidus. PMID:22504649

  19. Plectin-containing, centrally localized focal adhesions exert traction forces in primary lung epithelial cells

    PubMed Central

    Eisenberg, Jessica L.; Beaumont, Kristin G.; Takawira, Desire; Hopkinson, Susan B.; Mrksich, Milan; Budinger, G. R. Scott; Jones, Jonathan C. R.

    2013-01-01

    Summary Receptor clustering upon cell attachment to the substrate induces assembly of cytoplasmic protein complexes termed focal adhesions (FAs), which connect, albeit indirectly, the extracellular matrix to the cytoskeleton. A subset of cultured primary alveolar epithelial cells (AEC) display a unique pattern of vinculin/paxillin/talin-rich FAs in two concentric circles when cultured on glass and micropatterned substrates: one ring of FAs located at the cell periphery (pFAs), and another FA ring located centrally in the cell (cFAs). Unusually, cFAs associate with an aster-like actin array as well as keratin bundles. Moreover, cFAs show rapid paxillin turnover rates following fluorescence recovery after photobleaching and exert traction forces similar to those generated by FAs at the cell periphery. The plakin protein plectin localizes to cFAs and is normally absent from pFAs, whereas tensin, a marker of mature/fibrillar adhesions, is found in both cFAs and pFAs. In primary AEC in which plectin expression is depleted, cFAs are largely absent, with an attendant reorganization of both the keratin and actin cytoskeletons. We suggest that the mechanical environment in the lung gives rise to the assembly of unconventional FAs in AEC. These FAs not only show a distinctive arrangement, but also possess unique compositional and functional properties. PMID:23750011

  20. Current Understanding of Circulating Tumor Cells – Potential Value in Malignancies of the Central Nervous System

    PubMed Central

    Adamczyk, Lukasz A.; Williams, Hannah; Frankow, Aleksandra; Ellis, Hayley Patricia; Haynes, Harry R.; Perks, Claire; Holly, Jeff M. P.; Kurian, Kathreena M.

    2015-01-01

    Detection of circulating tumor cells (CTCs) in the blood via so-called “liquid biopsies” carries enormous clinical potential in malignancies of the central nervous system (CNS) because of the potential to follow disease evolution with a blood test, without the need for repeat neurosurgical procedures with their inherent risk of patient morbidity. To date, studies in non-CNS malignancies, particularly in breast cancer, show increasing reproducibility of detection methods for these rare tumor cells in the circulation. However, no method has yet received full recommendation to use in clinical practice, in part because of lack of a sufficient evidence base regarding clinical utility. In CNS malignancies, one of the main challenges is finding a suitable biomarker for identification of these cells, because automated systems, such as the widely used Cell Search system, are reliant on markers, such as the epithelial cell adhesion molecule, which are not present in CNS tumors. This review examines methods for CTC enrichment and detection, and reviews the progress in non-CNS tumors and the potential for using this technique in human brain tumors. PMID:26322014